Insulin Human Winthrop

1 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 

 

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1. NAME OF THE MEDICINAL PRODUCT 
 
Insulin Human Winthrop Rapid 100 IU/ml solution for injection in a vial 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each ml contains 100 IU insulin human (equivalent to 3.5 mg). 
Each vial contains 5 ml of solution for injection, equivalent to 500 IU insulin, or 10 ml of solution for 
injection, equivalent to 1000 IU insulin. One IU (International Unit) corresponds to 0.035 mg of 
anhydrous human insulin. 
 
Insulin Human Winthrop Rapid is a neutral insulin solution (regular insulin). 
 
Human insulin is produced by recombinant DNA technology in Escherichia coli. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Solution for injection in a vial. 
 
Clear, colourless solution. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Diabetes mellitus where treatment with insulin is required. Insulin Human Winthrop Rapid is also 
suitable for the treatment of hyperglycaemic coma and ketoacidosis, as well as for achieving pre-, 
intra- and post-operative stabilisation in patients with diabetes mellitus. 
 
4.2 Posology and method of administration 
 
Posology 
The desired blood glucose levels, the insulin preparations to be used and the insulin dose regimen 
(doses and timings) must be determined individually and adjusted to suit the patient’s diet, physical 
activity and life-style. 
 
Daily doses and timing of administration 
There are no fixed rules for insulin dose regimen. However, the average insulin requirement is often 
0.5 to 1.0 IU per kg body weight per day. The basal metabolic requirement is 40% to 60% of the total 
daily requirement. Insulin Human Winthrop Rapid is injected subcutaneously 15 to 20 minutes before 
a meal. 
 
In the treatment of severe hyperglycaemia or ketoacidosis in particular, insulin administration is part 
of a complex therapeutic regimen which includes measures to protect patients from possible severe 
complications of a relatively rapid lowering of blood glucose. This regimen requires close monitoring 
(metabolic status, acid-base and electrolyte status, vital parameters etc.) in an intensive care unit or 
similar setting. 
 
Secondary dose adjustment 
Improved metabolic control may result in increased insulin sensitivity, leading to a reduced insulin 
requirement. Dose adjustment may also be required, for example, if 
- the patient's weight changes, 

 

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- the patient's life-style changes, 
- other circumstances arise that may promote an increased susceptibility to hypo- or 

hyperglycaemia (see section 4.4). 
 
Special populations 
Elderly population (≧65 years old) 
In the elderly, progressive deterioration of renal function may lead to a steady decrease in insulin 
requirements. 
 
Renal impairment 
In patients with renal impairment, insulin requirements may be diminished due to reduced insulin 
metabolism. 
 
Hepatic impairment 
In patients with severe hepatic impairment, insulin requirements may be diminished due to reduced 
capacity for gluconeogenesis and reduced insulin metabolism. 
 
Method of administration 
Insulin Human Winthrop Rapid must not be used in external or implanted insulin pumps or in 
peristaltic pumps with silicone tubing. 
Only injection syringes designed for this strength of insulin (100 IU per ml) are to be used. The 
injection syringes must not contain any other medicinal product or residue (e.g. traces of heparin). 
 
Insulin Human Winthrop Rapid is administered subcutaneously. 
 
Insulin absorption and hence the blood-glucose-lowering effect of a dose may vary from one injection 
area to another (e.g. the abdominal wall compared with the thigh). Injection sites within an injection 
area must be rotated from one injection to the next. 
 
Insulin Human Winthrop Rapid may also be administered intravenously. Intravenous insulin therapy 
must generally take place in an intensive care unit or under comparable monitoring and treatment 
conditions (see "Daily doses and timing of administration"). 
 
For further details on handling, see section 6.6. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
 
4.4 Special warnings and precautions for use 
 
Patients hypersensitive to Insulin Human Winthrop Rapid for whom no better tolerated preparation is 
available must only continue treatment under close medical supervision and – where necessary – in 
conjunction with anti-allergic treatment. 
 
In patients with an allergy to animal insulin intradermal skin testing is recommended prior to a 
transfer to Insulin Human Winthrop Rapid, since they may experience immunological cross-reactions. 
 
In case of insufficient glucose control or a tendency to hyper- or hypoglycaemic episodes, the patient's 
adherence to the prescribed treatment regimen, injection sites and proper injection technique and all 
other relevant factors must be reviewed before dose adjustment is considered. 
 
Transfer to Insulin Human Winthrop Rapid 
Transferring a patient to another type or brand of insulin should be done under strict medical 
supervision. Changes in strength, brand (manufacturer), type (regular, NPH, lente, long-acting, etc.), 
origin (animal, human, human insulin analogue) and/or method of manufacture may result in the need 
for a change in dosage. 

 

 

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The need to adjust (e.g. reduce) the dose may become evident immediately after transfer. 
Alternatively, it may emerge gradually over a period of several weeks. 
 
Following transfer from an animal insulin to human insulin, dose regimen reduction may be required 
in particular in patients who 
- were previously already controlled on rather low blood glucose levels, 
- have a tendency to hypoglycaemia, 
- previously required high insulin doses due to the presence of insulin antibodies. 
 
Close metabolic monitoring is recommended during the transition and in the initial weeks thereafter. In 
patients who require high insulin doses because of the presence of insulin antibodies, transfer under 
medical supervision in a hospital or similar setting must be considered. 
 
Hypoglycaemia 
Hypoglycaemia may occur if the insulin dose is too high in relation to the insulin requirement. 
 
Particular caution should be exercised, and intensified blood glucose monitoring is advisable in 
patients in whom hypoglycaemic episodes might be of particular clinical relevance, such as in patients 
with significant stenoses of the coronary arteries or of the blood vessels supplying the brain (risk of 
cardiac or cerebral complications of hypoglycaemia) as well as in patients with proliferative 
retinopathy, particularly if not treated with photocoagulation (risk of transient amaurosis following 
hypoglycaemia). 
 
Patients should be aware of circumstances where warning symptoms of hypoglycaemia are 
diminished. The warning symptoms of hypoglycaemia may be changed, be less pronounced or be 
absent in certain risk groups. These include patients: 
- in whom glycaemic control is markedly improved, 
- in whom hypoglycaemia develops gradually, 
- who are elderly,  
- after transfer from animal insulin to human insulin, 
- in whom an autonomic neuropathy is present, 
- with a long history of diabetes, 
- suffering from a psychiatric illness, 
- receiving concurrent treatment with certain other medicinal products (see section 4.5). 
Such situations may result in severe hypoglycaemia (and possibly loss of consciousness) prior to the 
patient's awareness of hypoglycaemia. 
 
If normal or decreased values for glycated haemoglobin are noted, the possibility of recurrent, 
unrecognised (especially nocturnal) episodes of hypoglycaemia must be considered. 
 
Adherence of the patient to the dose regimen and dietary regimen, correct insulin administration and 
awareness of hypoglycaemia symptoms are essential to reduce the risk of hypoglycaemia. Factors 
increasing the susceptibility to hypoglycaemia require particularly close monitoring and may 
necessitate dose adjustment. These include: 
- change in the injection area, 
- improved insulin sensitivity (e.g. by removal of stress factors), 
- unaccustomed, increased or prolonged physical activity, 
- intercurrent illness (e.g. vomiting, diarrhoea), 
- inadequate food intake, 
- missed meals, 
- alcohol consumption, 
- certain uncompensated endocrine disorders (e.g. in hypothyroidism and in anterior pituitary or 

adrenocortical insufficiency), 
- concomitant treatment with certain other medicinal products. 
 

 

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Intercurrent illness 
Intercurrent illness requires intensified metabolic monitoring. In many cases, urine tests for ketones 
are indicated, and often it is necessary to adjust the insulin dose. The insulin requirement is often 
increased. Patients with type 1 diabetes must continue to consume at least a small amount of 
carbohydrates on a regular basis, even if they are able to eat only little or no food, or are vomiting etc. 
and they must never omit insulin entirely. 
 
Medication errors 
Medication errors have been reported in which other Insulin Human Winthrop formulations or other 
insulins have been accidentally administered. Insulin label must always be checked before each 
injection to avoid medication errors between insulin human and other insulins. 
 
Combination of Insulin Human Winthrop with pioglitazone 
Cases of cardiac failure have been reported when pioglitazone was used in combination with insulin, 
especially in patients with risk factors for development of cardiac heart failure. This should be kept in 
mind if treatment with the combination of pioglitazone and Insulin Human Winthrop is considered. If 
the combination is used, patients should be observed for signs and symptoms of heart failure, weight 
gain and oedema. Pioglitazone should be discontinued if any deterioration in cardiac symptoms 
occurs.  
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
A number of substances affect glucose metabolism and may require dose adjustment of human insulin. 
 
Substances that may enhance the blood-glucose-lowering effect and increase susceptibility to 
hypoglycaemia include oral antidiabetic medicinal products, angiotensin converting enzyme (ACE) 
inhibitors, disopyramide, fibrates, fluoxetine, monoamine oxidase (MAO) inhibitors, pentoxifylline, 
propoxyphene, salicylates and sulphonamide antibiotics. 
 
Substances that may reduce the blood-glucose-lowering effect include corticosteroids, danazol, 
diazoxide, diuretics, glucagon, isoniazid, oestrogens and progestogens (e.g. in oral contraceptives), 
phenothiazine derivatives, somatropin, sympathomimetic medicinal products (e.g. epinephrine 
[adrenaline], salbutamol, terbutaline), thyroid hormones, protease inhibitors and atypical antipsychotic 
medicinal products (e.g. olanzapine and clozapine). 
 
Beta-blockers, clonidine, lithium salts or alcohol may either potentiate or weaken the 
blood-glucose-lowering effect of insulin. Pentamidine may cause hypoglycaemia which may 
sometimes be followed by hyperglycaemia. 
 
In addition, under the influence of sympatholytic medicinal products such as beta-blockers, clonidine, 
guanethidine and reserpine, the signs of adrenergic counter-regulation may be reduced or absent. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy  
For insulin human, no clinical data on exposed pregnancies from controlled clinical studies are 
available. Insulin does cross the placental barrier, although not in clinically significant amount. A 
limited amount of data on pregnant women (less than 300 pregnancy outcomes reported) exposed to 
marketed insulin human indicates no safety issues in use of insulin human in pregnancy. Caution 
should be exercised when prescribing to pregnant women. 
 
It is essential for patients with pre-existing or gestational diabetes to maintain good metabolic control 
throughout pregnancy. Insulin requirements may decrease during the first trimester and generally 
increase during the second and third trimesters. Immediately after delivery, insulin requirements 
decline rapidly (increased risk of hypoglycaemia). Careful monitoring of glucose control is essential. 
 

 

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Breast-feeding 
No effects on the suckling child are anticipated. Insulin Human Winthrop Rapid can be used during 
breast-feeding. Breast-feeding women may require adjustments in insulin dose and diet. 
 
Fertility 
No clinical or animal data with insulin human on male or female fertility are available. 
 
4.7 Effects on ability to drive and use machines 
 
The patient's ability to concentrate and react may be impaired as a result of hypoglycaemia or 
hyperglycaemia or, for example, as a result of visual impairment. This may constitute a risk in 
situations where these abilities are of special importance (e.g. driving a car or using machines). 
 
Patients should be advised to take precautions to avoid hypoglycaemia whilst driving. This is 
particularly important in those who have reduced or absent awareness of the warning symptoms of 
hypoglycaemia or have frequent episodes of hypoglycaemia. It should be considered whether it is 
advisable to drive or use machines in these circumstances. 
 
4.8 Undesirable effects  
 
Summary of the safety profile  
Hypoglycaemia, in general the most frequent adverse reaction of insulin therapy, may occur if the 
insulin dose is too high in relation to the insulin requirement. In clinical studies and during marketed 
use, the frequency varies with patient population and dose regimens. Therefore, no specific frequency 
can be presented. 
 
Tabulated list of adverse reactions 
The following related adverse reactions from clinical investigations are listed below by system organ 
class and in order of decreasing incidence: very common (≥1/10); common (≥1/100 to <1/10); 
uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000), not known 
(cannot be estimated from the available data). 
 
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. 
 
MedDRA system 
organ classes 

Common Uncommon Not known 

Immune system 
disorders 

 Shock Immediate type 
allergic reactions 
(hypotension, 
angioneurotic oedema, 
bronchospasm, 
generalised skin 
reactions); 
Anti-insulin antibodies 

Metabolism and 
nutrition disorders 

Oedema  Hypoglycaemia; 
Sodium retention 

Eye disorders   Proliferative 
retinopathy; 
Diabetic retinopathy; 
Visual impairment 

Skin and subcutaneous 
tissue disorders 

  Lipodystrophy 

General disorders and 
administration site 
conditions 

Injection site reactions Injection site urticaria Injection site 
inflammation;  
Injection site pain; 
Injection site pruritus; 
Injection site erythema; 

 

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MedDRA system 
organ classes 

Common Uncommon Not known 

Injection site swelling 
 
Description of selected adverse reactions 
Immune system disorders 
Immediate type allergic reactions to insulin or to the excipients may be life-threatening. 
 
Insulin administration may cause anti-insulin antibodies to form. In rare cases, the presence of such 
anti-insulin antibodies may necessitate adjustment of the insulin dose in order to correct a tendency to 
hyper- or hypoglycaemia. 
 
Metabolism and nutrition disorders 
Severe hypoglycaemic attacks, especially if recurrent, may lead to neurological damage. 
Prolonged or severe hypoglycaemic episodes may be life-threatening. 
 
In many patients, the signs and symptoms of neuroglycopenia are preceded by signs of adrenergic 
counter-regulation. Generally, the greater and more rapid the decline in blood glucose, the more marked is 
the phenomenon of counter-regulation and its symptoms. 
 
Insulin may cause sodium retention and oedema, particularly if previously poor metabolic control is 
improved by intensified insulin therapy. 
 
Eyes disorders 
A marked change in glycaemic control may cause temporary visual impairment, due to temporary 
alteration in the turgidity and refractive index of the lens. 
 
Long-term improved glycaemic control decreases the risk of progression of diabetic retinopathy. 
However, intensification of insulin therapy with abrupt improvement in glycaemic control may be 
associated with temporary worsening of diabetic retinopathy. 
 
Skin and subcutaneous tissue disorders 
Lipodystrophy may occur at the injection site and delay local insulin absorption. Continuous rotation 
of the injection site within the given injection area may help to reduce or prevent these reactions. 
 
General disorders and administration site conditions 
Most minor reactions to insulins at the injection site usually resolve in a few days to a few weeks. 
 
4.9 Overdose 
 
Symptoms 
Insulin overdose may lead to severe and sometimes long-term and life-threatening hypoglycaemia. 
 
Management 
Mild episodes of hypoglycaemia can usually be treated with oral carbohydrates. Adjustments in dose 
regimen of the medicinal product, meal patterns, or physical activity may be needed. 
 
More severe episodes with coma, seizure, or neurologic impairment may be treated with 
intramuscular/subcutaneous glucagon or concentrated intravenous glucose. Sustained carbohydrate 
intake and observation may be necessary because hypoglycaemia may recur after apparent clinical 
recovery. 
 
 

 

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5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Drugs used in diabetes, insulins and analogues for injection, fast-acting, 
ATC Code: A10AB01. 
 
Mechanism of action 
Insulin 
- lowers blood glucose and promotes anabolic effects as well as decreasing catabolic effects, 
- increases the transport of glucose into cells as well as the formation of glycogen in the muscles 

and the liver, and improves pyruvate utilisation. It inhibits glycogenolysis and gluconeogenesis, 
- increases lipogenesis in the liver and adipose tissue and inhibits lipolysis, 
- promotes the uptake of amino acids into cells and promotes protein synthesis, 
- enhances the uptake of potassium into cells. 
 
Pharmacodynamic effects 
Insulin Human Winthrop Rapid is an insulin with rapid onset and short duration of action. Following 
subcutaneous injection, onset of action is within 30 minutes, the phase of maximum action is between 
1 and 4 hours after injection and the duration of action is 7 to 9 hours. 
 
5.2 Pharmacokinetic properties 
 
In healthy subjects, the serum half-life of insulin is approximately 4 to 6 minutes. It is longer in 
patients with severe renal insufficiency. However, it must be noted that the pharmacokinetics of 
insulin do not reflect its metabolic action. 
 
5.3 Preclinical safety data 
 
The acute toxicity was studied following subcutaneous administration in rats. No evidence of toxic 
effects was found. Local tolerability studies following subcutaneous and intramuscular administration 
in rabbits gave no remarkable findings. Studies of pharmacodynamic effects following subcutaneous 
administration in rabbits and dogs revealed the expected hypoglycaemic reactions. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Metacresol, 
sodium dihydrogen phosphate dihydrate, 
glycerol, 
sodium hydroxide, 
hydrochloric acid (for pH adjustment), 
water for injections. 
 
6.2 Incompatibilities 
 
This medicinal product must not be mixed with other medicinal products except those mentioned in 
section 6.6. 
 
Insulin Human Winthrop Rapid must not be mixed with solutions containing reducing substances such 
as thioles and sulphites.  
 
Mixing of insulins 
Insulin Human Winthrop Rapid must not be mixed with insulin human formulations designed 
specifically for use in insulin pumps.  

 

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Insulin Human Winthrop Rapid must also not be mixed with insulins of animal origin or with insulin 
analogues. 
Insulins of different concentration (e.g. 100 IU per ml and 40 IU per ml) must not be mixed. 
 
Care must be taken to ensure that no alcohol or other disinfectants enter the insulin solution. 
 
6.3 Shelf life 
 
2 years. 
 
Shelf life after first use of the vial 
The product may be stored for a maximum of 4 weeks not above 25°C and away from direct heat or 
direct light. 
Keep the vial in the outer carton in order to protect from light. 
It is recommended that the date of the first use be noted on the label. 
 
6.4 Special precautions for storage 
 
Unopened vials 
Store in a refrigerator (2°C - 8°C). 
Do not freeze. 
Do not put Insulin Human Winthrop Rapid next to the freezer compartment or a freezer pack. 
Keep the vial in the outer carton in order to protect from light. 
 
Opened vials 
For storageconditions after first opening of the medicinal product, see section 6.3. 
 
6.5 Nature and contents of container 
 
5 ml solution in a vial and 10 ml solution in a vial (type 1 colourless glass) with a flanged cap 
(aluminium), a stopper (chlorobutyl rubber (type 1)) and a tear-off cap (polypropylene). 
Packs of 1 and 5 vials are available. 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal and other handling 
 
Before withdrawing insulin from the vial for the first time, remove the plastic protective cap. 
 
Do not shake the vial vigorously as this may cause frothing. Froth may interfere with the correct 
measurement of the dose. 
 
Insulin Human Winthrop Rapid must only be used if the solution is clear, colourless, with no solid 
particles visible, and if it is of a water-like consistency. 
 
Insulin Human Winthrop Rapid must not be used in external or implanted insulin pumps or in 
peristaltic pumps with silicone tubing. 
 
It must be remembered that neutral regular insulin precipitates out at a pH of approximately 4.5 to 6.5. 
 
Insulin label must always be checked before each injection to avoid medication errors between insulin 
human and other insulins (see section 4.4). 
 
Mixing of insulins 
Insulin Human Winthrop Rapid may be mixed with all insulin human formulations, but not with those 
designed specifically for use in insulin pumps 
Concerning incompatibility with other insulins, see section 6.2. 
 

 

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If two different insulins have to be drawn into one single injection syringe, it is recommended that the 
shorter-acting insulin be drawn first to prevent contamination of the vial by the longer-acting 
preparation. It is advisable to inject immediately after mixing.  
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Sanofi-Aventis Deutschland GmbH, D-65926 Frankfurt am Main, Germany 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/06/368/011 
EU/1/06/368/012 
EU/1/06/368/169 
EU/1/06/368/170 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 17 January 2007 
Date of latest renewal: 17 January 2012  
 
 
10. DATE OF REVISION OF THE TEXT 
 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu 

 

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1. NAME OF THE MEDICINAL PRODUCT 
 
Insulin Human Winthrop Rapid 40 IU/ml solution for injection in a vial 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each ml contains 40 IU insulin human (equivalent to 1.4 mg).  
Each vial contains 10 ml of solution for injection, equivalent to 400 IU insulin. One IU (International 
Unit) corresponds to 0.035 mg of anhydrous human insulin. 
 
Insulin Human Winthrop Rapid is a neutral insulin solution (regular insulin). 
 
Human insulin is produced by recombinant DNA technology in Escherichia coli. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Solution for injection in a vial. 
 
Clear, colourless solution. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Diabetes mellitus where treatment with insulin is required. Insulin Human Winthrop Rapid is also 
suitable for the treatment of hyperglycaemic coma and ketoacidosis, as well as for achieving pre-, 
intra- and post-operative stabilisation in patients with diabetes mellitus. 
 
4.2 Posology and method of administration 
 
Posology 
The desired blood glucose levels, the insulin preparations to be used and the insulin dose regimen 
(doses and timings) must be determined individually and adjusted to suit the patient’s diet, physical 
activity and life-style. 
 
Daily doses and timing of administration 
There are no fixed rules for insulin dose regimen. However, the average insulin requirement is often 
0.5 to 1.0 IU per kg body weight per day. The basal metabolic requirement is 40% to 60% of the total 
daily requirement. Insulin Human Winthrop Rapid is injected subcutaneously 15 to 20 minutes before 
a meal. 
 
In the treatment of severe hyperglycaemia or ketoacidosis in particular, insulin administration is part 
of a complex therapeutic regimen which includes measures to protect patients from possible severe 
complications of a relatively rapid lowering of blood glucose. This regimen requires close monitoring 
(metabolic status, acid-base and electrolyte status, vital parameters etc.) in an intensive care unit or 
similar setting. 
 
Secondary dose adjustment 
Improved metabolic control may result in increased insulin sensitivity, leading to a reduced insulin 
requirement. Dose adjustment may also be required, for example, if 
- the patient's weight changes, 
- the patient's life-style changes, 

 

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- other circumstances arise that may promote an increased susceptibility to hypo- or 
hyperglycaemia (see section 4.4). 

 
Special populations 
Elderly population (≧65 years old) 
In the elderly, progressive deterioration of renal function may lead to a steady decrease in insulin 
requirements. 
 
Renal impairment 
In patients with renal impairment, insulin requirements may be diminished due to reduced insulin 
metabolism. 
 
Hepatic impairment 
In patients with severe hepatic impairment, insulin requirements may be diminished due to reduced 
capacity for gluconeogenesis and reduced insulin metabolism. 
 
Method of administration 
Insulin Human Winthrop Rapid must not be used in external or implanted insulin pumps or in 
peristaltic pumps with silicone tubing. 
 
Only injection syringes designed for this strength of insulin (40 IU per ml) are to be used. The 
injection syringes must not contain any other medicinal product or residue (e.g. traces of heparin). 
 
Insulin Human Winthrop Rapid is administered subcutaneously. 
 
Insulin absorption and hence the blood-glucose-lowering effect of a dose may vary from one injection 
area to another (e.g. the abdominal wall compared with the thigh). Injection sites within an injection 
area must be rotated from one injection to the next. 
 
Insulin Human Winthrop Rapid may also be administered intravenously. Intravenous insulin therapy 
must generally take place in an intensive care unit or under comparable monitoring and treatment 
conditions (see "Daily doses and timing of administration"). 
 
For further details on handling, see section 6.6. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
 
4.4 Special warnings and precautions for use 
 
Patients hypersensitive to Insulin Human Winthrop Rapid for whom no better tolerated preparation is 
available must only continue treatment under close medical supervision and – where necessary – in 
conjunction with anti-allergic treatment. 
 
In patients with an allergy to animal insulin intradermal skin testing is recommended prior to a 
transfer to Insulin Human Winthrop Rapid, since they may experience immunological cross-reactions. 
 
In case of insufficient glucose control or a tendency to hyper- or hypoglycaemic episodes, the patient's 
adherence to the prescribed treatment regimen, injection sites and proper injection technique and all 
other relevant factors must be reviewed before dose adjustment is considered. 
 
Transfer to Insulin Human Winthrop Rapid 
Transferring a patient to another type or brand of insulin should be done under strict medical 
supervision. Changes in strength, brand (manufacturer), type (regular, NPH, lente, long-acting, etc.), 
origin (animal, human, human insulin analogue) and/or method of manufacture may result in the need 
for a change in dosage. 

 

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The need to adjust (e.g. reduce) the dose may become evident immediately after transfer. 
Alternatively, it may emerge gradually over a period of several weeks. 
 
Following transfer from an animal insulin to human insulin, dose regimen reduction may be required 
in particular in patients who 
- were previously already controlled on rather low blood glucose levels, 
- have a tendency to hypoglycaemia, 
- previously required high insulin doses due to the presence of insulin antibodies. 
 
Close metabolic monitoring is recommended during the transition and in the initial weeks thereafter. In 
patients who require high insulin doses because of the presence of insulin antibodies, transfer under 
medical supervision in a hospital or similar setting must be considered. 
 
Hypoglycaemia 
Hypoglycaemia may occur if the insulin dose is too high in relation to the insulin requirement. 
 
Particular caution should be exercised, and intensified blood glucose monitoring is advisable in 
patients in whom hypoglycaemic episodes might be of particular clinical relevance, such as in patients 
with significant stenoses of the coronary arteries or of the blood vessels supplying the brain (risk of 
cardiac or cerebral complications of hypoglycaemia) as well as in patients with proliferative 
retinopathy, particularly if not treated with photocoagulation (risk of transient amaurosis following 
hypoglycaemia). 
 
Patients should be aware of circumstances where warning symptoms of hypoglycaemia are 
diminished. The warning symptoms of hypoglycaemia may be changed, be less pronounced or be 
absent in certain risk groups. These include patients: 
- in whom glycaemic control is markedly improved, 
- in whom hypoglycaemia develops gradually, 
- who are elderly,  
- after transfer from animal insulin to human insulin, 
- in whom an autonomic neuropathy is present, 
- with a long history of diabetes, 
- suffering from a psychiatric illness, 
- receiving concurrent treatment with certain other medicinal products (see section 4.5). 
Such situations may result in severe hypoglycaemia (and possibly loss of consciousness) prior to the 
patient's awareness of hypoglycaemia. 
 
If normal or decreased values for glycated haemoglobin are noted, the possibility of recurrent, 
unrecognised (especially nocturnal) episodes of hypoglycaemia must be considered. 
 
Adherence of the patient to the dose regimen and dietary regimen, correct insulin administration and 
awareness of hypoglycaemia symptoms are essential to reduce the risk of hypoglycaemia. Factors 
increasing the susceptibility to hypoglycaemia require particularly close monitoring and may 
necessitate dose adjustment. These include: 
- change in the injection area, 
- improved insulin sensitivity (e.g. by removal of stress factors), 
- unaccustomed, increased or prolonged physical activity, 
- intercurrent illness (e.g. vomiting, diarrhoea), 
- inadequate food intake, 
- missed meals, 
- alcohol consumption, 
- certain uncompensated endocrine disorders (e.g. in hypothyroidism and in anterior pituitary or 

adrenocortical insufficiency), 
- concomitant treatment with certain other medicinal products. 
 

 

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Intercurrent illness 
Intercurrent illness requires intensified metabolic monitoring. In many cases, urine tests for ketones 
are indicated, and often it is necessary to adjust the insulin dose. The insulin requirement is often 
increased. Patients with type 1 diabetes must continue to consume at least a small amount of 
carbohydrates on a regular basis, even if they are able to eat only little or no food, or are vomiting etc. 
and they must never omit insulin entirely. 
 
Medication errors 
Medication errors have been reported in which other Insulin Human Winthrop formulations or other 
insulins have been accidentally administered. Insulin label must always be checked before each 
injection to avoid medication errors between insulin human and other insulins. 
 
Combination of Insulin Human Winthrop with pioglitazone 
Cases of cardiac failure have been reported when pioglitazone was used in combination with insulin, 
especially in patients with risk factors for development of cardiac heart failure. This should be kept in 
mind if treatment with the combination of pioglitazone and Insulin Human Winthrop is considered. If 
the combination is used, patients should be observed for signs and symptoms of heart failure, weight 
gain and oedema. Pioglitazone should be discontinued if any deterioration in cardiac symptoms 
occurs.  
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
A number of substances affect glucose metabolism and may require dose adjustment of human insulin. 
 
Substances that may enhance the blood-glucose-lowering effect and increase susceptibility to 
hypoglycaemia include oral antidiabetic medicinal products, angiotensin converting enzyme (ACE) 
inhibitors, disopyramide, fibrates, fluoxetine, monoamine oxidase (MAO) inhibitors, pentoxifylline, 
propoxyphene, salicylates and sulphonamide antibiotics. 
 
Substances that may reduce the blood-glucose-lowering effect include corticosteroids, danazol, 
diazoxide, diuretics, glucagon, isoniazid, oestrogens and progestogens (e.g. in oral contraceptives), 
phenothiazine derivatives, somatropin, sympathomimetic medicinal products (e.g. epinephrine 
[adrenaline], salbutamol, terbutaline), thyroid hormones, protease inhibitors and atypical antipsychotic 
medicinal products (e.g. olanzapine and clozapine). 
 
Beta-blockers, clonidine, lithium salts or alcohol may either potentiate or weaken the 
blood-glucose-lowering effect of insulin. Pentamidine may cause hypoglycaemia which may 
sometimes be followed by hyperglycaemia. 
 
In addition, under the influence of sympatholytic medicinal products such as beta-blockers, clonidine, 
guanethidine and reserpine, the signs of adrenergic counter-regulation may be reduced or absent. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
For insulin human, no clinical data on exposed pregnancies from controlled clinical studies are 
available. Insulin does cross the placental barrier, although not in clinically significant amount. A 
limited amount of data on pregnant women (less than 300 pregnancy outcomes reported) exposed to 
marketed insulin human indicates no safety issues in use of insulin human in pregnancy. Caution 
should be exercised when prescribing to pregnant women. 
 
It is essential for patients with pre-existing or gestational diabetes to maintain good metabolic control 
throughout pregnancy. Insulin requirements may decrease during the first trimester and generally 
increase during the second and third trimesters. Immediately after delivery, insulin requirements 
decline rapidly (increased risk of hypoglycaemia). Careful monitoring of glucose control is essential. 
 

 

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Breast-feeding 
No effects on the suckling child are anticipated. Insulin Human Winthrop Rapid can be used during 
breast-feeding. Breast-feeding women may require adjustments in insulin dose and diet. 
 
Fertility 
No clinical or animal data with insulin human on male or female fertility are available. 
 
4.7 Effects on ability to drive and use machines 
 
The patient's ability to concentrate and react may be impaired as a result of hypoglycaemia or 
hyperglycaemia or, for example, as a result of visual impairment. This may constitute a risk in 
situations where these abilities are of special importance (e.g. driving a car or using machines). 
 
Patients should be advised to take precautions to avoid hypoglycaemia whilst driving. This is 
particularly important in those who have reduced or absent awareness of the warning symptoms of 
hypoglycaemia or have frequent episodes of hypoglycaemia. It should be considered whether it is 
advisable to drive or use machines in these circumstances. 
 
4.8 Undesirable effects 
 
Summary of the safety profile  
Hypoglycaemia, in general the most frequent adverse reaction of insulin therapy, may occur if the 
insulin dose is too high in relation to the insulin requirement. In clinical studies and during marketed 
use, the frequency varies with patient population and dose regimens. Therefore, no specific frequency 
can be presented. 
 
Tabulated list of adverse reactions 
The following related adverse reactions from clinical investigations are listed below by system organ 
class and in order of decreasing incidence: very common (≥1/10); common (≥1/100 to <1/10); 
uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000), not known 
(cannot be estimated from the available data). 
 
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. 
 
MedDRA system 
organ classes 

Common Uncommon Not known 

Immune system 
disorders 

 Shock Immediate type allergic 
reactions (hypotension, 
angioneurotic oedema, 
bronchospasm, 
generalised skin 
reactions); 
Anti-insulin antibodies 

Metabolism and 
nutrition disorders 

Oedema  Hypoglycaemia; 
Sodium retention 

Eye disorders   Proliferative retinopathy; 
Diabetic retinopathy; 
Visual impairment 

Skin and subcutaneous 
tissue disorders 

  Lipodystrophy 

General disorders and 
administration site 
conditions 

Injection site 
reactions 

Injection site urticaria Injection site 
inflammation;  
Injection site pain; 
Injection site pruritus; 
Injection site erythema; 
Injection site swelling 

 

 

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Description of selected adverse reactions 
Immune system disorders 
Immediate type allergic reactions to insulin or to the excipients may be life-threatening. 
 
Insulin administration may cause anti-insulin antibodies to form. In rare cases, the presence of such 
anti-insulin antibodies may necessitate adjustment of the insulin dose in order to correct a tendency to 
hyper- or hypoglycaemia. 
 
Metabolism and nutrition disorders 
Severe hypoglycaemic attacks, especially if recurrent, may lead to neurological damage. 
Prolonged or severe hypoglycaemic episodes may be life-threatening. 
 
In many patients, the signs and symptoms of neuroglycopenia are preceded by signs of adrenergic 
counter-regulation. Generally, the greater and more rapid the decline in blood glucose, the more 
marked is the phenomenon of counter-regulation and its symptoms. 
 
Insulin may cause sodium retention and oedema, particularly if previously poor metabolic control is 
improved by intensified insulin therapy. 
 
Eyes disorders 
A marked change in glycaemic control may cause temporary visual impairment, due to temporary 
alteration in the turgidity and refractive index of the lens. 
 
Long-term improved glycaemic control decreases the risk of progression of diabetic retinopathy. 
However, intensification of insulin therapy with abrupt improvement in glycaemic control may be 
associated with temporary worsening of diabetic retinopathy. 
 
Skin and subcutaneous tissue disorders 
Lipodystrophy may occur at the injection site and delay local insulin absorption. Continuous rotation 
of the injection site within the given injection area may help to reduce or prevent these reactions. 
 
General disorders and administration site conditions 
Most minor reactions to insulins at the injection site usually resolve in a few days to a few weeks. 
 
4.9 Overdose 
 
Symptoms 
Insulin overdose may lead to severe and sometimes long-term and life-threatening hypoglycaemia. 
 
Management 
Mild episodes of hypoglycaemia can usually be treated with oral carbohydrates. Adjustments in dose 
regimen of the medicinal product, meal patterns, or physical activity may be needed. 
 
More severe episodes with coma, seizure, or neurologic impairment may be treated with 
intramuscular/subcutaneous glucagon or concentrated intravenous glucose. Sustained carbohydrate 
intake and observation may be necessary because hypoglycaemia may recur after apparent clinical 
recovery. 
 
 

 

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5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Drugs used in diabetes, insulins and analogues for injection, fast-acting, 
ATC Code: A10AB01. 
 
Mechanism of action 
Insulin 
- lowers blood glucose and promotes anabolic effects as well as decreasing catabolic effects, 
- increases the transport of glucose into cells as well as the formation of glycogen in the muscles 

and the liver, and improves pyruvate utilisation. It inhibits glycogenolysis and gluconeogenesis, 
- increases lipogenesis in the liver and adipose tissue and inhibits lipolysis, 
- promotes the uptake of amino acids into cells and promotes protein synthesis, 
- enhances the uptake of potassium into cells. 
 
Pharmacodynamic effects 
Insulin Human Winthrop Rapid is an insulin with rapid onset and short duration of action. Following 
subcutaneous injection, onset of action is within 30 minutes, the phase of maximum action is between 
1 and 4 hours after injection and the duration of action is 7 to 9 hours. 
 
5.2 Pharmacokinetic properties 
 
In healthy subjects, the serum half-life of insulin is approximately 4 to 6 minutes. It is longer in 
patients with severe renal insufficiency. However, it must be noted that the pharmacokinetics of 
insulin do not reflect its metabolic action. 
 
5.3 Preclinical safety data 
 
The acute toxicity was studied following subcutaneous administration in rats. No evidence of toxic 
effects was found. Local tolerability studies following subcutaneous and intramuscular administration 
in rabbits gave no remarkable findings. Studies of pharmacodynamic effects following subcutaneous 
administration in rabbits and dogs revealed the expected hypoglycaemic reactions. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Metacresol, 
sodium dihydrogen phosphate dihydrate, 
glycerol, 
sodium hydroxide, 
hydrochloric acid (for pH adjustment), 
water for injections. 
 
6.2 Incompatibilities 
 
This medicinal product must not be mixed with other medicinal products except those mentioned in 
section 6.6. 
 
Insulin Human Winthrop Rapid must not be mixed with solutions containing reducing substances such 
as thioles and sulphites.  
 
Mixing of insulins 
Insulin Human Winthrop Rapid must not be mixed with insulin human formulations designed 
specifically for use in insulin pumps.  

 

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Insulin Human Winthrop Rapid must also not be mixed with insulins of animal origin or with insulin 
analogues. 
Insulins of different concentration (e.g. 100 IU per ml and 40 IU per ml) must not be mixed. 
 
Care must be taken to ensure that no alcohol or other disinfectants enter the insulin solution. 
 
6.3 Shelf life 
 
2 years. 
 
Shelf life after first use of the vial 
The product may be stored for a maximum of 4 weeks not above 25°C and away from direct heat or 
direct light. 
Keep the vial in the outer carton in order to protect from light. 
It is recommended that the date of the first use be noted on the label. 
 
6.4 Special precautions for storage 
 
Unopened vials 
Store in a refrigerator (2°C - 8°C). 
Do not freeze. 
Do not put Insulin Human Winthrop Rapid next to the freezer compartment or a freezer pack. 
Keep the vial in the outer carton in order to protect from light. 
 
Opened vials 
For storage conditions after first opening of the medicinal product, see section 6.3. 
 
6.5 Nature and contents of container 
 
10 ml solution in a vial (type 1 colourless glass) with a flanged cap (aluminium), a stopper 
(chlorobutyl rubber (type 1)) and a tear-off cap (polypropylene). 
Packs of 1 and 5 vials are available. 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal and other handling 
 
Before withdrawing insulin from the vial for the first time, remove the plastic protective cap. 
 
Do not shake the vial vigorously as this may cause frothing. Froth may interfere with the correct 
measurement of the dose. 
 
Insulin Human Winthrop Rapid must only be used if the solution is clear, colourless, with no solid 
particles visible, and if it is of a water-like consistency. 
 
Insulin Human Winthrop Rapid must not be used in external or implanted insulin pumps or in 
peristaltic pumps with silicone tubing. 
 
It must be remembered that neutral regular insulin precipitates out at a pH of approximately 4.5 to 6.5. 
 
Insulin label must always be checked before each injection to avoid medication errors between insulin 
human and other insulins (see section 4.4). 
 
Mixing of insulins 
Insulin Human Winthrop Rapid may be mixed with all insulin human formulations, but not with those 
designed specifically for use in insulin pumps.Concerning incompatibility with other insulins, see 
section 6.2. 
 

 

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If two different insulins have to be drawn into one single injection syringe, it is recommended that the 
shorter-acting insulin be drawn first to prevent contamination of the vial by the longer-acting 
preparation. It is advisable to inject immediately after mixing.  
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Sanofi-Aventis Deutschland GmbH, D-65926 Frankfurt am Main, Germany 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/06/368/001 
EU/1/06/368/002 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 17 January 2007 
Date of latest renewal: 17 January 2012 
 
 
10. DATE OF REVISION OF THE TEXT 
 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu 

 

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1. NAME OF THE MEDICINAL PRODUCT 
 
Insulin Human Winthrop Rapid 100 IU/ml solution for injection in a cartridge 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each ml contains 100 IU insulin human (equivalent to 3.5 mg).  
Each cartridge contains 3 ml of solution for injection, equivalent to 300 IU insulin. One IU 
(International Unit) corresponds to 0.035 mg of anhydrous human insulin. 
 
Insulin Human Winthrop Rapid is a neutral insulin solution (regular insulin). 
 
Human insulin is produced by recombinant DNA technology in Escherichia coli. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Solution for injection in a cartridge. 
 
Clear, colourless solution. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Diabetes mellitus where treatment with insulin is required. Insulin Human Winthrop Rapid is also 
suitable for the treatment of hyperglycaemic coma and ketoacidosis, as well as for achieving pre-, 
intra- and post-operative stabilisation in patients with diabetes mellitus. 
 
4.2 Posology and method of administration 
 
Posology 
The desired blood glucose levels, the insulin preparations to be used and the insulin dose regimen 
(doses and timings) must be determined individually and adjusted to suit the patient’s diet, physical 
activity and life-style. 
 
Daily doses and timing of administration 
There are no fixed rules for insulin dose regimen. However, the average insulin requirement is often 
0.5 to 1.0 IU per kg body weight per day. The basal metabolic requirement is 40% to 60% of the total 
daily requirement. Insulin Human Winthrop Rapid is injected subcutaneously 15 to 20 minutes before 
a meal. 
 
In the treatment of severe hyperglycaemia or ketoacidosis in particular, insulin administration is part 
of a complex therapeutic regimen which includes measures to protect patients from possible severe 
complications of a relatively rapid lowering of blood glucose. This regimen requires close monitoring 
(metabolic status, acid-base and electrolyte status, vital parameters etc.) in an intensive care unit or 
similar setting. 
 
Secondary dose adjustment 
Improved metabolic control may result in increased insulin sensitivity, leading to a reduced insulin 
requirement. Dose adjustment may also be required, for example, if 
- the patient's weight changes, 
- the patient's life-style changes, 

 

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- other circumstances arise that may promote an increased susceptibility to hypo- or 
hyperglycaemia (see section 4.4). 

 
Special populations 
Elderly population (≧65 years old) 
In the elderly, progressive deterioration of renal function may lead to a steady decrease in insulin 
requirements. 
 
Renal impairment 
In patients with renal impairment, insulin requirements may be diminished due to reduced insulin 
metabolism. 
 
Hepatic impairment 
In patients with severe hepatic impairment, insulin requirements may be diminished due to reduced 
capacity for gluconeogenesis and reduced insulin metabolism. 
 
Method of administration 
Insulin Human Winthrop Rapid must not be used in external or implanted insulin pumps or in 
peristaltic pumps with silicone tubing. 
 
Insulin Human Winthrop Rapid is administered subcutaneously. 
 
Insulin absorption and hence the blood-glucose-lowering effect of a dose may vary from one injection 
area to another (e.g. the abdominal wall compared with the thigh). Injection sites within an injection 
area must be rotated from one injection to the next. 
 
Insulin Human Winthrop Rapid may also be administered intravenously. Intravenous insulin therapy 
must generally take place in an intensive care unit or under comparable monitoring and treatment 
conditions (see "Daily doses and timing of administration"). 
 
For further details on handling, see section 6.6. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
 
4.4 Special warnings and precautions for use 
 
Patients hypersensitive to Insulin Human Winthrop Rapid for whom no better tolerated preparation is 
available must only continue treatment under close medical supervision and – where necessary – in 
conjunction with anti-allergic treatment. 
 
In patients with an allergy to animal insulin intradermal skin testing is recommended prior to a 
transfer to Insulin Human Winthrop Rapid, since they may experience immunological cross-reactions. 
 
In case of insufficient glucose control or a tendency to hyper- or hypoglycaemic episodes, the patient's 
adherence to the prescribed treatment regimen, injection sites and proper injection technique and all 
other relevant factors must be reviewed before dose adjustment is considered. 
 
Transfer to Insulin Human Winthrop Rapid 
Transferring a patient to another type or brand of insulin should be done under strict medical 
supervision. Changes in strength, brand (manufacturer), type (regular, NPH, lente, long-acting, etc.), 
origin (animal, human, human insulin analogue) and/or method of manufacture may result in the need 
for a change in dosage. 
The need to adjust (e.g. reduce) the dose may become evident immediately after transfer. 
Alternatively, it may emerge gradually over a period of several weeks. 
 

 

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Following transfer from an animal insulin to human insulin, dose regimen reduction may be required 
in particular in patients who 
- were previously already controlled on rather low blood glucose levels, 
- have a tendency to hypoglycaemia, 
- previously required high insulin doses due to the presence of insulin antibodies. 
 
Close metabolic monitoring is recommended during the transition and in the initial weeks thereafter. In 
patients who require high insulin doses because of the presence of insulin antibodies, transfer under 
medical supervision in a hospital or similar setting must be considered. 
 
Hypoglycaemia 
Hypoglycaemia may occur if the insulin dose is too high in relation to the insulin requirement. 
 
Particular caution should be exercised, and intensified blood glucose monitoring is advisable in 
patients in whom hypoglycaemic episodes might be of particular clinical relevance, such as in patients 
with significant stenoses of the coronary arteries or of the blood vessels supplying the brain (risk of 
cardiac or cerebral complications of hypoglycaemia) as well as in patients with proliferative 
retinopathy, particularly if not treated with photocoagulation (risk of transient amaurosis following 
hypoglycaemia). 
 
Patients should be aware of circumstances where warning symptoms of hypoglycaemia are 
diminished. The warning symptoms of hypoglycaemia may be changed, be less pronounced or be 
absent in certain risk groups. These include patients: 
- in whom glycaemic control is markedly improved, 
- in whom hypoglycaemia develops gradually, 
- who are elderly,  
- after transfer from animal insulin to human insulin, 
- in whom an autonomic neuropathy is present, 
- with a long history of diabetes, 
- suffering from a psychiatric illness, 
- receiving concurrent treatment with certain other medicinal products (see section 4.5). 
Such situations may result in severe hypoglycaemia (and possibly loss of consciousness) prior to the 
patient's awareness of hypoglycaemia. 
 
If normal or decreased values for glycated haemoglobin are noted, the possibility of recurrent, 
unrecognised (especially nocturnal) episodes of hypoglycaemia must be considered. 
 
Adherence of the patient to the dose regimen and dietary regimen, correct insulin administration and 
awareness of hypoglycaemia symptoms are essential to reduce the risk of hypoglycaemia. Factors 
increasing the susceptibility to hypoglycaemia require particularly close monitoring and may 
necessitate dose adjustment. These include: 
- change in the injection area, 
- improved insulin sensitivity (e.g. by removal of stress factors), 
- unaccustomed, increased or prolonged physical activity, 
- intercurrent illness (e.g. vomiting, diarrhoea), 
- inadequate food intake, 
- missed meals, 
- alcohol consumption, 
- certain uncompensated endocrine disorders (e.g. in hypothyroidism and in anterior pituitary or 

adrenocortical insufficiency), 
- concomitant treatment with certain other medicinal products. 
 
Intercurrent illness 
Intercurrent illness requires intensified metabolic monitoring. In many cases, urine tests for ketones 
are indicated, and often it is necessary to adjust the insulin dose. The insulin requirement is often 
increased. Patients with type 1 diabetes must continue to consume at least a small amount of 

 

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carbohydrates on a regular basis, even if they are able to eat only little or no food, or are vomiting etc. 
and they must never omit insulin entirely. 
 
Pens to be used with Insulin Human Winthrop Rapid cartridges 
The Insulin Human Winthrop Rapid cartridges should only be used with the following pens:  
- JuniorSTAR which delivers Insulin Human Winthrop Rapid in 0.5 unit dose increments 
- OptiPen, ClikSTAR, Tactipen, Autopen 24 and AllStar which all deliver Insulin Human Winthrop 
Rapid in 1 unit dose increments. 
These cartridges should not be used with any other reusable pen as the dosing accuracy has only been 
established with the listed pens.  
Not all of these pens may be marketed in your country. 
 
Medication errors 
Medication errors have been reported in which other Insulin Human Winthrop formulations or other 
insulins have been accidentally administered. Insulin label must always be checked before each 
injection to avoid medication errors between insulin human and other insulins. 
 
Combination of Insulin Human Winthrop with pioglitazone 
Cases of cardiac failure have been reported when pioglitazone was used in combination with insulin, 
especially in patients with risk factors for development of cardiac heart failure. This should be kept in 
mind if treatment with the combination of pioglitazone and Insulin Human Winthrop is considered. If 
the combination is used, patients should be observed for signs and symptoms of heart failure, weight 
gain and oedema. Pioglitazone should be discontinued if any deterioration in cardiac symptoms 
occurs.  
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
A number of substances affect glucose metabolism and may require dose adjustment of human insulin. 
 
Substances that may enhance the blood-glucose-lowering effect and increase susceptibility to 
hypoglycaemia include oral antidiabetic medicinal products, angiotensin converting enzyme (ACE) 
inhibitors, disopyramide, fibrates, fluoxetine, monoamine oxidase (MAO) inhibitors, pentoxifylline, 
propoxyphene, salicylates and sulphonamide antibiotics. 
 
Substances that may reduce the blood-glucose-lowering effect include corticosteroids, danazol, 
diazoxide, diuretics, glucagon, isoniazid, oestrogens and progestogens (e.g. in oral contraceptives), 
phenothiazine derivatives, somatropin, sympathomimetic medicinal products (e.g. epinephrine 
[adrenaline], salbutamol, terbutaline), thyroid hormones, protease inhibitors and atypical antipsychotic 
medicinal products (e.g. olanzapine and clozapine). 
 
Beta-blockers, clonidine, lithium salts or alcohol may either potentiate or weaken the 
blood-glucose-lowering effect of insulin. Pentamidine may cause hypoglycaemia which may 
sometimes be followed by hyperglycaemia. 
 
In addition, under the influence of sympatholytic medicinal products such as beta-blockers, clonidine, 
guanethidine and reserpine, the signs of adrenergic counter-regulation may be reduced or absent. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
For insulin human, no clinical data on exposed pregnancies from controlled clinical studies are 
available. Insulin does cross the placental barrier, although not in clinically significant amount. A 
limited amount of data on pregnant women (less than 300 pregnancy outcomes reported) exposed to 
marketed insulin human indicates no safety issues in use of insulin human in pregnancy. Caution 
should be exercised when prescribing to pregnant women. 
 

 

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It is essential for patients with pre-existing or gestational diabetes to maintain good metabolic control 
throughout pregnancy. Insulin requirements may decrease during the first trimester and generally 
increase during the second and third trimesters. Immediately after delivery, insulin requirements 
decline rapidly (increased risk of hypoglycaemia). Careful monitoring of glucose control is essential. 
 
Breast-feeding 
No effects on the suckling child are anticipated. Insulin Human Winthrop Rapid can be used during 
breast-feeding. Breast-feeding women may require adjustments in insulin dose and diet. 
 
Fertility 
No clinical or animal data with insulin human on male or female fertility are available. 
 
4.7 Effects on ability to drive and use machines 
 
The patient's ability to concentrate and react may be impaired as a result of hypoglycaemia or 
hyperglycaemia or, for example, as a result of visual impairment. This may constitute a risk in 
situations where these abilities are of special importance (e.g. driving a car or using machines). 
 
Patients should be advised to take precautions to avoid hypoglycaemia whilst driving. This is 
particularly important in those who have reduced or absent awareness of the warning symptoms of 
hypoglycaemia or have frequent episodes of hypoglycaemia. It should be considered whether it is 
advisable to drive or use machines in these circumstances. 
 
4.8 Undesirable effects 
 
Summary of the safety profile  
Hypoglycaemia, in general the most frequent adverse reaction of insulin therapy, may occur if the 
insulin dose is too high in relation to the insulin requirement. In clinical studies and during marketed 
use, the frequency varies with patient population and dose regimens. Therefore, no specific frequency 
can be presented. 
 
Tabulated list of adverse reactions 
The following related adverse reactions from clinical investigations are listed below by system organ 
class and in order of decreasing incidence: very common (≥1/10); common (≥1/100 to <1/10); 
uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000), not known 
(cannot be estimated from the available data). 
 
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. 
 
MedDRA system 
organ classes 

Common Uncommon Not known 

Immune system 
disorders 

 Shock Immediate type allergic 
reactions (hypotension, 
angioneurotic oedema, 
bronchospasm, 
generalised skin 
reactions); 
Anti-insulin antibodies 

Metabolism and 
nutrition disorders 

Oedema  Hypoglycaemia; 
Sodium retention 

Eye disorders   Proliferative retinopathy; 
Diabetic retinopathy; 
Visual impairment 

Skin and subcutaneous 
tissue disorders 

  Lipodystrophy 

General disorders and 
administration site 

Injection site reactions Injection site 
urticaria 

Injection site 
inflammation;  

 

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MedDRA system 
organ classes 

Common Uncommon Not known 

conditions Injection site pain; 
Injection site pruritus; 
Injection site erythema; 
Injection site swelling; 

 
Description of selected adverse reactions 
Immune system disorders 
Immediate type allergic reactions to insulin or to the excipients may be life-threatening. 
 
Insulin administration may cause anti-insulin antibodies to form. In rare cases, the presence of such 
anti-insulin antibodies may necessitate adjustment of the insulin dose in order to correct a tendency to 
hyper- or hypoglycaemia. 
 
Metabolism and nutrition disorders 
Severe hypoglycaemic attacks, especially if recurrent, may lead to neurological damage. 
Prolonged or severe hypoglycaemic episodes may be life-threatening. 
 
In many patients, the signs and symptoms of neuroglycopenia are preceded by signs of adrenergic 
counter-regulation. Generally, the greater and more rapid the decline in blood glucose, the more 
marked is the phenomenon of counter-regulation and its symptoms. 
 
Insulin may cause sodium retention and oedema, particularly if previously poor metabolic control is 
improved by intensified insulin therapy. 
 
Eyes disorders 
A marked change in glycaemic control may cause temporary visual impairment, due to temporary 
alteration in the turgidity and refractive index of the lens. 
 
Long-term improved glycaemic control decreases the risk of progression of diabetic retinopathy. 
However, intensification of insulin therapy with abrupt improvement in glycaemic control may be 
associated with temporary worsening of diabetic retinopathy. 
 
Skin and subcutaneous tissue disorders 
Lipodystrophy may occur at the injection site and delay local insulin absorption. Continuous rotation 
of the injection site within the given injection area may help to reduce or prevent these reactions. 
 
General disorders and administration site conditions 
Most minor reactions to insulins at the injection site usually resolve in a few days to a few weeks. 
 
4.9 Overdose 
 
Symptoms 
Insulin overdose may lead to severe and sometimes long-term and life-threatening hypoglycaemia. 
 
Management 
Mild episodes of hypoglycaemia can usually be treated with oral carbohydrates. Adjustments in dose 
regimen of the medicinal product, meal patterns, or physical activity may be needed. 
 
More severe episodes with coma, seizure, or neurologic impairment may be treated with 
intramuscular/subcutaneous glucagon or concentrated intravenous glucose. Sustained carbohydrate 
intake and observation may be necessary because hypoglycaemia may recur after apparent clinical 
recovery. 
 
 

 

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5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Drugs used in diabetes, insulins and analogues for injection, fast-acting, 
ATC Code: A10AB01. 
 
Mechanism of action 
Insulin 
- lowers blood glucose and promotes anabolic effects as well as decreasing catabolic effects, 
- increases the transport of glucose into cells as well as the formation of glycogen in the muscles 

and the liver, and improves pyruvate utilisation. It inhibits glycogenolysis and gluconeogenesis, 
- increases lipogenesis in the liver and adipose tissue and inhibits lipolysis, 
- promotes the uptake of amino acids into cells and promotes protein synthesis, 
- enhances the uptake of potassium into cells. 
 
Pharmacodynamic effects 
Insulin Human Winthrop Rapid is an insulin with rapid onset and short duration of action. Following 
subcutaneous injection, onset of action is within 30 minutes, the phase of maximum action is between 
1 and 4 hours after injection and the duration of action is 7 to 9 hours. 
 
5.2 Pharmacokinetic properties 
 
In healthy subjects, the serum half-life of insulin is approximately 4 to 6 minutes. It is longer in 
patients with severe renal insufficiency. However, it must be noted that the pharmacokinetics of 
insulin do not reflect its metabolic action. 
 
5.3 Preclinical safety data 
 
The acute toxicity was studied following subcutaneous administration in rats. No evidence of toxic 
effects was found. Local tolerability studies following subcutaneous and intramuscular administration 
in rabbits gave no remarkable findings. Studies of pharmacodynamic effects following subcutaneous 
administration in rabbits and dogs revealed the expected hypoglycaemic reactions. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Metacresol, 
sodium dihydrogen phosphate dihydrate, 
glycerol, 
sodium hydroxide, 
hydrochloric acid (for pH adjustment), 
water for injections. 
 
6.2 Incompatibilities 
 
This medicinal product must not be mixed with other medicinal products except those mentioned in 
section 6.6. 
 
Insulin Human Winthrop Rapid must not be mixed with solutions containing reducing substances such 
as thioles and sulphites.  
 
Mixing of insulins 
Insulin Human Winthrop Rapid must not be mixed with insulin human formulations designed 
specifically for use in insulin pumps.  

 

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Insulin Human Winthrop rapid must also not be mixed with insulins of animal origin or with insulin 
analogues. 
 
Care must be taken to ensure that no alcohol or other disinfectants enter the insulin solution. 
 
6.3 Shelf life 
 
2 years. 
 
Shelf life after first use of the cartridge 
The cartridge in-use (in the insulin pen) or carried as a spare may be stored for a maximum of 4 weeks 
not above 25°C and away from direct heat or direct light. 
The pen containing a cartridge must not be stored in the refrigerator. 
The pen cap must be put back on the pen after each injection in order to protect from light. 
 
6.4 Special precautions for storage 
 
Unopened cartridges 
Store in a refrigerator (2°C - 8°C). 
Do not freeze. 
Do not put Insulin Human Winthrop Rapid next to the freezer compartment or a freezer pack. 
Keep the cartridge in the outer carton in order to protect from light. 
 
In-use cartridges 
For storage conditions after first opening of the medicinal product, see section 6.3. 
 
6.5 Nature and contents of container 
 
3 ml solution in a cartridge (type 1 colourless glass) with a plunger (bromobutyl rubber (type 1)) and a 
flanged cap (aluminium) with a stopper (bromobutyl or laminate of polyisoprene and bromobutyl 
rubber (type 1)). 
Packs of 3, 4, 5, 6, 9 or 10 cartridges are available. 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal and other handling 
 
Insulin pen 
The Insulin Human Winthrop Rapid cartridges are to be used only in conjunction with the pens: 
OptiPen, ClikSTAR, Autopen 24, Tactipen, AllStar or JuniorSTAR (see section 4.4). Not all of these pens 
may be marketed in your country. 
 
The pen should be used as recommended in the information provided by the device manufacturer.  
 
The manufacturer’s instructions for using the pen must be followed carefully for loading the cartridge, 
attaching the injection needle, and administering the insulin injection. 
 
If the insulin pen is damaged or not working properly (due to mechanical defects) it has to be 
discarded, and a new insulin pen has to be used. 
 
If the pen malfunctions (see instructions for using the pen), the solution may be drawn from the 
cartridge into an injection syringe (suitable for an insulin with 100 IU/ml) and injected. 
 
Cartridges 
Before insertion into the pen, Insulin Human Winthrop Rapid must be kept at room temperature for 1 
to 2 hours. 
Inspect the cartridge before use. Insulin Human Winthrop Rapid must only be used if the solution is 
clear, colourless, with no solid particles visible, and if it is of a water-like consistency. 

 

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Air bubbles must be removed from the cartridge before injection (see instructions for using the pen). 
Empty cartridges must not be refilled. 
 
Insulin Human Winthrop Rapid must not be used in external or implanted insulin pumps or in 
peristaltic pumps with silicone tubing. 
 
It must be remembered that neutral regular insulin precipitates out at a pH of approximately 4.5 to 6.5. 
 
Insulin label must always be checked before each injection to avoid medication errors between insulin 
human and other insulins (see section 4.4). 
 
Mixing of insulins 
Insulin Human Winthrop Rapid may be mixed with all insulin human formulations, but not with those 
designed specifically for use in insulin pumps. Concerning incompatibility with other insulins, see 
section 6.2. 
 
Insulin Human Winthrop Rapid cartridges are not designed to allow any other insulin to be mixed in 
the cartridge. 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Sanofi-Aventis Deutschland GmbH, D-65926 Frankfurt am Main, Germany 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/06/368/088 
EU/1/06/368/013 
EU/1/06/368/014 
EU/1/06/368/093 
EU/1/06/368/098 
EU/1/06/368/015 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 17 January 2007 
Date of latest renewal: 17 January 2012 
 
 
10. DATE OF REVISION OF THE TEXT 
 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu 

 

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1. NAME OF THE MEDICINAL PRODUCT 
 
Insulin Human Winthrop Rapid SoloStar 100 IU/ml solution for injection in a pre-filled pen. 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each ml contains 100 IU insulin human (equivalent to 3.5 mg).  
Each pen contains 3 ml of solution for injection, equivalent to 300 IU insulin. One IU (International 
Unit) corresponds to 0.035 mg of anhydrous human insulin. 
 
Insulin Human Winthrop Rapid is a neutral insulin solution (regular insulin). 
 
Human insulin is produced by recombinant DNA technology in Escherichia coli. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Solution for injection in a pre-filled pen. 
 
Clear, colourless solution. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Diabetes mellitus where treatment with insulin is required. 
 
4.2 Posology and method of administration 
 
Posology 
The desired blood glucose levels, the insulin preparations to be used and the insulin dose regimen 
(doses and timings) must be determined individually and adjusted to suit the patient’s diet, physical 
activity and life-style. 
 
Daily doses and timing of administration 
There are no fixed rules for insulin dose regimen. However, the average insulin requirement is often 
0.5 to 1.0 IU per kg body weight per day. The basal metabolic requirement is 40% to 60% of the total 
daily requirement. Insulin Human Winthrop Rapid is injected subcutaneously 15 to 20 minutes before 
a meal. 
 
SoloStar delivers insulin in doses from 1 to 80 units in steps of 1 unit. Each pen contains multiple 
doses. 
 
Secondary dose adjustment 
Improved metabolic control may result in increased insulin sensitivity, leading to a reduced insulin 
requirement. Dose adjustment may also be required, for example, if 
- the patient's weight changes, 
- the patient's life-style changes, 
- other circumstances arise that may promote an increased susceptibility to hypo- or 

hyperglycaemia (see section 4.4). 
 

 

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Special populations 
Elderly population (≧65 years old) 
In the elderly, progressive deterioration of renal function may lead to a steady decrease in insulin 
requirements. 
 
Renal impairment 
In patients with renal impairment, insulin requirements may be diminished due to reduced insulin 
metabolism. 
 
Hepatic impairment 
In patients with severe hepatic impairment, insulin requirements may be diminished due to reduced 
capacity for gluconeogenesis and reduced insulin metabolism. 
 
Method of administration 
Insulin Human Winthrop Rapid is administered subcutaneously. 
 
Insulin absorption and hence the blood-glucose-lowering effect of a dose may vary from one injection 
area to another (e.g. the abdominal wall compared with the thigh). Injection sites within an injection 
area must be rotated from one injection to the next. 
 
Before using SoloStar, the Instructions for Use included in the Package Leaflet must be read carefully. 
 
For further details on handling, see section 6.6. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
 
4.4 Special warnings and precautions for use 
 
Patients hypersensitive to Insulin Human Winthrop Rapid for whom no better tolerated preparation is 
available must only continue treatment under close medical supervision and – where necessary – in 
conjunction with anti-allergic treatment. 
 
In patients with an allergy to animal insulin intradermal skin testing is recommended prior to a 
transfer to Insulin Human Winthrop Rapid, since they may experience immunological cross-reactions. 
 
In case of insufficient glucose control or a tendency to hyper- or hypoglycaemic episodes, the patient's 
adherence to the prescribed treatment regimen, injection sites and proper injection technique and all 
other relevant factors must be reviewed before dose adjustment is considered. 
 
Transfer to Insulin Human Winthrop Rapid 
Transferring a patient to another type or brand of insulin should be done under strict medical 
supervision. Changes in strength, brand (manufacturer), type (regular, NPH, lente, long-acting, etc.), 
origin (animal, human, human insulin analogue) and/or method of manufacture may result in the need 
for a change in dosage. 
The need to adjust (e.g. reduce) the dose may become evident immediately after transfer. 
Alternatively, it may emerge gradually over a period of several weeks. 
 
Following transfer from an animal insulin to human insulin, dose regimen reduction may be required 
in particular in patients who 
- were previously already controlled on rather low blood glucose levels, 
- have a tendency to hypoglycaemia, 
- previously required high insulin doses due to the presence of insulin antibodies. 
 

 

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Close metabolic monitoring is recommended during the transition and in the initial weeks thereafter. In 
patients who require high insulin doses because of the presence of insulin antibodies, transfer under 
medical supervision in a hospital or similar setting must be considered. 
 
Hypoglycaemia 
Hypoglycaemia may occur if the insulin dose is too high in relation to the insulin requirement. 
 
Particular caution should be exercised, and intensified blood glucose monitoring is advisable in 
patients in whom hypoglycaemic episodes might be of particular clinical relevance, such as in patients 
with significant stenoses of the coronary arteries or of the blood vessels supplying the brain (risk of 
cardiac or cerebral complications of hypoglycaemia) as well as in patients with proliferative 
retinopathy, particularly if not treated with photocoagulation (risk of transient amaurosis following 
hypoglycaemia). 
 
Patients should be aware of circumstances where warning symptoms of hypoglycaemia are 
diminished. The warning symptoms of hypoglycaemia may be changed, be less pronounced or be 
absent in certain risk groups. These include patients: 
- in whom glycaemic control is markedly improved, 
- in whom hypoglycaemia develops gradually, 
- who are elderly,  
- after transfer from animal insulin to human insulin, 
- in whom an autonomic neuropathy is present, 
- with a long history of diabetes, 
- suffering from a psychiatric illness, 
- receiving concurrent treatment with certain other medicinal products (see section 4.5). 
Such situations may result in severe hypoglycaemia (and possibly loss of consciousness) prior to the 
patient's awareness of hypoglycaemia. 
 
If normal or decreased values for glycated haemoglobin are noted, the possibility of recurrent, 
unrecognised (especially nocturnal) episodes of hypoglycaemia must be considered. 
 
Adherence of the patient to the dose regimen and dietary regimen, correct insulin administration and 
awareness of hypoglycaemia symptoms are essential to reduce the risk of hypoglycaemia. Factors 
increasing the susceptibility to hypoglycaemia require particularly close monitoring and may 
necessitate dose adjustment. These include: 
- change in the injection area, 
- improved insulin sensitivity (e.g. by removal of stress factors), 
- unaccustomed, increased or prolonged physical activity, 
- intercurrent illness (e.g. vomiting, diarrhoea), 
- inadequate food intake, 
- missed meals, 
- alcohol consumption, 
- certain uncompensated endocrine disorders (e.g. in hypothyroidism and in anterior pituitary or 

adrenocortical insufficiency), 
- concomitant treatment with certain other medicinal products. 
 
Intercurrent illness 
Intercurrent illness requires intensified metabolic monitoring. In many cases, urine tests for ketones 
are indicated, and often it is necessary to adjust the insulin dose. The insulin requirement is often 
increased. Patients with type 1 diabetes must continue to consume at least a small amount of 
carbohydrates on a regular basis, even if they are able to eat only little or no food, or are vomiting etc. 
and they must never omit insulin entirely. 
 
Handling of the pen 
Before using SoloStar, the Instructions for Use included in the Package Leaflet must be read carefully. 
SoloStar has to be used as recommended in these Instructions for Use (see section 6.6). 
 

 

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Medication errors 
Medication errors have been reported in which other Insulin Human Winthrop formulations or other 
insulins have been accidentally administered. Insulin label must always be checked before each 
injection to avoid medication errors between insulin human and other insulins. 
 
Combination of Insulin Human Winthrop with pioglitazone 
Cases of cardiac failure have been reported when pioglitazone was used in combination with insulin, 
especially in patients with risk factors for development of cardiac heart failure. This should be kept in 
mind if treatment with the combination of pioglitazone and Insulin Human Winthrop is considered. If 
the combination is used, patients should be observed for signs and symptoms of heart failure, weight 
gain and oedema. Pioglitazone should be discontinued if any deterioration in cardiac symptoms 
occurs.  
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
A number of substances affect glucose metabolism and may require dose adjustment of human insulin. 
 
Substances that may enhance the blood-glucose-lowering effect and increase susceptibility to 
hypoglycaemia include oral antidiabetic medicinal products, angiotensin converting enzyme (ACE) 
inhibitors, disopyramide, fibrates, fluoxetine, monoamine oxidase (MAO) inhibitors, pentoxifylline, 
propoxyphene, salicylates and sulphonamide antibiotics. 
 
Substances that may reduce the blood-glucose-lowering effect include corticosteroids, danazol, 
diazoxide, diuretics, glucagon, isoniazid, oestrogens and progestogens (e.g. in oral contraceptives), 
phenothiazine derivatives, somatropin, sympathomimetic medicinal products (e.g. epinephrine 
[adrenaline], salbutamol, terbutaline), thyroid hormones, protease inhibitors and atypical antipsychotic 
medicinal products (e.g. olanzapine and clozapine). 
 
Beta-blockers, clonidine, lithium salts or alcohol may either potentiate or weaken the 
blood-glucose-lowering effect of insulin. Pentamidine may cause hypoglycaemia which may 
sometimes be followed by hyperglycaemia. 
 
In addition, under the influence of sympatholytic medicinal products such as beta-blockers, clonidine, 
guanethidine and reserpine, the signs of adrenergic counter-regulation may be reduced or absent. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
For insulin human, no clinical data on exposed pregnancies from controlled clinical studies are 
available. Insulin does cross the placental barrier, although not in clinically significant amount. A 
limited amount of data on pregnant women (less than 300 pregnancy outcomes reported) exposed to 
marketed insulin human indicates no safety issues in use of insulin human in pregnancy. Caution 
should be exercised when prescribing to pregnant women. 
 
It is essential for patients with pre-existing or gestational diabetes to maintain good metabolic control 
throughout pregnancy. Insulin requirements may decrease during the first trimester and generally 
increase during the second and third trimesters. Immediately after delivery, insulin requirements 
decline rapidly (increased risk of hypoglycaemia). Careful monitoring of glucose control is essential. 
 
Breast-feeding 
No effects on the suckling child are anticipated. Insulin Human Winthrop Rapid can be used during 
breast-feeding. Breast-feeding women may require adjustments in insulin dose and diet. 
 
Fertility 
No clinical or animal data with insulin human on male or female fertility are available. 
 

 

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4.7 Effects on ability to drive and use machines 
 
The patient's ability to concentrate and react may be impaired as a result of hypoglycaemia or 
hyperglycaemia or, for example, as a result of visual impairment. This may constitute a risk in 
situations where these abilities are of special importance (e.g. driving a car or using machines). 
 
Patients should be advised to take precautions to avoid hypoglycaemia whilst driving. This is 
particularly important in those who have reduced or absent awareness of the warning symptoms of 
hypoglycaemia or have frequent episodes of hypoglycaemia. It should be considered whether it is 
advisable to drive or use machines in these circumstances. 
 
4.8 Undesirable effects 
 
Summary of the safety profile  
Hypoglycaemia, in general the most frequent adverse reaction of insulin therapy, may occur if the 
insulin dose is too high in relation to the insulin requirement. In clinical studies and during marketed 
use, the frequency varies with patient population and dose regimens. Therefore, no specific frequency 
can be presented. 
 
Tabulated list of adverse reactions 
The following related adverse reactions from clinical investigations are listed below by system organ 
class and in order of decreasing incidence: very common (≥1/10); common (≥1/100 to <1/10); 
uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000), not known 
(cannot be estimated from the available data). 
 
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. 
 
MedDRA system 
organ classes 

Common Uncommon Not known 

Immune system 
disorders 

 Shock Immediate type 
allergic reactions 
(hypotension, 
angioneurotic oedema, 
bronchospasm, 
generalised skin 
reactions); 
Anti-insulin antibodies 

Metabolism and 
nutrition disorders 

Oedema  Hypoglycaemia; 
Sodium retention 

Eye disorders   Proliferative 
retinopathy; 
Diabetic retinopathy; 
Visual impairment 

Skin and 
subcutaneous tissue 
disorders 

  Lipodystrophy 

General disorders 
and administration 
site conditions 

Injection site reactions Injection site 
urticaria 

Injection site 
inflammation;  
Injection site pain; 
Injection site pruritus; 
Injection site 
erythema; Injection 
site swelling 

 

 

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Description of selected adverse reactions 
Immune system disorders 
Immediate type allergic reactions to insulin or to the excipients may be life-threatening. 
 
Insulin administration may cause anti-insulin antibodies to form. In rare cases, the presence of such 
anti-insulin antibodies may necessitate adjustment of the insulin dose in order to correct a tendency to 
hyper- or hypoglycaemia. 
 
Metabolism and nutrition disorders 
Severe hypoglycaemic attacks, especially if recurrent, may lead to neurological damage. 
Prolonged or severe hypoglycaemic episodes may be life-threatening. 
 
In many patients, the signs and symptoms of neuroglycopenia are preceded by signs of adrenergic 
counter-regulation. Generally, the greater and more rapid the decline in blood glucose, the more 
marked is the phenomenon of counter-regulation and its symptoms. 
Insulin may cause sodium retention and oedema, particularly if previously poor metabolic control is 
improved by intensified insulin therapy. 
 
Eyes disorders 
A marked change in glycaemic control may cause temporary visual impairment, due to temporary 
alteration in the turgidity and refractive index of the lens. 
 
Long-term improved glycaemic control decreases the risk of progression of diabetic retinopathy. 
However, intensification of insulin therapy with abrupt improvement in glycaemic control may be 
associated with temporary worsening of diabetic retinopathy. 
 
Skin and subcutaneous tissue disorders 
Lipodystrophy may occur at the injection site and delay local insulin absorption. Continuous rotation 
of the injection site within the given injection area may help to reduce or prevent these reactions. 
 
General disorders and administration site conditions 
Most minor reactions to insulins at the injection site usually resolve in a few days to a few weeks. 
 
4.9 Overdose 
 
Symptoms 
Insulin overdose may lead to severe and sometimes long-term and life-threatening hypoglycaemia. 
 
Management 
Mild episodes of hypoglycaemia can usually be treated with oral carbohydrates. Adjustments in dose 
regimen of the medicinal product, meal patterns, or physical activity may be needed. 
 
More severe episodes with coma, seizure, or neurologic impairment may be treated with 
intramuscular/subcutaneous glucagon or concentrated intravenous glucose. Sustained carbohydrate 
intake and observation may be necessary because hypoglycaemia may recur after apparent clinical 
recovery. 
 
 

 

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5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Drugs used in diabetes, insulins and analogues for injection, fast-acting, 
ATC Code: A10AB01. 
 
Mechanism of action 
Insulin 
- lowers blood glucose and promotes anabolic effects as well as decreasing catabolic effects, 
- increases the transport of glucose into cells as well as the formation of glycogen in the muscles 

and the liver, and improves pyruvate utilisation. It inhibits glycogenolysis and gluconeogenesis, 
- increases lipogenesis in the liver and adipose tissue and inhibits lipolysis, 
- promotes the uptake of amino acids into cells and promotes protein synthesis, 
- enhances the uptake of potassium into cells. 
 
Pharmacodynamic effects 
Insulin Human Winthrop Rapid is an insulin with rapid onset and short duration of action. Following 
subcutaneous injection, onset of action is within 30 minutes, the phase of maximum action is between 
1 and 4 hours after injection and the duration of action is 7 to 9 hours. 
 
5.2 Pharmacokinetic properties 
 
In healthy subjects, the serum half-life of insulin is approximately 4 to 6 minutes. It is longer in 
patients with severe renal insufficiency. However, it must be noted that the pharmacokinetics of 
insulin do not reflect its metabolic action. 
 
5.3 Preclinical safety data 
 
The acute toxicity was studied following subcutaneous administration in rats. No evidence of toxic 
effects was found. Local tolerability studies following subcutaneous and intramuscular administration 
in rabbits gave no remarkable findings. Studies of pharmacodynamic effects following subcutaneous 
administration in rabbits and dogs revealed the expected hypoglycaemic reactions. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Metacresol, 
sodium dihydrogen phosphate dihydrate, 
glycerol, 
sodium hydroxide, 
hydrochloric acid (for pH adjustment), 
water for injections. 
 
6.2 Incompatibilities 
 
This medicinal product must not be mixed with other medicinal products except those mentioned in 
section 6.6. 
 
Insulin Human Winthrop Rapid must not be mixed with solutions containing reducing substances such 
as thioles and sulphites.  
 
Mixing of insulins 
Insulin Human Winthrop Rapid must not be mixed with any other insulin or with insulin analogues. 
 

 

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Care must be taken to ensure that no alcohol or other disinfectants enter the insulin solution. 
 
6.3 Shelf life 
 
2 years. 
 
Shelf life after first use of the pen 
The pen in-use or carried as a spare may be stored for a maximum of 4 weeks not above 25°C and 
away from direct heat or direct light. 
Pens in-use must not be stored in the refrigerator. 
The pen cap must be put back on the pen after each injection in order to protect from light. 
 
6.4 Special precautions for storage 
 
Not in-use pens 
Store in a refrigerator (2°C - 8°C). 
Do not freeze. 
Do not put Insulin Human Winthrop Rapid next to the freezer compartment or a freezer pack. 
Keep the pre-filled pen in the outer carton in order to protect from light. 
 
In-use pens 
For storage conditions after first opening of the medicinal product, see section 6.3. 
 
6.5 Nature and contents of container 
 
3 ml solution in a cartridge (type 1 colourless glass) with a plunger (bromobutyl rubber (type 1)) and a 
flanged cap (aluminium) with a stopper (bromobutyl or laminate of polyisoprene and bromobutyl 
rubber (type 1)). 
The cartridges are sealed in a disposable pen injector.  
Injection needles are not included in the pack. 
Packs of 3, 4, 5, 6, 9 or 10 pens are available. 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal and other handling 
 
Insulin Human Winthrop Rapid must only be used if the solution is clear, colourless, with no solid 
particles visible, and if it is of a water-like consistency. 
 
Empty pens must never be re-used and must be properly discarded. 
 
To prevent the possible transmission of disease, each pen must be used by one patient only. 
 
It must be remembered that neutral regular insulin precipitates out at a pH of approximately 4.5 to 6.5. 
 
Insulin label must always be checked before each injection to avoid medication errors between insulin 
human and other insulins (see section 4.4). 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 

 

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Handling of the pen 
The patient should be advised to read the instructions for use included in the package leaflet 
carefully before using SoloStar. 
 

 
Schematic diagram of the pen 

 
Important information for use of SoloStar: 
 
• Before each use, a new needle must always be carefully attached and a safety test must be 

performed. A dose should not be selected and/or the injection button should not be pressed 
without a needle attached. Only use needles that are compatible for use with SoloStar. 

• Special caution must be taken to avoid accidental needle injury and transmission of infection. 
• SoloStar must never be used if it is damaged or if the patient is not sure if it is working properly. 
• The patient must always have a spare SoloStar available in case the SoloStar is lost or damaged. 
 
Storage instructions  
 
Please check section 6.4 for instructions on how to store SoloStar. 
 
If SoloStar is in cool storage, it should be taken out 1 to 2 hours before injection to allow it to warm 
up. Cold insulin is more painful to inject. 
 
The used SoloStar must be discarded as required by your local authorities. 
 
Maintenance 
 
SoloStar has to be protected from dust and dirt. 
 
The outside of the SoloStar can be cleaned by wiping it with a damp cloth. 
 
The pen must not be soaked, washed or lubricated as this may damage it. 
 
SoloStar is designed to work accurately and safely. It should be handled with care. The patient should 
avoid situations where SoloStar may be damaged. If the patient is concerned that the SoloStar may be 
damaged, he must use a new one. 
 
Step 1. Check the insulin 
 
The label on the pen should be checked to make sure it contains the correct insulin. Insulin Human 
Winthrop SoloStar is white with a colour on the injection button. The injection button colour will vary 
based on the formulation of Insulin Human Winthrop insulin used. 
 
After removing the pen cap, the appearance of the insulin should also be checked: 
The insulin solution (Insulin Human Winthrop Rapid) must be clear, colourless, with no solid particles 
visible, and must have a water-like consistency. Do not use this SoloStar if insulin is cloudy, coloured 
or has particles. 
 
Step 2. Attach the needle 
 
Only needles that are compatible for use with SoloStar should be used. 
 

 

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A new sterile needle will be always used for each injection. After removing the cap, the needle should 
be carefully attached straight onto the pen. 
 
Step 3. Perform a safety test  
 
Prior to each injection, a safety test has to be performed to ensure that pen and needle work properly 
and to remove air bubbles. 
 
A dose of 2 units has to be selected. 
The outer and inner needle caps should be removed. 
 
While holding the pen with the needle pointing upwards, the insulin reservoir should be tapped gently 
with the finger so that any air bubbles rise up towards the needle. 
 
Then the injection button should be pressed in completely. 
 
If insulin has been expelled through the needle tip, then the pen and the needle are working properly. 
If no insulin appears at the needle tip, step 3 should be repeated until insulin appears at the needle tip. 
 
Step 4. Select the dose 
 
The dose can be set in steps of 1 unit, from a minimum of 1 unit to a maximum of 80 units. If a dose 
greater than 80 units is required, it should be given as two or more injections. 
 
The dose window must show “0” following the safety test. The dose can then be selected. 
 
Step 5. Inject the dose 
 
The patient should be informed on the injection technique by his health care professional. 
The needle should be inserted into the skin. 
The injection button should be pressed in completely. Then the injection button should be held down 
10 seconds before withdrawing the needle. This ensures that the full dose of insulin has been injected. 
 
Step 6. Remove and discard the needle 
 
The needle should always be removed after each injection and discarded. This helps prevent 
contamination and/or infection, entry of air into the insulin reservoir and leakage of insulin. Needles 
mut not be re-used. 
 
Special caution must be taken when removing and disposing of the needle. Recommended safety 
measures for removal and disposal of needles must be followed (e.g. a one handed capping technique) 
in order to reduce the risk of accidental needle injury and transmission of infectious diseases. 
 
The pen cap should be replaced on the pen. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Sanofi-Aventis Deutschland GmbH, D-65926 Frankfurt am Main, Germany 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/06/368/113 
EU/1/06/368/114 
EU/1/06/368/115 
EU/1/06/368/116 

 

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EU/1/06/368/117 
EU/1/06/368/118 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 17 January 2007 
Date of latest renewal: 17 January 2012 
 
 
10. DATE OF REVISION OF THE TEXT 
 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu 

 

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1. NAME OF THE MEDICINAL PRODUCT 
 
Insulin Human Winthrop Basal 100 IU/ml suspension for injection in a vial 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each ml contains 100 IU insulin human (equivalent to 3.5 mg).  
Each vial contains 5 ml of suspension for injection, equivalent to 500 IU insulin, or 10 ml of 
suspension for injection, equivalent to 1000 IU insulin. One IU (International Unit) corresponds to 
0.035 mg of anhydrous human insulin. 
 
Insulin Human Winthrop Basal is an isophane insulin suspension. 
 
Human insulin is produced by recombinant DNA technology in Escherichia coli. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Suspension for injection in a vial. 
 
After resuspension, milky-white suspension. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Diabetes mellitus where treatment with insulin is required. 
 
4.2 Posology and method of administration 
 
Posology 
The desired blood glucose levels, the insulin preparations to be used and the insulin dose regimen 
(doses and timings) must be determined individually and adjusted to suit the patient’s diet, physical 
activity and life-style. 
 
Daily doses and timing of administration 
There are no fixed rules for insulin dose regimen. However, the average insulin requirement is often 
0.5 to 1.0 IU per kg body weight per day. The basal metabolic requirement is 40% to 60% of the total 
daily requirement. Insulin Human Winthrop Basal is injected subcutaneously 45 to 60 minutes before 
a meal. 
 
Secondary dose adjustment 
Improved metabolic control may result in increased insulin sensitivity, leading to a reduced insulin 
requirement. Dose adjustment may also be required, for example, if 
- the patient's weight changes, 
- the patient's life-style changes, 
- other circumstances arise that may promote an increased susceptibility to hypo- or 

hyperglycaemia (see section 4.4). 
 
Special populations 
Elderly population (≧65 years old) 
In the elderly, progressive deterioration of renal function may lead to a steady decrease in insulin 
requirements. 

 

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Renal impairment 
In patients with renal impairment, insulin requirements may be diminished due to reduced insulin 
metabolism. 
 
Hepatic impairment 
In patients with severe hepatic impairment, insulin requirements may be diminished due to reduced 
capacity for gluconeogenesis and reduced insulin metabolism. 
 
Method of administration 
Insulin Human Winthrop Basal must not be administered intravenously and must not be used in 
infusion pumps or external or implanted insulin pumps. 
 
Only injection syringes designed for this strength of insulin (100 IU per ml) are to be used. The 
injection syringes must not contain any other medicinal product or residue (e.g. traces of heparin). 
 
Insulin Human Winthrop Basal is administered subcutaneously. Insulin Human Winthrop Basal must 
never be injected intravenously. 
 
Insulin absorption and hence the blood-glucose-lowering effect of a dose may vary from one injection 
area to another (e.g. the abdominal wall compared with the thigh). Injection sites within an injection 
area must be rotated from one injection to the next. 
 
For further details on handling, see section 6.6. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
 
4.4 Special warnings and precautions for use 
 
Patients hypersensitive to Insulin Human Winthrop Basal for whom no better tolerated preparation is 
available must only continue treatment under close medical supervision and – where necessary – in 
conjunction with anti-allergic treatment. 
 
In patients with an allergy to animal insulin intradermal skin testing is recommended prior to a 
transfer to Insulin Human Winthrop Basal, since they may experience immunological cross-reactions. 
 
In case of insufficient glucose control or a tendency to hyper- or hypoglycaemic episodes, the patient's 
adherence to the prescribed treatment regimen, injection sites and proper injection technique and all 
other relevant factors must be reviewed before dose adjustment is considered. 
 
Transfer to Insulin Human Winthrop Basal 
Transferring a patient to another type or brand of insulin should be done under strict medical 
supervision. Changes in strength, brand (manufacturer), type (regular, NPH, lente, long-acting, etc.), 
origin (animal, human, human insulin analogue) and/or method of manufacture may result in the need 
for a change in dosage. 
The need to adjust (e.g. reduce) the dose may become evident immediately after transfer. 
Alternatively, it may emerge gradually over a period of several weeks. 
 
Following transfer from an animal insulin to human insulin, dose regimen reduction may be required 
in particular in patients who 
- were previously already controlled on rather low blood glucose levels, 
- have a tendency to hypoglycaemia, 
- previously required high insulin doses due to the presence of insulin antibodies. 
 

 

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Close metabolic monitoring is recommended during the transition and in the initial weeks thereafter. In 
patients who require high insulin doses because of the presence of insulin antibodies, transfer under 
medical supervision in a hospital or similar setting must be considered. 
 
Hypoglycaemia 
Hypoglycaemia may occur if the insulin dose is too high in relation to the insulin requirement. 
 
Particular caution should be exercised, and intensified blood glucose monitoring is advisable in 
patients in whom hypoglycaemic episodes might be of particular clinical relevance, such as in patients 
with significant stenoses of the coronary arteries or of the blood vessels supplying the brain (risk of 
cardiac or cerebral complications of hypoglycaemia) as well as in patients with proliferative 
retinopathy, particularly if not treated with photocoagulation (risk of transient amaurosis following 
hypoglycaemia). 
 
Patients should be aware of circumstances where warning symptoms of hypoglycaemia are 
diminished. The warning symptoms of hypoglycaemia may be changed, be less pronounced or be 
absent in certain risk groups. These include patients: 
- in whom glycaemic control is markedly improved, 
- in whom hypoglycaemia develops gradually, 
- who are elderly,  
- after transfer from animal insulin to human insulin, 
- in whom an autonomic neuropathy is present, 
- with a long history of diabetes, 
- suffering from a psychiatric illness, 
- receiving concurrent treatment with certain other medicinal products (see section 4.5). 
Such situations may result in severe hypoglycaemia (and possibly loss of consciousness) prior to the 
patient's awareness of hypoglycaemia. 
 
If normal or decreased values for glycated haemoglobin are noted, the possibility of recurrent, 
unrecognised (especially nocturnal) episodes of hypoglycaemia must be considered. 
 
Adherence of the patient to the dose regimen and dietary regimen, correct insulin administration and 
awareness of hypoglycaemia symptoms are essential to reduce the risk of hypoglycaemia. Factors 
increasing the susceptibility to hypoglycaemia require particularly close monitoring and may 
necessitate dose adjustment. These include: 
- change in the injection area, 
- improved insulin sensitivity (e.g. by removal of stress factors), 
- unaccustomed, increased or prolonged physical activity, 
- intercurrent illness (e.g. vomiting, diarrhoea), 
- inadequate food intake, 
- missed meals, 
- alcohol consumption, 
- certain uncompensated endocrine disorders (e.g. in hypothyroidism and in anterior pituitary or 

adrenocortical insufficiency), 
- concomitant treatment with certain other medicinal products. 
 
Intercurrent illness 
Intercurrent illness requires intensified metabolic monitoring. In many cases, urine tests for ketones 
are indicated, and often it is necessary to adjust the insulin dose. The insulin requirement is often 
increased. Patients with type 1 diabetes must continue to consume at least a small amount of 
carbohydrates on a regular basis, even if they are able to eat only little or no food, or are vomiting etc. 
and they must never omit insulin entirely. 
 
Medication errors 
Medication errors have been reported in which other Insulin Human Winthrop formulations or other 
insulins have been accidentally administered. Insulin label must always be checked before each 
injection to avoid medication errors between insulin human and other insulins. 

 

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Combination of Insulin Human Winthrop with pioglitazone 
Cases of cardiac failure have been reported when pioglitazone was used in combination with insulin, 
especially in patients with risk factors for development of cardiac heart failure. This should be kept in 
mind if treatment with the combination of pioglitazone and Insulin Human Winthrop is considered. If 
the combination is used, patients should be observed for signs and symptoms of heart failure, weight 
gain and oedema. Pioglitazone should be discontinued if any deterioration in cardiac symptoms 
occurs.  
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
A number of substances affect glucose metabolism and may require dose adjustment of human insulin. 
 
Substances that may enhance the blood-glucose-lowering effect and increase susceptibility to 
hypoglycaemia include oral antidiabetic medicinal products, angiotensin converting enzyme (ACE) 
inhibitors, disopyramide, fibrates, fluoxetine, monoamine oxidase (MAO) inhibitors, pentoxifylline, 
propoxyphene, salicylates and sulphonamide antibiotics. 
 
Substances that may reduce the blood-glucose-lowering effect include corticosteroids, danazol, 
diazoxide, diuretics, glucagon, isoniazid, oestrogens and progestogens (e.g. in oral contraceptives), 
phenothiazine derivatives, somatropin, sympathomimetic medicinal products (e.g. epinephrine 
[adrenaline], salbutamol, terbutaline), thyroid hormones, protease inhibitors and atypical antipsychotic 
medicinal products (e.g. olanzapine and clozapine). 
 
Beta-blockers, clonidine, lithium salts or alcohol may either potentiate or weaken the 
blood-glucose-lowering effect of insulin. Pentamidine may cause hypoglycaemia which may 
sometimes be followed by hyperglycaemia. 
 
In addition, under the influence of sympatholytic medicinal products such as beta-blockers, clonidine, 
guanethidine and reserpine, the signs of adrenergic counter-regulation may be reduced or absent. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
For insulin human, no clinical data on exposed pregnancies from controlled clinical studies are 
available. Insulin does cross the placental barrier, although not in clinically significant amount. A 
limited amount of data on pregnant women (less than 300 pregnancy outcomes reported) exposed to 
marketed insulin human indicates no safety issues in use of insulin human in pregnancy. Caution 
should be exercised when prescribing to pregnant women. 
 
It is essential for patients with pre-existing or gestational diabetes to maintain good metabolic control 
throughout pregnancy. Insulin requirements may decrease during the first trimester and generally 
increase during the second and third trimesters. Immediately after delivery, insulin requirements 
decline rapidly (increased risk of hypoglycaemia). Careful monitoring of glucose control is essential. 
 
Breast-feeding 
No effects on the suckling child are anticipated. Insulin Human Winthrop Basal can be used during 
breast-feeding. Breast-feeding women may require adjustments in insulin dose and diet. 
 
Fertility 
No clinical or animal data with insulin human on male or female fertility are available. 
 

 

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4.7 Effects on ability to drive and use machines 
 
The patient's ability to concentrate and react may be impaired as a result of hypoglycaemia or 
hyperglycaemia or, for example, as a result of visual impairment. This may constitute a risk in 
situations where these abilities are of special importance (e.g. driving a car or using machines). 
 
Patients should be advised to take precautions to avoid hypoglycaemia whilst driving. This is 
particularly important in those who have reduced or absent awareness of the warning symptoms of 
hypoglycaemia or have frequent episodes of hypoglycaemia. It should be considered whether it is 
advisable to drive or use machines in these circumstances. 
 
4.8 Undesirable effects 
 
Summary of the safety profile  
Hypoglycaemia, in general the most frequent adverse reaction of insulin therapy, may occur if the 
insulin dose is too high in relation to the insulin requirement. In clinical studies and during marketed 
use, the frequency varies with patient population and dose regimens. Therefore, no specific frequency 
can be presented. 
 
Tabulated list of adverse reactions 
The following related adverse reactions from clinical investigations are listed below by system organ 
class and in order of decreasing incidence: very common (≥1/10); common (≥1/100 to <1/10); 
uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000), not known 
(cannot be estimated from the available data). 
 
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. 
 
MedDRA system 
organ classes 

Common Uncommon Not known 

Immune system 
disorders 

 Shock Immediate type 
allergic reactions 
(hypotension, 
angioneurotic oedema, 
bronchospasm, 
generalised skin 
reactions); 
Anti-insulin antibodies 

Metabolism and 
nutrition disorders 

Oedema  Hypoglycaemia; 
Sodium retention 

Eye disorders   Proliferative 
retinopathy; 
Diabetic retinopathy; 
Visual impairment 

Skin and subcutaneous 
tissue disorders 

  Lipodystrophy 

General disorders and 
administration site 
conditions 

Injection site reactions Injection site urticaria Injection site 
inflammation;  
Injection site pain; 
Injection site pruritus; 
Injection site erythema; 
Injection site swelling 

 

 

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Description of selected adverse reactions 
Immune system disorders 
Immediate type allergic reactions to insulin or to the excipients may be life-threatening. 
 
Insulin administration may cause anti-insulin antibodies to form. In rare cases, the presence of such 
anti-insulin antibodies may necessitate adjustment of the insulin dose in order to correct a tendency to 
hyper- or hypoglycaemia. 
 
Metabolism and nutrition disorders 
Severe hypoglycaemic attacks, especially if recurrent, may lead to neurological damage. 
Prolonged or severe hypoglycaemic episodes may be life-threatening. 
 
In many patients, the signs and symptoms of neuroglycopenia are preceded by signs of adrenergic 
counter-regulation. Generally, the greater and more rapid the decline in blood glucose, the more 
marked is the phenomenon of counter-regulation and its symptoms. 
Insulin may cause sodium retention and oedema, particularly if previously poor metabolic control is 
improved by intensified insulin therapy. 
 
Eyes disorders 
A marked change in glycaemic control may cause temporary visual impairment, due to temporary 
alteration in the turgidity and refractive index of the lens. 
 
Long-term improved glycaemic control decreases the risk of progression of diabetic retinopathy. 
However, intensification of insulin therapy with abrupt improvement in glycaemic control may be 
associated with temporary worsening of diabetic retinopathy. 
 
Skin and subcutaneous tissue disorders 
Lipodystrophy may occur at the injection site and delay local insulin absorption. Continuous rotation 
of the injection site within the given injection area may help to reduce or prevent these reactions. 
 
General disorders and administration site conditions 
Most minor reactions to insulins at the injection site usually resolve in a few days to a few weeks. 
 
4.9 Overdose 
 
Symptoms 
Insulin overdose may lead to severe and sometimes long-term and life-threatening hypoglycaemia. 
 
Management 
Mild episodes of hypoglycaemia can usually be treated with oral carbohydrates. Adjustments in dose 
regimen of the medicinal product, meal patterns, or physical activity may be needed. 
 
More severe episodes with coma, seizure, or neurologic impairment may be treated with 
intramuscular/subcutaneous glucagon or concentrated intravenous glucose. Sustained carbohydrate 
intake and observation may be necessary because hypoglycaemia may recur after apparent clinical 
recovery. 
 
 

 

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5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Drugs used in diabetes, insulins and analogues for injection, 
intermediate-acting, ATC Code: A10AC01. 
 
Mechanism of action 
Insulin 
- lowers blood glucose and promotes anabolic effects as well as decreasing catabolic effects, 
- increases the transport of glucose into cells as well as the formation of glycogen in the muscles 

and the liver, and improves pyruvate utilisation. It inhibits glycogenolysis and gluconeogenesis, 
- increases lipogenesis in the liver and adipose tissue and inhibits lipolysis, 
- promotes the uptake of amino acids into cells and promotes protein synthesis, 
- enhances the uptake of potassium into cells. 
 
Pharmacodynamic effects 
Insulin Human Winthrop Basal (an isophane insulin suspension) is an insulin with gradual onset and 
long duration of action. Following subcutaneous injection, onset of action is within 60 minutes, the 
phase of maximum action is between 3 and 4 hours after injection and the duration of action is 11 to 
20 hours. 
 
5.2 Pharmacokinetic properties 
 
In healthy subjects, the serum half-life of insulin is approximately 4 to 6 minutes. It is longer in 
patients with severe renal insufficiency. However, it must be noted that the pharmacokinetics of 
insulin do not reflect its metabolic action. 
 
5.3 Preclinical safety data 
 
The acute toxicity was studied following subcutaneous administration in rats. No evidence of toxic 
effects was found. Studies of pharmacodynamic effects following subcutaneous administration in 
rabbits and dogs revealed the expected hypoglycaemic reactions. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Protamine sulphate, 
metacresol, 
phenol, 
zinc chloride, 
sodium dihydrogen phosphate dihydrate, 
glycerol, 
sodium hydroxide, 
hydrochloric acid (for pH adjustment), 
water for injections. 
 
6.2 Incompatibilities 
 
This medicinal product must not be mixed with other medicinal products except those mentioned in 
section 6.6. 
 
Insulin Human Winthrop Basal must not be mixed with solutions containing reducing substances such 
as thioles and sulphites.  
 

 

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Mixing of insulins 
Insulin Human Winthrop Basal must not be mixed with insulin human formulations designed 
specifically for use in insulin pumps.  
Insulin Human Winthrop Basal must also not be mixed with insulins of animal origin or with insulin 
analogues. 
Insulins of different concentration (e.g. 100 IU per ml and 40 IU per ml) must not be mixed. 
 
Care must be taken to ensure that no alcohol or other disinfectants enter the insulin suspension. 
 
6.3 Shelf life 
 
2 years. 
 
Shelf life after first use of the vial 
The product may be stored for a maximum of 4 weeks not above 25°C and away from direct heat or 
direct light. 
Keep the vial in the outer carton in order to protect from light. 
It is recommended that the date of the first use be noted on the label. 
 
6.4 Special precautions for storage 
 
Unopened vials 
Store in a refrigerator (2°C - 8°C). 
Do not freeze. 
Do not put Insulin Human Winthrop Basal next to the freezer compartment or a freezer pack. 
Keep the vial in the outer carton in order to protect from light. 
 
Opened vials 
For storage conditions after first opening of the medicinal product, see section 6.3. 
 
6.5 Nature and contents of container 
 
5 ml suspension in a vial and 10 ml suspension in a vial (type 1 colourless glass) with a flanged cap 
(aluminium), a stopper (chlorobutyl rubber (type 1)) and a tear-off cap (polypropylene). 
Packs of 1 and 5 vials are available. 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal and other handling 
 
Before withdrawing insulin from the vial for the first time, remove the plastic protective cap. 
 
Immediately before withdrawal from the vial into the injection syringe, the insulin must be 
resuspended. This is best done by rolling the vial at an oblique angle between the palms of the hands. 
Do not shake the vial vigorously as this may lead to changes in the suspension (giving the vial a 
frosted appearance; see below) and cause frothing. Froth may interfere with the correct measurement 
of the dose. 
 
After resuspension, the fluid must have a uniformly milky appearance. Insulin Human Winthrop Basal 
must not be used if this cannot be achieved, i.e. if the suspension remains clear, for example, or if 
clumps, particles or flocculation appear in the insulin or stick to the wall or bottom of the vial. These 
changes sometimes give the vial a frosted appearance. In such cases, a new vial yielding a uniform 
suspension must be used. It is also necessary to change to a new vial if the insulin requirement 
changes substantially. 
 
Insulin Human Winthrop Basal must not be administered intravenously and must not be used in 
infusion pumps or external or implanted insulin pumps. 
 

 

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It must be remembered that insulin protamine crystals dissolve in an acid pH range. 
 
Insulin label must always be checked before each injection to avoid medication errors between insulin 
human and other insulins (see section 4.4). 
 
Mixing of insulins 
Insulin Human Winthrop Basal may be mixed with all insulin human formulations, but not with those 
designed specifically for use in insulin pumps Concerning incompatibility with other insulins, see 
section 6.2. 
 
If two different insulins have to be drawn into one single injection syringe, it is recommended that the 
shorter-acting insulin be drawn first to prevent contamination of the vial by the longer-acting 
preparation. It is advisable to inject immediately after mixing.  
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Sanofi-Aventis Deutschland GmbH, D-65926 Frankfurt am Main, Germany 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/06/368/020 
EU/1/06/368/021 
EU/1/06/368/171 
EU/1/06/368/172 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 17 January 2007 
Date of latest renewal: 17 January 2012 
 
 
10. DATE OF REVISION OF THE TEXT 
 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu 

 

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1. NAME OF THE MEDICINAL PRODUCT 
 
Insulin Human Winthrop Basal 40 IU/ml suspension for injection in a vial 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each ml contains 40 IU insulin human (equivalent to 1.4 mg).  
Each vial contains 10 ml of suspension for injection, equivalent to 400 IU insulin. One IU 
(International Unit) corresponds to 0.035 mg of anhydrous human insulin. 
 
Insulin Human Winthrop Basal is an isophane insulin suspension. 
 
Human insulin is produced by recombinant DNA technology in Escherichia coli. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Suspension for injection in a vial. 
 
After resuspension, milky-white suspension. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Diabetes mellitus where treatment with insulin is required. 
 
4.2 Posology and method of administration 
 
Posology 
The desired blood glucose levels, the insulin preparations to be used and the insulin dose regimen 
(doses and timings) must be determined individually and adjusted to suit the patient’s diet, physical 
activity and life-style. 
 
Daily doses and timing of administration 
There are no fixed rules for insulin dose regimen. However, the average insulin requirement is often 
0.5 to 1.0 IU per kg body weight per day. The basal metabolic requirement is 40% to 60% of the total 
daily requirement. Insulin Human Winthrop Basal is injected subcutaneously 45 to 60 minutes before 
a meal. 
 
Secondary dose adjustment 
Improved metabolic control may result in increased insulin sensitivity, leading to a reduced insulin 
requirement. Dose adjustment may also be required, for example, if 
- the patient's weight changes, 
- the patient's life-style changes, 
- other circumstances arise that may promote an increased susceptibility to hypo- or 

hyperglycaemia (see section 4.4). 
 
Special populations 
Elderly population (≧65 years old) 
In the elderly, progressive deterioration of renal function may lead to a steady decrease in insulin 
requirements. 
 

 

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Renal impairment 
In patients with renal impairment, insulin requirements may be diminished due to reduced insulin 
metabolism. 
 
Hepatic impairment 
In patients with severe hepatic impairment, insulin requirements may be diminished due to reduced 
capacity for gluconeogenesis and reduced insulin metabolism. 
 
Method of administration 
Insulin Human Winthrop Basal must not be administered intravenously and must not be used in 
infusion pumps or external or implanted insulin pumps. 
 
Only injection syringes designed for this strength of insulin (40 IU per ml) are to be used. The 
injection syringes must not contain any other medicinal product or residue (e.g. traces of heparin). 
 
Insulin Human Winthrop Basal is administered subcutaneously. Insulin Human Winthrop Basal must 
never be injected intravenously. 
 
Insulin absorption and hence the blood-glucose-lowering effect of a dose may vary from one injection 
area to another (e.g. the abdominal wall compared with the thigh). Injection sites within an injection 
area must be rotated from one injection to the next. 
 
Fur further details on handling, see section 6.6. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
 
4.4 Special warnings and precautions for use 
 
Patients hypersensitive to Insulin Human Winthrop Basal for whom no better tolerated preparation is 
available must only continue treatment under close medical supervision and – where necessary – in 
conjunction with anti-allergic treatment. 
 
In patients with an allergy to animal insulin intradermal skin testing is recommended prior to a 
transfer to Insulin Human Winthrop Basal, since they may experience immunological cross-reactions. 
 
In case of insufficient glucose control or a tendency to hyper- or hypoglycaemic episodes, the patient's 
adherence to the prescribed treatment regimen, injection sites and proper injection technique and all 
other relevant factors must be reviewed before dose adjustment is considered. 
 
Transfer to Insulin Human Winthrop Basal 
Transferring a patient to another type or brand of insulin should be done under strict medical 
supervision. Changes in strength, brand (manufacturer), type (regular, NPH, lente, long-acting, etc.), 
origin (animal, human, human insulin analogue) and/or method of manufacture may result in the need 
for a change in dosage. 
The need to adjust (e.g. reduce) the dose may become evident immediately after transfer. 
Alternatively, it may emerge gradually over a period of several weeks. 
 
Following transfer from an animal insulin to human insulin, dose regimen reduction may be required 
in particular in patients who 
- were previously already controlled on rather low blood glucose levels, 
- have a tendency to hypoglycaemia, 
- previously required high insulin doses due to the presence of insulin antibodies. 
 

 

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Close metabolic monitoring is recommended during the transition and in the initial weeks thereafter. In 
patients who require high insulin doses because of the presence of insulin antibodies, transfer under 
medical supervision in a hospital or similar setting must be considered. 
 
Hypoglycaemia 
Hypoglycaemia may occur if the insulin dose is too high in relation to the insulin requirement. 
 
Particular caution should be exercised, and intensified blood glucose monitoring is advisable in 
patients in whom hypoglycaemic episodes might be of particular clinical relevance, such as in patients 
with significant stenoses of the coronary arteries or of the blood vessels supplying the brain (risk of 
cardiac or cerebral complications of hypoglycaemia) as well as in patients with proliferative 
retinopathy, particularly if not treated with photocoagulation (risk of transient amaurosis following 
hypoglycaemia). 
 
Patients should be aware of circumstances where warning symptoms of hypoglycaemia are 
diminished. The warning symptoms of hypoglycaemia may be changed, be less pronounced or be 
absent in certain risk groups. These include patients: 
- in whom glycaemic control is markedly improved, 
- in whom hypoglycaemia develops gradually, 
- who are elderly,  
- after transfer from animal insulin to human insulin, 
- in whom an autonomic neuropathy is present, 
- with a long history of diabetes, 
- suffering from a psychiatric illness, 
- receiving concurrent treatment with certain other medicinal products (see section 4.5). 
Such situations may result in severe hypoglycaemia (and possibly loss of consciousness) prior to the 
patient's awareness of hypoglycaemia. 
 
If normal or decreased values for glycated haemoglobin are noted, the possibility of recurrent, 
unrecognised (especially nocturnal) episodes of hypoglycaemia must be considered. 
 
Adherence of the patient to the dose regimen and dietary regimen, correct insulin administration and 
awareness of hypoglycaemia symptoms are essential to reduce the risk of hypoglycaemia. Factors 
increasing the susceptibility to hypoglycaemia require particularly close monitoring and may 
necessitate dose adjustment. These include: 
- change in the injection area, 
- improved insulin sensitivity (e.g. by removal of stress factors), 
- unaccustomed, increased or prolonged physical activity, 
- intercurrent illness (e.g. vomiting, diarrhoea), 
- inadequate food intake, 
- missed meals, 
- alcohol consumption, 
- certain uncompensated endocrine disorders (e.g. in hypothyroidism and in anterior pituitary or 

adrenocortical insufficiency), 
- concomitant treatment with certain other medicinal products. 
 
Intercurrent illness 
Intercurrent illness requires intensified metabolic monitoring. In many cases, urine tests for ketones 
are indicated, and often it is necessary to adjust the insulin dose. The insulin requirement is often 
increased. Patients with type 1 diabetes must continue to consume at least a small amount of 
carbohydrates on a regular basis, even if they are able to eat only little or no food, or are vomiting etc. 
and they must never omit insulin entirely. 
 
Medication errors 
Medication errors have been reported in which other Insulin Human Winthrop formulations or other 
insulins have been accidentally administered. Insulin label must always be checked before each 
injection to avoid medication errors between insulin human and other insulins. 

 

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Combination of Insulin Human Winthrop with pioglitazone 
Cases of cardiac failure have been reported when pioglitazone was used in combination with insulin, 
especially in patients with risk factors for development of cardiac heart failure. This should be kept in 
mind if treatment with the combination of pioglitazone and Insulin Human Winthrop is considered. If 
the combination is used, patients should be observed for signs and symptoms of heart failure, weight 
gain and oedema. Pioglitazone should be discontinued if any deterioration in cardiac symptoms 
occurs.  
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
A number of substances affect glucose metabolism and may require dose adjustment of human insulin. 
 
Substances that may enhance the blood-glucose-lowering effect and increase susceptibility to 
hypoglycaemia include oral antidiabetic medicinal products, angiotensin converting enzyme (ACE) 
inhibitors, disopyramide, fibrates, fluoxetine, monoamine oxidase (MAO) inhibitors, pentoxifylline, 
propoxyphene, salicylates and sulphonamide antibiotics. 
 
Substances that may reduce the blood-glucose-lowering effect include corticosteroids, danazol, 
diazoxide, diuretics, glucagon, isoniazid, oestrogens and progestogens (e.g. in oral contraceptives), 
phenothiazine derivatives, somatropin, sympathomimetic medicinal products (e.g. epinephrine 
[adrenaline], salbutamol, terbutaline), thyroid hormones, protease inhibitors and atypical antipsychotic 
medicinal products (e.g. olanzapine and clozapine). 
 
Beta-blockers, clonidine, lithium salts or alcohol may either potentiate or weaken the 
blood-glucose-lowering effect of insulin. Pentamidine may cause hypoglycaemia which may 
sometimes be followed by hyperglycaemia. 
 
In addition, under the influence of sympatholytic medicinal products such as beta-blockers, clonidine, 
guanethidine and reserpine, the signs of adrenergic counter-regulation may be reduced or absent. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
For insulin human, no clinical data on exposed pregnancies from controlled clinical studies are 
available. Insulin does cross the placental barrier, although not in clinically significant amount. A 
limited amount of data on pregnant women (less than 300 pregnancy outcomes reported) exposed to 
marketed insulin human indicates no safety issues in use of insulin human in pregnancy. Caution 
should be exercised when prescribing to pregnant women. 
 
It is essential for patients with pre-existing or gestational diabetes to maintain good metabolic control 
throughout pregnancy. Insulin requirements may decrease during the first trimester and generally 
increase during the second and third trimesters. Immediately after delivery, insulin requirements 
decline rapidly (increased risk of hypoglycaemia). Careful monitoring of glucose control is essential. 
 
Breast-feeding 
No effects on the suckling child are anticipated. Insulin Human Winthrop Basal can be used during 
breast-feeding. Breast-feeding women may require adjustments in insulin dose and diet. 
 
Fertility 
No clinical or animal data with insulin human on male or female fertility are available. 
 

 

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4.7 Effects on ability to drive and use machines 
 
The patient's ability to concentrate and react may be impaired as a result of hypoglycaemia or 
hyperglycaemia or, for example, as a result of visual impairment. This may constitute a risk in 
situations where these abilities are of special importance (e.g. driving a car or using machines). 
 
Patients should be advised to take precautions to avoid hypoglycaemia whilst driving. This is 
particularly important in those who have reduced or absent awareness of the warning symptoms of 
hypoglycaemia or have frequent episodes of hypoglycaemia. It should be considered whether it is 
advisable to drive or use machines in these circumstances. 
 
4.8 Undesirable effects 
 
Summary of the safety profile  
Hypoglycaemia, in general the most frequent adverse reaction of insulin therapy, may occur if the 
insulin dose is too high in relation to the insulin requirement. In clinical studies and during marketed 
use, the frequency varies with patient population and dose regimens. Therefore, no specific frequency 
can be presented. 
 
Tabulated list of adverse reactions 
The following related adverse reactions from clinical investigations are listed below by system organ 
class and in order of decreasing incidence: very common (≥1/10); common (≥1/100 to <1/10); 
uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000), not known 
(cannot be estimated from the available data). 
 
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. 
 
MedDRA system 
organ classes 

Common Uncommon Not known 

Immune system 
disorders 

 Shock Immediate type 
allergic reactions 
(hypotension, 
angioneurotic oedema, 
bronchospasm, 
generalised skin 
reactions); 
Anti-insulin antibodies 

Metabolism and 
nutrition disorders 

Oedema  Hypoglycaemia; 
Sodium retention 

Eye disorders   Proliferative 
retinopathy; 
Diabetic retinopathy; 
Visual impairment 

Skin and 
subcutaneous tissue 
disorders 

  Lipodystrophy 

General disorders 
and administration 
site conditions 

Injection site reactions Injection site 
urticaria 

Injection site 
inflammation;  
Injection site pain; 
Injection site pruritus; 
Injection site 
erythema;  
Injection site swelling 

 

 

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Description of selected adverse reactions 
Immune system disorders 
Immediate type allergic reactions to insulin or to the excipients may be life-threatening. 
 
Insulin administration may cause anti-insulin antibodies to form. In rare cases, the presence of such 
anti-insulin antibodies may necessitate adjustment of the insulin dose in order to correct a tendency to 
hyper- or hypoglycaemia. 
 
Metabolism and nutrition disorders 
Severe hypoglycaemic attacks, especially if recurrent, may lead to neurological damage. 
Prolonged or severe hypoglycaemic episodes may be life-threatening. 
 
In many patients, the signs and symptoms of neuroglycopenia are preceded by signs of adrenergic 
counter-regulation. Generally, the greater and more rapid the decline in blood glucose, the more 
marked is the phenomenon of counter-regulation and its symptoms. 
Insulin may cause sodium retention and oedema, particularly if previously poor metabolic control is 
improved by intensified insulin therapy. 
 
Eyes disorders 
A marked change in glycaemic control may cause temporary visual impairment, due to temporary 
alteration in the turgidity and refractive index of the lens. 
 
Long-term improved glycaemic control decreases the risk of progression of diabetic retinopathy. 
However, intensification of insulin therapy with abrupt improvement in glycaemic control may be 
associated with temporary worsening of diabetic retinopathy. 
 
Skin and subcutaneous tissue disorders 
Lipodystrophy may occur at the injection site and delay local insulin absorption. Continuous rotation 
of the injection site within the given injection area may help to reduce or prevent these reactions. 
 
General disorders and administration site conditions 
Most minor reactions to insulins at the injection site usually resolve in a few days to a few weeks. 
 
4.9 Overdose 
 
Symptoms 
Insulin overdose may lead to severe and sometimes long-term and life-threatening hypoglycaemia. 
 
Management 
Mild episodes of hypoglycaemia can usually be treated with oral carbohydrates. Adjustments in dose 
regimen of the medicinal product, meal patterns, or physical activity may be needed. 
 
More severe episodes with coma, seizure, or neurologic impairment may be treated with 
intramuscular/subcutaneous glucagon or concentrated intravenous glucose. Sustained carbohydrate 
intake and observation may be necessary because hypoglycaemia may recur after apparent clinical 
recovery. 
 
 

 

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5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Drugs used in diabetes, insulins and analogues for injection, 
intermediate-acting, ATC Code: A10AC01. 
 
Mechanism of action 
Insulin 
- lowers blood glucose and promotes anabolic effects as well as decreasing catabolic effects, 
- increases the transport of glucose into cells as well as the formation of glycogen in the muscles 

and the liver, and improves pyruvate utilisation. It inhibits glycogenolysis and gluconeogenesis, 
- increases lipogenesis in the liver and adipose tissue and inhibits lipolysis, 
- promotes the uptake of amino acids into cells and promotes protein synthesis, 
- enhances the uptake of potassium into cells. 
 
Pharmacodynamic effects 
Insulin Human Winthrop Basal (an isophane insulin suspension) is an insulin with gradual onset and 
long duration of action. Following subcutaneous injection, onset of action is within 60 minutes, the 
phase of maximum action is between 3 and 4 hours after injection and the duration of action is 11 to 
20 hours. 
 
5.2 Pharmacokinetic properties 
 
In healthy subjects, the serum half-life of insulin is approximately 4 to 6 minutes. It is longer in 
patients with severe renal insufficiency. However, it must be noted that the pharmacokinetics of 
insulin do not reflect its metabolic action. 
 
5.3 Preclinical safety data 
 
The acute toxicity was studied following subcutaneous administration in rats. No evidence of toxic 
effects was found. Studies of pharmacodynamic effects following subcutaneous administration in 
rabbits and dogs revealed the expected hypoglycaemic reactions. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Protamine sulphate, 
metacresol, 
phenol, 
zinc chloride, 
sodium dihydrogen phosphate dihydrate, 
glycerol, 
sodium hydroxide, 
hydrochloric acid (for pH adjustment), 
water for injections. 
 
6.2 Incompatibilities 
 
This medicinal product must not be mixed with other medicinal products except those mentioned in 
section 6.6. 
 
Insulin Human Winthrop Basal must not be mixed with solutions containing reducing substances such 
as thioles and sulphites.  
 

 

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Mixing of insulins 
Insulin Human Winthrop Basal must not be mixed with insulin human formulations designed 
specifically for use in insulin pumps.  
Insulin Human Winthrop Basal must also not be mixed with insulins of animal origin or with insulin 
analogues. 
Insulins of different concentration (e.g. 100 IU per ml and 40 IU per ml) must not be mixed. 
 
Care must be taken to ensure that no alcohol or other disinfectants enter the insulin suspension. 
 
6.3 Shelf life 
 
2 years. 
 
Shelf life after first use of the vial 
The product may be stored for a maximum of 4 weeks not above 25°C and away from direct heat or 
direct light. 
Keep the vial in the outer carton in order to protect from light. 
It is recommended that the date of the first use be noted on the label. 
 
6.4 Special precautions for storage 
 
Unopened vials 
Store in a refrigerator (2°C - 8°C). 
Do not freeze. 
Do not put Insulin Human Winthrop Basal next to the freezer compartment or a freezer pack. 
Keep the vial in the outer carton in order to protect from light. 
 
Opened vials 
For storageconditions after first opening of the medicinal product, see section 6.3. 
 
6.5 Nature and contents of container 
 
10 ml suspension in a vial (type 1 colourless glass) with a flanged cap (aluminium), a stopper 
(chlorobutyl rubber (type 1)) and a tear-off cap (polypropylene). 
Packs of 1 and 5 vials are available. 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal and other handling 
 
Before withdrawing insulin from the vial for the first time, remove the plastic protective cap. 
 
Immediately before withdrawal from the vial into the injection syringe, the insulin must be 
resuspended. This is best done by rolling the vial at an oblique angle between the palms of the hands. 
Do not shake the vial vigorously as this may lead to changes in the suspension (giving the vial a 
frosted appearance; see below) and cause frothing. Froth may interfere with the correct measurement 
of the dose. 
 
After resuspension, the fluid must have a uniformly milky appearance. Insulin Human Winthrop Basal 
must not be used if this cannot be achieved, i.e. if the suspension remains clear, for example, or if 
clumps, particles or flocculation appear in the insulin or stick to the wall or bottom of the vial. These 
changes sometimes give the vial a frosted appearance. In such cases, a new vial yielding a uniform 
suspension must be used. It is also necessary to change to a new vial if the insulin requirement 
changes substantially. 
 
Insulin Human Winthrop Basal must not be administered intravenously and must not be used in 
infusion pumps or external or implanted insulin pumps. 
 

 

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It must be remembered that insulin protamine crystals dissolve in an acid pH range. 
 
Insulin label must always be checked before each injection to avoid medication errors between insulin 
human and other insulins (see section 4.4). 
 
Mixing of insulins 
Insulin Human Winthrop Basal may be mixed with all insulin human formulation, but not with those 
designed specifically for use in insulin pumps. Concerning incompatibility with other insulins, see 
section 6.2. 
 
If two different insulins have to be drawn into one single injection syringe, it is recommended that the 
shorter-acting insulin be drawn first to prevent contamination of the vial by the longer-acting 
preparation. It is advisable to inject immediately after mixing.  
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Sanofi-Aventis Deutschland GmbH, D-65926 Frankfurt am Main, Germany 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/06/368/003 
EU/1/06/368/004 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 17 January 2007 
Date of latest renewal: 17 January 2012 
 
 
10. DATE OF REVISION OF THE TEXT 
 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu 

 

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1. NAME OF THE MEDICINAL PRODUCT 
 
Insulin Human Winthrop Basal 100 IU/ml suspension for injection in a cartridge 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each ml contains 100 IU insulin human (equivalent to 3.5 mg).  
Each cartridge contains 3 ml of suspension for injection, equivalent to 300 IU insulin. One IU 
(International Unit) corresponds to 0.035 mg of anhydrous human insulin. 
 
Insulin Human Winthrop Basal is an isophane insulin suspension. 
 
Human insulin is produced by recombinant DNA technology in Escherichia coli. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Suspension for injection in a cartridge. 
 
After resuspension, milky-white suspension. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Diabetes mellitus where treatment with insulin is required. 
 
4.2 Posology and method of administration 
 
Posology 
The desired blood glucose levels, the insulin preparations to be used and the insulin dose regimen 
(doses and timings) must be determined individually and adjusted to suit the patient’s diet, physical 
activity and life-style. 
 
Daily doses and timing of administration 
There are no fixed rules for insulin dose regimen. However, the average insulin requirement is often 
0.5 to 1.0 IU per kg body weight per day. The basal metabolic requirement is 40% to 60% of the total 
daily requirement. Insulin Human Winthrop Basal is injected subcutaneously 45 to 60 minutes before 
a meal. 
 
Secondary dose adjustment 
Improved metabolic control may result in increased insulin sensitivity, leading to a reduced insulin 
requirement. Dose adjustment may also be required, for example, if 
- the patient's weight changes, 
- the patient's life-style changes, 
- other circumstances arise that may promote an increased susceptibility to hypo- or 

hyperglycaemia (see section 4.4). 
 
Special populations 
Elderly population (≧65 years old) 
In the elderly, progressive deterioration of renal function may lead to a steady decrease in insulin 
requirements. 
 

 

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Renal impairment 
In patients with renal impairment, insulin requirements may be diminished due to reduced insulin 
metabolism. 
 
Hepatic impairment 
In patients with severe hepatic impairment, insulin requirements may be diminished due to reduced 
capacity for gluconeogenesis and reduced insulin metabolism. 
 
Method of administration 
Insulin Human Winthrop Basal must not be administered intravenously and must not be used in 
infusion pumps or external or implanted insulin pumps. 
 
Insulin Human Winthrop Basal is administered subcutaneously. Insulin Human Winthrop Basal must 
never be injected intravenously. 
 
Insulin absorption and hence the blood-glucose-lowering effect of a dose may vary from one injection 
area to another (e.g. the abdominal wall compared with the thigh). Injection sites within an injection 
area must be rotated from one injection to the next. 
 
For further details on handling, see section 6.6. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
 
4.4 Special warnings and precautions for use 
 
Patients hypersensitive to Insulin Human Winthrop Basal for whom no better tolerated preparation is 
available must only continue treatment under close medical supervision and – where necessary – in 
conjunction with anti-allergic treatment. 
 
In patients with an allergy to animal insulin intradermal skin testing is recommended prior to a 
transfer to Insulin Human Winthrop Basal, since they may experience immunological cross-reactions. 
 
In case of insufficient glucose control or a tendency to hyper- or hypoglycaemic episodes, the patient's 
adherence to the prescribed treatment regimen, injection sites and proper injection technique and all 
other relevant factors must be reviewed before dose adjustment is considered. 
 
Transfer to Insulin Human Winthrop Basal 
Transferring a patient to another type or brand of insulin should be done under strict medical 
supervision. Changes in strength, brand (manufacturer), type (regular, NPH, lente, long-acting, etc.), 
origin (animal, human, human insulin analogue) and/or method of manufacture may result in the need 
for a change in dosage. 
The need to adjust (e.g. reduce) the dose may become evident immediately after transfer. 
Alternatively, it may emerge gradually over a period of several weeks. 
 
Following transfer from an animal insulin to human insulin, dose regimen reduction may be required 
in particular in patients who 
- were previously already controlled on rather low blood glucose levels, 
- have a tendency to hypoglycaemia, 
- previously required high insulin doses due to the presence of insulin antibodies. 
 
Close metabolic monitoring is recommended during the transition and in the initial weeks thereafter. In 
patients who require high insulin doses because of the presence of insulin antibodies, transfer under 
medical supervision in a hospital or similar setting must be considered. 
 

 

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Hypoglycaemia 
Hypoglycaemia may occur if the insulin dose is too high in relation to the insulin requirement. 
 
Particular caution should be exercised, and intensified blood glucose monitoring is advisable in 
patients in whom hypoglycaemic episodes might be of particular clinical relevance, such as in patients 
with significant stenoses of the coronary arteries or of the blood vessels supplying the brain (risk of 
cardiac or cerebral complications of hypoglycaemia) as well as in patients with proliferative 
retinopathy, particularly if not treated with photocoagulation (risk of transient amaurosis following 
hypoglycaemia). 
 
Patients should be aware of circumstances where warning symptoms of hypoglycaemia are 
diminished. The warning symptoms of hypoglycaemia may be changed, be less pronounced or be 
absent in certain risk groups. These include patients: 
- in whom glycaemic control is markedly improved, 
- in whom hypoglycaemia develops gradually, 
- who are elderly,  
- after transfer from animal insulin to human insulin, 
- in whom an autonomic neuropathy is present, 
- with a long history of diabetes, 
- suffering from a psychiatric illness, 
- receiving concurrent treatment with certain other medicinal products (see section 4.5). 
Such situations may result in severe hypoglycaemia (and possibly loss of consciousness) prior to the 
patient's awareness of hypoglycaemia. 
 
If normal or decreased values for glycated haemoglobin are noted, the possibility of recurrent, 
unrecognised (especially nocturnal) episodes of hypoglycaemia must be considered. 
 
Adherence of the patient to the dose regimen and dietary regimen, correct insulin administration and 
awareness of hypoglycaemia symptoms are essential to reduce the risk of hypoglycaemia. Factors 
increasing the susceptibility to hypoglycaemia require particularly close monitoring and may 
necessitate dose adjustment. These include: 
- change in the injection area, 
- improved insulin sensitivity (e.g. by removal of stress factors), 
- unaccustomed, increased or prolonged physical activity, 
- intercurrent illness (e.g. vomiting, diarrhoea), 
- inadequate food intake, 
- missed meals, 
- alcohol consumption, 
- certain uncompensated endocrine disorders (e.g. in hypothyroidism and in anterior pituitary or 

adrenocortical insufficiency), 
- concomitant treatment with certain other medicinal products. 
 
Intercurrent illness 
Intercurrent illness requires intensified metabolic monitoring. In many cases, urine tests for ketones 
are indicated, and often it is necessary to adjust the insulin dose. The insulin requirement is often 
increased. Patients with type 1 diabetes must continue to consume at least a small amount of 
carbohydrates on a regular basis, even if they are able to eat only little or no food, or are vomiting etc. 
and they must never omit insulin entirely. 
 
Pens to be used with Insulin Human Winthrop Basal cartridges 
The Insulin Human Winthrop Basal cartridges should only be used with the following pens:  
- JuniorSTAR which delivers Insulin Human Winthrop Basal in 0.5 unit dose increments 
- OptiPen, ClikSTAR, Tactipen, Autopen 24 and AllStar which all deliver Insulin Human Winthrop 
Basal in 1 unit dose increments. 
These cartridges should not be used with any other reusable pen as the dosing accuracy has only been 
established with the listed pens.  
Not all of these pens may be marketed in your country. 

 

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Medication errors 
Medication errors have been reported in which other Insulin Human Winthrop formulations or other 
insulins have been accidentally administered. Insulin label must always be checked before each 
injection to avoid medication errors between insulin human and other insulins. 
 
Combination of Insulin Human Winthrop with pioglitazone 
Cases of cardiac failure have been reported when pioglitazone was used in combination with insulin, 
especially in patients with risk factors for development of cardiac heart failure. This should be kept in 
mind if treatment with the combination of pioglitazone and Insulin Human Winthrop is considered. If 
the combination is used, patients should be observed for signs and symptoms of heart failure, weight 
gain and oedema. Pioglitazone should be discontinued if any deterioration in cardiac symptoms 
occurs.  
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
A number of substances affect glucose metabolism and may require dose adjustment of human insulin. 
 
Substances that may enhance the blood-glucose-lowering effect and increase susceptibility to 
hypoglycaemia include oral antidiabetic medicinal products, angiotensin converting enzyme (ACE) 
inhibitors, disopyramide, fibrates, fluoxetine, monoamine oxidase (MAO) inhibitors, pentoxifylline, 
propoxyphene, salicylates and sulphonamide antibiotics. 
 
Substances that may reduce the blood-glucose-lowering effect include corticosteroids, danazol, 
diazoxide, diuretics, glucagon, isoniazid, oestrogens and progestogens (e.g. in oral contraceptives), 
phenothiazine derivatives, somatropin, sympathomimetic medicinal products (e.g. epinephrine 
[adrenaline], salbutamol, terbutaline), thyroid hormones, protease inhibitors and atypical antipsychotic 
medicinal products (e.g. olanzapine and clozapine). 
 
Beta-blockers, clonidine, lithium salts or alcohol may either potentiate or weaken the 
blood-glucose-lowering effect of insulin. Pentamidine may cause hypoglycaemia which may 
sometimes be followed by hyperglycaemia. 
 
In addition, under the influence of sympatholytic medicinal products such as beta-blockers, clonidine, 
guanethidine and reserpine, the signs of adrenergic counter-regulation may be reduced or absent. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
For insulin human, no clinical data on exposed pregnancies from controlled clinical studies are 
available. Insulin does cross the placental barrier, although not in clinically significant amount. A 
limited amount of data on pregnant women (less than 300 pregnancy outcomes reported) exposed to 
marketed insulin human indicates no safety issues in use of insulin human in pregnancy. Caution 
should be exercised when prescribing to pregnant women. 
 
It is essential for patients with pre-existing or gestational diabetes to maintain good metabolic control 
throughout pregnancy. Insulin requirements may decrease during the first trimester and generally 
increase during the second and third trimesters. Immediately after delivery, insulin requirements 
decline rapidly (increased risk of hypoglycaemia). Careful monitoring of glucose control is essential. 
 
Breast-feeding 
No effects on the suckling child are anticipated. Insulin Human Winthrop Basal can be used during 
breast-feeding. Breast-feeding women may require adjustments in insulin dose and diet. 
 
Fertility 
No clinical or animal data with insulin human on male or female fertility are available. 
 

 

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4.7 Effects on ability to drive and use machines 
 
The patient's ability to concentrate and react may be impaired as a result of hypoglycaemia or 
hyperglycaemia or, for example, as a result of visual impairment. This may constitute a risk in 
situations where these abilities are of special importance (e.g. driving a car or using machines). 
 
Patients should be advised to take precautions to avoid hypoglycaemia whilst driving. This is 
particularly important in those who have reduced or absent awareness of the warning symptoms of 
hypoglycaemia or have frequent episodes of hypoglycaemia. It should be considered whether it is 
advisable to drive or use machines in these circumstances. 
 
4.8 Undesirable effects 
 
Summary of the safety profile  
Hypoglycaemia, in general the most frequent adverse reaction of insulin therapy, may occur if the 
insulin dose is too high in relation to the insulin requirement. In clinical studies and during marketed 
use, the frequency varies with patient population and dose regimens. Therefore, no specific frequency 
can be presented. 
 
Tabulated list of adverse reactions 
The following related adverse reactions from clinical investigations are listed below by system organ 
class and in order of decreasing incidence: very common (≥1/10); common (≥1/100 to <1/10); 
uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000), not known 
(cannot be estimated from the available data). 
 
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. 
 
MedDRA system 
organ classes 

Common Uncommon Not known 

Immune system 
disorders 

 Shock Immediate type allergic 
reactions (hypotension, 
angioneurotic oedema, 
bronchospasm, generalised 
skin reactions); 
Anti-insulin antibodies 

Metabolism and 
nutrition disorders 

Oedema  Hypoglycaemia; 
Sodium retention 

Eye disorders   Proliferative retinopathy; 
Diabetic retinopathy; 
Visual impairment 

Skin and 
subcutaneous tissue 
disorders 

  Lipodystrophy 

General disorders 
and administration 
site conditions 

Injection site 
reactions 

Injection site urticaria Injection site inflammation;  
Injection site pain; 
Injection site pruritus; 
Injection site erythema; 
Injection site swelling 

 
Description of selected adverse reactions 
Immune system disorders 
Immediate type allergic reactions to insulin or to the excipients may be life-threatening. 
 
Insulin administration may cause anti-insulin antibodies to form. In rare cases, the presence of such 
anti-insulin antibodies may necessitate adjustment of the insulin dose in order to correct a tendency to 
hyper- or hypoglycaemia. 
 

 

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Metabolism and nutrition disorders 
Severe hypoglycaemic attacks, especially if recurrent, may lead to neurological damage. 
Prolonged or severe hypoglycaemic episodes may be life-threatening. 
 
In many patients, the signs and symptoms of neuroglycopenia are preceded by signs of adrenergic 
counter-regulation. Generally, the greater and more rapid the decline in blood glucose, the more 
marked is the phenomenon of counter-regulation and its symptoms. 
Insulin may cause sodium retention and oedema, particularly if previously poor metabolic control is 
improved by intensified insulin therapy. 
 
Eyes disorders 
A marked change in glycaemic control may cause temporary visual impairment, due to temporary 
alteration in the turgidity and refractive index of the lens. 
 
Long-term improved glycaemic control decreases the risk of progression of diabetic retinopathy. 
However, intensification of insulin therapy with abrupt improvement in glycaemic control may be 
associated with temporary worsening of diabetic retinopathy. 
 
Skin and subcutaneous tissue disorders 
Lipodystrophy may occur at the injection site and delay local insulin absorption. Continuous rotation 
of the injection site within the given injection area may help to reduce or prevent these reactions. 
 
General disorders and administration site conditions 
Most minor reactions to insulins at the injection site usually resolve in a few days to a few weeks. 
 
4.9 Overdose 
 
Symptoms 
Insulin overdose may lead to severe and sometimes long-term and life-threatening hypoglycaemia. 
 
Management 
Mild episodes of hypoglycaemia can usually be treated with oral carbohydrates. Adjustments in dose 
regimen of the medicinal product, meal patterns, or physical activity may be needed. 
 
More severe episodes with coma, seizure, or neurologic impairment may be treated with 
intramuscular/subcutaneous glucagon or concentrated intravenous glucose. Sustained carbohydrate 
intake and observation may be necessary because hypoglycaemia may recur after apparent clinical 
recovery. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Drugs used in diabetes, insulins and analogues for injection, 
intermediate-acting, ATC Code: A10AC01. 
 
Mechanism of action 
Insulin 
- lowers blood glucose and promotes anabolic effects as well as decreasing catabolic effects, 
- increases the transport of glucose into cells as well as the formation of glycogen in the muscles 

and the liver, and improves pyruvate utilisation. It inhibits glycogenolysis and gluconeogenesis, 
- increases lipogenesis in the liver and adipose tissue and inhibits lipolysis, 
- promotes the uptake of amino acids into cells and promotes protein synthesis, 
- enhances the uptake of potassium into cells. 
 

 

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Pharmacodynamic effects 
Insulin Human Winthrop Basal (an isophane insulin suspension) is an insulin with gradual onset and 
long duration of action. Following subcutaneous injection, onset of action is within 60 minutes, the 
phase of maximum action is between 3 and 4 hours after injection and the duration of action is 11 to 
20 hours. 
 
5.2 Pharmacokinetic properties 
 
In healthy subjects, the serum half-life of insulin is approximately 4 to 6 minutes. It is longer in 
patients with severe renal insufficiency. However, it must be noted that the pharmacokinetics of 
insulin do not reflect its metabolic action. 
 
5.3 Preclinical safety data 
 
The acute toxicity was studied following subcutaneous administration in rats. No evidence of toxic 
effects was found. Studies of pharmacodynamic effects following subcutaneous administration in 
rabbits and dogs revealed the expected hypoglycaemic reactions. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Protamine sulphate, 
metacresol, 
phenol, 
zinc chloride, 
sodium dihydrogen phosphate dihydrate, 
glycerol, 
sodium hydroxide, 
hydrochloric acid (for pH adjustment), 
water for injections. 
 
6.2 Incompatibilities 
 
This medicinal product must not be mixed with other medicinal products except those mentioned in 
section 6.6. 
 
Insulin Human Winthrop Basal must not be mixed with solutions containing reducing substances such 
as thioles and sulphites.  
 
Mixing of insulins 
Insulin Human Winthrop Basal must not be mixed with insulin human formulations designed 
specifically for use in insulin pumps.  
Insulin Human Winthrop Basal must also not be mixed with insulins of animal origin or with insulin 
analogues. 
 
Care must be taken to ensure that no alcohol or other disinfectants enter the insulin suspension. 
 
6.3 Shelf life 
 
2 years. 
 
Shelf life after first use of the cartridge 
The cartridge in-use (in the insulin pen) or carried as a spare may be stored for a maximum of 4 weeks 
not above 25°C and away from direct heat or direct light. 
The pen containing a cartridge must not be stored in the refrigerator. 

 

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The pen cap must be put back on the pen after each injection in order to protect from light. 
 
6.4 Special precautions for storage 
 
Unopened cartridges 
Store in a refrigerator (2°C - 8°C). 
Do not freeze. 
Do not put Insulin Human Winthrop Basal next to the freezer compartment or a freezer pack. 
Keep the cartridge in the outer carton in order to protect from light. 
 
In-use cartridges 
For storage conditions after first opening of the medicinal product, see section 6.3. 
 
6.5 Nature and contents of container 
 
3 ml suspension in a cartridge (type 1 colourless glass) with a plunger (bromobutyl rubber (type 1)) 
and a flanged cap (aluminium) with a stopper (bromobutyl or laminate of polyisoprene and 
bromobutyl rubber (type 1)).  
Each cartridge contains 3 balls (stainless steel). 
Packs of 3, 4, 5, 6, 9 or 10 cartridges are available. 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal and other handling 
 
Insulin pen 
The Insulin Human Winthrop Basal cartridges are to be used only in conjunction with the pens: OptiPen, 
ClikSTAR, Autopen 24, Tactipen, AllStar or JuniorSTAR (see section 4.4). Not all of these pens may be 
marketed in your country. 
 
The pen should be used as recommended in the information provided by the device manufacturer.  
 
The manufacturer’s instructions for using the pen must be followed carefully for loading the cartridge, 
attaching the injection needle, and administering the insulin injection. 
 
If the insulin pen is damaged or not working properly (due to mechanical defects) it has to be 
discarded, and a new insulin pen has to be used. 
 
If the pen malfunctions (see instructions for using the pen), the suspension may be drawn from the 
cartridge into an injection syringe (suitable for an insulin with 100 IU/ml) and injected. 
 
Cartridges 
Before insertion into the pen, Insulin Human Winthrop Basal must be kept at room temperature for 1 
to 2 hours and then resuspended to check the contents. This is best done by gently tilting the cartridge 
back and forth (at least ten times). Each cartridge contains three small metal balls to facilitate quick 
and thorough mixing of the contents. 
 
Later on, when the cartridge has been inserted into the pen, the insulin must be resuspended again 
prior to each injection. This is best done by gently tilting the pen back and forth (at least ten times). 
 
After resuspension, the fluid must have a uniformly milky appearance. Insulin Human Winthrop Basal 
must not be used if this cannot be achieved, i.e. if the suspension remains clear, for example, or if 
clumps, particles or flocculation appear in the insulin or stick to the wall or bottom of the cartridge. 
These changes sometimes give the cartridge a frosted appearance. In such cases, a new cartridge 
yielding a uniform suspension must be used. It is also necessary to change to a new cartridge if the 
insulin requirement changes substantially. 
 

 

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Air bubbles must be removed from the cartridge before injection (see instructions for using the pen). 
Empty cartridges must not be refilled. 
 
Insulin Human Winthrop Basal must not be administered intravenously and must not be used in 
infusion pumps or external or implanted insulin pumps. 
 
It must be remembered that insulin protamine crystals dissolve in an acid pH range. 
 
Insulin label must always be checked before each injection to avoid medication errors between insulin 
human and other insulins (see section 4.4). 
 
Mixing of insulins 
Insulin Human Winthrop Basal may be mixed with all insulin human formulations, but not with those 
designed specifically for use in insulin pumps. Concerning incompatibility with other insulins, see 
section 6.2. 
 
Insulin Human Winthrop Basal cartridges are not designed to allow any other insulin to be mixed in 
the cartridge. 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Sanofi-Aventis Deutschland GmbH, D-65926 Frankfurt am Main, Germany 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/06/368/089 
EU/1/06/368/022 
EU/1/06/368/023 
EU/1/06/368/094 
EU/1/06/368/099 
EU/1/06/368/024 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 17 January 2007 
Date of latest renewal: 17 January 2012 
 
 
10. DATE OF REVISION OF THE TEXT 
 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu 

 

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1. NAME OF THE MEDICINAL PRODUCT 
 
Insulin Human Winthrop Basal SoloStar 100 IU/ml suspension for injection in a pre-filled pen. 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each ml contains 100 IU insulin human (equivalent to 3.5 mg).  
Each pen contains 3 ml of suspension for injection, equivalent to 300 IU insulin. One IU (International 
Unit) corresponds to 0.035 mg of anhydrous human insulin. 
 
Insulin Human Winthrop Basal is an isophane insulin suspension. 
 
Human insulin is produced by recombinant DNA technology in Escherichia coli. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Suspension for injection in a pre-filled pen. 
 
After resuspension, milky-white suspension. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Diabetes mellitus where treatment with insulin is required. 
 
4.2 Posology and method of administration 
 
Posology 
The desired blood glucose levels, the insulin preparations to be used and the insulin dose regimen 
(doses and timings) must be determined individually and adjusted to suit the patient’s diet, physical 
activity and life-style. 
 
Daily doses and timing of administration 
There are no fixed rules for insulin dose regimen. However, the average insulin requirement is often 
0.5 to 1.0 IU per kg body weight per day. The basal metabolic requirement is 40% to 60% of the total 
daily requirement. Insulin Human Winthrop Basal is injected subcutaneously 45 to 60 minutes before 
a meal. 
 
SoloStar delivers insulin in doses from 1 to 80 units in steps of 1 unit. Each pen contains multiple 
doses. 
 
Secondary dose adjustment 
Improved metabolic control may result in increased insulin sensitivity, leading to a reduced insulin 
requirement. Dose adjustment may also be required, for example, if 
- the patient's weight changes, 
- the patient's life-style changes, 
- other circumstances arise that may promote an increased susceptibility to hypo- or 

hyperglycaemia (see section 4.4). 
 

 

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Special populations 
Elderly population (≧65 years old) 
In the elderly, progressive deterioration of renal function may lead to a steady decrease in insulin 
requirements. 
 
Renal impairment 
In patients with renal impairment, insulin requirements may be diminished due to reduced insulin 
metabolism. 
 
Hepatic impairment 
In patients with severe hepatic impairment, insulin requirements may be diminished due to reduced 
capacity for gluconeogenesis and reduced insulin metabolism. 
 
Method of administration 
Insulin Human Winthrop Basal is administered subcutaneously. Insulin Human Winthrop Basal must 
never be injected intravenously. 
 
Insulin absorption and hence the blood-glucose-lowering effect of a dose may vary from one injection 
area to another (e.g. the abdominal wall compared with the thigh). Injection sites within an injection 
area must be rotated from one injection to the next. 
 
Before using SoloStar, the Instructions for Use included in the Package Leaflet must be read carefully. 
 
For further details on handling, see section 6.6. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
 
4.4 Special warnings and precautions for use 
 
Patients hypersensitive to Insulin Human Winthrop Basal for whom no better tolerated preparation is 
available must only continue treatment under close medical supervision and – where necessary – in 
conjunction with anti-allergic treatment. 
 
In patients with an allergy to animal insulin intradermal skin testing is recommended prior to a 
transfer to Insulin Human Winthrop Basal, since they may experience immunological cross-reactions. 
 
In case of insufficient glucose control or a tendency to hyper- or hypoglycaemic episodes, the patient's 
adherence to the prescribed treatment regimen, injection sites and proper injection technique and all 
other relevant factors must be reviewed before dose adjustment is considered. 
 
Transfer to Insulin Human Winthrop Basal 
Transferring a patient to another type or brand of insulin should be done under strict medical 
supervision. Changes in strength, brand (manufacturer), type (regular, NPH, lente, long-acting, etc.), 
origin (animal, human, human insulin analogue) and/or method of manufacture may result in the need 
for a change in dosage. 
The need to adjust (e.g. reduce) the dose may become evident immediately after transfer. 
Alternatively, it may emerge gradually over a period of several weeks. 
 
Following transfer from an animal insulin to human insulin, dose regimen reduction may be required 
in particular in patients who 
- were previously already controlled on rather low blood glucose levels, 
- have a tendency to hypoglycaemia, 
- previously required high insulin doses due to the presence of insulin antibodies. 
 

 

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Close metabolic monitoring is recommended during the transition and in the initial weeks thereafter. In 
patients who require high insulin doses because of the presence of insulin antibodies, transfer under 
medical supervision in a hospital or similar setting must be considered. 
 
Hypoglycaemia 
Hypoglycaemia may occur if the insulin dose is too high in relation to the insulin requirement. 
 
Particular caution should be exercised, and intensified blood glucose monitoring is advisable in 
patients in whom hypoglycaemic episodes might be of particular clinical relevance, such as in patients 
with significant stenoses of the coronary arteries or of the blood vessels supplying the brain (risk of 
cardiac or cerebral complications of hypoglycaemia) as well as in patients with proliferative 
retinopathy, particularly if not treated with photocoagulation (risk of transient amaurosis following 
hypoglycaemia). 
 
Patients should be aware of circumstances where warning symptoms of hypoglycaemia are 
diminished. The warning symptoms of hypoglycaemia may be changed, be less pronounced or be 
absent in certain risk groups. These include patients: 
- in whom glycaemic control is markedly improved, 
- in whom hypoglycaemia develops gradually, 
- who are elderly,  
- after transfer from animal insulin to human insulin, 
- in whom an autonomic neuropathy is present, 
- with a long history of diabetes, 
- suffering from a psychiatric illness, 
- receiving concurrent treatment with certain other medicinal products (see section 4.5). 
Such situations may result in severe hypoglycaemia (and possibly loss of consciousness) prior to the 
patient's awareness of hypoglycaemia. 
 
If normal or decreased values for glycated haemoglobin are noted, the possibility of recurrent, 
unrecognised (especially nocturnal) episodes of hypoglycaemia must be considered. 
 
Adherence of the patient to the dose regimen and dietary regimen, correct insulin administration and 
awareness of hypoglycaemia symptoms are essential to reduce the risk of hypoglycaemia. Factors 
increasing the susceptibility to hypoglycaemia require particularly close monitoring and may 
necessitate dose adjustment. These include: 
- change in the injection area, 
- improved insulin sensitivity (e.g. by removal of stress factors), 
- unaccustomed, increased or prolonged physical activity, 
- intercurrent illness (e.g. vomiting, diarrhoea), 
- inadequate food intake, 
- missed meals, 
- alcohol consumption, 
- certain uncompensated endocrine disorders (e.g. in hypothyroidism and in anterior pituitary or 

adrenocortical insufficiency), 
- concomitant treatment with certain other medicinal products. 
 
Intercurrent illness 
Intercurrent illness requires intensified metabolic monitoring. In many cases, urine tests for ketones 
are indicated, and often it is necessary to adjust the insulin dose. The insulin requirement is often 
increased. Patients with type 1 diabetes must continue to consume at least a small amount of 
carbohydrates on a regular basis, even if they are able to eat only little or no food, or are vomiting etc. 
and they must never omit insulin entirely. 
 
Handling of the pen 
Before using SoloStar, the Instructions for Use included in the Package Leaflet must be read carefully. 
SoloStar has to be used as recommended in these Instructions for Use (see section 6.6). 
 

 

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Medication errors 
Medication errors have been reported in which other Insulin Human Winthrop formulations or other 
insulins have been accidentally administered. Insulin label must always be checked before each 
injection to avoid medication errors between insulin human and other insulins. 
 
Combination of Insulin Human Winthrop with pioglitazone 
Cases of cardiac failure have been reported when pioglitazone was used in combination with insulin, 
especially in patients with risk factors for development of cardiac heart failure. This should be kept in 
mind if treatment with the combination of pioglitazone and Insulin Human Winthrop is considered. If 
the combination is used, patients should be observed for signs and symptoms of heart failure, weight 
gain and oedema. Pioglitazone should be discontinued if any deterioration in cardiac symptoms 
occurs.  
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
A number of substances affect glucose metabolism and may require dose adjustment of human insulin. 
 
Substances that may enhance the blood-glucose-lowering effect and increase susceptibility to 
hypoglycaemia include oral antidiabetic medicinal products, angiotensin converting enzyme (ACE) 
inhibitors, disopyramide, fibrates, fluoxetine, monoamine oxidase (MAO) inhibitors, pentoxifylline, 
propoxyphene, salicylates and sulphonamide antibiotics. 
 
Substances that may reduce the blood-glucose-lowering effect include corticosteroids, danazol, 
diazoxide, diuretics, glucagon, isoniazid, oestrogens and progestogens (e.g. in oral contraceptives), 
phenothiazine derivatives, somatropin, sympathomimetic medicinal products (e.g. epinephrine 
[adrenaline], salbutamol, terbutaline), thyroid hormones, protease inhibitors and atypical antipsychotic 
medicinal products (e.g. olanzapine and clozapine). 
 
Beta-blockers, clonidine, lithium salts or alcohol may either potentiate or weaken the 
blood-glucose-lowering effect of insulin. Pentamidine may cause hypoglycaemia which may 
sometimes be followed by hyperglycaemia. 
 
In addition, under the influence of sympatholytic medicinal products such as beta-blockers, clonidine, 
guanethidine and reserpine, the signs of adrenergic counter-regulation may be reduced or absent. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
For insulin human, no clinical data on exposed pregnancies from controlled clinical studies are 
available. Insulin does cross the placental barrier, although not in clinically significant amount. A 
limited amount of data on pregnant women (less than 300 pregnancy outcomes reported) exposed to 
marketed insulin human indicates no safety issues in use of insulin human in pregnancy. Caution 
should be exercised when prescribing to pregnant women. 
 
It is essential for patients with pre-existing or gestational diabetes to maintain good metabolic control 
throughout pregnancy. Insulin requirements may decrease during the first trimester and generally 
increase during the second and third trimesters. Immediately after delivery, insulin requirements 
decline rapidly (increased risk of hypoglycaemia). Careful monitoring of glucose control is essential. 
 
Breast-feeding 
No effects on the suckling child are anticipated. Insulin Human Winthrop Basal can be used during 
breast-feeding. Breast-feeding women may require adjustments in insulin dose and diet. 
 
Fertility 
No clinical or animal data with insulin human on male or female fertility are available. 
 

 

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4.7 Effects on ability to drive and use machines 
 
The patient's ability to concentrate and react may be impaired as a result of hypoglycaemia or 
hyperglycaemia or, for example, as a result of visual impairment. This may constitute a risk in 
situations where these abilities are of special importance (e.g. driving a car or using machines). 
 
Patients should be advised to take precautions to avoid hypoglycaemia whilst driving. This is 
particularly important in those who have reduced or absent awareness of the warning symptoms of 
hypoglycaemia or have frequent episodes of hypoglycaemia. It should be considered whether it is 
advisable to drive or use machines in these circumstances. 
 
4.8 Undesirable effects 
 
Summary of the safety profile  
Hypoglycaemia, in general the most frequent adverse reaction of insulin therapy, may occur if the 
insulin dose is too high in relation to the insulin requirement. In clinical studies and during marketed 
use, the frequency varies with patient population and dose regimens. Therefore, no specific frequency 
can be presented. 
 
Tabulated list of adverse reactions 
The following related adverse reactions from clinical investigations are listed below by system organ 
class and in order of decreasing incidence: very common (≥1/10); common (≥1/100 to <1/10); 
uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000), not known 
(cannot be estimated from the available data). 
 
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. 
 
MedDRA system 
organ classes 

Common Uncommon Not known 

Immune system 
disorders 

 Shock Immediate type allergic 
reactions (hypotension, 
angioneurotic oedema, 
bronchospasm, 
generalised skin 
reactions); 
Anti-insulin antibodies 

Metabolism and 
nutrition disorders 

Oedema  Hypoglycaemia; 
Sodium retention 

Eye disorders   Proliferative retinopathy; 
Diabetic retinopathy; 
Visual impairment 

Skin and subcutaneous 
tissue disorders 

  Lipodystrophy 

General disorders and 
administration site 
conditions 

Injection site reactions Injection site 
urticaria 

Injection site 
inflammation;  
Injection site pain; 
Injection site pruritus; 
Injection site erythema; 
Injection site swelling 

 
Description of selected adverse reactions 
Immune system disorders 
Immediate type allergic reactions to insulin or to the excipients may be life-threatening. 
 
Insulin administration may cause anti-insulin antibodies to form. In rare cases, the presence of such 
anti-insulin antibodies may necessitate adjustment of the insulin dose in order to correct a tendency to 
hyper- or hypoglycaemia. 

 

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Metabolism and nutrition disorders 
Severe hypoglycaemic attacks, especially if recurrent, may lead to neurological damage. 
Prolonged or severe hypoglycaemic episodes may be life-threatening. 
 
In many patients, the signs and symptoms of neuroglycopenia are preceded by signs of adrenergic 
counter-regulation. Generally, the greater and more rapid the decline in blood glucose, the more 
marked is the phenomenon of counter-regulation and its symptoms. 
Insulin may cause sodium retention and oedema, particularly if previously poor metabolic control is 
improved by intensified insulin therapy. 
 
Eyes disorders 
A marked change in glycaemic control may cause temporary visual impairment, due to temporary 
alteration in the turgidity and refractive index of the lens. 
 
Long-term improved glycaemic control decreases the risk of progression of diabetic retinopathy. 
However, intensification of insulin therapy with abrupt improvement in glycaemic control may be 
associated with temporary worsening of diabetic retinopathy. 
 
Skin and subcutaneous tissue disorders 
Lipodystrophy may occur at the injection site and delay local insulin absorption. Continuous rotation 
of the injection site within the given injection area may help to reduce or prevent these reactions. 
 
General disorders and administration site conditions 
Most minor reactions to insulins at the injection site usually resolve in a few days to a few weeks. 
 
4.9 Overdose 
 
Symptoms 
Insulin overdose may lead to severe and sometimes long-term and life-threatening hypoglycaemia. 
 
Management 
Mild episodes of hypoglycaemia can usually be treated with oral carbohydrates. Adjustments in dose 
regimen of the medicinal product, meal patterns, or physical activity may be needed. 
 
More severe episodes with coma, seizure, or neurologic impairment may be treated with 
intramuscular/subcutaneous glucagon or concentrated intravenous glucose. Sustained carbohydrate 
intake and observation may be necessary because hypoglycaemia may recur after apparent clinical 
recovery. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Drugs used in diabetes, insulins and analogues for injection, 
intermediate-acting, ATC Code: A10AC01. 
 
Mechanism of action 
Insulin 
- lowers blood glucose and promotes anabolic effects as well as decreasing catabolic effects, 
- increases the transport of glucose into cells as well as the formation of glycogen in the muscles 

and the liver, and improves pyruvate utilisation. It inhibits glycogenolysis and gluconeogenesis, 
- increases lipogenesis in the liver and adipose tissue and inhibits lipolysis, 
- promotes the uptake of amino acids into cells and promotes protein synthesis, 
- enhances the uptake of potassium into cells. 
 

 

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Pharmacodynamic effects 
Insulin Human Winthrop Basal (an isophane insulin suspension) is an insulin with gradual onset and 
long duration of action. Following subcutaneous injection, onset of action is within 60 minutes, the 
phase of maximum action is between 3 and 4 hours after injection and the duration of action is 11 to 
20 hours. 
 
5.2 Pharmacokinetic properties 
 
In healthy subjects, the serum half-life of insulin is approximately 4 to 6 minutes. It is longer in 
patients with severe renal insufficiency. However, it must be noted that the pharmacokinetics of 
insulin do not reflect its metabolic action. 
 
5.3 Preclinical safety data 
 
The acute toxicity was studied following subcutaneous administration in rats. No evidence of toxic 
effects was found. Studies of pharmacodynamic effects following subcutaneous administration in 
rabbits and dogs revealed the expected hypoglycaemic reactions. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Protamine sulphate, 
metacresol, 
phenol, 
zinc chloride, 
sodium dihydrogen phosphate dihydrate, 
glycerol, 
sodium hydroxide, 
hydrochloric acid (for pH adjustment), 
water for injections. 
 
6.2 Incompatibilities 
 
This medicinal product must not be mixed with other medicinal products except those mentioned in 
section 6.6. 
 
Insulin Human Winthrop Basal must not be mixed with solutions containing reducing substances such 
as thioles and sulphites.  
 
Mixing of insulins 
Insulin Human Winthrop Basal must not be mixed with any other insulin or with insulin analogues. 
 
Care must be taken to ensure that no alcohol or other disinfectants enter the insulin suspension. 
 
6.3 Shelf life 
 
2 years. 
 
Shelf life after first use of the pen 
The pen in-use or carried as a spare may be stored for a maximum of 4 weeks not above 25°C and 
away from direct heat or direct light. 
Pens in-use must not be stored in the refrigerator. 
The pen cap must be put back on the pen after each injection in order to protect from light. 
 

 

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6.4 Special precautions for storage 
 
Not in-use pens 
Store in a refrigerator (2°C - 8°C). 
Do not freeze. 
Do not put Insulin Human Winthrop Basal next to the freezer compartment or a freezer pack. 
Keep the pre-filled pen in the outer carton in order to protect from light. 
 
In-use pens 
For storage conditions after first opening of the medicinal product, see section 6.3. 
 
6.5 Nature and contents of container 
 
3 ml suspension in a cartridge (type 1 colourless glass) with a plunger (bromobutyl rubber (type 1)) 
and a flanged cap (aluminium) with a stopper (bromobutyl or laminate of polyisoprene and 
bromobutyl rubber (type 1)).  
Each cartridge contains 3 balls (stainless steel). 
The cartridges are sealed in a disposable pen injector. 
Injection needles are not included in the pack. 
Packs of 3, 4, 5, 6, 9 or 10 pens are available. 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal and other handling 
 
Before first use, Insulin Human Winthrop Basal must be kept at room temperature for 1 to 2 hours and 
then resuspended to check the contents. This is best done by gently tilting the pen back and forth (at 
least ten times). Each cartridge contains three small metal balls to facilitate quick and thorough mixing 
of the contents. Later on, the insulin must be resuspended again prior to each injection. 
 
After resuspension, the fluid must have a uniformly milky appearance. Insulin Human Winthrop Basal 
must not be used if this cannot be achieved, i.e. if the suspension remains clear, for example, or if 
clumps, particles or flocculation appear in the insulin or stick to the wall or bottom of the cartridge. 
These changes sometimes give the cartridge a frosted appearance. In such cases, a new pen yielding a 
uniform suspension must be used. It is also necessary to change to a new pen if the insulin 
requirement changes substantially. 
 
Empty pens must never be re-used and must be properly discarded. 
 
To prevent the possible transmission of disease, each pen must be used by one patient only. 
 
It must be remembered that insulin protamine crystals dissolve in an acid pH range. 
 
Insulin label must always be checked before each injection to avoid medication errors between insulin 
human and other insulins (see section 4.4). 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 

 

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Handling of the pen 
The patient should be advised to read the instructions for use included in the package leaflet 
carefully before using SoloStar. 
 

 
Schematic diagram of the pen 

 
Important information for use of SoloStar: 
 
• Before each use, a new needle must always be carefully attached and a safety test must be 

performed. A dose should not be selected and/or the injection button should not be pressed 
without a needle attached. Only use needles that are compatible for use with SoloStar. 

• Special caution must be taken to avoid accidental needle injury and transmission of infection. 
• SoloStar must never be used if it is damaged or if the patient is not sure if it is working properly. 
• The patient must always have a spare SoloStar available in case the SoloStar is lost or damaged. 
 
Storage instructions  
 
Please check section 6.4 for instructions on how to store SoloStar. 
 
If SoloStar is in cool storage, it should be taken out 1 to 2 hours before injection to allow it to warm 
up. Cold insulin is more painful to inject. 
 
The used SoloStar must be discarded as required by your local authorities. 
 
Maintenance 
 
SoloStar has to be protected from dust and dirt. 
 
The outside of the SoloStar can be cleaned by wiping it with a damp cloth. 
 
The pen must not be soaked, washed or lubricated as this may damage it. 
 
SoloStar is designed to work accurately and safely. It should be handled with care. The patient should 
avoid situations where SoloStar may be damaged. If the patient is concerned that the SoloStar may be 
damaged, he must use a new one. 
 
Step 1. Check the insulin 
 
The label on the pen should be checked to make sure it contains the correct insulin. Insulin Human 
Winthrop SoloStar is white with a colour on the injection button. The injection button colour will vary 
based on the formulation of Insulin Human Winthrop insulin used. 
 
After removing the pen cap, the appearance of the insulin should also be checked: 
The insulin suspensions (Insulin Human Winthrop Basal or Insulin Human Winthrop mixtures) should 
be mixed by turning SoloStar up and down at least 10 times to resuspend the insulin. The pen should 
be turned gently to avoid foaming in the cartridge. After mixing, the insulin suspensions must have an 
evenly milky-white appearance. 
 
Step 2. Attach the needle 
 
Only needles that are compatible for use with SoloStar should be used. 

 

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A new sterile needle will be always used for each injection. After removing the cap, the needle should 
be carefully attached straight onto the pen. 
 
Step 3. Perform a safety test  
 
Prior to each injection, a safety test has to be performed to ensure that pen and needle work properly 
and to remove air bubbles. 
 
A dose of 2 units has to be selected. 
The outer and inner needle caps should be removed. 
 
While holding the pen with the needle pointing upwards, the insulin reservoir should be tapped gently 
with the finger so that any air bubbles rise up towards the needle. 
 
Then the injection button should be pressed in completely. 
 
If insulin has been expelled through the needle tip, then the pen and the needle are working properly. 
If no insulin appears at the needle tip, step 3 should be repeated until insulin appears at the needle tip. 
 
Step 4. Select the dose 
 
The dose can be set in steps of 1 unit, from a minimum of 1 unit to a maximum of 80 units. If a dose 
greater than 80 units is required, it should be given as two or more injections. 
 
The dose window must show “0” following the safety test. The dose can then be selected. 
 
Step 5. Inject the dose 
 
The patient should be informed on the injection technique by his health care professional.  
The needle should be inserted into the skin. 
The injection button should be pressed in completely. Then the injection button should be held down 
10 seconds before withdrawing the needle. This ensures that the full dose of insulin has been injected. 
 
Step 6. Remove and discard the needle 
 
The needle should always be removed after each injection and discarded. This helps prevent 
contamination and/or infection, entry of air into the insulin reservoir and leakage of insulin. Needles 
mut not be re-used. 
 
Special caution must be taken when removing and disposing of the needle. Recommended safety 
measures for removal and disposal of needles must be followed (e.g. a one handed capping technique) 
in order to reduce the risk of accidental needle injury and transmission of infectious diseases. 
 
The pen cap should be replaced on the pen. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Sanofi-Aventis Deutschland GmbH, D-65926 Frankfurt am Main, Germany 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/06/368/119 
EU/1/06/368/120 
EU/1/06/368/121 

 

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EU/1/06/368/122 
EU/1/06/368/123 
EU/1/06/368/124 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 17 January 2007 
Date of latest renewal: 17 January 2012 
 
 
10. DATE OF REVISION OF THE TEXT 
 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu 

 

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1. NAME OF THE MEDICINAL PRODUCT 
 

Insulin Human Winthrop Comb 15 100 IU/ml suspension for injection in a vial 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each ml contains 100 IU insulin human (equivalent to 3.5 mg).  
Each vial contains 5 ml of suspension for injection, equivalent to 500 IU insulin. One IU 
(International Unit) corresponds to 0.035 mg of anhydrous human insulin. 
 
Insulin Human Winthrop Comb 15 is a biphasic isophane insulin suspension consisting of 15% 
dissolved insulin and 85% crystalline protamine insulin. 
 
Human insulin is produced by recombinant DNA technology in Escherichia coli. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Suspension for injection in a vial. 
 
After resuspension, milky-white suspension. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Diabetes mellitus where treatment with insulin is required. 
 
4.2 Posology and method of administration 
 
Posology 
The desired blood glucose levels, the insulin preparations to be used and the insulin dose regimen 
(doses and timings) must be determined individually and adjusted to suit the patient’s diet, physical 
activity and life-style. 
 
Daily doses and timing of administration 
There are no fixed rules for insulin dose regimen. However, the average insulin requirement is often 
0.5 to 1.0 IU per kg body weight per day. The basal metabolic requirement is 40% to 60% of the total 
daily requirement. Insulin Human Winthrop Comb 15 is injected subcutaneously 30 to 45 minutes 
before a meal. 
 
Secondary dose adjustment 
Improved metabolic control may result in increased insulin sensitivity, leading to a reduced insulin 
requirement. Dose adjustment may also be required, for example, if 
- the patient's weight changes, 
- the patient's life-style changes, 
- other circumstances arise that may promote an increased susceptibility to hypo- or 

hyperglycaemia (see section 4.4). 
 
Special populations 
Elderly population (≧65 years old) 
In the elderly, progressive deterioration of renal function may lead to a steady decrease in insulin 
requirements. 

 

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Renal impairment 
In patients with renal impairment, insulin requirements may be diminished due to reduced insulin 
metabolism. 
 
Hepatic impairment 
In patients with severe hepatic impairment, insulin requirements may be diminished due to reduced 
capacity for gluconeogenesis and reduced insulin metabolism. 
 
Method of administration 
Insulin Human Winthrop Comb 15 must not be administered intravenously and must not be used in 
infusion pumps or external or implanted insulin pumps. 
 
Only injection syringes designed for this strength of insulin (100 IU per ml) are to be used. The 
injection syringes must not contain any other medicinal product or residue (e.g. traces of heparin). 
 
Insulin Human Winthrop Comb 15 is administered subcutaneously. Insulin Human Winthrop 
Comb 15 must never be injected intravenously. 
 
Insulin absorption and hence the blood–glucose-lowering effect of a dose may vary from one injection 
area to another (e.g. the abdominal wall compared with the thigh). Injection sites within an injection 
area must be rotated from one injection to the next. 
 
For further details on handling, see section 6.6. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
 
4.4 Special warnings and precautions for use 
 
Patients hypersensitive to Insulin Human Winthrop Comb 15 for whom no better tolerated preparation 
is available must only continue treatment under close medical supervision and – where necessary – in 
conjunction with anti-allergic treatment. 
 
In patients with an allergy to animal insulin intradermal skin testing is recommended prior to a 
transfer to Insulin Human Winthrop Comb 15, since they may experience immunological 
cross-reactions. 
 
In case of insufficient glucose control or a tendency to hyper- or hypoglycaemic episodes, the patient's 
adherence to the prescribed treatment regimen, injection sites and proper injection technique and all 
other relevant factors must be reviewed before dose adjustment is considered. 
 
Transfer to Insulin Human Winthrop Comb 15 
Transferring a patient to another type or brand of insulin should be done under strict medical 
supervision. Changes in strength, brand (manufacturer), type (regular, NPH, lente, long-acting, etc.), 
origin (animal, human, human insulin analogue) and/or method of manufacture may result in the need 
for a change in dosage. 
The need to adjust (e.g. reduce) the dose may become evident immediately after transfer. 
Alternatively, it may emerge gradually over a period of several weeks. 
 
Following transfer from an animal insulin to human insulin, dose regimen reduction may be required 
in particular in patients who 
- were previously already controlled on rather low blood glucose levels, 
- have a tendency to hypoglycaemia, 
- previously required high insulin doses due to the presence of insulin antibodies. 
 

 

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Close metabolic monitoring is recommended during the transition and in the initial weeks thereafter. In 
patients who require high insulin doses because of the presence of insulin antibodies, transfer under 
medical supervision in a hospital or similar setting must be considered. 
 
Hypoglycaemia 
Hypoglycaemia may occur if the insulin dose is too high in relation to the insulin requirement. 
 
Particular caution should be exercised, and intensified blood glucose monitoring is advisable in 
patients in whom hypoglycaemic episodes might be of particular clinical relevance, such as in patients 
with significant stenoses of the coronary arteries or of the blood vessels supplying the brain (risk of 
cardiac or cerebral complications of hypoglycaemia) as well as in patients with proliferative 
retinopathy, particularly if not treated with photocoagulation (risk of transient amaurosis following 
hypoglycaemia). 
 
Patients should be aware of circumstances where warning symptoms of hypoglycaemia are 
diminished. The warning symptoms of hypoglycaemia may be changed, be less pronounced or be 
absent in certain risk groups. These include patients: 
- in whom glycaemic control is markedly improved, 
- in whom hypoglycaemia develops gradually, 
- who are elderly,  
- after transfer from animal insulin to human insulin, 
- in whom an autonomic neuropathy is present, 
- with a long history of diabetes, 
- suffering from a psychiatric illness, 
- receiving concurrent treatment with certain other medicinal products (see section 4.5). 
Such situations may result in severe hypoglycaemia (and possibly loss of consciousness) prior to the 
patient's awareness of hypoglycaemia. 
 
If normal or decreased values for glycated haemoglobin are noted, the possibility of recurrent, 
unrecognised (especially nocturnal) episodes of hypoglycaemia must be considered. 
 
Adherence of the patient to the dose regimen and dietary regimen, correct insulin administration and 
awareness of hypoglycaemia symptoms are essential to reduce the risk of hypoglycaemia. Factors 
increasing the susceptibility to hypoglycaemia require particularly close monitoring and may 
necessitate dose adjustment. These include: 
- change in the injection area, 
- improved insulin sensitivity (e.g. by removal of stress factors), 
- unaccustomed, increased or prolonged physical activity, 
- intercurrent illness (e.g. vomiting, diarrhoea), 
- inadequate food intake, 
- missed meals, 
- alcohol consumption, 
- certain uncompensated endocrine disorders (e.g. in hypothyroidism and in anterior pituitary or 

adrenocortical insufficiency), 
- concomitant treatment with certain other medicinal products. 
 
Intercurrent illness 
Intercurrent illness requires intensified metabolic monitoring. In many cases, urine tests for ketones 
are indicated, and often it is necessary to adjust the insulin dose. The insulin requirement is often 
increased. Patients with type 1 diabetes must continue to consume at least a small amount of 
carbohydrates on a regular basis, even if they are able to eat only little or no food, or are vomiting etc. 
and they must never omit insulin entirely. 
 
Medication errors 
Medication errors have been reported in which other Insulin Human Winthrop formulations or other 
insulins have been accidentally administered. Insulin label must always be checked before each 
injection to avoid medication errors between insulin human and other insulins. 

 

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Combination of Insulin Human Winthrop with pioglitazone 
Cases of cardiac failure have been reported when pioglitazone was used in combination with insulin, 
especially in patients with risk factors for development of cardiac heart failure. This should be kept in 
mind if treatment with the combination of pioglitazone and Insulin Human Winthrop is considered. If 
the combination is used, patients should be observed for signs and symptoms of heart failure, weight 
gain and oedema. Pioglitazone should be discontinued if any deterioration in cardiac symptoms 
occurs.  
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
A number of substances affect glucose metabolism and may require dose adjustment of human insulin. 
 
Substances that may enhance the blood-glucose-lowering effect and increase susceptibility to 
hypoglycaemia include oral antidiabetic medicinal products, angiotensin converting enzyme (ACE) 
inhibitors, disopyramide, fibrates, fluoxetine, monoamine oxidase (MAO) inhibitors, pentoxifylline, 
propoxyphene, salicylates and sulphonamide antibiotics. 
 
Substances that may reduce the blood-glucose-lowering effect include corticosteroids, danazol, 
diazoxide, diuretics, glucagon, isoniazid, oestrogens and progestogens (e.g. in oral contraceptives), 
phenothiazine derivatives, somatropin, sympathomimetic medicinal products (e.g. epinephrine 
[adrenaline], salbutamol, terbutaline), thyroid hormones, protease inhibitors and atypical antipsychotic 
medicinal products (e.g. olanzapine and clozapine). 
 
Beta-blockers, clonidine, lithium salts or alcohol may either potentiate or weaken the 
blood-glucose-lowering effect of insulin. Pentamidine may cause hypoglycaemia which may 
sometimes be followed by hyperglycaemia. 
 
In addition, under the influence of sympatholytic medicinal products such as beta-blockers, clonidine, 
guanethidine and reserpine, the signs of adrenergic counter-regulation may be reduced or absent. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
For insulin human, no clinical data on exposed pregnancies from controlled clinical studies are 
available. Insulin does cross the placental barrier, although not in clinically significant amount. A 
limited amount of data on pregnant women (less than 300 pregnancy outcomes reported) exposed to 
marketed insulin human indicates no safety issues in use of insulin human in pregnancy. Caution 
should be exercised when prescribing to pregnant women. 
 
It is essential for patients with pre-existing or gestational diabetes to maintain good metabolic control 
throughout pregnancy. Insulin requirements may decrease during the first trimester and generally 
increase during the second and third trimesters. Immediately after delivery, insulin requirements 
decline rapidly (increased risk of hypoglycaemia). Careful monitoring of glucose control is essential. 
 
Breast-feeding 
No effects on the suckling child are anticipated. Insulin Human Winthrop Comb 15 can be used during 
breast-feeding. Breast-feeding women may require adjustments in insulin dose and diet. 
 
Fertility 
No clinical or animal data with insulin human on male or female fertility are available. 
 

 

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4.7 Effects on ability to drive and use machines 
 
The patient's ability to concentrate and react may be impaired as a result of hypoglycaemia or 
hyperglycaemia or, for example, as a result of visual impairment. This may constitute a risk in 
situations where these abilities are of special importance (e.g. driving a car or using machines). 
 
Patients should be advised to take precautions to avoid hypoglycaemia whilst driving. This is 
particularly important in those who have reduced or absent awareness of the warning symptoms of 
hypoglycaemia or have frequent episodes of hypoglycaemia. It should be considered whether it is 
advisable to drive or use machines in these circumstances. 
 
4.8 Undesirable effects 
 
Summary of the safety profile  
Hypoglycaemia, in general the most frequent adverse reaction of insulin therapy, may occur if the 
insulin dose is too high in relation to the insulin requirement. In clinical studies and during marketed 
use, the frequency varies with patient population and dose regimens. Therefore, no specific frequency 
can be presented. 
 
Tabulated list of adverse reactions 
The following related adverse reactions from clinical investigations are listed below by system organ 
class and in order of decreasing incidence: very common (≥1/10); common (≥1/100 to <1/10); 
uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000), not known 
(cannot be estimated from the available data). 
 
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. 
 
MedDRA system 
organ classes 

Common Uncommon Not known 

Immune system 
disorders 

 Shock Immediate type 
allergic reactions 
(hypotension, 
angioneurotic oedema, 
bronchospasm, 
generalised skin 
reactions); 
Anti-insulin antibodies 

Metabolism and 
nutrition disorders 

Oedema  Hypoglycaemia; 
Sodium retention 

Eye disorders   Proliferative 
retinopathy; 
Diabetic retinopathy; 
Visual impairment 

Skin and 
subcutaneous tissue 
disorders 

  Lipodystrophy 

General disorders 
and administration 
site conditions 

Injection site reactions Injection site 
urticaria 

Injection site 
inflammation;  
Injection site pain; 
Injection site pruritus; 
Injection site 
erythema;  
Injection site swelling 

 

 

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Description of selected adverse reactions 
Immune system disorders 
Immediate type allergic reactions to insulin or to the excipients may be life-threatening. 
 
Insulin administration may cause anti-insulin antibodies to form. In rare cases, the presence of such 
anti-insulin antibodies may necessitate adjustment of the insulin dose in order to correct a tendency to 
hyper- or hypoglycaemia. 
 
Metabolism and nutrition disorders 
Severe hypoglycaemic attacks, especially if recurrent, may lead to neurological damage. 
Prolonged or severe hypoglycaemic episodes may be life-threatening. 
 
In many patients, the signs and symptoms of neuroglycopenia are preceded by signs of adrenergic 
counter-regulation. Generally, the greater and more rapid the decline in blood glucose, the more 
marked is the phenomenon of counter-regulation and its symptoms. 
Insulin may cause sodium retention and oedema, particularly if previously poor metabolic control is 
improved by intensified insulin therapy. 
 
Eyes disorders 
A marked change in glycaemic control may cause temporary visual impairment, due to temporary 
alteration in the turgidity and refractive index of the lens. 
 
Long-term improved glycaemic control decreases the risk of progression of diabetic retinopathy. 
However, intensification of insulin therapy with abrupt improvement in glycaemic control may be 
associated with temporary worsening of diabetic retinopathy. 
 
Skin and subcutaneous tissue disorders 
Lipodystrophy may occur at the injection site and delay local insulin absorption. Continuous rotation 
of the injection site within the given injection area may help to reduce or prevent these reactions. 
 
General disorders and administration site conditions 
Most minor reactions to insulins at the injection site usually resolve in a few days to a few weeks. 
 
4.9 Overdose 
 
Symptoms 
Insulin overdose may lead to severe and sometimes long-term and life-threatening hypoglycaemia. 
 
Management 
Mild episodes of hypoglycaemia can usually be treated with oral carbohydrates. Adjustments in dose 
regimen of the medicinal product, meal patterns, or physical activity may be needed. 
 
More severe episodes with coma, seizure, or neurologic impairment may be treated with 
intramuscular/subcutaneous glucagon or concentrated intravenous glucose. Sustained carbohydrate 
intake and observation may be necessary because hypoglycaemia may recur after apparent clinical 
recovery. 
 
 

 

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5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Drugs used in diabetes, insulins and analogues for injection, 
intermediate-acting combined with fast-acting, ATC Code: A10AD01. 
 
Mechanism of action 
Insulin 
- lowers blood glucose and promotes anabolic effects as well as decreasing catabolic effects, 
- increases the transport of glucose into cells as well as the formation of glycogen in the muscles 

and the liver, and improves pyruvate utilisation. It inhibits glycogenolysis and gluconeogenesis, 
- increases lipogenesis in the liver and adipose tissue and inhibits lipolysis, 
- promotes the uptake of amino acids into cells and promotes protein synthesis, 
- enhances the uptake of potassium into cells. 
 
Pharmacodynamic effects 
Insulin Human Winthrop Comb 15 (a biphasic isophane insulin suspension with 15% dissolved 
insulin) is an insulin with gradual onset and long duration of action. Following subcutaneous injection, 
onset of action is within 30 to 60 minutes, the phase of maximum action is between 2 and 4 hours after 
injection and the duration of action is 11 to 20 hours. 
 
5.2 Pharmacokinetic properties 
 
In healthy subjects, the serum half-life of insulin is approximately 4 to 6 minutes. It is longer in 
patients with severe renal insufficiency. However, it must be noted that the pharmacokinetics of 
insulin do not reflect its metabolic action. 
 
5.3 Preclinical safety data 
 
The acute toxicity was studied following subcutaneous administration in rats. No evidence of toxic 
effects was found. Studies of pharmacodynamic effects following subcutaneous administration in 
rabbits and dogs revealed the expected hypoglycaemic reactions. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Protamine sulphate, 
metacresol, 
phenol, 
zinc chloride, 
sodium dihydrogen phosphate dihydrate, 
glycerol, 
sodium hydroxide, 
hydrochloric acid (for pH adjustment), 
water for injections. 
 
6.2 Incompatibilities 
 
This medicinal product must not be mixed with other medicinal products except those mentioned in 
section 6.6. 
 
Insulin Human Winthrop Comb 15 must not be mixed with solutions containing reducing substances 
such as thioles and sulphites.  
 

 

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Mixing of insulins 
Insulin Human Winthrop Comb 15 must not be mixed with insulin human formulations designed 
specifically for use in insulin pumps.  
Insulin Human Winthrop Comb 15 must also not be mixed with insulins of animal origin or with 
insulin analogues. 
Insulins of different concentration (e.g. 100 IU per ml and 40 IU per ml) must not be mixed. 
 
Care must be taken to ensure that no alcohol or other disinfectants enter the insulin suspension. 
 
6.3 Shelf life 
 
2 years. 
 
Shelf life after first use of the vial 
The product may be stored for a maximum of 4 weeks not above 25°C and away from direct heat or 
direct light. 
Keep the vial in the outer carton in order to protect from light. 
It is recommended that the date of the first use be noted on the label. 
 
6.4 Special precautions for storage 
 
Unopened vials 
Store in a refrigerator (2°C -8°C). 
Do not freeze. 
Do not put Insulin Human Winthrop Comb 15 next to the freezer compartment or a freezer pack. 
Keep the vial in the outer carton in order to protect from light. 
 
Opened vials 
For storage conditions after first opening of the medicinal product, see section 6.3. 
 
6.5 Nature and contents of container 
 
5 ml suspension in a vial (type 1 colourless glass) with a flanged cap (aluminium), a stopper 
(chlorobutyl rubber (type 1)) and a tear-off cap (polypropylene). 
Packs of 1 and 5 vials are available. 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal and other handling 
 
Before withdrawing insulin from the vial for the first time, remove the plastic protective cap. 
 
Immediately before withdrawal from the vial into the injection syringe, the insulin must be 
resuspended. This is best done by rolling the vial at an oblique angle between the palms of the hands. 
Do not shake the vial vigorously as this may lead to changes in the suspension (giving the vial a 
frosted appearance; see below) and cause frothing. Froth may interfere with the correct measurement 
of the dose. 
 
After resuspension, the fluid must have a uniformly milky appearance. Insulin Human Winthrop 
Comb 15 must not be used if this cannot be achieved, i.e. if the suspension remains clear, for example, 
or if clumps, particles or flocculation appear in the insulin or stick to the wall or bottom of the vial. 
These changes sometimes give the vial a frosted appearance. In such cases, a new vial yielding a 
uniform suspension must be used. It is also necessary to change to a new vial if the insulin 
requirement changes substantially. 
 
Insulin Human Winthrop Comb 15 must not be administered intravenously and must not be used in 
infusion pumps or external or implanted insulin pumps. 
 

 

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It must be remembered that 
- insulin protamine crystals dissolve in an acid pH range, 
- the soluble insulin part precipitates out at a pH of approximately 4.5 to 6.5. 
 
Insulin label must always be checked before each injection to avoid medication errors between insulin 
human and other insulins (see section 4.4). 
 
Mixing of insulins 
Insulin Human Winthrop Comb 15 may be mixed with all insulin human formulations, but not with 
those designed specifically for use in insulin pumps. Concerning incompatibility with other insulins, 
see section 6.2. 
 
If two different insulins have to be drawn into one single injection syringe, it is recommended that the 
shorter-acting insulin be drawn first to prevent contamination of the vial by the longer-acting 
preparation. It is advisable to inject immediately after mixing.  
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Sanofi-Aventis Deutschland GmbH, D-65926 Frankfurt am Main, Germany 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/06/368/029 
EU/1/06/368/030 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 17 January 2007 
Date of latest renewal: 17 January 2012 
 
 
10. DATE OF REVISION OF THE TEXT 
 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu 

 

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1. NAME OF THE MEDICINAL PRODUCT 
 
Insulin Human Winthrop Comb 15 40 IU/ml suspension for injection in a vial 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each ml contains 40 IU insulin human (equivalent to 1.4 mg).  
Each vial contains 10 ml of suspension for injection, equivalent to 400 IU insulin. One IU 
(International Unit) corresponds to 0.035 mg of anhydrous human insulin. 
 
Insulin Human Winthrop Comb 15 is a biphasic isophane insulin suspension consisting of 15% 
dissolved insulin and 85% crystalline protamine insulin. 
 
Human insulin is produced by recombinant DNA technology in Escherichia coli. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Suspension for injection in a vial. 
 
After resuspension, milky-white suspension. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Diabetes mellitus where treatment with insulin is required. 
 
4.2 Posology and method of administration 
 
Posology 
The desired blood glucose levels, the insulin preparations to be used and the insulin dose regimen 
(doses and timings) must be determined individually and adjusted to suit the patient’s diet, physical 
activity and life-style. 
 
Daily doses and timing of administration 
There are no fixed rules for insulin dose regimen. However, the average insulin requirement is often 
0.5 to 1.0 IU per kg body weight per day. The basal metabolic requirement is 40% to 60% of the total 
daily requirement. Insulin Human Winthrop Comb 15 is injected subcutaneously 30 to 45 minutes 
before a meal. 
 
Secondary dose adjustment 
Improved metabolic control may result in increased insulin sensitivity, leading to a reduced insulin 
requirement. Dose adjustment may also be required, for example, if 
- the patient's weight changes, 
- the patient's life-style changes, 
- other circumstances arise that may promote an increased susceptibility to hypo- or 

hyperglycaemia (see section 4.4). 
 
Special populations 
Elderly population (≧65 years old) 
In the elderly, progressive deterioration of renal function may lead to a steady decrease in insulin 
requirements. 

 

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Renal impairment 
In patients with renal impairment, insulin requirements may be diminished due to reduced insulin 
metabolism. 
 
Hepatic impairment 
In patients with severe hepatic impairment, insulin requirements may be diminished due to reduced 
capacity for gluconeogenesis and reduced insulin metabolism. 
 
Method of administration 
Insulin Human Winthrop Comb 15 must not be administered intravenously and must not be used in 
infusion pumps or external or implanted insulin pumps. 
 
Only injection syringes designed for this strength of insulin (40 IU per ml) are to be used. The 
injection syringes must not contain any other medicinal product or residue (e.g. traces of heparin). 
 
Insulin Human Winthrop Comb 15 is administered subcutaneously. Insulin Human Winthrop 
Comb 15 must never be injected intravenously. 
 
Insulin absorption and hence the blood-glucose-lowering effect of a dose may vary from one injection 
area to another (e.g. the abdominal wall compared with the thigh). Injection sites within an injection 
area must be rotated from one injection to the next. 
 
For further details on handling, see section 6.6. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
 
4.4 Special warnings and precautions for use 
 
Patients hypersensitive to Insulin Human Winthrop Comb 15 for whom no better tolerated preparation 
is available must only continue treatment under close medical supervision and – where necessary – in 
conjunction with anti-allergic treatment. 
 
In patients with an allergy to animal insulin intradermal skin testing is recommended prior to a 
transfer to Insulin Human Winthrop Comb 15, since they may experience immunological 
cross-reactions. 
 
In case of insufficient glucose control or a tendency to hyper- or hypoglycaemic episodes, the patient's 
adherence to the prescribed treatment regimen, injection sites and proper injection technique and all 
other relevant factors must be reviewed before dose adjustment is considered. 
 
Transfer to Insulin Human Winthrop Comb 15 
Transferring a patient to another type or brand of insulin should be done under strict medical 
supervision. Changes in strength, brand (manufacturer), type (regular, NPH, lente, long-acting, etc.), 
origin (animal, human, human insulin analogue) and/or method of manufacture may result in the need 
for a change in dosage. 
The need to adjust (e.g. reduce) the dose may become evident immediately after transfer. 
Alternatively, it may emerge gradually over a period of several weeks. 
 
Following transfer from an animal insulin to human insulin, dose regimen reduction may be required 
in particular in patients who 
- were previously already controlled on rather low blood glucose levels, 
- have a tendency to hypoglycaemia, 
- previously required high insulin doses due to the presence of insulin antibodies. 
 

 

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Close metabolic monitoring is recommended during the transition and in the initial weeks thereafter. In 
patients who require high insulin doses because of the presence of insulin antibodies, transfer under 
medical supervision in a hospital or similar setting must be considered. 
 
Hypoglycaemia 
Hypoglycaemia may occur if the insulin dose is too high in relation to the insulin requirement. 
 
Particular caution should be exercised, and intensified blood glucose monitoring is advisable in 
patients in whom hypoglycaemic episodes might be of particular clinical relevance, such as in patients 
with significant stenoses of the coronary arteries or of the blood vessels supplying the brain (risk of 
cardiac or cerebral complications of hypoglycaemia) as well as in patients with proliferative 
retinopathy, particularly if not treated with photocoagulation (risk of transient amaurosis following 
hypoglycaemia). 
 
Patients should be aware of circumstances where warning symptoms of hypoglycaemia are 
diminished. The warning symptoms of hypoglycaemia may be changed, be less pronounced or be 
absent in certain risk groups. These include patients: 
- in whom glycaemic control is markedly improved, 
- in whom hypoglycaemia develops gradually, 
- who are elderly,  
- after transfer from animal insulin to human insulin, 
- in whom an autonomic neuropathy is present, 
- with a long history of diabetes, 
- suffering from a psychiatric illness, 
- receiving concurrent treatment with certain other medicinal products (see section 4.5). 
Such situations may result in severe hypoglycaemia (and possibly loss of consciousness) prior to the 
patient's awareness of hypoglycaemia. 
 
If normal or decreased values for glycated haemoglobin are noted, the possibility of recurrent, 
unrecognised (especially nocturnal) episodes of hypoglycaemia must be considered. 
 
Adherence of the patient to the dose regimen and dietary regimen, correct insulin administration and 
awareness of hypoglycaemia symptoms are essential to reduce the risk of hypoglycaemia. Factors 
increasing the susceptibility to hypoglycaemia require particularly close monitoring and may 
necessitate dose adjustment. These include: 
- change in the injection area, 
- improved insulin sensitivity (e.g. by removal of stress factors), 
- unaccustomed, increased or prolonged physical activity, 
- intercurrent illness (e.g. vomiting, diarrhoea), 
- inadequate food intake, 
- missed meals, 
- alcohol consumption, 
- certain uncompensated endocrine disorders (e.g. in hypothyroidism and in anterior pituitary or 

adrenocortical insufficiency), 
- concomitant treatment with certain other medicinal products. 
 
Intercurrent illness 
Intercurrent illness requires intensified metabolic monitoring. In many cases, urine tests for ketones 
are indicated, and often it is necessary to adjust the insulin dose. The insulin requirement is often 
increased. Patients with type 1 diabetes must continue to consume at least a small amount of 
carbohydrates on a regular basis, even if they are able to eat only little or no food, or are vomiting etc. 
and they must never omit insulin entirely. 
 
Medication errors 
Medication errors have been reported in which other Insulin Human Winthrop formulations or other 
insulins have been accidentally administered. Insulin label must always be checked before each 
injection to avoid medication errors between insulin human and other insulins. 

 

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Combination of Insulin Human Winthrop with pioglitazone 
Cases of cardiac failure have been reported when pioglitazone was used in combination with insulin, 
especially in patients with risk factors for development of cardiac heart failure. This should be kept in 
mind if treatment with the combination of pioglitazone and Insulin Human Winthrop is considered. If 
the combination is used, patients should be observed for signs and symptoms of heart failure, weight 
gain and oedema. Pioglitazone should be discontinued if any deterioration in cardiac symptoms 
occurs.  
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
A number of substances affect glucose metabolism and may require dose adjustment of human insulin. 
 
Substances that may enhance the blood-glucose-lowering effect and increase susceptibility to 
hypoglycaemia include oral antidiabetic medicinal products, angiotensin converting enzyme (ACE) 
inhibitors, disopyramide, fibrates, fluoxetine, monoamine oxidase (MAO) inhibitors, pentoxifylline, 
propoxyphene, salicylates and sulphonamide antibiotics. 
 
Substances that may reduce the blood-glucose-lowering effect include corticosteroids, danazol, 
diazoxide, diuretics, glucagon, isoniazid, oestrogens and progestogens (e.g. in oral contraceptives), 
phenothiazine derivatives, somatropin, sympathomimetic medicinal products (e.g. epinephrine 
[adrenaline], salbutamol, terbutaline), thyroid hormones, protease inhibitors and atypical antipsychotic 
medicinal products (e.g. olanzapine and clozapine). 
 
Beta-blockers, clonidine, lithium salts or alcohol may either potentiate or weaken the 
blood-glucose-lowering effect of insulin. Pentamidine may cause hypoglycaemia which may 
sometimes be followed by hyperglycaemia. 
 
In addition, under the influence of sympatholytic medicinal products such as beta-blockers, clonidine, 
guanethidine and reserpine, the signs of adrenergic counter-regulation may be reduced or absent. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
For insulin human, no clinical data on exposed pregnancies from controlled clinical studies are 
available. Insulin does cross the placental barrier, although not in clinically significant amount. A 
limited amount of data on pregnant women (less than 300 pregnancy outcomes reported) exposed to 
marketed insulin human indicates no safety issues in use of insulin human in pregnancy. Caution 
should be exercised when prescribing to pregnant women. 
 
It is essential for patients with pre-existing or gestational diabetes to maintain good metabolic control 
throughout pregnancy. Insulin requirements may decrease during the first trimester and generally 
increase during the second and third trimesters. Immediately after delivery, insulin requirements 
decline rapidly (increased risk of hypoglycaemia). Careful monitoring of glucose control is essential. 
 
Breast-feeding 
No effects on the suckling child are anticipated. Insulin Human Winthrop Comb 15 can be used during 
breast-feeding. Breast-feeding women may require adjustments in insulin dose and diet. 
 
Fertility 
No clinical or animal data with insulin human on male or female fertility are available. 
 

 

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4.7 Effects on ability to drive and use machines 
 
The patient's ability to concentrate and react may be impaired as a result of hypoglycaemia or 
hyperglycaemia or, for example, as a result of visual impairment. This may constitute a risk in 
situations where these abilities are of special importance (e.g. driving a car or using machines). 
 
Patients should be advised to take precautions to avoid hypoglycaemia whilst driving. This is 
particularly important in those who have reduced or absent awareness of the warning symptoms of 
hypoglycaemia or have frequent episodes of hypoglycaemia. It should be considered whether it is 
advisable to drive or use machines in these circumstances. 
 
4.8 Undesirable effects 
 
Summary of the safety profile  
Hypoglycaemia, in general the most frequent adverse reaction of insulin therapy, may occur if the 
insulin dose is too high in relation to the insulin requirement. In clinical studies and during marketed 
use, the frequency varies with patient population and dose regimens. Therefore, no specific frequency 
can be presented. 
 
Tabulated list of adverse reactions 
The following related adverse reactions from clinical investigations are listed below by system organ 
class and in order of decreasing incidence: very common (≥1/10); common (≥1/100 to <1/10); 
uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000), not known 
(cannot be estimated from the available data). 
 
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. 
 
MedDRA system 
organ classes 

Common Uncommon Not known 

Immune system 
disorders 

 Shock Immediate type 
allergic reactions 
(hypotension, 
angioneurotic oedema, 
bronchospasm, 
generalised skin 
reactions); 
Anti-insulin antibodies 

Metabolism and 
nutrition disorders 

Oedema  Hypoglycaemia; 
Sodium retention 

Eye disorders   Proliferative 
retinopathy; 
Diabetic retinopathy; 
Visual impairment 

Skin and 
subcutaneous tissue 
disorders 

  Lipodystrophy 

General disorders 
and administration 
site conditions 

Injection site reactions Injection site 
urticaria 

Injection site 
inflammation;  
Injection site pain; 
Injection site pruritus; 
Injection site 
erythema;  
Injection site swelling 

 

 

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Description of selected adverse reactions 
Immune system disorders 
Immediate type allergic reactions to insulin or to the excipients may be life-threatening. 
 
Insulin administration may cause anti-insulin antibodies to form. In rare cases, the presence of such 
anti-insulin antibodies may necessitate adjustment of the insulin dose in order to correct a tendency to 
hyper- or hypoglycaemia. 
 
Metabolism and nutrition disorders 
Severe hypoglycaemic attacks, especially if recurrent, may lead to neurological damage. 
Prolonged or severe hypoglycaemic episodes may be life-threatening. 
 
In many patients, the signs and symptoms of neuroglycopenia are preceded by signs of adrenergic 
counter-regulation. Generally, the greater and more rapid the decline in blood glucose, the more 
marked is the phenomenon of counter-regulation and its symptoms.Insulin may cause sodium 
retention and oedema, particularly if previously poor metabolic control is improved by intensified 
insulin therapy. 
 
Eyes disorders 
A marked change in glycaemic control may cause temporary visual impairment, due to temporary 
alteration in the turgidity and refractive index of the lens. 
 
Long-term improved glycaemic control decreases the risk of progression of diabetic retinopathy. 
However, intensification of insulin therapy with abrupt improvement in glycaemic control may be 
associated with temporary worsening of diabetic retinopathy. 
 
Skin and subcutaneous tissue disorders 
Lipodystrophy may occur at the injection site and delay local insulin absorption. Continuous rotation 
of the injection site within the given injection area may help to reduce or prevent these reactions. 
 
General disorders and administration site conditions 
Most minor reactions to insulins at the injection site usually resolve in a few days to a few weeks. 
 
4.9 Overdose 
 
Symptoms 
Insulin overdose may lead to severe and sometimes long-term and life-threatening hypoglycaemia. 
 
Management 
Mild episodes of hypoglycaemia can usually be treated with oral carbohydrates. Adjustments in dose 
regimen of the medicinal product, meal patterns, or physical activity may be needed. 
 
More severe episodes with coma, seizure, or neurologic impairment may be treated with 
intramuscular/subcutaneous glucagon or concentrated intravenous glucose. Sustained carbohydrate 
intake and observation may be necessary because hypoglycaemia may recur after apparent clinical 
recovery. 
 
 

 

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5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Drugs used in diabetes, insulins and analogues for injection, 
intermediate-acting combined with fast-acting, ATC Code: A10AD01. 
 
Mechanism of action 
Insulin 
- lowers blood glucose and promotes anabolic effects as well as decreasing catabolic effects, 
- increases the transport of glucose into cells as well as the formation of glycogen in the muscles 

and the liver, and improves pyruvate utilisation. It inhibits glycogenolysis and gluconeogenesis, 
- increases lipogenesis in the liver and adipose tissue and inhibits lipolysis, 
- promotes the uptake of amino acids into cells and promotes protein synthesis, 
- enhances the uptake of potassium into cells. 
 
Pharmacodynamic effects 
Insulin Human Winthrop Comb 15 (a biphasic isophane insulin suspension with 15% dissolved 
insulin) is an insulin with gradual onset and long duration of action. Following subcutaneous injection, 
onset of action is within 30 to 60 minutes, the phase of maximum action is between 2 and 4 hours after 
injection and the duration of action is 11 to 20 hours. 
 
5.2 Pharmacokinetic properties 
 
In healthy subjects, the serum half-life of insulin is approximately 4 to 6 minutes. It is longer in 
patients with severe renal insufficiency. However, it must be noted that the pharmacokinetics of 
insulin do not reflect its metabolic action. 
 
5.3 Preclinical safety data 
The acute toxicity was studied following subcutaneous administration in rats. No evidence of toxic 
effects was found. Studies of pharmacodynamic effects following subcutaneous administration in 
rabbits and dogs revealed the expected hypoglycaemic reactions. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Protamine sulphate, 
metacresol, 
phenol, 
zinc chloride, 
sodium dihydrogen phosphate dihydrate, 
glycerol, 
sodium hydroxide, 
hydrochloric acid (for pH adjustment), 
water for injections. 
 
6.2 Incompatibilities 
 
This medicinal product must not be mixed with other medicinal products except those mentioned in 
section 6.6. 
 
Insulin Human Winthrop Comb 15 must not be mixed with solutions containing reducing substances 
such as thioles and sulphites.  
 

 

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Mixing of insulins 
Insulin Human Winthrop Comb 15 must not be mixed with insulin human formulations designed 
specifically for use in insulin pumps.  
Insulin Human Winthrop Comb 15 must also not be mixed with insulins of animal origin or with 
insulin analogues. 
Insulins of different concentration (e.g. 100 IU per ml and 40 IU per ml) must not be mixed. 
 
Care must be taken to ensure that no alcohol or other disinfectants enter the insulin suspension. 
 
6.3 Shelf life 
 
2 years. 
 
Shelf life after first use of the vial 
The product may be stored for a maximum of 4 weeks not above 25°C and away from direct heat or 
direct light. 
Keep the vial in the outer carton in order to protect from light. 
It is recommended that the date of the first use be noted on the label. 
 
6.4 Special precautions for storage 
 
Unopened vials 
Store in a refrigerator (2°C - 8°C). 
Do not freeze. 
Do not put Insulin Human Winthrop Comb 15 next to the freezer compartment or a freezer pack. 
Keep the vial in the outer carton in order to protect from light. 
 
Opened vials 
For storage conditions after first opening of the medicinal product, see section 6.3. 
 
6.5 Nature and contents of container 
 
10 ml suspension in a vial (type 1 colourless glass) with a flanged cap (aluminium), a stopper 
(chlorobutyl rubber (type 1)) and a tear-off cap (polypropylene). 
Packs of 1 and 5 vials are available. 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal and other handling 
 
Before withdrawing insulin from the vial for the first time, remove the plastic protective cap. 
 
Immediately before withdrawal from the vial into the injection syringe, the insulin must be 
resuspended. This is best done by rolling the vial at an oblique angle between the palms of the hands. 
Do not shake the vial vigorously as this may lead to changes in the suspension (giving the vial a 
frosted appearance; see below) and cause frothing. Froth may interfere with the correct measurement 
of the dose. 
 
After resuspension, the fluid must have a uniformly milky appearance. Insulin Human Winthrop 
Comb 15 must not be used if this cannot be achieved, i.e. if the suspension remains clear, for example, 
or if clumps, particles or flocculation appear in the insulin or stick to the wall or bottom of the vial. 
These changes sometimes give the vial a frosted appearance. In such cases, a new vial yielding a 
uniform suspension must be used. It is also necessary to change to a new vial if the insulin 
requirement changes substantially. 
 
Insulin Human Winthrop Comb 15 must not be administered intravenously and must not be used in 
infusion pumps or external or implanted insulin pumps. 
 

 

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It must be remembered that 
- insulin protamine crystals dissolve in an acid pH range, 
- the soluble insulin part precipitates out at a pH of approximately 4.5 to 6.5. 
 
Insulin label must always be checked before each injection to avoid medication errors between insulin 
human and other insulins (see section 4.4). 
 
Mixing of insulins 
Insulin Human Winthrop Comb 15 may be mixed with all insulin human fomulations, but not with 
those designed specifically for use in insulin pumps. Concerning incompatibility with other insulins, 
see section 6.2. 
 
If two different insulins have to be drawn into one single injection syringe, it is recommended that the 
shorter-acting insulin be drawn first to prevent contamination of the vial by the longer-acting 
preparation. It is advisable to inject immediately after mixing.  
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Sanofi-Aventis Deutschland GmbH, D-65926 Frankfurt am Main, Germany 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/06/368/005 
EU/1/06/368/006 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 17 January 2007 
Date of latest renewal: 17 January 2012 
 
 
10. DATE OF REVISION OF THE TEXT 
 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu 

 

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1. NAME OF THE MEDICINAL PRODUCT 
 
Insulin Human Winthrop Comb 15 100 IU/ml suspension for injection in a cartridge 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each ml contains 100 IU insulin human (equivalent to 3.5 mg).  
Each cartridge contains 3 ml of suspension for injection, equivalent to 300 IU insulin. One IU 
(International Unit) corresponds to 0.035 mg of anhydrous human insulin. 
 
Insulin Human Winthrop Comb 15 is a biphasic isophane insulin suspension consisting of 15% 
dissolved insulin and 85% crystalline protamine insulin. 
 
Human insulin is produced by recombinant DNA technology in Escherichia coli. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Suspension for injectionin a cartridge. 
 
After resuspension, milky-white suspension. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Diabetes mellitus where treatment with insulin is required. 
 
4.2 Posology and method of administration 
 
Posology 
The desired blood glucose levels, the insulin preparations to be used and the insulin dose regimen 
(doses and timings) must be determined individually and adjusted to suit the patient’s diet, physical 
activity and life-style. 
 
Daily doses and timing of administration 
There are no fixed rules for insulin dose regimen. However, the average insulin requirement is often 
0.5 to 1.0 IU per kg body weight per day. The basal metabolic requirement is 40% to 60% of the total 
daily requirement. Insulin Human Winthrop Comb 15 is injected subcutaneously 30 to 45 minutes 
before a meal. 
 
Secondary dose adjustment 
Improved metabolic control may result in increased insulin sensitivity, leading to a reduced insulin 
requirement. Dose adjustment may also be required, for example, if 
- the patient's weight changes, 
- the patient's life-style changes, 
- other circumstances arise that may promote an increased susceptibility to hypo- or 

hyperglycaemia (see section 4.4). 
 
Special populations 
Elderly population (≧65 years old) 
In the elderly, progressive deterioration of renal function may lead to a steady decrease in insulin 
requirements. 

 

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Renal impairment 
In patients with renal impairment, insulin requirements may be diminished due to reduced insulin 
metabolism. 
 
Hepatic impairment 
In patients with severe hepatic impairment, insulin requirements may be diminished due to reduced 
capacity for gluconeogenesis and reduced insulin metabolism. 
 
Method of administration 
Insulin Human Winthrop Comb 15 must not be administered intravenously and must not be used in 
infusion pumps or external or implanted insulin pumps. 
 
Insulin Human Winthrop Comb 15 is administered subcutaneously. Insulin Human Winthrop 
Comb 15 must never be injected intravenously. 
 
Insulin absorption and hence the blood-glucose-lowering effect of a dose may vary from one injection 
area to another (e.g. the abdominal wall compared with the thigh). Injection sites within an injection 
area must be rotated from one injection to the next. 
 
For further details on handling, see section 6.6. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
 
4.4 Special warnings and precautions for use 
 
Patients hypersensitive to Insulin Human Winthrop Comb 15 for whom no better tolerated preparation 
is available must only continue treatment under close medical supervision and – where necessary – in 
conjunction with anti-allergic treatment. 
 
In patients with an allergy to animal insulin intradermal skin testing is recommended prior to a 
transfer to Insulin Human Winthrop Comb 15, since they may experience immunological 
cross-reactions. 
 
In case of insufficient glucose control or a tendency to hyper- or hypoglycaemic episodes, the patient's 
adherence to the prescribed treatment regimen, injection sites and proper injection technique and all 
other relevant factors must be reviewed before dose adjustment is considered. 
 
Transfer to Insulin Human Winthrop Comb 15 
Transferring a patient to another type or brand of insulin should be done under strict medical 
supervision. Changes in strength, brand (manufacturer), type (regular, NPH, lente, long-acting, etc.), 
origin (animal, human, human insulin analogue) and/or method of manufacture may result in the need 
for a change in dosage. 
The need to adjust (e.g. reduce) the dose may become evident immediately after transfer. 
Alternatively, it may emerge gradually over a period of several weeks. 
 
Following transfer from an animal insulin to human insulin, dose regimen reduction may be required 
in particular in patients who 
- were previously already controlled on rather low blood glucose levels, 
- have a tendency to hypoglycaemia, 
- previously required high insulin doses due to the presence of insulin antibodies. 
 
Close metabolic monitoring is recommended during the transition and in the initial weeks thereafter. In 
patients who require high insulin doses because of the presence of insulin antibodies, transfer under 
medical supervision in a hospital or similar setting must be considered. 

 

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Hypoglycaemia 
Hypoglycaemia may occur if the insulin dose is too high in relation to the insulin requirement. 
 
Particular caution should be exercised, and intensified blood glucose monitoring is advisable in 
patients in whom hypoglycaemic episodes might be of particular clinical relevance, such as in patients 
with significant stenoses of the coronary arteries or of the blood vessels supplying the brain (risk of 
cardiac or cerebral complications of hypoglycaemia) as well as in patients with proliferative 
retinopathy, particularly if not treated with photocoagulation (risk of transient amaurosis following 
hypoglycaemia). 
 
Patients should be aware of circumstances where warning symptoms of hypoglycaemia are 
diminished. The warning symptoms of hypoglycaemia may be changed, be less pronounced or be 
absent in certain risk groups. These include patients: 
- in whom glycaemic control is markedly improved, 
- in whom hypoglycaemia develops gradually, 
- who are elderly,  
- after transfer from animal insulin to human insulin, 
- in whom an autonomic neuropathy is present, 
- with a long history of diabetes, 
- suffering from a psychiatric illness, 
- receiving concurrent treatment with certain other medicinal products (see section 4.5). 
Such situations may result in severe hypoglycaemia (and possibly loss of consciousness) prior to the 
patient's awareness of hypoglycaemia. 
 
If normal or decreased values for glycated haemoglobin are noted, the possibility of recurrent, 
unrecognised (especially nocturnal) episodes of hypoglycaemia must be considered. 
 
Adherence of the patient to the dose regimen and dietary regimen, correct insulin administration and 
awareness of hypoglycaemia symptoms are essential to reduce the risk of hypoglycaemia. Factors 
increasing the susceptibility to hypoglycaemia require particularly close monitoring and may 
necessitate dose adjustment. These include: 
- change in the injection area, 
- improved insulin sensitivity (e.g. by removal of stress factors), 
- unaccustomed, increased or prolonged physical activity, 
- intercurrent illness (e.g. vomiting, diarrhoea), 
- inadequate food intake, 
- missed meals, 
- alcohol consumption, 
- certain uncompensated endocrine disorders (e.g. in hypothyroidism and in anterior pituitary or 

adrenocortical insufficiency), 
- concomitant treatment with certain other medicinal products. 
 
Intercurrent illness 
Intercurrent illness requires intensified metabolic monitoring. In many cases, urine tests for ketones 
are indicated, and often it is necessary to adjust the insulin dose. The insulin requirement is often 
increased. Patients with type 1 diabetes must continue to consume at least a small amount of 
carbohydrates on a regular basis, even if they are able to eat only little or no food, or are vomiting etc. 
and they must never omit insulin entirely. 
 
Pens to be used with Insulin Human Winthrop Comb 15 cartridges 
The Insulin Human Winthrop Comb 15 cartridges should only be used with the following pens:  
- JuniorSTAR which delivers Insulin Human Winthrop Comb 15 in 0.5 unit dose increments 
- OptiPen, ClikSTAR, Tactipen, Autopen 24 and AllStar which all deliver Insulin Human Winthrop 
Comb 15 in 1 unit dose increments. 
These cartridges should not be used with any other reusable pen as the dosing accuracy has only been 
established with the listed pens.  

 

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Not all of these pens may be marketed in your country. 
 
Medication errors 
Medication errors have been reported in which other Insulin Human Winthrop formulations or other 
insulins have been accidentally administered. Insulin label must always be checked before each 
injection to avoid medication errors between insulin human and other insulins. 
 
Combination of Insulin Human Winthrop with pioglitazone 
Cases of cardiac failure have been reported when pioglitazone was used in combination with insulin, 
especially in patients with risk factors for development of cardiac heart failure. This should be kept in 
mind if treatment with the combination of pioglitazone and Insulin Human Winthrop is considered. If 
the combination is used, patients should be observed for signs and symptoms of heart failure, weight 
gain and oedema. Pioglitazone should be discontinued if any deterioration in cardiac symptoms 
occurs.  
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
A number of substances affect glucose metabolism and may require dose adjustment of human insulin. 
 
Substances that may enhance the blood-glucose-lowering effect and increase susceptibility to 
hypoglycaemia include oral antidiabetic medicinal products, angiotensin converting enzyme (ACE) 
inhibitors, disopyramide, fibrates, fluoxetine, monoamine oxidase (MAO) inhibitors, pentoxifylline, 
propoxyphene, salicylates and sulphonamide antibiotics. 
 
Substances that may reduce the blood-glucose-lowering effect include corticosteroids, danazol, 
diazoxide, diuretics, glucagon, isoniazid, oestrogens and progestogens (e.g. in oral contraceptives), 
phenothiazine derivatives, somatropin, sympathomimetic medicinal products (e.g. epinephrine 
[adrenaline], salbutamol, terbutaline), thyroid hormones, protease inhibitors and atypical antipsychotic 
medicinal products (e.g. olanzapine and clozapine). 
 
Beta-blockers, clonidine, lithium salts or alcohol may either potentiate or weaken the 
blood-glucose-lowering effect of insulin. Pentamidine may cause hypoglycaemia which may 
sometimes be followed by hyperglycaemia. 
 
In addition, under the influence of sympatholytic medicinal products such as beta-blockers, clonidine, 
guanethidine and reserpine, the signs of adrenergic counter-regulation may be reduced or absent. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
For insulin human, no clinical data on exposed pregnancies from controlled clinical studies are 
available. Insulin does cross the placental barrier, although not in clinically significant amount. A 
limited amount of data on pregnant women (less than 300 pregnancy outcomes reported) exposed to 
marketed insulin human indicates no safety issues in use of insulin human in pregnancy. Caution 
should be exercised when prescribing to pregnant women. 
 
It is essential for patients with pre-existing or gestational diabetes to maintain good metabolic control 
throughout pregnancy. Insulin requirements may decrease during the first trimester and generally 
increase during the second and third trimesters. Immediately after delivery, insulin requirements 
decline rapidly (increased risk of hypoglycaemia). Careful monitoring of glucose control is essential. 
 
Breast-feeding 
No effects on the suckling child are anticipated. Insulin Human Winthrop Comb 15 can be used during 
breast-feeding. Breast-feeding women may require adjustments in insulin dose and diet. 
 
Fertility 
No clinical or animal data with insulin human on male or female fertility are available. 

 

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4.7 Effects on ability to drive and use machines 
 
The patient's ability to concentrate and react may be impaired as a result of hypoglycaemia or 
hyperglycaemia or, for example, as a result of visual impairment. This may constitute a risk in 
situations where these abilities are of special importance (e.g. driving a car or using machines). 
 
Patients should be advised to take precautions to avoid hypoglycaemia whilst driving. This is 
particularly important in those who have reduced or absent awareness of the warning symptoms of 
hypoglycaemia or have frequent episodes of hypoglycaemia. It should be considered whether it is 
advisable to drive or use machines in these circumstances. 
 
4.8 Undesirable effects 
 
Summary of the safety profile  
Hypoglycaemia, in general the most frequent adverse reaction of insulin therapy, may occur if the 
insulin dose is too high in relation to the insulin requirement. In clinical studies and during marketed 
use, the frequency varies with patient population and dose regimens. Therefore, no specific frequency 
can be presented. 
 
Tabulated list of adverse reactions 
The following related adverse reactions from clinical investigations are listed below by system organ 
class and in order of decreasing incidence: very common (≥1/10); common (≥1/100 to <1/10); 
uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000), not known 
(cannot be estimated from the available data). 
 
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. 
 
MedDRA system 
organ classes 

Common Uncommon Not known 

Immune system 
disorders 

 Shock Immediate type allergic 
reactions (hypotension, 
angioneurotic oedema, 
bronchospasm, 
generalised skin 
reactions); 
Anti-insulin antibodies 

Metabolism and 
nutrition disorders 

Oedema  Hypoglycaemia; 
Sodium retention 

Eye disorders   Proliferative retinopathy; 
Diabetic retinopathy; 
Visual impairment 

Skin and subcutaneous 
tissue disorders 

  Lipodystrophy 

General disorders and 
administration site 
conditions 

Injection site reactions Injection site 
urticaria 

Injection site 
inflammation;  
Injection site pain; 
Injection site pruritus; 
Injection site erythema; 
Injection site swelling 

 
Description of selected adverse reactions 
Immune system disorders 
Immediate type allergic reactions to insulin or to the excipients may be life-threatening. 
 

 

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Insulin administration may cause anti-insulin antibodies to form. In rare cases, the presence of such 
anti-insulin antibodies may necessitate adjustment of the insulin dose in order to correct a tendency to 
hyper- or hypoglycaemia. 
 
Metabolism and nutrition disordersSevere hypoglycaemic attacks, especially if recurrent, may lead to 
neurological damage. 
Prolonged or severe hypoglycaemic episodes may be life-threatening. 
 
In many patients, the signs and symptoms of neuroglycopenia are preceded by signs of adrenergic 
counter-regulation. Generally, the greater and more rapid the decline in blood glucose, the more 
marked is the phenomenon of counter-regulation and its symptoms. 
Insulin may cause sodium retention and oedema, particularly if previously poor metabolic control is 
improved by intensified insulin therapy. 
 
Eyes disorders 
A marked change in glycaemic control may cause temporary visual impairment, due to temporary 
alteration in the turgidity and refractive index of the lens. 
 
Long-term improved glycaemic control decreases the risk of progression of diabetic retinopathy. 
However, intensification of insulin therapy with abrupt improvement in glycaemic control may be 
associated with temporary worsening of diabetic retinopathy. 
 
Skin and subcutaneous tissue disorders 
Lipodystrophy may occur at the injection site and delay local insulin absorption. Continuous rotation 
of the injection site within the given injection area may help to reduce or prevent these reactions. 
 
General disorders and administration site conditions 
Most minor reactions to insulins at the injection site usually resolve in a few days to a few weeks. 
 
4.9 Overdose 
 
Symptoms 
Insulin overdose may lead to severe and sometimes long-term and life-threatening hypoglycaemia. 
 
Management 
Mild episodes of hypoglycaemia can usually be treated with oral carbohydrates. Adjustments in dose 
regimen of the medicinal product, meal patterns, or physical activity may be needed. 
 
More severe episodes with coma, seizure, or neurologic impairment may be treated with 
intramuscular/subcutaneous glucagon or concentrated intravenous glucose. Sustained carbohydrate 
intake and observation may be necessary because hypoglycaemia may recur after apparent clinical 
recovery. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Drugs used in diabetes, insulins and analogues for injection, 
intermediate-acting combined with fast-acting, ATC Code: A10AD01. 
 
Mechanism of action 
Insulin 
- lowers blood glucose and promotes anabolic effects as well as decreasing catabolic effects, 
- increases the transport of glucose into cells as well as the formation of glycogen in the muscles 

and the liver, and improves pyruvate utilisation. It inhibits glycogenolysis and gluconeogenesis, 
- increases lipogenesis in the liver and adipose tissue and inhibits lipolysis, 

 

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- promotes the uptake of amino acids into cells and promotes protein synthesis, 
- enhances the uptake of potassium into cells. 
 
Pharmacodynamic effects 
Insulin Human Winthrop Comb 15 (a biphasic isophane insulin suspension with 15% dissolved 
insulin) is an insulin with gradual onset and long duration of action. Following subcutaneous injection, 
onset of action is within 30 to 60 minutes, the phase of maximum action is between 2 and 4 hours after 
injection and the duration of action is 11 to 20 hours. 
 
5.2 Pharmacokinetic properties 
 
In healthy subjects, the serum half-life of insulin is approximately 4 to 6 minutes. It is longer in 
patients with severe renal insufficiency. However, it must be noted that the pharmacokinetics of 
insulin do not reflect its metabolic action. 
 
5.3 Preclinical safety data 
 
The acute toxicity was studied following subcutaneous administration in rats. No evidence of toxic 
effects was found. Studies of pharmacodynamic effects following subcutaneous administration in 
rabbits and dogs revealed the expected hypoglycaemic reactions. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Protamine sulphate, 
metacresol, 
phenol, 
zinc chloride, 
sodium dihydrogen phosphate dihydrate, 
glycerol, 
sodium hydroxide, 
hydrochloric acid (for pH adjustment), 
water for injections. 
 
6.2 Incompatibilities 
 
This medicinal product must not be mixed with other medicinal products except those mentioned in 
section 6.6. 
 
Insulin Human Winthrop Comb 15 must not be mixed with solutions containing reducing substances 
such as thioles and sulphites.  
 
Mixing of insulins 
Insulin Human Winthrop Comb 15 must not be mixed with insulin human formulations designed 
specifically for use in insulin pumps.  
Insulin Human Winthrop Comb 15 must also not be mixed with insulins of animal origin or with 
insulin analogues. 
 
Care must be taken to ensure that no alcohol or other disinfectants enter the insulin suspension. 
 
6.3 Shelf life 
 
2 years. 
 
Shelf life after first use of the cartridge 

 

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The cartridge in-use (in the insulin pen) or carried as a spare may be stored for a maximum of 4 weeks 
not above 25°C and away from direct heat or direct light. 
The pen containing a cartridge must not be stored in the refrigerator. 
The pen cap must be put back on the pen after each injection in order to protect from light. 
 
6.4 Special precautions for storage 
 
Unopened cartridges 
Store in a refrigerator (2°C - 8°C). 
Do not freeze. 
Do not put Insulin Human Winthrop Comb 15 next to the freezer compartment or a freezer pack. 
Keep the cartridge in the outer carton in order to protect from light. 
 
In-use cartridges 
For storage conditions after first opening of the medicinal product, see section 6.3. 
 
6.5 Nature and contents of container 
 
3 ml suspension in a cartridge (type 1 colourless glass) with a plunger (bromobutyl rubber (type 1)) 
and a flanged cap (aluminium) with a stopper (bromobutyl or laminate of polyisoprene and 
bromobutyl rubber (type 1)). 
Each cartridge contains 3 balls (stainless steel). 
Packs of 3, 4, 5, 6, 9 or 10 cartridges are available. 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal and other handling 
 
Insulin pen 
The Insulin Human Winthrop Comb 15 cartridges are to be used only in conjunction with the pens: 
OptiPen, ClikSTAR, Autopen 24, Tactipen, AllStar or JuniorSTAR (see section 4.4). Not all of these pens 
may be marketed in your country. 
 
The pen should be used as recommended in the information provided by the device manufacturer.  
 
The manufacturer’s instructions for using the pen must be followed carefully for loading the cartridge, 
attaching the injection needle, and administering the insulin injection. 
 
If the insulin pen is damaged or not working properly (due to mechanical defects) it has to be 
discarded, and a new insulin pen has to be used. 
 
If the pen malfunctions (see instructions for using the pen), the suspension may be drawn from the 
cartridge into an injection syringe (suitable for an insulin with 100 IU/ml) and injected. 
 
Cartridges 
Before insertion into the pen, Insulin Human Winthrop Comb 15 must be kept at room temperature for 
1 to 2 hours and then resuspended to check the contents. This is best done by gently tilting the 
cartridge back and forth (at least ten times). Each cartridge contains three small metal balls to facilitate 
quick and thorough mixing of the contents. 
 
Later on, when the cartridge has been inserted into the pen, the insulin must be resuspended again 
prior to each injection. This is best done by gently tilting the pen back and forth (at least ten times). 
 
After resuspension, the fluid must have a uniformly milky appearance. Insulin Human Winthrop 
Comb 15 must not be used if this cannot be achieved, i.e. if the suspension remains clear, for example, 
or if clumps, particles or flocculation appear in the insulin or stick to the wall or bottom of the 
cartridge. These changes sometimes give the cartridge a frosted appearance. In such cases, a new 

 

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cartridge yielding a uniform suspension must be used. It is also necessary to change to a new cartridge 
if the insulin requirement changes substantially. 
 
Air bubbles must be removed from the cartridge before injection (see instructions for using the pen). 
Empty cartridges must not be refilled. 
 
Insulin Human Winthrop Comb 15 must not be administered intravenously and must not be used in 
infusion pumps or external or implanted insulin pumps. 
 
It must be remembered that 
- insulin protamine crystals dissolve in an acid pH range, 
- the soluble insulin part precipitates out at a pH of approximately 4.5 to 6.5. 
 
Insulin label must always be checked before each injection to avoid medication errors between insulin 
human and other insulins (see section 4.4). 
 
Mixing of insulins 
Insulin Human Winthrop Comb 15 may be mixed with all insulin human formulations, but not with 
those designed specifically for use in insulin pumps. Concerning incompatibility with other insulins, 
see section 6.2. 
 
Insulin Human Winthrop Comb 15 cartridges are not designed to allow any other insulin to be mixed 
in the cartridge. 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Sanofi-Aventis Deutschland GmbH, D-65926 Frankfurt am Main, Germany 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/06/368/090 
EU/1/06/368/031 
EU/1/06/368/032 
EU/1/06/368/095 
EU/1/06/368/100 
EU/1/06/368/033 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 17 January 2007 
Date of latest renewal: 17 January 2012 
 
 
10. DATE OF REVISION OF THE TEXT 
 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu 

 

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1. NAME OF THE MEDICINAL PRODUCT 
 
Insulin Human Winthrop Comb 15 SoloStar 100 IU/ml suspension for injection in a pre-filled pen. 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each ml contains 100 IU insulin human (equivalent to 3.5 mg).  
Each pen contains 3 ml of suspension for injection, equivalent to 300 IU insulin. One IU (International 
Unit) corresponds to 0.035 mg of anhydrous human insulin. 
 
Insulin Human Winthrop Comb 15 is a biphasic isophane insulin suspension consisting of 15% 
dissolved insulin and 85% crystalline protamine insulin. 
 
Human insulin is produced by recombinant DNA technology in Escherichia coli. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Suspension for injection in a pre-filled pen. 
 
After resuspension, milky-white suspension. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Diabetes mellitus where treatment with insulin is required. 
 
4.2 Posology and method of administration 
 
Posology 
The desired blood glucose levels, the insulin preparations to be used and the insulin dose regimen 
(doses and timings) must be determined individually and adjusted to suit the patient’s diet, physical 
activity and life-style. 
 
Daily doses and timing of administration 
There are no fixed rules for insulin dose regimen. However, the average insulin requirement is often 
0.5 to 1.0 IU per kg body weight per day. The basal metabolic requirement is 40% to 60% of the total 
daily requirement. Insulin Human Winthrop Comb 15 is injected subcutaneously 30 to 45 minutes 
before a meal. 
 
SoloStar delivers insulin in doses from 1 to 80 units in steps of 1 unit. Each pen contains multiple 
doses. 
 
Secondary dose adjustment 
Improved metabolic control may result in increased insulin sensitivity, leading to a reduced insulin 
requirement. Dose adjustment may also be required, for example, if 
- the patient's weight changes, 
- the patient's life-style changes, 
- other circumstances arise that may promote an increased susceptibility to hypo- or 

hyperglycaemia (see section 4.4). 
 

 

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Special populations 
Elderly population (≧65 years old) 
In the elderly, progressive deterioration of renal function may lead to a steady decrease in insulin 
requirements. 
 
Renal impairment 
In patients with renal impairment, insulin requirements may be diminished due to reduced insulin 
metabolism. 
 
Hepatic impairment 
In patients with severe hepatic impairment, insulin requirements may be diminished due to reduced 
capacity for gluconeogenesis and reduced insulin metabolism. 
 
Method of administration 
Insulin Human Winthrop Comb 15 is administered subcutaneously. Insulin Human Winthrop 
Comb 15 must never be injected intravenously. 
 
Insulin absorption and hence the blood-glucose-lowering effect of a dose may vary from one injection 
area to another (e.g. the abdominal wall compared with the thigh). Injection sites within an injection 
area must be rotated from one injection to the next. 
 
Before using SoloStar, the Instructions for Use included in the Package Leaflet must be read carefully. 
 
For further details on handling, see section 6.6. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
 
4.4 Special warnings and precautions for use 
 
Patients hypersensitive to Insulin Human Winthrop Comb 15 for whom no better tolerated preparation 
is available must only continue treatment under close medical supervision and – where necessary – in 
conjunction with anti-allergic treatment. 
 
In patients with an allergy to animal insulin intradermal skin testing is recommended prior to a 
transfer to Insulin Human Winthrop Comb 15, since they may experience immunological 
cross-reactions. 
 
In case of insufficient glucose control or a tendency to hyper- or hypoglycaemic episodes, the patient's 
adherence to the prescribed treatment regimen, injection sites and proper injection technique and all 
other relevant factors must be reviewed before dose adjustment is considered. 
 
Transfer to Insulin Human Winthrop Comb 15 
Transferring a patient to another type or brand of insulin should be done under strict medical 
supervision. Changes in strength, brand (manufacturer), type (regular, NPH, lente, long-acting, etc.), 
origin (animal, human, human insulin analogue) and/or method of manufacture may result in the need 
for a change in dosage. 
The need to adjust (e.g. reduce) the dose may become evident immediately after transfer. 
Alternatively, it may emerge gradually over a period of several weeks. 
 
Following transfer from an animal insulin to human insulin, dose regimen reduction may be required 
in particular in patients who 
- were previously already controlled on rather low blood glucose levels, 
- have a tendency to hypoglycaemia, 
- previously required high insulin doses due to the presence of insulin antibodies. 
 

 

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Close metabolic monitoring is recommended during the transition and in the initial weeks thereafter. In 
patients who require high insulin doses because of the presence of insulin antibodies, transfer under 
medical supervision in a hospital or similar setting must be considered. 
 
Hypoglycaemia 
Hypoglycaemia may occur if the insulin dose is too high in relation to the insulin requirement. 
 
Particular caution should be exercised, and intensified blood glucose monitoring is advisable in 
patients in whom hypoglycaemic episodes might be of particular clinical relevance, such as in patients 
with significant stenoses of the coronary arteries or of the blood vessels supplying the brain (risk of 
cardiac or cerebral complications of hypoglycaemia) as well as in patients with proliferative 
retinopathy, particularly if not treated with photocoagulation (risk of transient amaurosis following 
hypoglycaemia). 
 
Patients should be aware of circumstances where warning symptoms of hypoglycaemia are 
diminished. The warning symptoms of hypoglycaemia may be changed, be less pronounced or be 
absent in certain risk groups. These include patients: 
- in whom glycaemic control is markedly improved, 
- in whom hypoglycaemia develops gradually, 
- who are elderly,  
- after transfer from animal insulin to human insulin, 
- in whom an autonomic neuropathy is present, 
- with a long history of diabetes, 
- suffering from a psychiatric illness, 
- receiving concurrent treatment with certain other medicinal products (see section 4.5). 
Such situations may result in severe hypoglycaemia (and possibly loss of consciousness) prior to the 
patient's awareness of hypoglycaemia. 
 
If normal or decreased values for glycated haemoglobin are noted, the possibility of recurrent, 
unrecognised (especially nocturnal) episodes of hypoglycaemia must be considered. 
 
Adherence of the patient to the dose regimen and dietary regimen, correct insulin administration and 
awareness of hypoglycaemia symptoms are essential to reduce the risk of hypoglycaemia. Factors 
increasing the susceptibility to hypoglycaemia require particularly close monitoring and may 
necessitate dose adjustment. These include: 
- change in the injection area, 
- improved insulin sensitivity (e.g. by removal of stress factors), 
- unaccustomed, increased or prolonged physical activity, 
- intercurrent illness (e.g. vomiting, diarrhoea), 
- inadequate food intake, 
- missed meals, 
- alcohol consumption, 
- certain uncompensated endocrine disorders (e.g. in hypothyroidism and in anterior pituitary or 

adrenocortical insufficiency), 
- concomitant treatment with certain other medicinal products. 
 
Intercurrent illness 
Intercurrent illness requires intensified metabolic monitoring. In many cases, urine tests for ketones 
are indicated, and often it is necessary to adjust the insulin dose. The insulin requirement is often 
increased. Patients with type 1 diabetes must continue to consume at least a small amount of 
carbohydrates on a regular basis, even if they are able to eat only little or no food, or are vomiting etc. 
and they must never omit insulin entirely. 
 
Handling of the pen 
Before using SoloStar, the Instructions for Use included in the Package Leaflet must be read carefully. 
SoloStar has to be used as recommended in these Instructions for Use (see section 6.6). 
 

 

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Medication errors 
Medication errors have been reported in which other Insulin Human Winthrop formulations or other 
insulins have been accidentally administered. Insulin label must always be checked before each 
injection to avoid medication errors between insulin human and other insulins. 
 
Combination of Insulin Human Winthrop with pioglitazone 
Cases of cardiac failure have been reported when pioglitazone was used in combination with insulin, 
especially in patients with risk factors for development of cardiac heart failure. This should be kept in 
mind if treatment with the combination of pioglitazone and Insulin Human Winthrop is considered. If 
the combination is used, patients should be observed for signs and symptoms of heart failure, weight 
gain and oedema. Pioglitazone should be discontinued if any deterioration in cardiac symptoms 
occurs.  
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
A number of substances affect glucose metabolism and may require dose adjustment of human insulin. 
 
Substances that may enhance the blood-glucose-lowering effect and increase susceptibility to 
hypoglycaemia include oral antidiabetic medicinal products, angiotensin converting enzyme (ACE) 
inhibitors, disopyramide, fibrates, fluoxetine, monoamine oxidase (MAO) inhibitors, pentoxifylline, 
propoxyphene, salicylates and sulphonamide antibiotics. 
 
Substances that may reduce the blood-glucose-lowering effect include corticosteroids, danazol, 
diazoxide, diuretics, glucagon, isoniazid, oestrogens and progestogens (e.g. in oral contraceptives), 
phenothiazine derivatives, somatropin, sympathomimetic medicinal products (e.g. epinephrine 
[adrenaline], salbutamol, terbutaline), thyroid hormones, protease inhibitors and atypical antipsychotic 
medicinal products (e.g. olanzapine and clozapine). 
 
Beta-blockers, clonidine, lithium salts or alcohol may either potentiate or weaken the 
blood-glucose-lowering effect of insulin. Pentamidine may cause hypoglycaemia which may 
sometimes be followed by hyperglycaemia. 
 
In addition, under the influence of sympatholytic medicinal products such as beta-blockers, clonidine, 
guanethidine and reserpine, the signs of adrenergic counter-regulation may be reduced or absent. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
For insulin human, no clinical data on exposed pregnancies from controlled clinical studies are 
available. Insulin does cross the placental barrier, although not in clinically significant amount. A 
limited amount of data on pregnant women (less than 300 pregnancy outcomes reported) exposed to 
marketed insulin human indicates no safety issues in use of insulin human in pregnancy. Caution 
should be exercised when prescribing to pregnant women. 
 
It is essential for patients with pre-existing or gestational diabetes to maintain good metabolic control 
throughout pregnancy. Insulin requirements may decrease during the first trimester and generally 
increase during the second and third trimesters. Immediately after delivery, insulin requirements 
decline rapidly (increased risk of hypoglycaemia). Careful monitoring of glucose control is essential. 
 
Breast-feeding 
No effects on the suckling child are anticipated. Insulin Human Winthrop Comb 15 can be used during 
breast-feeding. Breast-feeding women may require adjustments in insulin dose and diet. 
 
Fertility 
No clinical or animal data with insulin human on male or female fertility are available. 
 

 

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4.7 Effects on ability to drive and use machines 
 
The patient's ability to concentrate and react may be impaired as a result of hypoglycaemia or 
hyperglycaemia or, for example, as a result of visual impairment. This may constitute a risk in 
situations where these abilities are of special importance (e.g. driving a car or using machines). 
 
Patients should be advised to take precautions to avoid hypoglycaemia whilst driving. This is 
particularly important in those who have reduced or absent awareness of the warning symptoms of 
hypoglycaemia or have frequent episodes of hypoglycaemia. It should be considered whether it is 
advisable to drive or use machines in these circumstances. 
 
4.8 Undesirable effects 
 
Summary of the safety profile  
Hypoglycaemia, in general the most frequent adverse reaction of insulin therapy, may occur if the 
insulin dose is too high in relation to the insulin requirement. In clinical studies and during marketed 
use, the frequency varies with patient population and dose regimens. Therefore, no specific frequency 
can be presented. 
 
Tabulated list of adverse reactions 
The following related adverse reactions from clinical investigations are listed below by system organ 
class and in order of decreasing incidence: very common (≥1/10); common (≥1/100 to <1/10); 
uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000), not known 
(cannot be estimated from the available data). 
 
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. 
 
MedDRA system 
organ classes 

Common Uncommon Not known 

Immune system 
disorders 

 Shock Immediate type allergic 
reactions (hypotension, 
angioneurotic oedema, 
bronchospasm, 
generalised skin 
reactions); 
Anti-insulin antibodies 

Metabolism and 
nutrition disorders 

Oedema  Hypoglycaemia; 
Sodium retention 

Eye disorders   Proliferative retinopathy; 
Diabetic retinopathy; 
Visual impairment 

Skin and subcutaneous 
tissue disorders 

  Lipodystrophy 

General disorders and 
administration site 
conditions 

Injection site reactions Injection site 
urticaria 

Injection site 
inflammation;  
Injection site pain; 
Injection site pruritus; 
Injection site erythema; 
Injection site swelling 

 
Description of selected adverse reactions 
Immune system disorders 
Immediate type allergic reactions to insulin or to the excipients may be life-threatening. 
 
Insulin administration may cause anti-insulin antibodies to form. In rare cases, the presence of such 
anti-insulin antibodies may necessitate adjustment of the insulin dose in order to correct a tendency to 
hyper- or hypoglycaemia. 

 

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Metabolism and nutrition disorders 
Severe hypoglycaemic attacks, especially if recurrent, may lead to neurological damage. 
Prolonged or severe hypoglycaemic episodes may be life-threatening. 
 
In many patients, the signs and symptoms of neuroglycopenia are preceded by signs of adrenergic 
counter-regulation. Generally, the greater and more rapid the decline in blood glucose, the more 
marked is the phenomenon of counter-regulation and its symptoms. 
 
Insulin may cause sodium retention and oedema, particularly if previously poor metabolic control is 
improved by intensified insulin therapy. 
 
Eyes disorders 
A marked change in glycaemic control may cause temporary visual impairment, due to temporary 
alteration in the turgidity and refractive index of the lens. 
 
Long-term improved glycaemic control decreases the risk of progression of diabetic retinopathy. 
However, intensification of insulin therapy with abrupt improvement in glycaemic control may be 
associated with temporary worsening of diabetic retinopathy. 
 
Skin and subcutaneous tissue disorders 
Lipodystrophy may occur at the injection site and delay local insulin absorption. Continuous rotation 
of the injection site within the given injection area may help to reduce or prevent these reactions. 
 
General disorders and administration site conditions 
Most minor reactions to insulins at the injection site usually resolve in a few days to a few weeks. 
 
4.9 Overdose 
 
Symptoms 
Insulin overdose may lead to severe and sometimes long-term and life-threatening hypoglycaemia. 
 
Management 
Mild episodes of hypoglycaemia can usually be treated with oral carbohydrates. Adjustments in dose 
regimen of the medicinal product, meal patterns, or physical activity may be needed. 
 
More severe episodes with coma, seizure, or neurologic impairment may be treated with 
intramuscular/subcutaneous glucagon or concentrated intravenous glucose. Sustained carbohydrate 
intake and observation may be necessary because hypoglycaemia may recur after apparent clinical 
recovery. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Drugs used in diabetes, insulins and analogues for injection, 
intermediate-acting combined with fast-acting, ATC Code: A10AD01. 
 
Mechanism of action 
Insulin 
- lowers blood glucose and promotes anabolic effects as well as decreasing catabolic effects, 
- increases the transport of glucose into cells as well as the formation of glycogen in the muscles 

and the liver, and improves pyruvate utilisation. It inhibits glycogenolysis and gluconeogenesis, 
- increases lipogenesis in the liver and adipose tissue and inhibits lipolysis, 
- promotes the uptake of amino acids into cells and promotes protein synthesis, 
- enhances the uptake of potassium into cells. 

 

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Pharmacodynamic effects 
Insulin Human Winthrop Comb 15 (a biphasic isophane insulin suspension with 15% dissolved 
insulin) is an insulin with gradual onset and long duration of action. Following subcutaneous injection, 
onset of action is within 30 to 60 minutes, the phase of maximum action is between 2 and 4 hours after 
injection and the duration of action is 11 to 20 hours. 
 
5.2 Pharmacokinetic properties 
 
In healthy subjects, the serum half-life of insulin is approximately 4 to 6 minutes. It is longer in 
patients with severe renal insufficiency. However, it must be noted that the pharmacokinetics of 
insulin do not reflect its metabolic action. 
 
5.3 Preclinical safety data 
 
The acute toxicity was studied following subcutaneous administration in rats. No evidence of toxic 
effects was found. Studies of pharmacodynamic effects following subcutaneous administration in 
rabbits and dogs revealed the expected hypoglycaemic reactions. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Protamine sulphate, 
metacresol, 
phenol, 
zinc chloride, 
sodium dihydrogen phosphate dihydrate, 
glycerol, 
sodium hydroxide, 
hydrochloric acid (for pH adjustment), 
water for injections. 
 
6.2 Incompatibilities 
 
This medicinal product must not be mixed with other medicinal products except those mentioned in 
section 6.6. 
 
Insulin Human Winthrop Comb 15 must not be mixed with solutions containing reducing substances 
such as thioles and sulphites.  
 
Mixing of insulins 
Insulin Human Winthrop Comb 15 must not be mixed with any other insulin or with insulin 
analogues. 
 
Care must be taken to ensure that no alcohol or other disinfectants enter the insulin suspension. 
 
6.3 Shelf life 
 
2 years. 
 
Shelf life after first use of the pen 
The pen in-use or carried as a spare may be stored for a maximum of 4 weeks not above 25°C and 
away from direct heat or direct light. 
Pens in-use must not be stored in the refrigerator. 
The pen cap must be put back on the pen after each injection in order to protect from light. 

 

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6.4 Special precautions for storage 
 
Not in-use pens 
Store in a refrigerator (2°C - 8°C). 
Do not freeze. 
Do not put Insulin Human Winthrop Comb 15 next to the freezer compartment or a freezer pack. 
Keep the pre-filled pen in the outer carton in order to protect from light. 
 
In-use pens 
For storage conditions after first opening of the medicinal product, see section 6.3. 
 
6.5 Nature and contents of container 
 
3 ml suspension in a cartridge (type 1 colourless glass) with a plunger (bromobutyl rubber (type 1)) 
and a flanged cap (aluminium) with a stopper (bromobutyl or laminate of polyisoprene and 
bromobutyl rubber (type 1)). 
Each cartridge contains 3 balls (stainless steel). 
The cartridges are sealed in a disposable pen injector. 
Injection needles are not included in the pack. 
Packs of 3, 4, 5, 6, 9 or 10 pens are available. 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal and other handling 
 
Before first use, Insulin Human Winthrop Comb 15 must be kept at room temperature for 1 to 2 hours 
and then resuspended to check the contents. This is best done by gently tilting the pen back and forth 
(at least ten times). Each cartridge contains three small metal balls to facilitate quick and thorough 
mixing of the contents. Later on, the insulin must be resuspended again prior to each injection. 
 
After resuspension, the fluid must have a uniformly milky appearance. Insulin Human Winthrop 
Comb 15 must not be used if this cannot be achieved, i.e. if the suspension remains clear, for example, 
or if clumps, particles or flocculation appear in the insulin or stick to the wall or bottom of the 
cartridge. These changes sometimes give the cartridge a frosted appearance. In such cases, a new pen 
yielding a uniform suspension must be used. It is also necessary to change to a new pen if the insulin 
requirement changes substantially. 
 
Empty pens must never be re-used and must be properly discarded. 
 
To prevent the possible transmission of disease, each pen must be used by one patient only. 
 
It must be remembered that 
- insulin protamine crystals dissolve in an acid pH range, 
- the soluble insulin part precipitates out at a pH of approximately 4.5 to 6.5. 
 
Insulin label must always be checked before each injection to avoid medication errors between insulin 
human and other insulins (see section 4.4). 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 

 

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Handling of the pen 
The patient should be advised to read the instructions for use included in the package leaflet 
carefully before using SoloStar. 
 

 
Schematic diagram of the pen 

 
Important information for use of SoloStar: 
 
• Before each use, a new needle must always be carefully attached and a safety test must be 

performed. A dose should not be selected and/or the injection button should not be pressed 
without a needle attached. Only use needles that are compatible for use with SoloStar. 

• Special caution must be taken to avoid accidental needle injury and transmission of infection. 
• SoloStar must never be used if it is damaged or if the patient is not sure if it is working properly.  
• The patient must always have a spare SoloStar available in case the SoloStar is lost or damaged. 
 
Storage instructions  
 
Please check section 6.4 for instructions on how to store SoloStar. 
 
If SoloStar is in cool storage, it should be taken out 1 to 2 hours before injection to allow it to warm 
up. Cold insulin is more painful to inject. 
 
The used SoloStar must be discarded as required by your local authorities. 
 
Maintenance 
 
SoloStar has to be protected from dust and dirt. 
 
The outside of the SoloStar can be cleaned by wiping it with a damp cloth. 
 
The pen must not be soaked, washed or lubricated as this may damage it. 
 
SoloStar is designed to work accurately and safely. It should be handled with care. The patient should 
avoid situations where SoloStar may be damaged. If the patient is concerned that the SoloStar may be 
damaged, he must use a new one. 
 
Step 1. Check the insulin 
 
The label on the pen should be checked to make sure it contains the correct insulin. Insulin Human 
Winthrop SoloStar is white with a colour on the injection button. The injection button colour will vary 
based on the formulation of Insulin Human Winthrop insulin used. 
 
After removing the pen cap, the appearance of the insulin should also be checked: 
The insulin suspensions (Insulin Human Winthrop Basal or Insulin Human Winthrop mixtures) should 
be mixed by turning SoloStar up and down at least 10 times to resuspend the insulin. The pen should 
be turned gently to avoid foaming in the cartridge. After mixing, the insulin suspensions must have an 
evenly milky-white appearance. 
 
Step 2. Attach the needle 
 
Only needles that are compatible for use with SoloStar should be used. 

 

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A new sterile needle will be always used for each injection. After removing the cap, the needle should 
be carefully attached straight onto the pen. 
 
Step 3. Perform a safety test  
 
Prior to each injection, a safety test has to be performed to ensure that pen and needle work properly 
and to remove air bubbles. 
 
A dose of 2 units has to be selected. 
The outer and inner needle caps should be removed. 
 
While holding the pen with the needle pointing upwards, the insulin reservoir should be tapped gently 
with the finger so that any air bubbles rise up towards the needle. 
 
Then the injection button should be pressed in completely. 
 
If insulin has been expelled through the needle tip, then the pen and the needle are working properly. 
If no insulin appears at the needle tip, step 3 should be repeated until insulin appears at the needle tip. 
 
Step 4. Select the dose 
 
The dose can be set in steps of 1 unit, from a minimum of 1 unit to a maximum of 80 units. If a dose 
greater than 80 units is required, it should be given as two or more injections. 
 
The dose window must show “0” following the safety test. The dose can then be selected. 
 
Step 5. Inject the dose 
 
The patient should be informed on the injection technique by his health care professional.  
The needle should be inserted into the skin. 
The injection button should be pressed in completely. Then the injection button should be held down 
10 seconds before withdrawing the needle. This ensures that the full dose of insulin has been injected. 
 
Step 6. Remove and discard the needle 
 
The needle should always be removed after each injection and discarded. This helps prevent 
contamination and/or infection, entry of air into the insulin reservoir and leakage of insulin. Needles 
mut not be re-used. 
 
Special caution must be taken when removing and disposing of the needle. Recommended safety 
measures for removal and disposal of needles must be followed (e.g. a one handed capping technique) 
in order to reduce the risk of accidental needle injury and transmission of infectious diseases. 
 
The pen cap should be replaced on the pen. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Sanofi-Aventis Deutschland GmbH, D-65926 Frankfurt am Main, Germany 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/06/368/125 
EU/1/06/368/126 
EU/1/06/368/127 

 

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EU/1/06/368/128 
EU/1/06/368/129 
EU/1/06/368/130 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 17 January 2007 
Date of latest renewal: 17 January 2012 
 
 
10. DATE OF REVISION OF THE TEXT 
 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu 

 

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1. NAME OF THE MEDICINAL PRODUCT 
 
Insulin Human Winthrop Comb 25 100 IU/ml suspension for injection in a vial 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each ml contains 100 IU insulin human (equivalent to 3.5 mg).  
Each vial contains 5 ml of suspension for injection, equivalent to 500 IU insulin. One IU 
(International Unit) corresponds to 0.035 mg of anhydrous human insulin. 
 
Insulin Human Winthrop Comb 25 is a biphasic isophane insulin suspension consisting of 25% 
dissolved insulin and 75% crystalline protamine insulin. 
 
Human insulin is produced by recombinant DNA technology in Escherichia coli. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Suspension for injection in a vial. 
 
After resuspension, milky-white suspension. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Diabetes mellitus where treatment with insulin is required. 
 
4.2 Posology and method of administration 
 
Posology 
The desired blood glucose levels, the insulin preparations to be used and the insulin dose regimen 
(doses and timings) must be determined individually and adjusted to suit the patient’s diet, physical 
activity and life-style. 
 
Daily doses and timing of administration 
There are no fixed rules for insulin dose regimen. However, the average insulin requirement is often 
0.5 to 1.0 IU per kg body weight per day. The basal metabolic requirement is 40% to 60% of the total 
daily requirement. Insulin Human Winthrop Comb 25 is injected subcutaneously 30 to 45 minutes 
before a meal. 
 
Secondary dose adjustment 
Improved metabolic control may result in increased insulin sensitivity, leading to a reduced insulin 
requirement. Dose adjustment may also be required, for example, if 
- the patient's weight changes, 
- the patient's life-style changes, 
- other circumstances arise that may promote an increased susceptibility to hypo- or 

hyperglycaemia (see section 4.4). 
 

 

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Special populations 
Elderly population (≧65 years old) 
In the elderly, progressive deterioration of renal function may lead to a steady decrease in insulin 
requirements. 
 
Renal impairment 
In patients with renal impairment, insulin requirements may be diminished due to reduced insulin 
metabolism. 
 
Hepatic impairment 
In patients with severe hepatic impairment, insulin requirements may be diminished due to reduced 
capacity for gluconeogenesis and reduced insulin metabolism. 
 
Method of administration 
Insulin Human Winthrop Comb 25 must not be administered intravenously and must not be used in 
infusion pumps or external or implanted insulin pumps. 
 
Only injection syringes designed for this strength of insulin (100 IU per ml) are to be used. The 
injection syringes must not contain any other medicinal product or residue (e.g. traces of heparin). 
 
Insulin Human Winthrop Comb 25 is administered subcutaneously. Insulin Human Winthrop 
Comb 25 must never be injected intravenously. 
 
Insulin absorption and hence the blood-glucose-lowering effect of a dose may vary from one injection 
area to another (e.g. the abdominal wall compared with the thigh). Injection sites within an injection 
area must be rotated from one injection to the next. 
 
For further details on handling, see section 6.6. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
 
4.4 Special warnings and precautions for use 
 
Patients hypersensitive to Insulin Human Winthrop Comb 25 for whom no better tolerated preparation 
is available must only continue treatment under close medical supervision and – where necessary – in 
conjunction with anti-allergic treatment. 
 
In patients with an allergy to animal insulin intradermal skin testing is recommended prior to a 
transfer to Insulin Human Winthrop Comb 25, since they may experience immunological 
cross-reactions. 
 
In case of insufficient glucose control or a tendency to hyper- or hypoglycaemic episodes, the patient's 
adherence to the prescribed treatment regimen, injection sites and proper injection technique and all 
other relevant factors must be reviewed before dose adjustment is considered. 
 
Transfer to Insulin Human Winthrop Comb 25 
Transferring a patient to another type or brand of insulin should be done under strict medical 
supervision. Changes in strength, brand (manufacturer), type (regular, NPH, lente, long-acting, etc.), 
origin (animal, human, human insulin analogue) and/or method of manufacture may result in the need 
for a change in dosage. 
The need to adjust (e.g. reduce) the dose may become evident immediately after transfer. 
Alternatively, it may emerge gradually over a period of several weeks. 
 

 

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Following transfer from an animal insulin to human insulin, dose regimen reduction may be required 
in particular in patients who 
- were previously already controlled on rather low blood glucose levels, 
- have a tendency to hypoglycaemia, 
- previously required high insulin doses due to the presence of insulin antibodies. 
 
Close metabolic monitoring is recommended during the transition and in the initial weeks thereafter. In 
patients who require high insulin doses because of the presence of insulin antibodies, transfer under 
medical supervision in a hospital or similar setting must be considered. 
 
Hypoglycaemia 
Hypoglycaemia may occur if the insulin dose is too high in relation to the insulin requirement. 
 
Particular caution should be exercised, and intensified blood glucose monitoring is advisable in 
patients in whom hypoglycaemic episodes might be of particular clinical relevance, such as in patients 
with significant stenoses of the coronary arteries or of the blood vessels supplying the brain (risk of 
cardiac or cerebral complications of hypoglycaemia) as well as in patients with proliferative 
retinopathy, particularly if not treated with photocoagulation (risk of transient amaurosis following 
hypoglycaemia). 
 
Patients should be aware of circumstances where warning symptoms of hypoglycaemia are 
diminished. The warning symptoms of hypoglycaemia may be changed, be less pronounced or be 
absent in certain risk groups. These include patients: 
- in whom glycaemic control is markedly improved, 
- in whom hypoglycaemia develops gradually, 
- who are elderly,  
- after transfer from animal insulin to human insulin, 
- in whom an autonomic neuropathy is present, 
- with a long history of diabetes, 
- suffering from a psychiatric illness, 
- receiving concurrent treatment with certain other medicinal products (see section 4.5). 
Such situations may result in severe hypoglycaemia (and possibly loss of consciousness) prior to the 
patient's awareness of hypoglycaemia. 
 
If normal or decreased values for glycated haemoglobin are noted, the possibility of recurrent, 
unrecognised (especially nocturnal) episodes of hypoglycaemia must be considered. 
 
Adherence of the patient to the dose regimen and dietary regimen, correct insulin administration and 
awareness of hypoglycaemia symptoms are essential to reduce the risk of hypoglycaemia. Factors 
increasing the susceptibility to hypoglycaemia require particularly close monitoring and may 
necessitate dose adjustment. These include: 
- change in the injection area, 
- improved insulin sensitivity (e.g. by removal of stress factors), 
- unaccustomed, increased or prolonged physical activity, 
- intercurrent illness (e.g. vomiting, diarrhoea), 
- inadequate food intake, 
- missed meals, 
- alcohol consumption, 
- certain uncompensated endocrine disorders (e.g. in hypothyroidism and in anterior pituitary or 

adrenocortical insufficiency), 
- concomitant treatment with certain other medicinal products. 
 
Intercurrent illness 
Intercurrent illness requires intensified metabolic monitoring. In many cases, urine tests for ketones 
are indicated, and often it is necessary to adjust the insulin dose. The insulin requirement is often 
increased. Patients with type 1 diabetes must continue to consume at least a small amount of 

 

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carbohydrates on a regular basis, even if they are able to eat only little or no food, or are vomiting etc. 
and they must never omit insulin entirely. 
 
Medication errors 
Medication errors have been reported in which other Insulin Human Winthrop formulations or other 
insulins have been accidentally administered. Insulin label must always be checked before each 
injection to avoid medication errors between insulin human and other insulins. 
 
Combination of Insulin Human Winthrop with pioglitazone 
Cases of cardiac failure have been reported when pioglitazone was used in combination with insulin, 
especially in patients with risk factors for development of cardiac heart failure. This should be kept in 
mind if treatment with the combination of pioglitazone and Insulin Human Winthrop is considered. If 
the combination is used, patients should be observed for signs and symptoms of heart failure, weight 
gain and oedema. Pioglitazone should be discontinued if any deterioration in cardiac symptoms 
occurs.  
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
A number of substances affect glucose metabolism and may require dose adjustment of human insulin. 
 
Substances that may enhance the blood-glucose-lowering effect and increase susceptibility to 
hypoglycaemia include oral antidiabetic medicinal products, angiotensin converting enzyme (ACE) 
inhibitors, disopyramide, fibrates, fluoxetine, monoamine oxidase (MAO) inhibitors, pentoxifylline, 
propoxyphene, salicylates and sulphonamide antibiotics. 
 
Substances that may reduce the blood-glucose-lowering effect include corticosteroids, danazol, 
diazoxide, diuretics, glucagon, isoniazid, oestrogens and progestogens (e.g. in oral contraceptives), 
phenothiazine derivatives, somatropin, sympathomimetic medicinal products (e.g. epinephrine 
[adrenaline], salbutamol, terbutaline), thyroid hormones, protease inhibitors and atypical antipsychotic 
medicinal products (e.g. olanzapine and clozapine). 
 
Beta-blockers, clonidine, lithium salts or alcohol may either potentiate or weaken the 
blood-glucose-lowering effect of insulin. Pentamidine may cause hypoglycaemia which may 
sometimes be followed by hyperglycaemia. 
 
In addition, under the influence of sympatholytic medicinal products such as beta-blockers, clonidine, 
guanethidine and reserpine, the signs of adrenergic counter-regulation may be reduced or absent. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
For insulin human, no clinical data on exposed pregnancies from controlled clinical studies are 
available. Insulin does cross the placental barrier, although not in clinically significant amount. A 
limited amount of data on pregnant women (less than 300 pregnancy outcomes reported) exposed to 
marketed insulin human indicates no safety issues in use of insulin human in pregnancy. Caution 
should be exercised when prescribing to pregnant women. 
 
It is essential for patients with pre-existing or gestational diabetes to maintain good metabolic control 
throughout pregnancy. Insulin requirements may decrease during the first trimester and generally 
increase during the second and third trimesters. Immediately after delivery, insulin requirements 
decline rapidly (increased risk of hypoglycaemia). Careful monitoring of glucose control is essential. 
 
Breast-feeding 
No effects on the suckling child are anticipated. Insulin Human Winthrop Comb 25 can be used during 
breast-feeding. Breast-feeding women may require adjustments in insulin dose and diet. 
 

 

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Fertility 
No clinical or animal data with insulin human on male or female fertility are available. 
 
4.7 Effects on ability to drive and use machines 
 
The patient's ability to concentrate and react may be impaired as a result of hypoglycaemia or 
hyperglycaemia or, for example, as a result of visual impairment. This may constitute a risk in 
situations where these abilities are of special importance (e.g. driving a car or using machines). 
 
Patients should be advised to take precautions to avoid hypoglycaemia whilst driving. This is 
particularly important in those who have reduced or absent awareness of the warning symptoms of 
hypoglycaemia or have frequent episodes of hypoglycaemia. It should be considered whether it is 
advisable to drive or use machines in these circumstances. 
 
4.8 Undesirable effects 
 
Summary of the safety profile  
Hypoglycaemia, in general the most frequent adverse reaction of insulin therapy, may occur if the 
insulin dose is too high in relation to the insulin requirement. In clinical studies and during marketed 
use, the frequency varies with patient population and dose regimens. Therefore, no specific frequency 
can be presented. 
 
Tabulated list of adverse reactions 
The following related adverse reactions from clinical investigations are listed below by system organ 
class and in order of decreasing incidence: very common (≥1/10); common (≥1/100 to <1/10); 
uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000), not known 
(cannot be estimated from the available data). 
 
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. 
 
MedDRA system 
organ classes 

Common Uncommon Not known 

Immune system 
disorders 

 Shock Immediate type 
allergic reactions 
(hypotension, 
angioneurotic oedema, 
bronchospasm, 
generalised skin 
reactions); 
Anti-insulin antibodies 

Metabolism and 
nutrition disorders 

Oedema  Hypoglycaemia; 
Sodium retention 

Eye disorders   Proliferative 
retinopathy; 
Diabetic retinopathy; 
Visual impairment 

Skin and 
subcutaneous tissue 
disorders 

  Lipodystrophy 

General disorders 
and administration 
site conditions 

Injection site reactions Injection site 
urticaria 

Injection site 
inflammation;  
Injection site pain; 
Injection site pruritus; 
Injection site 
erythema;  
Injection site swelling 

 

 

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Description of selected adverse reactions 
Immune system disorders 
Immediate type allergic reactions to insulin or to the excipients may be life-threatening. 
 
Insulin administration may cause anti-insulin antibodies to form. In rare cases, the presence of such 
anti-insulin antibodies may necessitate adjustment of the insulin dose in order to correct a tendency to 
hyper- or hypoglycaemia. 
 
Metabolism and nutrition disorders 
Severe hypoglycaemic attacks, especially if recurrent, may lead to neurological damage. 
Prolonged or severe hypoglycaemic episodes may be life-threatening. 
 
In many patients, the signs and symptoms of neuroglycopenia are preceded by signs of adrenergic 
counter-regulation. Generally, the greater and more rapid the decline in blood glucose, the more 
marked is the phenomenon of counter-regulation and its symptoms. 
 
Insulin may cause sodium retention and oedema, particularly if previously poor metabolic control is 
improved by intensified insulin therapy. 
 
Eyes disorders 
A marked change in glycaemic control may cause temporary visual impairment, due to temporary 
alteration in the turgidity and refractive index of the lens. 
 
Long-term improved glycaemic control decreases the risk of progression of diabetic retinopathy. 
However, intensification of insulin therapy with abrupt improvement in glycaemic control may be 
associated with temporary worsening of diabetic retinopathy. 
 
Skin and subcutaneous tissue disorders 
Lipodystrophy may occur at the injection site and delay local insulin absorption. Continuous rotation 
of the injection site within the given injection area may help to reduce or prevent these reactions. 
 
General disorders and administration site conditions 
Most minor reactions to insulins at the injection site usually resolve in a few days to a few weeks. 
 
4.9 Overdose 
 
Symptoms 
Insulin overdose may lead to severe and sometimes long-term and life-threatening hypoglycaemia. 
 
Management 
Mild episodes of hypoglycaemia can usually be treated with oral carbohydrates. Adjustments in dose 
regimen of the medicinal product, meal patterns, or physical activity may be needed. 
 
More severe episodes with coma, seizure, or neurologic impairment may be treated with 
intramuscular/subcutaneous glucagon or concentrated intravenous glucose. Sustained carbohydrate 
intake and observation may be necessary because hypoglycaemia may recur after apparent clinical 
recovery. 
 
 

 

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5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Drugs used in diabetes, insulins and analogues for injection, 
intermediate-acting combined with fast-acting, ATC Code: A10AD01. 
 
Mechanism of action 
Insulin 
- lowers blood glucose and promotes anabolic effects as well as decreasing catabolic effects, 
- increases the transport of glucose into cells as well as the formation of glycogen in the muscles 

and the liver, and improves pyruvate utilisation. It inhibits glycogenolysis and gluconeogenesis, 
- increases lipogenesis in the liver and adipose tissue and inhibits lipolysis, 
- promotes the uptake of amino acids into cells and promotes protein synthesis, 
- enhances the uptake of potassium into cells. 
 
Pharmacodynamic effects 
Insulin Human Winthrop Comb 25 (a biphasic isophane insulin suspension with 25% dissolved 
insulin) is an insulin with gradual onset and long duration of action. Following subcutaneous injection, 
onset of action is within 30 to 60 minutes, the phase of maximum action is between 2 and 4 hours after 
injection and the duration of action is 12 to 19 hours. 
 
5.2 Pharmacokinetic properties 
 
In healthy subjects, the serum half-life of insulin is approximately 4 to 6 minutes. It is longer in 
patients with severe renal insufficiency. However, it must be noted that the pharmacokinetics of 
insulin do not reflect its metabolic action. 
 
5.3 Preclinical safety data 
 
The acute toxicity was studied following subcutaneous administration in rats. No evidence of toxic 
effects was found. Studies of pharmacodynamic effects following subcutaneous administration in 
rabbits and dogs revealed the expected hypoglycaemic reactions. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Protamine sulphate, 
metacresol, 
phenol, 
zinc chloride, 
sodium dihydrogen phosphate dihydrate, 
glycerol, 
sodium hydroxide, 
hydrochloric acid (for pH adjustment), 
water for injections. 
 
6.2 Incompatibilities 
 
This medicinal product must not be mixed with other medicinal products except those mentioned in 
section 6.6. 
 
Insulin Human Winthrop Comb 25 must not be mixed with solutions containing reducing substances 
such as thioles and sulphites.  
 

 

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Mixing of insulins 
Insulin Human Winthrop Comb 25 must not be mixed with insulin human formulations designed 
specifically for use in insulin pumps.  
Insulin Human Winthrop Comb 25 must also not be mixed with insulins of animal origin or with 
insulin analogues. 
Insulins of different concentration (e.g. 100 IU per ml and 40 IU per ml) must not be mixed. 
 
Care must be taken to ensure that no alcohol or other disinfectants enter the insulin suspension. 
 
6.3 Shelf life 
 
2 years. 
 
Shelf life after first use of the vial 
The product may be stored for a maximum of 4 weeks not above 25°C and away from direct heat or 
direct light. 
Keep the vial in the outer carton in order to protect from light. 
It is recommended that the date of the first use be noted on the label. 
 
6.4 Special precautions for storage 
 
Unopened vials 
Store in a refrigerator (2°C - 8°C). 
Do not freeze. 
Do not put Insulin Human Winthrop Comb 25 next to the freezer compartment or a freezer pack. 
Keep the vial in the outer carton in order to protect from light. 
 
Opened vials 
For storage conditions after first opening of the medicinal product, see section 6.3. 
 
6.5 Nature and contents of container 
 
5 ml suspension in a vial (type 1 colourless glass) with a flanged cap (aluminium), a stopper 
(chlorobutyl rubber (type 1)) and a tear-off cap (polypropylene). 
Packs of 1 and 5 vials are available. 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal and other handling 
 
Before withdrawing insulin from the vial for the first time, remove the plastic protective cap. 
 
Immediately before withdrawal from the vial into the injection syringe, the insulin must be 
resuspended. This is best done by rolling the vial at an oblique angle between the palms of the hands. 
Do not shake the vial vigorously as this may lead to changes in the suspension (giving the vial a 
frosted appearance; see below) and cause frothing. Froth may interfere with the correct measurement 
of the dose. 
 
After resuspension, the fluid must have a uniformly milky appearance. Insulin Human Winthrop 
Comb 25 must not be used if this cannot be achieved, i.e. if the suspension remains clear, for example, 
or if clumps, particles or flocculation appear in the insulin or stick to the wall or bottom of the vial. 
These changes sometimes give the vial a frosted appearance. In such cases, a new vial yielding a 
uniform suspension must be used. It is also necessary to change to a new vial if the insulin 
requirement changes substantially. 
 
Insulin Human Winthrop Comb 25 must not be administered intravenously and must not be used in 
infusion pumps or external or implanted insulin pumps. 
 

 

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It must be remembered that 
- insulin protamine crystals dissolve in an acid pH range, 
- the soluble insulin part precipitates out at a pH of approximately 4.5 to 6.5. 
 
Insulin label must always be checked before each injection to avoid medication errors between insulin 
human and other insulins (see section 4.4). 
 
Mixing of insulins 
Insulin Human Winthrop Comb 25 may be mixed with all insulin human formulations, but not with 
those designed specifically for use in insulin pumps. Concerning incompatibility with other insulins, 
see section 6.2. 
 
If two different insulins have to be drawn into one single injection syringe, it is recommended that the 
shorter-acting insulin be drawn first to prevent contamination of the vial by the longer-acting 
preparation. It is advisable to inject immediately after mixing.  
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Sanofi-Aventis Deutschland GmbH, D-65926 Frankfurt am Main, Germany 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/06/368/038 
EU/1/06/368/039 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 17 January 2007 
Date of latest renewal: 17 January 2012 
 
 
10. DATE OF REVISION OF THE TEXT 
 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu 

 

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1. NAME OF THE MEDICINAL PRODUCT 
 
Insulin Human Winthrop Comb 25 40 IU/ml suspension for injection in a vial 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each ml contains 40 IU insulin human (equivalent to 1.4 mg).  
Each vial contains 10 ml of suspension for injection, equivalent to 400 IU insulin. One IU 
(International Unit) corresponds to 0.035 mg of anhydrous human insulin. 
 
Insulin Human Winthrop Comb 25 is a biphasic isophane insulin suspension consisting of 25% 
dissolved insulin and 75% crystalline protamine insulin. 
 
Human insulin is produced by recombinant DNA technology in Escherichia coli. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Suspension for injection in a vial. 
 
After resuspension, milky-white suspension. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Diabetes mellitus where treatment with insulin is required. 
 
4.2 Posology and method of administration 
 
Posology 
The desired blood glucose levels, the insulin preparations to be used and the insulin dose regimen 
(doses and timings) must be determined individually and adjusted to suit the patient’s diet, physical 
activity and life-style. 
 
Daily doses and timing of administration 
There are no fixed rules for insulin dose regimen. However, the average insulin requirement is often 
0.5 to 1.0 IU per kg body weight per day. The basal metabolic requirement is 40% to 60% of the total 
daily requirement. Insulin Human Winthrop Comb 25 is injected subcutaneously 30 to 45 minutes 
before a meal. 
 
Secondary dose adjustment 
Improved metabolic control may result in increased insulin sensitivity, leading to a reduced insulin 
requirement. Dose adjustment may also be required, for example, if 
- the patient's weight changes, 
- the patient's life-style changes, 
- other circumstances arise that may promote an increased susceptibility to hypo- or 

hyperglycaemia (see section 4.4). 
 
Special populations 
Elderly population (≧65 years old) 
In the elderly, progressive deterioration of renal function may lead to a steady decrease in insulin 
requirements. 

 

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Renal impairment 
In patients with renal impairment, insulin requirements may be diminished due to reduced insulin 
metabolism. 
 
Hepatic impairment 
In patients with severe hepatic impairment, insulin requirements may be diminished due to reduced 
capacity for gluconeogenesis and reduced insulin metabolism. 
 
Method of administration 
Insulin Human Winthrop Comb 25 must not be administered intravenously and must not be used in 
infusion pumps or external or implanted insulin pumps. 
 
Only injection syringes designed for this strength of insulin (40 IU per ml) are to be used. The 
injection syringes must not contain any other medicinal product or residue (e.g. traces of heparin). 
 
Insulin Human Winthrop Comb 25 is administered subcutaneously. Insulin Human Winthrop 
Comb 25 must never be injected intravenously. 
 
Insulin absorption and hence the blood–glucose-lowering effect of a dose may vary from one injection 
area to another (e.g. the abdominal wall compared with the thigh). Injection sites within an injection 
area must be rotated from one injection to the next. 
 
For further details on handling, see section 6.6. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
 
4.4 Special warnings and precautions for use 
 
Patients hypersensitive to Insulin Human Winthrop Comb 25 for whom no better tolerated preparation 
is available must only continue treatment under close medical supervision and – where necessary – in 
conjunction with anti-allergic treatment. 
 
In patients with an allergy to animal insulin intradermal skin testing is recommended prior to a 
transfer to Insulin Human Winthrop Comb 25, since they may experience immunological 
cross-reactions. 
 
In case of insufficient glucose control or a tendency to hyper- or hypoglycaemic episodes, the patient's 
adherence to the prescribed treatment regimen, injection sites and proper injection technique and all 
other relevant factors must be reviewed before dose adjustment is considered. 
 
Transfer to Insulin Human Winthrop Comb 25 
Transferring a patient to another type or brand of insulin should be done under strict medical 
supervision. Changes in strength, brand (manufacturer), type (regular, NPH, lente, long-acting, etc.), 
origin (animal, human, human insulin analogue) and/or method of manufacture may result in the need 
for a change in dosage. 
The need to adjust (e.g. reduce) the dose may become evident immediately after transfer. 
Alternatively, it may emerge gradually over a period of several weeks. 
 
Following transfer from an animal insulin to human insulin, dose regimen reduction may be required 
in particular in patients who 
- were previously already controlled on rather low blood glucose levels, 
- have a tendency to hypoglycaemia, 
- previously required high insulin doses due to the presence of insulin antibodies. 
 

 

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Close metabolic monitoring is recommended during the transition and in the initial weeks thereafter. In 
patients who require high insulin doses because of the presence of insulin antibodies, transfer under 
medical supervision in a hospital or similar setting must be considered. 
 
Hypoglycaemia 
Hypoglycaemia may occur if the insulin dose is too high in relation to the insulin requirement. 
 
Particular caution should be exercised, and intensified blood glucose monitoring is advisable in 
patients in whom hypoglycaemic episodes might be of particular clinical relevance, such as in patients 
with significant stenoses of the coronary arteries or of the blood vessels supplying the brain (risk of 
cardiac or cerebral complications of hypoglycaemia) as well as in patients with proliferative 
retinopathy, particularly if not treated with photocoagulation (risk of transient amaurosis following 
hypoglycaemia). 
 
Patients should be aware of circumstances where warning symptoms of hypoglycaemia are 
diminished. The warning symptoms of hypoglycaemia may be changed, be less pronounced or be 
absent in certain risk groups. These include patients: 
- in whom glycaemic control is markedly improved, 
- in whom hypoglycaemia develops gradually, 
- who are elderly,  
- after transfer from animal insulin to human insulin, 
- in whom an autonomic neuropathy is present, 
- with a long history of diabetes, 
- suffering from a psychiatric illness, 
- receiving concurrent treatment with certain other medicinal products (see section 4.5). 
Such situations may result in severe hypoglycaemia (and possibly loss of consciousness) prior to the 
patient's awareness of hypoglycaemia. 
 
If normal or decreased values for glycated haemoglobin are noted, the possibility of recurrent, 
unrecognised (especially nocturnal) episodes of hypoglycaemia must be considered. 
 
Adherence of the patient to the dose regimen and dietary regimen, correct insulin administration and 
awareness of hypoglycaemia symptoms are essential to reduce the risk of hypoglycaemia. Factors 
increasing the susceptibility to hypoglycaemia require particularly close monitoring and may 
necessitate dose adjustment. These include: 
- change in the injection area, 
- improved insulin sensitivity (e.g. by removal of stress factors), 
- unaccustomed, increased or prolonged physical activity, 
- intercurrent illness (e.g. vomiting, diarrhoea), 
- inadequate food intake, 
- missed meals, 
- alcohol consumption, 
- certain uncompensated endocrine disorders (e.g. in hypothyroidism and in anterior pituitary or 

adrenocortical insufficiency), 
- concomitant treatment with certain other medicinal products. 
 
Intercurrent illness 
Intercurrent illness requires intensified metabolic monitoring. In many cases, urine tests for ketones 
are indicated, and often it is necessary to adjust the insulin dose. The insulin requirement is often 
increased. Patients with type 1 diabetes must continue to consume at least a small amount of 
carbohydrates on a regular basis, even if they are able to eat only little or no food, or are vomiting etc. 
and they must never omit insulin entirely. 
 
Medication errors 
Medication errors have been reported in which other Insulin Human Winthrop formulations or other 
insulins have been accidentally administered. Insulin label must always be checked before each 
injection to avoid medication errors between insulin human and other insulins. 

 

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Combination of Insulin Human Winthrop with pioglitazone 
Cases of cardiac failure have been reported when pioglitazone was used in combination with insulin, 
especially in patients with risk factors for development of cardiac heart failure. This should be kept in 
mind if treatment with the combination of pioglitazone and Insulin Human Winthrop is considered. If 
the combination is used, patients should be observed for signs and symptoms of heart failure, weight 
gain and oedema. Pioglitazone should be discontinued if any deterioration in cardiac symptoms 
occurs.  
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
A number of substances affect glucose metabolism and may require dose adjustment of human insulin. 
 
Substances that may enhance the blood-glucose-lowering effect and increase susceptibility to 
hypoglycaemia include oral antidiabetic medicinal products, angiotensin converting enzyme (ACE) 
inhibitors, disopyramide, fibrates, fluoxetine, monoamine oxidase (MAO) inhibitors, pentoxifylline, 
propoxyphene, salicylates and sulphonamide antibiotics. 
 
Substances that may reduce the blood-glucose-lowering effect include corticosteroids, danazol, 
diazoxide, diuretics, glucagon, isoniazid, oestrogens and progestogens (e.g. in oral contraceptives), 
phenothiazine derivatives, somatropin, sympathomimetic medicinal products (e.g. epinephrine 
[adrenaline], salbutamol, terbutaline), thyroid hormones, protease inhibitors and atypical antipsychotic 
medicinal products (e.g. olanzapine and clozapine). 
 
Beta-blockers, clonidine, lithium salts or alcohol may either potentiate or weaken the 
blood-glucose-lowering effect of insulin. Pentamidine may cause hypoglycaemia which may 
sometimes be followed by hyperglycaemia. 
 
In addition, under the influence of sympatholytic medicinal products such as beta-blockers, clonidine, 
guanethidine and reserpine, the signs of adrenergic counter-regulation may be reduced or absent. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
For insulin human, no clinical data on exposed pregnancies from controlled clinical studies are 
available. Insulin does cross the placental barrier, although not in clinically significant amount. A 
limited amount of data on pregnant women (less than 300 pregnancy outcomes reported) exposed to 
marketed insulin human indicates no safety issues in use of insulin human in pregnancy. Caution 
should be exercised when prescribing to pregnant women. 
 
It is essential for patients with pre-existing or gestational diabetes to maintain good metabolic control 
throughout pregnancy. Insulin requirements may decrease during the first trimester and generally 
increase during the second and third trimesters. Immediately after delivery, insulin requirements 
decline rapidly (increased risk of hypoglycaemia). Careful monitoring of glucose control is essential. 
 
Breast-feeding 
No effects on the suckling child are anticipated. Insulin Human Winthrop Comb 25 can be used during 
breast-feeding. Breast-feeding women may require adjustments in insulin dose and diet. 
 
Fertility 
No clinical or animal data with insulin human on male or female fertility are available. 
 

 

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4.7 Effects on ability to drive and use machines 
 
The patient's ability to concentrate and react may be impaired as a result of hypoglycaemia or 
hyperglycaemia or, for example, as a result of visual impairment. This may constitute a risk in 
situations where these abilities are of special importance (e.g. driving a car or using machines). 
 
Patients should be advised to take precautions to avoid hypoglycaemia whilst driving. This is 
particularly important in those who have reduced or absent awareness of the warning symptoms of 
hypoglycaemia or have frequent episodes of hypoglycaemia. It should be considered whether it is 
advisable to drive or use machines in these circumstances. 
 
4.8 Undesirable effects 
 
Summary of the safety profile  
Hypoglycaemia, in general the most frequent adverse reaction of insulin therapy, may occur if the 
insulin dose is too high in relation to the insulin requirement. In clinical studies and during marketed 
use, the frequency varies with patient population and dose regimens. Therefore, no specific frequency 
can be presented. 
 
Tabulated list of adverse reactions 
The following related adverse reactions from clinical investigations are listed below by system organ 
class and in order of decreasing incidence: very common (≥1/10); common (≥1/100 to <1/10); 
uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000), not known 
(cannot be estimated from the available data). 
 
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. 
 
MedDRA system 
organ classes 

Common Uncommon Not known 

Immune system 
disorders 

 Shock Immediate type 
allergic reactions 
(hypotension, 
angioneurotic oedema, 
bronchospasm, 
generalised skin 
reactions); 
Anti-insulin antibodies 

Metabolism and 
nutrition disorders 

Oedema  Hypoglycaemia; 
Sodium retention 

Eye disorders   Proliferative 
retinopathy; 
Diabetic retinopathy; 
Visual impairment 

Skin and subcutaneous 
tissue disorders 

  Lipodystrophy 

General disorders and 
administration site 
conditions 

Injection site reactions Injection site urticaria Injection site 
inflammation;  
Injection site pain; 
Injection site pruritus; 
Injection site erythema; 
Injection site swelling 

 

 

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Description of selected adverse reactions 
Immune system disorders 
Immediate type allergic reactions to insulin or to the excipients may be life-threatening. 
 
Insulin administration may cause anti-insulin antibodies to form. In rare cases, the presence of such 
anti-insulin antibodies may necessitate adjustment of the insulin dose in order to correct a tendency to 
hyper- or hypoglycaemia. 
 
Metabolism and nutrition disorders 
Severe hypoglycaemic attacks, especially if recurrent, may lead to neurological damage. 
Prolonged or severe hypoglycaemic episodes may be life-threatening. 
 
In many patients, the signs and symptoms of neuroglycopenia are preceded by signs of adrenergic 
counter-regulation. Generally, the greater and more rapid the decline in blood glucose, the more 
marked is the phenomenon of counter-regulation and its symptoms. 
Insulin may cause sodium retention and oedema, particularly if previously poor metabolic control is 
improved by intensified insulin therapy. 
 
Eyes disorders 
A marked change in glycaemic control may cause temporary visual impairment, due to temporary 
alteration in the turgidity and refractive index of the lens. 
 
Long-term improved glycaemic control decreases the risk of progression of diabetic retinopathy. 
However, intensification of insulin therapy with abrupt improvement in glycaemic control may be 
associated with temporary worsening of diabetic retinopathy. 
 
Skin and subcutaneous tissue disorders 
Lipodystrophy may occur at the injection site and delay local insulin absorption. Continuous rotation 
of the injection site within the given injection area may help to reduce or prevent these reactions. 
 
General disorders and administration site conditions 
Most minor reactions to insulins at the injection site usually resolve in a few days to a few weeks. 
 
4.9 Overdose 
 
Symptoms 
Insulin overdose may lead to severe and sometimes long-term and life-threatening hypoglycaemia. 
 
Management 
Mild episodes of hypoglycaemia can usually be treated with oral carbohydrates. Adjustments in dose 
regimen of the medicinal product, meal patterns, or physical activity may be needed. 
 
More severe episodes with coma, seizure, or neurologic impairment may be treated with 
intramuscular/subcutaneous glucagon or concentrated intravenous glucose. Sustained carbohydrate 
intake and observation may be necessary because hypoglycaemia may recur after apparent clinical 
recovery. 
 
 

 

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5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Drugs used in diabetes, insulins and analogues for injection, 
intermediate-acting combined with fast-acting, ATC Code: A10AD01. 
 
Mechanism of action 
Insulin 
- lowers blood glucose and promotes anabolic effects as well as decreasing catabolic effects, 
- increases the transport of glucose into cells as well as the formation of glycogen in the muscles 

and the liver, and improves pyruvate utilisation. It inhibits glycogenolysis and gluconeogenesis, 
- increases lipogenesis in the liver and adipose tissue and inhibits lipolysis, 
- promotes the uptake of amino acids into cells and promotes protein synthesis, 
- enhances the uptake of potassium into cells. 
 
Pharmacodynamic effects 
Insulin Human Winthrop Comb 25 (a biphasic isophane insulin suspension with 25% dissolved 
insulin) is an insulin with gradual onset and long duration of action. Following subcutaneous injection, 
onset of action is within 30 to 60 minutes, the phase of maximum action is between 2 and 4 hours after 
injection and the duration of action is 12 to 19 hours. 
 
5.2 Pharmacokinetic properties 
 
In healthy subjects, the serum half-life of insulin is approximately 4 to 6 minutes. It is longer in 
patients with severe renal insufficiency. However, it must be noted that the pharmacokinetics of 
insulin do not reflect its metabolic action. 
 
5.3 Preclinical safety data 
 
The acute toxicity was studied following subcutaneous administration in rats. No evidence of toxic 
effects was found. Studies of pharmacodynamic effects following subcutaneous administration in 
rabbits and dogs revealed the expected hypoglycaemic reactions. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Protamine sulphate, 
metacresol, 
phenol, 
zinc chloride, 
sodium dihydrogen phosphate dihydrate, 
glycerol, 
sodium hydroxide, 
hydrochloric acid (for pH adjustment), 
water for injections. 
 
6.2 Incompatibilities 
 
This medicinal product must not be mixed with other medicinal products except those mentioned in 
section 6.6. 
 
Insulin Human Winthrop Comb 25 must not be mixed with solutions containing reducing substances 
such as thioles and sulphites.  
 

 

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Mixing of insulins 
Insulin Human Winthrop Comb 25 must not be mixed with insulin human formulations designed 
specifically for use in insulin pumps.  
Insulin Human Winthrop Comb 25 must also not be mixed with insulins of animal origin or with 
insulin analogues. 
Insulins of different concentration (e.g. 100 IU per ml and 40 IU per ml) must not be mixed. 
 
Care must be taken to ensure that no alcohol or other disinfectants enter the insulin suspension. 
 
6.3 Shelf life 
 
2 years. 
 
Shelf life after first use of the vial 
The product may be stored for a maximum of 4 weeks not above 25°C and away from direct heat or 
direct light. 
Keep the vial in the outer carton in order to protect from light. 
It is recommended that the date of the first use be noted on the label. 
 
6.4 Special precautions for storage 
 
Unopened vials 
Store in a refrigerator (2°C - 8°C). 
Do not freeze. 
Do not put Insulin Human Winthrop Comb 25 next to the freezer compartment or a freezer pack. 
Keep the vial in the outer carton in order to protect from light. 
 
Opened vials 
For storage conditions after first opening of the medicinal product, see section 6.3. 
 
6.5 Nature and contents of container 
 
10 ml suspension in a vial (type 1 colourless glass) with a flanged cap (aluminium), a stopper 
(chlorobutyl rubber (type 1)) and a tear-off cap (polypropylene). 
Packs of 1 and 5 vials are available. 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal and other handling 
 
Before withdrawing insulin from the vial for the first time, remove the plastic protective cap. 
 
Immediately before withdrawal from the vial into the injection syringe, the insulin must be 
resuspended. This is best done by rolling the vial at an oblique angle between the palms of the hands. 
Do not shake the vial vigorously as this may lead to changes in the suspension (giving the vial a 
frosted appearance; see below) and cause frothing. Froth may interfere with the correct measurement 
of the dose. 
 
After resuspension, the fluid must have a uniformly milky appearance. Insulin Human Winthrop 
Comb 25 must not be used if this cannot be achieved, i.e. if the suspension remains clear, for example, 
or if clumps, particles or flocculation appear in the insulin or stick to the wall or bottom of the vial. 
These changes sometimes give the vial a frosted appearance. In such cases, a new vial yielding a 
uniform suspension must be used. It is also necessary to change to a new vial if the insulin 
requirement changes substantially. 
 
Insulin Human Winthrop Comb 25 must not be administered intravenously and must not be used in 
infusion pumps or external or implanted insulin pumps. 
 

 

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It must be remembered that 
- insulin protamine crystals dissolve in an acid pH range, 
- the soluble insulin part precipitates out at a pH of approximately 4.5 to 6.5. 
 
Insulin label must always be checked before each injection to avoid medication errors between insulin 
human and other insulins (see section 4.4). 
 
Mixing of insulins 
Insulin Human Winthrop Comb 25 may be mixed with all insulin human formulations, but not with 
those designed specifically for use in insulin pumps. Concerning incompatibility with other insulins, 
see section 6.2. 
 
If two different insulins have to be drawn into one single injection syringe, it is recommended that the 
shorter-acting insulin be drawn first to prevent contamination of the vial by the longer-acting 
preparation. It is advisable to inject immediately after mixing.  
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Sanofi-Aventis Deutschland GmbH, D-65926 Frankfurt am Main, Germany 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/06/368/007 
EU/1/06/368/008 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 17 January 2007 
Date of latest renewal: 17 January 2012 
 
 
10. DATE OF REVISION OF THE TEXT 
 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu 

 

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1. NAME OF THE MEDICINAL PRODUCT 
 
Insulin Human Winthrop Comb 25 100 IU/ml suspension for injection in a cartridge 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each ml contains 100 IU insulin human (equivalent to 3.5 mg).  
Each cartridge contains 3 ml of suspension for injection, equivalent to 300 IU insulin. One IU 
(International Unit) corresponds to 0.035 mg of anhydrous human insulin. 
 
Insulin Human Winthrop Comb 25 is a biphasic isophane insulin suspension consisting of 25% 
dissolved insulin and 75% crystalline protamine insulin. 
 
Human insulin is produced by recombinant DNA technology in Escherichia coli. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Suspension for injection in a cartridge. 
 
After resuspension, milky-white suspension. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Diabetes mellitus where treatment with insulin is required. 
 
4.2 Posology and method of administration 
 
Posology 
The desired blood glucose levels, the insulin preparations to be used and the insulin dose regimen 
(doses and timings) must be determined individually and adjusted to suit the patient’s diet, physical 
activity and life-style. 
 
Daily doses and timing of administration 
There are no fixed rules for insulin dose regimen. However, the average insulin requirement is often 
0.5 to 1.0 IU per kg body weight per day. The basal metabolic requirement is 40% to 60% of the total 
daily requirement. Insulin Human Winthrop Comb 25 is injected subcutaneously 30 to 45 minutes 
before a meal. 
 
Secondary dose adjustment 
Improved metabolic control may result in increased insulin sensitivity, leading to a reduced insulin 
requirement. Dose adjustment may also be required, for example, if 
- the patient's weight changes, 
- the patient's life-style changes, 
- other circumstances arise that may promote an increased susceptibility to hypo- or 

hyperglycaemia (see section 4.4). 
 
Special populations 
Elderly population (≧65 years old) 
In the elderly, progressive deterioration of renal function may lead to a steady decrease in insulin 
requirements. 

 

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Renal impairment 
In patients with renal impairment, insulin requirements may be diminished due to reduced insulin 
metabolism. 
 
Hepatic impairment 
In patients with severe hepatic impairment, insulin requirements may be diminished due to reduced 
capacity for gluconeogenesis and reduced insulin metabolism. 
 
Method of administration 
Insulin Human Winthrop Comb 25 must not be administered intravenously and must not be used in 
infusion pumps or external or implanted insulin pumps. 
 
Insulin Human Winthrop Comb 25 is administered subcutaneously. Insulin Human Winthrop 
Comb 25 must never be injected intravenously. 
 
Insulin absorption and hence the blood-glucose-lowering effect of a dose may vary from one injection 
area to another (e.g. the abdominal wall compared with the thigh). Injection sites within an injection 
area must be rotated from one injection to the next. 
 
For further details on handling, see section 6.6. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
 
4.4 Special warnings and precautions for use 
 
Patients hypersensitive to Insulin Human Winthrop Comb 25 for whom no better tolerated preparation 
is available must only continue treatment under close medical supervision and – where necessary – in 
conjunction with anti-allergic treatment. 
 
In patients with an allergy to animal insulin intradermal skin testing is recommended prior to a 
transfer to Insulin Human Winthrop Comb 25, since they may experience immunological 
cross-reactions. 
 
In case of insufficient glucose control or a tendency to hyper- or hypoglycaemic episodes, the patient's 
adherence to the prescribed treatment regimen, injection sites and proper injection technique and all 
other relevant factors must be reviewed before dose adjustment is considered. 
 
Transfer to Insulin Human Winthrop Comb 25 
Transferring a patient to another type or brand of insulin should be done under strict medical 
supervision. Changes in strength, brand (manufacturer), type (regular, NPH, lente, long-acting, etc.), 
origin (animal, human, human insulin analogue) and/or method of manufacture may result in the need 
for a change in dosage. 
The need to adjust (e.g. reduce) the dose may become evident immediately after transfer. 
Alternatively, it may emerge gradually over a period of several weeks. 
 
Following transfer from an animal insulin to human insulin, dose regimen reduction may be required 
in particular in patients who 
- were previously already controlled on rather low blood glucose levels, 
- have a tendency to hypoglycaemia, 
- previously required high insulin doses due to the presence of insulin antibodies. 
 
Close metabolic monitoring is recommended during the transition and in the initial weeks thereafter. In 
patients who require high insulin doses because of the presence of insulin antibodies, transfer under 
medical supervision in a hospital or similar setting must be considered. 

 

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Hypoglycaemia 
Hypoglycaemia may occur if the insulin dose is too high in relation to the insulin requirement. 
 
Particular caution should be exercised, and intensified blood glucose monitoring is advisable in 
patients in whom hypoglycaemic episodes might be of particular clinical relevance, such as in patients 
with significant stenoses of the coronary arteries or of the blood vessels supplying the brain (risk of 
cardiac or cerebral complications of hypoglycaemia) as well as in patients with proliferative 
retinopathy, particularly if not treated with photocoagulation (risk of transient amaurosis following 
hypoglycaemia). 
 
Patients should be aware of circumstances where warning symptoms of hypoglycaemia are 
diminished. The warning symptoms of hypoglycaemia may be changed, be less pronounced or be 
absent in certain risk groups. These include patients: 
- in whom glycaemic control is markedly improved, 
- in whom hypoglycaemia develops gradually, 
- who are elderly,  
- after transfer from animal insulin to human insulin, 
- in whom an autonomic neuropathy is present, 
- with a long history of diabetes, 
- suffering from a psychiatric illness, 
- receiving concurrent treatment with certain other medicinal products (see section 4.5). 
Such situations may result in severe hypoglycaemia (and possibly loss of consciousness) prior to the 
patient's awareness of hypoglycaemia. 
 
If normal or decreased values for glycated haemoglobin are noted, the possibility of recurrent, 
unrecognised (especially nocturnal) episodes of hypoglycaemia must be considered. 
 
Adherence of the patient to the dose regimen and dietary regimen, correct insulin administration and 
awareness of hypoglycaemia symptoms are essential to reduce the risk of hypoglycaemia. Factors 
increasing the susceptibility to hypoglycaemia require particularly close monitoring and may 
necessitate dose adjustment. These include: 
- change in the injection area, 
- improved insulin sensitivity (e.g. by removal of stress factors), 
- unaccustomed, increased or prolonged physical activity, 
- intercurrent illness (e.g. vomiting, diarrhoea), 
- inadequate food intake, 
- missed meals, 
- alcohol consumption, 
- certain uncompensated endocrine disorders (e.g. in hypothyroidism and in anterior pituitary or 

adrenocortical insufficiency), 
- concomitant treatment with certain other medicinal products. 
 
Intercurrent illness 
Intercurrent illness requires intensified metabolic monitoring. In many cases, urine tests for ketones 
are indicated, and often it is necessary to adjust the insulin dose. The insulin requirement is often 
increased. Patients with type 1 diabetes must continue to consume at least a small amount of 
carbohydrates on a regular basis, even if they are able to eat only little or no food, or are vomiting etc. 
and they must never omit insulin entirely. 
 
Pens to be used with Insulin Human Winthrop Comb 25 cartridges 
The Insulin Human Winthrop Comb 25 cartridges should only be used with the following pens:  
- JuniorSTAR which delivers Insulin Human Winthrop Comb 25 in 0.5 unit dose increments 
- OptiPen, ClikSTAR, Tactipen, Autopen 24 and AllStar which all deliver Insulin Human Winthrop 
Comb 25 in 1 unit dose increments. 
These cartridges should not be used with any other reusable pen as the dosing accuracy has only been 
established with the listed pens.  

 

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Not all of these pens may be marketed in your country. 
 
Medication errors 
Medication errors have been reported in which other Insulin Human Winthrop formulations or other 
insulins have been accidentally administered. Insulin label must always be checked before each 
injection to avoid medication errors between insulin human and other insulins. 
 
Combination of Insulin Human Winthrop with pioglitazone 
Cases of cardiac failure have been reported when pioglitazone was used in combination with insulin, 
especially in patients with risk factors for development of cardiac heart failure. This should be kept in 
mind if treatment with the combination of pioglitazone and Insulin Human Winthrop is considered. If 
the combination is used, patients should be observed for signs and symptoms of heart failure, weight 
gain and oedema. Pioglitazone should be discontinued if any deterioration in cardiac symptoms 
occurs.  
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
A number of substances affect glucose metabolism and may require dose adjustment of human insulin. 
 
Substances that may enhance the blood-glucose-lowering effect and increase susceptibility to 
hypoglycaemia include oral antidiabetic medicinal products, angiotensin converting enzyme (ACE) 
inhibitors, disopyramide, fibrates, fluoxetine, monoamine oxidase (MAO) inhibitors, pentoxifylline, 
propoxyphene, salicylates and sulphonamide antibiotics. 
 
Substances that may reduce the blood-glucose-lowering effect include corticosteroids, danazol, 
diazoxide, diuretics, glucagon, isoniazid, oestrogens and progestogens (e.g. in oral contraceptives), 
phenothiazine derivatives, somatropin, sympathomimetic medicinal products (e.g. epinephrine 
[adrenaline], salbutamol, terbutaline), thyroid hormones, protease inhibitors and atypical antipsychotic 
medicinal products (e.g. olanzapine and clozapine). 
 
Beta-blockers, clonidine, lithium salts or alcohol may either potentiate or weaken the 
blood-glucose-lowering effect of insulin. Pentamidine may cause hypoglycaemia which may 
sometimes be followed by hyperglycaemia. 
 
In addition, under the influence of sympatholytic medicinal products such as beta-blockers, clonidine, 
guanethidine and reserpine, the signs of adrenergic counter-regulation may be reduced or absent. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
For insulin human, no clinical data on exposed pregnancies from controlled clinical studies are 
available. Insulin does cross the placental barrier, although not in clinically significant amount. A 
limited amount of data on pregnant women (less than 300 pregnancy outcomes reported) exposed to 
marketed insulin human indicates no safety issues in use of insulin human in pregnancy. Caution 
should be exercised when prescribing to pregnant women. 
 
It is essential for patients with pre-existing or gestational diabetes to maintain good metabolic control 
throughout pregnancy. Insulin requirements may decrease during the first trimester and generally 
increase during the second and third trimesters. Immediately after delivery, insulin requirements 
decline rapidly (increased risk of hypoglycaemia). Careful monitoring of glucose control is essential. 
 
Breast-feeding 
No effects on the suckling child are anticipated. Insulin Human Winthrop Comb 25 can be used during 
breast-feeding. Breast-feeding women may require adjustments in insulin dose and diet. 
 
Fertility 
No clinical or animal data with insulin human on male or female fertility are available. 

 

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4.7 Effects on ability to drive and use machines 
 
The patient's ability to concentrate and react may be impaired as a result of hypoglycaemia or 
hyperglycaemia or, for example, as a result of visual impairment. This may constitute a risk in 
situations where these abilities are of special importance (e.g. driving a car or using machines). 
 
Patients should be advised to take precautions to avoid hypoglycaemia whilst driving. This is 
particularly important in those who have reduced or absent awareness of the warning symptoms of 
hypoglycaemia or have frequent episodes of hypoglycaemia. It should be considered whether it is 
advisable to drive or use machines in these circumstances. 
 
4.8 Undesirable effects 
 
Summary of the safety profile  
Hypoglycaemia, in general the most frequent adverse reaction of insulin therapy, may occur if the 
insulin dose is too high in relation to the insulin requirement. In clinical studies and during marketed 
use, the frequency varies with patient population and dose regimens. Therefore, no specific frequency 
can be presented. 
 
Tabulated list of adverse reactions 
The following related adverse reactions from clinical investigations are listed below by system organ 
class and in order of decreasing incidence: very common (≥1/10); common (≥1/100 to <1/10); 
uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000), not known 
(cannot be estimated from the available data). 
 
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. 
 
MedDRA system 
organ classes 

Common Uncommon Not known 

Immune system 
disorders 

 Shock Immediate type allergic 
reactions (hypotension, 
angioneurotic oedema, 
bronchospasm, 
generalised skin 
reactions); 
Anti-insulin antibodies 

Metabolism and 
nutrition disorders 

Oedema  Hypoglycaemia; 
Sodium retention 

Eye disorders   Proliferative retinopathy; 
Diabetic retinopathy; 
Visual impairment 

Skin and subcutaneous 
tissue disorders 

  Lipodystrophy 

General disorders and 
administration site 
conditions 

Injection site reactions Injection site 
urticaria 

Injection site 
inflammation;  
Injection site pain; 
Injection site pruritus; 
Injection site erythema; 
Injection site swelling 

 
Description of selected adverse reactions 
Immune system disorders 
Immediate type allergic reactions to insulin or to the excipients may be life-threatening. 
 

 

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Insulin administration may cause anti-insulin antibodies to form. In rare cases, the presence of such 
anti-insulin antibodies may necessitate adjustment of the insulin dose in order to correct a tendency to 
hyper- or hypoglycaemia. 
 
Metabolism and nutrition disorders 
Severe hypoglycaemic attacks, especially if recurrent, may lead to neurological damage. 
Prolonged or severe hypoglycaemic episodes may be life-threatening. 
 
In many patients, the signs and symptoms of neuroglycopenia are preceded by signs of adrenergic 
counter-regulation. Generally, the greater and more rapid the decline in blood glucose, the more 
marked is the phenomenon of counter-regulation and its symptoms. 
 
Insulin may cause sodium retention and oedema, particularly if previously poor metabolic control is 
improved by intensified insulin therapy. 
 
Eyes disorders 
A marked change in glycaemic control may cause temporary visual impairment, due to temporary 
alteration in the turgidity and refractive index of the lens. 
 
Long-term improved glycaemic control decreases the risk of progression of diabetic retinopathy. 
However, intensification of insulin therapy with abrupt improvement in glycaemic control may be 
associated with temporary worsening of diabetic retinopathy. 
 
Skin and subcutaneous tissue disorders 
Lipodystrophy may occur at the injection site and delay local insulin absorption. Continuous rotation 
of the injection site within the given injection area may help to reduce or prevent these reactions. 
 
General disorders and administration site conditions 
Most minor reactions to insulins at the injection site usually resolve in a few days to a few weeks. 
 
4.9 Overdose 
 
Symptoms 
Insulin overdose may lead to severe and sometimes long-term and life-threatening hypoglycaemia. 
 
Management 
Mild episodes of hypoglycaemia can usually be treated with oral carbohydrates. Adjustments in dose 
regimen of the medicinal product, meal patterns, or physical activity may be needed. 
 
More severe episodes with coma, seizure, or neurologic impairment may be treated with 
intramuscular/subcutaneous glucagon or concentrated intravenous glucose. Sustained carbohydrate 
intake and observation may be necessary because hypoglycaemia may recur after apparent clinical 
recovery. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Drugs used in diabetes, insulins and analogues for injection, 
intermediate-acting combined with fast-acting, ATC Code: A10AD01. 
 
Mechanism of action 
Insulin 
- lowers blood glucose and promotes anabolic effects as well as decreasing catabolic effects, 
- increases the transport of glucose into cells as well as the formation of glycogen in the muscles 

and the liver, and improves pyruvate utilisation. It inhibits glycogenolysis and gluconeogenesis, 

 

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- increases lipogenesis in the liver and adipose tissue and inhibits lipolysis, 
- promotes the uptake of amino acids into cells and promotes protein synthesis, 
- enhances the uptake of potassium into cells. 
 
Pharmacodynamic effects 
Insulin Human Winthrop Comb 25 (a biphasic isophane insulin suspension with 25% dissolved 
insulin) is an insulin with gradual onset and long duration of action. Following subcutaneous injection, 
onset of action is within 30 to 60 minutes, the phase of maximum action is between 2 and 4 hours after 
injection and the duration of action is 12 to 19 hours. 
 
5.2 Pharmacokinetic properties 
 
In healthy subjects, the serum half-life of insulin is approximately 4 to 6 minutes. It is longer in 
patients with severe renal insufficiency. However, it must be noted that the pharmacokinetics of 
insulin do not reflect its metabolic action. 
 
5.3 Preclinical safety data 
 
The acute toxicity was studied following subcutaneous administration in rats. No evidence of toxic 
effects was found. Studies of pharmacodynamic effects following subcutaneous administration in 
rabbits and dogs revealed the expected hypoglycaemic reactions. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Protamine sulphate, 
metacresol, 
phenol, 
zinc chloride, 
sodium dihydrogen phosphate dihydrate, 
glycerol, 
sodium hydroxide, 
hydrochloric acid (for pH adjustment), 
water for injections. 
 
6.2 Incompatibilities 
 
This medicinal product must not be mixed with other medicinal products except those mentioned in 
section 6.6. 
 
Insulin Human Winthrop Comb 25 must not be mixed with solutions containing reducing substances 
such as thioles and sulphites.  
 
Mixing of insulins 
Insulin Human Winthrop Comb 25 must not be mixed with insulin human formulations designed 
specifically for use in insulin pumps.  
Insulin Human Winthrop Comb 25 must also not be mixed with insulins of animal origin or with 
insulin analogues. 
 
Care must be taken to ensure that no alcohol or other disinfectants enter the insulin suspension. 
 
6.3 Shelf life 
 
2 years. 
 

 

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Shelf life after first use of the cartridge 
The cartridge in-use (in the insulin pen) or carried as a spare may be stored for a maximum of 4 weeks 
not above 25°C and away from direct heat or direct light. 
The pen containing a cartridge must not be stored in the refrigerator. 
The pen cap must be put back on the pen after each injection in order to protect from light. 
 
6.4 Special precautions for storage 
 
Unopened cartridges 
Store in a refrigerator (2°C - 8°C). 
Do not freeze. 
Do not put Insulin Human Winthrop Comb 25 next to the freezer compartment or a freezer pack. 
Keep the cartridge in the outer carton in order to protect from light. 
 
In-use cartridges 
For storage conditions after first opening of the medicinal product, see section 6.3. 
 
6.5 Nature and contents of container 
 
3 ml suspension in a cartridge (type 1 colourless glass) with a plunger (bromobutyl rubber (type 1)) 
and a flanged cap (aluminium) with a stopper (bromobutyl or laminate of polyisoprene and 
bromobutyl rubber (type 1)). 
Each cartridge contains 3 balls (stainless steel). 
Packs of 3, 4, 5, 6, 9 or 10 cartridges are available. 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal and other handling 
 
Insulin pen 
The Insulin Human Winthrop Comb 25 cartridges are to be used only in conjunction with the pens: 
OptiPen, ClikSTAR, Autopen 24, Tactipen, AllStar or JuniorSTAR (see section 4.4). Not all of these pens 
may be marketed in your country. 
 
The pen should be used as recommended in the information provided by the device manufacturer.  
 
The manufacturer’s instructions for using the pen must be followed carefully for loading the cartridge, 
attaching the injection needle, and administering the insulin injection. 
 
If the insulin pen is damaged or not working properly (due to mechanical defects) it has to be 
discarded, and a new insulin pen has to be used. 
 
If the pen malfunctions (see instructions for using the pen), the suspension may be drawn from the 
cartridge into an injection syringe (suitable for an insulin with 100 IU/ml) and injected. 
 
Cartridges 
Before insertion into the pen, Insulin Human Winthrop Comb 25 must be kept at room temperature for 
1 to 2 hours and then resuspended to check the contents. This is best done by gently tilting the 
cartridge back and forth (at least ten times). Each cartridge contains three small metal balls to facilitate 
quick and thorough mixing of the contents. 
 
Later on, when the cartridge has been inserted into the pen, the insulin must be resuspended again 
prior to each injection. This is best done by gently tilting the pen back and forth (at least ten times). 
 
After resuspension, the fluid must have a uniformly milky appearance. Insulin Human Winthrop 
Comb 25 must not be used if this cannot be achieved, i.e. if the suspension remains clear, for example, 
or if clumps, particles or flocculation appear in the insulin or stick to the wall or bottom of the 
cartridge. These changes sometimes give the cartridge a frosted appearance. In such cases, a new 

 

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cartridge yielding a uniform suspension must be used. It is also necessary to change to a new cartridge 
if the insulin requirement changes substantially. 
 
Air bubbles must be removed from the cartridge before injection (see instructions for using the pen). 
Empty cartridges must not be refilled. 
 
Insulin Human Winthrop Comb 25 must not be administered intravenously and must not be used in 
infusion pumps or external or implanted insulin pumps. 
 
It must be remembered that 
- insulin protamine crystals dissolve in an acid pH range, 
- the soluble insulin part precipitates out at a pH of approximately 4.5 to 6.5. 
 
Insulin label must always be checked before each injection to avoid medication errors between insulin 
human and other insulins (see section 4.4). 
 
Mixing of insulins 
Insulin Human Winthrop Comb 25 may be mixed with all insulin human formulations, but not with 
those designed specifically for use in insulin pumps. Concerning incompatibility with other insulins, 
see section 6.2. 
 
Insulin Human Winthrop Comb 25 cartridges are not designed to allow any other insulin to be mixed 
in the cartridge. 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Sanofi-Aventis Deutschland GmbH, D-65926 Frankfurt am Main, Germany 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/06/368/091 
EU/1/06/368/040 
EU/1/06/368/041 
EU/1/06/368/096 
EU/1/06/368/101 
EU/1/06/368/042 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 17 January 2007 
Date of latest renewal: 17 January 2012 
 
 
10. DATE OF REVISION OF THE TEXT 
 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu 

 

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1. NAME OF THE MEDICINAL PRODUCT 
 
Insulin Human Winthrop Comb 25 SoloStar 100 IU/ml suspension for injection in a pre-filled pen. 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each ml contains 100 IU insulin human (equivalent to 3.5 mg).  
Each pen contains 3 ml of suspension for injection, equivalent to 300 IU insulin. One IU (International 
Unit) corresponds to 0.035 mg of anhydrous human insulin. 
 
Insulin Human Winthrop Comb 25 is a biphasic isophane insulin suspension consisting of 25% 
dissolved insulin and 75% crystalline protamine insulin. 
 
Human insulin is produced by recombinant DNA technology in Escherichia coli. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Suspension for injection in a pre-filled pen. 
 
After resuspension, milky-white suspension. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Diabetes mellitus where treatment with insulin is required. 
 
4.2 Posology and method of administration 
 
Posology 
The desired blood glucose levels, the insulin preparations to be used and the insulin dose regimen 
(doses and timings) must be determined individually and adjusted to suit the patient’s diet, physical 
activity and life-style. 
 
Daily doses and timing of administration 
There are no fixed rules for insulin dose regimen. However, the average insulin requirement is often 
0.5 to 1.0 IU per kg body weight per day. The basal metabolic requirement is 40% to 60% of the total 
daily requirement. Insulin Human Winthrop Comb 25 is injected subcutaneously 30 to 45 minutes 
before a meal. 
 
SoloStar delivers insulin in doses from 1 to 80 units in steps of 1 unit. Each pen contains multiple 
doses. 
 
Secondary dose adjustment 
Improved metabolic control may result in increased insulin sensitivity, leading to a reduced insulin 
requirement. Dose adjustment may also be required, for example, if 
- the patient's weight changes, 
- the patient's life-style changes, 
- other circumstances arise that may promote an increased susceptibility to hypo- or 

hyperglycaemia (see section 4.4). 
 

 

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Special populations 
Elderly population (≧65 years old) 
In the elderly, progressive deterioration of renal function may lead to a steady decrease in insulin 
requirements. 
 
Renal impairment 
In patients with renal impairment, insulin requirements may be diminished due to reduced insulin 
metabolism. 
 
Hepatic impairment 
In patients with severe hepatic impairment, insulin requirements may be diminished due to reduced 
capacity for gluconeogenesis and reduced insulin metabolism. 
 
Method of administration 
Insulin Human Winthrop Comb 25 is administered subcutaneously. Insulin Human Winthrop 
Comb 25 must never be injected intravenously. 
 
Insulin absorption and hence the blood-glucose-lowering effect of a dose may vary from one injection 
area to another (e.g. the abdominal wall compared with the thigh). Injection sites within an injection 
area must be rotated from one injection to the next. 
 
Before using SoloStar, the Instructions for Use included in the Package Leaflet must be read carefully. 
 
For further details on handling, see section 6.6. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
 
4.4 Special warnings and precautions for use 
 
Patients hypersensitive to Insulin Human Winthrop Comb 25 for whom no better tolerated preparation 
is available must only continue treatment under close medical supervision and – where necessary – in 
conjunction with anti-allergic treatment. 
 
In patients with an allergy to animal insulin intradermal skin testing is recommended prior to a 
transfer to Insulin Human Winthrop Comb 25, since they may experience immunological 
cross-reactions. 
 
In case of insufficient glucose control or a tendency to hyper- or hypoglycaemic episodes, the patient's 
adherence to the prescribed treatment regimen, injection sites and proper injection technique and all 
other relevant factors must be reviewed before dose adjustment is considered. 
 
Transfer to Insulin Human Winthrop Comb 25 
Transferring a patient to another type or brand of insulin should be done under strict medical 
supervision. Changes in strength, brand (manufacturer), type (regular, NPH, lente, long-acting, etc.), 
origin (animal, human, human insulin analogue) and/or method of manufacture may result in the need 
for a change in dosage. 
The need to adjust (e.g. reduce) the dose may become evident immediately after transfer. 
Alternatively, it may emerge gradually over a period of several weeks. 
 
Following transfer from an animal insulin to human insulin, dose regimen reduction may be required 
in particular in patients who 
- were previously already controlled on rather low blood glucose levels, 
- have a tendency to hypoglycaemia, 
- previously required high insulin doses due to the presence of insulin antibodies. 
 

 

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Close metabolic monitoring is recommended during the transition and in the initial weeks thereafter. In 
patients who require high insulin doses because of the presence of insulin antibodies, transfer under 
medical supervision in a hospital or similar setting must be considered. 
 
Hypoglycaemia 
Hypoglycaemia may occur if the insulin dose is too high in relation to the insulin requirement. 
 
Particular caution should be exercised, and intensified blood glucose monitoring is advisable in 
patients in whom hypoglycaemic episodes might be of particular clinical relevance, such as in patients 
with significant stenoses of the coronary arteries or of the blood vessels supplying the brain (risk of 
cardiac or cerebral complications of hypoglycaemia) as well as in patients with proliferative 
retinopathy, particularly if not treated with photocoagulation (risk of transient amaurosis following 
hypoglycaemia). 
 
Patients should be aware of circumstances where warning symptoms of hypoglycaemia are 
diminished. The warning symptoms of hypoglycaemia may be changed, be less pronounced or be 
absent in certain risk groups. These include patients: 
- in whom glycaemic control is markedly improved, 
- in whom hypoglycaemia develops gradually, 
- who are elderly,  
- after transfer from animal insulin to human insulin, 
- in whom an autonomic neuropathy is present, 
- with a long history of diabetes, 
- suffering from a psychiatric illness, 
- receiving concurrent treatment with certain other medicinal products (see section 4.5). 
Such situations may result in severe hypoglycaemia (and possibly loss of consciousness) prior to the 
patient's awareness of hypoglycaemia. 
 
If normal or decreased values for glycated haemoglobin are noted, the possibility of recurrent, 
unrecognised (especially nocturnal) episodes of hypoglycaemia must be considered. 
 
Adherence of the patient to the dose regimen and dietary regimen, correct insulin administration and 
awareness of hypoglycaemia symptoms are essential to reduce the risk of hypoglycaemia. Factors 
increasing the susceptibility to hypoglycaemia require particularly close monitoring and may 
necessitate dose adjustment. These include: 
- change in the injection area, 
- improved insulin sensitivity (e.g. by removal of stress factors), 
- unaccustomed, increased or prolonged physical activity, 
- intercurrent illness (e.g. vomiting, diarrhoea), 
- inadequate food intake, 
- missed meals, 
- alcohol consumption, 
- certain uncompensated endocrine disorders (e.g. in hypothyroidism and in anterior pituitary or 

adrenocortical insufficiency), 
- concomitant treatment with certain other medicinal products. 
 
Intercurrent illness 
Intercurrent illness requires intensified metabolic monitoring. In many cases, urine tests for ketones 
are indicated, and often it is necessary to adjust the insulin dose. The insulin requirement is often 
increased. Patients with type 1 diabetes must continue to consume at least a small amount of 
carbohydrates on a regular basis, even if they are able to eat only little or no food, or are vomiting etc. 
and they must never omit insulin entirely. 
 
Handling of the pen 
Before using SoloStar, the Instructions for Use included in the Package Leaflet must be read carefully. 
SoloStar has to be used as recommended in these Instructions for Use (see section 6.6). 
 

 

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Medication errors 
Medication errors have been reported in which other Insulin Human Winthrop formulations or other 
insulins have been accidentally administered. Insulin label must always be checked before each 
injection to avoid medication errors between insulin human and other insulins. 
 
Combination of Insulin Human Winthrop with pioglitazone 
Cases of cardiac failure have been reported when pioglitazone was used in combination with insulin, 
especially in patients with risk factors for development of cardiac heart failure. This should be kept in 
mind if treatment with the combination of pioglitazone and Insulin Human Winthrop is considered. If 
the combination is used, patients should be observed for signs and symptoms of heart failure, weight 
gain and oedema. Pioglitazone should be discontinued if any deterioration in cardiac symptoms 
occurs.  
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
A number of substances affect glucose metabolism and may require dose adjustment of human insulin. 
 
Substances that may enhance the blood-glucose-lowering effect and increase susceptibility to 
hypoglycaemia include oral antidiabetic medicinal products, angiotensin converting enzyme (ACE) 
inhibitors, disopyramide, fibrates, fluoxetine, monoamine oxidase (MAO) inhibitors, pentoxifylline, 
propoxyphene, salicylates and sulphonamide antibiotics. 
 
Substances that may reduce the blood-glucose-lowering effect include corticosteroids, danazol, 
diazoxide, diuretics, glucagon, isoniazid, oestrogens and progestogens (e.g. in oral contraceptives), 
phenothiazine derivatives, somatropin, sympathomimetic medicinal products (e.g. epinephrine 
[adrenaline], salbutamol, terbutaline), thyroid hormones, protease inhibitors and atypical antipsychotic 
medicinal products (e.g. olanzapine and clozapine). 
 
Beta-blockers, clonidine, lithium salts or alcohol may either potentiate or weaken the 
blood-glucose-lowering effect of insulin. Pentamidine may cause hypoglycaemia which may 
sometimes be followed by hyperglycaemia. 
 
In addition, under the influence of sympatholytic medicinal products such as beta-blockers, clonidine, 
guanethidine and reserpine, the signs of adrenergic counter-regulation may be reduced or absent. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
For insulin human, no clinical data on exposed pregnancies from controlled clinical studies are 
available. Insulin does cross the placental barrier, although not in clinically significant amount. A 
limited amount of data on pregnant women (less than 300 pregnancy outcomes reported) exposed to 
marketed insulin human indicates no safety issues in use of insulin human in pregnancy. Caution 
should be exercised when prescribing to pregnant women. 
 
It is essential for patients with pre-existing or gestational diabetes to maintain good metabolic control 
throughout pregnancy. Insulin requirements may decrease during the first trimester and generally 
increase during the second and third trimesters. Immediately after delivery, insulin requirements 
decline rapidly (increased risk of hypoglycaemia). Careful monitoring of glucose control is essential. 
 
Breast-feeding 
No effects on the suckling child are anticipated. Insulin Human Winthrop Comb 25 can be used during 
breast-feeding. Breast-feeding women may require adjustments in insulin dose and diet. 
 
Fertility 
No clinical or animal data with insulin human on male or female fertility are available. 
 

 

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4.7 Effects on ability to drive and use machines 
 
The patient's ability to concentrate and react may be impaired as a result of hypoglycaemia or 
hyperglycaemia or, for example, as a result of visual impairment. This may constitute a risk in 
situations where these abilities are of special importance (e.g. driving a car or using machines). 
 
Patients should be advised to take precautions to avoid hypoglycaemia whilst driving. This is 
particularly important in those who have reduced or absent awareness of the warning symptoms of 
hypoglycaemia or have frequent episodes of hypoglycaemia. It should be considered whether it is 
advisable to drive or use machines in these circumstances. 
 
4.8 Undesirable effects 
 
Summary of the safety profile  
Hypoglycaemia, in general the most frequent adverse reaction of insulin therapy, may occur if the 
insulin dose is too high in relation to the insulin requirement. In clinical studies and during marketed 
use, the frequency varies with patient population and dose regimens. Therefore, no specific frequency 
can be presented. 
 
Tabulated list of adverse reactions 
The following related adverse reactions from clinical investigations are listed below by system organ 
class and in order of decreasing incidence: very common (≥1/10); common (≥1/100 to <1/10); 
uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000), not known 
(cannot be estimated from the available data). 
 
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. 
 
MedDRA system 
organ classes 

Common Uncommon Not known 

Immune system 
disorders 

 Shock Immediate type allergic 
reactions (hypotension, 
angioneurotic oedema, 
bronchospasm, 
generalised skin 
reactions); 
Anti-insulin antibodies 

Metabolism and 
nutrition disorders 

Oedema  Hypoglycaemia; 
Sodium retention 

Eye disorders   Proliferative retinopathy; 
Diabetic retinopathy; 
Visual impairment 

Skin and subcutaneous 
tissue disorders 

  Lipodystrophy 

General disorders and 
administration site 
conditions 

Injection site reactions Injection site 
urticaria 

Injection site 
inflammation;  
Injection site pain; 
Injection site pruritus; 
Injection site erythema; 
Injection site swelling 

 
Description of selected adverse reactions 
Immune system disorders 
Immediate type allergic reactions to insulin or to the excipients may be life-threatening. 
 
Insulin administration may cause anti-insulin antibodies to form. In rare cases, the presence of such 
anti-insulin antibodies may necessitate adjustment of the insulin dose in order to correct a tendency to 
hyper- or hypoglycaemia. 

 

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Metabolism and nutrition disorders 
Severe hypoglycaemic attacks, especially if recurrent, may lead to neurological damage. 
Prolonged or severe hypoglycaemic episodes may be life-threatening. 
 
In many patients, the signs and symptoms of neuroglycopenia are preceded by signs of adrenergic 
counter-regulation. Generally, the greater and more rapid the decline in blood glucose, the more 
marked is the phenomenon of counter-regulation and its symptoms. 
Insulin may cause sodium retention and oedema, particularly if previously poor metabolic control is 
improved by intensified insulin therapy. 
 
Eyes disorders 
A marked change in glycaemic control may cause temporary visual impairment, due to temporary 
alteration in the turgidity and refractive index of the lens. 
 
Long-term improved glycaemic control decreases the risk of progression of diabetic retinopathy. 
However, intensification of insulin therapy with abrupt improvement in glycaemic control may be 
associated with temporary worsening of diabetic retinopathy. 
 
Skin and subcutaneous tissue disorders 
Lipodystrophy may occur at the injection site and delay local insulin absorption. Continuous rotation 
of the injection site within the given injection area may help to reduce or prevent these reactions. 
 
General disorders and administration site conditions 
Most minor reactions to insulins at the injection site usually resolve in a few days to a few weeks. 
 
4.9 Overdose 
 
Symptoms 
Insulin overdose may lead to severe and sometimes long-term and life-threatening hypoglycaemia. 
 
Management 
Mild episodes of hypoglycaemia can usually be treated with oral carbohydrates. Adjustments in dose 
regimen of the medicinal product, meal patterns, or physical activity may be needed. 
 
More severe episodes with coma, seizure, or neurologic impairment may be treated with 
intramuscular/subcutaneous glucagon or concentrated intravenous glucose. Sustained carbohydrate 
intake and observation may be necessary because hypoglycaemia may recur after apparent clinical 
recovery. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Drugs used in diabetes, insulins and analogues for injection, 
intermediate-acting combined with fast-acting, ATC Code: A10AD01. 
 
Mechanism of action 
Insulin 
- lowers blood glucose and promotes anabolic effects as well as decreasing catabolic effects, 
- increases the transport of glucose into cells as well as the formation of glycogen in the muscles 

and the liver, and improves pyruvate utilisation. It inhibits glycogenolysis and gluconeogenesis, 
- increases lipogenesis in the liver and adipose tissue and inhibits lipolysis, 
- promotes the uptake of amino acids into cells and promotes protein synthesis, 
- enhances the uptake of potassium into cells. 
 

 

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Pharmacodynamic effects 
Insulin Human Winthrop Comb 25 (a biphasic isophane insulin suspension with 25% dissolved 
insulin) is an insulin with gradual onset and long duration of action. Following subcutaneous injection, 
onset of action is within 30 to 60 minutes, the phase of maximum action is between 2 and 4 hours after 
injection and the duration of action is 12 to 19 hours. 
 
5.2 Pharmacokinetic properties 
 
In healthy subjects, the serum half-life of insulin is approximately 4 to 6 minutes. It is longer in 
patients with severe renal insufficiency. However, it must be noted that the pharmacokinetics of 
insulin do not reflect its metabolic action. 
 
5.3 Preclinical safety data 
 
The acute toxicity was studied following subcutaneous administration in rats. No evidence of toxic 
effects was found. Studies of pharmacodynamic effects following subcutaneous administration in 
rabbits and dogs revealed the expected hypoglycaemic reactions. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Protamine sulphate, 
metacresol, 
phenol, 
zinc chloride, 
sodium dihydrogen phosphate dihydrate, 
glycerol, 
sodium hydroxide, 
hydrochloric acid (for pH adjustment), 
water for injections. 
 
6.2 Incompatibilities 
 
This medicinal product must not be mixed with other medicinal products except those mentioned in 
section 6.6. 
 
Insulin Human Winthrop Comb 25 must not be mixed with solutions containing reducing substances 
such as thioles and sulphites.  
 
Mixing of insulins 
Insulin Human Winthrop Comb 25 must not be mixed with any other insulin or with insulin 
analogues. 
 
Care must be taken to ensure that no alcohol or other disinfectants enter the insulin suspension. 
 
6.3 Shelf life 
 
2 years. 
 
Shelf life after first use of the pen 
The pen in-use or carried as a spare may be stored for a maximum of 4 weeks not above 25°C and 
away from direct heat or direct light. 
Pens in-use must not be stored in the refrigerator. 
The pen cap must be put back on the pen after each injection in order to protect from light. 
 

 

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6.4 Special precautions for storage 
 
Not in-use pens 
Store in a refrigerator (2°C - 8°C). 
Do not freeze. 
Do not put Insulin Human Winthrop Comb 25 next to the freezer compartment or a freezer pack. 
Keep the pre-filled pen in the outer carton in order to protect from light. 
 
In-use pens 
For storage conditions after first opening of the medicinal product, see section 6.3. 
 
6.5 Nature and contents of container 
 
3 ml suspension in a cartridge (type 1 colourless glass) with a plunger (bromobutyl rubber (type 1)) 
and a flanged cap (aluminium) with a stopper (bromobutyl or laminate of polyisoprene and 
bromobutyl rubber (type 1)). 
Each cartridge contains 3 balls (stainless steel). 
The cartridges are sealed in a disposable pen injector.  
Injection needles are not included in the pack. 
Packs of 3, 4, 5, 6, 9 or 10 pens are available. 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal and other handling 
 
Before first use, Insulin Human Winthrop Comb 25 must be kept at room temperature for 1 to 2 hours 
and then resuspended to check the contents. This is best done by gently tilting the pen back and forth 
(at least ten times). Each cartridge contains three small metal balls to facilitate quick and thorough 
mixing of the contents. Later on, the insulin must be resuspended again prior to each injection. 
 
After resuspension, the fluid must have a uniformly milky appearance. Insulin Human Winthrop 
Comb 25 must not be used if this cannot be achieved, i.e. if the suspension remains clear, for example, 
or if clumps, particles or flocculation appear in the insulin or stick to the wall or bottom of the 
cartridge. These changes sometimes give the cartridge a frosted appearance. In such cases, a new pen 
yielding a uniform suspension must be used. It is also necessary to change to a new pen if the insulin 
requirement changes substantially. 
 
Empty pens must never be re-used and must be properly discarded. 
 
To prevent the possible transmission of disease, each pen must be used by one patient only. 
 
It must be remembered that 
- insulin protamine crystals dissolve in an acid pH range, 
- the soluble insulin part precipitates out at a pH of approximately 4.5 to 6.5. 
 
Insulin label must always be checked before each injection to avoid medication errors between insulin 
human and other insulins (see section 4.4). 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 

 

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Handling of the pen 
The patient should be advised to read the instructions for use included in the package leaflet 
carefully before using SoloStar. 
 

 
Schematic diagram of the pen 

 
Important information for use of SoloStar: 
 
• Before each use, a new needle must always be carefully attached and a safety test must be 

performed. A dose should not be selected and/or the injection button should not be pressed 
without a needle attached. Only use needles that are compatible for use with SoloStar. 

• Special caution must be taken to avoid accidental needle injury and transmission of infection. 
• SoloStar must never be used if it is damaged or if the patient is not sure if it is working properly. 
• The patient must always have a spare SoloStar available in case the SoloStar is lost or damaged. 
 
Storage instructions  
 
Please check section 6.4 for instructions on how to store SoloStar. 
 
If SoloStar is in cool storage, it should be taken out 1 to 2 hours before injection to allow it to warm 
up. Cold insulin is more painful to inject. 
 
The used SoloStar must be discarded as required by your local authorities. 
 
Maintenance 
 
SoloStar has to be protected from dust and dirt. 
 
The outside of the SoloStar can be cleaned by wiping it with a damp cloth. 
 
The pen must not be soaked, washed or lubricated as this may damage it. 
 
SoloStar is designed to work accurately and safely. It should be handled with care. The patient should 
avoid situations where SoloStar may be damaged. If the patient is concerned that the SoloStar may be 
damaged, he must use a new one. 
 
Step 1. Check the insulin 
 
The label on the pen should be checked to make sure it contains the correct insulin. Insulin Human 
Winthrop SoloStar is white with a colour on the injection button. The injection button colour will vary 
based on the formulation of Insulin Human Winthrop insulin used. 
 
After removing the pen cap, the appearance of the insulin should also be checked: 
The insulin suspensions (Insulin Human Winthrop Basal or Insulin Human Winthrop mixtures) should 
be mixed by turning SoloStar up and down at least 10 times to resuspend the insulin. The pen should 
be turned gently to avoid foaming in the cartridge. After mixing, the insulin suspensions must have an 
evenly milky-white appearance. 
 
Step 2. Attach the needle 
 
Only needles that are compatible for use with SoloStar should be used. 

 

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A new sterile needle will be always used for each injection. After removing the cap, the needle should 
be carefully attached straight onto the pen. 
 
Step 3. Perform a safety test  
 
Prior to each injection, a safety test has to be performed to ensure that pen and needle work properly 
and to remove air bubbles. 
 
A dose of 2 units has to be selected. 
The outer and inner needle caps should be removed. 
 
While holding the pen with the needle pointing upwards, the insulin reservoir should be tapped gently 
with the finger so that any air bubbles rise up towards the needle. 
 
Then the injection button should be pressed in completely. 
 
If insulin has been expelled through the needle tip, then the pen and the needle are working properly. 
If no insulin appears at the needle tip, step 3 should be repeated until insulin appears at the needle tip. 
 
Step 4. Select the dose 
 
The dose can be set in steps of 1 unit, from a minimum of 1 unit to a maximum of 80 units. If a dose 
greater than 80 units is required, it should be given as two or more injections. 
 
The dose window must show “0” following the safety test. The dose can then be selected. 
 
Step 5. Inject the dose 
 
The patient should be informed on the injection technique by his health care professional.  
The needle should be inserted into the skin. 
The injection button should be pressed in completely. Then the injection button should be held down 
10 seconds before withdrawing the needle. This ensures that the full dose of insulin has been injected. 
 
Step 6. Remove and discard the needle 
 
The needle should always be removed after each injection and discarded. This helps prevent 
contamination and/or infection, entry of air into the insulin reservoir and leakage of insulin. Needles 
mut not be re-used. 
 
Special caution must be taken when removing and disposing of the needle. Recommended safety 
measures for removal and disposal of needles must be followed (e.g. a one handed capping technique) 
in order to reduce the risk of accidental needle injury and transmission of infectious diseases. 
 
The pen cap should be replaced on the pen. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Sanofi-Aventis Deutschland GmbH, D-65926 Frankfurt am Main, Germany 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/06/368/131 
EU/1/06/368/132 
EU/1/06/368/133 

 

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EU/1/06/368/134 
EU/1/06/368/135 
EU/1/06/368/136 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 17 January 2007 
Date of latest renewal: 17 January 2012 
 
 
10. DATE OF REVISION OF THE TEXT 
 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu 

 

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1. NAME OF THE MEDICINAL PRODUCT 
 
Insulin Human Winthrop Comb 30 100 IU/ml suspension for injection in a vial 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each ml contains 100 IU insulin human (equivalent to 3.5 mg).  
Each vial contains 5 ml of suspension for injection, equivalent to 500 IU insulin, or 10 ml of 
suspension for injection, equivalent to 1000 IU insulin. One IU (International Unit) corresponds to 
0.035 mg of anhydrous human insulin. 
 
Insulin Human Winthrop Comb 30 is a biphasic isophane insulin suspension consisting of 30% 
dissolved insulin and 70% crystalline protamine insulin. 
 
Human insulin is produced by recombinant DNA technology in Escherichia coli. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Suspension for injection in a vial. 
 
After resuspension, milky-white suspension. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Diabetes mellitus where treatment with insulin is required. 
 
4.2 Posology and method of administration 
 
Posology 
The desired blood glucose levels, the insulin preparations to be used and the insulin dose regimen 
(doses and timings) must be determined individually and adjusted to suit the patient’s diet, physical 
activity and life-style. 
 
Daily doses and timing of administration 
There are no fixed rules for insulin dose regimen. However, the average insulin requirement is often 
0.5 to 1.0 IU per kg body weight per day. The basal metabolic requirement is 40% to 60% of the total 
daily requirement. Insulin Human Winthrop Comb 30 is injected subcutaneously 30 to 45 minutes 
before a meal. 
 
Secondary dose adjustment 
Improved metabolic control may result in increased insulin sensitivity, leading to a reduced insulin 
requirement. Dose adjustment may also be required, for example, if 
- the patient's weight changes, 
- the patient's life-style changes, 
- other circumstances arise that may promote an increased susceptibility to hypo- or 

hyperglycaemia (see section 4.4). 
 
Special populations 
Elderly population (≧65 years old) 

 

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In the elderly, progressive deterioration of renal function may lead to a steady decrease in insulin 
requirements. 
 
Renal impairment 
In patients with renal impairment, insulin requirements may be diminished due to reduced insulin 
metabolism. 
 
Hepatic impairment 
In patients with severe hepatic impairment, insulin requirements may be diminished due to reduced 
capacity for gluconeogenesis and reduced insulin metabolism. 
 
Method of administration 
Insulin Human Winthrop Comb 30 must not be administered intravenously and must not be used in 
infusion pumps or external or implanted insulin pumps. 
 
Only injection syringes designed for this strength of insulin (100 IU per ml) are to be used. The 
injection syringes must not contain any other medicinal product or residue (e.g. traces of heparin). 
 
Insulin Human Winthrop Comb 30 is administered subcutaneously. Insulin Human Winthrop 
Comb 30 must never be injected intravenously. 
 
Insulin absorption and hence the blood-glucose-lowering effect of a dose may vary from one injection 
area to another (e.g. the abdominal wall compared with the thigh). Injection sites within an injection 
area must be rotated from one injection to the next. 
 
For further details on handling, see section 6.6. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
 
4.4 Special warnings and precautions for use 
 
Patients hypersensitive to Insulin Human Winthrop Comb 30 for whom no better tolerated preparation 
is available must only continue treatment under close medical supervision and – where necessary – in 
conjunction with anti-allergic treatment. 
 
In patients with an allergy to animal insulin intradermal skin testing is recommended prior to a 
transfer to Insulin Human Winthrop Comb 30, since they may experience immunological 
cross-reactions. 
 
In case of insufficient glucose control or a tendency to hyper- or hypoglycaemic episodes, the patient's 
adherence to the prescribed treatment regimen, injection sites and proper injection technique and all 
other relevant factors must be reviewed before dose adjustment is considered. 
 
Transfer to Insulin Human Winthrop Comb 30 
Transferring a patient to another type or brand of insulin should be done under strict medical 
supervision. Changes in strength, brand (manufacturer), type (regular, NPH, lente, long-acting, etc.), 
origin (animal, human, human insulin analogue) and/or method of manufacture may result in the need 
for a change in dosage. 
The need to adjust (e.g. reduce) the dose may become evident immediately after transfer. 
Alternatively, it may emerge gradually over a period of several weeks. 
 
Following transfer from an animal insulin to human insulin, dose regimen reduction may be required 
in particular in patients who 
- were previously already controlled on rather low blood glucose levels, 
- have a tendency to hypoglycaemia, 

 

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- previously required high insulin doses due to the presence of insulin antibodies. 
 
Close metabolic monitoring is recommended during the transition and in the initial weeks thereafter. In 
patients who require high insulin doses because of the presence of insulin antibodies, transfer under 
medical supervision in a hospital or similar setting must be considered. 
 
Hypoglycaemia 
Hypoglycaemia may occur if the insulin dose is too high in relation to the insulin requirement. 
 
Particular caution should be exercised, and intensified blood glucose monitoring is advisable in 
patients in whom hypoglycaemic episodes might be of particular clinical relevance, such as in patients 
with significant stenoses of the coronary arteries or of the blood vessels supplying the brain (risk of 
cardiac or cerebral complications of hypoglycaemia) as well as in patients with proliferative 
retinopathy, particularly if not treated with photocoagulation (risk of transient amaurosis following 
hypoglycaemia). 
 
Patients should be aware of circumstances where warning symptoms of hypoglycaemia are 
diminished. The warning symptoms of hypoglycaemia may be changed, be less pronounced or be 
absent in certain risk groups. These include patients: 
- in whom glycaemic control is markedly improved, 
- in whom hypoglycaemia develops gradually, 
- who are elderly,  
- after transfer from animal insulin to human insulin, 
- in whom an autonomic neuropathy is present, 
- with a long history of diabetes, 
- suffering from a psychiatric illness, 
- receiving concurrent treatment with certain other medicinal products (see section 4.5). 
Such situations may result in severe hypoglycaemia (and possibly loss of consciousness) prior to the 
patient's awareness of hypoglycaemia. 
 
If normal or decreased values for glycated haemoglobin are noted, the possibility of recurrent, 
unrecognised (especially nocturnal) episodes of hypoglycaemia must be considered. 
 
Adherence of the patient to the dose regimen and dietary regimen, correct insulin administration and 
awareness of hypoglycaemia symptoms are essential to reduce the risk of hypoglycaemia. Factors 
increasing the susceptibility to hypoglycaemia require particularly close monitoring and may 
necessitate dose adjustment. These include: 
- change in the injection area, 
- improved insulin sensitivity (e.g. by removal of stress factors), 
- unaccustomed, increased or prolonged physical activity, 
- intercurrent illness (e.g. vomiting, diarrhoea), 
- inadequate food intake, 
- missed meals, 
- alcohol consumption, 
- certain uncompensated endocrine disorders (e.g. in hypothyroidism and in anterior pituitary or 

adrenocortical insufficiency), 
- concomitant treatment with certain other medicinal products. 
 
Intercurrent illness 
Intercurrent illness requires intensified metabolic monitoring. In many cases, urine tests for ketones 
are indicated, and often it is necessary to adjust the insulin dose. The insulin requirement is often 
increased. Patients with type 1 diabetes must continue to consume at least a small amount of 
carbohydrates on a regular basis, even if they are able to eat only little or no food, or are vomiting etc. 
and they must never omit insulin entirely. 
 
Medication errors 

 

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Medication errors have been reported in which other Insulin Human Winthrop formulations or other 
insulins have been accidentally administered. Insulin label must always be checked before each 
injection to avoid medication errors between insulin human and other insulins. 
 
Combination of Insulin Human Winthrop with pioglitazone 
Cases of cardiac failure have been reported when pioglitazone was used in combination with insulin, 
especially in patients with risk factors for development of cardiac heart failure. This should be kept in 
mind if treatment with the combination of pioglitazone and Insulin Human Winthrop is considered. If 
the combination is used, patients should be observed for signs and symptoms of heart failure, weight 
gain and oedema. Pioglitazone should be discontinued if any deterioration in cardiac symptoms 
occurs.  
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
A number of substances affect glucose metabolism and may require dose adjustment of human insulin. 
 
Substances that may enhance the blood-glucose-lowering effect and increase susceptibility to 
hypoglycaemia include oral antidiabetic medicinal products, angiotensin converting enzyme (ACE) 
inhibitors, disopyramide, fibrates, fluoxetine, monoamine oxidase (MAO) inhibitors, pentoxifylline, 
propoxyphene, salicylates and sulphonamide antibiotics. 
 
Substances that may reduce the blood-glucose-lowering effect include corticosteroids, danazol, 
diazoxide, diuretics, glucagon, isoniazid, oestrogens and progestogens (e.g. in oral contraceptives), 
phenothiazine derivatives, somatropin, sympathomimetic medicinal products (e.g. epinephrine 
[adrenaline], salbutamol, terbutaline), thyroid hormones, protease inhibitors and atypical antipsychotic 
medicinal products (e.g. olanzapine and clozapine). 
 
Beta-blockers, clonidine, lithium salts or alcohol may either potentiate or weaken the 
blood-glucose-lowering effect of insulin. Pentamidine may cause hypoglycaemia which may 
sometimes be followed by hyperglycaemia. 
 
In addition, under the influence of sympatholytic medicinal products such as beta-blockers, clonidine, 
guanethidine and reserpine, the signs of adrenergic counter-regulation may be reduced or absent. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
For insulin human, no clinical data on exposed pregnancies from controlled clinical studies are 
available. Insulin does cross the placental barrier, although not in clinically significant amount. A 
limited amount of data on pregnant women (less than 300 pregnancy outcomes reported) exposed to 
marketed insulin human indicates no safety issues in use of insulin human in pregnancy. Caution 
should be exercised when prescribing to pregnant women. 
 
It is essential for patients with pre-existing or gestational diabetes to maintain good metabolic control 
throughout pregnancy. Insulin requirements may decrease during the first trimester and generally 
increase during the second and third trimesters. Immediately after delivery, insulin requirements 
decline rapidly (increased risk of hypoglycaemia). Careful monitoring of glucose control is essential. 
 
Breast-feeding 
No effects on the suckling child are anticipated. Insulin Human Winthrop Comb 30 can be used during 
breast-feeding. Breast-feeding women may require adjustments in insulin dose and diet. 
 
Fertility 
No clinical or animal data with insulin human on male or female fertility are available. 
 

 

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4.7 Effects on ability to drive and use machines 
 
The patient's ability to concentrate and react may be impaired as a result of hypoglycaemia or 
hyperglycaemia or, for example, as a result of visual impairment. This may constitute a risk in 
situations where these abilities are of special importance (e.g. driving a car or using machines). 
 
Patients should be advised to take precautions to avoid hypoglycaemia whilst driving. This is 
particularly important in those who have reduced or absent awareness of the warning symptoms of 
hypoglycaemia or have frequent episodes of hypoglycaemia. It should be considered whether it is 
advisable to drive or use machines in these circumstances. 
 
4.8 Undesirable effects 
 
Summary of the safety profile  
Hypoglycaemia, in general the most frequent adverse reaction of insulin therapy, may occur if the 
insulin dose is too high in relation to the insulin requirement. In clinical studies and during marketed 
use, the frequency varies with patient population and dose regimens. Therefore, no specific frequency 
can be presented. 
 
Tabulated list of adverse reactions 
The following related adverse reactions from clinical investigations are listed below by system organ 
class and in order of decreasing incidence: very common (≥1/10); common (≥1/100 to <1/10); 
uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000), not known 
(cannot be estimated from the available data). 
 
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. 
 
MedDRA system 
organ classes 

Common Uncommon Not known 

Immune system 
disorders 

 Shock Immediate type allergic 
reactions (hypotension, 
angioneurotic oedema, 
bronchospasm, 
generalised skin 
reactions); 
Anti-insulin antibodies 

Metabolism and 
nutrition disorders 

Oedema  Hypoglycaemia; 
Sodium retention 

Eye disorders   Proliferative retinopathy; 
Diabetic retinopathy; 
Visual impairment 

Skin and subcutaneous 
tissue disorders 

  Lipodystrophy 

General disorders and 
administration site 
conditions 

Injection site reactions Injection site 
urticaria 

Injection site 
inflammation;  
Injection site pain ; 
Injection site pruritus; 
Injection site erythema; 
Injection site swelling 

 

 

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Description of selected adverse reactions 
Immune system disorders 
Immediate type allergic reactions to insulin or to the excipients may be life-threatening. 
 
Insulin administration may cause anti-insulin antibodies to form. In rare cases, the presence of such 
anti-insulin antibodies may necessitate adjustment of the insulin dose in order to correct a tendency to 
hyper- or hypoglycaemia. 
 
Metabolism and nutrition disorders 
Severe hypoglycaemic attacks, especially if recurrent, may lead to neurological damage. 
Prolonged or severe hypoglycaemic episodes may be life-threatening. 
 
In many patients, the signs and symptoms of neuroglycopenia are preceded by signs of adrenergic 
counter-regulation. Generally, the greater and more rapid the decline in blood glucose, the more 
marked is the phenomenon of counter-regulation and its symptoms. 
Insulin may cause sodium retention and oedema, particularly if previously poor metabolic control is 
improved by intensified insulin therapy. 
 
Eyes disorders 
A marked change in glycaemic control may cause temporary visual impairment, due to temporary 
alteration in the turgidity and refractive index of the lens. 
 
Long-term improved glycaemic control decreases the risk of progression of diabetic retinopathy. 
However, intensification of insulin therapy with abrupt improvement in glycaemic control may be 
associated with temporary worsening of diabetic retinopathy. 
 
Skin and subcutaneous tissue disorders 
Lipodystrophy may occur at the injection site and delay local insulin absorption. Continuous rotation 
of the injection site within the given injection area may help to reduce or prevent these reactions. 
 
General disorders and administration site conditions 
Most minor reactions to insulins at the injection site usually resolve in a few days to a few weeks. 
 
4.9 Overdose 
 
Symptoms 
Insulin overdose may lead to severe and sometimes long-term and life-threatening hypoglycaemia. 
 
Management 
Mild episodes of hypoglycaemia can usually be treated with oral carbohydrates. Adjustments in dose 
regimen of the medicinal product, meal patterns, or physical activity may be needed. 
 
More severe episodes with coma, seizure, or neurologic impairment may be treated with 
intramuscular/subcutaneous glucagon or concentrated intravenous glucose. Sustained carbohydrate 
intake and observation may be necessary because hypoglycaemia may recur after apparent clinical 
recovery. 
 
 

 

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5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Drugs used in diabetes, insulins and analogues for injection, 
intermediate-acting combined with fast-acting, ATC Code: A10AD01. 
 
Mechanism of action 
Insulin 
- lowers blood glucose and promotes anabolic effects as well as decreasing catabolic effects, 
- increases the transport of glucose into cells as well as the formation of glycogen in the muscles 

and the liver, and improves pyruvate utilisation. It inhibits glycogenolysis and gluconeogenesis, 
- increases lipogenesis in the liver and adipose tissue and inhibits lipolysis, 
- promotes the uptake of amino acids into cells and promotes protein synthesis, 
- enhances the uptake of potassium into cells. 
 
Pharmacodynamic effects 
Insulin Human Winthrop Comb 30 (a biphasic isophane insulin suspension with 30% dissolved 
insulin) is an insulin with gradual onset and long duration of action. Following subcutaneous injection, 
onset of action is within 30 to 60 minutes, the phase of maximum action is between 2 and 4 hours after 
injection and the duration of action is 12 to 19 hours. 
 
5.2 Pharmacokinetic properties 
 
In healthy subjects, the serum half-life of insulin is approximately 4 to 6 minutes. It is longer in 
patients with severe renal insufficiency. However, it must be noted that the pharmacokinetics of 
insulin do not reflect its metabolic action. 
 
5.3 Preclinical safety data 
 
The acute toxicity was studied following subcutaneous administration in rats. No evidence of toxic 
effects was found. Studies of pharmacodynamic effects following subcutaneous administration in 
rabbits and dogs revealed the expected hypoglycaemic reactions. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Protamine sulphate, 
metacresol, 
phenol, 
zinc chloride, 
sodium dihydrogen phosphate dihydrate, 
glycerol, 
sodium hydroxide, 
hydrochloric acid (for pH adjustment), 
water for injections. 
 
6.2 Incompatibilities 
 
This medicinal product must not be mixed with other medicinal products except those mentioned in 
section 6.6. 
 
Insulin Human Winthrop Comb 30 must not be mixed with solutions containing reducing substances 
such as thioles and sulphites.  
 

 

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Mixing of insulins 
Insulin Human Winthrop Comb 30 must not be mixed with insulin human formulations designed 
specifically for use in insulin pumps.  
Insulin Human Winthrop Comb 30 must also not be mixed with insulins of animal origin or with 
insulin analogues. 
Insulins of different concentration (e.g. 100 IU per ml and 40 IU per ml) must not be mixed. 
 
Care must be taken to ensure that no alcohol or other disinfectants enter the insulin suspension. 
 
6.3 Shelf life 
 
2 years. 
 
Shelf life after first use of the vial 
The product may be stored for a maximum of 4 weeks not above 25°C and away from direct heat or 
direct light. 
Keep the vial in the outer carton in order to protect from light. 
It is recommended that the date of the first use be noted on the label. 
 
6.4 Special precautions for storage 
 
Unopened vials 
Store in a refrigerator (2°C - 8°C). 
Do not freeze. 
Do not put Insulin Human Winthrop Comb 30 next to the freezer compartment or a freezer pack. 
Keep the vial in the outer carton in order to protect from light. 
 
Opened vials 
For storage conditions after first opening of the medicinal product, see section 6.3. 
 
6.5 Nature and contents of container 
 
5 ml suspension in a vial and 10 ml suspension in a vial (type 1 colourless glass) with a flanged cap 
(aluminium), a stopper (chlorobutyl rubber (type 1)) and a tear-off cap (polypropylene). 
Packs of 1 and 5 vials are available. 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal and other handling 
 
Before withdrawing insulin from the vial for the first time, remove the plastic protective cap. 
 
Immediately before withdrawal from the vial into the injection syringe, the insulin must be 
resuspended. This is best done by rolling the vial at an oblique angle between the palms of the hands. 
Do not shake the vial vigorously as this may lead to changes in the suspension (giving the vial a 
frosted appearance; see below) and cause frothing. Froth may interfere with the correct measurement 
of the dose. 
 
After resuspension, the fluid must have a uniformly milky appearance. Insulin Human Winthrop 
Comb 30 must not be used if this cannot be achieved, i.e. if the suspension remains clear, for example, 
or if clumps, particles or flocculation appear in the insulin or stick to the wall or bottom of the vial. 
These changes sometimes give the vial a frosted appearance. In such cases, a new vial yielding a 
uniform suspension must be used. It is also necessary to change to a new vial if the insulin 
requirement changes substantially. 
 
Insulin Human Winthrop Comb 30 must not be administered intravenously and must not be used in 
infusion pumps or external or implanted insulin pumps. 
 

 

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It must be remembered that 
- insulin protamine crystals dissolve in an acid pH range, 
- the soluble insulin part precipitates out at a pH of approximately 4.5 to 6.5. 
 
Insulin label must always be checked before each injection to avoid medication errors between insulin 
human and other insulins (see section 4.4). 
 
Mixing of insulins 
Insulin Human Winthrop Comb 30 may be mixed with all insulin human formulations, but not with 
those designed specifically for use in insulin pumps. Concerning incompatibility with other insulins, 
see section 6.2. 
 
If two different insulins have to be drawn into one single injection syringe, it is recommended that the 
shorter-acting insulin be drawn first to prevent contamination of the vial by the longer-acting 
preparation. It is advisable to inject immediately after mixing.  
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Sanofi-Aventis Deutschland GmbH, D-65926 Frankfurt am Main, Germany 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/06/368/143 
EU/1/06/368/144 
EU/1/06/368/173 
EU/1/06/368/174 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 17 January 2007 
Date of latest renewal: 17 January 2012 
 
 
10. DATE OF REVISION OF THE TEXT 
 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu 

 

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1. NAME OF THE MEDICINAL PRODUCT 
 
Insulin Human Winthrop Comb 30 100 IU/ml suspension for injection in a cartridge 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each ml contains 100 IU insulin human (equivalent to 3.5 mg).  
Each cartridge contains 3 ml of suspension for injection, equivalent to 300 IU insulin. One IU 
(International Unit) corresponds to 0.035 mg of anhydrous human insulin. 
 
Insulin Human Winthrop Comb 30 is a biphasic isophane insulin suspension consisting of 30% 
dissolved insulin and 70% crystalline protamine insulin. 
 
Human insulin is produced by recombinant DNA technology in Escherichia coli. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Suspension for injection in a cartridge. 
 
After resuspension, milky-white suspension. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Diabetes mellitus where treatment with insulin is required. 
 
4.2 Posology and method of administration 
 
Posology 
The desired blood glucose levels, the insulin preparations to be used and the insulin dose regimen 
(doses and timings) must be determined individually and adjusted to suit the patient’s diet, physical 
activity and life-style. 
 
Daily doses and timing of administration 
There are no fixed rules for insulin dose regimen. However, the average insulin requirement is often 
0.5 to 1.0 IU per kg body weight per day. The basal metabolic requirement is 40% to 60% of the total 
daily requirement. Insulin Human Winthrop Comb 30 is injected subcutaneously 30 to 45 minutes 
before a meal. 
 
Secondary dose adjustment 
Improved metabolic control may result in increased insulin sensitivity, leading to a reduced insulin 
requirement. Dose adjustment may also be required, for example, if 
- the patient's weight changes, 
- the patient's life-style changes, 
- other circumstances arise that may promote an increased susceptibility to hypo- or 

hyperglycaemia (see section 4.4). 
 
Special populations 
Elderly population (≧65 years old) 
In the elderly, progressive deterioration of renal function may lead to a steady decrease in insulin 
requirements. 

 

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Renal impairment 
In patients with renal impairment, insulin requirements may be diminished due to reduced insulin 
metabolism. 
 
Hepatic impairment 
In patients with severe hepatic impairment, insulin requirements may be diminished due to reduced 
capacity for gluconeogenesis and reduced insulin metabolism. 
 
Method of administration 
Insulin Human Winthrop Comb 30 must not be administered intravenously and must not be used in 
infusion pumps or external or implanted insulin pumps. 
 
Insulin Human Winthrop Comb 30 is administered subcutaneously. Insulin Human Winthrop 
Comb 30 must never be injected intravenously. 
 
Insulin absorption and hence the blood-glucose-lowering effect of a dose may vary from one injection 
area to another (e.g. the abdominal wall compared with the thigh). Injection sites within an injection 
area must be rotated from one injection to the next. 
 
For further details on handling, see section 6.6. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
 
4.4 Special warnings and precautions for use 
 
Patients hypersensitive to Insulin Human Winthrop Comb 30 for whom no better tolerated preparation 
is available must only continue treatment under close medical supervision and – where necessary – in 
conjunction with anti-allergic treatment. 
 
In patients with an allergy to animal insulin intradermal skin testing is recommended prior to a 
transfer to Insulin Human Winthrop Comb 30, since they may experience immunological 
cross-reactions. 
 
In case of insufficient glucose control or a tendency to hyper- or hypoglycaemic episodes, the patient's 
adherence to the prescribed treatment regimen, injection sites and proper injection technique and all 
other relevant factors must be reviewed before dose adjustment is considered. 
 
Transfer to Insulin Human Winthrop Comb 30 
Transferring a patient to another type or brand of insulin should be done under strict medical 
supervision. Changes in strength, brand (manufacturer), type (regular, NPH, lente, long-acting, etc.), 
origin (animal, human, human insulin analogue) and/or method of manufacture may result in the need 
for a change in dosage. 
The need to adjust (e.g. reduce) the dose may become evident immediately after transfer. 
Alternatively, it may emerge gradually over a period of several weeks. 
 
Following transfer from an animal insulin to human insulin, dose regimen reduction may be required 
in particular in patients who 
- were previously already controlled on rather low blood glucose levels, 
- have a tendency to hypoglycaemia, 
- previously required high insulin doses due to the presence of insulin antibodies. 
 
Close metabolic monitoring is recommended during the transition and in the initial weeks thereafter. In 
patients who require high insulin doses because of the presence of insulin antibodies, transfer under 
medical supervision in a hospital or similar setting must be considered. 

 

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Hypoglycaemia 
Hypoglycaemia may occur if the insulin dose is too high in relation to the insulin requirement. 
 
Particular caution should be exercised, and intensified blood glucose monitoring is advisable in 
patients in whom hypoglycaemic episodes might be of particular clinical relevance, such as in patients 
with significant stenoses of the coronary arteries or of the blood vessels supplying the brain (risk of 
cardiac or cerebral complications of hypoglycaemia) as well as in patients with proliferative 
retinopathy, particularly if not treated with photocoagulation (risk of transient amaurosis following 
hypoglycaemia). 
 
Patients should be aware of circumstances where warning symptoms of hypoglycaemia are 
diminished. The warning symptoms of hypoglycaemia may be changed, be less pronounced or be 
absent in certain risk groups. These include patients: 
- in whom glycaemic control is markedly improved, 
- in whom hypoglycaemia develops gradually, 
- who are elderly,  
- after transfer from animal insulin to human insulin, 
- in whom an autonomic neuropathy is present, 
- with a long history of diabetes, 
- suffering from a psychiatric illness, 
- receiving concurrent treatment with certain other medicinal products (see section 4.5). 
Such situations may result in severe hypoglycaemia (and possibly loss of consciousness) prior to the 
patient's awareness of hypoglycaemia. 
 
If normal or decreased values for glycated haemoglobin are noted, the possibility of recurrent, 
unrecognised (especially nocturnal) episodes of hypoglycaemia must be considered. 
 
Adherence of the patient to the dose regimen and dietary regimen, correct insulin administration and 
awareness of hypoglycaemia symptoms are essential to reduce the risk of hypoglycaemia. Factors 
increasing the susceptibility to hypoglycaemia require particularly close monitoring and may 
necessitate dose adjustment. These include: 
- change in the injection area, 
- improved insulin sensitivity (e.g. by removal of stress factors), 
- unaccustomed, increased or prolonged physical activity, 
- intercurrent illness (e.g. vomiting, diarrhoea), 
- inadequate food intake, 
- missed meals, 
- alcohol consumption, 
- certain uncompensated endocrine disorders (e.g. in hypothyroidism and in anterior pituitary or 

adrenocortical insufficiency), 
- concomitant treatment with certain other medicinal products. 
 
Intercurrent illness 
Intercurrent illness requires intensified metabolic monitoring. In many cases, urine tests for ketones 
are indicated, and often it is necessary to adjust the insulin dose. The insulin requirement is often 
increased. Patients with type 1 diabetes must continue to consume at least a small amount of 
carbohydrates on a regular basis, even if they are able to eat only little or no food, or are vomiting etc. 
and they must never omit insulin entirely. 
 
Pens to be used with Insulin Human Winthrop Comb 30 cartridges 
The Insulin Human Winthrop Comb 30 cartridges should only be used with the following pens:  
- JuniorSTAR which delivers Insulin Human Winthrop Comb 30 in 0.5 unit dose increments 
- OptiPen, ClikSTAR, Tactipen, Autopen 24 and AllStar which all deliver Insulin Human Winthrop 
Comb 30 in 1 unit dose increments. 
These cartridges should not be used with any other reusable pen as the dosing accuracy has only been 
established with the listed pens.  

 

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Not all of these pens may be marketed in your country. 
 
Medication errors 
Medication errors have been reported in which other Insulin Human Winthrop formulations or other 
insulins have been accidentally administered. Insulin label must always be checked before each 
injection to avoid medication errors between insulin human and other insulins. 
 
Combination of Insulin Human Winthrop with pioglitazone 
Cases of cardiac failure have been reported when pioglitazone was used in combination with insulin, 
especially in patients with risk factors for development of cardiac heart failure. This should be kept in 
mind if treatment with the combination of pioglitazone and Insulin Human Winthrop is considered. If 
the combination is used, patients should be observed for signs and symptoms of heart failure, weight 
gain and oedema. Pioglitazone should be discontinued if any deterioration in cardiac symptoms 
occurs.  
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
A number of substances affect glucose metabolism and may require dose adjustment of human insulin. 
 
Substances that may enhance the blood-glucose-lowering effect and increase susceptibility to 
hypoglycaemia include oral antidiabetic medicinal products, angiotensin converting enzyme (ACE) 
inhibitors, disopyramide, fibrates, fluoxetine, monoamine oxidase (MAO) inhibitors, pentoxifylline, 
propoxyphene, salicylates and sulphonamide antibiotics. 
 
Substances that may reduce the blood-glucose-lowering effect include corticosteroids, danazol, 
diazoxide, diuretics, glucagon, isoniazid, oestrogens and progestogens (e.g. in oral contraceptives), 
phenothiazine derivatives, somatropin, sympathomimetic medicinal products (e.g. epinephrine 
[adrenaline], salbutamol, terbutaline), thyroid hormones, protease inhibitors and atypical antipsychotic 
medicinal products (e.g. olanzapine and clozapine). 
 
Beta-blockers, clonidine, lithium salts or alcohol may either potentiate or weaken the 
blood-glucose-lowering effect of insulin. Pentamidine may cause hypoglycaemia which may 
sometimes be followed by hyperglycaemia. 
 
In addition, under the influence of sympatholytic medicinal products such as beta-blockers, clonidine, 
guanethidine and reserpine, the signs of adrenergic counter-regulation may be reduced or absent. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
For insulin human, no clinical data on exposed pregnancies from controlled clinical studies are 
available. Insulin does cross the placental barrier, although not in clinically significant amount. A 
limited amount of data on pregnant women (less than 300 pregnancy outcomes reported) exposed to 
marketed insulin human indicates no safety issues in use of insulin human in pregnancy. Caution 
should be exercised when prescribing to pregnant women. 
 
It is essential for patients with pre-existing or gestational diabetes to maintain good metabolic control 
throughout pregnancy. Insulin requirements may decrease during the first trimester and generally 
increase during the second and third trimesters. Immediately after delivery, insulin requirements 
decline rapidly (increased risk of hypoglycaemia). Careful monitoring of glucose control is essential. 
 
Breast-feeding 
No effects on the suckling child are anticipated. Insulin Human Winthrop Comb 30 can be used during 
breast-feeding. Breast-feeding women may require adjustments in insulin dose and diet. 
 
Fertility 
No clinical or animal data with insulin human on male or female fertility are available. 

 

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4.7 Effects on ability to drive and use machines 
 
The patient's ability to concentrate and react may be impaired as a result of hypoglycaemia or 
hyperglycaemia or, for example, as a result of visual impairment. This may constitute a risk in 
situations where these abilities are of special importance (e.g. driving a car or using machines). 
 
Patients should be advised to take precautions to avoid hypoglycaemia whilst driving. This is 
particularly important in those who have reduced or absent awareness of the warning symptoms of 
hypoglycaemia or have frequent episodes of hypoglycaemia. It should be considered whether it is 
advisable to drive or use machines in these circumstances. 
 
4.8 Undesirable effects 
 
Summary of the safety profile  
Hypoglycaemia, in general the most frequent adverse reaction of insulin therapy, may occur if the 
insulin dose is too high in relation to the insulin requirement. In clinical studies and during marketed 
use, the frequency varies with patient population and dose regimens. Therefore, no specific frequency 
can be presented. 
 
Tabulated list of adverse reactions 
The following related adverse reactions from clinical investigations are listed below by system organ 
class and in order of decreasing incidence: very common (≥1/10); common (≥1/100 to <1/10); 
uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000), not known 
(cannot be estimated from the available data). 
 
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. 
 
MedDRA system 
organ classes 

Common Uncommon Not known 

Immune system 
disorders 

 Shock Immediate type allergic 
reactions (hypotension, 
angioneurotic oedema, 
bronchospasm, 
generalised skin 
reactions); 
Anti-insulin antibodies 

Metabolism and 
nutrition disorders 

Oedema  Hypoglycaemia; 
Sodium retention 

Eye disorders   Proliferative retinopathy; 
Diabetic retinopathy; 
Visual impairment 

Skin and subcutaneous 
tissue disorders 

  Lipodystrophy 

General disorders and 
administration site 
conditions 

Injection site reactions Injection site 
urticaria 

Injection site 
inflammation;  
Injection site pain; 
Injection site pruritus; 
Injection site erythema; 
Injection site swelling 

 
Description of selected adverse reactions 
Immune system disorders 
Immediate type allergic reactions to insulin or to the excipients may be life-threatening. 
 

 

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Insulin administration may cause anti-insulin antibodies to form. In rare cases, the presence of such 
anti-insulin antibodies may necessitate adjustment of the insulin dose in order to correct a tendency to 
hyper- or hypoglycaemia. 
 
Metabolism and nutrition disorders 
Severe hypoglycaemic attacks, especially if recurrent, may lead to neurological damage. 
Prolonged or severe hypoglycaemic episodes may be life-threatening. 
 
In many patients, the signs and symptoms of neuroglycopenia are preceded by signs of adrenergic 
counter-regulation. Generally, the greater and more rapid the decline in blood glucose, the more 
marked is the phenomenon of counter-regulation and its symptoms. 
Insulin may cause sodium retention and oedema, particularly if previously poor metabolic control is 
improved by intensified insulin therapy. 
 
Eyes disorders 
A marked change in glycaemic control may cause temporary visual impairment, due to temporary 
alteration in the turgidity and refractive index of the lens. 
 
Long-term improved glycaemic control decreases the risk of progression of diabetic retinopathy. 
However, intensification of insulin therapy with abrupt improvement in glycaemic control may be 
associated with temporary worsening of diabetic retinopathy. 
 
Skin and subcutaneous tissue disorders 
Lipodystrophy may occur at the injection site and delay local insulin absorption. Continuous rotation 
of the injection site within the given injection area may help to reduce or prevent these reactions. 
 
General disorders and administration site conditions 
Most minor reactions to insulins at the injection site usually resolve in a few days to a few weeks. 
 
4.9 Overdose 
 
Symptoms 
Insulin overdose may lead to severe and sometimes long-term and life-threatening hypoglycaemia. 
 
Management 
Mild episodes of hypoglycaemia can usually be treated with oral carbohydrates. Adjustments in dose 
regimen of the medicinal product, meal patterns, or physical activity may be needed. 
 
More severe episodes with coma, seizure, or neurologic impairment may be treated with 
intramuscular/subcutaneous glucagon or concentrated intravenous glucose. Sustained carbohydrate 
intake and observation may be necessary because hypoglycaemia may recur after apparent clinical 
recovery. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Drugs used in diabetes, insulins and analogues for injection, 
intermediate-acting combined with fast-acting, ATC Code: A10AD01. 
 
Mechanism of action 
Insulin 
- lowers blood glucose and promotes anabolic effects as well as decreasing catabolic effects, 
- increases the transport of glucose into cells as well as the formation of glycogen in the muscles 

and the liver, and improves pyruvate utilisation. It inhibits glycogenolysis and gluconeogenesis, 
- increases lipogenesis in the liver and adipose tissue and inhibits lipolysis, 

 

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- promotes the uptake of amino acids into cells and promotes protein synthesis, 
- enhances the uptake of potassium into cells. 
 
Pharmacodynamic effects 
Insulin Human Winthrop Comb 30 (a biphasic isophane insulin suspension with 30% dissolved 
insulin) is an insulin with gradual onset and long duration of action. Following subcutaneous injection, 
onset of action is within 30 to 60 minutes, the phase of maximum action is between 2 and 4 hours after 
injection and the duration of action is 12 to 19 hours. 
 
5.2 Pharmacokinetic properties 
 
In healthy subjects, the serum half-life of insulin is approximately 4 to 6 minutes. It is longer in 
patients with severe renal insufficiency. However, it must be noted that the pharmacokinetics of 
insulin do not reflect its metabolic action. 
 
5.3 Preclinical safety data 
 
The acute toxicity was studied following subcutaneous administration in rats. No evidence of toxic 
effects was found. Studies of pharmacodynamic effects following subcutaneous administration in 
rabbits and dogs revealed the expected hypoglycaemic reactions. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Protamine sulphate, 
metacresol, 
phenol, 
zinc chloride, 
sodium dihydrogen phosphate dihydrate, 
glycerol, 
sodium hydroxide, 
hydrochloric acid (for pH adjustment), 
water for injections. 
 
6.2 Incompatibilities 
 
This medicinal product must not be mixed with other medicinal products except those mentioned in 
section 6.6. 
 
Insulin Human Winthrop Comb 30 must not be mixed with solutions containing reducing substances 
such as thioles and sulphites.  
 
Mixing of insulins 
Insulin Human Winthrop Comb 30 must not be mixed with insulin human formulations designed 
specifically for use in insulin pumps.  
Insulin Human Winthrop Comb 30 must also not be mixed with insulins of animal origin or with 
insulin analogues. 
 
Care must be taken to ensure that no alcohol or other disinfectants enter the insulin suspension. 
 
6.3 Shelf life 
 
2 years. 
 
Shelf life after first use of the cartridge 

 

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The cartridge in-use (in the insulin pen) or carried as a spare may be stored for a maximum of 4 weeks 
not above 25°C and away from direct heat or direct light. 
The pen containing a cartridge must not be stored in the refrigerator. 
The pen cap must be put back on the pen after each injection in order to protect from light. 
 
6.4 Special precautions for storage 
 
Unopened cartridges 
Store in a refrigerator (2°C - 8°C). 
Do not freeze. 
Do not put Insulin Human Winthrop Comb 30 next to the freezer compartment or a freezer pack. 
Keep the cartridge in the outer carton in order to protect from light. 
 
In-use cartridges 
For storage conditions after first opening of the medicinal product, see section 6.3. 
 
6.5 Nature and contents of container 
 
3 ml suspension in a cartridge (type 1 colourless glass) with a plunger (bromobutyl rubber (type 1)) 
and a flanged cap (aluminium) with a stopper (bromobutyl or laminate of polyisoprene and 
bromobutyl rubber (type 1)). 
Each cartridge contains 3 balls (stainless steel). 
Packs of 3, 4, 5, 6, 9 or 10 cartridges are available. 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal and other handling 
 
Insulin pen 
The Insulin Human Winthrop Comb 30 cartridges are to be used only in conjunction with the pens: 
OptiPen, ClikSTAR, Autopen 24, Tactipen, AllStar or JuniorSTAR (see section 4.4). Not all of these pens 
may be marketed in your country. 
 
The pen should be used as recommended in the information provided by the device manufacturer.  
 
The manufacturer’s instructions for using the pen must be followed carefully for loading the cartridge, 
attaching the injection needle, and administering the insulin injection. 
 
If the insulin pen is damaged or not working properly (due to mechanical defects) it has to be 
discarded, and a new insulin pen has to be used. 
 
If the pen malfunctions (see instructions for using the pen), the suspension may be drawn from the 
cartridge into an injection syringe (suitable for an insulin with 100 IU/ml) and injected. 
 
Cartridges 
Before insertion into the pen, Insulin Human Winthrop Comb 30 must be kept at room temperature for 
1 to 2 hours and then resuspended to check the contents. This is best done by gently tilting the 
cartridge back and forth (at least ten times). Each cartridge contains three small metal balls to facilitate 
quick and thorough mixing of the contents. 
 
Later on, when the cartridge has been inserted into the pen, the insulin must be resuspended again 
prior to each injection. This is best done by gently tilting the pen back and forth (at least ten times). 
 
After resuspension, the fluid must have a uniformly milky appearance. Insulin Human Winthrop 
Comb 30 must not be used if this cannot be achieved, i.e. if the suspension remains clear, for example, 
or if clumps, particles or flocculation appear in the insulin or stick to the wall or bottom of the 
cartridge. These changes sometimes give the cartridge a frosted appearance. In such cases, a new 

 

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cartridge yielding a uniform suspension must be used. It is also necessary to change to a new cartridge 
if the insulin requirement changes substantially. 
 
Air bubbles must be removed from the cartridge before injection (see instructions for using the pen). 
Empty cartridges must not be refilled. 
 
Insulin Human Winthrop Comb 30 must not be administered intravenously and must not be used in 
infusion pumps or external or implanted insulin pumps. 
 
It must be remembered that 
- insulin protamine crystals dissolve in an acid pH range, 
- the soluble insulin part precipitates out at a pH of approximately 4.5 to 6.5. 
 
Insulin label must always be checked before each injection to avoid medication errors between insulin 
human and other insulins (see section 4.4). 
 
Mixing of insulins 
Insulin Human Winthrop Comb 30 may be mixed with all insulin human formulations, but not with 
those designed specifically for use in insulin pumps. Concernig incompatibility with other insulins, 
see section 6.2. 
 
Insulin Human Winthrop Comb 30 cartridges are not designed to allow any other insulin to be mixed 
in the cartridge. 
 
Any unused medicinalproduct or waste material should be disposed of in accordance with local 
requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Sanofi-Aventis Deutschland GmbH, D-65926 Frankfurt am Main, Germany 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/06/368/145 
EU/1/06/368/146 
EU/1/06/368/147 
EU/1/06/368/148 
EU/1/06/368/149 
EU/1/06/368/150 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 17 January 2007 
Date of latest renewal: 17 January 2012 
 
 
10. DATE OF REVISION OF THE TEXT 
 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu 

 

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1. NAME OF THE MEDICINAL PRODUCT 
 
Insulin Human Winthrop Comb 30 SoloStar 100 IU/ml suspension for injection in a pre-filled pen. 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each ml contains 100 IU insulin human (equivalent to 3.5 mg).  
Each pen contains 3 ml of suspension for injection, equivalent to 300 IU insulin. One IU (International 
Unit) corresponds to 0.035 mg of anhydrous human insulin. 
 
Insulin Human Winthrop Comb 30 is a biphasic isophane insulin suspension consisting of 30% 
dissolved insulin and 70% crystalline protamine insulin. 
 
Human insulin is produced by recombinant DNA technology in Escherichia coli. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Suspension for injection in a pre-filled pen. 
 
After resuspension, milky-white suspension. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Diabetes mellitus where treatment with insulin is required. 
 
4.2 Posology and method of administration 
 
Posology 
The desired blood glucose levels, the insulin preparations to be used and the insulin dose regimen 
(doses and timings) must be determined individually and adjusted to suit the patient’s diet, physical 
activity and life-style. 
 
Daily doses and timing of administration 
There are no fixed rules for insulin dose regimen. However, the average insulin requirement is often 
0.5 to 1.0 IU per kg body weight per day. The basal metabolic requirement is 40% to 60% of the total 
daily requirement. Insulin Human Winthrop Comb 30 is injected subcutaneously 30 to 45 minutes 
before a meal. 
 
SoloStar delivers insulin in doses from 1 to 80 units in steps of 1 unit. Each pen contains multiple 
doses. 
 
Secondary dose adjustment 
Improved metabolic control may result in increased insulin sensitivity, leading to a reduced insulin 
requirement. Dose adjustment may also be required, for example, if 
- the patient's weight changes, 
- the patient's life-style changes, 
- other circumstances arise that may promote an increased susceptibility to hypo- or 

hyperglycaemia (see section 4.4). 
 

 

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Special populations 
Elderly population (≧65 years old) 
In the elderly, progressive deterioration of renal function may lead to a steady decrease in insulin 
requirements. 
 
Renal impairment 
In patients with renal impairment, insulin requirements may be diminished due to reduced insulin 
metabolism. 
 
Hepatic impairment 
In patients with severe hepatic impairment, insulin requirements may be diminished due to reduced 
capacity for gluconeogenesis and reduced insulin metabolism. 
 
Method of administration 
Insulin Human Winthrop Comb 30 is administered subcutaneously. Insulin Human Winthrop 
Comb 30 must never be injected intravenously. 
 
Insulin absorption and hence the blood-glucose-lowering effect of a dose may vary from one injection 
area to another (e.g. the abdominal wall compared with the thigh). Injection sites within an injection 
area must be rotated from one injection to the next. 
 
Before using SoloStar, the Instructions for Use included in the Package Leaflet must be read carefully. 
 
For further details on handling, see section 6.6. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
 
4.4 Special warnings and precautions for use 
 
Patients hypersensitive to Insulin Human Winthrop Comb 30 for whom no better tolerated preparation 
is available must only continue treatment under close medical supervision and – where necessary – in 
conjunction with anti-allergic treatment. 
 
In patients with an allergy to animal insulin intradermal skin testing is recommended prior to a 
transfer to Insulin Human Winthrop Comb 30, since they may experience immunological 
cross-reactions. 
 
In case of insufficient glucose control or a tendency to hyper- or hypoglycaemic episodes, the patient's 
adherence to the prescribed treatment regimen, injection sites and proper injection technique and all 
other relevant factors must be reviewed before dose adjustment is considered. 
 
Transfer to Insulin Human Winthrop Comb 30 
Transferring a patient to another type or brand of insulin should be done under strict medical 
supervision. Changes in strength, brand (manufacturer), type (regular, NPH, lente, long-acting, etc.), 
origin (animal, human, human insulin analogue) and/or method of manufacture may result in the need 
for a change in dosage. 
The need to adjust (e.g. reduce) the dose may become evident immediately after transfer. 
Alternatively, it may emerge gradually over a period of several weeks. 
 
Following transfer from an animal insulin to human insulin, dose regimen reduction may be required 
in particular in patients who 
- were previously already controlled on rather low blood glucose levels, 
- have a tendency to hypoglycaemia, 
- previously required high insulin doses due to the presence of insulin antibodies. 
 

 

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Close metabolic monitoring is recommended during the transition and in the initial weeks thereafter. In 
patients who require high insulin doses because of the presence of insulin antibodies, transfer under 
medical supervision in a hospital or similar setting must be considered. 
 
Hypoglycaemia 
Hypoglycaemia may occur if the insulin dose is too high in relation to the insulin requirement. 
 
Particular caution should be exercised, and intensified blood glucose monitoring is advisable in 
patients in whom hypoglycaemic episodes might be of particular clinical relevance, such as in patients 
with significant stenoses of the coronary arteries or of the blood vessels supplying the brain (risk of 
cardiac or cerebral complications of hypoglycaemia) as well as in patients with proliferative 
retinopathy, particularly if not treated with photocoagulation (risk of transient amaurosis following 
hypoglycaemia). 
 
Patients should be aware of circumstances where warning symptoms of hypoglycaemia are 
diminished. The warning symptoms of hypoglycaemia may be changed, be less pronounced or be 
absent in certain risk groups. These include patients: 
- in whom glycaemic control is markedly improved, 
- in whom hypoglycaemia develops gradually, 
- who are elderly,  
- after transfer from animal insulin to human insulin, 
- in whom an autonomic neuropathy is present, 
- with a long history of diabetes, 
- suffering from a psychiatric illness, 
- receiving concurrent treatment with certain other medicinal products (see section 4.5). 
Such situations may result in severe hypoglycaemia (and possibly loss of consciousness) prior to the 
patient's awareness of hypoglycaemia. 
 
If normal or decreased values for glycated haemoglobin are noted, the possibility of recurrent, 
unrecognised (especially nocturnal) episodes of hypoglycaemia must be considered. 
 
Adherence of the patient to the dose regimen and dietary regimen, correct insulin administration and 
awareness of hypoglycaemia symptoms are essential to reduce the risk of hypoglycaemia. Factors 
increasing the susceptibility to hypoglycaemia require particularly close monitoring and may 
necessitate dose adjustment. These include: 
- change in the injection area, 
- improved insulin sensitivity (e.g. by removal of stress factors), 
- unaccustomed, increased or prolonged physical activity, 
- intercurrent illness (e.g. vomiting, diarrhoea), 
- inadequate food intake, 
- missed meals, 
- alcohol consumption, 
- certain uncompensated endocrine disorders (e.g. in hypothyroidism and in anterior pituitary or 

adrenocortical insufficiency), 
- concomitant treatment with certain other medicinal products. 
 
Intercurrent illness 
Intercurrent illness requires intensified metabolic monitoring. In many cases, urine tests for ketones 
are indicated, and often it is necessary to adjust the insulin dose. The insulin requirement is often 
increased. Patients with type 1 diabetes must continue to consume at least a small amount of 
carbohydrates on a regular basis, even if they are able to eat only little or no food, or are vomiting etc. 
and they must never omit insulin entirely. 
 
Handling of the pen 
Before using SoloStar, the Instructions for Use included in the Package Leaflet must be read carefully. 
SoloStar has to be used as recommended in these Instructions for Use (see section 6.6). 
 

 

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Medication errors 
Medication errors have been reported in which other Insulin Human Winthrop formulations or other 
insulins have been accidentally administered. Insulin label must always be checked before each 
injection to avoid medication errors between insulin human and other insulins. 
 
Combination of Insulin Human Winthrop with pioglitazone 
Cases of cardiac failure have been reported when pioglitazone was used in combination with insulin, 
especially in patients with risk factors for development of cardiac heart failure. This should be kept in 
mind if treatment with the combination of pioglitazone and Insulin Human Winthrop is considered. If 
the combination is used, patients should be observed for signs and symptoms of heart failure, weight 
gain and oedema. Pioglitazone should be discontinued if any deterioration in cardiac symptoms 
occurs.  
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
A number of substances affect glucose metabolism and may require dose adjustment of human insulin. 
 
Substances that may enhance the blood-glucose-lowering effect and increase susceptibility to 
hypoglycaemia include oral antidiabetic medicinal products, angiotensin converting enzyme (ACE) 
inhibitors, disopyramide, fibrates, fluoxetine, monoamine oxidase (MAO) inhibitors, pentoxifylline, 
propoxyphene, salicylates and sulphonamide antibiotics. 
 
Substances that may reduce the blood-glucose-lowering effect include corticosteroids, danazol, 
diazoxide, diuretics, glucagon, isoniazid, oestrogens and progestogens (e.g. in oral contraceptives), 
phenothiazine derivatives, somatropin, sympathomimetic medicinal products (e.g. epinephrine 
[adrenaline], salbutamol, terbutaline), thyroid hormones, protease inhibitors and atypical antipsychotic 
medicinal products (e.g. olanzapine and clozapine). 
 
Beta-blockers, clonidine, lithium salts or alcohol may either potentiate or weaken the 
blood-glucose-lowering effect of insulin. Pentamidine may cause hypoglycaemia which may 
sometimes be followed by hyperglycaemia. 
 
In addition, under the influence of sympatholytic medicinal products such as beta-blockers, clonidine, 
guanethidine and reserpine, the signs of adrenergic counter-regulation may be reduced or absent. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
For insulin human, no clinical data on exposed pregnancies from controlled clinical studies are 
available. Insulin does cross the placental barrier, although not in clinically significant amount. A 
limited amount of data on pregnant women (less than 300 pregnancy outcomes reported) exposed to 
marketed insulin human indicates no safety issues in use of insulin human in pregnancy. Caution 
should be exercised when prescribing to pregnant women. 
 
It is essential for patients with pre-existing or gestational diabetes to maintain good metabolic control 
throughout pregnancy. Insulin requirements may decrease during the first trimester and generally 
increase during the second and third trimesters. Immediately after delivery, insulin requirements 
decline rapidly (increased risk of hypoglycaemia). Careful monitoring of glucose control is essential. 
 
Breast-feeding 
No effects on the suckling child are anticipated. Insulin Human Winthrop Comb 30 can be used during 
breast-feeding. Breast-feeding women may require adjustments in insulin dose and diet. 
 
Fertility 
No clinical or animal data with insulin human on male or female fertility are available. 
 

 

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4.7 Effects on ability to drive and use machines 
 
The patient's ability to concentrate and react may be impaired as a result of hypoglycaemia or 
hyperglycaemia or, for example, as a result of visual impairment. This may constitute a risk in 
situations where these abilities are of special importance (e.g. driving a car or using machines). 
 
Patients should be advised to take precautions to avoid hypoglycaemia whilst driving. This is 
particularly important in those who have reduced or absent awareness of the warning symptoms of 
hypoglycaemia or have frequent episodes of hypoglycaemia. It should be considered whether it is 
advisable to drive or use machines in these circumstances. 
 
4.8 Undesirable effects 
 
Summary of the safety profile  
Hypoglycaemia, in general the most frequent adverse reaction of insulin therapy, may occur if the 
insulin dose is too high in relation to the insulin requirement. In clinical studies and during marketed 
use, the frequency varies with patient population and dose regimens. Therefore, no specific frequency 
can be presented. 
 
Tabulated list of adverse reactions 
The following related adverse reactions from clinical investigations are listed below by system organ 
class and in order of decreasing incidence: very common (≥1/10); common (≥1/100 to <1/10); 
uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000), not known 
(cannot be estimated from the available data). 
 
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. 
 
MedDRA system 
organ classes 

Common Uncommon Not known 

Immune system 
disorders 

 Shock Immediate type allergic 
reactions (hypotension, 
angioneurotic oedema, 
bronchospasm, 
generalised skin 
reactions); 
Anti-insulin antibodies 

Metabolism and 
nutrition disorders 

Oedema  Hypoglycaemia; 
Sodium retention 

Eye disorders   Proliferative retinopathy; 
Diabetic retinopathy; 
Visual impairment 

Skin and subcutaneous 
tissue disorders 

  Lipodystrophy 

General disorders and 
administration site 
conditions 

Injection site reactions Injection site 
urticaria 

Injection site 
inflammation;  
Injection site pain; 
Injection site pruritus; 
Injection site erythema; 
Injection site swelling 

 
Description of selected adverse reactions 
Immune system disorders 
Immediate type allergic reactions to insulin or to the excipients may be life-threatening. 
 
Insulin administration may cause anti-insulin antibodies to form. In rare cases, the presence of such 
anti-insulin antibodies may necessitate adjustment of the insulin dose in order to correct a tendency to 
hyper- or hypoglycaemia. 

 

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Metabolism and nutrition disorders 
Severe hypoglycaemic attacks, especially if recurrent, may lead to neurological damage. 
Prolonged or severe hypoglycaemic episodes may be life-threatening. 
 
In many patients, the signs and symptoms of neuroglycopenia are preceded by signs of adrenergic 
counter-regulation. Generally, the greater and more rapid the decline in blood glucose, the more 
marked is the phenomenon of counter-regulation and its symptoms. 
Insulin may cause sodium retention and oedema, particularly if previously poor metabolic control is 
improved by intensified insulin therapy. 
 
Eyes disorders 
A marked change in glycaemic control may cause temporary visual impairment, due to temporary 
alteration in the turgidity and refractive index of the lens. 
 
Long-term improved glycaemic control decreases the risk of progression of diabetic retinopathy. 
However, intensification of insulin therapy with abrupt improvement in glycaemic control may be 
associated with temporary worsening of diabetic retinopathy. 
 
Skin and subcutaneous tissue disorders 
Lipodystrophy may occur at the injection site and delay local insulin absorption. Continuous rotation 
of the injection site within the given injection area may help to reduce or prevent these reactions. 
 
General disorders and administration site conditions 
Most minor reactions to insulins at the injection site usually resolve in a few days to a few weeks. 
 
4.9 Overdose 
 
Symptoms 
Insulin overdose may lead to severe and sometimes long-term and life-threatening hypoglycaemia. 
 
Management 
Mild episodes of hypoglycaemia can usually be treated with oral carbohydrates. Adjustments in dose 
regimen of the medicinal product, meal patterns, or physical activity may be needed. 
 
More severe episodes with coma, seizure, or neurologic impairment may be treated with 
intramuscular/subcutaneous glucagon or concentrated intravenous glucose. Sustained carbohydrate 
intake and observation may be necessary because hypoglycaemia may recur after apparent clinical 
recovery. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Drugs used in diabetes, insulins and analogues for injection, 
intermediate-acting combined with fast-acting, ATC Code: A10AD01. 
 
Mechanism of action 
Insulin 
- lowers blood glucose and promotes anabolic effects as well as decreasing catabolic effects, 
- increases the transport of glucose into cells as well as the formation of glycogen in the muscles 

and the liver, and improves pyruvate utilisation. It inhibits glycogenolysis and gluconeogenesis, 
- increases lipogenesis in the liver and adipose tissue and inhibits lipolysis, 
- promotes the uptake of amino acids into cells and promotes protein synthesis, 
- enhances the uptake of potassium into cells. 
 

 

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Pharmacodynamic effects 
Insulin Human Winthrop Comb 30 (a biphasic isophane insulin suspension with 30% dissolved 
insulin) is an insulin with gradual onset and long duration of action. Following subcutaneous injection, 
onset of action is within 30 to 60 minutes, the phase of maximum action is between 2 and 4 hours after 
injection and the duration of action is 12 to 19 hours. 
 
5.2 Pharmacokinetic properties 
 
In healthy subjects, the serum half-life of insulin is approximately 4 to 6 minutes. It is longer in 
patients with severe renal insufficiency. However, it must be noted that the pharmacokinetics of 
insulin do not reflect its metabolic action. 
 
5.3 Preclinical safety data 
 
The acute toxicity was studied following subcutaneous administration in rats. No evidence of toxic 
effects was found. Studies of pharmacodynamic effects following subcutaneous administration in 
rabbits and dogs revealed the expected hypoglycaemic reactions. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Protamine sulphate, 
metacresol, 
phenol, 
zinc chloride, 
sodium dihydrogen phosphate dihydrate, 
glycerol, 
sodium hydroxide, 
hydrochloric acid (for pH adjustment), 
water for injections. 
 
6.2 Incompatibilities 
 
This medicinal product must not be mixed with other medicinal products except those mentioned in 
section 6.6. 
 
Insulin Human Winthrop Comb 30 must not be mixed with solutions containing reducing substances 
such as thioles and sulphites.  
 
Mixing of insulins 
Insulin Human Winthrop Comb 30 must not be mixed with any other insulin or with insulin 
analogues. 
 
Care must be taken to ensure that no alcohol or other disinfectants enter the insulin suspension. 
 
6.3 Shelf life 
 
2 years. 
 
Shelf life after first use of the pen 
The pen in-use or carried as a spare may be stored for a maximum of 4 weeks not above 25°C and 
away from direct heat or direct light. 
Pens in-use must not be stored in the refrigerator. 
The pen cap must be put back on the pen after each injection in order to protect from light. 
 

 

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6.4 Special precautions for storage 
 
Not in-use pens: 
Store in a refrigerator (2°C - 8°C). 
Do not freeze. 
Do not put Insulin Human Winthrop Comb 30 next to the freezer compartment or a freezer pack. 
Keep the pre-filled pen in the outer carton in order to protect from light. 
 
In-use pens 
For storage conditions after first opening of the medicinal product, see section 6.3. 
 
6.5 Nature and contents of container 
 
3 ml suspension in a cartridge (type 1 colourless glass) with a plunger (bromobutyl rubber (type 1)) 
and a flanged cap (aluminium) with a stopper (bromobutyl or laminate of polyisoprene and 
bromobutyl rubber (type 1)). 
Each cartridge contains 3 balls (stainless steel). 
The cartridges are sealed in a disposable pen injector.  
Injection needles are not included in the pack. 
Packs of 3, 4, 5, 6, 9 or 10 pens are available. 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal and other handling 
 
Before first use, Insulin Human Winthrop Comb 30 must be kept at room temperature for 1 to 2 hours 
and then resuspended to check the contents. This is best done by gently tilting the pen back and forth 
(at least ten times). Each cartridge contains three small metal balls to facilitate quick and thorough 
mixing of the contents. Later on, the insulin must be resuspended again prior to each injection. 
 
After resuspension, the fluid must have a uniformly milky appearance. Insulin Human Winthrop 
Comb 30 must not be used if this cannot be achieved, i.e. if the suspension remains clear, for example, 
or if clumps, particles or flocculation appear in the insulin or stick to the wall or bottom of the 
cartridge. These changes sometimes give the cartridge a frosted appearance. In such cases, a new pen 
yielding a uniform suspension must be used. It is also necessary to change to a new pen if the insulin 
requirement changes substantially. 
 
Empty pens must never be re-used and must be properly discarded. 
 
To prevent the possible transmission of disease, each pen must be used by one patient only. 
 
It must be remembered that 
- insulin protamine crystals dissolve in an acid pH range, 
- the soluble insulin part precipitates out at a pH of approximately 4.5 to 6.5. 
 
Insulin label must always be checked before each injection to avoid medication errors between insulin 
human and other insulins (see section 4.4). 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 

 

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Handling of the pen 
The patient should be advised to read the instructions for use included in the package leaflet 
carefully before using SoloStar. 
 

 
Schematic diagram of the pen 

 
Important information for use of SoloStar: 
 
• Before each use, a new needle must always be carefully attached and a safety test must be 

performed. A dose should not be selected and/or the injection button should not be pressed 
without a needle attached. Only use needles that are compatible for use with SoloStar. 

• Special caution must be taken to avoid accidental needle injury and transmission of infection. 
• SoloStar must never be used if it is damaged or if the patient is not sure if it is working properly. 
• The patient must always have a spare SoloStar available in case the SoloStar is lost or damaged. 
 
Storage instructions  
 
Please check section 6.4 for instructions on how to store SoloStar. 
 
If SoloStar is in cool storage, it should be taken out 1 to 2 hours before injection to allow it to warm 
up. Cold insulin is more painful to inject. 
 
The used SoloStar must be discarded as required by your local authorities. 
 
Maintenance 
 
SoloStar has to be protected from dust and dirt. 
 
The outside of the SoloStar can be cleaned by wiping it with a damp cloth. 
 
The pen must not be soaked, washed or lubricated as this may damage it. 
 
SoloStar is designed to work accurately and safely. It should be handled with care. The patient should 
avoid situations where SoloStar may be damaged. If the patient is concerned that the SoloStar may be 
damaged, he must use a new one. 
 
Step 1. Check the insulin 
 
The label on the pen should be checked to make sure it contains the correct insulin. Insulin Human 
Winthrop SoloStar is white with a colour on the injection button. The injection button colour will vary 
based on the formulation of Insulin Human Winthrop insulin used. 
 
After removing the pen cap, the appearance of the insulin should also be checked: 
The insulin suspensions (Insulin Human Winthrop Basal or Insulin Human Winthrop mixtures) should 
be mixed by turning SoloStar up and down at least 10 times to resuspend the insulin. The pen should 
be turned gently to avoid foaming in the cartridge. After mixing, the insulin suspensions must have an 
evenly milky-white appearance. 
 
Step 2. Attach the needle 
 
Only needles that are compatible for use with SoloStar should be used. 

 

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A new sterile needle will be always used for each injection. After removing the cap, the needle should 
be carefully attached straight onto the pen. 
 
Step 3. Perform a safety test  
 
Prior to each injection, a safety test has to be performed to ensure that pen and needle work properly 
and to remove air bubbles. 
 
A dose of 2 units has to be selected. 
The outer and inner needle caps should be removed. 
 
While holding the pen with the needle pointing upwards, the insulin reservoir should be tapped gently 
with the finger so that any air bubbles rise up towards the needle. 
 
Then the injection button should be pressed in completely. 
 
If insulin has been expelled through the needle tip, then the pen and the needle are working properly. 
If no insulin appears at the needle tip, step 3 should be repeated until insulin appears at the needle tip. 
 
Step 4. Select the dose 
 
The dose can be set in steps of 1 unit, from a minimum of 1 unit to a maximum of 80 units. If a dose 
greater than 80 units is required, it should be given as two or more injections. 
 
The dose window must show “0” following the safety test. The dose can then be selected. 
 
Step 5. Inject the dose 
 
The patient should be informed on the injection technique by his health care professional.  
The needle should be inserted into the skin. 
The injection button should be pressed in completely. Then the injection button should be held down 
10 seconds before withdrawing the needle. This ensures that the full dose of insulin has been injected. 
 
Step 6. Remove and discard the needle 
 
The needle should always be removed after each injection and discarded. This helps prevent 
contamination and/or infection, entry of air into the insulin reservoir and leakage of insulin. Needles 
mut not be re-used. 
 
Special caution must be taken when removing and disposing of the needle. Recommended safety 
measures for removal and disposal of needles must be followed (e.g. a one handed capping technique) 
in order to reduce the risk of accidental needle injury and transmission of infectious diseases. 
 
The pen cap should be replaced on the pen. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Sanofi-Aventis Deutschland GmbH, D-65926 Frankfurt am Main, Germany 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/06/368/163 
EU/1/06/368/164 
EU/1/06/368/165 

 

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EU/1/06/368/166 
EU/1/06/368/167 
EU/1/06/368/168 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 17 January 2007 
Date of latest renewal: 17 January 2012 
 
 
10. DATE OF REVISION OF THE TEXT 
 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu 

 

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1. NAME OF THE MEDICINAL PRODUCT 
 
Insulin Human Winthrop Comb 50 100 IU/ml suspension for injection in a vial 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each ml contains 100 IU insulin human (equivalent to 3.5 mg).  
Each vial contains 5 ml of suspension for injection, equivalent to 500 IU insulin. One IU 
(International Unit) corresponds to 0.035 mg of anhydrous human insulin. 
 
Insulin Human Winthrop Comb 50 is a biphasic isophane insulin suspension consisting of 50% 
dissolved insulin and 50% crystalline protamine insulin. 
 
Human insulin is produced by recombinant DNA technology in Escherichia coli. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Suspension for injection in a vial. 
 
After resuspension, milky-white suspension. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Diabetes mellitus where treatment with insulin is required. 
 
4.2 Posology and method of administration 
 
Posology 
The desired blood glucose levels, the insulin preparations to be used and the insulin dose regimen 
(doses and timings) must be determined individually and adjusted to suit the patient’s diet, physical 
activity and life-style. 
 
Daily doses and timing of administration 
There are no fixed rules for insulin dose regimen. However, the average insulin requirement is often 
0.5 to 1.0 IU per kg body weight per day. The basal metabolic requirement is 40% to 60% of the total 
daily requirement. Insulin Human Winthrop Comb 50 is injected subcutaneously 20 to 30 minutes 
before a meal. 
 
Secondary dose adjustment 
Improved metabolic control may result in increased insulin sensitivity, leading to a reduced insulin 
requirement. Dose adjustment may also be required, for example, if 
- the patient's weight changes, 
- the patient's life-style changes, 
- other circumstances arise that may promote an increased susceptibility to hypo- or 

hyperglycaemia (see section 4.4). 
 
Special populations 
Elderly population (≧65 years old) 
In the elderly, progressive deterioration of renal function may lead to a steady decrease in insulin 
requirements. 

 

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Renal impairment 
In patients with renal impairment, insulin requirements may be diminished due to reduced insulin 
metabolism. 
 
Hepatic impairment 
In patients with severe hepatic impairment, insulin requirements may be diminished due to reduced 
capacity for gluconeogenesis and reduced insulin metabolism. 
 
Method of administration 
Insulin Human Winthrop Comb 50 must not be administered intravenously and must not be used in 
infusion pumps or external or implanted insulin pumps. 
 
Only injection syringes designed for this strength of insulin (100 IU per ml) are to be used. The 
injection syringes must not contain any other medicinal product or residue (e.g. traces of heparin). 
 
Insulin Human Winthrop Comb 50 is administered subcutaneously. Insulin Human Winthrop 
Comb 50 must never be injected intravenously. 
 
Insulin absorption and hence the blood-glucose-lowering effect of a dose may vary from one injection 
area to another (e.g. the abdominal wall compared with the thigh). Injection sites within an injection 
area must be rotated from one injection to the next. 
 
For further details on handling, see section 6.6. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
 
4.4 Special warnings and precautions for use 
 
Patients hypersensitive to Insulin Human Winthrop Comb 50 for whom no better tolerated preparation 
is available must only continue treatment under close medical supervision and – where necessary – in 
conjunction with anti-allergic treatment. 
 
In patients with an allergy to animal insulin intradermal skin testing is recommended prior to a 
transfer to Insulin Human Winthrop Comb 50, since they may experience immunological 
cross-reactions. 
 
In case of insufficient glucose control or a tendency to hyper- or hypoglycaemic episodes, the patient's 
adherence to the prescribed treatment regimen, injection sites and proper injection technique and all 
other relevant factors must be reviewed before dose adjustment is considered. 
 
Transfer to Insulin Human Winthrop Comb 50 
Transferring a patient to another type or brand of insulin should be done under strict medical 
supervision. Changes in strength, brand (manufacturer), type (regular, NPH, lente, long-acting, etc.), 
origin (animal, human, human insulin analogue) and/or method of manufacture may result in the need 
for a change in dosage. 
The need to adjust (e.g. reduce) the dose may become evident immediately after transfer. 
Alternatively, it may emerge gradually over a period of several weeks. 
 
Following transfer from an animal insulin to human insulin, dose regimen reduction may be required 
in particular in patients who 
- were previously already controlled on rather low blood glucose levels, 
- have a tendency to hypoglycaemia, 
- previously required high insulin doses due to the presence of insulin antibodies. 
 

 

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Close metabolic monitoring is recommended during the transition and in the initial weeks thereafter. In 
patients who require high insulin doses because of the presence of insulin antibodies, transfer under 
medical supervision in a hospital or similar setting must be considered. 
 
Hypoglycaemia 
Hypoglycaemia may occur if the insulin dose is too high in relation to the insulin requirement. 
 
Particular caution should be exercised, and intensified blood glucose monitoring is advisable in 
patients in whom hypoglycaemic episodes might be of particular clinical relevance, such as in patients 
with significant stenoses of the coronary arteries or of the blood vessels supplying the brain (risk of 
cardiac or cerebral complications of hypoglycaemia) as well as in patients with proliferative 
retinopathy, particularly if not treated with photocoagulation (risk of transient amaurosis following 
hypoglycaemia). 
 
Patients should be aware of circumstances where warning symptoms of hypoglycaemia are 
diminished. The warning symptoms of hypoglycaemia may be changed, be less pronounced or be 
absent in certain risk groups. These include patients: 
- in whom glycaemic control is markedly improved, 
- in whom hypoglycaemia develops gradually, 
- who are elderly,  
- after transfer from animal insulin to human insulin, 
- in whom an autonomic neuropathy is present, 
- with a long history of diabetes, 
- suffering from a psychiatric illness, 
- receiving concurrent treatment with certain other medicinal products (see section 4.5). 
Such situations may result in severe hypoglycaemia (and possibly loss of consciousness) prior to the 
patient's awareness of hypoglycaemia. 
 
If normal or decreased values for glycated haemoglobin are noted, the possibility of recurrent, 
unrecognised (especially nocturnal) episodes of hypoglycaemia must be considered. 
 
Adherence of the patient to the dose regimen and dietary regimen, correct insulin administration and 
awareness of hypoglycaemia symptoms are essential to reduce the risk of hypoglycaemia. Factors 
increasing the susceptibility to hypoglycaemia require particularly close monitoring and may 
necessitate dose adjustment. These include: 
- change in the injection area, 
- improved insulin sensitivity (e.g. by removal of stress factors), 
- unaccustomed, increased or prolonged physical activity, 
- intercurrent illness (e.g. vomiting, diarrhoea), 
- inadequate food intake, 
- missed meals, 
- alcohol consumption, 
- certain uncompensated endocrine disorders (e.g. in hypothyroidism and in anterior pituitary or 

adrenocortical insufficiency), 
- concomitant treatment with certain other medicinal products. 
 
Intercurrent illness 
Intercurrent illness requires intensified metabolic monitoring. In many cases, urine tests for ketones 
are indicated, and often it is necessary to adjust the insulin dose. The insulin requirement is often 
increased. Patients with type 1 diabetes must continue to consume at least a small amount of 
carbohydrates on a regular basis, even if they are able to eat only little or no food, or are vomiting etc. 
and they must never omit insulin entirely. 
 
Medication errors 
Medication errors have been reported in which other Insulin Human Winthrop formulations or other 
insulins have been accidentally administered. Insulin label must always be checked before each 
injection to avoid medication errors between insulin human and other insulins. 

 

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Combination of Insulin Human Winthrop with pioglitazone 
Cases of cardiac failure have been reported when pioglitazone was used in combination with insulin, 
especially in patients with risk factors for development of cardiac heart failure. This should be kept in 
mind if treatment with the combination of pioglitazone and Insulin Human Winthrop is considered. If 
the combination is used, patients should be observed for signs and symptoms of heart failure, weight 
gain and oedema. Pioglitazone should be discontinued if any deterioration in cardiac symptoms 
occurs.  
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
A number of substances affect glucose metabolism and may require dose adjustment of human insulin. 
 
Substances that may enhance the blood-glucose-lowering effect and increase susceptibility to 
hypoglycaemia include oral antidiabetic medicinal products, angiotensin converting enzyme (ACE) 
inhibitors, disopyramide, fibrates, fluoxetine, monoamine oxidase (MAO) inhibitors, pentoxifylline, 
propoxyphene, salicylates and sulphonamide antibiotics. 
 
Substances that may reduce the blood-glucose-lowering effect include corticosteroids, danazol, 
diazoxide, diuretics, glucagon, isoniazid, oestrogens and progestogens (e.g. in oral contraceptives), 
phenothiazine derivatives, somatropin, sympathomimetic medicinal products (e.g. epinephrine 
[adrenaline], salbutamol, terbutaline), thyroid hormones, protease inhibitors and atypical antipsychotic 
medicinal products (e.g. olanzapine and clozapine). 
 
Beta-blockers, clonidine, lithium salts or alcohol may either potentiate or weaken the 
blood-glucose-lowering effect of insulin. Pentamidine may cause hypoglycaemia which may 
sometimes be followed by hyperglycaemia. 
 
In addition, under the influence of sympatholytic medicinal products such as beta-blockers, clonidine, 
guanethidine and reserpine, the signs of adrenergic counter-regulation may be reduced or absent. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
For insulin human, no clinical data on exposed pregnancies from controlled clinical studies are 
available. Insulin does cross the placental barrier, although not in clinically significant amount. A 
limited amount of data on pregnant women (less than 300 pregnancy outcomes reported) exposed to 
marketed insulin human indicates no safety issues in use of insulin human in pregnancy. Caution 
should be exercised when prescribing to pregnant women. 
 
It is essential for patients with pre-existing or gestational diabetes to maintain good metabolic control 
throughout pregnancy. Insulin requirements may decrease during the first trimester and generally 
increase during the second and third trimesters. Immediately after delivery, insulin requirements 
decline rapidly (increased risk of hypoglycaemia). Careful monitoring of glucose control is essential. 
 
Breast-feeding 
No effects on the suckling child are anticipated. Insulin Human Winthrop Comb 50 can be used during 
breast-feeding. Breast-feeding women may require adjustments in insulin dose and diet. 
 
Fertility 
No clinical or animal data with insulin human on male or female fertility are available. 
 

 

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4.7 Effects on ability to drive and use machines 
 
The patient's ability to concentrate and react may be impaired as a result of hypoglycaemia or 
hyperglycaemia or, for example, as a result of visual impairment. This may constitute a risk in 
situations where these abilities are of special importance (e.g. driving a car or using machines). 
 
Patients should be advised to take precautions to avoid hypoglycaemia whilst driving. This is 
particularly important in those who have reduced or absent awareness of the warning symptoms of 
hypoglycaemia or have frequent episodes of hypoglycaemia. It should be considered whether it is 
advisable to drive or use machines in these circumstances. 
 
4.8 Undesirable effects 
 
Summary of the safety profile  
Hypoglycaemia, in general the most frequent adverse reaction of insulin therapy, may occur if the 
insulin dose is too high in relation to the insulin requirement. In clinical studies and during marketed 
use, the frequency varies with patient population and dose regimens. Therefore, no specific frequency 
can be presented. 
 
Tabulated list of adverse reactions 
The following related adverse reactions from clinical investigations are listed below by system organ 
class and in order of decreasing incidence: very common (≥1/10); common (≥1/100 to <1/10); 
uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000), not known 
(cannot be estimated from the available data). 
 
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. 
 
MedDRA system 
organ classes 

Common Uncommon Not known 

Immune system 
disorders 

 Shock Immediate type 
allergic reactions 
(hypotension, 
angioneurotic oedema, 
bronchospasm, 
generalised skin 
reactions); 
Anti-insulin antibodies 

Metabolism and 
nutrition disorders 

Oedema  Hypoglycaemia; 
Sodium retention 

Eye disorders   Proliferative 
retinopathy; 
Diabetic retinopathy; 
Visual impairment 

Skin and 
subcutaneous tissue 
disorders 

  Lipodystrophy 

General disorders 
and administration 
site conditions 

Injection site reactions Injection site 
urticaria 

Injection site 
inflammation;  
Injection site pain; 
Injection site pruritus; 
Injection site 
erythema;  
Injection site swelling 

 

 

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Description of selected adverse reactions 
Immune system disorders 
Immediate type allergic reactions to insulin or to the excipients may be life-threatening. 
 
Insulin administration may cause anti-insulin antibodies to form. In rare cases, the presence of such 
anti-insulin antibodies may necessitate adjustment of the insulin dose in order to correct a tendency to 
hyper- or hypoglycaemia. 
 
Metabolism and nutrition disorders 
Severe hypoglycaemic attacks, especially if recurrent, may lead to neurological damage. 
Prolonged or severe hypoglycaemic episodes may be life-threatening. 
 
In many patients, the signs and symptoms of neuroglycopenia are preceded by signs of adrenergic 
counter-regulation. Generally, the greater and more rapid the decline in blood glucose, the more 
marked is the phenomenon of counter-regulation and its symptoms. 
Insulin may cause sodium retention and oedema, particularly if previously poor metabolic control is 
improved by intensified insulin therapy. 
 
Eyes disorders 
A marked change in glycaemic control may cause temporary visual impairment, due to temporary 
alteration in the turgidity and refractive index of the lens. 
 
Long-term improved glycaemic control decreases the risk of progression of diabetic retinopathy. 
However, intensification of insulin therapy with abrupt improvement in glycaemic control may be 
associated with temporary worsening of diabetic retinopathy. 
 
Skin and subcutaneous tissue disorders 
Lipodystrophy may occur at the injection site and delay local insulin absorption. Continuous rotation 
of the injection site within the given injection area may help to reduce or prevent these reactions. 
 
General disorders and administration site conditions 
Most minor reactions to insulins at the injection site usually resolve in a few days to a few weeks. 
 
4.9 Overdose 
 
Symptoms 
Insulin overdose may lead to severe and sometimes long-term and life-threatening hypoglycaemia. 
 
Management 
Mild episodes of hypoglycaemia can usually be treated with oral carbohydrates. Adjustments in dose 
regimen of the medicinal product, meal patterns, or physical activity may be needed. 
 
More severe episodes with coma, seizure, or neurologic impairment may be treated with 
intramuscular/subcutaneous glucagon or concentrated intravenous glucose. Sustained carbohydrate 
intake and observation may be necessary because hypoglycaemia may recur after apparent clinical 
recovery. 
 
 

 

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5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Drugs used in diabetes, insulins and analogues for injection, 
intermediate-acting combined with fast-acting, ATC Code: A10AD01. 
 
Mechanism of action 
Insulin 
- lowers blood glucose and promotes anabolic effects as well as decreasing catabolic effects, 
- increases the transport of glucose into cells as well as the formation of glycogen in the muscles 

and the liver, and improves pyruvate utilisation. It inhibits glycogenolysis and gluconeogenesis, 
- increases lipogenesis in the liver and adipose tissue and inhibits lipolysis, 
- promotes the uptake of amino acids into cells and promotes protein synthesis, 
- enhances the uptake of potassium into cells. 
 
Pharmacodynamic effects 
Insulin Human Winthrop Comb 50 (a biphasic isophane insulin suspension with 50% dissolved 
insulin) is an insulin with rapid onset and moderately long duration of action. Following subcutaneous 
injection, onset of action is within 30 minutes, the phase of maximum action is between 1.5 and 
4 hours after injection and the duration of action is 12 to 16 hours. 
 
5.2 Pharmacokinetic properties 
 
In healthy subjects, the serum half-life of insulin is approximately 4 to 6 minutes. It is longer in 
patients with severe renal insufficiency. However, it must be noted that the pharmacokinetics of 
insulin do not reflect its metabolic action. 
 
5.3 Preclinical safety data 
 
The acute toxicity was studied following subcutaneous administration in rats. No evidence of toxic 
effects was found. Studies of pharmacodynamic effects following subcutaneous administration in 
rabbits and dogs revealed the expected hypoglycaemic reactions. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Protamine sulphate, 
metacresol, 
phenol, 
zinc chloride, 
sodium dihydrogen phosphate dihydrate, 
glycerol, 
sodium hydroxide, 
hydrochloric acid (for pH adjustment), 
water for injections. 
 
6.2 Incompatibilities 
 
This medicinal product must not be mixed with other medicinal products except those mentioned in 
section 6.6. 
 
Insulin Human Winthrop Comb 50 must not be mixed with solutions containing reducing substances 
such as thioles and sulphites.  
 

 

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Mixing of insulins 
Insulin Human Winthrop Comb 50 must not be mixed with insulin human formulations designed 
specifically for use in insulin pumps.  
Insulin Human Winthrop Comb 50 must also not be mixed with insulins of animal origin or with 
insulin analogues. 
Insulins of different concentration (e.g. 100 IU per ml and 40 IU per ml) must not be mixed. 
 
Care must be taken to ensure that no alcohol or other disinfectants enter the insulin suspension. 
 
6.3 Shelf life 
 
2 years. 
 
Shelf life after first use of the vial 
The product may be stored for a maximum of 4 weeks not above 25°C and away from direct heat or 
direct light. 
Keep the vial in the outer carton in order to protect from light. 
It is recommended that the date of the first use be noted on the label. 
 
6.4 Special precautions for storage 
 
Unopened vials 
Store in a refrigerator (2°C - 8°C). 
Do not freeze. 
Do not put Insulin Human Winthrop Comb 50 next to the freezer compartment or a freezer pack. 
Keep the vial in the outer carton in order to protect from light. 
 
Opened vials 
For storage conditions after first opening of the medicinal product, see section 6.3. 
 
6.5 Nature and contents of container 
 
5 ml suspension in a vial (type 1 colourless glass) with a flanged cap (aluminium), a stopper 
(chlorobutyl rubber (type 1)) and a tear-off cap (polypropylene). 
Packs of 1 and 5 vials are available. 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal and other handling 
 
Before withdrawing insulin from the vial for the first time, remove the plastic protective cap. 
 
Immediately before withdrawal from the vial into the injection syringe, the insulin must be 
resuspended. This is best done by rolling the vial at an oblique angle between the palms of the hands. 
Do not shake the vial vigorously as this may lead to changes in the suspension (giving the vial a 
frosted appearance; see below) and cause frothing. Froth may interfere with the correct measurement 
of the dose. 
 
After resuspension, the fluid must have a uniformly milky appearance. Insulin Human Winthrop 
Comb 50 must not be used if this cannot be achieved, i.e. if the suspension remains clear, for example, 
or if clumps, particles or flocculation appear in the insulin or stick to the wall or bottom of the vial. 
These changes sometimes give the vial a frosted appearance. In such cases, a new vial yielding a 
uniform suspension must be used. It is also necessary to change to a new vial if the insulin 
requirement changes substantially. 
 
Insulin Human Winthrop Comb 50 must not be administered intravenously and must not be used in 
infusion pumps or external or implanted insulin pumps. 
 

 

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It must be remembered that 
- insulin protamine crystals dissolve in an acid pH range, 
- the soluble insulin part precipitates out at a pH of approximately 4.5 to 6.5. 
 
Insulin label must always be checked before each injection to avoid medication errors between insulin 
human and other insulins (see section 4.4). 
 
Mixing of insulins 
Insulin Human Winthrop Comb 50 may be mixed with all insulin human formulations, but not with 
those designed specifically for use in insulin pumps. Concerning incompatibility with other insulins, 
see section 6.2. 
 
If two different insulins have to be drawn into one single injection syringe, it is recommended that the 
shorter-acting insulin be drawn first to prevent contamination of the vial by the longer-acting 
preparation. It is advisable to inject immediately after mixing.  
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Sanofi-Aventis Deutschland GmbH, D-65926 Frankfurt am Main, Germany 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/06/368/047 
EU/1/06/368/048 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 17 January 2007 
Date of latest renewal: 17 January 2012 
 
 
10. DATE OF REVISION OF THE TEXT 
 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu 

 

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1. NAME OF THE MEDICINAL PRODUCT 
 
Insulin Human Winthrop Comb 50 40 IU/ml suspension for injection in a vial 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each ml contains 40 IU insulin human (equivalent to 1.4 mg) of the active substance.  
Each vial contains 10 ml of suspension for injection, equivalent to 400 IU insulin. One IU 
(International Unit) corresponds to 0.035 mg of anhydrous human insulin. 
 
Insulin Human Winthrop Comb 50 is a biphasic isophane insulin suspension consisting of 50% 
dissolved insulin and 50% crystalline protamine insulin. 
 
Human insulin is produced by recombinant DNA technology in Escherichia coli. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Suspension for injection in a vial. 
 
After resuspension, milky-white suspension. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Diabetes mellitus where treatment with insulin is required. 
 
4.2 Posology and method of administration 
 
Posology 
The desired blood glucose levels, the insulin preparations to be used and the insulin dose regimen 
(doses and timings) must be determined individually and adjusted to suit the patient’s diet, physical 
activity and life-style. 
 
Daily doses and timing of administration 
There are no fixed rules for insulin dose regimen. However, the average insulin requirement is often 
0.5 to 1.0 IU per kg body weight per day. The basal metabolic requirement is 40% to 60% of the total 
daily requirement. Insulin Human Winthrop Comb 50 is injected subcutaneously 20 to 30 minutes 
before a meal. 
 
Secondary dose adjustment 
Improved metabolic control may result in increased insulin sensitivity, leading to a reduced insulin 
requirement. Dose adjustment may also be required, for example, if 
- the patient's weight changes, 
- the patient's life-style changes, 
- other circumstances arise that may promote an increased susceptibility to hypo- or 

hyperglycaemia (see section 4.4). 
 
Special populations 
Elderly population (≧65 years old) 
In the elderly, progressive deterioration of renal function may lead to a steady decrease in insulin 
requirements. 

 

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Renal impairment 
In patients with renal impairment, insulin requirements may be diminished due to reduced insulin 
metabolism. 
 
Hepatic impairment 
In patients with severe hepatic impairment, insulin requirements may be diminished due to reduced 
capacity for gluconeogenesis and reduced insulin metabolism. 
 
Method of administration 
Insulin Human Winthrop Comb 50 must not be administered intravenously and must not be used in 
infusion pumps or external or implanted insulin pumps. 
 
Only injection syringes designed for this strength of insulin (40 IU per ml) are to be used. The 
injection syringes must not contain any other medicinal product or residue (e.g. traces of heparin). 
 
Insulin Human Winthrop Comb 50 is administered subcutaneously. Insulin Human Winthrop 
Comb 50 must never be injected intravenously. 
 
Insulin absorption and hence the blood-glucose-lowering effect of a dose may vary from one injection 
area to another (e.g. the abdominal wall compared with the thigh). Injection sites within an injection 
area must be rotated from one injection to the next. 
 
For further details on handling, see section 6.6. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
 
4.4 Special warnings and precautions for use 
 
Patients hypersensitive to Insulin Human Winthrop Comb 50 for whom no better tolerated preparation 
is available must only continue treatment under close medical supervision and – where necessary – in 
conjunction with anti-allergic treatment. 
 
In patients with an allergy to animal insulin intradermal skin testing is recommended prior to a 
transfer to Insulin Human Winthrop Comb 50, since they may experience immunological 
cross-reactions. 
 
In case of insufficient glucose control or a tendency to hyper- or hypoglycaemic episodes, the patient's 
adherence to the prescribed treatment regimen, injection sites and proper injection technique and all 
other relevant factors must be reviewed before dose adjustment is considered. 
 
Transfer to Insulin Human Winthrop Comb 50 
Transferring a patient to another type or brand of insulin should be done under strict medical 
supervision. Changes in strength, brand (manufacturer), type (regular, NPH, lente, long-acting, etc.), 
origin (animal, human, human insulin analogue) and/or method of manufacture may result in the need 
for a change in dosage. 
The need to adjust (e.g. reduce) the dose may become evident immediately after transfer. 
Alternatively, it may emerge gradually over a period of several weeks. 
 
Following transfer from an animal insulin to human insulin, dose regimen reduction may be required 
in particular in patients who 
- were previously already controlled on rather low blood glucose levels, 
- have a tendency to hypoglycaemia, 
- previously required high insulin doses due to the presence of insulin antibodies. 
 

 

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Close metabolic monitoring is recommended during the transition and in the initial weeks thereafter. In 
patients who require high insulin doses because of the presence of insulin antibodies, transfer under 
medical supervision in a hospital or similar setting must be considered. 
 
Hypoglycaemia 
Hypoglycaemia may occur if the insulin dose is too high in relation to the insulin requirement. 
 
Particular caution should be exercised, and intensified blood glucose monitoring is advisable in 
patients in whom hypoglycaemic episodes might be of particular clinical relevance, such as in patients 
with significant stenoses of the coronary arteries or of the blood vessels supplying the brain (risk of 
cardiac or cerebral complications of hypoglycaemia) as well as in patients with proliferative 
retinopathy, particularly if not treated with photocoagulation (risk of transient amaurosis following 
hypoglycaemia). 
 
Patients should be aware of circumstances where warning symptoms of hypoglycaemia are 
diminished. The warning symptoms of hypoglycaemia may be changed, be less pronounced or be 
absent in certain risk groups. These include patients: 
- in whom glycaemic control is markedly improved, 
- in whom hypoglycaemia develops gradually, 
- who are elderly,  
- after transfer from animal insulin to human insulin, 
- in whom an autonomic neuropathy is present, 
- with a long history of diabetes, 
- suffering from a psychiatric illness, 
- receiving concurrent treatment with certain other medicinal products (see section 4.5). 
Such situations may result in severe hypoglycaemia (and possibly loss of consciousness) prior to the 
patient's awareness of hypoglycaemia. 
 
If normal or decreased values for glycated haemoglobin are noted, the possibility of recurrent, 
unrecognised (especially nocturnal) episodes of hypoglycaemia must be considered. 
 
Adherence of the patient to the dose regimen and dietary regimen, correct insulin administration and 
awareness of hypoglycaemia symptoms are essential to reduce the risk of hypoglycaemia. Factors 
increasing the susceptibility to hypoglycaemia require particularly close monitoring and may 
necessitate dose adjustment. These include: 
- change in the injection area, 
- improved insulin sensitivity (e.g. by removal of stress factors), 
- unaccustomed, increased or prolonged physical activity, 
- intercurrent illness (e.g. vomiting, diarrhoea), 
- inadequate food intake, 
- missed meals, 
- alcohol consumption, 
- certain uncompensated endocrine disorders (e.g. in hypothyroidism and in anterior pituitary or 

adrenocortical insufficiency), 
- concomitant treatment with certain other medicinal products. 
 
Intercurrent illness 
Intercurrent illness requires intensified metabolic monitoring. In many cases, urine tests for ketones 
are indicated, and often it is necessary to adjust the insulin dose. The insulin requirement is often 
increased. Patients with type 1 diabetes must continue to consume at least a small amount of 
carbohydrates on a regular basis, even if they are able to eat only little or no food, or are vomiting etc. 
and they must never omit insulin entirely. 
 
Medication errors 
Medication errors have been reported in which other Insulin Human Winthrop formulations or other 
insulins have been accidentally administered. Insulin label must always be checked before each 
injection to avoid medication errors between insulin human and other insulins. 

 

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Combination of Insulin Human Winthrop with pioglitazone 
Cases of cardiac failure have been reported when pioglitazone was used in combination with insulin, 
especially in patients with risk factors for development of cardiac heart failure. This should be kept in 
mind if treatment with the combination of pioglitazone and Insulin Human Winthrop is considered. If 
the combination is used, patients should be observed for signs and symptoms of heart failure, weight 
gain and oedema. Pioglitazone should be discontinued if any deterioration in cardiac symptoms 
occurs.  
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
A number of substances affect glucose metabolism and may require dose adjustment of human insulin. 
 
Substances that may enhance the blood-glucose-lowering effect and increase susceptibility to 
hypoglycaemia include oral antidiabetic medicinal products, angiotensin converting enzyme (ACE) 
inhibitors, disopyramide, fibrates, fluoxetine, monoamine oxidase (MAO) inhibitors, pentoxifylline, 
propoxyphene, salicylates and sulphonamide antibiotics. 
 
Substances that may reduce the blood-glucose-lowering effect include corticosteroids, danazol, 
diazoxide, diuretics, glucagon, isoniazid, oestrogens and progestogens (e.g. in oral contraceptives), 
phenothiazine derivatives, somatropin, sympathomimetic medicinal products (e.g. epinephrine 
[adrenaline], salbutamol, terbutaline), thyroid hormones, protease inhibitors and atypical antipsychotic 
medicinal products (e.g. olanzapine and clozapine). 
 
Beta-blockers, clonidine, lithium salts or alcohol may either potentiate or weaken the 
blood-glucose-lowering effect of insulin. Pentamidine may cause hypoglycaemia which may 
sometimes be followed by hyperglycaemia. 
 
In addition, under the influence of sympatholytic medicinal products such as beta-blockers, clonidine, 
guanethidine and reserpine, the signs of adrenergic counter-regulation may be reduced or absent. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
For insulin human, no clinical data on exposed pregnancies from controlled clinical studies are 
available. Insulin does cross the placental barrier, although not in clinically significant amount. A 
limited amount of data on pregnant women (less than 300 pregnancy outcomes reported) exposed to 
marketed insulin human indicates no safety issues in use of insulin human in pregnancy. Caution 
should be exercised when prescribing to pregnant women. 
 
It is essential for patients with pre-existing or gestational diabetes to maintain good metabolic control 
throughout pregnancy. Insulin requirements may decrease during the first trimester and generally 
increase during the second and third trimesters. Immediately after delivery, insulin requirements 
decline rapidly (increased risk of hypoglycaemia). Careful monitoring of glucose control is essential. 
 
Breast-feeding 
No effects on the suckling child are anticipated. Insulin Human Winthrop Comb 50 can be used during 
breast-feeding. Breast-feeding women may require adjustments in insulin dose and diet. 
 
Fertility 
No clinical or animal data with insulin human on male or female fertility are available. 
 

 

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4.7 Effects on ability to drive and use machines 
 
The patient's ability to concentrate and react may be impaired as a result of hypoglycaemia or 
hyperglycaemia or, for example, as a result of visual impairment. This may constitute a risk in 
situations where these abilities are of special importance (e.g. driving a car or using machines). 
 
Patients should be advised to take precautions to avoid hypoglycaemia whilst driving. This is 
particularly important in those who have reduced or absent awareness of the warning symptoms of 
hypoglycaemia or have frequent episodes of hypoglycaemia. It should be considered whether it is 
advisable to drive or use machines in these circumstances. 
 
4.8 Undesirable effects 
 
Summary of the safety profile  
Hypoglycaemia, in general the most frequent adverse reaction of insulin therapy, may occur if the 
insulin dose is too high in relation to the insulin requirement. In clinical studies and during marketed 
use, the frequency varies with patient population and dose regimens. Therefore, no specific frequency 
can be presented. 
 
Tabulated list of adverse reactions 
The following related adverse reactions from clinical investigations are listed below by system organ 
class and in order of decreasing incidence: very common (≥1/10); common (≥1/100 to <1/10); 
uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000), not known 
(cannot be estimated from the available data). 
 
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. 
 
MedDRA system 
organ classes 

Common Uncommon Not known 

Immune system 
disorders 

 Shock Immediate type 
allergic reactions 
(hypotension, 
angioneurotic oedema, 
bronchospasm, 
generalised skin 
reactions); 
Anti-insulin antibodies 

Metabolism and 
nutrition disorders 

Oedema  Hypoglycaemia; 
Sodium retention 

Eye disorders   Proliferative 
retinopathy; 
Diabetic retinopathy; 
Visual impairment 

Skin and 
subcutaneous tissue 
disorders 

  Lipodystrophy 

General disorders 
and administration 
site conditions 

Injection site reactions Injection site urticaria Injection site 
inflammation;  
Injection site pain; 
Injection site pruritus; 
Injection site 
erythema;  
Injection site swelling 

 

 

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Description of selected adverse reactions 
Immune system disorders 
Immediate type allergic reactions to insulin or to the excipients may be life-threatening. 
 
Insulin administration may cause anti-insulin antibodies to form. In rare cases, the presence of such 
anti-insulin antibodies may necessitate adjustment of the insulin dose in order to correct a tendency to 
hyper- or hypoglycaemia. 
 
Metabolism and nutrition disorders 
Severe hypoglycaemic attacks, especially if recurrent, may lead to neurological damage. 
Prolonged or severe hypoglycaemic episodes may be life-threatening. 
 
In many patients, the signs and symptoms of neuroglycopenia are preceded by signs of adrenergic 
counter-regulation. Generally, the greater and more rapid the decline in blood glucose, the more 
marked is the phenomenon of counter-regulation and its symptoms. 
Insulin may cause sodium retention and oedema, particularly if previously poor metabolic control is 
improved by intensified insulin therapy. 
 
Eyes disorders 
A marked change in glycaemic control may cause temporary visual impairment, due to temporary 
alteration in the turgidity and refractive index of the lens. 
 
Long-term improved glycaemic control decreases the risk of progression of diabetic retinopathy. 
However, intensification of insulin therapy with abrupt improvement in glycaemic control may be 
associated with temporary worsening of diabetic retinopathy. 
 
Skin and subcutaneous tissue disorders 
Lipodystrophy may occur at the injection site and delay local insulin absorption. Continuous rotation 
of the injection site within the given injection area may help to reduce or prevent these reactions. 
 
General disorders and administration site conditions 
Most minor reactions to insulins at the injection site usually resolve in a few days to a few weeks. 
 
4.9 Overdose 
 
Symptoms 
Insulin overdose may lead to severe and sometimes long-term and life-threatening hypoglycaemia. 
 
Management 
Mild episodes of hypoglycaemia can usually be treated with oral carbohydrates. Adjustments in dose 
regimen of the medicinal product, meal patterns, or physical activity may be needed. 
 
More severe episodes with coma, seizure, or neurologic impairment may be treated with 
intramuscular/subcutaneous glucagon or concentrated intravenous glucose. Sustained carbohydrate 
intake and observation may be necessary because hypoglycaemia may recur after apparent clinical 
recovery. 
 
 

 

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5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Drugs used in diabetes, insulins and analogues for injection, 
intermediate-acting combined with fast-acting, ATC Code: A10AD01. 
 
Mechanism of action 
Insulin 
- lowers blood glucose and promotes anabolic effects as well as decreasing catabolic effects, 
- increases the transport of glucose into cells as well as the formation of glycogen in the muscles 

and the liver, and improves pyruvate utilisation. It inhibits glycogenolysis and gluconeogenesis, 
- increases lipogenesis in the liver and adipose tissue and inhibits lipolysis, 
- promotes the uptake of amino acids into cells and promotes protein synthesis, 
- enhances the uptake of potassium into cells. 
 
Pharmacodynamic effects 
Insulin Human Winthrop Comb 50 (a biphasic isophane insulin suspension with 50% dissolved 
insulin) is an insulin with rapid onset and moderately long duration of action. Following subcutaneous 
injection, onset of action is within 30 minutes, the phase of maximum action is between 1.5 and 
4 hours after injection and the duration of action is 12 to 16 hours. 
 
5.2 Pharmacokinetic properties 
 
In healthy subjects, the serum half-life of insulin is approximately 4 to 6 minutes. It is longer in 
patients with severe renal insufficiency. However, it must be noted that the pharmacokinetics of 
insulin do not reflect its metabolic action. 
 
5.3 Preclinical safety data 
 
The acute toxicity was studied following subcutaneous administration in rats. No evidence of toxic 
effects was found. Studies of pharmacodynamic effects following subcutaneous administration in 
rabbits and dogs revealed the expected hypoglycaemic reactions. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Protamine sulphate, 
metacresol, 
phenol, 
zinc chloride, 
sodium dihydrogen phosphate dihydrate, 
glycerol, 
sodium hydroxide, 
hydrochloric acid (for pH adjustment), 
water for injections. 
 
6.2 Incompatibilities 
 
This medicinal product must not be mixed with other medicinal products except those mentioned in 
section 6.6. 
 
Insulin Human Winthrop Comb 50 must not be mixed with solutions containing reducing substances 
such as thioles and sulphites.  
 

 

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Mixing of insulins 
Insulin Human Winthrop Comb 50 must not be mixed with insulin human formulations designed 
specifically for use in insulin pumps.  
Insulin Human Winthrop Comb 50 must also not be mixed with insulins of animal origin or with 
insulin analogues. 
Insulins of different concentration (e.g. 100 IU per ml and 40 IU per ml) must not be mixed. 
 
Care must be taken to ensure that no alcohol or other disinfectants enter the insulin suspension. 
 
6.3 Shelf life 
 
2 years. 
 
Shelf life after first use of the vial 
The product may be stored for a maximum of 4 weeks not above 25°C and away from direct heat or 
direct light. 
Keep the vial in the outer carton in order to protect from light. 
It is recommended that the date of the first use be noted on the label. 
 
6.4 Special precautions for storage 
 
Unopened vials 
Store in a refrigerator (2°C - 8°C). 
Do not freeze. 
Do not put Insulin Human Winthrop Comb 50 next to the freezer compartment or a freezer pack. 
Keep the vial in the outer carton in order to protect from light. 
 
Opened vials 
For storage conditions after first opening of the medicinal product, see section 6.3. 
 
6.5 Nature and contents of container 
 
10 ml suspension in a vial (type 1 colourless glass) with a flanged cap (aluminium), a stopper 
(chlorobutyl rubber (type 1)) and a tear-off cap (polypropylene). 
Packs of 1 and 5 vials are available. 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal and other handling 
 
Before withdrawing insulin from the vial for the first time, remove the plastic protective cap. 
 
Immediately before withdrawal from the vial into the injection syringe, the insulin must be 
resuspended. This is best done by rolling the vial at an oblique angle between the palms of the hands. 
Do not shake the vial vigorously as this may lead to changes in the suspension (giving the vial a 
frosted appearance; see below) and cause frothing. Froth may interfere with the correct measurement 
of the dose. 
 
After resuspension, the fluid must have a uniformly milky appearance. Insulin Human Winthrop 
Comb 50 must not be used if this cannot be achieved, i.e. if the suspension remains clear, for example, 
or if clumps, particles or flocculation appear in the insulin or stick to the wall or bottom of the vial. 
These changes sometimes give the vial a frosted appearance. In such cases, a new vial yielding a 
uniform suspension must be used. It is also necessary to change to a new vial if the insulin 
requirement changes substantially. 
 
Insulin Human Winthrop Comb 50 must not be administered intravenously and must not be used in 
infusion pumps or external or implanted insulin pumps. 
 

 

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It must be remembered that 
- insulin protamine crystals dissolve in an acid pH range, 
- the soluble insulin part precipitates out at a pH of approximately 4.5 to 6.5. 
 
Insulin label must always be checked before each injection to avoid medication errors between insulin 
human and other insulins (see section 4.4). 
 
Mixing of insulins 
Insulin Human Winthrop Comb 50 may be mixed with all insulin human formulations, but notwith 
those designed specifically for use in insulin pumps. Concerning incompatibility with other insulins, 
see section 6.2. 
 
If two different insulins have to be drawn into one single injection syringe, it is recommended that the 
shorter-acting insulin be drawn first to prevent contamination of the vial by the longer-acting 
preparation. It is advisable to inject immediately after mixing.  
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Sanofi-Aventis Deutschland GmbH, D-65926 Frankfurt am Main, Germany 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/06/368/009 
EU/1/06/368/010 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 17 January 2007 
Date of latest renewal: 17 January 2012 
 
 
10. DATE OF REVISION OF THE TEXT 
 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu 

 

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1. NAME OF THE MEDICINAL PRODUCT 
 
Insulin Human Winthrop Comb 50 100 IU/ml suspension for injection in a cartridge 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each ml contains 100 IU insulin human (equivalent to 3.5 mg).  
Each cartridge contains 3 ml of suspension for injection, equivalent to 300 IU insulin. One IU 
(International Unit) corresponds to 0.035 mg of anhydrous human insulin. 
 
Insulin Human Winthrop Comb 50 is a biphasic isophane insulin suspension consisting of 50% 
dissolved insulin and 50% crystalline protamine insulin. 
 
Human insulin is produced by recombinant DNA technology in Escherichia coli. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Suspension for injection in a cartridge. 
 
After resuspension, milky-white suspension. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Diabetes mellitus where treatment with insulin is required. 
 
4.2 Posology and method of administration 
 
Posology 
The desired blood glucose levels, the insulin preparations to be used and the insulin dose regimen 
(doses and timings) must be determined individually and adjusted to suit the patient’s diet, physical 
activity and life-style. 
 
Daily doses and timing of administration 
There are no fixed rules for insulin dose regimen. However, the average insulin requirement is often 
0.5 to 1.0 IU per kg body weight per day. The basal metabolic requirement is 40% to 60% of the total 
daily requirement. Insulin Human Winthrop Comb 50 is injected subcutaneously 20 to 30 minutes 
before a meal. 
 
Secondary dose adjustment 
Improved metabolic control may result in increased insulin sensitivity, leading to a reduced insulin 
requirement. Dose adjustment may also be required, for example, if 
- the patient's weight changes, 
- the patient's life-style changes, 
- other circumstances arise that may promote an increased susceptibility to hypo- or 

hyperglycaemia (see section 4.4). 
 
Special populations 
Elderly population (≧65 years old) 
In the elderly, progressive deterioration of renal function may lead to a steady decrease in insulin 
requirements. 

 

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Renal impairment 
In patients with renal impairment, insulin requirements may be diminished due to reduced insulin 
metabolism. 
 
Hepatic impairment 
In patients with severe hepatic impairment, insulin requirements may be diminished due to reduced 
capacity for gluconeogenesis and reduced insulin metabolism. 
 
Method of administration 
Insulin Human Winthrop Comb 50 must not be administered intravenously and must not be used in 
infusion pumps or external or implanted insulin pumps. 
 
Insulin Human Winthrop Comb 50 is administered subcutaneously. Insulin Human Winthrop 
Comb 50 must never be injected intravenously. 
 
Insulin absorption and hence the blood-glucose-lowering effect of a dose may vary from one injection 
area to another (e.g. the abdominal wall compared with the thigh). Injection sites within an injection 
area must be rotated from one injection to the next. 
 
For further details on handling, see section 6.6. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
 
4.4 Special warnings and precautions for use 
 
Patients hypersensitive to Insulin Human Winthrop Comb 50 for whom no better tolerated preparation 
is available must only continue treatment under close medical supervision and – where necessary – in 
conjunction with anti-allergic treatment. 
 
In patients with an allergy to animal insulin intradermal skin testing is recommended prior to a 
transfer to Insulin Human Winthrop Comb 50, since they may experience immunological 
cross-reactions. 
 
In case of insufficient glucose control or a tendency to hyper- or hypoglycaemic episodes, the patient's 
adherence to the prescribed treatment regimen, injection sites and proper injection technique and all 
other relevant factors must be reviewed before dose adjustment is considered. 
 
Transfer to Insulin Human Winthrop Comb 50 
Transferring a patient to another type or brand of insulin should be done under strict medical 
supervision. Changes in strength, brand (manufacturer), type (regular, NPH, lente, long-acting, etc.), 
origin (animal, human, human insulin analogue) and/or method of manufacture may result in the need 
for a change in dosage. 
The need to adjust (e.g. reduce) the dose may become evident immediately after transfer. 
Alternatively, it may emerge gradually over a period of several weeks. 
 
Following transfer from an animal insulin to human insulin, dose regimen reduction may be required 
in particular in patients who 
- were previously already controlled on rather low blood glucose levels, 
- have a tendency to hypoglycaemia, 
- previously required high insulin doses due to the presence of insulin antibodies. 
 
Close metabolic monitoring is recommended during the transition and in the initial weeks thereafter. In 
patients who require high insulin doses because of the presence of insulin antibodies, transfer under 
medical supervision in a hospital or similar setting must be considered. 

 

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Hypoglycaemia 
Hypoglycaemia may occur if the insulin dose is too high in relation to the insulin requirement. 
 
Particular caution should be exercised, and intensified blood glucose monitoring is advisable in 
patients in whom hypoglycaemic episodes might be of particular clinical relevance, such as in patients 
with significant stenoses of the coronary arteries or of the blood vessels supplying the brain (risk of 
cardiac or cerebral complications of hypoglycaemia) as well as in patients with proliferative 
retinopathy, particularly if not treated with photocoagulation (risk of transient amaurosis following 
hypoglycaemia). 
 
Patients should be aware of circumstances where warning symptoms of hypoglycaemia are 
diminished. The warning symptoms of hypoglycaemia may be changed, be less pronounced or be 
absent in certain risk groups. These include patients: 
- in whom glycaemic control is markedly improved, 
- in whom hypoglycaemia develops gradually, 
- who are elderly,  
- after transfer from animal insulin to human insulin, 
- in whom an autonomic neuropathy is present, 
- with a long history of diabetes, 
- suffering from a psychiatric illness, 
- receiving concurrent treatment with certain other medicinal products (see section 4.5). 
Such situations may result in severe hypoglycaemia (and possibly loss of consciousness) prior to the 
patient's awareness of hypoglycaemia. 
 
If normal or decreased values for glycated haemoglobin are noted, the possibility of recurrent, 
unrecognised (especially nocturnal) episodes of hypoglycaemia must be considered. 
 
Adherence of the patient to the dose regimen and dietary regimen, correct insulin administration and 
awareness of hypoglycaemia symptoms are essential to reduce the risk of hypoglycaemia. Factors 
increasing the susceptibility to hypoglycaemia require particularly close monitoring and may 
necessitate dose adjustment. These include: 
- change in the injection area, 
- improved insulin sensitivity (e.g. by removal of stress factors), 
- unaccustomed, increased or prolonged physical activity, 
- intercurrent illness (e.g. vomiting, diarrhoea), 
- inadequate food intake, 
- missed meals, 
- alcohol consumption, 
- certain uncompensated endocrine disorders (e.g. in hypothyroidism and in anterior pituitary or 

adrenocortical insufficiency), 
- concomitant treatment with certain other medicinal products. 
 
Intercurrent illness 
Intercurrent illness requires intensified metabolic monitoring. In many cases, urine tests for ketones 
are indicated, and often it is necessary to adjust the insulin dose. The insulin requirement is often 
increased. Patients with type 1 diabetes must continue to consume at least a small amount of 
carbohydrates on a regular basis, even if they are able to eat only little or no food, or are vomiting etc. 
and they must never omit insulin entirely. 
 
Pens to be used with Insulin Human Winthrop Comb 50 cartridges 
The Insulin Human Winthrop Comb 50 cartridges should only be used with the following pens:  
- JuniorSTAR which delivers Insulin Human Winthrop Comb 50 in 0.5 unit dose increments 
- OptiPen, ClikSTAR, Tactipen, Autopen 24 and AllStar which all deliver Insulin Human Winthrop 
Comb 50 in 1 unit dose increments. 
These cartridges should not be used with any other reusable pen as the dosing accuracy has only been 
established with the listed pens.  

 

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Not all of these pens may be marketed in your country. 
 
Medication errors 
Medication errors have been reported in which other Insulin Human Winthrop formulations or other 
insulins have been accidentally administered. Insulin label must always be checked before each 
injection to avoid medication errors between insulin human and other insulins. 
 
Combination of Insulin Human Winthrop with pioglitazone 
Cases of cardiac failure have been reported when pioglitazone was used in combination with insulin, 
especially in patients with risk factors for development of cardiac heart failure. This should be kept in 
mind if treatment with the combination of pioglitazone and Insulin Human Winthrop is considered. If 
the combination is used, patients should be observed for signs and symptoms of heart failure, weight 
gain and oedema. Pioglitazone should be discontinued if any deterioration in cardiac symptoms 
occurs.  
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
A number of substances affect glucose metabolism and may require dose adjustment of human insulin. 
 
Substances that may enhance the blood-glucose-lowering effect and increase susceptibility to 
hypoglycaemia include oral antidiabetic medicinal products, angiotensin converting enzyme (ACE) 
inhibitors, disopyramide, fibrates, fluoxetine, monoamine oxidase (MAO) inhibitors, pentoxifylline, 
propoxyphene, salicylates and sulphonamide antibiotics. 
 
Substances that may reduce the blood-glucose-lowering effect include corticosteroids, danazol, 
diazoxide, diuretics, glucagon, isoniazid, oestrogens and progestogens (e.g. in oral contraceptives), 
phenothiazine derivatives, somatropin, sympathomimetic medicinal products (e.g. epinephrine 
[adrenaline], salbutamol, terbutaline), thyroid hormones, protease inhibitors and atypical antipsychotic 
medicinal products (e.g. olanzapine and clozapine). 
 
Beta-blockers, clonidine, lithium salts or alcohol may either potentiate or weaken the 
blood-glucose-lowering effect of insulin. Pentamidine may cause hypoglycaemia which may 
sometimes be followed by hyperglycaemia. 
 
In addition, under the influence of sympatholytic medicinal products such as beta-blockers, clonidine, 
guanethidine and reserpine, the signs of adrenergic counter-regulation may be reduced or absent. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
For insulin human, no clinical data on exposed pregnancies from controlled clinical studies are 
available. Insulin does cross the placental barrier, although not in clinically significant amount. A 
limited amount of data on pregnant women (less than 300 pregnancy outcomes reported) exposed to 
marketed insulin human indicates no safety issues in use of insulin human in pregnancy. Caution 
should be exercised when prescribing to pregnant women. 
 
It is essential for patients with pre-existing or gestational diabetes to maintain good metabolic control 
throughout pregnancy. Insulin requirements may decrease during the first trimester and generally 
increase during the second and third trimesters. Immediately after delivery, insulin requirements 
decline rapidly (increased risk of hypoglycaemia). Careful monitoring of glucose control is essential. 
 
Breast-feeding 
No effects on the suckling child are anticipated. Insulin Human Winthrop Comb 50 can be used during 
breast-feeding. Breast-feeding women may require adjustments in insulin dose and diet. 
 
Fertility 
No clinical or animal data with insulin human on male or female fertility are available. 

 

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4.7 Effects on ability to drive and use machines 
 
The patient's ability to concentrate and react may be impaired as a result of hypoglycaemia or 
hyperglycaemia or, for example, as a result of visual impairment. This may constitute a risk in 
situations where these abilities are of special importance (e.g. driving a car or using machines). 
 
Patients should be advised to take precautions to avoid hypoglycaemia whilst driving. This is 
particularly important in those who have reduced or absent awareness of the warning symptoms of 
hypoglycaemia or have frequent episodes of hypoglycaemia. It should be considered whether it is 
advisable to drive or use machines in these circumstances. 
 
4.8 Undesirable effects 
 
Summary of the safety profile  
Hypoglycaemia, in general the most frequent adverse reaction of insulin therapy, may occur if the 
insulin dose is too high in relation to the insulin requirement. In clinical studies and during marketed 
use, the frequency varies with patient population and dose regimens. Therefore, no specific frequency 
can be presented. 
 
Tabulated list of adverse reactions 
The following related adverse reactions from clinical investigations are listed below by system organ 
class and in order of decreasing incidence: very common (≥1/10); common (≥1/100 to <1/10); 
uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000), not known 
(cannot be estimated from the available data). 
 
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. 
 
MedDRA system 
organ classes 

Common Uncommon Not known 

Immune system 
disorders 

 Shock Immediate type allergic 
reactions (hypotension, 
angioneurotic oedema, 
bronchospasm, 
generalised skin 
reactions); 
Anti-insulin antibodies 

Metabolism and 
nutrition disorders 

Oedema  Hypoglycaemia; 
Sodium retention 

Eye disorders   Proliferative retinopathy; 
Diabetic retinopathy; 
Visual impairment 

Skin and subcutaneous 
tissue disorders 

  Lipodystrophy 

General disorders and 
administration site 
conditions 

Injection site reactions Injection site 
urticaria 

Injection site 
inflammation;  
Injection site pain; 
Injection site pruritus; 
Injection site erythema; 
Injection site swelling 

 
Description of selected adverse reactions 
Immune system disorders 
Immediate type allergic reactions to insulin or to the excipients may be life-threatening. 
 

 

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Insulin administration may cause anti-insulin antibodies to form. In rare cases, the presence of such 
anti-insulin antibodies may necessitate adjustment of the insulin dose in order to correct a tendency to 
hyper- or hypoglycaemia. 
 
Metabolism and nutrition disorders 
Severe hypoglycaemic attacks, especially if recurrent, may lead to neurological damage. 
Prolonged or severe hypoglycaemic episodes may be life-threatening. 
 
In many patients, the signs and symptoms of neuroglycopenia are preceded by signs of adrenergic 
counter-regulation. Generally, the greater and more rapid the decline in blood glucose, the more 
marked is the phenomenon of counter-regulation and its symptoms. 
 
Insulin may cause sodium retention and oedema, particularly if previously poor metabolic control is 
improved by intensified insulin therapy. 
 
Eyes disorders 
A marked change in glycaemic control may cause temporary visual impairment, due to temporary 
alteration in the turgidity and refractive index of the lens. 
 
Long-term improved glycaemic control decreases the risk of progression of diabetic retinopathy. 
However, intensification of insulin therapy with abrupt improvement in glycaemic control may be 
associated with temporary worsening of diabetic retinopathy. 
 
Skin and subcutaneous tissue disorders 
Lipodystrophy may occur at the injection site and delay local insulin absorption. Continuous rotation 
of the injection site within the given injection area may help to reduce or prevent these reactions. 
 
General disorders and administration site conditions 
Most minor reactions to insulins at the injection site usually resolve in a few days to a few weeks. 
 
4.9 Overdose 
 
Symptoms 
Insulin overdose may lead to severe and sometimes long-term and life-threatening hypoglycaemia. 
 
Management 
Mild episodes of hypoglycaemia can usually be treated with oral carbohydrates. Adjustments in dose 
regimen of the medicinal product, meal patterns, or physical activity may be needed. 
 
More severe episodes with coma, seizure, or neurologic impairment may be treated with 
intramuscular/subcutaneous glucagon or concentrated intravenous glucose. Sustained carbohydrate 
intake and observation may be necessary because hypoglycaemia may recur after apparent clinical 
recovery. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Drugs used in diabetes, insulins and analogues for injection, 
intermediate-acting combined with fast-acting, ATC Code: A10AD01. 
 
Mechanism of action 
Insulin 
- lowers blood glucose and promotes anabolic effects as well as decreasing catabolic effects, 
- increases the transport of glucose into cells as well as the formation of glycogen in the muscles 

and the liver, and improves pyruvate utilisation. It inhibits glycogenolysis and gluconeogenesis, 

 

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- increases lipogenesis in the liver and adipose tissue and inhibits lipolysis, 
- promotes the uptake of amino acids into cells and promotes protein synthesis, 
- enhances the uptake of potassium into cells. 
 
Pharmacodynamic effects 
Insulin Human Winthrop Comb 50 (a biphasic isophane insulin suspension with 50% dissolved 
insulin) is an insulin with rapid onset and moderately long duration of action. Following subcutaneous 
injection, onset of action is within 30 minutes, the phase of maximum action is between 1.5 and 
4 hours after injection and the duration of action is 12 to 16 hours. 
 
5.2 Pharmacokinetic properties 
 
In healthy subjects, the serum half-life of insulin is approximately 4 to 6 minutes. It is longer in 
patients with severe renal insufficiency. However, it must be noted that the pharmacokinetics of 
insulin do not reflect its metabolic action. 
 
5.3 Preclinical safety data 
 
The acute toxicity was studied following subcutaneous administration in rats. No evidence of toxic 
effects was found. Studies of pharmacodynamic effects following subcutaneous administration in 
rabbits and dogs revealed the expected hypoglycaemic reactions. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Protamine sulphate, 
metacresol, 
phenol, 
zinc chloride, 
sodium dihydrogen phosphate dihydrate, 
glycerol, 
sodium hydroxide, 
hydrochloric acid (for pH adjustment), 
water for injections. 
 
6.2 Incompatibilities 
 
This medicinal product must not be mixed with other medicinal products except those mentioned in 
section 6.6. 
 
Insulin Human Winthrop Comb 50 must not be mixed with solutions containing reducing substances 
such as thioles and sulphites.  
 
Mixing of insulins 
Insulin Human Winthrop Comb 50 must not be mixed with insulin human formulations designed 
specifically for use in insulin pumps.  
Insulin Human Winthrop Comb 50 must also not be mixed with insulins of animal origin or with 
insulin analogues. 
 
Care must be taken to ensure that no alcohol or other disinfectants enter the insulin suspension. 
 
6.3 Shelf life 
 
2 years. 
 

 

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Shelf life after first use of the cartridge 
The cartridge in-use (in the insulin pen) or carried as a spare may be stored for a maximum of 4 weeks 
not above 25°C and away from direct heat or direct light. 
The pen containing a cartridge must not be stored in the refrigerator. 
The pen cap must be put back on the pen after each injection in order to protect from light. 
 
6.4 Special precautions for storage 
 
Unopened cartridges 
Store in a refrigerator (2°C - 8°C). 
Do not freeze. 
Do not put Insulin Human Winthrop Comb 50 next to the freezer compartment or a freezer pack. 
Keep the cartridge in the outer carton in order to protect from light. 
 
In-use cartridges 
For storage conditions after first opening of the medicinal product, see section 6.3. 
 
6.5 Nature and contents of container 
 
3 ml suspension in a cartridge (type 1 colourless glass) with a plunger (bromobutyl rubber (type 1)) 
and a flanged cap (aluminium) with a stopper (bromobutyl or laminate of polyisoprene and 
bromobutyl rubber (type 1)). 
Each cartridge contains 3 balls (stainless steel). 
Packs of 3, 4, 5, 6, 9 or 10 cartridges are available. 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal and other handling 
 
Insulin pen 
The Insulin Human Winthrop Comb 50 cartridges are to be used only in conjunction with the pens: 
OptiPen, ClikSTAR, Autopen 24, Tactipen, AllStar or JuniorSTAR (see section 4.4). Not all of these pens 
may be marketed in your country. 
 
The pen should be used as recommended in the information provided by the device manufacturer.  
 
The manufacturer’s instructions for using the pen must be followed carefully for loading the cartridge, 
attaching the injection needle, and administering the insulin injection. 
 
If the insulin pen is damaged or not working properly (due to mechanical defects) it has to be 
discarded, and a new insulin pen has to be used. 
 
If the pen malfunctions (see instructions for using the pen), the suspension may be drawn from the 
cartridge into an injection syringe (suitable for an insulin with 100 IU/ml) and injected. 
 
Cartridges 
Before insertion into the pen, Insulin Human Winthrop Comb 50 must be kept at room temperature for 
1 to 2 hours and then resuspended to check the contents. This is best done by gently tilting the 
cartridge back and forth (at least ten times). Each cartridge contains three small metal balls to facilitate 
quick and thorough mixing of the contents. 
 
Later on, when the cartridge has been inserted into the pen, the insulin must be resuspended again 
prior to each injection. This is best done by gently tilting the pen back and forth (at least ten times). 
 
After resuspension, the fluid must have a uniformly milky appearance. Insulin Human Winthrop 
Comb 50 must not be used if this cannot be achieved, i.e. if the suspension remains clear, for example, 
or if clumps, particles or flocculation appear in the insulin or stick to the wall or bottom of the 
cartridge. These changes sometimes give the cartridge a frosted appearance. In such cases, a new 

 

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cartridge yielding a uniform suspension must be used. It is also necessary to change to a new cartridge 
if the insulin requirement changes substantially. 
 
Air bubbles must be removed from the cartridge before injection (see instructions for using the pen). 
Empty cartridges must not be refilled. 
 
Insulin Human Winthrop Comb 50 must not be administered intravenously and must not be used in 
infusion pumps or external or implanted insulin pumps. 
 
It must be remembered that 
- insulin protamine crystals dissolve in an acid pH range, 
- the soluble insulin part precipitates out at a pH of approximately 4.5 to 6.5. 
 
Insulin label must always be checked before each injection to avoid medication errors between insulin 
human and other insulins (see section 4.4). 
 
Mixing of insulins 
Insulin Human Winthrop Comb 50 may be mixed with all insulin human formulations, but not with 
those designed specifically for use in insulin pumps. Concerning incompatibility with other insulins, 
see section 6.2. 
 
Insulin Human Winthrop Comb 50 cartridges are not designed to allow any other insulin to be mixed 
in the cartridge. 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Sanofi-Aventis Deutschland GmbH, D-65926 Frankfurt am Main, Germany 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/06/368/092 
EU/1/06/368/049 
EU/1/06/368/050 
EU/1/06/368/097 
EU/1/06/368/102 
EU/1/06/368/051 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 17 January 2007 
Date of latest renewal: 17 January 2012 
 
 
10. DATE OF REVISION OF THE TEXT 
 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu 

 

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1. NAME OF THE MEDICINAL PRODUCT 
 
Insulin Human Winthrop Comb 50 SoloStar 100 IU/ml suspension for injection in a pre-filled pen. 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each ml contains 100 IU insulin human (equivalent to 3.5 mg).  
Each pen contains 3 ml of suspension for injection, equivalent to 300 IU insulin. One IU (International 
Unit) corresponds to 0.035 mg of anhydrous human insulin. 
 
Insulin Human Winthrop Comb 50 is a biphasic isophane insulin suspension consisting of 50% 
dissolved insulin and 50% crystalline protamine insulin. 
 
Human insulin is produced by recombinant DNA technology in Escherichia coli. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Suspension for injection in a pre-filled pen. 
 
After resuspension, milky-white suspension. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Diabetes mellitus where treatment with insulin is required. 
 
4.2 Posology and method of administration 
 
Posology 
The desired blood glucose levels, the insulin preparations to be used and the insulin dose regimen 
(doses and timings) must be determined individually and adjusted to suit the patient’s diet, physical 
activity and life-style. 
 
Daily doses and timing of administration 
There are no fixed rules for insulin dose regimen. However, the average insulin requirement is often 
0.5 to 1.0 IU per kg body weight per day. The basal metabolic requirement is 40% to 60% of the total 
daily requirement. Insulin Human Winthrop Comb 50 is injected subcutaneously 20 to 30 minutes 
before a meal. 
 
SoloStar delivers insulin in doses from 1 to 80 units in steps of 1 unit. Each pen contains multiple 
doses. 
 
Secondary dose adjustment 
Improved metabolic control may result in increased insulin sensitivity, leading to a reduced insulin 
requirement. Dose adjustment may also be required, for example, if 
- the patient's weight changes, 
- the patient's life-style changes, 
- other circumstances arise that may promote an increased susceptibility to hypo- or 

hyperglycaemia (see section 4.4). 
 

 

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Special populations 
Elderly population (≧65 years old) 
In the elderly, progressive deterioration of renal function may lead to a steady decrease in insulin 
requirements. 
 
Renal impairment 
In patients with renal impairment, insulin requirements may be diminished due to reduced insulin 
metabolism. 
 
Hepatic impairment 
In patients with severe hepatic impairment, insulin requirements may be diminished due to reduced 
capacity for gluconeogenesis and reduced insulin metabolism. 
 
Method of administration 
Insulin Human Winthrop Comb 50 is administered subcutaneously. Insulin Human Winthrop 
Comb 50 must never be injected intravenously. 
 
Insulin absorption and hence the blood-glucose-lowering effect of a dose may vary from one injection 
area to another (e.g. the abdominal wall compared with the thigh). Injection sites within an injection 
area must be rotated from one injection to the next. 
 
Before using SoloStar, the Instructions for Use included in the Package Leaflet must be read carefully. 
 
For further details on handling, see section 6.6. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
 
4.4 Special warnings and precautions for use 
 
Patients hypersensitive to Insulin Human Winthrop Comb 50 for whom no better tolerated preparation 
is available must only continue treatment under close medical supervision and – where necessary – in 
conjunction with anti-allergic treatment. 
 
In patients with an allergy to animal insulin intradermal skin testing is recommended prior to a 
transfer to Insulin Human Winthrop Comb 50, since they may experience immunological 
cross-reactions. 
 
In case of insufficient glucose control or a tendency to hyper- or hypoglycaemic episodes, the patient's 
adherence to the prescribed treatment regimen, injection sites and proper injection technique and all 
other relevant factors must be reviewed before dose adjustment is considered. 
 
Transfer to Insulin Human Winthrop Comb 50 
Transferring a patient to another type or brand of insulin should be done under strict medical 
supervision. Changes in strength, brand (manufacturer), type (regular, NPH, lente, long-acting, etc.), 
origin (animal, human, human insulin analogue) and/or method of manufacture may result in the need 
for a change in dosage. 
The need to adjust (e.g. reduce) the dose may become evident immediately after transfer. 
Alternatively, it may emerge gradually over a period of several weeks. 
 
Following transfer from an animal insulin to human insulin, dose regimen reduction may be required 
in particular in patients who 
- were previously already controlled on rather low blood glucose levels, 
- have a tendency to hypoglycaemia, 
- previously required high insulin doses due to the presence of insulin antibodies. 
 

 

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Close metabolic monitoring is recommended during the transition and in the initial weeks thereafter. In 
patients who require high insulin doses because of the presence of insulin antibodies, transfer under 
medical supervision in a hospital or similar setting must be considered. 
 
Hypoglycaemia 
Hypoglycaemia may occur if the insulin dose is too high in relation to the insulin requirement. 
 
Particular caution should be exercised, and intensified blood glucose monitoring is advisable in 
patients in whom hypoglycaemic episodes might be of particular clinical relevance, such as in patients 
with significant stenoses of the coronary arteries or of the blood vessels supplying the brain (risk of 
cardiac or cerebral complications of hypoglycaemia) as well as in patients with proliferative 
retinopathy, particularly if not treated with photocoagulation (risk of transient amaurosis following 
hypoglycaemia). 
 
Patients should be aware of circumstances where warning symptoms of hypoglycaemia are 
diminished. The warning symptoms of hypoglycaemia may be changed, be less pronounced or be 
absent in certain risk groups. These include patients: 
- in whom glycaemic control is markedly improved, 
- in whom hypoglycaemia develops gradually, 
- who are elderly,  
- after transfer from animal insulin to human insulin, 
- in whom an autonomic neuropathy is present, 
- with a long history of diabetes, 
- suffering from a psychiatric illness, 
- receiving concurrent treatment with certain other medicinal products (see section 4.5). 
Such situations may result in severe hypoglycaemia (and possibly loss of consciousness) prior to the 
patient's awareness of hypoglycaemia. 
 
If normal or decreased values for glycated haemoglobin are noted, the possibility of recurrent, 
unrecognised (especially nocturnal) episodes of hypoglycaemia must be considered. 
 
Adherence of the patient to the dose regimen and dietary regimen, correct insulin administration and 
awareness of hypoglycaemia symptoms are essential to reduce the risk of hypoglycaemia. Factors 
increasing the susceptibility to hypoglycaemia require particularly close monitoring and may 
necessitate dose adjustment. These include: 
- change in the injection area, 
- improved insulin sensitivity (e.g. by removal of stress factors), 
- unaccustomed, increased or prolonged physical activity, 
- intercurrent illness (e.g. vomiting, diarrhoea), 
- inadequate food intake, 
- missed meals, 
- alcohol consumption, 
- certain uncompensated endocrine disorders (e.g. in hypothyroidism and in anterior pituitary or 

adrenocortical insufficiency), 
- concomitant treatment with certain other medicinal products. 
 
Intercurrent illness 
Intercurrent illness requires intensified metabolic monitoring. In many cases, urine tests for ketones 
are indicated, and often it is necessary to adjust the insulin dose. The insulin requirement is often 
increased. Patients with type 1 diabetes must continue to consume at least a small amount of 
carbohydrates on a regular basis, even if they are able to eat only little or no food, or are vomiting etc. 
and they must never omit insulin entirely. 
 
Handling of the pen 
Before using SoloStar, the Instructions for Use included in the Package Leaflet must be read carefully. 
SoloStar has to be used as recommended in these Instructions for Use (see section 6.6). 
 

 

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Medication errors 
Medication errors have been reported in which other Insulin Human Winthrop formulations or other 
insulins have been accidentally administered. Insulin label must always be checked before each 
injection to avoid medication errors between insulin human and other insulins. 
 
Combination of Insulin Human Winthrop with pioglitazone 
Cases of cardiac failure have been reported when pioglitazone was used in combination with insulin, 
especially in patients with risk factors for development of cardiac heart failure. This should be kept in 
mind if treatment with the combination of pioglitazone and Insulin Human Winthrop is considered. If 
the combination is used, patients should be observed for signs and symptoms of heart failure, weight 
gain and oedema. Pioglitazone should be discontinued if any deterioration in cardiac symptoms 
occurs.  
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
A number of substances affect glucose metabolism and may require dose adjustment of human insulin. 
 
Substances that may enhance the blood-glucose-lowering effect and increase susceptibility to 
hypoglycaemia include oral antidiabetic medicinal products, angiotensin converting enzyme (ACE) 
inhibitors, disopyramide, fibrates, fluoxetine, monoamine oxidase (MAO) inhibitors, pentoxifylline, 
propoxyphene, salicylates and sulphonamide antibiotics. 
 
Substances that may reduce the blood-glucose-lowering effect include corticosteroids, danazol, 
diazoxide, diuretics, glucagon, isoniazid, oestrogens and progestogens (e.g. in oral contraceptives), 
phenothiazine derivatives, somatropin, sympathomimetic medicinal products (e.g. epinephrine 
[adrenaline], salbutamol, terbutaline), thyroid hormones, protease inhibitors and atypical antipsychotic 
medicinal products (e.g. olanzapine and clozapine). 
 
Beta-blockers, clonidine, lithium salts or alcohol may either potentiate or weaken the 
blood-glucose-lowering effect of insulin. Pentamidine may cause hypoglycaemia which may 
sometimes be followed by hyperglycaemia. 
 
In addition, under the influence of sympatholytic medicinal products such as beta-blockers, clonidine, 
guanethidine and reserpine, the signs of adrenergic counter-regulation may be reduced or absent. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
For insulin human, no clinical data on exposed pregnancies from controlled clinical studies are 
available. Insulin does cross the placental barrier, although not in clinically significant amount. A 
limited amount of data on pregnant women (less than 300 pregnancy outcomes reported) exposed to 
marketed insulin human indicates no safety issues in use of insulin human in pregnancy. Caution 
should be exercised when prescribing to pregnant women. 
 
It is essential for patients with pre-existing or gestational diabetes to maintain good metabolic control 
throughout pregnancy. Insulin requirements may decrease during the first trimester and generally 
increase during the second and third trimesters. Immediately after delivery, insulin requirements 
decline rapidly (increased risk of hypoglycaemia). Careful monitoring of glucose control is essential. 
 
Breast-feeding 
No effects on the suckling child are anticipated. Insulin Human Winthrop Comb 50 can be used during 
breast-feeding. Breast-feeding women may require adjustments in insulin dose and diet. 
 
Fertility 
No clinical or animal data with insulin human on male or female fertility are available. 
 

 

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4.7 Effects on ability to drive and use machines 
 
The patient's ability to concentrate and react may be impaired as a result of hypoglycaemia or 
hyperglycaemia or, for example, as a result of visual impairment. This may constitute a risk in 
situations where these abilities are of special importance (e.g. driving a car or using machines). 
 
Patients should be advised to take precautions to avoid hypoglycaemia whilst driving. This is 
particularly important in those who have reduced or absent awareness of the warning symptoms of 
hypoglycaemia or have frequent episodes of hypoglycaemia. It should be considered whether it is 
advisable to drive or use machines in these circumstances. 
 
4.8 Undesirable effects 
 
Summary of the safety profile  
Hypoglycaemia, in general the most frequent adverse reaction of insulin therapy, may occur if the 
insulin dose is too high in relation to the insulin requirement. In clinical studies and during marketed 
use, the frequency varies with patient population and dose regimens. Therefore, no specific frequency 
can be presented. 
 
Tabulated list of adverse reactions 
The following related adverse reactions from clinical investigations are listed below by system organ 
class and in order of decreasing incidence: very common (≥1/10); common (≥1/100 to <1/10); 
uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000), not known 
(cannot be estimated from the available data). 
 
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. 
 
MedDRA system 
organ classes 

Common Uncommon Not known 

Immune system 
disorders 

 Shock Immediate type allergic 
reactions (hypotension, 
angioneurotic oedema, 
bronchospasm, 
generalised skin 
reactions); 
Anti-insulin antibodies 

Metabolism and 
nutrition disorders 

Oedema  Hypoglycaemia; 
Sodium retention 

Eye disorders   Proliferative retinopathy; 
Diabetic retinopathy; 
Visual impairment 

Skin and subcutaneous 
tissue disorders 

  Lipodystrophy 

General disorders and 
administration site 
conditions 

Injection site reactions Injection site 
urticaria 

Injection site 
inflammation;  
Injection site pain; 
Injection site pruritus; 
Injection site erythema; 
Injection site swelling 

 
Description of selected adverse reactions 
Immune system disorders 
Immediate type allergic reactions to insulin or to the excipients may be life-threatening. 
 
Insulin administration may cause anti-insulin antibodies to form. In rare cases, the presence of such 
anti-insulin antibodies may necessitate adjustment of the insulin dose in order to correct a tendency to 
hyper- or hypoglycaemia. 

 

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Metabolism and nutrition disorders 
Severe hypoglycaemic attacks, especially if recurrent, may lead to neurological damage. 
Prolonged or severe hypoglycaemic episodes may be life-threatening. 
 
In many patients, the signs and symptoms of neuroglycopenia are preceded by signs of adrenergic 
counter-regulation. Generally, the greater and more rapid the decline in blood glucose, the more 
marked is the phenomenon of counter-regulation and its symptoms. 
 
Insulin may cause sodium retention and oedema, particularly if previously poor metabolic control is 
improved by intensified insulin therapy. 
 
Eyes disorders 
A marked change in glycaemic control may cause temporary visual impairment, due to temporary 
alteration in the turgidity and refractive index of the lens. 
 
Long-term improved glycaemic control decreases the risk of progression of diabetic retinopathy. 
However, intensification of insulin therapy with abrupt improvement in glycaemic control may be 
associated with temporary worsening of diabetic retinopathy. 
 
Skin and subcutaneous tissue disorders 
Lipodystrophy may occur at the injection site and delay local insulin absorption. Continuous rotation 
of the injection site within the given injection area may help to reduce or prevent these reactions. 
 
General disorders and administration site conditions 
Most minor reactions to insulins at the injection site usually resolve in a few days to a few weeks. 
 
4.9 Overdose 
 
Symptoms 
Insulin overdose may lead to severe and sometimes long-term and life-threatening hypoglycaemia. 
 
Management 
Mild episodes of hypoglycaemia can usually be treated with oral carbohydrates. Adjustments in dose 
regimen of the medicinal product, meal patterns, or physical activity may be needed. 
 
More severe episodes with coma, seizure, or neurologic impairment may be treated with 
intramuscular/subcutaneous glucagon or concentrated intravenous glucose. Sustained carbohydrate 
intake and observation may be necessary because hypoglycaemia may recur after apparent clinical 
recovery. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Drugs used in diabetes, insulins and analogues for injection, 
intermediate-acting combined with fast-acting, ATC Code: A10AD01. 
 
Mechanism of action 
Insulin 
- lowers blood glucose and promotes anabolic effects as well as decreasing catabolic effects, 
- increases the transport of glucose into cells as well as the formation of glycogen in the muscles 

and the liver, and improves pyruvate utilisation. It inhibits glycogenolysis and gluconeogenesis, 
- increases lipogenesis in the liver and adipose tissue and inhibits lipolysis, 
- promotes the uptake of amino acids into cells and promotes protein synthesis, 
- enhances the uptake of potassium into cells. 

 

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Pharmacodynamic effects 
Insulin Human Winthrop Comb 50 (a biphasic isophane insulin suspension with 50% dissolved 
insulin) is an insulin with rapid onset and moderately long duration of action. Following subcutaneous 
injection, onset of action is within 30 minutes, the phase of maximum action is between 1.5 and 
4 hours after injection and the duration of action is 12 to 16 hours. 
 
5.2 Pharmacokinetic properties 
 
In healthy subjects, the serum half-life of insulin is approximately 4 to 6 minutes. It is longer in 
patients with severe renal insufficiency. However, it must be noted that the pharmacokinetics of 
insulin do not reflect its metabolic action. 
 
5.3 Preclinical safety data 
 
The acute toxicity was studied following subcutaneous administration in rats. No evidence of toxic 
effects was found. Studies of pharmacodynamic effects following subcutaneous administration in 
rabbits and dogs revealed the expected hypoglycaemic reactions. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Protamine sulphate, 
metacresol, 
phenol, 
zinc chloride, 
sodium dihydrogen phosphate dihydrate, 
glycerol, 
sodium hydroxide, 
hydrochloric acid (for pH adjustment), 
water for injections. 
 
6.2 Incompatibilities 
 
This medicinal product must not be mixed with other medicinal products except those mentioned in 
section 6.6. 
 
Insulin Human Winthrop Comb 50 must not be mixed with solutions containing reducing substances 
such as thioles and sulphites.  
 
Mixing of insulins 
Insulin Human Winthrop Comb 50 must not be mixed with any other insulin or with insulin 
analogues. 
 
Care must be taken to ensure that no alcohol or other disinfectants enter the insulin suspension. 
 
6.3 Shelf life 
 
2 years. 
 
Shelf life after first use of the pen 
The pen in-use or carried as a spare may be stored for a maximum of 4 weeks not above 25°C and 
away from direct heat or direct light. 
Pens in-use must not be stored in the refrigerator. 
The pen cap must be put back on the pen after each injection in order to protect from light. 

 

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6.4 Special precautions for storage 
 
Not in-use pens 
Store in a refrigerator (2°C – 8°C). 
Do not freeze. 
Do not put Insulin Human Winthrop Comb 50 next to the freezer compartment or a freezer pack. 
Keep the pre-filled pen in the outer carton in order to protect from light. 
 
In-use pens 
For storage conditions after first opening of the medicinal product, see section 6.3. 
 
6.5 Nature and contents of container 
 
3 ml suspension in a cartridge (type 1 colourless glass) with a plunger (bromobutyl rubber (type 1)) 
and a flanged cap (aluminium) with a stopper (bromobutyl or laminate of polyisoprene and 
bromobutyl rubber (type 1)). 
Each cartridge contains 3 balls (stainless steel). 
The cartridges are sealed in a disposable pen injector. 
Injection needles are not included in the pack. 
Packs of 3, 4, 5, 6, 9 or 10 pens are available. 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal and other handling 
 
Before first use, Insulin Human Winthrop Comb 50 must be kept at room temperature for 1 to 2 hours 
and then resuspended to check the contents. This is best done by gently tilting the pen back and forth 
(at least ten times). Each cartridge contains three small metal balls to facilitate quick and thorough 
mixing of the contents. Later on, the insulin must be resuspended again prior to each injection. 
 
After resuspension, the fluid must have a uniformly milky appearance. Insulin Human Winthrop 
Comb 50 must not be used if this cannot be achieved, i.e. if the suspension remains clear, for example, 
or if clumps, particles or flocculation appear in the insulin or stick to the wall or bottom of the 
cartridge. These changes sometimes give the cartridge a frosted appearance. In such cases, a new pen 
yielding a uniform suspension must be used. It is also necessary to change to a new pen if the insulin 
requirement changes substantially. 
Empty pens must never be re-used and must be properly discarded. 
 
To prevent the possible transmission of disease, each pen must be used by one patient only. 
 
It must be remembered that 
- insulin protamine crystals dissolve in an acid pH range, 
- the soluble insulin part precipitates out at a pH of approximately 4.5 to 6.5. 
 
Insulin label must always be checked before each injection to avoid medication errors between insulin 
human and other insulins (see section 4.4). 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 

 

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Handling of the pen 
The patient should be advised to read the instructions for use included in the package leaflet 
carefully before using SoloStar. 
 

 
Schematic diagram of the pen 

 
Important information for use of SoloStar: 
 
• Before each use, a new needle must always be carefully attached and a safety test must be 

performed. A dose should not be selected and/or the injection button should not be pressed 
without a needle attached. Only use needles that are compatible for use with SoloStar. 

• Special caution must be taken to avoid accidental needle injury and transmission of infection. 
• SoloStar must never be used if it is damaged or if the patient is not sure if it is working properly. 
• The patient must always have a spare SoloStar available in case the SoloStar is lost or damaged. 
 
Storage instructions  
 
Please check section 6.4 for instructions on how to store SoloStar. 
 
If SoloStar is in cool storage, it should be taken out 1 to 2 hours before injection to allow it to warm 
up. Cold insulin is more painful to inject. 
 
The used SoloStar must be discarded as required by your local authorities. 
 
Maintenance 
 
SoloStar has to be protected from dust and dirt. 
 
The outside of the SoloStar can be cleaned by wiping it with a damp cloth. 
 
The pen must not be soaked, washed or lubricated as this may damage it. 
 
SoloStar is designed to work accurately and safely. It should be handled with care. The patient should 
avoid situations where SoloStar may be damaged. If the patient is concerned that the SoloStar may be 
damaged, he must use a new one. 
 
Step 1. Check the insulin 
 
The label on the pen should be checked to make sure it contains the correct insulin. Insulin Human 
Winthrop SoloStar is white with a colour on the injection button. The injection button colour will vary 
based on the formulation of Insulin Human Winthrop insulin used. 
 
After removing the pen cap, the appearance of the insulin should also be checked: 
The insulin suspensions (Insulin Human Winthrop Basal or Insulin Human Winthrop mixtures) should 
be mixed by turning SoloStar up and down at least 10 times to resuspend the insulin. The pen should 
be turned gently to avoid foaming in the cartridge. After mixing, the insulin suspensions must have an 
evenly milky-white appearance. 
 
Step 2. Attach the needle 
 
Only needles that are compatible for use with SoloStar should be used. 

 

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A new sterile needle will be always used for each injection. After removing the cap, the needle should 
be carefully attached straight onto the pen. 
 
Step 3. Perform a safety test  
 
Prior to each injection, a safety test has to be performed to ensure that pen and needle work properly 
and to remove air bubbles. 
 
Select a dose of 2 units. 
The outer and inner needle caps should be removed. 
 
While holding the pen with the needle pointing upwards, the insulin reservoir should be tapped gently 
with the finger so that any air bubbles rise up towards the needle. 
 
Then the injection button should be pressed in completely. 
 
If insulin has been expelled through the needle tip, then the pen and the needle are working properly. 
If no insulin appears at the needle tip, step 3 should be repeated until insulin appears at the needle tip. 
 
Step 4. Select the dose 
 
The dose can be set in steps of 1 unit, from a minimum of 1 unit to a maximum of 80 units. If a dose 
greater than 80 units is required, it should be given as two or more injections. 
 
The dose window must show “0” following the safety test. The dose can then be selected. 
 
Step 5. Inject the dose 
 
The patient should be informed on the injection technique by his health care professional. 
The needle should be inserted into the skin. 
The injection button should be pressed in completely. Then the injection button should be held down 
10 seconds before withdrawing the needle. This ensures that the full dose of insulin has been injected. 
 
Step 6. Remove and discard the needle 
 
The needle should always be removed after each injection and discarded. This helps prevent 
contamination and/or infection, entry of air into the insulin reservoir and leakage of insulin. Needles 
mut not be re-used. 
 
Special caution must be taken when removing and disposing of the needle. Recommended safety 
measures for removal and disposal of needles must be followed (e.g. a one handed capping technique) 
in order to reduce the risk of accidental needle injury and transmission of infectious diseases. 
 
The pen cap should be replaced on the pen. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Sanofi-Aventis Deutschland GmbH, D-65926 Frankfurt am Main, Germany 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/06/368/137 
EU/1/06/368/138 
EU/1/06/368/139 

 

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EU/1/06/368/140 
EU/1/06/368/141 
EU/1/06/368/142 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 17 January 2007 
Date of latest renewal: 17 January 2012 
 
 
10. DATE OF REVISION OF THE TEXT 
 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu 

 

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1. NAME OF THE MEDICINAL PRODUCT 
 
Insulin Human Winthrop Infusat 100 IU/ml solution for injection in a vial 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each ml contains 100 IU insulin human (equivalent to 3.5 mg).  
Each vial contains 10 ml of solution for injection, equivalent to 1000 IU insulin. One IU (International 
Unit) corresponds to 0.035 mg of anhydrous human insulin. 
 
Insulin Human Winthrop Infusat is a neutral insulin solution (regular insulin). 
 
Human insulin is produced by recombinant DNA technology in Escherichia coli. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Solution for injection in a vial. 
 
Clear, colourless solution. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Diabetes mellitus where treatment with insulin is required. 
 
4.2 Posology and method of administration 
 
Posology 
Insulin Human Winthrop Infusat has been specially designed for use in external portable insulin 
pumps. It is specially stabilised to minimise loss of efficacy which may result from mechanical and 
thermal stress in such pumps. Insulin Human Winthrop Infusat is therefore also suitable for 
continuous insulin infusion with other, conventional injection syringe pumps. 
 
The desired blood glucose levels and the insulin dose regimen must be determined individually and 
adjusted to suit the patient's diet, physical activity and life-style. 
 
Daily doses and timing of administration 
When used in external portable insulin pumps, part of the daily insulin dose is infused continuously 
("basal rate"), and the rest is administered in the form of bolus injections before meals. Refer to the 
operating instructions for detailed information about the infusion pump, its functions and the 
necessary safety precautions. 
 
There are no fixed rules for insulin dose regimen. However, the average insulin requirement is often 
0.5 to 1.0 IU per kg body weight per day. The basal metabolic requirement is 40% to 60% of the total 
daily requirement. Consequently, about 40% to 60% of the daily dose is administered at a basal rate, 
and the rest is given as bolus injections before meals. 
 
Secondary dose adjustment 
Improved metabolic control may result in increased insulin sensitivity, leading to a reduced insulin 
requirement. Dose adjustment may also be required, for example, if 
- the patient's weight changes, 

 

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- the patient's life-style changes, 
- other circumstances arise that may promote an increased susceptibility to hypo- or 

hyperglycaemia (see section 4.4). 
 
Special populations 
Elderly population (≧65 years old) 
In the elderly, progressive deterioration of renal function may lead to a steady decrease in insulin 
requirements. 
 
Renal impairment 
In patients with renal impairment, insulin requirements may be diminished due to reduced insulin 
metabolism. 
 
Hepatic impairment 
In patients with severe hepatic impairment, insulin requirements may be diminished due to reduced 
capacity for gluconeogenesis and reduced insulin metabolism. 
 
Method of administration 
Insulin Human Winthrop Infusat must not be used in peristaltic pumps with silicone tubing. Refer to 
the technical manual for contraindications relating to the use of insulin pumps. 
 
Insulin Human Winthrop Infusat may be infused by the subcutaneous route. It is designed for use in 
the Hoechst Infusor and H-Tron insulin pumps. It may also be used in other insulin pumps for which it 
has been shown that they are suitable for this insulin (see pump manual). Only tetrafluoroethylene or 
polyethylene catheters must be used. Insulin Human Winthrop Infusat must not be used in peristaltic 
pumps with silicone tubing.  
 
Insulin must always be infused under aseptic conditions. This is facilitated by the special equipment 
available for the insulin pumps (e.g. catheters, cannulas). 
 
Insulin absorption and hence the blood-glucose-lowering effect of a dose may vary from one injection 
area to another (e.g. the abdominal wall compared with the thigh). The puncture site within a given 
injection area must be changed regularly (generally, every 1 to 3 days). 
 
For further details on handling, see section 6.6. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
 
4.4 Special warnings and precautions for use 
 
Patients hypersensitive to Insulin Human Winthrop Infusat for whom no better tolerated preparation is 
available must only continue treatment under close medical supervision and – where necessary – in 
conjunction with anti-allergic treatment. 
 
In patients with an allergy to animal insulin intradermal skin testing is recommended prior to a 
transfer to Insulin Human Winthrop Infusat, since they may experience immunological 
cross-reactions. 
 
In case of hypoglycaemia, the insulin pump should temporarily be turned off, at least until the patient 
has recovered complete consciousness. 
 
In case of insufficient glucose control or a tendency to hyper- or hypoglycaemic episodes, the patient's 
adherence to the prescribed treatment regimen, injection sites and proper injection technique and all 
other relevant factors must be reviewed before dose adjustment is considered. 
 

 

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Transfer to Insulin Human Winthrop Infusat 
Transferring a patient to another type or brand of insulin should be done under strict medical 
supervision. Changes in strength, brand (manufacturer), type (regular, NPH, lente, long-acting, etc.), 
origin (animal, human, human insulin analogue) and/or method of manufacture may result in the need 
for a change in dosage. 
The need to adjust (e.g. reduce) the dose may become evident immediately after transfer. 
Alternatively, it may emerge gradually over a period of several weeks. 
 
Following transfer from an animal insulin to human insulin, dose regimen reduction may be required 
in particular in patients who 
- were previously already controlled on rather low blood glucose levels, 
- have a tendency to hypoglycaemia, 
- previously required high insulin doses due to the presence of insulin antibodies. 
 
Close metabolic monitoring is recommended during the transition and in the initial weeks thereafter. In 
patients who require high insulin doses because of the presence of insulin antibodies, transfer under 
medical supervision in a hospital or similar setting must be considered. 
 
Hypoglycaemia 
Hypoglycaemia may occur if the insulin dose is too high in relation to the insulin requirement. 
 
Particular caution should be exercised, and intensified blood glucose monitoring is advisable in 
patients in whom hypoglycaemic episodes might be of particular clinical relevance, such as in patients 
with significant stenoses of the coronary arteries or of the blood vessels supplying the brain (risk of 
cardiac or cerebral complications of hypoglycaemia) as well as in patients with proliferative 
retinopathy, particularly if not treated with photocoagulation (risk of transient amaurosis following 
hypoglycaemia). 
 
Patients should be aware of circumstances where warning symptoms of hypoglycaemia are 
diminished. The warning symptoms of hypoglycaemia may be changed, be less pronounced or be 
absent in certain risk groups. These include patients: 
- in whom glycaemic control is markedly improved, 
- in whom hypoglycaemia develops gradually, 
- who are elderly,  
- after transfer from animal insulin to human insulin, 
- in whom an autonomic neuropathy is present, 
- with a long history of diabetes, 
- suffering from a psychiatric illness, 
- receiving concurrent treatment with certain other medicinal products (see section 4.5). 
Such situations may result in severe hypoglycaemia (and possibly loss of consciousness) prior to the 
patient's awareness of hypoglycaemia. 
 
If normal or decreased values for glycated haemoglobin are noted, the possibility of recurrent, 
unrecognised (especially nocturnal) episodes of hypoglycaemia must be considered. 
 
Adherence of the patient to the dose regimen and dietary regimen, correct insulin administration and 
awareness of hypoglycaemia symptoms are essential to reduce the risk of hypoglycaemia. Factors 
increasing the susceptibility to hypoglycaemia require particularly close monitoring and may 
necessitate dose adjustment. These include: 
- change in the injection area, 
- improved insulin sensitivity (e.g. by removal of stress factors), 
- unaccustomed, increased or prolonged physical activity, 
- intercurrent illness (e.g. vomiting, diarrhoea), 
- inadequate food intake, 
- missed meals, 
- alcohol consumption, 

 

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- certain uncompensated endocrine disorders (e.g. in hypothyroidism and in anterior pituitary or 
adrenocortical insufficiency), 

- concomitant treatment with certain other medicinal products. 
 
Insulin pump faults 
Hyperglycaemia, ketoacidosis and coma may develop within hours if the pump catheter is obstructed 
completely. Whenever the patient notices a rapid increase in blood glucose which does not respond to 
a bolus dose, a check must be made for possible catheter obstruction. 
 
In the event of a pump malfunction, patients must always have injection devices (injection syringe or 
pen) and insulin available for subcutaneous injection. For details on safety precautions in the use of 
insulin pumps, refer to the operator’s manual. 
 
Intercurrent illness 
Intercurrent illness requires intensified metabolic monitoring. In many cases, urine tests for ketones 
are indicated, and often it is necessary to adjust the insulin dose. The insulin requirement is often 
increased. Patients with type 1 diabetes must continue to consume at least a small amount of 
carbohydrates on a regular basis, even if they are able to eat only little or no food, or are vomiting etc. 
and they must never omit insulin entirely. 
 
Medication errors 
Medication errors have been reported in which other Insulin Human Winthrop formulations or other 
insulins have been accidentally administered. Insulin label must always be checked before each 
injection to avoid medication errors between insulin human and other insulins. 
 
Combination of Insulin Human Winthrop with pioglitazone 
Cases of cardiac failure have been reported when pioglitazone was used in combination with insulin, 
especially in patients with risk factors for development of cardiac heart failure. This should be kept in 
mind if treatment with the combination of pioglitazone and Insulin Human Winthrop is considered. If 
the combination is used, patients should be observed for signs and symptoms of heart failure, weight 
gain and oedema. Pioglitazone should be discontinued if any deterioration in cardiac symptoms 
occurs.  
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
A number of substances affect glucose metabolism and may require dose adjustment of human insulin. 
 
Substances that may enhance the blood-glucose-lowering effect and increase susceptibility to 
hypoglycaemia include oral antidiabetic medicinal products, angiotensin converting enzyme (ACE) 
inhibitors, disopyramide, fibrates, fluoxetine, monoamine oxidase (MAO) inhibitors, pentoxifylline, 
propoxyphene, salicylates and sulphonamide antibiotics. 
 
Substances that may reduce the blood-glucose-lowering effect include corticosteroids, danazol, 
diazoxide, diuretics, glucagon, isoniazid, oestrogens and progestogens (e.g. in oral contraceptives), 
phenothiazine derivatives, somatropin, sympathomimetic medicinal products (e.g. epinephrine 
[adrenaline], salbutamol, terbutaline), thyroid hormones, protease inhibitors and atypical antipsychotic 
medicinal products (e.g. olanzapine and clozapine). 
 
Beta-blockers, clonidine, lithium salts or alcohol may either potentiate or weaken the 
blood-glucose-lowering effect of insulin. Pentamidine may cause hypoglycaemia which may 
sometimes be followed by hyperglycaemia. 
 
In addition, under the influence of sympatholytic medicinal products such as beta-blockers, clonidine, 
guanethidine and reserpine, the signs of adrenergic counter-regulation may be reduced or absent. 
 

 

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4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
For insulin human, no clinical data on exposed pregnancies from controlled clinical studies are 
available. Insulin does cross the placental barrier, although not in clinically significant amount. A 
limited amount of data on pregnant women (less than 300 pregnancy outcomes reported) exposed to 
marketed insulin human indicates no safety issues in use of insulin human in pregnancy. Caution 
should be exercised when prescribing to pregnant women. 
 
It is essential for patients with pre-existing or gestational diabetes to maintain good metabolic control 
throughout pregnancy. Insulin requirements may decrease during the first trimester and generally 
increase during the second and third trimesters. Immediately after delivery, insulin requirements 
decline rapidly (increased risk of hypoglycaemia). Careful monitoring of glucose control is essential. 
 
Breast-feeding 
No effects on the suckling child are anticipated. Insulin Human Winthrop Rapid can be used during 
breast-feeding. Breast-feeding women may require adjustments in insulin dose and diet. 
 
Fertility 
No clinical or animal data with insulin human on male or female fertility are available. 
 
4.7 Effects on ability to drive and use machines 
 
The patient's ability to concentrate and react may be impaired as a result of hypoglycaemia or 
hyperglycaemia or, for example, as a result of visual impairment. This may constitute a risk in 
situations where these abilities are of special importance (e.g. driving a car or using machines). 
 
Patients should be advised to take precautions to avoid hypoglycaemia whilst driving. This is 
particularly important in those who have reduced or absent awareness of the warning symptoms of 
hypoglycaemia or have frequent episodes of hypoglycaemia. It should be considered whether it is 
advisable to drive or use machines in these circumstances. 
 
4.8 Undesirable effects 
 
Summary of the safety profile  
Hypoglycaemia, in general the most frequent adverse reaction of insulin therapy, may occur if the 
insulin dose is too high in relation to the insulin requirement. In clinical studies and during marketed 
use, the frequency varies with patient population and dose regimens. Therefore, no specific frequency 
can be presented. 
 
Tabulated list of adverse reactions 
The following related adverse reactions from clinical investigations are listed below by system organ 
class and in order of decreasing incidence: very common (≥1/10); common (≥1/100 to <1/10); 
uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000), not known 
(cannot be estimated from the available data). 
 
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. 
 

 

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MedDRA system 
organ classes 

Common Uncommon Not known 

Immune system 
disorders 

 Shock Immediate type 
allergic reactions 
(hypotension, 
angioneurotic oedema, 
bronchospasm, 
generalised skin 
reactions); 
Anti-insulin antibodies 

Metabolism and 
nutrition disorders 

Oedema  Hypoglycaemia; 
Sodium retention 

Eye disorders   Proliferative 
retinopathy; 
Diabetic retinopathy; 
Visual impairment 

Skin and subcutaneous 
tissue disorders 

  Lipodystrophy 

General disorders and 
administration site 
conditions 

Injection site reactions Injection site urticaria Injection site 
inflammation;  
Injection site pain; 
Injection site pruritus; 
Injection site erythema; 
Injection site swelling 

 
Description of selected adverse reactions 
Immune system disorders 
Immediate type allergic reactions to insulin or to the excipients may be life-threatening. 
 
Insulin administration may cause anti-insulin antibodies to form. In rare cases, the presence of such 
anti-insulin antibodies may necessitate adjustment of the insulin dose in order to correct a tendency to 
hyper- or hypoglycaemia. 
 
Metabolism and nutrition disorders 
Severe hypoglycaemic attacks, especially if recurrent, may lead to neurological damage. 
Prolonged or severe hypoglycaemic episodes may be life-threatening. 
 
In many patients, the signs and symptoms of neuroglycopenia are preceded by signs of adrenergic 
counter-regulation. Generally, the greater and more rapid the decline in blood glucose, the more 
marked is the phenomenon of counter-regulation and its symptoms. 
 
Insulin may cause sodium retention and oedema, particularly if previously poor metabolic control is 
improved by intensified insulin therapy. 
 
Eyes disorders 
A marked change in glycaemic control may cause temporary visual impairment, due to temporary 
alteration in the turgidity and refractive index of the lens. 
 
Long-term improved glycaemic control decreases the risk of progression of diabetic retinopathy. 
However, intensification of insulin therapy with abrupt improvement in glycaemic control may be 
associated with temporary worsening of diabetic retinopathy. 
 
Skin and subcutaneous tissue disorders 
Lipodystrophy may occur at the injection site and delay local insulin absorption. Continuous rotation 
of the injection site within the given injection area may help to reduce or prevent these reactions. 
 

 

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General disorders and administration site conditions 
Most minor reactions to insulins at the injection site usually resolve in a few days to a few weeks. 
 
4.9 Overdose 
 
Symptoms 
Insulin overdose may lead to severe and sometimes long-term and life-threatening hypoglycaemia. 
 
Management 
Mild episodes of hypoglycaemia can usually be treated with oral carbohydrates. Adjustments in dose 
regimen of the medicinal product, meal patterns, or physical activity may be needed. 
 
More severe episodes with coma, seizure, or neurologic impairment may be treated with 
intramuscular/subcutaneous glucagon or concentrated intravenous glucose. Sustained carbohydrate 
intake and observation may be necessary because hypoglycaemia may recur after apparent clinical 
recovery. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Drugs used in diabetes, insulins and analogues for injection, fast-acting, 
ATC Code: A10AB01. 
 
Mechanism of action 
Insulin 
- lowers blood glucose and promotes anabolic effects as well as decreasing catabolic effects, 
- increases the transport of glucose into cells as well as the formation of glycogen in the muscles 
 and the liver, and improves pyruvate utilisation. It inhibits glycogenolysis and gluconeogenesis, 
- increases lipogenesis in the liver and adipose tissue and inhibits lipolysis, 
- promotes the uptake of amino acids into cells and promotes protein synthesis, 
- enhances the uptake of potassium into cells. 
 
Pharmacodynamic effects 
Insulin Human Winthrop Infusat is an insulin with rapid onset and short duration of action. 
 
5.2 Pharmacokinetic properties 
 
In healthy subjects, the serum half-life of insulin is approximately 4 to 6 minutes. It is longer in 
patients with severe renal insufficiency. However, it must be noted that the pharmacokinetics of 
insulin do not reflect its metabolic action. 
 
5.3 Preclinical safety data 
 
The acute toxicity was studied following subcutaneous administration in rats. No evidence of toxic 
effects was found. Local tolerability studies following subcutaneous and intramuscular administration 
in rabbits gave no remarkable findings. Studies of pharmacodynamic effects following subcutaneous 
administration in rabbits and dogs revealed the expected hypoglycaemic reactions. 
 
 

 

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6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Phenol, 
zinc chloride, 
trometamol, 
poloxamer 171, 
glycerol, 
hydrochloric acid (for pH adjustment), 
water for injections. 
 
6.2 Incompatibilities 
 
This medicinal product must not be mixed with other medicinal products except those mentioned in 
section 6.6. 
 
Insulin Human Winthrop Infusat must not be mixed with solutions containing reducing substances 
such as thioles and sulphites.  
 
Mixing of insulins 
Insulin Human Winthrop Infusat must not be mixed with any other insulin or with insulin analogues. 
 
Care must be taken to ensure that no alcohol or other disinfectants enter the insulin solution. 
 
6.3 Shelf life 
 
2 years. 
 
Insulin that has been filled into the pump reservoir may be used for two weeks thereafter. 
 
Shelf life after first use of the vial 
The product may be stored for a maximum of 4 weeks not above 25°C and away from direct heat or 
direct light.  
Keep the vial in the outer carton in order to protect from light. 
It is recommended that the date of the first use be noted on the label. 
 
6.4 Special precautions for storage 
 
Unopened vials 
Store in a refrigerator (2°C - 8°C). 
Do not freeze. 
Do not put Insulin Human Winthrop Infusat next to the freezer compartment or a freezer pack. 
Keep the vial in the outer carton in order to protect from light. 
 
Opened vials 
For storage conditions after first opening of the medicinal product, see section 6.3. 
 
6.5 Nature and contents of container 
 
10 ml solution in a vial (type 1 colourless glass) with a flanged cap (aluminium), a stopper 
(chlorobutyl rubber (type 1)) and a tear-off cap (polypropylene). 
Packs of 3 vials are available. 
 

 

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6.6 Special precautions for disposal and other handling 
 
Insulin Human Winthrop Infusat must only be used if the solution is clear, colourless, with no solid 
particles visible, and if it is of a water-like consistency. 
 
For use in an infusion pump, Insulin Human Winthrop Infusat is filled into the sterile cartridge of the 
pump. The cartridge must only be used once. 
 
Before use, the filled cartridge must be kept at room temperature for 1 to 2 hours. Air bubbles must be 
removed before starting the infusion (see the operator’s manual for the pump). 
 
If the infusion pump malfunctions, the solution may be drawn from the cartridge into an injection 
syringe (suitable for an insulin with 100 IU/ml) and injected. 
 
Insulin Human Winthrop Infusat must not be used in peristaltic pumps with silicone tubing. Refer to 
the technical manual for contraindications relating to the use of insulin pumps. 
 
It must be remembered that neutral regular insulin precipitates out at a pH of approximately 4.5 to 6.5. 
 
Insulin label must always be checked before each injection to avoid medication errors between insulin 
human and other insulins (see section 4.4). 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Sanofi-Aventis Deutschland GmbH, D-65926 Frankfurt am Main, Germany 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/06/368/056 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 17 January 2007 
Date of latest renewal: 17 January 2012 
 
 
10. DATE OF REVISION OF THE TEXT 
 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu 

 

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1. NAME OF THE MEDICINAL PRODUCT 
 
Insulin Human Winthrop Infusat 100 IU/ml solution for injection in a cartridge 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each ml contains 100 IU insulin human (equivalent to 3.5 mg).  
Each cartridge contains 3.15 ml of solution for injection, equivalent to 315 IU insulin. One IU 
(International Unit) corresponds to 0.035 mg of anhydrous human insulin. 
 
Insulin Human Winthrop Infusat is a neutral insulin solution (regular insulin). 
 
Human insulin is produced by recombinant DNA technology in Escherichia coli. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Solution for injection in a cartridge. 
 
Clear, colourless solution. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Diabetes mellitus where treatment with insulin is required. 
 
4.2 Posology and method of administration 
 
Posology 
Insulin Human Winthrop Infusat has been specially designed for use in external portable insulin 
pumps. It is specially stabilised to minimise loss of efficacy which may result from mechanical and 
thermal stress in such pumps. Insulin Human Winthrop Infusat is therefore also suitable for 
continuous insulin infusion with other, conventional injection syringe pumps. 
 
The desired blood glucose levels and the insulin dose regimen must be determined individually and 
adjusted to suit the patient's diet, physical activity and life-style. 
 
Daily doses and timing of administration 
When used in external portable insulin pumps, part of the daily insulin dose is infused continuously 
("basal rate"), and the rest is administered in the form of bolus injections before meals. Refer to the 
operating instructions for detailed information about the infusion pump, its functions and the 
necessary safety precautions. 
 
There are no fixed rules for insulin dose regimen. However, the average insulin requirement is often 
0.5 to 1.0 IU per kg body weight per day. The basal metabolic requirement is 40% to 60% of the total 
daily requirement. Consequently, about 40% to 60% of the daily dose is administered at a basal rate, 
and the rest is given as bolus injections before meals. 
 
Secondary dose adjustment 
Improved metabolic control may result in increased insulin sensitivity, leading to a reduced insulin 
requirement. Dose adjustment may also be required, for example, if 
- the patient's weight changes, 

 

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- the patient's life-style changes, 
- other circumstances arise that may promote an increased susceptibility to hypo- or 

hyperglycaemia (see section 4.4). 
 
Special populations 
Elderly population (≧65 years old) 
In the elderly, progressive deterioration of renal function may lead to a steady decrease in insulin 
requirements. 
 
Renal impairment 
In patients with renal impairment, insulin requirements may be diminished due to reduced insulin 
metabolism. 
 
Hepatic impairment 
In patients with severe hepatic impairment, insulin requirements may be diminished due to reduced 
capacity for gluconeogenesis and reduced insulin metabolism. 
 
Method of administration 
Insulin Human Winthrop Infusat must not be used in peristaltic pumps with silicone tubing. Refer to 
the technical manual for contraindications relating to the use of insulin pumps. 
 
Insulin Human Winthrop Infusat in cartridges may be infused by the subcutaneous route. It is 
designed for use in the Hoechst Infusor and H-Tron insulin pumps. It may also be used in other insulin 
pumps for which it has been shown that they are suitable for this insulin and this type of cartridge (see 
pump manual). Only tetrafluoroethylene or polyethylene catheters must be used. 
 
Insulin must always be infused under aseptic conditions. This is facilitated by the special equipment 
available for the insulin pumps (e.g. catheters, cannulas). 
 
Insulin absorption and hence the blood-glucose-lowering effect of a dose may vary from one injection 
area to another (e.g. the abdominal wall compared with the thigh). The puncture site within a given 
injection area must be changed regularly (generally, every 1 to 3 days). 
 
For further details on handling, see section 6.6. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
 
4.4 Special warnings and precautions for use 
 
Patients hypersensitive to Insulin Human Winthrop Infusat for whom no better tolerated preparation is 
available must only continue treatment under close medical supervision and – where necessary – in 
conjunction with anti-allergic treatment. 
 
In patients with an allergy to animal insulin intradermal skin testing is recommended prior to a 
transfer to Insulin Human Winthrop Infusat, since they may experience immunological 
cross-reactions. 
 
In case of hypoglycaemia, the insulin pump should temporarily be turned off, at least until the patient 
has recovered complete consciousness. 
 
In case of insufficient glucose control or a tendency to hyper- or hypoglycaemic episodes, the patient's 
adherence to the prescribed treatment regimen, injection sites and proper injection technique and all 
other relevant factors must be reviewed before dose adjustment is considered. 
 

 

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Transfer to Insulin Human Winthrop Infusat 
Transferring a patient to another type or brand of insulin should be done under strict medical 
supervision. Changes in strength, brand (manufacturer), type (regular, NPH, lente, long-acting, etc.), 
origin (animal, human, human insulin analogue) and/or method of manufacture may result in the need 
for a change in dosage. 
The need to adjust (e.g. reduce) the dose may become evident immediately after transfer. 
Alternatively, it may emerge gradually over a period of several weeks. 
 
Following transfer from an animal insulin to human insulin, dose regimen reduction may be required 
in particular in patients who 
- were previously already controlled on rather low blood glucose levels, 
- have a tendency to hypoglycaemia, 
- previously required high insulin doses due to the presence of insulin antibodies. 
 
Close metabolic monitoring is recommended during the transition and in the initial weeks thereafter. In 
patients who require high insulin doses because of the presence of insulin antibodies, transfer under 
medical supervision in a hospital or similar setting must be considered. 
 
Hypoglycaemia 
Hypoglycaemia may occur if the insulin dose is too high in relation to the insulin requirement. 
 
Particular caution should be exercised, and intensified blood glucose monitoring is advisable in 
patients in whom hypoglycaemic episodes might be of particular clinical relevance, such as in patients 
with significant stenoses of the coronary arteries or of the blood vessels supplying the brain (risk of 
cardiac or cerebral complications of hypoglycaemia) as well as in patients with proliferative 
retinopathy, particularly if not treated with photocoagulation (risk of transient amaurosis following 
hypoglycaemia). 
 
Patients should be aware of circumstances where warning symptoms of hypoglycaemia are 
diminished. The warning symptoms of hypoglycaemia may be changed, be less pronounced or be 
absent in certain risk groups. These include patients: 
- in whom glycaemic control is markedly improved, 
- in whom hypoglycaemia develops gradually, 
- who are elderly,  
- after transfer from animal insulin to human insulin, 
- in whom an autonomic neuropathy is present, 
- with a long history of diabetes, 
- suffering from a psychiatric illness, 
- receiving concurrent treatment with certain other medicinal products (see section 4.5). 
Such situations may result in severe hypoglycaemia (and possibly loss of consciousness) prior to the 
patient's awareness of hypoglycaemia. 
 
If normal or decreased values for glycated haemoglobin are noted, the possibility of recurrent, 
unrecognised (especially nocturnal) episodes of hypoglycaemia must be considered. 
 
Adherence of the patient to the dose regimen and dietary regimen, correct insulin administration and 
awareness of hypoglycaemia symptoms are essential to reduce the risk of hypoglycaemia. Factors 
increasing the susceptibility to hypoglycaemia require particularly close monitoring and may 
necessitate dose adjustment. These include: 
- change in the injection area, 
- improved insulin sensitivity (e.g. by removal of stress factors), 
- unaccustomed, increased or prolonged physical activity, 
- intercurrent illness (e.g. vomiting, diarrhoea), 
- inadequate food intake, 
- missed meals, 
- alcohol consumption, 

 

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- certain uncompensated endocrine disorders (e.g. in hypothyroidism and in anterior pituitary or 
adrenocortical insufficiency), 

- concomitant treatment with certain other medicinal products. 
 
Insulin pump faults 
Hyperglycaemia, ketoacidosis and coma may develop within hours if the pump catheter is obstructed 
completely. Whenever the patient notices a rapid increase in blood glucose which does not respond to 
a bolus dose, a check must be made for possible catheter obstruction. 
 
In the event of a pump malfunction, patients must always have injection devices (injection syringe or 
pen) and insulin available for subcutaneous injection. For details on safety precautions in the use of 
insulin pumps, refer to the operator’s manual. 
 
Intercurrent illness 
Intercurrent illness requires intensified metabolic monitoring. In many cases, urine tests for ketones 
are indicated, and often it is necessary to adjust the insulin dose. The insulin requirement is often 
increased. Patients with type 1 diabetes must continue to consume at least a small amount of 
carbohydrates on a regular basis, even if they are able to eat only little or no food, or are vomiting etc. 
and they must never omit insulin entirely. 
 
Medication errors 
Medication errors have been reported in which other Insulin Human Winthrop formulations or other 
insulins have been accidentally administered. Insulin label must always be checked before each 
injection to avoid medication errors between insulin human and other insulins. 
 
Combination of Insulin Human Winthrop with pioglitazone 
Cases of cardiac failure have been reported when pioglitazone was used in combination with insulin, 
especially in patients with risk factors for development of cardiac heart failure. This should be kept in 
mind if treatment with the combination of pioglitazone and Insulin Human Winthrop is considered. If 
the combination is used, patients should be observed for signs and symptoms of heart failure, weight 
gain and oedema. Pioglitazone should be discontinued if any deterioration in cardiac symptoms 
occurs.  
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
A number of substances affect glucose metabolism and may require dose adjustment of human insulin. 
 
Substances that may enhance the blood-glucose-lowering effect and increase susceptibility to 
hypoglycaemia include oral antidiabetic medicinal products, angiotensin converting enzyme (ACE) 
inhibitors, disopyramide, fibrates, fluoxetine, monoamine oxidase (MAO) inhibitors, pentoxifylline, 
propoxyphene, salicylates and sulphonamide antibiotics. 
 
Substances that may reduce the blood-glucose-lowering effect include corticosteroids, danazol, 
diazoxide, diuretics, glucagon, isoniazid, oestrogens and progestogens (e.g. in oral contraceptives), 
phenothiazine derivatives, somatropin, sympathomimetic medicinal products (e.g. epinephrine 
[adrenaline], salbutamol, terbutaline), thyroid hormones, protease inhibitors and atypical antipsychotic 
medicinal products (e.g. olanzapine and clozapine). 
 
Beta-blockers, clonidine, lithium salts or alcohol may either potentiate or weaken the 
blood-glucose-lowering effect of insulin. Pentamidine may cause hypoglycaemia which may 
sometimes be followed by hyperglycaemia. 
 
In addition, under the influence of sympatholytic medicinal products such as beta-blockers, clonidine, 
guanethidine and reserpine, the signs of adrenergic counter-regulation may be reduced or absent. 
 

 

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4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
For insulin human, no clinical data on exposed pregnancies from controlled clinical studies are 
available. Insulin does cross the placental barrier, although not in clinically significant amount. A 
limited amount of data on pregnant women (less than 300 pregnancy outcomes reported) exposed to 
marketed insulin human indicates no safety issues in use of insulin human in pregnancy. Caution 
should be exercised when prescribing to pregnant women. 
 
It is essential for patients with pre-existing or gestational diabetes to maintain good metabolic control 
throughout pregnancy. Insulin requirements may decrease during the first trimester and generally 
increase during the second and third trimesters. Immediately after delivery, insulin requirements 
decline rapidly (increased risk of hypoglycaemia). Careful monitoring of glucose control is essential. 
 
Breast-feeding 
No effects on the suckling child are anticipated. Insulin Human Winthrop Rapid can be used during 
breast-feeding. Breast-feeding women may require adjustments in insulin dose and diet. 
 
Fertility 
No clinical or animal data with insulin human on male or female fertility are available. 
 
4.7 Effects on ability to drive and use machines 
 
The patient's ability to concentrate and react may be impaired as a result of hypoglycaemia or 
hyperglycaemia or, for example, as a result of visual impairment. This may constitute a risk in 
situations where these abilities are of special importance (e.g. driving a car or using machines). 
 
Patients should be advised to take precautions to avoid hypoglycaemia whilst driving. This is 
particularly important in those who have reduced or absent awareness of the warning symptoms of 
hypoglycaemia or have frequent episodes of hypoglycaemia. It should be considered whether it is 
advisable to drive or use machines in these circumstances. 
 
4.8 Undesirable effects 
 
Summary of the safety profile  
Hypoglycaemia, in general the most frequent adverse reaction of insulin therapy, may occur if the 
insulin dose is too high in relation to the insulin requirement. In clinical studies and during marketed 
use, the frequency varies with patient population and dose regimens. Therefore, no specific frequency 
can be presented. 
 
Tabulated list of adverse reactions 
The following related adverse reactions from clinical investigations are listed below by system organ 
class and in order of decreasing incidence: very common (≥1/10); common (≥1/100 to <1/10); 
uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000), not known 
(cannot be estimated from the available data). 
 
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. 
 

 

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MedDRA system 
organ classes 

Common Uncommon Not known 

Immune system 
disorders 

 Shock Immediate type 
allergic reactions 
(hypotension, 
angioneurotic oedema, 
bronchospasm, 
generalised skin 
reactions); 
Anti-insulin antibodies 

Metabolism and 
nutrition disorders 

Oedema  Hypoglycaemia; 
Sodium retention 

Eye disorders   Proliferative 
retinopathy; 
Diabetic retinopathy; 
Visual impairment 

Skin and subcutaneous 
tissue disorders 

  Lipodystrophy 

General disorders and 
administration site 
conditions 

Injection site reactions Injection site urticaria Injection site 
inflammation;  
Injection site pain; 
Injection site pruritus; 
Injection site erythema; 
Injection site swelling 

 
Description of selected adverse reactions 
Immune system disorders 
Immediate type allergic reactions to insulin or to the excipients may be life-threatening. 
 
Insulin administration may cause anti-insulin antibodies to form. In rare cases, the presence of such 
anti-insulin antibodies may necessitate adjustment of the insulin dose in order to correct a tendency to 
hyper- or hypoglycaemia. 
 
Metabolism and nutrition disorders 
Severe hypoglycaemic attacks, especially if recurrent, may lead to neurological damage. 
Prolonged or severe hypoglycaemic episodes may be life-threatening. 
 
In many patients, the signs and symptoms of neuroglycopenia are preceded by signs of adrenergic 
counter-regulation. Generally, the greater and more rapid the decline in blood glucose, the more 
marked is the phenomenon of counter-regulation and its symptoms. 
Insulin may cause sodium retention and oedema, particularly if previously poor metabolic control is 
improved by intensified insulin therapy. 
 
Eyes disorders 
A marked change in glycaemic control may cause temporary visual impairment, due to temporary 
alteration in the turgidity and refractive index of the lens. 
 
Long-term improved glycaemic control decreases the risk of progression of diabetic retinopathy. 
However, intensification of insulin therapy with abrupt improvement in glycaemic control may be 
associated with temporary worsening of diabetic retinopathy. 
 
Skin and subcutaneous tissue disorders 
Lipodystrophy may occur at the injection site and delay local insulin absorption. Continuous rotation 
of the injection site within the given injection area may help to reduce or prevent these reactions. 
 
General disorders and administration site conditions 
Most minor reactions to insulins at the injection site usually resolve in a few days to a few weeks. 

 

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4.9 Overdose 
 
Symptoms 
Insulin overdose may lead to severe and sometimes long-term and life-threatening hypoglycaemia. 
 
Management 
Mild episodes of hypoglycaemia can usually be treated with oral carbohydrates. Adjustments in dose 
regimen of the medicinal product, meal patterns, or physical activity may be needed. 
 
More severe episodes with coma, seizure, or neurologic impairment may be treated with 
intramuscular/subcutaneous glucagon or concentrated intravenous glucose. Sustained carbohydrate 
intake and observation may be necessary because hypoglycaemia may recur after apparent clinical 
recovery. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Drugs used in diabetes, insulins and analogues for injection, fast-acting, 
ATC Code: A10AB01. 
 
Mechanism of action 
Insulin 
- lowers blood glucose and promotes anabolic effects as well as decreasing catabolic effects, 
- increases the transport of glucose into cells as well as the formation of glycogen in the muscles 
 and the liver, and improves pyruvate utilisation. It inhibits glycogenolysis and gluconeogenesis, 
- increases lipogenesis in the liver and adipose tissue and inhibits lipolysis, 
- promotes the uptake of amino acids into cells and promotes protein synthesis, 
- enhances the uptake of potassium into cells. 
 
Pharmacodynamic effects 
Insulin Human Winthrop Infusat is an insulin with rapid onset and short duration of action. 
 
5.2 Pharmacokinetic properties 
 
In healthy subjects, the serum half-life of insulin is approximately 4 to 6 minutes. It is longer in 
patients with severe renal insufficiency. However, it must be noted that the pharmacokinetics of 
insulin do not reflect its metabolic action. 
 
5.3 Preclinical safety data 
 
The acute toxicity was studied following subcutaneous administration in rats. No evidence of toxic 
effects was found. Local tolerability studies following subcutaneous and intramuscular administration 
in rabbits gave no remarkable findings. Studies of pharmacodynamic effects following subcutaneous 
administration in rabbits and dogs revealed the expected hypoglycaemic reactions. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Phenol, 
zinc chloride, 
trometamol, 
poloxamer 171, 

 

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glycerol, 
hydrochloric acid (for pH adjustment), 
water for injections. 
 
6.2 Incompatibilities 
 
This medicinal product must not be mixed with other medicinal products except those mentioned in 
section 6.6. 
 
Insulin Human Winthrop Infusat must not be mixed with solutions containing reducing substances 
such as thioles and sulphites.  
 
Mixing of insulins 
Insulin Human Winthrop Infusat must not be mixed with any other insulin or with insulin analogues. 
 
Care must be taken to ensure that no alcohol or other disinfectants enter the insulin solution. 
 
6.3 Shelf life 
 
2 years. 
 
Shelf life after first use of the cartridge 
The product (cartridges in-use in the pump) may be stored for a maximum of 2 weeks. 
 
6.4 Special precautions for storage 
 
Unopened cartridges 
Store in a refrigerator (2°C - 8°C). 
Do not freeze. 
Do not put Insulin Human Winthrop Infusat next to the freezer compartment or a freezer pack. 
Keep the cartridge in the outer carton in order to protect from light. 
 
In use cartridges 
For storage conditions after first opening of the medicinal product, see section 6.3. 
 
6.5 Nature and contents of container 
 
3.15 ml solution in a cartridge (type 1 colourless glass) with a plunger (fluoropolymer coated rubber 
(type 1, mixture of chlorobutyl and natural rubber)), a flanged cap (aluminium) and a stopper with 
hole (bromobutyl rubber (type 1), a Luer cone attachment (colourless polyethylene) and a Luer cap 
(colourless polyethylene). 
Packs of 5 cartridges are available. 
 
6.6 Special precautions for disposal and other handling 
 
Insulin Human Winthrop Infusat must only be used if the solution is clear, colourless, with no solid 
particles visible, and if it is of a water-like consistency. 
 
Before use, Insulin Human Winthrop Infusat must be kept at room temperature for 1 to 2 hours. Air 
bubbles must be removed before starting the infusion (see the operator’s manual for the pump). 
 
If the infusion pump malfunctions, the solution may be drawn from the cartridge into an injection 
syringe (suitable for an insulin with 100 IU/ml) and injected. 
 
Insulin Human Winthrop Infusat must not be used in peristaltic pumps with silicone tubing. Refer to 
the technical manual for contraindications relating to the use of insulin pumps. 
 

 

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It must be remembered that neutral regular insulin precipitates out at a pH of approximately 4.5 to 6.5. 
 
Insulin label must always be checked before each injection to avoid medication errors between insulin 
human and other insulins (see section 4.4). 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Sanofi-Aventis Deutschland GmbH, D-65926 Frankfurt am Main, Germany 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/06/368/057 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 17 January 2007 
Date of latest renewal: 17 January 2012 
 
 
10. DATE OF REVISION OF THE TEXT 
 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu 

 

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ANNEX II 
 
A. MANUFACTURER(S) OF THE BIOLOGICAL ACTIVE 

SUBSTANCE(S) AND MANUFACTURER(S) 
RESPONSIBLE FOR BATCH RELEASE 

 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY 

AND USE 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE 

MARKETING AUTHORISATION 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO 

THE SAFE AND EFFECTIVE USE OF THE MEDICINAL 
PRODUCT 

 
 

 

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A. MANUFACTURER(S) OF THE BIOLOGICAL ACTIVE SUBSTANCE(S) AND 
MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 

 
Name and address of the manufacturer of the biological active substance 
 
Sanofi-Aventis Deutschland GmbH 
Industriepark Höchst 
Brüningstraße 50 
D-65926 Frankfurt / Main 
Germany 
 
Name and address of the manufacturer responsible for batch release 
 
Sanofi-Aventis Deutschland GmbH 
Industriepark Höchst 
Brüningstraße 50 
D-65926 Frankfurt / Main 
Germany 
 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
 
Medicinal product subject to medical prescription. 
 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 
 
• Periodic Safety Update Reports 
The marketing authorisation holder shall submit periodic safety update reports for this product in 
accordance with the requirements set out in the list of Union reference dates (EURD list) ) provided 
for under Article 107c(7) of Directive 2001/83/EC and published on the European medicines 
web-portal. 
 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 
• Risk Management Plan (RMP) 
 
The MAH shall perform the required pharmacovigilance activities and interventions detailed in the 
agreed RMP presented in Module 1.8.2 of the Marketing Authorisation and any agreed subsequent 
updates of the RMP. 

 
An updated RMP should be submitted: 
• At the request of the European Medicines Agency 
• Whenever the risk management system is modified, especially as the result of new information 

being received that may lead to a significant change to the benefit/risk profile or as the result of 
an important (pharmacovigilance or risk minimisation) milestone being reached. 

 
If the submission of a PSUR and the update of a RMP coincide, they can be submitted at the same 
time. 
 
 

 

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ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 

 

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A. LABELLING 

 

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PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
OUTER CARTONS / FOR 100 IU/ml: 5 ml and 10 ml VIAL 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Insulin Human Winthrop Rapid 100 IU/ml solution for injection in a vial. 
 
Insulin human 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
1 ml contains 100 IU (3.5 mg) insulin human. 
 
Insulin with a rapid onset and short duration of action. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: metacresol, sodium dihydrogen phosphate dihydrate, glycerol, sodium hydroxide, 
hydrochloric acid (for pH adjustment), water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection in a vial. 
1 vial of 5 ml 
5 vials of 5 ml 
1 vial of 10 ml 
5 vials of 10 ml 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Subcutaneous or intravenous use. 
Read the package leaflet before use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
Use only clear and colourless solutions.  
 
 
8. EXPIRY DATE 
 
EXP 
 

 

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Once in-use, vials may be kept for up to 4 weeks. Do not store above 25°C and protect from direct 
heat and light. 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Unopened vials:  
Store in a refrigerator. 
Do not freeze. Keep the vial in the outer carton in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Sanofi-Aventis Deutschland GmbH 
D-65926 Frankfurt am Main, Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/06/368/011 (1 vial of 5 ml) 
EU/1/06/368/012 (5 vials of 5 ml) 
EU/1/06/368/169 (1 vial of 10 ml) 
EU/1/06/368/170 (5 vials of 10 ml) 
 
 
13. BATCH NUMBER 
 
BN 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. BRAILLE 
 
Insulin Human Winthrop Rapid 

 

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MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
VIAL LABEL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Insulin Human Winthrop Rapid 100 IU/ml solution for injection. 
 
Insulin human 
 
Subcutaneous or intravenous use. 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot  
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
5 ml 
10 ml 
 
 
6. OTHER 

 

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PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
OUTER CARTONS / FOR 40 IU/ml: 10 ml VIAL 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Insulin Human Winthrop Rapid 40 IU/ml solution for injection in a vial. 
 
Insulin human 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
1 ml contains 40 IU (1.4 mg) insulin human. 
 
Insulin with a rapid onset and short duration of action. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: metacresol, sodium dihydrogen phosphate dihydrate, glycerol, sodium hydroxide, 
hydrochloric acid (for pH adjustment), water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection in a vial. 
1 vial of 10 ml 
5 vials of 10 ml 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Subcutaneous or intravenous use. 
Read the package leaflet before use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
Use only clear and colourless solutions.  
 
 
8. EXPIRY DATE 
 
EXP 
 
Once in-use, vials may be kept for up to 4 weeks. Do not store above 25°C and protect from direct 
heat and light. 

 

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9. SPECIAL STORAGE CONDITIONS 
 
Unopened vials:  
Store in a refrigerator. 
Do not freeze. Keep the vial in the outer carton in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Sanofi-Aventis Deutschland GmbH 
D-65926 Frankfurt am Main, Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/06/368/001 (1 vial of 10 ml) 
EU/1/06/368/002 (5 vials of 10 ml) 
 
 
13. BATCH NUMBER 
 
BN 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. BRAILLE 
 
Insulin Human Winthrop Rapid 

 

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MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
VIAL LABEL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Insulin Human Winthrop Rapid 40 IU/ml solution for injection. 
 
Insulin human 
 
Subcutaneous or intravenous use. 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot  
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
10 ml 
 
 
6. OTHER 

 

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PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
OUTER CARTONS / 3 ML CARTRIDGES 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Insulin Human Winthrop Rapid 100 IU/ml solution for injection in a cartridge. 
 
Insulin human 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
1 ml contains 100 IU (3.5 mg) insulin human. 
 
Insulin with a rapid onset and short duration of action. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: metacresol, sodium dihydrogen phosphate dihydrate, glycerol, sodium hydroxide, 
hydrochloric acid (for pH adjustment), water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection in a cartridge. 
3 cartridges of 3 ml 
4 cartridges of 3 ml 
5 cartridges of 3 ml 
6 cartridges of 3 ml 
9 cartridges of 3 ml 
10 cartridges of 3 ml 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Subcutaneous or intravenous use.  
The Insulin Human Winthrop Rapid cartridges are to be used only with the pens: OptiPen, ClikSTAR, 
Tactipen, Autopen 24, AllStar, JuniorSTAR. 
Not all of these pens may be marketed in your country. 
 
Read the package leaflet before use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
Use only clear and colourless solutions.  

 

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If the insulin pen is damaged or not working properly (due to mechanical defects) it has to be 
discarded, and a new insulin pen has to be used. 
 
 
8. EXPIRY DATE 
 
EXP 
 
Once in-use, cartridges may be kept for up to 4 weeks. Do not store above 25°C and protect from 
direct heat and light. When in-use (in the pen), do not store in a refrigerator. 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Unopened cartridges: 
Store in a refrigerator. 
Do not freeze. Keep the cartridge in the outer carton in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Sanofi-Aventis Deutschland GmbH 
D-65926 Frankfurt am Main, Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/06/368/088 (3 cartridges of 3 ml) 
EU/1/06/368/013 (4 cartridges of 3 ml) 
EU/1/06/368/014 (5 cartridges of 3 ml) 
EU/1/06/368/093 (6 cartridges of 3 ml) 
EU/1/06/368/098 (9 cartridges of 3 ml) 
EU/1/06/368/015 (10 cartridges of 3 ml) 
 
 
13. BATCH NUMBER 
 
BN 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. BRAILLE 
 
Insulin Human Winthrop Rapid 

 

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MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
TEXT TO APPEAR ON THE ALUMINIUM FOIL WHICH IS USED FOR SEALING 
TRANSPARENT PLASTIC TRAY CONTAINING THE CARTRIDGE 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
 
3. EXPIRY DATE 
 
 
4. BATCH NUMBER 
 
 
5. OTHER 
 
After inserting a new cartridge: 
You must check that your insulin pen is working properly before you inject the first dose. Consult 
your insulin pen instruction booklet for further details.

 

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MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
CARTRIGE LABEL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Insulin Human Winthrop Rapid 100 IU/ml solution for injection. 
 
Insulin human 
 
Subcutaneous or intravenous use. 
 
 
2. METHOD OF ADMINISTRATION 
 
Use specific pens: see leaflet. 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot  
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
3 ml 
 
 
6. OTHER 
 
 
 
 

 

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PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
OUTER CARTONS / 3 ML PRE-FILLED PEN SOLOSTAR 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Insulin Human Winthrop Rapid SoloStar 100 IU/ml solution for injection in a pre-filled pen 
 
Insulin human 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
1 ml contains 100 IU (3.5 mg) insulin human. 
 
Insulin with a rapid onset and short duration of action. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: metacresol, sodium dihydrogen phosphate dihydrate, glycerol, sodium hydroxide, 
hydrochloric acid (for pH adjustment), water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection in a pre-filled pen. 
3 pens of 3 ml 
4 pens of 3 ml 
5 pens of 3 ml 
6 pens of 3 ml 
9 pens of 3 ml 
10 pens of 3 ml 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Subcutaneous use.  
Read the package leaflet before use. 
Open here 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
Use only clear and colourless solutions.  
Only use injection needles that have been approved for use with SoloStar. 
 

 

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8. EXPIRY DATE 
 
EXP 
 
Once in-use, pens may be kept for up to 4 weeks. Do not store above 25°C and protect from direct 
heat and light. When in-use, do not store in a refrigerator. 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Not in-use pens: 
Store in a refrigerator. 
Do not freeze. Keep the pen in the outer carton in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Sanofi-Aventis Deutschland GmbH 
D-65926 Frankfurt am Main, Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/06/368/113 (3 pens of 3 ml) 
EU/1/06/368/114 (4 pens of 3 ml) 
EU/1/06/368/115 (5 pens of 3 ml) 
EU/1/06/368/116 (6 pens of 3 ml) 
EU/1/06/368/117 (9 pens of 3 ml) 
EU/1/06/368/118 (10 pens of 3 ml) 
 
 
13. BATCH NUMBER 
 
BN 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. BRAILLE 
 
Insulin Human Winthrop Rapid SoloStar 
 

 

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MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
PEN LABEL SOLOSTAR 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Insulin Human Winthrop Rapid SoloStar 100 IU/ml solution for injection 
 
Insulin human 
 
Subcutaneous use. 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot  
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
3 ml 
 
 
6. OTHER 
 
 
 

 

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PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
OUTER CARTONS / FOR 100 IU/ml: 5 ml and 10 ml VIAL 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Insulin Human Winthrop Basal 100 IU/ml suspension for injection in a vial 
 
Insulin human 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
1 ml contains 100 IU (3.5 mg) insulin human. 
 
Insulin with a gradual onset and long duration of action. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: protamine sulphate, metacresol, phenol, zinc chloride, sodium dihydrogen phosphate 
dihydrate, glycerol, sodium hydroxide, hydrochloric acid (for pH adjustment), water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Suspension for injection in a vial. 
1 vial of 5 ml 
5 vials of 5 ml 
1 vial of 10 ml 
5 vials of 10 ml 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Subcutaneous use. 
Read the package leaflet before use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and  reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
Mix thoroughly.  
 
 
8. EXPIRY DATE 
 
EXP 
 

 

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Once in-use, vials may be kept for up to 4 weeks. Do not store above 25°C and protect from direct 
heat and light. 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Unopened vials:  
Store in a refrigerator. 
Do not freeze. Keep the vial in the outer carton in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Sanofi-Aventis Deutschland GmbH 
D-65926 Frankfurt am Main, Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/06/368/020 (1 vial of 5 ml) 
EU/1/06/368/021 (5 vials of 5 ml) 
EU/1/06/368/171 (1 vial of 10 ml) 
EU/1/06/368/172 (5 vials of 10 ml) 
 
 
13. BATCH NUMBER 
 
BN 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. BRAILLE 
 
Insulin Human Winthrop Basal 

 

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MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
VIAL LABEL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Insulin Human Winthrop Basal 100 IU/ml suspension for injection 
 
Insulin human 
 
Subcutaneous use. 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot  
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
5 ml 
10 ml 
 
 
6. OTHER 

 

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PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
OUTER CARTONS / FOR 40 IU/ml: 10 ml VIAL 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Insulin Human Winthrop Basal 40 IU/ml suspension for injection in a vial 
 
Insulin human 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
1 ml contains 40 IU (1.4 mg) insulin human. 
 
Insulin with a gradual onset and long duration of action. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: protamine sulphate, metacresol, phenol, zinc chloride, sodium dihydrogen phosphate 
dihydrate, glycerol, sodium hydroxide, hydrochloric acid (for pH adjustment), water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Suspension for injection in a vial. 
1 vial of 10 ml 
5 vials of 10 ml 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Subcutaneous use. 
Read the package leaflet before use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
Mix thoroughly.  
 
 
8. EXPIRY DATE 
 
EXP 
 
Once in-use, vials may be kept for up to 4 weeks. Do not store above 25°C and protect from direct 
heat and light.  

 

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9. SPECIAL STORAGE CONDITIONS 
 
Unopened vials:  
Store in a refrigerator. 
Do not freeze. Keep the vial in the outer carton in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Sanofi-Aventis Deutschland GmbH 
D-65926 Frankfurt am Main, Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/06/368/003 (1 vial of 10 ml) 
EU/1/06/368/004 (5 vials of 10 ml) 
 
 
13. BATCH NUMBER 
 
BN 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. BRAILLE 
 
Insulin Human Winthrop Basal  

 

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MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
VIAL LABEL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Insulin Human Winthrop Basal 40 IU/ml suspension for injection 
 
Insulin human 
 
Subcutaneous use. 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot  
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
10 ml 
 
 
6. OTHER 

 

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PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
OUTER CARTONS/3 ML CARTRIDGE 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Insulin Human Winthrop Basal 100 IU/ml suspension for injection in a cartridge 
 
Insulin human 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
1 ml contains 100 IU (3.5 mg) insulin human. 
 
Insulin with a gradual onset and long duration of action. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: protamine sulphate, metacresol, phenol, zinc chloride, sodium dihydrogen phosphate 
dihydrate, glycerol, sodium hydroxide, hydrochloric acid (for pH adjustment), water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Suspension for injection in a cartridge. 
3 cartridges of 3 ml 
4 cartridges of 3 ml 
5 cartridges of 3 ml 
6 cartridges of 3 ml 
9 cartridges of 3 ml 
10 cartridges of 3 ml 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Subcutaneous use.  
The Insulin Human Winthrop Basal cartridges are to be used only with the pens: OptiPen, ClikSTAR, 
Tactipen, Autopen 24, AllStar, JuniorSTAR. 
Not all of these pens may be marketed in your country. 
 
Read the package leaflet before use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
Mix thoroughly.  

 

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If the insulin pen is damaged or not working properly (due to mechanical defects) it has to be 
discarded, and a new insulin pen has to be used. 
 
 
8. EXPIRY DATE 
 
EXP 
 
Once in-use, cartridges may be kept for up to 4 weeks. Do not store above 25°C and protect from 
direct heat and light. When in-use (in the pen), do not store in a refrigerator. 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Unopened cartridges: 
Store in a refrigerator. 
Do not freeze. Keep the cartridge in the outer carton in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Sanofi-Aventis Deutschland GmbH 
D-65926 Frankfurt am Main, Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/06/368/089 (3 cartridges of 3 ml) 
EU/1/06/368/022 (4 cartridges of 3 ml) 
EU/1/06/368/023 (5 cartridges of 3 ml) 
EU/1/06/368/094 (6 cartridges of 3 ml) 
EU/1/06/368/099 (9 cartridges of 3 ml) 
EU/1/06/368/024 (10 cartridges of 3 ml) 
 
 
13. BATCH NUMBER 
 
BN 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. BRAILLE 
 
Insulin Human Winthrop Basal  

 

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MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
TEXT TO APPEAR ON THE ALUMINIUM FOIL WHICH IS USED FOR SEALING 
TRANSPARENT PLASTIC TRAY CONTAINING THE CARTRIDGE 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
 
3. EXPIRY DATE 
 
 
4. BATCH NUMBER 
 
 
5. OTHER 
 
After inserting a new cartridge: 
You must check that your insulin pen is working properly before you inject the first dose. Consult 
your insulin pen instruction booklet for further details.

 

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MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
CARTRIDGE LABEL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Insulin Human Winthrop Basal 100 IU/ml suspension for injection 
 
Insulin human 
 
Subcutaneous use. 
 
 
2. METHOD OF ADMINISTRATION 
 
Use specific pens: see leaflet. 
 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot  
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
3 ml 
 
 
6. OTHER 
 
 
 
 

 

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PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
OUTER CARTONS / 3 ML PRE-FILLED PEN SOLOSTAR 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Insulin Human Winthrop Basal SoloStar 100 IU/ml suspension for injection in a pre-filled pen 
 
Insulin human 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
1 ml contains 100 IU (3.5 mg) insulin human. 
 
Insulin with a gradual onset and long duration of action. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: protamine sulphate, metacresol, phenol, zinc chloride, sodium dihydrogen phosphate 
dihydrate, glycerol, sodium hydroxide, hydrochloric acid (for pH adjustment), water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Suspension for injection in a pre-filled pen. 
3 pens of 3 ml 
4 pens of 3 ml 
5 pens of 3 ml 
6 pens of 3 ml 
9 pens of 3 ml 
10 pens of 3 ml 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Subcutaneous use. 
Read the package leaflet before use. 
Open here 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
Mix thoroughly.  
Only use injection needles that have been approved for use with SoloStar. 
 

 

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8. EXPIRY DATE 
 
EXP 
 
Once in-use, pens may be kept for up to 4 weeks. Do not store above 25°C and protect from direct 
heat and light. When in-use, do not store in a refrigerator. 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Not in-use pens: 
Store in a refrigerator. 
Do not freeze. Keep the pen in the outer carton in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Sanofi-Aventis Deutschland GmbH 
D-65926 Frankfurt am Main, Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/06/368/119 (3 pens of 3 ml) 
EU/1/06/368/120 (4 pens of 3 ml) 
EU/1/06/368/121(5 pens of 3 ml) 
EU/1/06/368/122 (6 pens of 3 ml) 
EU/1/06/368/123 (9 pens of 3 ml) 
EU/1/06/368/124 (10 pens of 3 ml) 
 
 
13. BATCH NUMBER 
 
BN 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. BRAILLE 
 
Insulin Human Winthrop Basal SoloStar

 

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MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
PEN LABEL SOLOSTAR 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Insulin Human Winthrop Basal SoloStar 100 IU/ml suspension for injection 
 
Insulin human 
 
Subcutaneous use. 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot  
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
3 ml 
 
 
6. OTHER 
 
 
 
 

 

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PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
OUTER CARTONS / FOR 100 IU/ml: 5 ml VIAL 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Insulin Human Winthrop Comb 15 100 IU/ml suspension for injection in a vial 
 
Insulin human 
 
15% dissolved insulin, 85% crystalline protamine insulin 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
1 ml contains 100 IU (3.5 mg) insulin human. 
 
Insulin with a gradual onset and long duration of action. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: protamine sulphate, metacresol, phenol, zinc chloride, sodium dihydrogen phosphate 
dihydrate, glycerol, sodium hydroxide, hydrochloric acid (for pH adjustment), water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Suspension for injection in a vial. 
1 vial of 5 ml 
5 vials of 5 ml 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Subcutaneous use.  
Read the package leaflet before use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
Mix thoroughly.  
 
 
8. EXPIRY DATE 
 
EXP 
 

 

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Once in-use, vials may be kept for up to 4 weeks. Do not store above 25°C and protect from direct 
heat and light. 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Unopened vials:  
Store in a refrigerator. 
Do not freeze. Keep the vial in the outer carton in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Sanofi-Aventis Deutschland GmbH 
D-65926 Frankfurt am Main, Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/06/368/029 (1 vial of 5 ml) 
EU/1/06/368/030 (5 vials of 5 ml) 
 
 
13. BATCH NUMBER 
 
BN 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. BRAILLE 
 
Insulin Human Winthrop Comb 15  
 
 

 

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MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
VIAL LABEL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Insulin Human Winthrop Comb 15 100 IU/ml suspension for injection 
 
Insulin human 
 
Subcutaneous use. 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot  
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
5 ml 
 
 
6. OTHER 

 

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PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
OUTER CARTONS / FOR 40 IU/ml: 10 ml VIAL 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Insulin Human Winthrop Comb 15 40 IU/ml suspension for injection in a vial 
 
Insulin human 
 
15% dissolved insulin, 85% crystalline protamine insulin 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
1 ml contains 40 IU (1.4 mg) insulin human. 
 
Insulin with a gradual onset and long duration of action. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: protamine sulphate, metacresol, phenol, zinc chloride, sodium dihydrogen phosphate 
dihydrate, glycerol, sodium hydroxide, hydrochloric acid (for pH adjustment), water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Suspension for injection in a vial.  
1 vial of 10 ml 
5 vials of 10 ml 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Subcutaneous use.  
Read the package leaflet before use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
Mix thoroughly.  
 
 
8. EXPIRY DATE 
 
EXP 
 

 

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Once in-use, vials may be kept for up to 4 weeks. Do not store above 25°C and protect from direct 
heat and light. 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Unopened vials:  
Store in a refrigerator. 
Do not freeze. Keep the vial in the outer carton in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Sanofi-Aventis Deutschland GmbH 
D-65926 Frankfurt am Main, Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/06/368/005 (1 vial of 10 ml) 
EU/1/06/368/006 (5 vials of 10 ml) 
 
 
13. BATCH NUMBER 
 
BN 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. BRAILLE 
 
Insulin Human Winthrop Comb 15 

 

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MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
VIAL LABEL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Insulin Human Winthrop Comb 15 40 IU/ml suspension for injection 
 
Insulin human 
 
Subcutaneous use. 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot  
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
10 ml 
 
 
6. OTHER 

 

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PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
OUTER CARTONS / 3 ML CARTRIDGE 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Insulin Human Winthrop Comb 15 100 IU/ml suspension for injection in a cartridge 
 
Insulin human 
 
15% dissolved insulin, 85% crystalline protamine insulin 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
1 ml contains 100 IU (3.5 mg) insulin human. 
 
Insulin with a gradual onset and long duration of action. 
 
3. LIST OF EXCIPIENTS 
 
Excipients: protamine sulphate, metacresol, phenol, zinc chloride, sodium dihydrogen phosphate 
dihydrate, glycerol, sodium hydroxide, hydrochloric acid (for pH adjustment), water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Suspension for injection in a cartridge. 
3 cartridges of 3 ml 
4 cartridges of 3 ml 
5 cartridges of 3 ml 
6 cartridges of 3 ml 
9 cartridges of 3 ml 
10 cartridges of 3 ml 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Subcutaneous use.  
The Insulin Human Winthrop Comb 15 cartridges are to be used only with the pens: OptiPen, 
ClikSTAR, Tactipen, Autopen 24, AllStar, JuniorSTAR.  
Not all of these pens may be marketed in your country. 
 
Read the package leaflet before use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 

 

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7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
Mix thoroughly.  
If the insulin pen is damaged or not working properly (due to mechanical defects) it has to be 
discarded, and a new insulin pen has to be used. 
 
 
8. EXPIRY DATE 
 
EXP 
 
Once in-use, cartridges may be kept for up to 4 weeks. Do not store above 25°C and protect from 
direct heat and light. When in-use (in the pen), do not store in a refrigerator. 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Unopened cartridges: 
Store in a refrigerator. 
Do not freeze. Keep the cartridge in the outer carton in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Sanofi-Aventis Deutschland GmbH 
D-65926 Frankfurt am Main, Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/06/368/090 (3 cartridges of 3 ml) 
EU/1/06/368/031 (4 cartridges of 3 ml) 
EU/1/06/368/032 (5 cartridges of 3 ml) 
EU/1/06/368/095 (6 cartridges of 3 ml) 
EU/1/06/368/100 (9 cartridges of 3 ml) 
EU/1/06/368/033 (10 cartridges of 3 ml) 
 
 
13. BATCH NUMBER 
 
BN 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 

 

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16. BRAILLE 
 
Insulin Human Winthrop Comb 15 

 

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MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
TEXT TO APPEAR ON THE ALUMINIUM FOIL WHICH IS USED FOR SEALING 
TRANSPARENT PLASTIC TRAY CONTAINING THE CARTRIDGE 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
 
3. EXPIRY DATE 
 
 
4. BATCH NUMBER 
 
 
5. OTHER 
 
After inserting a new cartridge: 
You must check that your insulin pen is working properly before you inject the first dose. Consult 
your insulin pen instruction booklet for further details.

 

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MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
CARTRIDGE LABEL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Insulin Human Winthrop Comb 15 100 IU/ml suspension for injection 
 
Insulin human 
 
Subcutaneous use. 
 
 
2. METHOD OF ADMINISTRATION 
 
Use specific pens: see leaflet. 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot  
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
3 ml 
 
 
6. OTHER 
 
 
 

 

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PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
OUTER CARTONS / 3 ML PRE-FILLED PEN  
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Insulin Human Winthrop Comb 15 SoloStar 100 IU/ml suspension for injection in a pre-filled pen. 
 
Insulin human 
 
15% dissolved insulin, 85% crystalline protamine insulin 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
1 ml contains 100 IU (3.5 mg) insulin human. 
 
Insulin with a gradual onset and long duration of action. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: protamine sulphate, metacresol, phenol, zinc chloride, sodium dihydrogen phosphate 
dihydrate, glycerol, sodium hydroxide, hydrochloric acid (for pH adjustment), water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Suspension for injection in a pre-filled pen. 
3 pens of 3 ml 
4 pens of 3 ml 
5 pens of 3 ml 
6 pens of 3 ml 
9 pens of 3 ml 
10 pens of 3 ml 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Subcutaneous use. 
Read the package leaflet before use. 
Open here 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
Mix thoroughly. 
Only use injection needles that have been approved for use with SoloStar. 

 

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8. EXPIRY DATE 
 
EXP 
 
Once in-use, pens may be kept for up to 4 weeks. Do not store above 25°C and protect from direct 
heat and light. When in-use, do not store in a refrigerator. 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Not in-use pens: 
Store in a refrigerator. 
Do not freeze. Keep the pen in the outer carton in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Sanofi-Aventis Deutschland GmbH 
D-65926 Frankfurt am Main, Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/06/368/125 (3 pens of 3 ml) 
EU/1/06/368/126 (4 pens of 3 ml) 
EU/1/06/368/127 (5 pens of 3 ml) 
EU/1/06/368/128 (6 pens of 3 ml) 
EU/1/06/368/129 (9 pens of 3 ml) 
EU/1/06/368/130 (10 pens of 3 ml) 
 
 
13. BATCH NUMBER 
 
BN 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. BRAILLE 
 
Insulin Human Winthrop Comb 15 SoloStar

 

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MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
PEN LABEL SOLOSTAR 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Insulin Human Winthrop Comb 15 SoloStar 100 IU/ml suspension for injection 
 
Insulin human 
 
Subcutaneous use. 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot  
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
3 ml 
 
 
6. OTHER 
 
 

 

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PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
OUTER CARTONS / FOR 100 IU/ml: 5 ml VIAL 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Insulin Human Winthrop Comb 25 100 IU/ml suspension for injection in a vial 
 
Insulin human 
 
25% dissolved insulin, 75% crystalline protamine insulin 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
1 ml contains 100 IU (3.5 mg) insulin human. 
 
Insulin with a gradual onset and long duration of action. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: protamine sulphate, metacresol, phenol, zinc chloride, sodium dihydrogen phosphate 
dihydrate, glycerol, sodium hydroxide, hydrochloric acid (for pH adjustment), water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Suspension for injection in a vial. 
1 vial of 5 ml 
5 vials of 5 ml 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Subcutaneous use.  
Read the package leaflet before use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
Mix thoroughly.  
 
 
8. EXPIRY DATE 
 
EXP 
 

 

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Once in-use, vials may be kept for up to 4 weeks. Do not store above 25°C and protect from direct 
heat and light. 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Unopened vials: 
Store in a refrigerator. 
Do not freeze. Keep the vial in the outer carton in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Sanofi-Aventis Deutschland GmbH 
D-65926 Frankfurt am Main, Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/06/368/038 (1 vial of 5 ml) 
EU/1/06/368/039 (5 vials of 5 ml) 
 
 
13. BATCH NUMBER 
 
BN 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. BRAILLE 
 
Insulin Human Winthrop Comb 25 

 

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MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
VIAL LABEL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Insulin Human Winthrop Comb 25 100 IU/ml suspension for injection 
 
Insulin human 
 
Subcutaneous use. 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot  
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
5 ml 
 
 
6. OTHER 

 

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PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
OUTER CARTONS / FOR 40 IU/ml: 10 ml VIAL 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Insulin Human Winthrop Comb 25 40 IU/ml suspension for injection in a vial 
 
Insulin human 
 
25% dissolved insulin, 75% crystalline protamine insulin 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
1 ml contains 40 IU (1.4 mg) insulin human. 
 
Insulin with a gradual onset and long duration of action. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: protamine sulphate, metacresol, phenol, zinc chloride, sodium dihydrogen phosphate 
dihydrate, glycerol, sodium hydroxide, hydrochloric acid (for pH adjustment), water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Suspension for injection in a vial. 
1 vial of 10 ml 
5 vials of 10 ml 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Subcutaneous use.  
Read the package leaflet before use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
Mix thoroughly.  
 
 
8. EXPIRY DATE 
 
EXP 
 

 

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Once in-use, vials may be kept for up to 4 weeks. Do not store above 25°C and protect from direct 
heat and light. 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Unopened vials: 
Store in a refrigerator. 
Do not freeze. Keep the vial in the outer carton in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Sanofi-Aventis Deutschland GmbH 
D-65926 Frankfurt am Main, Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/06/368/007 (1 vial of 10 ml) 
EU/1/06/368/008 (5 vials of 10 ml) 
 
 
13. BATCH NUMBER 
 
BN 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. BRAILLE 
 
Insulin Human Winthrop Comb 25 

 

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MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
VIAL LABEL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Insulin Human Winthrop Comb 25 40 IU/ml suspension for injection 
 
Insulin human 
 
Subcutaneous use. 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot  
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
10 ml 
 
 
6. OTHER 

 

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PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
OUTER CARTONS / 3 ML CARTRIDGE 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Insulin Human Winthrop Comb 25 100 IU/ml suspension for injection in a cartridge 
 
Insulin human 
 
25% dissolved insulin, 75% crystalline protamine insulin 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
1 ml contains 100 IU (3.5 mg) insulin human. 
 
Insulin with a gradual onset and long duration of action. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: protamine sulphate, metacresol, phenol, zinc chloride, sodium dihydrogen phosphate 
dihydrate, glycerol, sodium hydroxide, hydrochloric acid (for pH adjustment), water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Suspension for injection in a cartridge. 
3 cartridges of 3 ml 
4 cartridges of 3 ml 
5 cartridges of 3 ml 
6 cartridges of 3 ml 
9 cartridges of 3 ml 
10 cartridges of 3 ml 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Subcutaneous use.  
The Insulin Human Winthrop Comb 25 cartridges are to be used only with the pens: OptiPen, 
ClikSTAR, Tactipen, Autopen 24, AllStar, JuniorSTAR.  
Not all of these pens may be marketed in your country. 
 
Read the package leaflet before use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

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Mix thoroughly.  
If the insulin pen is damaged or not working properly (due to mechanical defects) it has to be 
discarded, and a new insulin pen has to be used. 
 
 
8. EXPIRY DATE 
 
EXP 
 
Once in-use, cartridges may be kept for up to 4 weeks. Do not store above 25°C and protect from 
direct heat and light. When in-use (in the pen), do not store in a refrigerator. 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Unopened cartridges: 
Store in a refrigerator. 
Do not freeze. Keep the cartridge in the outer carton in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Sanofi-Aventis Deutschland GmbH 
D-65926 Frankfurt am Main, Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/06/368/091 (3 cartridges of 3 ml) 
EU/1/06/368/040 (4 cartridges of 3 ml) 
EU/1/06/368/041 (5 cartridges of 3 ml) 
EU/1/06/368/096 (6 cartridges of 3 ml) 
EU/1/06/368/101 (9 cartridges of 3 ml) 
EU/1/06/368/042 (10 cartridges of 3 ml) 
 
 
13. BATCH NUMBER 
 
BN 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 

 

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16. BRAILLE 
 
Insulin Human Winthrop Comb 25 

 

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MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
TEXT TO APPEAR ON THE ALUMINIUM FOIL WHICH IS USED FOR SEALING 
TRANSPARENT PLASTIC TRAY CONTAINING THE CARTRIDGE 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
 
3. EXPIRY DATE 
 
 
4. BATCH NUMBER 
 
 
5. OTHER 
 
After inserting a new cartridge: 
You must check that your insulin pen is working properly before you inject the first dose. Consult 
your insulin pen instruction booklet for further details.

 

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MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
CARTRIDGE LABEL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Insulin Human Winthrop Comb 25 100 IU/ml suspension for injection 
 
Insulin human 
 
Subcutaneous use. 
 
 
2. METHOD OF ADMINISTRATION 
 
Use specific pens: see leaflet. 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot  
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
3 ml 
 
 
6. OTHER 
 
 
 
 

 

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PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
OUTER CARTONS / 3 ML PRE-FILLED PEN SOLOSTAR 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Insulin Human Winthrop Comb 25 SoloStar 100 IU/ml suspension for injection in a pre-filled pen 
 
Insulin human 
 
25% dissolved insulin, 75% crystalline protamine insulin 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
1 ml contains 100 IU (3.5 mg) insulin human. 
 
Insulin with a gradual onset and long duration of action. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: protamine sulphate, metacresol, phenol, zinc chloride, sodium dihydrogen phosphate 
dihydrate, glycerol, sodium hydroxide, hydrochloric acid (for pH adjustment), water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Suspension for injection in a pre-filled pen. 
3 pens of 3 ml 
4 pens of 3 ml 
5 pens of 3 ml 
6 pens of 3 ml 
9 pens of 3 ml 
10 pens of 3 ml 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Subcutaneous use. 
Read the package leaflet before use. 
Open here 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
Mix thoroughly.  

 

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Only use injection needles that have been approved for use with SoloStar. 
 
 
8. EXPIRY DATE 
 
EXP 
 
Once in-use, pens may be kept for up to 4 weeks. Do not store above 25°C and protect from direct 
heat and light. When in-use, do not store in a refrigerator. 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Not in-use pens: 
Store in a refrigerator. 
Do not freeze. Keep the pen in the outer carton in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Sanofi-Aventis Deutschland GmbH 
D-65926 Frankfurt am Main, Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/06/368/131 (3 pens of 3 ml) 
EU/1/06/368/132 (4 pens of 3 ml) 
EU/1/06/368/133 (5 pens of 3 ml) 
EU/1/06/368/134 (6 pens of 3 ml) 
EU/1/06/368/135 (9 pens of 3 ml) 
EU/1/06/368/136 (10 pens of 3 ml) 
 
 
13. BATCH NUMBER 
 
BN 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. BRAILLE 
 
Insulin Human Winthrop Comb 25 SoloStar

 

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MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
PEN LABEL SOLOSTAR 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Insulin Human Winthrop Comb 25 SoloStar 100 IU/ml suspension for injection 
 
Insulin human 
 
Subcutaneous use. 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot  
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
3 ml 
 
 
6. OTHER 
 
 
 

 

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PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
OUTER CARTONS / FOR 100 IU/ml: 5 ml and 10 ml VIAL 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Insulin Human Winthrop Comb 30 100 IU/ml suspension for injection in a vial 
 
Insulin human 
 
30% dissolved insulin, 70% crystalline protamine insulin 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
1 ml contains 100 IU (3.5 mg) insulin human. 
 
Insulin with a gradual onset and long duration of action. 
 
 
3. LIST OF EXCIPIENTS 

 
Excipients: protamine sulphate, metacresol, phenol, zinc chloride, sodium dihydrogen phosphate 
dihydrate, glycerol, sodium hydroxide, hydrochloric acid (for pH adjustment), water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Suspension for injection in a vial. 
1 vial of 5 ml 
5 vials of 5 ml 
1 vial of 10 ml 
5 vials of 10 ml 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Subcutaneous use.  
Read the package leaflet before use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
Mix thoroughly.  
 
8. EXPIRY DATE 
 

 

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EXP 
 
Once in-use, vials may be kept for up to 4 weeks. Do not store above 25°C and protect from direct 
heat and light. 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Unopened vials:  
Store in a refrigerator. 
Do not freeze. Keep the vial in the outer carton in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Sanofi-Aventis Deutschland GmbH 
D-65926 Frankfurt am Main, Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/06/368/143 (1 vial of 5 ml) 
EU/1/06/368/144 (5 vials of 5 ml) 
EU/1/06/368/173 (1 vial of 10 ml) 
EU/1/06/368/174 (5 vials of 10 ml) 
 
 
13. BATCH NUMBER 
 
BN 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. BRAILLE 
 
Insulin Human Winthrop Comb 30

 

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MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
VIAL LABEL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Insulin Human Winthrop Comb 30 100 IU/ml suspension for injection 
 
Insulin human 
 
Subcutaneous use. 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot  
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
5 ml 
10 ml 
 
 
6. OTHER 

 

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300 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
OUTER CARTONS / 3 ML CARTRIDGE 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Insulin Human Winthrop Comb 30 100 IU/ml suspension for injection in a cartridge 
 
Insulin human 
 
30% dissolved insulin, 70% crystalline protamine insulin 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
1 ml contains 100 IU (3.5 mg) insulin human. 
 
Insulin with a gradual onset and long duration of action. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: protamine sulphate, metacresol, phenol, zinc chloride, sodium dihydrogen phosphate 
dihydrate, glycerol, sodium hydroxide, hydrochloric acid (for pH adjustment), water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Suspension for injection in a cartridge. 
3 cartridges of 3 ml 
4 cartridges of 3 ml 
5 cartridges of 3 ml 
6 cartridges of 3 ml 
9 cartridges of 3 ml 
10 cartridges of 3 ml 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Subcutaneous use.  
The Insulin Human Winthrop Comb 30 cartridges are to be used only with the pens: OptiPen, 
ClikSTAR, Tactipen, Autopen 24,AllStar, JuniorSTAR.  
Not all of these pens may be marketed in your country. 
 
Read the package leaflet before use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

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Mix thoroughly.  
If the insulin pen is damaged or not working properly (due to mechanical defects) it has to be 
discarded, and a new insulin pen has to be used. 
 
 
8. EXPIRY DATE 
 
EXP 
 
Once in-use, cartridges may be kept for up to 4 weeks. Do not store above 25°C and protect from 
direct heat and light. When in-use (in the pen), do not store in a refrigerator. 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Unopened cartridges: 
Store in a refrigerator. 
Do not freeze. Keep the cartridge in the outer carton in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Sanofi-Aventis Deutschland GmbH 
D-65926 Frankfurt am Main, Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/06/368/145 (3 cartridges of 3 ml) 
EU/1/06/368/146 (4 cartridges of 3 ml) 
EU/1/06/368/147 (5 cartridges of 3 ml) 
EU/1/06/368/148 (6 cartridges of 3 ml) 
EU/1/06/368/149 (9 cartridges of 3 ml) 
EU/1/06/368/150 (10 cartridges of 3 ml) 
 
 
13. BATCH NUMBER 
 
BN 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 

 

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16. BRAILLE 
 
Insulin Human Winthrop Comb 30 

 

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MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
TEXT TO APPEAR ON THE ALUMINIUM FOIL WHICH IS USED FOR SEALING 
TRANSPARENT PLASTIC TRAY CONTAINING THE CARTRIDGE 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
 
3. EXPIRY DATE 
 
 
4. BATCH NUMBER 
 
 
5. OTHER 
 
After inserting a new cartridge: 
You must check that your insulin pen is working properly before you inject the first dose. Consult 
your insulin pen instruction booklet for further details.

 

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MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
CARTRIDGE LABEL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Insulin Human Winthrop Comb 30 100 IU/ml suspension for injection 
 
Insulin human 
 
Subcutaneous use. 
 
 
2. METHOD OF ADMINISTRATION 
 
Use specific pens: see leaflet. 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot  
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
3 ml 
 
 
6. OTHER 
 
 
 
 

 

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PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
OUTER CARTONS / 3 ML PRE-FILLED PEN SOLOSTAR 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Insulin Human Winthrop Comb 30 SoloStar 100 IU/ml suspension for injection in a pre-filled pen 
 
Insulin human 
 
30% dissolved insulin, 70% crystalline protamine insulin 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
1 ml contains 100 IU (3.5 mg) insulin human. 
 
Insulin with a gradual onset and long duration of action. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: protamine sulphate, metacresol, phenol, zinc chloride, sodium dihydrogen phosphate 
dihydrate, glycerol, sodium hydroxide, hydrochloric acid (for pH adjustment), water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Suspension for injection in a pre-filled pen. 
3 pens of 3 ml 
4 pens of 3 ml 
5 pens of 3 ml 
6 pens of 3 ml 
9 pens of 3 ml 
10 pens of 3 ml 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Subcutaneous use. 
Read the package leaflet before use. 
Open here 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
Mix thoroughly.  

 

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Only use injection needles that have been approved for use with SoloStar. 
 
 
8. EXPIRY DATE 
 
EXP 
 
Once in-use, pens may be kept for up to 4 weeks. Do not store above 25°C and protect from direct 
heat and light. When in-use, do not store in a refrigerator. 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Not in-use pens: 
Store in a refrigerator. 
Do not freeze. Keep the pen in the outer carton in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Sanofi-Aventis Deutschland GmbH 
D-65926 Frankfurt am Main, Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/06/368/163 (3 pens of 3 ml) 
EU/1/06/368/164 (4 pens of 3 ml) 
EU/1/06/368/165 (5 pens of 3 ml) 
EU/1/06/368/166 (6 pens of 3 ml) 
EU/1/06/368/167 (9 pens of 3 ml) 
EU/1/06/368/168 (10 pens of 3 ml) 
 
 
13. BATCH NUMBER 
 
BN 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. BRAILLE 
 
Insulin Human Winthrop Comb 30 SoloStar

 

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MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
PEN LABEL SOLOSTAR 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Insulin Human Winthrop Comb 30 SoloStar 100 IU/ml suspension for injection 
 
Insulin human 
 
Subcutaneous use. 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot  
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
3 ml 
 
 
6. OTHER 
 
 
 

 

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PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
OUTER CARTONS / FOR 100 IU/ml: 5 ml VIAL 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Insulin Human Winthrop Comb 50 100 IU/ml suspension for injection in a vial 
 
Insulin human 
 
50% dissolved insulin, 50% crystalline protamine insulin 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
1 ml contains 100 IU (3.5 mg) insulin human. 
 
Insulin with a rapid onset and moderately long duration of action. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: protamine sulphate, metacresol, phenol, zinc chloride, sodium dihydrogen phosphate 
dihydrate, glycerol, sodium hydroxide, hydrochloric acid (for pH adjustment), water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Suspension for injection in a vial. 
1 vial of 5 ml 
5 vials of 5 ml 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Subcutaneous use.  
Read the package leaflet before use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
Mix thoroughly.  
 
8. EXPIRY DATE 
 
EXP 
 

 

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Once in-use, vials may be kept for up to 4 weeks. Do not store above 25°C and protect from direct 
heat and light. 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Unopened vials:  
Store in a refrigerator. 
Do not freeze. Keep the vial in the outer carton in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Sanofi-Aventis Deutschland GmbH 
D-65926 Frankfurt am Main, Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/06/368/047 (1 vial of 5 ml) 
EU/1/06/368/048 (5 vials of 5 ml) 
 
 
13. BATCH NUMBER 
 
BN 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. BRAILLE 
 
Insulin Human Winthrop Comb 50 

 

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MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
VIAL LABEL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Insulin Human Winthrop Comb 50 100 IU/ml suspension for injection 
 
Insulin human 
 
Subcutaneous use. 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot  
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
5 ml 
 
 
6. OTHER 

 

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PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTONS / FOR 40 IU/ml: 10 ml VIAL 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Insulin Human Winthrop Comb 50 40 IU/ml suspension for injection in a vial 
 
Insulin human 
 
50% dissolved insulin, 50% crystalline protamine insulin 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
1 ml contains 40 IU (1.4 mg) insulin human. 
 
Insulin with a rapid onset and moderately long duration of action. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: protamine sulphate, metacresol, phenol, zinc chloride, sodium dihydrogen phosphate 
dihydrate, glycerol, sodium hydroxide, hydrochloric acid (for pH adjustment), water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Suspension for injection in a vial. 
1 vial of 10 ml 
5 vials of 10 ml 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Subcutaneous use.  
Read the package leaflet before use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
Mix thoroughly.  
 
8. EXPIRY DATE 
 
EXP 
 

 

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Once in-use, vials may be kept for up to 4 weeks. Do not store above 25°C and protect from direct 
heat and light. 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Unopened vials:  
Store in a refrigerator. 
Do not freeze. Keep the vial in the outer carton in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Sanofi-Aventis Deutschland GmbH 
D-65926 Frankfurt am Main, Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/06/368/009 (1 vial of 10 ml) 
EU/1/06/368/010 (5 vials of 10 ml) 
 
 
13. BATCH NUMBER 
 
BN 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. BRAILLE 
 
Insulin Human Winthrop Comb 50 

 

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MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
VIAL LABEL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Insulin Human Winthrop Comb 50 40 IU/ml suspension for injection 
 
Insulin human 
 
Subcutaneous use. 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot  
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
10 ml 
 
 
6. OTHER 

 

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PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
OUTER CARTONS / 3 ML CARTRIDGE 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Insulin Human Winthrop Comb 50 100 IU/ml suspension for injection in a cartridge 
 
Insulin human 
 
50% dissolved insulin, 50% crystalline protamine insulin 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
1 ml contains 100 IU (3.5 mg) insulin human. 
 
Insulin with a rapid onset and moderately long duration of action. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: protamine sulphate, metacresol, phenol, zinc chloride, sodium dihydrogen phosphate 
dihydrate, glycerol, sodium hydroxide, hydrochloric acid (for pH adjustment), water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Suspension for injection in a cartridge. 
3 cartridges of 3 ml 
4 cartridges of 3 ml 
5 cartridges of 3 ml 
6 cartridges of 3 ml 
9 cartridges of 3 ml 
10 cartridges of 3 ml 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Subcutaneous use.  
The Insulin Human Winthrop Comb 50 cartridges are to be used only with the pens: OptiPen, 
ClikSTAR, Tactipen, Autopen 24, AllStar, JuniorSTAR.  
Not all of these pens may be marketed in your country. 
 
Read the package leaflet before use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 

 

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Mix thoroughly.  
If the insulin pen is damaged or not working properly (due to mechanical defects) it has to be 
discarded, and a new insulin pen has to be used. 
 
 
8. EXPIRY DATE 
 
EXP 
 
Once in-use, cartridges may be kept for up to 4 weeks. Do not store above 25°C and protect from 
direct heat and light. When in-use (in the pen), do not store in a refrigerator. 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Unopened cartridges: 
Store in a refrigerator. 
Do not freeze. Keep the cartridge in the outer carton in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Sanofi-Aventis Deutschland GmbH 
D-65926 Frankfurt am Main, Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/06/368/092 (3 cartridges of 3 ml) 
EU/1/06/368/049 (4 cartridges of 3 ml) 
EU/1/06/368/050 (5 cartridges of 3 ml) 
EU/1/06/368/097 (6 cartridges of 3 ml) 
EU/1/06/368/102 (9 cartridges of 3 ml) 
EU/1/06/368/051 (10 cartridges of 3 ml) 
 
 
13. BATCH NUMBER 
 
BN 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 

 

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16. BRAILLE 
 
Insulin Human Winthrop Comb 50 

 

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MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
TEXT TO APPEAR ON THE ALUMINIUM FOIL WHICH IS USED FOR SEALING 
TRANSPARENT PLASTIC TRAY CONTAINING THE CARTRIDGE 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
 
3. EXPIRY DATE 
 
 
4. BATCH NUMBER 
 
 
5. OTHER 
 
After inserting a new cartridge: 
You must check that your insulin pen is working properly before you inject the first dose. Consult 
your insulin pen instruction booklet for further details. 
 

 

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MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
CARTRIDGE LABEL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Insulin Human Winthrop Comb 50 100 IU/ml suspension for injection 
 
Insulin human 
 
Subcutaneous use. 
 
 
2. METHOD OF ADMINISTRATION 
 
Use specific pens: see leaflet. 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot  
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
3 ml 
 
 
6. OTHER 
 
 
 
 

 

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319 

 
 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
OUTER CARTONS / 3 ML PRE-FILLED PEN SOLOSTAR 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Insulin Human Winthrop Comb 50 SoloStar 100 IU/ml suspension for injection in a pre-filled pen. 
 
Insulin human 
 
50% dissolved insulin, 50% crystalline protamine insulin 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
1 ml contains 100 IU (3.5 mg) insulin human. 
 
Insulin with a rapid onset and moderately long duration of action. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: protamine sulphate, metacresol, phenol, zinc chloride, sodium dihydrogen phosphate 
dihydrate, glycerol, sodium hydroxide, hydrochloric acid (for pH adjustment), water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Suspension for injection in a pre-filled pen. 
3 pens of 3 ml 
4 pens of 3 ml 
5 pens of 3 ml 
6 pens of 3 ml 
9 pens of 3 ml 
10 pens of 3 ml 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Subcutaneous use. 
Read the package leaflet before use. 
Open here 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
Mix thoroughly.  

 

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Only use injection needles that have been approved for use with SoloStar. 
 
 
8. EXPIRY DATE 
 
EXP 
 
Once in-use, pens may be kept for up to 4 weeks. Do not store above 25°C and protect from direct 
heat and light. When in-use, do not store in a refrigerator. 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Not in-use pens: 
Store in a refrigerator. 
Do not freeze. Keep the pen in the outer carton in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Sanofi-Aventis Deutschland GmbH 
D-65926 Frankfurt am Main, Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/06/368/137 (3 pens of 3 ml) 
EU/1/06/368/138 (4 pens of 3 ml) 
EU/1/06/368/139 (5 pens of 3 ml) 
EU/1/06/368/140 (6 pens of 3 ml) 
EU/1/06/368/141 (9 pens of 3 ml) 
EU/1/06/368/142 (10 pens of 3 ml) 
 
 
13. BATCH NUMBER 
 
BN 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. BRAILLE 
 
Insulin Human Winthrop Comb 50 SoloStar

 

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MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
PEN LABEL SOLOSTAR 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Insulin Human Winthrop Comb 50 SoloStar 100 IU/ml suspension for injection. 
 
Insulin human 
 
Subcutaneous use. 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot  
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
3 ml 
 
 
6. OTHER 
 
 
 

 

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322 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
OUTER CARTONS / 10 ML VIAL 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Insulin Human Winthrop Infusat 100 IU/ml solution for injection in a vial. 
 
Insulin human 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
1 ml contains 100 IU (3.5 mg) insulin human. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: phenol, zinc chloride, trometamol, glycerol, poloxamer 171, hydrochloric acid (for pH 
adjustment), water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection in a vial. 
3 vials of 10 ml 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Subcutaneous use. For use in insulin pumps, which are suitable for insulins containing 100 IU/ml. 
Read the package leaflet before use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
Use only clear and colourless solutions.  
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Unopened vials:  
Store in a refrigerator. 

 

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Do not freeze. Keep the vial in the outer carton in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Sanofi-Aventis Deutschland GmbH 
D-65926 Frankfurt am Main, Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/06/368/056 
 
 
13. BATCH NUMBER 
 
BN 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. BRAILLE 
 
Insulin Human Winthrop Infusat  

 

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MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
VIAL LABEL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Insulin Human Winthrop Infusat 100 IU/ml solution for injection. 
 
Insulin human 
 
Subcutaneous use. 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot  
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
10 ml 
 
 
6. OTHER 

 

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325 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
OUTER CARTONS / 3.15 ML CARTRIDGE 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Insulin Human Winthrop Infusat 100 IU/ml solution for injection in a cartridge. 
 
Insulin human 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
1 ml contains 100 IU (3.5 mg) insulin human. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: phenol, zinc chloride, trometamol, glycerol, poloxamer 171, hydrochloric acid (for pH 
adjustment), water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection in a cartridge. 
5 cartridges of 3.15 ml 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Subcutaneous use. For use in insulin pumps, which are suitable for insulins containing 100 IU/ml. 
Read the package leaflet before use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
Use only clear and colourless solutions.  
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Unopened cartridges: 
Store in a refrigerator. 

 

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Do not freeze. Keep the cartridge in the outer carton in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Sanofi-Aventis Deutschland GmbH 
D-65926 Frankfurt am Main, Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/06/368/057 
 
 
13. BATCH NUMBER 
 
BN 

 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. BRAILLE 
 
Insulin Human Winthrop Infusat  
 

 

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MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
CARTRIDGE LABEL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Insulin Human Winthrop Infusat 100 IU/ml solution for injection. 
 
Insulin human 
 
Subcutaneous use. 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot  
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
3.15 ml 
 
 
6. OTHER 
 

 

 

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B. PACKAGE LEAFLET 

 

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Package leaflet: Information for the user 

 
Insulin Human Winthrop Rapid 100 IU/ml solution for injection in a vial 

Insulin human 
 
 
Read all of this leaflet carefully before you start using this medicine because it contains 
important information for you. 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor, pharmacist or nurse. 
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours. 
- If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible 

side effects not listed in this leaflet.  
 
What is in this leaflet 
1. What Insulin Human Winthrop Rapid is and what it is used for 
2. What you need to know before you use Insulin Human Winthrop Rapid 
3. How to use Insulin Human Winthrop Rapid 
4. Possible side effects 
5. How to store Insulin Human Winthrop Rapid 
6. Contents of the pack and other information 
 
 
1. What Insulin Human Winthrop Rapid is and what it is used for 
 
Insulin Human Winthrop Rapid contains the active substance insulin human which is made by a 
biotechnology process and is identical with the body's own insulin. 
 
Insulin Human Winthrop Rapid is an insulin solution with a rapid onset and short duration of action. 
 
Insulin Human Winthrop Rapid is used to reduce high blood sugar in patients with diabetes mellitus 
who need treatment with insulin. Diabetes mellitus is a disease where your body does not produce 
enough insulin to control the level of blood sugar. Insulin Human Winthrop Rapid may also be used 
for treating hyperglycaemic coma (coma caused by too much blood sugar) and ketoacidosis (build-up 
of acid in the blood because the body is breaking down fat instead of sugar) as well as for controlling 
blood sugar before, during and after surgery. 
 
 
2. What you need to know before you use Insulin Human Winthrop Rapid 
 
Do not use Insulin Human Winthrop Rapid 
 
If you are allergic to insulin or any of the other ingredients of this medicine (listed in section 6). 
 
Warnings and precautions 
 
Talk to your doctor, pharmacist or nurse before using Insulin Human Winthrop Rapid. 
Follow closely the instructions for dosage, monitoring (blood and urine tests), diet and physical 
activity (physical work and exercise) as discussed with your doctor. 
 
If you are allergic to this medicine or to animal insulins, talk to your doctor. 
 

 

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Special patient groups 
If you have liver or kidneys problems or if you are elderly, speak to your doctor as you may need a 
lower dose. 
 
Travel 
Before travelling, consult your doctor. You may need to talk about 
- the availability of your insulin in the country you are visiting, 
- supplies of insulin, injection syringes etc., 
- correct storage of your insulin while travelling, 
- timing of meals and insulin administration while travelling, 
- the possible effects of changing to different time zones, 
- possible new health risks in the countries to be visited, 
- what you should do in emergency situations when you feel unwell or become ill. 
 
Illnesses and injuries 
In the following situations, the management of your diabetes may require a lot of care: 
- If you are ill or have a major injury then your blood sugar level may increase (hyperglycaemia). 
- If you are not eating enough, your blood sugar level may become too low (hypoglycaemia). 
In most cases you will need a doctor. Make sure that you contact a doctor early.  
 
If you have type 1 diabetes (insulin dependent diabetes mellitus), do not stop your insulin and 
continue to get enough carbohydrates. Always tell people who are caring for you or treating you that 
you require insulin. 
 
Some patients with long-standing type 2 diabetes mellitus and heart disease or previous stroke who 
were treated with pioglitazone and insulin experienced the development of heart failure. Inform your 
doctor as soon as possible if you experience signs of heart failure such as unusual shortness of breath 
or rapid increase in weight or localised swelling (oedema). 
 
Other medicines and Insulin Human Winthrop Rapid 
 
Some medicines cause changes in the blood sugar level (decrease, increase or both depending on the 
situation). In each case, it may be necessary to adjust your insulin dosage to avoid blood sugar levels 
that are either too low or too high. Be careful when you start or stop taking another medicine. 
 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines, Before taking a medicine ask your doctor if it can affect your blood sugar level, and what 
action, if any, you need to take. 
 
Medicines that may cause your blood sugar level to fall (hypoglycaemia) include:  
- all other medicines to treat diabetes, 
- angiotensin converting enzyme (ACE) inhibitors (used to treat certain heart conditions or high 

blood pressure), 
- disopyramide (used to treat certain heart conditions), 
- fluoxetine (used to treat depression), 
- fibrates (used to lower high levels of blood lipids), 
- monoamine oxidase (MAO) inhibitors (used to treat depression), 
- pentoxifylline, propoxyphene, salicylates (such as aspirin, used to relieve pain and lower fever), 
- sulfonamide antibiotics. 
 
Medicines that may cause your blood sugar level to rise (hyperglycaemia) include:  
- corticosteroids (such as "cortisone", used to treat inflammation),  
- danazol (medicine acting on ovulation),  
- diazoxide (used to treat high blood pressure),  
- diuretics (used to treat high blood pressure or excessive fluid retention),  
- glucagon (pancreas hormone used to treat severe hypoglycaemia),  
- isoniazid (used to treat tuberculosis),  

 

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- oestrogens and progestogens (such as in the contraceptive pill used for birth control),  
- phenothiazine derivatives (used to treat psychiatric disorders),  
- somatropin (growth hormone),  
- sympathomimetic medicines (such as epinephrine [adrenaline] or salbutamol, terbutaline used to 

treat asthma), 
- thyroid hormones (used to treat the thyroid gland disorders), 
- protease inhibitors (used to treat HIV), 
- atypical antipsychotic medicines (such as olanzapine and clozapine). 
 
Your blood sugar level may either rise or fall if you take:  
- beta-blockers (used to treat high blood pressure),  
- clonidine (used to treat high blood pressure),  
- lithium salts (used to treat psychiatric disorders).  
Pentamidine (used to treat some infections caused by parasites) may cause hypoglycaemia which may 
sometimes be followed by hyperglycaemia. 
 
Beta-blockers like other sympatholytic medicines (such as clonidine, guanethidine, and reserpine) may 
weaken or suppress entirely the first warning symptoms which help you to recognise a 
hypoglycaemia. 
 
If you are not sure whether you are taking one of those medicines ask your doctor or pharmacist. 
 
Insulin Human Winthrop Rapid with alcohol 
 
Your blood sugar levels may either rise or fall if you drink alcohol. 
 
Pregnancy and breast-feeding 
 
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor or pharmacist for advice before taking this medicine. 
 
Inform your doctor if you are planning to become pregnant, or if you are already pregnant. Your 
insulin dosage may need to be changed during pregnancy and after giving birth. Particularly careful 
control of your diabetes, and prevention of hypoglycaemia, is important for the health of your baby.  
 
If you are breast-feeding consult your doctor as you may require adjustments in your insulin doses and 
your diet. 
 
Driving and using machines 
 
Your ability to concentrate or react may be reduced if: 
- you have hypoglycaemia (low blood sugar levels), 
- you have hyperglycaemia (high blood sugar levels), 
- you have problems with your sight.  
Keep this possible problem in mind in all situations where you might put yourself and others at risk 
(such as driving a car or using machines). You should contact your doctor for advice on driving if: 
- you have frequent episodes of hypoglycaemia, 
- the first warning symptoms which help you to recognise hypoglycaemia are reduced or absent. 
 
Important information about some of the ingredients of Insulin Human Winthrop Rapid 
 
This medicine contains less than 1 mmol (23 mg) sodium per dose, i.e. it is essentially ‘sodium-free’. 
 
 

 

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3. How to use Insulin Human Winthrop Rapid 
 
Dose 
 
Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor 
or pharmacist if you are not sure. 
 
Based on your life-style and the results of your blood sugar (glucose) tests, your doctor will 
- determine how much Insulin Human Winthrop Rapid per day you will need, 
- tell you when to check your blood sugar level, and whether you need to carry out urine tests, 
- tell you when you may need to inject a higher or lower dose of Insulin Human Winthrop Rapid. 
 
Many factors may influence your blood sugar level. You should know these factors so that you are 
able to react correctly to changes in your blood sugar level and to prevent it from becoming too high 
or too low. See the box at the end of this leaflet for further information. 
 
Frequency of administration 
 
Insulin Human Winthrop Rapid is injected under the skin 15 to 20 minutes before a meal. 
 
Method of administration 
 
Insulin Human Winthrop Rapid is a solution for injection under the skin or, in exceptional 
circumstances, into a vein (blood vessel).  
 
Your doctor will show you in which area of the skin you should inject your insulin. With each 
injection, change the puncture site within the particular area of skin that you are using. 
 
Insulin administration into a vein for example to treat severe hyperglycaemia and ketoacidosis, 
requires experience and special safety precautions. For these reasons, it must be done in a clinic or a 
similar setting. 
 
Do not use Insulin Human Winthrop Rapid in insulin pumps – special insulin preparations are 
available for use in such devices. Also do not use it in peristaltic pumps with silicone tubing. 
 
How to handle the vials 
 
Insulin Human Winthrop Rapid contains 100 IU insulin per ml. Only injection syringes designed for 
this insulin concentration (100 IU per ml) must be used. The injection syringes must not contain any 
other medicines or traces of medicines (such as traces of heparin). 
 
Before the first withdrawal of insulin you must remove the safety tear-off cap on the vial. 
 
Insulin Human Winthrop Rapid must only be used if the solution is clear, colourless, with no solid 
particles visible, and has a water-like consistency. 
 
Do not shake the vial vigorously as this could cause froth to form. Froth can make it difficult for you 
to measure the correct dose. 
 
Special care before injection 
 
Before injection remove any air bubbles. Make sure that neither alcohol nor other disinfectants or 
other substances contaminate the insulin. Do not mix insulin with any other medicines except with 
insulin human preparations as detailed below. 
 

 

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Insulin Human Winthrop Rapid may be mixed with all insulin human preparations, EXCEPT those 
specially designed for use in insulin pumps. Also, it must NOT be mixed with animal source insulins 
or insulin analogues. 
 
Your doctor will tell you if you have to mix insulin human preparations. If you need to inject a 
mixture, draw Insulin Human Winthrop Rapid into the injection syringe before the other insulin. Inject 
as soon as you have mixed them. Do not mix insulins of different strengths (for example 100 IU per 
ml and 40 IU per ml). 
 
If you use more Insulin Human Winthrop Rapid than you should 
- If you have injected too much Insulin Human Winthrop Rapid, your blood sugar level may 

become too low (hypoglycaemia). Check your blood sugar frequently. In general, to prevent 
hypoglycaemia you must eat more food and monitor your blood sugar. For information on the 
treatment of hypoglycaemia, see box at the end of this leaflet. 

 
If you forget to use Insulin Human Winthrop Rapid 
- If you have missed a dose of Insulin Human Winthrop Rapid or if you have not injected 

enough insulin, your blood sugar level may become too high (hyperglycaemia). Check your 
blood sugar frequently. For information on the treatment of hyperglycaemia, see box at the end 
of this leaflet. 

 
- Do not take a double dose to make up for a forgotten dose. 
 
If you stop using Insulin Human Winthrop Rapid 
 
This could lead to severe hyperglycaemia (very high blood sugar) and ketoacidosis (build-up of acid 
in the blood because the body is breaking down fat instead of sugar). Do not stop Insulin Human 
Winthrop Rapid without speaking to a doctor, who will tell you what needs to be done. 
 
If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse. 
 
Insulin Mix-ups 
 
You must always check the insulin label before each injection to avoid mix-ups between Insulin 
Human Winthrop Rapid and other insulins.  
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
The most frequent side effect is hypoglycaemia (low blood sugar). The specific frequency cannot be 
estimated from available data (frequency not known). Serious hypoglycaemia may cause a heart attack 
or brain damage and may be life-threatening. For further information on the side effects of low blood 
sugar or high blood sugar, see the box at the end of this leaflet. 
 
Severe allergic reactions to insulin may occur which may become life-threatening. Such reactions to 
insulin or to the excipients can cause large-scale skin reactions (rash and itching all over the body); 
severe swelling of skin or mucous membranes (angiooedema), shortness of breath, a fall in blood 
pressure with rapid heart beat and sweating. Frequency of these reactions cannot be estimated from 
available data.  
 
Side effects reported commonly (may affect up to 1 in 10 people) 
• Oedema 
Insulin treatment may cause temporary build-up of water in the body with swelling in the calves and 
ankles. 
• Injection site reactions 

 

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Side effects reported uncommonly (may affect up to 1 in 100 people) 
• Severe allergic reaction with low blood pressure (shock) 
• Injection site urticaria (itchy rash) 
 
Other side effects include (frequency cannot be estimated from the available data) 
• Sodium retention 
• Eye reactions 
A marked change (improvement or worsening) in your blood sugar control can disturb your vision 
temporarily. If you have proliferative retinopathy (an eye disease related to diabetes) severe 
hypoglycaemic attacks may cause temporary loss of vision. 
• Skin changes at the injection site (lipodystrophy) 
If you inject your insulin too often at the same skin site, fatty tissue under the skin at this site may 
either shrink or thicken. Insulin that you inject in such a site may not work very well. Changing the 
injection site with each injection may help to prevent such skin changes. 
• Skin and allergic reactions 
Other mild reactions at the injection site (such as injection site redness, unusually intense pain on 
injection site, itching, injection site swelling or injection site inflammation) may occur. They can also 
spread around the injection site. Most minor reactions to insulins usually resolve in a few days to a 
few weeks. 
 
Insulin treatment can cause the body to produce antibodies to insulin (substances that act against 
insulin). However, only very rarely, this will require a change to your insulin dosage. 
 
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side 
effects not listed in this leaflet. 
 
 
5. How to store Insulin Human Winthrop Rapid 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date which is stated on the carton and on the label of the vial 
after “EXP”. The expiry date refers to the last day of that month. 
 
Unopened vials 
Store in a refrigerator (2°C – 8°C). Do not freeze. Do not put Insulin Human Winthrop Rapid next to 
the freezer compartment or a freezer pack. Keep the vial in the outer carton in order to protect from 
light. 
 
Opened vials 
Once in-use, the vial may be stored for a maximum of 4 weeks in the outer carton not above 25°C and 
away from direct heat (for example next to a heating unit) or direct light (direct sunlight or next to a 
lamp). Do not use the vial after this time period. It is recommended that the date of the first use be 
noted on the label. 
 
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment. 
 
 

 

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6. Contents of the pack and other information 
 
What Insulin Human Winthrop Rapid contains 
- The active substance is insulin human. One ml of Insulin Human Winthrop Rapid contains 

100 IU (International Units) of the active substance insulin human. 
- The other ingredients are: metacresol, sodium dihydrogen phosphate dihydrate, glycerol, 

sodium hydroxide (see section 2 under “Important information about some of the ingredients of 
Insulin Human Winthrop Rapid”), hydrochloric acid (for pH adjustment) and water for 
injections. 

 
What Insulin Human Winthrop Rapid looks like and contents of the pack 
Insulin Human Winthrop Rapid is a clear, colourless solution for injection, with no solid particles 
visible, and of a water-like consistency. 
 
Insulin Human Winthrop Rapid is supplied in vials containing 5 ml of solution for injection 
(equivalent to 500 IU) or 10 ml of solution for injection (equivalent to 1000 IU). Packs of 1 and 
5 vials of 5 ml or 10 ml are available. Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder and Manufacturer 
Sanofi-Aventis Deutschland GmbH 
D-65926 Frankfurt am Main  
Germany 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
Sanofi Belgium 
Tél/Tel: +32 (0)2 710 54 00 
 

Lietuva 
UAB «SANOFI-AVENTIS LIETUVA» 
Tel: +370 5 2755224 
 

България 
sanofi-aventis Bulgaria EOOD 
Тел.: +359 (0)2 970 53 00 
 

Luxembourg/Luxemburg 
Sanofi Belgium  
Tél/Tel: +32 (0)2 710 54 00 (Belgique/Belgien) 
 

Česká republika 
sanofi-aventis, s.r.o. 
Tel: +420 233 086 111 
 

Magyarország 
SANOFI-AVENTIS Zrt. 
Tel.: +36 1 505 0050 
 

Danmark 
sanofi-aventis Denmark A/S 
Tlf: +45 45 16 70 00 
 

Malta 
Sanofi Malta Ltd. 
Tel: +356 21493022 
 

Deutschland 
Zentiva Pharma GmbH 
Tel: +49 (0)180 20 200 10 
 

Nederland 
sanofi-aventis Netherlands B.V. 
Tel: +31 (0)182 557 755 
 

Eesti 
sanofi-aventis Estonia OÜ 
Tel: +372 627 34 88 
 

Norge 
Aventis Pharma NorgeAS 
Tlf: +47 67 10 71 00 
 

Ελλάδα 
sanofi-aventis AEBE 
Τηλ: +30 210 900 16 00 
 

Österreich 
sanofi-aventis GmbH 
Tel: +43 1 80 185 – 0 
 

 

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España 
sanofi-aventis, S.A. 
Tel: +34 93 485 94 00 
 

Polska 
sanofi-aventis Sp. z o.o. 
Tel.: +48 22 280 00 00 
 

France 
sanofi-aventis France 
Tél: 0 800 222 555 
Appel depuis l’étranger : +33 1 57 63 23 23 
 

Portugal 
Sanofi - Produtos Farmacêuticos, Lda. 
Tel: +351 21 35 89 400 
 

Hrvatska 
sanofi-aventis Croatia d.o.o. 
Tel: +385 1 600 34 00 

România 
Sanofi Romania SRL 
Tel: +40 (0) 21 317 31 36 
 

Ireland 
sanofi-aventis Ireland Ltd. T/A SANOFI 
Tel: +353 (0) 1 403 56 00 
 

Slovenija 
sanofi-aventis d.o.o. 
Tel: +386 1 560 48 00 
 

Ísland 
Vistor hf. 
Sími: +354 535 7000 
 

Slovenská republika 
sanofi-aventis Pharma Slovakia s.r.o. 
Tel: +421 2 33 100 100 
 

Italia 
Sanofi S.p.A. 
Tel: 800 13 12 12 (domande di tipo tecnico)  
800 536389 (altre domande) 
 

Suomi/Finland 
Sanofi Oy 
Puh/Tel: +358 (0) 201 200 300 
 

Κύπρος 
sanofi-aventis Cyprus Ltd. 
Τηλ: +357 22 871600 
 

Sverige 
Sanofi AB 
Tel: +46 (0)8 634 50 00 
 

Latvija 
sanofi-aventis Latvia SIA 
Tel: +371 67 33 24 51 
 

United Kingdom 
Sanofi 
Tel: +44 (0) 845 372 7101 
 

 
This leaflet was last revised in {date} 
 
 
Other source of information 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu/ 
 
 
 
 

HYPERGLYCAEMIA AND HYPOGLYCAEMIA 
 

Always carry some sugar (at least 20 grams) with you. 
Carry some information with you to show you are diabetic. 

 
HYPERGLYCAEMIA (high blood sugar levels) 

 
If your blood sugar is too high (hyperglycaemia), you may not have injected enough insulin. 
 
Why does hyperglycaemia occur? 
 
Examples include: 

 

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- you have not injected your insulin or not injected enough, or if it has become less effective, for 
example through incorrect storage, 

- you are doing less exercise than usual, you are under stress (emotional distress, excitement), or 
you have an injury, operation, infection or fever, 

- you are taking or have taken certain other medicines (see section 2, "Other medicines and 
Insulin Human Winthrop Rapid"). 

 
Warning symptoms of hyperglycaemia 
 
Thirst, increased need to urinate, tiredness, dry skin, reddening of the face, loss of appetite, low blood 
pressure, fast heart beat, and glucose and ketone bodies in urine. Stomach pain, fast and deep 
breathing, sleepiness or even loss of consciousness may be signs of a serious condition (ketoacidosis) 
resulting from lack of insulin. 
 
What should you do if you experience hyperglycaemia 
 
Test your blood sugar level and your urine for ketones as soon as any of the above symptoms 
occur. Severe hyperglycaemia or ketoacidosis must always be treated by a doctor, normally in a 
hospital. 
 

HYPOGLYCAEMIA (low blood sugar levels) 
 
If your blood sugar level falls too much you may become unconscious. Serious hypoglycaemia may 
cause a heart attack or brain damage and may be life-threatening. You normally should be able to 
recognise when your blood sugar is falling too much so that you can take the right actions. 
 
Why does hypoglycaemia occur? 
 
Examples include: 
- you inject too much insulin, 
- you miss meals or delay them, 
- you do not eat enough, or eat food containing less carbohydrate than normal (sugar and 

substances similar to sugar are called carbohydrates; however, artificial sweeteners are NOT 
carbohydrates), 

- you lose carbohydrates due to vomiting or diarrhoea, 
- you drink alcohol, particularly if you are not eating much, 
- you are doing more exercise than usual or a different type of physical activity, 
- you are recovering from an injury or operation or other stress, 
- you are recovering from an illness or from fever, 
- you are taking or have stopped taking certain other medicines (see section 2, "Other medicines 

and Insulin Human Winthrop Rapid"). 
 
Hypoglycaemia is also more likely to occur if: 
- you have just begun insulin treatment or changed to another insulin preparation, 
- your blood sugar levels are almost normal or are unstable, 
- you change the area of skin where you inject insulin (for example from the thigh to the upper 

arm), 
- you suffer from severe kidney or liver disease, or some other disease such as hypothyroidism. 
 
Warning symptoms of hypoglycaemia 
 
- In your body 
Examples of symptoms that tell you that your blood sugar level is falling too much or too fast: 
sweating, clammy skin, anxiety, fast heart beat, high blood pressure, palpitations and irregular 
heartbeat. These symptoms often develop before the symptoms of a low sugar level in the brain. 
 
- In your brain 

 

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Examples of symptoms that indicate a low sugar level in the brain: headaches, intense hunger, nausea, 
vomiting, tiredness, sleepiness, sleep disturbances, restlessness, aggressive behaviour, lapses in 
concentration, impaired reactions, depression, confusion, speech disturbances (sometimes total loss of 
speech), visual disorders, trembling, paralysis, tingling sensations (paraesthesia), numbness and 
tingling sensations in the area of the mouth, dizziness, loss of self-control, inability to look after 
yourself, convulsions, loss of consciousness. 
 
The first symptoms which alert you to hypoglycaemia ("warning symptoms") may change, be weaker 
or may be missing altogether if 
- you are elderly, if you have had diabetes for a long time or if you suffer from a certain type of 

nervous disease (diabetic autonomic neuropathy), 
- you have recently suffered hypoglycaemia (for example the day before) or if it develops slowly, 
- you have almost normal or, at least, greatly improved blood sugar levels, 
- you have recently changed from an animal insulin to a human insulin such as Insulin Human 

Winthrop, 
- you are taking or have taken certain other medicines (see section 2, "Other medicines and 

Insulin Human Winthrop Rapid"). 
 
In such a case, you may develop severe hypoglycaemia (and even faint) before you are aware of the 
problem. Be familiar with your warning symptoms. If necessary, more frequent blood sugar testing 
can help to identify mild hypoglycaemic episodes that may otherwise be overlooked. If you are not 
confident about recognising your warning symptoms, avoid situations (such as driving a car) in which 
you or others would be put at risk by hypoglycaemia. 
 
What should you do if you experience hypoglycaemia 
 
1. Do not inject insulin. Immediately take about 10 to 20 g sugar, such as glucose, sugar cubes or a 

sugar-sweetened beverage. Caution: Artificial sweeteners and foods with artificial sweeteners 
(such as diet drinks) are of no help in treating hypoglycaemia. 

2. Then eat something that has a long-acting effect in raising your blood sugar (such as bread or 
pasta). Your doctor or nurse should have discussed this with you previously. 

3. If the hypoglycaemia comes back again take another 10 to 20 g sugar. 
4. Speak to a doctor immediately if you are not able to control the hypoglycaemia or if it recurs. 
 
Tell your relatives, friends and close colleagues the following: 
If you are not able to swallow or if you are unconscious, you will require an injection of glucose or 
glucagon (a medicine which increases blood sugar). These injections are justified even if it is not 
certain that you have hypoglycaemia. 
 
It is advisable to test your blood sugar immediately after taking glucose to check that you really have 
hypoglycaemia. 
 
 

 

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Package leaflet: Information for the user 

 
Insulin Human Winthrop Rapid 40 IU/ml solution for injection in a vial 

Insulin human 
 
 
Read all of this leaflet carefully before you start using this medicine because it contains 
important information for you. 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor, pharmacist or nurse. 
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours. 
- If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible 

side effects not listed in this leaflet. 
 
What is in this leaflet: 
1. What Insulin Human Winthrop Rapid is and what it is used for 
2. What you need to know before you use Insulin Human Winthrop Rapid 
3. How to use Insulin Human Winthrop Rapid 
4. Possible side effects 
5. How to store Insulin Human Winthrop Rapid 
6. Contents of the pack and other information 
 
 
1. What Insulin Human Winthrop Rapid is and what it is used for 
 
Insulin Human Winthrop Rapid contains the active substance insulin human which is made by a 
biotechnology process and is identical with the body's own insulin. 
 
Insulin Human Winthrop Rapid is an insulin solution with a rapid onset and short duration of action. 
 
Insulin Human Winthrop Rapid is used to reduce high blood sugar in patients with diabetes mellitus 
who need treatment with insulin. Diabetes mellitus is a disease where your body does not produce 
enough insulin to control the level of blood sugar. Insulin Human Winthrop Rapid may also be used 
for treating hyperglycaemic coma (coma caused by too much blood sugar) and ketoacidosis (build-up 
of acid in the blood because the body is breaking down fat instead of sugar) as well as for controlling 
blood sugar before, during and after surgery. 
 
 
2. What you need to know before you use Insulin Human Winthrop Rapid 
 
Do not use Insulin Human Winthrop Rapid 
 
If you are allergic to insulin or any of the other ingredients of this medicine (listed in section 6). 
 
Warnings and precautions 
 
Talk to your doctor, pharmacist or nurse before using Insulin Human Winthrop Rapid. 
Follow closely the instructions for dosage, monitoring (blood and urine tests), diet and physical 
activity (physical work and exercise) as discussed with your doctor. 
 
If you are allergic to this medicine or to animal insulins, talk to your doctor. 
 
Special patient groups 
If you have liver or kidneys problems or if you are elderly, speak to your doctor as you may need a 
lower dose. 

 

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Travel 
Before travelling, consult your doctor. You may need to talk about 
- the availability of your insulin in the country you are visiting, 
- supplies of insulin, injection syringes etc., 
- correct storage of your insulin while travelling, 
- timing of meals and insulin administration while travelling, 
- the possible effects of changing to different time zones, 
- possible new health risks in the countries to be visited, 
- what you should do in emergency situations when you feel unwell or become ill. 
 
Illnesses and injuries 
In the following situations, the management of your diabetes may require a lot of care: 
- If you are ill or have a major injury then your blood sugar level may increase (hyperglycaemia).  
- If you are not eating enough, your blood sugar level may become too low (hypoglycaemia).  
In most cases you will need a doctor. Make sure that you contact a doctor early.  
 
If you have type 1 diabetes (insulin dependent diabetes mellitus), do not stop your insulin and 
continue to get enough carbohydrates. Always tell people who are caring for you or treating you that 
you require insulin. 
 
Some patients with long-standing type 2 diabetes mellitus and heart disease or previous stroke who 
were treated with pioglitazone and insulin experienced the development of heart failure. Inform your 
doctor as soon as possible if you experience signs of heart failure such as unusual shortness of breath 
or rapid increase in weight or localised swelling (oedema). 
 
Other medicines and Insulin Human Winthrop Rapid 
 
Some medicines cause changes in the blood sugar level (decrease, increase or both depending on the 
situation). In each case, it may be necessary to adjust your insulin dosage to avoid blood sugar levels 
that are either too low or too high. Be careful when you start or stop taking another medicine. 
 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines. Before taking a medicine ask your doctor if it can affect your blood sugar level, and what 
action, if any, you need to take. 
 
Medicines that may cause your blood sugar level to fall (hypoglycaemia) include:  
- all other medicines to treat diabetes,  
- angiotensin converting enzyme (ACE) inhibitors (used to treat certain heart conditions or high 

blood pressure),  
- disopyramide (used to treat certain heart conditions),  
- fluoxetine (used to treat depression),  
- fibrates (used to lower high levels of blood lipids),  
- monoamine oxidase (MAO) inhibitors (used to treat depression),  
- pentoxifylline, propoxyphene, salicylates (such as aspirin, used to relieve pain and lower fever), 
- sulfonamide antibiotics. 
 
Medicines that may cause your blood sugar level to rise (hyperglycaemia) include:  
- corticosteroids (such as "cortisone", used to treat inflammation),  
- danazol (medicine acting on ovulation),  
- diazoxide (used to treat high blood pressure),  
- diuretics (used to treat high blood pressure or excessive fluid retention),  
- glucagon (pancreas hormone used to treat severe hypoglycaemia),  
- isoniazid (used to treat tuberculosis),  
- oestrogens and progestogens (such as in the contraceptive pill used for birth control),  
- phenothiazine derivatives (used to treat psychiatric disorders),  
- somatropin (growth hormone),  

 

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- sympathomimetic medicines (such as epinephrine [adrenaline] or salbutamol, terbutaline used to 
treat asthma), 

- thyroid hormones (used to treat the thyroid gland disorders), 
- protease inhibitors (used to treat HIV), 
- atypical antipsychotic medicines (such as olanzapine and clozapine). 
 
Your blood sugar level may either rise or fall if you take:  
- beta-blockers (used to treat high blood pressure),  
- clonidine (used to treat high blood pressure), 
- lithium salts (used to treat psychiatric disorders).  
Pentamidine (used to treat some infections caused by parasites) may cause hypoglycaemia which may 
sometimes be followed by hyperglycaemia. 
 
Beta-blockers like other sympatholytic medicines (such as clonidine, guanethidine, and reserpine) may 
weaken or suppress entirely the first warning symptoms which help you to recognise a 
hypoglycaemia. 
 
If you are not sure whether you are taking one of those medicines ask your doctor or pharmacist. 
 
Insulin Human Winthrop Rapid alcohol 
 
Your blood sugar levels may either rise or fall if you drink alcohol. 
 
Pregnancy and breast-feeding 
 
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor or pharmacist for advice before taking this medicine. 
 
Inform your doctor if you are planning to become pregnant, or if you are already pregnant. Your 
insulin dosage may need to be changed during pregnancy and after giving birth. Particularly careful 
control of your diabetes, and prevention of hypoglycaemia, is important for the health of your baby.  
 
If you are breast--eeding consult your doctor as you may require adjustments in your insulin doses and 
your diet. 
 
Driving and using machines 
 
Your ability to concentrate or react may be reduced if: 
- you have hypoglycaemia (low blood sugar levels), 
- you have hyperglycaemia (high blood sugar levels), 
- you have problems with your sight.  
Keep this possible problem in mind in all situations where you might put yourself and others at risk 
(such as driving a car or using machines). You should contact your doctor for advice on driving if: 
- you have frequent episodes of hypoglycaemia, 
- the first warning symptoms which help you to recognise hypoglycaemia are reduced or absent. 
 
Important information about some of the ingredients of Insulin Human Winthrop Rapid  
 
This medicine contains less than 1 mmol (23 mg) sodium per dose, i.e. it is essentially ‘sodium-free’. 
 
 

 

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3. How to use Insulin Human Winthrop Rapid 
 
Dose 
 
Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor 
or pharmacist if you are not sure. 
 
Based on your life-style and the results of your blood sugar (glucose) tests, your doctor will 
- determine how much Insulin Human Winthrop Rapid per day you will need, 
- tell you when to check your blood sugar level, and whether you need to carry out urine tests, 
- tell you when you may need to inject a higher or lower dose of Insulin Human Winthrop Rapid. 
 
Many factors may influence your blood sugar level. You should know these factors so that you are 
able to react correctly to changes in your blood sugar level and to prevent it from becoming too high 
or too low. See the box at the end of this leaflet for further information. 
 
Frequency of administration 
 
Insulin Human Winthrop Rapid is injected under the skin 15 to 20 minutes before a meal. 
 
Method of administration 
 
Insulin Human Winthrop Rapid is a solution for injection under the skin or, in exceptional 
circumstances, into a vein (blood vessel).  
 
Your doctor will show you in which area of the skin you should inject your insulin. With each 
injection, change the puncture site within the particular area of skin that you are using. 
 
Insulin administration into a vein for example to treat severe hyperglycaemia and ketoacidosis, 
requires experience and special safety precautions. For these reasons, it must be done in a clinic or a 
similar setting. 
 
Do not use Insulin Human Winthrop Rapid in insulin pumps – special insulin preparations are 
available for use in such devices. Also do not use it in peristaltic pumps with silicone tubing. 
 
How to handle the vials 
 
Insulin Human Winthrop Rapid contains 40 IU insulin per ml. Only injection syringes designed for 
this insulin concentration (40 IU per ml) must be used. The injection syringes must not contain any 
other medicines or traces of medicines (such as traces of heparin). 
 
Before the first withdrawal of insulin you must remove the safety tear-off cap on the vial. 
 
Insulin Human Winthrop Rapid must only be used if the solution is clear, colourless, with no solid 
particles visible, and has a water-like consistency. 
 
Do not shake the vial vigorously as this could cause froth to form. Froth can make it difficult for you 
to measure the correct dose. 
 
Special care before injection 
 
Before injection remove any air bubbles. Make sure that neither alcohol nor other disinfectants or 
other substances contaminate the insulin. Do not mix insulin with any other medicines except with 
insulin human preparations as detailed below. 
 

 

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Insulin Human Winthrop Rapid may be mixed with all insulin human preparations, EXCEPT those 
specially designed for use in insulin pumps. Also, it must NOT be mixed with animal source insulins 
or insulin analogues. 
 
Your doctor will tell you if you have to mix insulin human preparations. If you need to inject a 
mixture, draw Insulin Human Winthrop Rapid into the injection syringe before the other insulin. Inject 
as soon as you have mixed them. Do not mix insulins of different strengths (for example 100 IU per 
ml and 40 IU per ml). 
 
If you use more Insulin Human Winthrop Rapid than you should 
- If you have injected too much Insulin Human Winthrop Rapid, your blood sugar level may 

become too low (hypoglycaemia). Check your blood sugar frequently. In general, to prevent 
hypoglycaemia you must eat more food and monitor your blood sugar. For information on the 
treatment of hypoglycaemia, see box at the end of this leaflet. 

 
If you forget to use Insulin Human Winthrop Rapid 
- If you have missed a dose of Insulin Human Winthrop Rapid or if you have not injected 

enough insulin, your blood sugar level may become too high (hyperglycaemia). Check your 
blood sugar frequently. For information on the treatment of hyperglycaemia, see box at the end 
of this leaflet. 

 
- Do not take a double dose to make up for a forgotten dose. 
 
If you stop using Insulin Human Winthrop Rapid 
 
This could lead to severe hyperglycaemia (very high blood sugar) and ketoacidosis (build-up of acid 
in the blood because the body is breaking down fat instead of sugar). Do not stop Insulin Human 
Winthrop Rapid without speaking to a doctor, who will tell you what needs to be done. 
 
If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse. 
 
Insulin Mix-ups 
 
You must always check the insulin label before each injection to avoid mix-ups between Insulin 
Human Winthrop Rapid and other insulins.  
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
The most frequent side effect is hypoglycaemia (low blood sugar). The specific frequency cannnot 
be estimated from available data (frequency not known). Serious hypoglycaemia may cause a heart 
attack or brain damage and may be life-threatening. For further information on the side effects of low 
blood sugar or high blood sugar, see the box at the end of this leaflet. 
 
Severe allergic reactions to insulin may occur which may become life-threatening. Such reactions to 
insulin or to the excipients can cause large-scale skin reactions (rash and itching all over the body); 
severe swelling of skin or mucous membranes (angiooedema), shortness of breath, a fall in blood 
pressure with rapid heart beat and sweating. Frequency of these reactions cannot be estimated from 
available data. 
 
Side effects reported commonly (may affect up to 1 in 10 people) 
• Oedema 
Insulin treatment may cause temporary build-up of water in the body with swelling in the calves and 
ankles. 
• Injection site reactions 

 

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Side effects reported uncommonly (may affect up to 1 in 100 people) 
• Severe allergic reaction with low blood pressure (shock) 
• Injection site urticaria (itchy rash) 
 
Other side effects include (frequency cannot be estimated from the available data) 
• Sodium retention 
• Eye reactions 
A marked change (improvement or worsening) in your blood sugar control can disturb your vision 
temporarily. If you have proliferative retinopathy (an eye disease related to diabetes) severe 
hypoglycaemic attacks may cause temporary loss of vision. 
• Skin changes at the injection site (lipodystrophy) 
If you inject your insulin too often at the same skin site, fatty tissue under the skin at this site may 
either shrink or thicken. Insulin that you inject in such a site may not work very well. Changing the 
injection site with each injection may help to prevent such skin changes. 
• Skin and allergic reactions 
Other mild reactions at the injection site (such as injection site redness, unusually intense pain on 
injection site, itching, injection site swelling or injection site inflammation) may occur. They can also 
spread around the injection site. Most minor reactions to insulins usually resolve in a few days to a 
few weeks. 
 
Insulin treatment can cause the body to produce antibodies to insulin (substances that act against 
insulin). However, only very rarely, this will require a change to your insulin dosage. 
 
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side 
effects not listed in this leaflet. 
 
 
5. How to store Insulin Human Rapid 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date which is stated on the carton and on the label of the vial 
after “EXP”. The expiry date refers to the last day of that month. 
 
Unopened vials 
Store in a refrigerator (2°C - 8°C). Do not freeze. Do not put Insulin Human Winthrop Rapid next to 
the freezer compartment or a freezer pack. Keep the vial in the outer carton in order to protect from 
light. 
 
Opened vials 
Once in-use, the vial may be stored for a maximum of 4 weeks in the outer carton not above 25°C and 
away from direct heat (for example next to a heating unit) or direct light (direct sunlight or next to a 
lamp) Do not use the vial after this time period. It is recommended that the date of the first use be 
noted on the label. 
 
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Insulin Human Winthrop Rapid contains 
- The active substance is insulin human. One ml of Insulin Human Winthrop Rapid contains 

40 IU (International Units) of the active substance insulin human. 
- The other ingredients are: metacresol, sodium dihydrogen phosphate dihydrate, glycerol, 

sodium hydroxide (see section 2 under “Important information about some of the ingredients of 

 

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Insulin Human Winthrop Rapid”), hydrochloric acid (for pH adjustment) and water for 
injections. 

 
What Insulin Human Winthrop Rapid looks like and contents of the pack 
Insulin Human Winthrop Rapid is a clear, colourless solution for injection, with no solid particles 
visible, and of a water-like consistency. 
 
Insulin Human Winthrop Rapid is supplied in vials containing 10 ml solution (400 IU). Packs of 1 and 
5 vials of 10 ml are available. Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder and Manufacturer 
Sanofi-Aventis Deutschland GmbH 
D-65926 Frankfurt am Main 
Germany 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
Sanofi Belgium 
Tél/Tel: +32 (0)2 710 54 00 
 

Lietuva 
UAB «SANOFI-AVENTIS LIETUVA» 
Tel: +370 5 2755224 
 

България 
sanofi-aventis Bulgaria EOOD 
Тел.: +359 (0)2 970 53 00 
 

Luxembourg/Luxemburg 
Sanofi Belgium  
Tél/Tel: +32 (0)2 710 54 00 (Belgique/Belgien) 
 

Česká republika 
sanofi-aventis, s.r.o. 
Tel: +420 233 086 111 
 

Magyarország 
SANOFI-AVENTIS Zrt. 
Tel.: +36 1 505 0050 
 

Danmark 
sanofi-aventis Denmark A/S 
Tlf: +45 45 16 70 00 
 

Malta 
Sanofi Malta Ltd. 
Tel: +356 21493022 
 

Deutschland 
Zentiva Pharma GmbH 
Tel: +49 (0)180 20 200 10 
 

Nederland 
sanofi-aventis Netherlands B.V. 
Tel: +31 (0)182 557 755 
 

Eesti 
sanofi-aventis Estonia OÜ 
Tel: +372 627 34 88 
 

Norge 
Aventis Pharma Norge AS 
Tlf: +47 67 10 71 00 
 

Ελλάδα 
sanofi-aventis AEBE 
Τηλ: +30 210 900 16 00 
 

Österreich 
sanofi-aventis GmbH 
Tel: +43 1 80 185 – 0 
 

España 
sanofi-aventis, S.A. 
Tel: +34 93 485 94 00 
 

Polska 
sanofi-aventis Sp. z o.o. 
Tel.: +48 22 280 00 00 
 

France 
sanofi-aventis France 
Tél: 0 800 222 555 
Appel depuis l’étranger : +33 1 57 63 23 23 
 

Portugal 
Sanofi - Produtos Farmacêuticos, Lda. 
Tel: +351 21 35 89 400 
 

 

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Hrvatska 
sanofi-aventis Croatia d.o.o. 
Tel: +385 1 600 34 00 

România 
Sanofi Romania SRL 
Tel: +40 (0) 21 317 31 36 
 

Ireland 
sanofi-aventis Ireland Ltd. T/A SANOFI 
Tel: +353 (0) 1 403 56 00 
 

Slovenija 
sanofi-aventis d.o.o. 
Tel: +386 1 560 48 00 
 

Ísland 
Vistor hf. 
Sími: +354 535 7000 
 

Slovenská republika 
sanofi-aventis Pharma Slovakia s.r.o. 
Tel: +421 2 33 100 100 
 

Italia 
Sanofi S.p.A. 
Tel: 800 13 12 12 (domande di tipo tecnico)  
800 536389 (altre domande) 
 

Suomi/Finland 
Sanofi Oy 
Puh/Tel: +358 (0) 201 200 300 
 

Κύπρος 
sanofi-aventis Cyprus Ltd. 
Τηλ: +357 22 871600 
 

Sverige 
Sanofi AB 
Tel: +46 (0)8 634 50 00 
 

Latvija 
sanofi-aventis Latvia SIA 
Tel: +371 67 33 24 51 
 

United Kingdom 
Sanofi 
Tel: +44 (0) 845 372 7101 
 

 
This leaflet was last revised in {date} 
 
 
Other source of information 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu/ 
 
 
 
 

HYPERGLYCAEMIA AND HYPOGLYCAEMIA 
 

Always carry some sugar (at least 20 grams) with you. 
Carry some information with you to show you are diabetic. 

 
HYPERGLYCAEMIA (high blood sugar levels) 

 
If your blood sugar is too high (hyperglycaemia), you may not have injected enough insulin. 
 
Why does hyperglycaemia occur? 
 
Examples include: 
- you have not injected your insulin or not injected enough, or if it has become less effective, for 

example through incorrect storage, 
- you are doing less exercise than usual, you are under stress (emotional distress, excitement), or 

you have an injury, operation, infection or fever, 
- you are taking or have taken certain other medicines (see section 2, "Other medicines and 

Insulin Human Winthrop Rapid "). 
 

 

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Warning symptoms of hyperglycaemia 
 
Thirst, increased need to urinate, tiredness, dry skin, reddening of the face, loss of appetite, low blood 
pressure, fast heart beat, and glucose and ketone bodies in urine. Stomach pain, fast and deep 
breathing, sleepiness or even loss of consciousness may be signs of a serious condition (ketoacidosis) 
resulting from lack of insulin. 
 
What should you do if you experience hyperglycaemia 
 
Test your blood sugar level and your urine for ketones as soon as any of the above symptoms 
occur. Severe hyperglycaemia or ketoacidosis must always be treated by a doctor, normally in a 
hospital. 
 

HYPOGLYCAEMIA (low blood sugar levels) 
 
If your blood sugar level falls too much you may become unconscious. Serious hypoglycaemia may 
cause a heart attack or brain damage and may be life-threatening. You normally should be able to 
recognise when your blood sugar is falling too much so that you can take the right actions. 
 
Why does hypoglycaemia occur? 
 
Examples include: 
- you inject too much insulin, 
- you miss meals or delay them, 
- you do not eat enough, or eat food containing less carbohydrate than normal (sugar and 

substances similar to sugar are called carbohydrates; however, artificial sweeteners are NOT 
carbohydrates), 

- you lose carbohydrates due to vomiting or diarrhoea, 
- you drink alcohol, particularly if you are not eating much, 
- you are doing more exercise than usual or a different type of physical activity, 
- you are recovering from an injury or operation or other stress, 
- you are recovering from an illness or from fever, 
- you are taking or have stopped taking certain other medicines (see section 2, "Other medicines 

and Insulin Human Winthrop Rapid "). 
 
Hypoglycaemia is also more likely to occur if: 
- you have just begun insulin treatment or changed to another insulin preparation, 
- your blood sugar levels are almost normal or are unstable, 
- you change the area of skin where you inject insulin (for example from the thigh to the upper 

arm), 
- you suffer from severe kidney or liver disease, or some other disease such as hypothyroidism. 
 
Warning symptoms of hypoglycaemia 
 
- In your body 
Examples of symptoms that tell you that your blood sugar level is falling too much or too fast: 
sweating, clammy skin, anxiety, fast heart beat, high blood pressure, palpitations and irregular 
heartbeat. These symptoms often develop before the symptoms of a low sugar level in the brain. 
 
- In your brain 
Examples of symptoms that indicate a low sugar level in the brain: headaches, intense hunger, nausea, 
vomiting, tiredness, sleepiness, sleep disturbances, restlessness, aggressive behaviour, lapses in 
concentration, impaired reactions, depression, confusion, speech disturbances (sometimes total loss of 
speech), visual disorders, trembling, paralysis, tingling sensations (paraesthesia), numbness and 
tingling sensations in the area of the mouth, dizziness, loss of self-control, inability to look after 
yourself, convulsions, loss of consciousness. 
 

 

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The first symptoms which alert you to hypoglycaemia ("warning symptoms") may change, be weaker 
or may be missing altogether if 
- you are elderly, if you have had diabetes for a long time or if you suffer from a certain type of 

nervous disease (diabetic autonomic neuropathy), 
- you have recently suffered hypoglycaemia (for example the day before) or if it develops slowly, 
- you have almost normal or, at least, greatly improved blood sugar levels, 
- you have recently changed from an animal insulin to a human insulin such as Insulin Human 

Winthrop, 
- you are taking or have taken certain other medicines (see section 2, "Other medicines and 

Insulin Human Winthrop Rapid"). 
 
In such a case, you may develop severe hypoglycaemia (and even faint) before you are aware of the 
problem. Be familiar with your warning symptoms. If necessary, more frequent blood sugar testing 
can help to identify mild hypoglycaemic episodes that may otherwise be overlooked. If you are not 
confident about recognising your warning symptoms, avoid situations (such as driving a car) in which 
you or others would be put at risk by hypoglycaemia. 
 
What should you do if you experience hypoglycaemia 
 
1. Do not inject insulin. Immediately take about 10 to 20 g sugar, such as glucose, sugar cubes or a 

sugar-sweetened beverage. Caution: Artificial sweeteners and foods with artificial sweeteners 
(such as diet drinks) are of no help in treating hypoglycaemia. 

2. Then eat something that has a long-acting effect in raising your blood sugar (such as bread or 
pasta). Your doctor or nurse should have discussed this with you previously. 

3. If the hypoglycaemia comes back again take another 10 to 20 g sugar. 
4. Speak to a doctor immediately if you are not able to control the hypoglycaemia or if it recurs. 
 
Tell your relatives, friends and close colleagues the following: 
If you are not able to swallow or if you are unconscious, you will require an injection of glucose or 
glucagon (a medicine which increases blood sugar). These injections are justified even if it is not 
certain that you have hypoglycaemia. 
 
It is advisable to test your blood sugar immediately after taking glucose to check that you really have 
hypoglycaemia. 
 
 

 

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Package leaflet: Information for the user 

 
Insulin Human Winthrop Rapid 100 IU/ml solution for injection in a cartridge 

Insulin human 
 
 
Read all of this leaflet carefully before you start using this medicine because it contains 
important information for you. The instructions for using the insulin pen are provided with 
your insulin pen. Refer to them before using your medicine. 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor, pharmacist or nurse. 
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours. 
- If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible 

side effects not listed in this leaflet. 
 
What is in this leaflet: 
1. What Insulin Human Winthrop Rapid is and what it is used for 
2. What you need to know before you use Insulin Human Winthrop Rapid 
3. How to use Insulin Human Winthrop Rapid 
4. Possible side effects 
5. How to store Insulin Human Winthrop Rapid 
6. Contents of the pack and other information 
 
 
1. What Insulin Human Winthrop Rapid is and what it is used for 
 
Insulin Human Winthrop Rapid contains the active substance insulin human which is made by a 
biotechnology process and is identical with the body's own insulin. 
 
Insulin Human Winthrop Rapid is an insulin solution with a rapid onset and short duration of action.  
 
Insulin Human Winthrop Rapid is used to reduce high blood sugar in patients with diabetes mellitus 
who need treatment with insulin. Diabetes mellitus is a disease where your body does not produce 
enough insulin to control the level of blood sugar. Insulin Human Winthrop Rapid may also be used 
for treating hyperglycaemic coma (coma caused by too much blood sugar) and ketoacidosis (build-up 
of acid in the blood because the body is breaking down fat instead of sugar) as well as for controlling 
blood sugar before, during and after surgery. 
 
 
2. What you need to know before you use Insulin Human Winthrop Rapid 
 
Do not use Insulin Human Winthrop Rapid 
 
If you are allergic to insulin or any of the other ingredients of this medicine (listed in section 6).  
 
Warnings and precautions 
 
Talk to your doctor, pharmacist or nurse before using Insulin Human Winthrop Rapid. 
Follow closely the instructions for dosage, monitoring (blood and urine tests), diet and physical 
activity (physical work and exercise) as discussed with your doctor. 
 
If you are allergic to this medicine or to animal insulins, talk to your doctor. 
 

 

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Special patient groups 
If you have liver or kidneys problems or if you are elderly, speak to your doctor as you may need a 
lower dose. 
 
Travel 
Before travelling, consult your doctor. You may need to talk about 
- the availability of your insulin in the country you are visiting, 
- supplies of insulin, injection syringes etc., 
- correct storage of your insulin while travelling, 
- timing of meals and insulin administration while travelling, 
- the possible effects of changing to different time zones, 
- possible new health risks in the countries to be visited, 
- what you should do in emergency situations when you feel unwell or become ill. 
 
Illnesses and injuries 
In the following situations, the management of your diabetes may require a lot of care: 
- If you are ill or have a major injury then your blood sugar level may increase (hyperglycaemia).  
- If you are not eating enough, your blood sugar level may become too low (hypoglycaemia).  
In most cases you will need a doctor. Make sure that you contact a doctor early.  
 
If you have type 1 diabetes (insulin dependent diabetes mellitus), do not stop your insulin and 
continue to get enough carbohydrates. Always tell people who are caring for you or treating you that 
you require insulin. 
 
Some patients with long-standing type 2 diabetes mellitus and heart disease or previous stroke who 
were treated with pioglitazone and insulin experienced the development of heart failure. Inform your 
doctor as soon as possible if you experience signs of heart failure such as unusual shortness of breath 
or rapid increase in weight or localised swelling (oedema). 
 
Oher medicines and Insulin Human Winthrop Rapid 
 
Some medicines cause changes in the blood sugar level (decrease, increase or both depending on the 
situation). In each case, it may be necessary to adjust your insulin dosage to avoid blood sugar levels 
that are either too low or too high. Be careful when you start or stop taking another medicine. 
 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines. Before taking a medicine ask your doctor if it can affect your blood sugar level, and what 
action, if any, you need to take. 
 
Medicines that may cause your blood sugar level to fall (hypoglycaemia) include:  
- all other medicines to treat diabetes, 
- angiotensin converting enzyme (ACE) inhibitors (used to treat certain heart conditions or high 

blood pressure), 
- disopyramide (used to treat certain heart conditions), 
- fluoxetine (used to treat depression), 
- fibrates (used to lower high levels of blood lipids), 
- monoamine oxidase (MAO) inhibitors (used to treat depression), 
- pentoxifylline, propoxyphene, salicylates (such as aspirin, used to relieve pain and lower fever), 
- sulfonamide antibiotics. 
 
Medicines that may cause your blood sugar level to rise (hyperglycaemia) include:  
- corticosteroids (such as "cortisone", used to treat inflammation), 
- danazol (medicine acting on ovulation), 
- diazoxide (used to treat high blood pressure), 
- diuretics (used to treat high blood pressure or excessive fluid retention), 
- glucagon (pancreas hormone used to treat severe hypoglycaemia), 
- isoniazid (used to treat tuberculosis),  

 

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- oestrogens and progestogens (such as in the contraceptive pill used for birth control), 
- phenothiazine derivatives (used to treat psychiatric disorders), 
- somatropin (growth hormone), 
- sympathomimetic medicines (such as epinephrine [adrenaline] or salbutamol, terbutaline used to 

treat asthma), 
- thyroid hormones (used to treat the thyroid gland disorders), 
- protease inhibitors (used to treat HIV), 
- atypical antipsychotic medicines (such as olanzapine and clozapine). 
 
Your blood sugar level may either rise or fall if you take:  
- beta-blockers (used to treat high blood pressure), 
- clonidine (used to treat high blood pressure), 
- lithium salts (used to treat psychiatric disorders). 
Pentamidine (used to treat some infections caused by parasites) may cause hypoglycaemia which may 
sometimes be followed by hyperglycaemia. 
 
Beta-blockers like other sympatholytic medicines (such as clonidine, guanethidine, and reserpine) may 
weaken or suppress entirely the first warning symptoms which help you to recognise a 
hypoglycaemia. 
 
If you are not sure whether you are taking one of those medicines ask your doctor or pharmacist. 
 
Insulin Human Winthrop Rapid with alcohol 
 
Your blood sugar levels may either rise or fall if you drink alcohol. 
 
Pregnancy and breast-feeding 
 
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor or pharmacist for advice before taking this medicine. 
 
Inform your doctor if you are planning to become pregnant, or if you are already pregnant. Your 
insulin dosage may need to be changed during pregnancy and after giving birth. Particularly careful 
control of your diabetes, and prevention of hypoglycaemia, is important for the health of your baby.  
 
If you are breast-feeding consult your doctor as you may require adjustments in your insulin doses and 
your diet. 
 
Driving and using machines 
 
Your ability to concentrate or react may be reduced if: 
- you have hypoglycaemia (low blood sugar levels), 
- you have hyperglycaemia (high blood sugar levels), 
- you have problems with your sight.  
Keep this possible problem in mind in all situations where you might put yourself and others at risk 
(such as driving a car or using machines). You should contact your doctor for advice on driving if: 
- you have frequent episodes of hypoglycaemia, 
- the first warning symptoms which help you to recognise hypoglycaemia are reduced or absent. 
 
Important information about some of the ingredients of Insulin Human Winthrop Rapid  
 
This medicine contains less than 1 mmol (23 mg) sodium per dose, i.e. it is essentially ‘sodium-free’. 
 
 

 

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3. How to use Insulin Human Winthrop Rapid 
 
Dose 
 
Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor 
or pharmacist if you are not sure. 
 
Based on your life-style and the results of your blood sugar (glucose) tests, your doctor will 
- determine how much Insulin Human Winthrop Rapid per day you will need, 
- tell you when to check your blood sugar level, and whether you need to carry out urine tests, 
- tell you when you may need to inject a higher or lower dose of Insulin Human Winthrop Rapid. 
 
Many factors may influence your blood sugar level. You should know these factors so that you are 
able to react correctly to changes in your blood sugar level and to prevent it from becoming too high 
or too low. See the box at the end of this leaflet for further information. 
 
Frequency of administration 
 
Insulin Human Winthrop Rapid is injected under the skin 15 to 20 minutes before a meal. 
 
Method of administration 
 
Insulin Human Winthrop Rapid is a solution for injection under the skin or, in exceptional 
circumstances, into a vein (blood vessel).  
 
Your doctor will show you in which area of the skin you should inject your insulin. With each 
injection, change the puncture site within the particular area of skin that you are using. 
 
Insulin administration into a vein for example to treat severe hyperglycaemia and ketoacidosis, 
requires experience and special safety precautions. For these reasons, it must be done in a clinic or a 
similar setting. 
 
Do not use Insulin Human Winthrop Rapid in insulin pumps - special insulin preparations are 
available for use in such devices. Also do not use it in peristaltic pumps with silicone tubing. 
 
How to handle the cartridges 
 
To ensure you get the accurate dose, the Insulin Human Winthrop Rapid cartridges are to be used only 
with the following pens: 
- JuniorSTAR which delivers doses in steps of 0.5 units  
- OptiPen, ClikSTAR, Tactipen, Autopen 24 or AllStar which deliver doses in steps of 1 unit. 
Not all of these pens may be marketed in your country.  
 
The pen should be used as recommended in the information provided by the device manufacturer. The 
manufacturer’s instructions for using the pen must be followed carefully for loading the cartridge, 
attaching the injection needle, and administering the insulin injection. 
 
Keep the cartridge at room temperature for 1 or 2 hours before inserting it into the pen. 
 
Look at the cartridge before you use it. Only use it if the solution is clear, colourless, with no solid 
particles visible, and has a water-like consistency. 
 
Special care before injection 
 
Before injection remove any air bubbles (see instructions for using the pen). Make sure that neither 
alcohol nor other disinfectants or other substances contaminate the insulin. 
- Do not re-fill and re-use empty cartridges. 

 

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- Do not add any other insulin to the cartridge. 
- Do not mix insulin with any other medicines. 
 
Problems with the pen? 
 
Refer to the manufacturer’s instructions for using the pen. 
If the insulin pen is damaged or not working properly (due to mechanical defects) it has to be 
discarded, and a new insulin pen has to be used. 
 
If the pen does not function well, you can draw the insulin from the cartridge into an injection syringe. 
Therefore, keep injection syringes and needles as well. However, use only those injection syringes 
which are designed for an insulin concentration of 100 IU (International Units) per ml. 
 
If you use more Insulin Human Winthrop Rapid than you should 
- If you have injected too much Insulin Human Winthrop Rapid, your blood sugar level may 

become too low (hypoglycaemia). Check your blood sugar frequently. In general, to prevent 
hypoglycaemia you must eat more food and monitor your blood sugar. For information on the 
treatment of hypoglycaemia, see box at the end of this leaflet. 

 
If you forget to use Insulin Human Winthrop Rapid 
- If you have missed a dose of Insulin Human Winthrop Rapid or if you have not injected 

enough insulin, your blood sugar level may become too high (hyperglycaemia). Check your 
blood sugar frequently. For information on the treatment of hyperglycaemia, see box at the end 
of this leaflet. 

 
- Do not take a double dose to make up for a forgotten dose. 
 
If you stop using Insulin Human Winthrop Rapid 
 
This could lead to severe hyperglycaemia (very high blood sugar) and ketoacidosis (build-up of acid 
in the blood because the body is breaking down fat instead of sugar). Do not stop Insulin Human 
Winthrop Rapid without speaking to a doctor, who will tell you what needs to be done. 
 
If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse. 
 
Insulin Mix-ups 
 
You must always check the insulin label before each injection to avoid mix-ups between Insulin 
Human Winthrop Rapid and other insulins.  
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
The most frequent side effect is hypoglycaemia (low blood sugar). The specific frequency cannot be 
estimated from available data (frequency not known). Serious hypoglycaemia may cause a heart attack 
or brain damage and may be life-threatening. For further information on the side effects of low blood 
sugar or high blood sugar, see the box at the end of this leaflet. 
 
Severe allergic reactions to insulin may occur which may become life-threatening. Such reactions to 
insulin or to the excipients can cause large-scale skin reactions (rash and itching all over the body); 
severe swelling of skin or mucous membranes (angiooedema), shortness of breath, a fall in blood 
pressure with rapid heart beat and sweating. Frequency of these reactions cannot be estimated from 
available data. 
 

 

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Side effects reported commonly (may affect up to 1 in 10 people) 
• Oedema 
Insulin treatment may cause temporary build-up of water in the body with swelling in the calves and 
ankles. 
• Injection site reactions 
 
Side effects reported uncommonly (may affect up to 1 in 100 people) 
• Severe allergic reaction with low blood pressure (shock) 
• Injection site urticaria (itchy rash) 
 
Other side effects include (frequency cannot be estimated from the available data) 
• Sodium retention 
• Eye reactions 
A marked change (improvement or worsening) in your blood sugar control can disturb your vision 
temporarily. If you have proliferative retinopathy (an eye disease related to diabetes) severe 
hypoglycaemic attacks may cause temporary loss of vision. 
• Skin changes at the injection site (lipodystrophy) 
If you inject your insulin too often at the same skin site, fatty tissue under the skin at this site may 
either shrink or thicken. Insulin that you inject in such a site may not work very well. Changing the 
injection site with each injection may help to prevent such skin changes. 
• Skin and allergic reactions 
Other mild reactions at the injection site (such as injection site redness, unusually intense pain on 
injection site, itching, injection site swelling or injection site inflammation) may occur. They can also 
spread around the injection site. Most minor reactions to insulins usually resolve in a few days to a 
few weeks. 
 
Insulin treatment can cause the body to produce antibodies to insulin (substances that act against 
insulin). However, only very rarely, this will require a change to your insulin dosage. 
 
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side 
effects not listed in this leaflet. 
 
 
5. How to store Insulin Human Winthrop Rapid 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date which is stated on the carton and on the label of the 
cartridge after “EXP”. The expiry date refers to the last day of that month. 
 
Unopened cartridges 
Store in a refrigerator (2°C - 8°C). Do not freeze. Do not put Insulin Human Winthrop Rapid next to 
the freezer compartment or a freezer pack. Keep the cartridge in the outer carton in order to protect 
from light. 
 
In-use cartridges 
Cartridges in-use (in the insulin pen) or carried as a spare may be stored for a maximum of 4 weeks 
not above 25°C and away from direct heat (for example next to a heating unit) or direct light (direct 
sunlight or next to a lamp). The cartridge in-use must not be stored in a refrigerator. Do not use the 
cartridge after this time period. 
 
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment. 
 
 

 

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6. Contents of the pack and other information 
 
What Insulin Human Winthrop Rapid contains 
- The active substance is insulin human. One ml of Insulin Human Winthrop Rapid contains 

100 IU (International Units) of the active substance insulin human. 
- The other ingredients are: metacresol, sodium dihydrogen phosphate dihydrate, glycerol, 

sodium hydroxide (see section 2 under “Important information about some of the ingredients of 
Insulin Human Winthrop Rapid”), hydrochloric acid (for pH adjustment) and water for 
injections. 

 
What Insulin Human Winthrop Rapid looks like and contents of the pack 
Insulin Human Winthrop Rapid is a clear, colourless solution for injection, with no solid particles 
visible, and of a water-like consistency. 
 
Insulin Human Winthrop Rapid is supplied in cartridges containing 3 ml solution (300 IU). Packs of 3, 
4, 5, 6, 9 and 10 cartridges of 3 ml are available. Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder and Manufacturer 
Sanofi-Aventis Deutschland GmbH 
D-65926 Frankfurt am Main 
Germany 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
Sanofi Belgium 
Tél/Tel: +32 (0)2 710 54 00 
 

Lietuva 
UAB «SANOFI-AVENTIS LIETUVA» 
Tel: +370 5 2755224 
 

България 
sanofi-aventis Bulgaria EOOD 
Тел.: +359 (0)2 970 53 00 
 

Luxembourg/Luxemburg 
Sanofi Belgium  
Tél/Tel: +32 (0)2 710 54 00 (Belgique/Belgien) 
 

Česká republika 
sanofi-aventis, s.r.o. 
Tel: +420 233 086 111 
 

Magyarország 
SANOFI-AVENTIS Zrt. 
Tel.: +36 1 505 0050 
 

Danmark 
sanofi-aventis Denmark A/S 
Tlf: +45 45 16 70 00 
 

Malta 
Sanofi Malta Ltd. 
Tel: +356 21493022 
 

Deutschland 
Zentiva Pharma GmbH 
Tel: +49 (0)180 20 200 10 
 

Nederland 
sanofi-aventis Netherlands B.V. 
Tel: +31 (0)182 557 755 
 

Eesti 
sanofi-aventis Estonia OÜ 
Tel: +372 627 34 88 
 

Norge 
Aventis Pharma Norge AS 
Tlf: +47 67 10 71 00 
 

Ελλάδα 
sanofi-aventis AEBE 
Τηλ: +30 210 900 16 00 
 

Österreich 
sanofi-aventis GmbH 
Tel: +43 1 80 185 – 0 
 

España 
sanofi-aventis, S.A. 
Tel: +34 93 485 94 00 
 

Polska 
sanofi-aventis Sp. z o.o. 
Tel.: +48 22 280 00 00 
 

 

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France 
sanofi-aventis France 
Tél: 0 800 222 555 
Appel depuis l’étranger : +33 1 57 63 23 23 
 

Portugal 
Sanofi - Produtos Farmacêuticos, Lda. 
Tel: +351 21 35 89 400 
 

Hrvatska 
sanofi-aventis Croatia d.o.o. 
Tel: +385 1 600 34 00 

România 
Sanofi Romania SRL 
Tel: +40 (0) 21 317 31 36 
 

Ireland 
sanofi-aventis Ireland Ltd. T/A SANOFI 
Tel: +353 (0) 1 403 56 00 
 

Slovenija 
sanofi-aventis d.o.o. 
Tel: +386 1 560 48 00 
 

Ísland 
Vistor hf. 
Sími: +354 535 7000 
 

Slovenská republika 
sanofi-aventis Pharma Slovakia s.r.o. 
Tel: +421 2 33 100 100 
 

Italia 
Sanofi S.p.A. 
Tel: 800 13 12 12 (domande di tipo tecnico)  
800 536389 (altre domande) 
 

Suomi/Finland 
Sanofi Oy 
Puh/Tel: +358 (0) 201 200 300 
 

Κύπρος 
sanofi-aventis Cyprus Ltd. 
Τηλ: +357 22 871600 
 

Sverige 
Sanofi AB 
Tel: +46 (0)8 634 50 00 
 

Latvija 
sanofi-aventis Latvia SIA 
Tel: +371 67 33 24 51 
 

United Kingdom 
Sanofi 
Tel: +44 (0) 845 372 7101 
 

 
This leaflet was last revised in {date} 
 
 
Other source of information 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu/ 
 
 
 
 

HYPERGLYCAEMIA AND HYPOGLYCAEMIA 
 

Always carry some sugar (at least 20 grams) with you. 
Carry some information with you to show you are diabetic. 

 
HYPERGLYCAEMIA (high blood sugar levels) 

 
If your blood sugar is too high (hyperglycaemia), you may not have injected enough insulin. 
 
Why does hyperglycaemia occur? 
 
Examples include: 
- you have not injected your insulin or not injected enough, or if it has become less effective, for 

example through incorrect storage, 
- your insulin pen does not work properly, 

 

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- you are doing less exercise than usual, you are under stress (emotional distress, excitement), or 
you have an injury, operation, infection or fever, 

- you are taking or have taken certain other medicines (see section 2, "Other medicines and 
Insulin Human Winthrop Rapid"). 

 
Warning symptoms of hyperglycaemia 
 
Thirst, increased need to urinate, tiredness, dry skin, reddening of the face, loss of appetite, low blood 
pressure, fast heart beat, and glucose and ketone bodies in urine. Stomach pain, fast and deep 
breathing, sleepiness or even loss of consciousness may be signs of a serious condition (ketoacidosis) 
resulting from lack of insulin. 
 
What should you do if you experience hyperglycaemia 
 
Test your blood sugar level and your urine for ketones as soon as any of the above symptoms 
occur. Severe hyperglycaemia or ketoacidosis must always be treated by a doctor, normally in a 
hospital. 
 

HYPOGLYCAEMIA (low blood sugar levels) 
 
If your blood sugar level falls too much you may become unconscious. Serious hypoglycaemia may 
cause a heart attack or brain damage and may be life-threatening. You normally should be able to 
recognise when your blood sugar is falling too much so that you can take the right actions. 
 
Why does hypoglycaemia occur? 
 
Examples include: 
- you inject too much insulin, 
- you miss meals or delay them, 
- you do not eat enough, or eat food containing less carbohydrate than normal (sugar and 

substances similar to sugar are called carbohydrates; however, artificial sweeteners are NOT 
carbohydrates), 

- you lose carbohydrates due to vomiting or diarrhoea, 
- you drink alcohol, particularly if you are not eating much, 
- you are doing more exercise than usual or a different type of physical activity, 
- you are recovering from an injury or operation or other stress, 
- you are recovering from an illness or from fever, 
- you are taking or have stopped taking certain other medicines (see section 2, "Other medicines 

and Insulin Human Winthrop Rapid"). 
 
Hypoglycaemia is also more likely to occur if: 
- you have just begun insulin treatment or changed to another insulin preparation, 
- your blood sugar levels are almost normal or are unstable, 
- you change the area of skin where you inject insulin (for example from the thigh to the upper 

arm), 
- you suffer from severe kidney or liver disease, or some other disease such as hypothyroidism. 
 
Warning symptoms of hypoglycaemia 
 
- In your body 
Examples of symptoms that tell you that your blood sugar level is falling too much or too fast: 
sweating, clammy skin, anxiety, fast heart beat, high blood pressure, palpitations and irregular 
heartbeat. These symptoms often develop before the symptoms of a low sugar level in the brain. 
 
- In your brain 
Examples of symptoms that indicate a low sugar level in the brain: headaches, intense hunger, nausea, 
vomiting, tiredness, sleepiness, sleep disturbances, restlessness, aggressive behaviour, lapses in 

 

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concentration, impaired reactions, depression, confusion, speech disturbances (sometimes total loss of 
speech), visual disorders, trembling, paralysis, tingling sensations (paraesthesia), numbness and 
tingling sensations in the area of the mouth, dizziness, loss of self-control, inability to look after 
yourself, convulsions, loss of consciousness. 
 
The first symptoms which alert you to hypoglycaemia ("warning symptoms") may change, be weaker 
or may be missing altogether if 
- you are elderly, if you have had diabetes for a long time or if you suffer from a certain type of 

nervous disease (diabetic autonomic neuropathy), 
- you have recently suffered hypoglycaemia (for example the day before) or if it develops slowly, 
- you have almost normal or, at least, greatly improved blood sugar levels, 
- you have recently changed from an animal insulin to a human insulin such as Insulin Human 

Winthrop, 
- you are taking or have taken certain other medicines (see section 2, "Other medicines and 

Insulin Human Winthrop Rapid"). 
 
In such a case, you may develop severe hypoglycaemia (and even faint) before you are aware of the 
problem. Be familiar with your warning symptoms. If necessary, more frequent blood sugar testing 
can help to identify mild hypoglycaemic episodes that may otherwise be overlooked. If you are not 
confident about recognising your warning symptoms, avoid situations (such as driving a car) in which 
you or others would be put at risk by hypoglycaemia. 
 
What should you do if you experience hypoglycaemia 
 
1. Do not inject insulin. Immediately take about 10 to 20 g sugar, such as glucose, sugar cubes or a 

sugar-sweetened beverage. Caution: Artificial sweeteners and foods with artificial sweeteners 
(such as diet drinks) are of no help in treating hypoglycaemia. 

2. Then eat something that has a long-acting effect in raising your blood sugar (such as bread or 
pasta). Your doctor or nurse should have discussed this with you previously. 

3. If the hypoglycaemia comes back again take another 10 to 20 g sugar. 
4. Speak to a doctor immediately if you are not able to control the hypoglycaemia or if it recurs. 
 
Tell your relatives, friends and close colleagues the following: 
If you are not able to swallow or if you are unconscious, you will require an injection of glucose or 
glucagon (a medicine which increases blood sugar). These injections are justified even if it is not 
certain that you have hypoglycaemia. 
 
It is advisable to test your blood sugar immediately after taking glucose to check that you really have 
hypoglycaemia. 
 
 

 

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Package leaflet: Information for the user 

 
Insulin Human Winthrop Rapid SoloStar 100 IU/ml, solution for injection in a pre-filled pen 

Insulin human 
 
 
Read all of this leaflet carefully, including the Instructions for Use of Insulin Winthrop Rapid 
SoloStar, pre-filled pen, before you start using this medicine because it contains important 
information for you. 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor, pharmacist or nurse. 
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours. 
- If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible 

side effects not listed in this leaflet. 
 
What is in this leaflet: 
1. What Insulin Human Winthrop Rapid is and what it is used for 
2. What you need to know before you use Insulin Human Winthrop Rapid 
3. How to use Insulin Human Winthrop Rapid 
4. Possible side effects 
5. How to store Insulin Human Winthrop Rapid 
6. Contents of the pack and other information 
 
 
1. What Insulin Human Winthrop Rapid is and what it is used for 
 
Insulin Human Winthrop Rapid contains the active substance insulin human which is made by a 
biotechnology process and is identical with the body's own insulin. 
 
Insulin Human Winthrop Rapid is an insulin solution with a rapid onset and short duration of action. It 
comes in cartridges sealed in disposable pen injectors, SoloStar. 
 
Insulin Human Winthrop Rapid is used to reduce high blood sugar in patients with diabetes mellitus 
who need treatment with insulin. Diabetes mellitus is a disease where your body does not produce 
enough insulin to control the level of blood sugar. 
 
 
2. What you need to know before you use Insulin Human Winthrop Rapid 
 
Do not use Insulin Human Winthrop Rapid 
 
If you are allergic to insulin or any of the other ingredients of this medicine (listed in section 6).  
 
Warnings and precautions 
 
Talk to your doctor, pharmacist or nurse before using Insulin Human Winthrop Rapid. 
Follow closely the instructions for dosage, monitoring (blood and urine tests), diet and physical 
activity (physical work and exercise), injection technique as discussed with your doctor. 
 
If you are allergic to this medicine or to animal insulins, talk to your doctor. 
 
Special patient groups 
If you have liver or kidneys problems or if you are elderly, speak to your doctor as you may need a 
lower dose. 
 

 

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Travel 
Before travelling, consult your doctor. You may need to talk about 
- the availability of your insulin in the country you are visiting, 
- supplies of insulin, injection syringes etc., 
- correct storage of your insulin while travelling, 
- timing of meals and insulin administration while travelling, 
- the possible effects of changing to different time zones, 
- possible new health risks in the countries to be visited, 
- what you should do in emergency situations when you feel unwell or become ill. 
 
Illnesses and injuries 
In the following situations, the management of your diabetes may require a lot of care: 
- If you are ill or have a major injury then your blood sugar level may increase (hyperglycaemia).  
- If you are not eating enough, your blood sugar level may become too low (hypoglycaemia).  
In most cases you will need a doctor. Make sure that you contact a doctor early.  
 
If you have type 1 diabetes (insulin dependent diabetes mellitus), do not stop your insulin and 
continue to get enough carbohydrates. Always tell people who are caring for you or treating you that 
you require insulin. 
 
Some patients with long-standing type 2 diabetes mellitus and heart disease or previous stroke who 
were treated with pioglitazone and insulin experienced the development of heart failure. Inform your 
doctor as soon as possible if you experience signs of heart failure such as unusual shortness of breath 
or rapid increase in weight or localised swelling (oedema). 
 
Other medicines and Insulin Human Winthrop Rapid 
 
Some medicines cause changes in the blood sugar level (decrease, increase or both depending on the 
situation). In each case, it may be necessary to adjust your insulin dosage to avoid blood sugar levels 
that are either too low or too high. Be careful when you start or stop taking another medicine. 
 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines. Before taking a medicine ask your doctor if it can affect your blood sugar level, and what 
action, if any, you need to take. 
 
Medicines that may cause your blood sugar level to fall (hypoglycaemia) include:  
- all other medicines to treat diabetes,  
- angiotensin converting enzyme (ACE) inhibitors (used to treat certain heart conditions or high 

blood pressure),  
- disopyramide (used to treat certain heart conditions),  
- fluoxetine (used to treat depression),  
- fibrates (used to lower high levels of blood lipids),  
- monoamine oxidase (MAO) inhibitors (used to treat depression),  
- pentoxifylline, propoxyphene, salicylates (such as aspirin, used to relieve pain and lower fever), 
- sulfonamide antibiotics. 
 
Medicines that may cause your blood sugar level to rise (hyperglycaemia) include:  
- corticosteroids (such as "cortisone", used to treat inflammation),  
- danazol (medicine acting on ovulation),  
- diazoxide (used to treat high blood pressure),  
- diuretics (used to treat high blood pressure or excessive fluid retention),  
- glucagon (pancreas hormone used to treat severe hypoglycaemia),  
- isoniazid (used to treat tuberculosis),  
- oestrogens and progestogens (such as in the contraceptive pill used for birth control),  
- phenothiazine derivatives (used to treat psychiatric disorders),  
- somatropin (growth hormone),  

 

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- sympathomimetic medicines (such as epinephrine [adrenaline] or salbutamol, terbutaline used to 
treat asthma), 

- thyroid hormones (used to treat the thyroid gland disorders), 
- protease inhibitors (used to treat HIV), 
- atypical antipsychotic medicines (such as olanzapine and clozapine). 
 
Your blood sugar level may either rise or fall if you take:  
- beta-blockers (used to treat high blood pressure),  
- clonidine (used to treat high blood pressure), 
- lithium salts (used to treat psychiatric disorders).  
Pentamidine (used to treat some infections caused by parasites) may cause hypoglycaemia which may 
sometimes be followed by hyperglycaemia. 
 
Beta-blockers like other sympatholytic medicines (such as clonidine, guanethidine, and reserpine) may 
weaken or suppress entirely the first warning symptoms which help you to recognise a 
hypoglycaemia. 
 
If you are not sure whether you are taking one of those medicines ask your doctor or pharmacist. 
 
Insulin Human Winthrop Rapid with alcohol 
 
Your blood sugar levels may either rise or fall if you drink alcohol. 
 
Pregnancy and breast-feeding 
 
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor or pharmacist for advice before taking this medicine. 
 
Inform your doctor if you are planning to become pregnant, or if you are already pregnant. Your 
insulin dosage may need to be changed during pregnancy and after giving birth. Particularly careful 
control of your diabetes, and prevention of hypoglycaemia, is important for the health of your baby.  
 
If you are breast-feeding consult your doctor as you may require adjustments in your insulin doses and 
your diet. 
 
Driving and using machines 
 
Your ability to concentrate or react may be reduced if: 
- you have hypoglycaemia (low blood sugar levels), 
- you have hyperglycaemia (high blood sugar levels), 
- you have problems with your sight.  
Keep this possible problem in mind in all situations where you might put yourself and others at risk 
(such as driving a car or using machines). You should contact your doctor for advice on driving if: 
- you have frequent episodes of hypoglycaemia, 
- the first warning symptoms which help you to recognise hypoglycaemia are reduced or absent. 
 
Important information about some of the ingredients of Insulin Human Winthrop Rapid  
 
This medicine contains less than 1 mmol (23 mg) sodium per dose, i.e. it is essentially ‘sodium-free’. 
 
 

 

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3. How to use Insulin Human Winthrop Rapid 
 
Dose 
 
Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor 
or pharmacist if you are not sure. 
 
Based on your life-style and the results of your blood sugar (glucose) tests, your doctor will 
- determine how much Insulin Human Winthrop Rapid per day you will need, 
- tell you when to check your blood sugar level, and whether you need to carry out urine tests, 
- tell you when you may need to inject a higher or lower dose of Insulin Human Winthrop Rapid. 
 
Many factors may influence your blood sugar level. You should know these factors so that you are 
able to react correctly to changes in your blood sugar level and to prevent it from becoming too high 
or too low. See the box at the end of this leaflet for further information. 
 
Frequency of administration 
 
Insulin Human Winthrop Rapid is injected under the skin 15 to 20 minutes before a meal. 
 
Method of administration 
 
Insulin Human Winthrop Rapid is a solution for injection under the skin. 
 
SoloStar delivers insulin in doses from 1 to 80 units in steps of 1 unit. Each pen contains multiple 
doses. 
 
Your doctor will show you in which area of the skin you should inject your insulin. With each 
injection, change the puncture site within the particular area of skin that you are using. 
 
How to handle SoloStar 
 
SoloStar is a pre-filled disposable pen containing human insulin. 
 
Read carefully the "SoloStar Instructions for Use" included in this package leaflet. You must 
use the pen as described in these Instructions for Use. 
 
A new injection needle must be attached before each use. Only use needles that have been approved 
for use with SoloStar. 
A safety test must be performed before each injection. 
 
Look at the cartridge before you use the pen. Do not use Insulin Human Winthrop Rapid if you notice 
particles in it. Only use Insulin Human Winthrop Rapid if the solution is clear, colourless and 
waterlike. 
 
Always use a new pen if you notice that your blood sugar control is unexpectedly getting worse. If 
you think you have a problem with SoloStar, consult your doctor, pharmacist or nurse. 
 
To prevent the possible transmission of disease, each pen must be used by one patient only. 
 
Special care before injection 
 
Make sure that neither alcohol nor other disinfectants or other substances contaminate the insulin. 
 
Do not mix insulin with any other medicines. Insulin Human Winthrop Rapid SoloStar pre-filled pen, 
is not designed to allow any other insulin to be mixed in the cartridge. 
 

 

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Empty pens must not be re-filled and must be properly discarded. 
 
Do not use SoloStar if it is damaged or not working properly (due to mechanical defects), it has to be 
discarded and a new SoloStar has to be used. 
 
If you use more Insulin Human Winthrop Rapid than you should 
- If you have injected too much Insulin Human Winthrop Rapid, your blood sugar level may 

become too low (hypoglycaemia). Check your blood sugar frequently. In general, to prevent 
hypoglycaemia you must eat more food and monitor your blood sugar. For information on the 
treatment of hypoglycaemia, see box at the end of this leaflet. 

 
If you forget to use Insulin Human Winthrop Rapid 
- If you have missed a dose of Insulin Human Winthrop Rapid or if you have not injected 

enough insulin, your blood sugar level may become too high (hyperglycaemia). Check your 
blood sugar frequently. For information on the treatment of hyperglycaemia, see box at the end 
of this leaflet. 

 
- Do not take a double dose to make up for a forgotten dose. 
 
If you stop using Insulin Human Winthrop Rapid 
 
This could lead to severe hyperglycaemia (very high blood sugar) and ketoacidosis (build-up of acid 
in the blood because the body is breaking down fat instead of sugar). Do not stop Insulin Human 
Winthrop Rapid without speaking to a doctor, who will tell you what needs to be done. 
 
If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse. 
 
Insulin Mix-ups 
 
You must always check the insulin label before each injection to avoid mix-ups between Insulin 
Human Winthrop Rapid and other insulins.  
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
The most frequent side effect is hypoglycaemia (low blood sugar). The specific frequency cannot be 
estimated from available data (frequency not known). Serious hypoglycaemia may cause a heart attack 
or brain damage and may be life-threatening. For further information on the side effects of low blood 
sugar or high blood sugar, see the box at the end of this leaflet. 
 
Severe allergic reactions to insulin may occur which may become life-threatening. Such reactions to 
insulin or to the excipients can cause large-scale skin reactions (rash and itching all over the body); 
severe swelling of skin or mucous membranes (angiooedema), shortness of breath, a fall in blood 
pressure with rapid heart beat and sweating. Frequency of these reactions cannot be estimated from 
available data. 
 
Side effects reported commonly (may affect up to 1 in 10 people) 
• Oedema 
Insulin treatment may cause temporary build-up of water in the body with swelling in the calves and 
ankles. 
• Injection site reactions 
 
Side effects reported uncommonly (may affect up to 1 in 100 people) 
• Severe allergic reaction with low blood pressure (shock) 
• Injection site urticaria (itchy rash) 

 

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Other side effects include (frequency annot be estimated from the available data) 
• Sodium retention 
• Eye reactions 
A marked change (improvement or worsening) in your blood sugar control can disturb your vision 
temporarily. If you have proliferative retinopathy (an eye disease related to diabetes) severe 
hypoglycaemic attacks may cause temporary loss of vision.  
• Skin changes at the injection site (lipodystrophy) 
If you inject your insulin too often at the same skin site, fatty tissue under the skin at this site may 
either shrink or thicken. Insulin that you inject in such a site may not work very well. Changing the 
injection site with each injection may help to prevent such skin changes. 
• Skin and allergic reactions 
Other mild reactions at the injection site (such as injection site redness, unusually intense pain on 
injection site, itching, injection site swelling or injection site inflammation) may occur. They can also 
spread around the injection site. Most minor reactions to insulins usually resolve in a few days to a 
few weeks. 
 
Insulin treatment can cause the body to produce antibodies to insulin (substances that act against 
insulin). However, only very rarely, this will require a change to your insulin dosage. 
 
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side 
effects not listed in this leaflet. 
 
 
5. How to store Insulin Human Winthrop Rapid 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date which is stated on the carton and on the label of the pen 
after “EXP”. The expiry date refers to the last day of that month. 
 
Not in-use pens 
Store in a refrigerator (2°C - 8°C). Do not freeze. Do not put the pre-filled pen next to the freezer 
compartment or a freezer pack. Keep the pre-filled pen in the outer carton in order to protect from 
light. 
 
In-use pens 
Pre-filled pens in-use or carried as a spare may be stored for a maximum of 4 weeks not above 25°C 
and away from direct heat (for example next to a heating unit) or direct light (direct sunlight or next to 
a lamp). The pen in-use must not be stored in a refrigerator. Do not use the pen after this time period.  
 
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Insulin Human Winthrop Rapid contains 
- The active substance is insulin human. One ml of Insulin Human Winthrop Rapid contains 

100 IU (International Units) of the active substance insulin human. 
- The other ingredients are: metacresol, sodium dihydrogen phosphate dihydrate, glycerol, 

sodium hydroxide (see section 2 under “Important information about some of the ingredients of 
Insulin Human Winthrop Rapid”), hydrochloric acid (for pH adjustment) and water for 
injections. 

 

 

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What Insulin Human Winthrop Rapid looks like and contents of the pack 
Insulin Human Winthrop Rapid is a clear, colourless solution for injection, with no solid particles 
visible, and of a water-like consistency. 
 
Insulin Human Winthrop Rapid is supplied in pre-filled pens, SoloStar, containing 3 ml solution 
(300 IU). Packs of 3, 4, 5, 6, 9 and 10 pens of 3 ml are available. Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder and Manufacturer 
Sanofi-Aventis Deutschland GmbH 
D-65926 Frankfurt am Main 
Germany 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
Sanofi Belgium 
Tél/Tel: +32 (0)2 710 54 00 
 

Lietuva 
UAB «SANOFI-AVENTIS LIETUVA» 
Tel: +370 5 2755224 
 

България 
sanofi-aventis Bulgaria EOOD 
Тел.: +359 (0)2 970 53 00 
 

Luxembourg/Luxemburg 
Sanofi Belgium  
Tél/Tel: +32 (0)2 710 54 00 (Belgique/Belgien) 
 

Česká republika 
sanofi-aventis, s.r.o. 
Tel: +420 233 086 111 
 

Magyarország 
SANOFI-AVENTIS Zrt. 
Tel.: +36 1 505 0050 
 

Danmark 
sanofi-aventis Denmark A/S 
Tlf: +45 45 16 70 00 
 

Malta 
Sanofi Malta Ltd. 
Tel: +356 21493022 
 

Deutschland 
Zentiva Pharma GmbH 
Tel: +49 (0)180 20 200 10 
 

Nederland 
sanofi-aventis Netherlands B.V. 
Tel: +31 (0)182 557 755 
 

Eesti 
sanofi-aventis Estonia OÜ 
Tel: +372 627 34 88 
 

Norge 
Aventis Pharma Norge AS 
Tlf: +47 67 10 71 00 
 

Ελλάδα 
sanofi-aventis AEBE 
Τηλ: +30 210 900 16 00 
 

Österreich 
sanofi-aventis GmbH 
Tel: +43 1 80 185 – 0 
 

España 
sanofi-aventis, S.A. 
Tel: +34 93 485 94 00 
 

Polska 
sanofi-aventis Sp. z o.o. 
Tel.: +48 22 280 00 00 
 

France 
sanofi-aventis France 
Tél: 0 800 222 555 
Appel depuis l’étranger : +33 1 57 63 23 23 
 

Portugal 
Sanofi - Produtos Farmacêuticos, Lda. 
Tel: +351 21 35 89 400 
 

 

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Hrvatska 
sanofi-aventis Croatia d.o.o. 
Tel: +385 1 600 34 00 

România 
Sanofi Romania SRL 
Tel: +40 (0) 21 317 31 36 
 

Ireland 
sanofi-aventis Ireland Ltd. T/A SANOFI 
Tel: +353 (0) 1 403 56 00 
 

Slovenija 
sanofi-aventis d.o.o. 
Tel: +386 1 560 48 00 
 

Ísland 
Vistor hf. 
Sími: +354 535 7000 
 

Slovenská republika 
sanofi-aventis Pharma Slovakia s.r.o. 
Tel: +421 2 33 100 100 
 

Italia 
Sanofi S.p.A. 
Tel: 800 13 12 12 (domande di tipo tecnico)  
800 536389 (altre domande) 
 

Suomi/Finland 
Sanofi Oy 
Puh/Tel: +358 (0) 201 200 300 
 

Κύπρος 
sanofi-aventis Cyprus Ltd. 
Τηλ: +357 22 871600 
 

Sverige 
Sanofi AB 
Tel: +46 (0)8 634 50 00 
 

Latvija 
sanofi-aventis Latvia SIA 
Tel: +371 67 33 24 51 
 

United Kingdom 
Sanofi 
Tel: +44 (0) 845 372 7101 
 

 
This leaflet was last revised in {date} 
 
 
Other source of information 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu/ 
 
 
 
 

HYPERGLYCAEMIA AND HYPOGLYCAEMIA 
 

Always carry some sugar (at least 20 grams) with you. 
Carry some information with you to show you are diabetic. 

 
HYPERGLYCAEMIA (high blood sugar levels) 

 
If your blood sugar is too high (hyperglycaemia), you may not have injected enough insulin. 
 
Why does hyperglycaemia occur? 
 
Examples include: 
- you have not injected your insulin or not injected enough, or if it has become less effective, for 

example through incorrect storage, 
- your insulin pen does not work properly, 
- you are doing less exercise than usual, you are under stress (emotional distress, excitement), or 

you have an injury, operation, infection or fever, 
- you are taking or have taken certain other medicines (see section 2, "Other medicines and 

Insulin Human Winthrop Rapid"). 
 
Warning symptoms of hyperglycaemia 

 

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Thirst, increased need to urinate, tiredness, dry skin, reddening of the face, loss of appetite, low blood 
pressure, fast heart beat, and glucose and ketone bodies in urine. Stomach pain, fast and deep 
breathing, sleepiness or even loss of consciousness may be signs of a serious condition (ketoacidosis) 
resulting from lack of insulin. 
 
What should you do if you experience hyperglycaemia 
 
Test your blood sugar level and your urine for ketones as soon as any of the above symptoms 
occur. Severe hyperglycaemia or ketoacidosis must always be treated by a doctor, normally in a 
hospital. 
 

HYPOGLYCAEMIA (low blood sugar levels) 
 
If your blood sugar level falls too much you may become unconscious. Serious hypoglycaemia may 
cause a heart attack or brain damage and may be life-threatening. You normally should be able to 
recognise when your blood sugar is falling too much so that you can take the right actions. 
 
Why does hypoglycaemia occur? 
 
Examples include: 
- you inject too much insulin, 
- you miss meals or delay them, 
- you do not eat enough, or eat food containing less carbohydrate than normal (sugar and 

substances similar to sugar are called carbohydrates; however, artificial sweeteners are NOT 
carbohydrates), 

- you lose carbohydrates due to vomiting or diarrhoea, 
- you drink alcohol, particularly if you are not eating much, 
- you are doing more exercise than usual or a different type of physical activity, 
- you are recovering from an injury or operation or other stress, 
- you are recovering from an illness or from fever, 
- you are taking or have stopped taking certain other medicines (see section 2, "Other medicines 

and Insulin Human Winthrop Rapid"). 
 
Hypoglycaemia is also more likely to occur if: 
- you have just begun insulin treatment or changed to another insulin preparation, 
- your blood sugar levels are almost normal or are unstable, 
- you change the area of skin where you inject insulin (for example from the thigh to the upper 

arm), 
- you suffer from severe kidney or liver disease, or some other disease such as hypothyroidism. 
 
Warning symptoms of hypoglycaemia 
 
- In your body 
Examples of symptoms that tell you that your blood sugar level is falling too much or too fast: 
sweating, clammy skin, anxiety, fast heart beat, high blood pressure, palpitations and irregular 
heartbeat. These symptoms often develop before the symptoms of a low sugar level in the brain. 
 
- In your brain 
Examples of symptoms that indicate a low sugar level in the brain: headaches, intense hunger, nausea, 
vomiting, tiredness, sleepiness, sleep disturbances, restlessness, aggressive behaviour, lapses in 
concentration, impaired reactions, depression, confusion, speech disturbances (sometimes total loss of 
speech), visual disorders, trembling, paralysis, tingling sensations (paraesthesia), numbness and 
tingling sensations in the area of the mouth, dizziness, loss of self-control, inability to look after 
yourself, convulsions, loss of consciousness. 
 

 

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The first symptoms which alert you to hypoglycaemia ("warning symptoms") may change, be weaker 
or may be missing altogether if 
- you are elderly, if you have had diabetes for a long time or if you suffer from a certain type of 

nervous disease (diabetic autonomic neuropathy), 
- you have recently suffered hypoglycaemia (for example the day before) or if it develops slowly, 
- you have almost normal or, at least, greatly improved blood sugar levels, 
- you have recently changed from an animal insulin to a human insulin such as Insulin Human 

Winthrop, 
- you are taking or have taken certain other medicines (see section 2, "Other medicines and 

Insulin Human Winthrop Rapid"). 
 
In such a case, you may develop severe hypoglycaemia (and even faint) before you are aware of the 
problem. Be familiar with your warning symptoms. If necessary, more frequent blood sugar testing 
can help to identify mild hypoglycaemic episodes that may otherwise be overlooked. If you are not 
confident about recognising your warning symptoms, avoid situations (such as driving a car) in which 
you or others would be put at risk by hypoglycaemia. 
 
What should you do if you experience hypoglycaemia 
 
1. Do not inject insulin. Immediately take about 10 to 20 g sugar, such as glucose, sugar cubes or a 

sugar-sweetened beverage. Caution: Artificial sweeteners and foods with artificial sweeteners 
(such as diet drinks) are of no help in treating hypoglycaemia. 

2. Then eat something that has a long-acting effect in raising your blood sugar (such as bread or 
pasta). Your doctor or nurse should have discussed this with you previously. 

3. If the hypoglycaemia comes back again take another 10 to 20 g sugar. 
4. Speak to a doctor immediately if you are not able to control the hypoglycaemia or if it recurs. 
 
Tell your relatives, friends and close colleagues the following: 
If you are not able to swallow or if you are unconscious, you will require an injection of glucose or 
glucagon (a medicine which increases blood sugar). These injections are justified even if it is not 
certain that you have hypoglycaemia. 
 
It is advisable to test your blood sugar immediately after taking glucose to check that you really have 
hypoglycaemia. 
 
 

 

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Insulin Human Winthrop Rapid SoloStar solution for injection in a pre-filled pen. Instructions 
for Use. 
 
SoloStar is a prefilled pen for the injection of insulin. Your doctor has decided that SoloStar is 
appropriate for you based on your ability to handle SoloStar. Talk with your doctor, pharmacist or 
nurse about proper injection technique before using SoloStar. 
 
Read these instructions carefully before using your SoloStar. If you are not able to use SoloStar or 
follow all the instructions completely on your own, you must use SoloStar only if you have help from 
a person who is able to follow the instructions completely. Hold the pen as shown in this leaflet. To 
ensure that you read the dose correctly, hold the pen horizontally, with the needle on the left and the 
dosage selector to the right as shown in the illustrations below. 
 
Follow these instructions completely each time you use SoloStar to ensure that you get an 
accurate dose. If you do not follow these instructions completely, you may get too much or too 
little insulin, which may affect your blood glucose. 
 
You can set doses from 1 to 80 units in steps of 1 unit. Each pen contains multiple doses. 
 
Keep this leaflet for future reference. 
 
If you have any questions about SoloStar or about diabetes, ask your doctor, pharmacist or nurse or 
call the local sanofi-aventis number on the front of this leaflet. 
 

 
Schematic diagram of the pen 

 
 
Important information for use of SoloStar: 
 
• Always attach a new needle before each use. Only use needles that have been approved for use 

with SoloStar. 
• Do not select a dose and/or press the injection button without a needle attached. 
• Always perform the safety test before each injection (see Step 3). 
• This pen is only for your use. Do not share it with anyone else.  
• If your injection is given by another person, special caution must be taken by this person to avoid 

accidental needle injury and transmission of infection. 
• Never use SoloStar if it is damaged or if you are not sure that it is working properly. 
• Always have a spare SoloStar in case your SoloStar is lost or damaged. 
 
 
Step 1. Check the insulin 
 
A. Check the label on your SoloStar to make sure you have the correct insulin. Insulin Human 

Winthrop SoloStar is white with a colour on the injection button. The injection button colour 
will vary based on the formulation of Insulin Human Winthrop insulin used. The pictures below 
are for illustrative purposes only. 

 
B. Take off the pen cap. 
 
C. Check the appearance of your insulin.  

 

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If you are using clear insulin (Insulin Human Winthrop Rapid), do not use this pen if the insulin 
is cloudy, coloured or has particles. 

 

   
 

 
 
 
Step 2. Attach the needle 
 
Always use a new sterile needle for each injection. This helps prevent contamination, and potential 
needle blocks. 
 
Before use of needle, carefully read the “Instructions for Use” accompanying the needles. 
 
Please note: The needles shown are for illustrative purposes only. 

 
A. Remove the protective seal from a new needle. 
 
B. Line up the needle with the pen, and keep it straight as you attach it (screw or push on, 

depending on the needle type). 
 

 . 
 

• If the needle is not kept straight while you attach it, it can damage the rubber seal and cause 
leakage, or break the needle. 

 

   
 
 
Step 3. Perform a safety test  
 
Always perform the safety test before each injection. This ensures that you get an accurate dose by: 
• ensuring that pen and needle work properly 
• removing air bubbles 
 
A. Select a dose of 2 units by turning the dosage selector. 

 

 

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B. Take off the outer needle cap and keep it to remove the used needle after injection. Take off the 

inner needle cap and discard it.  
 

   
 
C. Hold the pen with the needle pointing upwards. 
 
D. Tap the insulin reservoir so that any air bubbles rise up towards the needle. 
 
E. Press the injection button all the way in. Check if insulin comes out of the needle tip. 

   
 
You may have to perform the safety test several times before insulin is seen.  
 
• If no insulin comes out, check for air bubbles and repeat the safety test two more times to 

remove them. 
• If still no insulin comes out, the needle may be blocked. Change the needle and try again. 
• If no insulin comes out after changing the needle, your SoloStar may be damaged. Do not use 

this SoloStar. 
 
Step 4. Select the dose 
 
You can set the dose in steps of 1 unit, from a minimum of 1 unit to a maximum of 80 units. If you 
need a dose greater than 80 units, you should give it as two or more injections. 
 
A. Check that the dose window shows “0” following the safety test. 
 
B. Select your required dose (in the example below, the selected dose is 30 units). If you turn past 

your dose, you can turn back down. 
 

  
 

 

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• Do not push the injection button while turning, as insulin will come out. 
 
• You cannot turn the dosage selector past the number of units left in the pen. Do not force the 

dosage selector to turn. In this case, either you can inject what is remaining in the pen and 
complete your dose with a new SoloStar or use a new SoloStar for your full dose. 

 
 
Step 5. Inject the dose 
 
A. Use the injection method as instructed by your doctor, pharmacist or nurse.  
 
B. Insert the needle into the skin. 
 

   
 
C. Deliver the dose by pressing the injection button in all the way. The number in the dose window 

will return to “0” as you inject.  

   
 

D. Keep the injection button pressed all the way in. Slowly count to 10 before you withdraw the 
needle from the skin. This ensures that the full dose will be delivered. 
 
The pen plunger moves with each dose. The plunger will reach the end of the cartridge when 
the total of 300 units of insulin have been used. 

 
 
Step 6. Remove and discard the needle 
 
Always remove the needle after each injection and store SoloStar without a needle attached.  
This helps prevent: 
• Contamination and/or infection  
• Entry of air into the insulin reservoir and leakage of insulin, which can cause inaccurate dosing. 
 
A. Put the outer needle cap back on the needle, and use it to unscrew the needle from the pen. To 

reduce the risk of accidental needle injury, never replace the inner needle cap.  
 

• If your injection is given by another person, or if you are giving an injection to another person, 
special caution must be taken by this person when removing and disposing of the needle. Follow 
recommended safety measures for removal and disposal of needles (e.g. contact your doctor, 
pharmacist or nurse) in order to reduce the risk of accidental needle injury and transmission of 
infectious diseases. 

 
B. Dispose of the needle safely.  
 
C. Always put the pen cap back on the pen, then store the pen until your next injection. 
 
 

 

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Storage instructions  
 
Please check the reverse (insulin) side of this leaflet for instructions on how to store SoloStar. 
 
If your SoloStar is in cool storage, take it out 1 to 2 hours before you inject to allow it to warm up. 
Cold insulin is more painful to inject. 
 
Discard your used SoloStar as required by your local authorities. 
 
 
Maintenance 
 
Protect your SoloStar from dust and dirt. 
 
You can clean the outside of your SoloStar by wiping it with a damp cloth.  
 
Do not soak, wash or lubricate the pen as this may damage it.  
 
Your SoloStar is designed to work accurately and safely. It should be handled with care. Avoid 
situations where SoloStar might be damaged. If you are concerned that your SoloStar may be 
damaged, use a new one. 
 
 

 

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Package leaflet: Information for the user 

 
Insulin Human Winthrop Basal 100 IU/ml suspension for injection in a vial 

Insulin human 
 
 
Read all of this leaflet carefully before you start using this medicine because it contains 
important information for you. 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor, pharmacist or nurse. 
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours. 
- If you get any side effects , talk to your doctor, pharmacist or nurse. This includes any possible 

side effects not listed in this leaflet. 
 
What is in this leaflet: 
1. What Insulin Human Winthrop Basal is and what it is used for 
2. What you need to know before you use Insulin Human Winthrop Basal 
3. How to use Insulin Human Winthrop Basal 
4. Possible side effects 
5. How to store Insulin Human Winthrop Basal 
6. Contents of the pack and other information 
 
 
1. What Insulin Human Winthrop Basal is and what it is used for 
 
Insulin Human Winthrop Basal contains the active substance insulin human which is made by a 
biotechnology process and is identical with the body's own insulin. 
 
Insulin Human Winthrop Basal is an insulin preparation with a gradual onset and long duration of 
action. The insulin is present as tiny crystals of insulin protamine.  
 
Insulin Human Winthrop Basal is used to reduce high blood sugar in patients with diabetes mellitus 
who need treatment with insulin. Diabetes mellitus is a disease where your body does not produce 
enough insulin to control the level of blood sugar. 
 
 
2. What you need to know before you use Insulin Human Winthrop Basal 
 
Do not use Insulin Human Winthrop Basal 
 
If you are allergic to insulin or any of the other ingredients of this medicine (listed in section 6).  
 
Warnings and precautions 
 
Talk to your doctor, pharmacist or nurse before using Insulin Human Winthrop Basal 
Follow closely the instructions for dosage, monitoring (blood and urine tests), diet and physical 
activity (physical work and exercise) as discussed with your doctor. 
 
If you are allergic to this medicine or to animal insulins, talk to your doctor. 
 
Special patient groups 
If you have liver or kidneys problems or if you are elderly, speak to your doctor as you may need a 
lower dose. 
 

 

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Travel 
Before travelling, consult your doctor. You may need to talk about 
- the availability of your insulin in the country you are visiting, 
- supplies of insulin, injection syringes etc., 
- correct storage of your insulin while travelling, 
- timing of meals and insulin administration while travelling, 
- the possible effects of changing to different time zones, 
- possible new health risks in the countries to be visited, 
- what you should do in emergency situations when you feel unwell or become ill. 
 
Illnesses and injuries 
In the following situations, the management of your diabetes may require a lot of care: 
- If you are ill or have a major injury then your blood sugar level may increase (hyperglycaemia).  
- If you are not eating enough, your blood sugar level may become too low (hypoglycaemia).  
In most cases you will need a doctor. Make sure that you contact a doctor early.  
 
If you have type 1 diabetes (insulin dependent diabetes mellitus), do not stop your insulin and 
continue to get enough carbohydrates. Always tell people who are caring for you or treating you that 
you require insulin. 
 
Some patients with long-standing type 2 diabetes mellitus and heart disease or previous stroke who 
were treated with pioglitazone and insulin experienced the development of heart failure. Inform your 
doctor as soon as possible if you experience signs of heart failure such as unusual shortness of breath 
or rapid increase in weight or localised swelling (oedema). 
 
Other medicines and Insulin Human Winthrop Basal 
 
Some medicines cause changes in the blood sugar level (decrease, increase or both depending on the 
situation). In each case, it may be necessary to adjust your insulin dosage to avoid blood sugar levels 
that are either too low or too high. Be careful when you start or stop taking another medicine. 
 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines. Before taking a medicine ask your doctor if it can affect your blood sugar level, and what 
action, if any, you need to take. 
 
Medicines that may cause your blood sugar level to fall (hypoglycaemia) include:  
- all other medicines to treat diabetes,  
- angiotensin converting enzyme (ACE) inhibitors (used to treat certain heart conditions or high 

blood pressure),  
- disopyramide (used to treat certain heart conditions),  
- fluoxetine (used to treat depression),  
- fibrates (used to lower high levels of blood lipids),  
- monoamine oxidase (MAO) inhibitors (used to treat depression),  
- pentoxifylline, propoxyphene, salicylates (such as aspirin, used to relieve pain and lower fever), 
- sulfonamide antibiotics. 
 
Medicines that may cause your blood sugar level to rise (hyperglycaemia) include:  
- corticosteroids (such as "cortisone", used to treat inflammation),  
- danazol (medicine acting on ovulation),  
- diazoxide (used to treat high blood pressure),  
- diuretics (used to treat high blood pressure or excessive fluid retention),  
- glucagon (pancreas hormone used to treat severe hypoglycaemia),  
- isoniazid (used to treat tuberculosis),  
- oestrogens and progestogens (such as in the contraceptive pill used for birth control),  
- phenothiazine derivatives (used to treat psychiatric disorders),  
- somatropin (growth hormone),  

 

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- sympathomimetic medicines (such as epinephrine [adrenaline] or salbutamol, terbutaline used to 
treat asthma), 

- thyroid hormones (used to treat the thyroid gland disorders), 
- protease inhibitors (used to treat HIV), 
- atypical antipsychotic medicines (such as olanzapine and clozapine). 
 
Your blood sugar level may either rise or fall if you take:  
- beta-blockers (used to treat high blood pressure),  
- clonidine (used to treat high blood pressure), 
- lithium salts (used to treat psychiatric disorders).  
Pentamidine (used to treat some infections caused by parasites) may cause hypoglycaemia which may 
sometimes be followed by hyperglycaemia. 
 
Beta-blockers like other sympatholytic medicines (such as clonidine, guanethidine, and reserpine) may 
weaken or suppress entirely the first warning symptoms which help you to recognise a 
hypoglycaemia. 
 
If you are not sure whether you are taking one of those medicines ask your doctor or pharmacist. 
 
Insulin Human Winthrop Basal with alcohol 
 
Your blood sugar levels may either rise or fall if you drink alcohol. 
 
Pregnancy and breast-feeding 
 
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor or pharmacist for advice before taking this medicine. 
 
Inform your doctor if you are planning to become pregnant, or if you are already pregnant. Your 
insulin dosage may need to be changed during pregnancy and after giving birth. Particularly careful 
control of your diabetes, and prevention of hypoglycaemia, is important for the health of your baby.  
 
If you are breast-feeding consult your doctor as you may require adjustments in your insulin doses and 
your diet. 
 
Driving and using machines 
 
Your ability to concentrate or react may be reduced if: 
- you have hypoglycaemia (low blood sugar levels), 
- you have hyperglycaemia (high blood sugar levels), 
- you have problems with your sight.  
Keep this possible problem in mind in all situations where you might put yourself and others at risk 
(such as driving a car or using machines). You should contact your doctor for advice on driving if: 
- you have frequent episodes of hypoglycaemia, 
- the first warning symptoms which help you to recognise hypoglycaemia are reduced or absent. 
 
Important information about some of the ingredients of Insulin Human Winthrop Basal 
 
This medicine contains less than 1 mmol (23 mg) sodium per dose, i.e. it is essentially ‘sodium-free’. 
 
 

 

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3. How to use Insulin Human Winthrop Basal 
 
Dose 
 
Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor 
or pharmacist if you are not sure. 
 
Based on your life-style and the results of your blood sugar (glucose) tests, your doctor will 
- determine how much Insulin Human Winthrop Basal per day you will need, 
- tell you when to check your blood sugar level, and whether you need to carry out urine tests, 
- tell you when you may need to inject a higher or lower dose of Insulin Human Winthrop Basal. 
 
Many factors may influence your blood sugar level. You should know these factors so that you are 
able to react correctly to changes in your blood sugar level and to prevent it from becoming too high 
or too low. See the box at the end of this leaflet for further information. 
 
Frequency of administration 
 
Insulin Human Winthrop Basal is injected under the skin 45 to 60 minutes before a meal.  
 
Method of administration 
 
Insulin Human Winthrop Basal is a fluid (suspension) for injection under the skin. 
 
Do NOT inject Insulin Human Winthrop Basal into a vein (blood vessel). 
 
Your doctor will show you in which area of the skin you should inject your insulin. With each 
injection, change the puncture site within the particular area of skin that you are using. 
 
Do not use it in insulin pumps or other infusion pumps - special insulin preparations are available for 
use in such devices. 
 
How to handle the vials 
 
Insulin Human Winthrop Basal contains 100 IU insulin per ml. Only injection syringes designed for 
this insulin concentration (100 IU per ml) must be used. The injection syringes must not contain any 
other medicines or traces of medicines (such as traces of heparin). 
 
Before the first withdrawal of insulin you must remove the safety tear-off cap on the vial. 
 
Mix the insulin well immediately before each injection. This is best done by rolling the vial tilted 
between the palms of the hands. Do not shake the vial vigorously as this could damage the insulin and 
cause froth to form. Froth can make it difficult for you to measure the correct dose. 
 
After mixing, the suspension must have a uniform milky-white appearance. It must not be used if it 
remains clear or if, for example, clumps, flakes, particles or anything similar are in the suspension or 
on the sides or bottom of the vial. A new vial with a uniform suspension on mixing must then be used. 
 
Always use a new vial if you notice that your blood sugar control is unexpectedly getting worse. This 
is because the insulin may have lost some of its effectiveness. If you think you may have a problem 
with your insulin, have it checked by your doctor or pharmacist. 
 
Special care before injection 
 
Before injection remove any air bubbles. Make sure that neither alcohol nor other disinfectants or 
other substances contaminate the insulin. Do not mix insulin with any other medicines except with 
insulin human preparations as detailed below. 

 

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Insulin Human Winthrop Basal may be mixed with all insulin human preparations, EXCEPT those 
specially designed for use in insulin pumps. Also, it must NOT be mixed with animal source insulins 
or insulin analogues. 
 
Your doctor will tell you if you have to mix insulin human preparations. If you need to inject a 
mixture, draw the other insulin into the injection syringe before Insulin Human Winthrop Basal. Inject 
as soon as you have mixed them. Do not mix insulins of different strengths (for example 100 IU per 
ml and 40 IU per ml). 
 
If you use more Insulin Human Winthrop Basal than you should 
- If you have injected too much Insulin Human Winthrop Basal, your blood sugar level may 

become too low (hypoglycaemia). Check your blood sugar frequently. In general, to prevent 
hypoglycaemia you must eat more food and monitor your blood sugar. For information on the 
treatment of hypoglycaemia, see box at the end of this leaflet. 

 
If you forget to use Insulin Human Winthrop Basal 
- If you have missed a dose of Insulin Human Winthrop Basal or if you have not injected 

enough insulin, your blood sugar level may become too high (hyperglycaemia). Check your 
blood sugar frequently. For information on the treatment of hyperglycaemia, see box at the end of 
this leaflet. 

 
- Do not take a double dose to make up for a forgotten dose. 
 
If you stop using Insulin Human Winthrop Basal 
 
This could lead to severe hyperglycaemia (very high blood sugar) and ketoacidosis (build-up of acid 
in the blood because the body is breaking down fat instead of sugar). Do not stop Insulin Human 
Winthrop Basal without speaking to a doctor, who will tell you what needs to be done. 
 
If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse. 
 
Insulin Mix-ups 
 
You must always check the insulin label before each injection to avoid mix-ups between Insulin 
Human Winthrop Basal and other insulins.  
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
The most frequent side effect is hypoglycaemia (low blood sugar). The specific frequency cannot be 
estimated from available data (frequency not known). Serious hypoglycaemia may cause a heart attack 
or brain damage and may be life-threatening. For further information on the side effects of low blood 
sugar or high blood sugar, see the box at the end of this leaflet. 
 
Severe allergic reactions to insulin may occur which may become life-threatening. Such reactions to 
insulin or to the excipients can cause large-scale skin reactions (rash and itching all over the body); 
severe swelling of skin or mucous membranes (angiooedema), shortness of breath, a fall in blood 
pressure with rapid heart beat and sweating.Frequency of these reactions cannot be estimated from 
available data. 
 

 

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Side effects reported commonly (may affect up to 1 in 10 people) 
• Oedema 
Insulin treatment may cause temporary build-up of water in the body with swelling in the calves and 
ankles. 
• Injection site reactions 
 
Side effects reported uncommonly (may affect up to 1 in 100 people) 
• Severe allergic reaction with low blood pressure (shock) 
• Injection site urticaria (itchy rash) 
 
Other side effects include (frequency cannot be estimated from the available data) 
• Sodium retention 
• Eye reactions 
A marked change (improvement or worsening) in your blood sugar control can disturb your vision 
temporarily. If you have proliferative retinopathy (an eye disease related to diabetes) severe 
hypoglycaemic attacks may cause temporary loss of vision. 
• Skin changes at the injection site (lipodystrophy) 
If you inject your insulin too often at the same skin site, fatty tissue under the skin at this site may 
either shrink or thicken. Insulin that you inject in such a site may not work very well. Changing the 
injection site with each injection may help to prevent such skin changes. 
• Skin and allergic reactions 
Other mild reactions at the injection site (such as injection site redness, unusually intense pain on 
injection site, itching, injection site swelling or injection site inflammation) may occur. They can also 
spread around the injection site. Most minor reactions to insulins usually resolve in a few days to a 
few weeks. 
 
Insulin treatment can cause the body to produce antibodies to insulin (substances that act against 
insulin). However, only very rarely, this will require a change to your insulin dosage. 
 
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side 
effects not listed in this leaflet. 
 
 
5. How to store Insulin Human Winthrop Basal 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date which is stated on the carton and on the label of the vial 
after “EXP”. The expiry date refers to the last day of that month. 
 
Unopened vials 
Store in a refrigerator (2°C - 8°C). Do not freeze. Do not put Insulin Human Winthrop Basal next to 
the freezer compartment or a freezer pack. Keep the vial in the outer carton in order to protect from 
light. 
 
Opened vials 
Once in-use, the vial may be stored for a maximum of 4 weeks in the outer carton not above 25°C and 
away from direct heat (for example next to a heating unit) or direct light (direct sunlight or next to a 
lamp). Do not use the vial after this time period. It is recommended that the date of the first use be 
noted on the label. 
 
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment. 
 
 

 

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6. Contents of the pack and other information 
 
What Insulin Human Winthrop Basal contains 
- The active substance is insulin human. One ml of Insulin Human Winthrop Basal contains 

100 IU (International Units) of the active substance insulin human. 
- The other ingredients are: protamine sulphate, metacresol, phenol, zinc chloride, sodium 

dihydrogen phosphate dihydrate, glycerol, sodium hydroxide (see section 2 under “Important 
information about some of the ingredients of Insulin Human Winthrop Basal”), hydrochloric 
acid (for pH adjustment) and water for injections. 

 
What Insulin Human Winthrop Basal looks like and contents of the pack 
After mixing, Insulin Human Winthrop Basal is a uniformly milky fluid (suspension for injection), 
with no clumps, particles or flocculation visible. 
 
Insulin Human Winthrop Basal is supplied in vials containing 5 ml of suspension for injection 
(500 IU) or 10 ml of suspension for injection (equivalent to 1000 IU). Packs of 1 and 5 vials of 5 ml or 
10 ml are available. Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder and Manufacturer 
Sanofi-Aventis Deutschland GmbH 
D-65926 Frankfurt am Main 
Germany 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
Sanofi Belgium 
Tél/Tel: +32 (0)2 710 54 00 
 

Lietuva 
UAB «SANOFI-AVENTIS LIETUVA» 
Tel: +370 5 2755224 
 

България 
sanofi-aventis Bulgaria EOOD 
Тел.: +359 (0)2 970 53 00 
 

Luxembourg/Luxemburg 
Sanofi Belgium  
Tél/Tel: +32 (0)2 710 54 00 (Belgique/Belgien) 
 

Česká republika 
sanofi-aventis, s.r.o. 
Tel: +420 233 086 111 
 

Magyarország 
SANOFI-AVENTIS Zrt. 
Tel.: +36 1 505 0050 
 

Danmark 
sanofi-aventis Denmark A/S 
Tlf: +45 45 16 70 00 
 

Malta 
Sanofi Malta Ltd. 
Tel: +356 21493022 
 

Deutschland 
Zentiva Pharma GmbH 
Tel: +49 (0)180 20 200 10 
 

Nederland 
sanofi-aventis Netherlands B.V. 
Tel: +31 (0)182 557 755 
 

Eesti 
sanofi-aventis Estonia OÜ 
Tel: +372 627 34 88 
 

Norge 
Aventis Pharma Norge AS 
Tlf: +47 67 10 71 00 
 

Ελλάδα 
sanofi-aventis AEBE 
Τηλ: +30 210 900 16 00 
 

Österreich 
sanofi-aventis GmbH 
Tel: +43 1 80 185 – 0 
 

 

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España 
sanofi-aventis, S.A. 
Tel: +34 93 485 94 00 
 

Polska 
sanofi-aventis Sp. z o.o. 
Tel.: +48 22 280 00 00 
 

France 
sanofi-aventis France 
Tél: 0 800 222 555 
Appel depuis l’étranger : +33 1 57 63 23 23 
 

Portugal 
Sanofi - Produtos Farmacêuticos, Lda. 
Tel: +351 21 35 89 400 
 

Hrvatska 
sanofi-aventis Croatia d.o.o. 
Tel: +385 1 600 34 00 

România 
Sanofi Romania SRL 
Tel: +40 (0) 21 317 31 36 
 

Ireland 
sanofi-aventis Ireland Ltd. T/A SANOFI 
Tel: +353 (0) 1 403 56 00 
 

Slovenija 
sanofi-aventis d.o.o. 
Tel: +386 1 560 48 00 
 

Ísland 
Vistor hf. 
Sími: +354 535 7000 
 

Slovenská republika 
sanofi-aventis Pharma Slovakia s.r.o. 
Tel: +421 2 33 100 100 
 

Italia 
Sanofi S.p.A. 
Tel: 800 13 12 12 (domande di tipo tecnico)  
800 536389 (altre domande) 
 

Suomi/Finland 
Sanofi Oy 
Puh/Tel: +358 (0) 201 200 300 
 

Κύπρος 
sanofi-aventis Cyprus Ltd. 
Τηλ: +357 22 871600 
 

Sverige 
Sanofi AB 
Tel: +46 (0)8 634 50 00 
 

Latvija 
sanofi-aventis Latvia SIA 
Tel: +371 67 33 24 51 
 

United Kingdom 
Sanofi 
Tel: +44 (0) 845 372 7101 
 

 
This leaflet was last revised in {date} 
 
 
Other source of information 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu/ 
 
 
 
 

HYPERGLYCAEMIA AND HYPOGLYCAEMIA 
 

Always carry some sugar (at least 20 grams) with you. 
Carry some information with you to show you are diabetic. 

 
HYPERGLYCAEMIA (high blood sugar levels) 

 
If your blood sugar is too high (hyperglycaemia), you may not have injected enough insulin. 
 
Why does hyperglycaemia occur? 
 
Examples include: 

 

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- you have not injected your insulin or not injected enough, or if it has become less effective, for 
example through incorrect storage, 

- you are doing less exercise than usual, you are under stress (emotional distress, excitement), or 
you have an injury, operation, infection or fever, 

- you are taking or have taken certain other medicines (see section 2, "Other medicines and 
Insulin Human Winthrop Basal"). 

 
Warning symptoms of hyperglycaemia 
 
Thirst, increased need to urinate, tiredness, dry skin, reddening of the face, loss of appetite, low blood 
pressure, fast heart beat, and glucose and ketone bodies in urine. Stomach pain, fast and deep 
breathing, sleepiness or even loss of consciousness may be signs of a serious condition (ketoacidosis) 
resulting from lack of insulin. 
 
What should you do if you experience hyperglycaemia 
 
Test your blood sugar level and your urine for ketones as soon as any of the above symptoms 
occur. Severe hyperglycaemia or ketoacidosis must always be treated by a doctor, normally in a 
hospital. 
 

HYPOGLYCAEMIA (low blood sugar levels) 
 
If your blood sugar level falls too much you may become unconscious. Serious hypoglycaemia may 
cause a heart attack or brain damage and may be life-threatening. You normally should be able to 
recognise when your blood sugar is falling too much so that you can take the right actions. 
 
Why does hypoglycaemia occur? 
 
Examples include: 
- you inject too much insulin, 
- you miss meals or delay them, 
- you do not eat enough, or eat food containing less carbohydrate than normal (sugar and 

substances similar to sugar are called carbohydrates; however, artificial sweeteners are NOT 
carbohydrates), 

- you lose carbohydrates due to vomiting or diarrhoea, 
- you drink alcohol, particularly if you are not eating much, 
- you are doing more exercise than usual or a different type of physical activity, 
- you are recovering from an injury or operation or other stress, 
- you are recovering from an illness or from fever, 
- you are taking or have stopped taking certain other medicines (see section 2, "Other medicines 

and Insulin Human Winthrop Basal"). 
 
Hypoglycaemia is also more likely to occur if: 
- you have just begun insulin treatment or changed to another insulin preparation, 
- your blood sugar levels are almost normal or are unstable, 
- you change the area of skin where you inject insulin (for example from the thigh to the upper 

arm), 
- you suffer from severe kidney or liver disease, or some other disease such as hypothyroidism. 
 
Warning symptoms of hypoglycaemia 
 
- In your body 
Examples of symptoms that tell you that your blood sugar level is falling too much or too fast: 
sweating, clammy skin, anxiety, fast heart beat, high blood pressure, palpitations and irregular 
heartbeat. These symptoms often develop before the symptoms of a low sugar level in the brain. 
 
- In your brain 

 

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Examples of symptoms that indicate a low sugar level in the brain: headaches, intense hunger, nausea, 
vomiting, tiredness, sleepiness, sleep disturbances, restlessness, aggressive behaviour, lapses in 
concentration, impaired reactions, depression, confusion, speech disturbances (sometimes total loss of 
speech), visual disorders, trembling, paralysis, tingling sensations (paraesthesia), numbness and 
tingling sensations in the area of the mouth, dizziness, loss of self-control, inability to look after 
yourself, convulsions, loss of consciousness. 
 
The first symptoms which alert you to hypoglycaemia ("warning symptoms") may change, be weaker 
or may be missing altogether if 
- you are elderly, if you have had diabetes for a long time or if you suffer from a certain type of 

nervous disease (diabetic autonomic neuropathy), 
- you have recently suffered hypoglycaemia (for example the day before) or if it develops slowly, 
- you have almost normal or, at least, greatly improved blood sugar levels, 
- you have recently changed from an animal insulin to a human insulin such as Insulin Human 

Winthrop, 
- you are taking or have taken certain other medicines (see section 2, "Other medicines and 
Insulin Human Winthrop Basal"). 
 
In such a case, you may develop severe hypoglycaemia (and even faint) before you are aware of the 
problem. Be familiar with your warning symptoms. If necessary, more frequent blood sugar testing 
can help to identify mild hypoglycaemic episodes that may otherwise be overlooked. If you are not 
confident about recognising your warning symptoms, avoid situations (such as driving a car) in which 
you or others would be put at risk by hypoglycaemia. 
 
What should you do if you experience hypoglycaemia 
 
1. Do not inject insulin. Immediately take about 10 to 20 g sugar, such as glucose, sugar cubes or a 

sugar-sweetened beverage. Caution: Artificial sweeteners and foods with artificial sweeteners 
(such as diet drinks) are of no help in treating hypoglycaemia. 

2. Then eat something that has a long-acting effect in raising your blood sugar (such as bread or 
pasta). Your doctor or nurse should have discussed this with you previously. 

3. If the hypoglycaemia comes back again take another 10 to 20 g sugar. 
4. Speak to a doctor immediately if you are not able to control the hypoglycaemia or if it recurs. 
 
Tell your relatives, friends and close colleagues the following: 
If you are not able to swallow or if you are unconscious, you will require an injection of glucose or 
glucagon (a medicine which increases blood sugar). These injections are justified even if it is not 
certain that you have hypoglycaemia. 
 
It is advisable to test your blood sugar immediately after taking glucose to check that you really have 
hypoglycaemia. 
 
 

 

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Package leaflet: Information for the user 

 
Insulin Human Winthrop Basal 40 IU/ml suspension for injection in a vial 

Insulin human 
 
 
Read all of this leaflet carefully before you start using this medicine because it contains 
important information for you. 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor, pharmacist or nurse. 
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours. 
- If you get any side effects , talk to your doctor, pharmacist or nurse. This includes any possible 

side effects not listed in this leaflet. 
 
What is in this leaflet: 
1. What Insulin Human Winthrop Basal is and what it is used for 
2. What you need to know before you use Insulin Human Winthrop Basal 
3. How to use Insulin Human Winthrop Basal 
4. Possible side effects 
5. How to store Insulin Human Winthrop Basal 
6. Contents of the pack and other information 
 
 
1. What Insulin Human Winthrop Basal is and what it is used for 
 
Insulin Human Winthrop Basal contains the active substance insulin human which is made by a 
biotechnology process and is identical with the body's own insulin. 
 
Insulin Human Winthrop Basal is an insulin preparation with a gradual onset and long duration of 
action. The insulin is present as tiny crystals of insulin protamine. 
 
Insulin Human Winthrop Basal is used to reduce high blood sugar in patients with diabetes mellitus 
who need treatment with insulin. Diabetes mellitus is a disease where your body does not produce 
enough insulin to control the level of blood sugar. 
 
 
2. What you need to know before you use Insulin Human Winthrop Basal 
 
Do not use Insulin Human Winthrop Basal 
 
If you are allergic to insulin or any of the other ingredients of this medicine (listed in section 6).  
 
Warnings and precautions 
 
Talk to your doctor, pharmacist or nurse before using Insulin Human Winthrop Basal. 
Follow closely the instructions for dosage, monitoring (blood and urine tests), diet and physical 
activity (physical work and exercise) as discussed with your doctor. 
 
If you are allergic to this medicine or to animal insulins, talk to your doctor. 
 
Special patient groups 
If you have liver or kidneys problems or if you are elderly, speak to your doctor as you may need a 
lower dose. 
 

 

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Travel 
Before travelling, consult your doctor. You may need to talk about 
- the availability of your insulin in the country you are visiting, 
- supplies of insulin, injection syringes etc., 
- correct storage of your insulin while travelling, 
- timing of meals and insulin administration while travelling, 
- the possible effects of changing to different time zones, 
- possible new health risks in the countries to be visited, 
- what you should do in emergency situations when you feel unwell or become ill. 
 
Illnesses and injuries 
In the following situations, the management of your diabetes may require a lot of care: 
- If you are ill or have a major injury then your blood sugar level may increase (hyperglycaemia).  
- If you are not eating enough, your blood sugar level may become too low (hypoglycaemia).  
In most cases you will need a doctor. Make sure that you contact a doctor early.  
 
If you have type 1 diabetes (insulin dependent diabetes mellitus), do not stop your insulin and 
continue to get enough carbohydrates. Always tell people who are caring for you or treating you that 
you require insulin. 
 
Some patients with long-standing type 2 diabetes mellitus and heart disease or previous stroke who 
were treated with pioglitazone and insulin experienced the development of heart failure. Inform your 
doctor as soon as possible if you experience signs of heart failure such as unusual shortness of breath 
or rapid increase in weight or localised swelling (oedema). 
 
Other medicines and Insulin Human Winthrop Basal 
 
Some medicines cause changes in the blood sugar level (decrease, increase or both depending on the 
situation). In each case, it may be necessary to adjust your insulin dosage to avoid blood sugar levels 
that are either too low or too high. Be careful when you start or stop taking another medicine. 
 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines. Before taking a medicine ask your doctor if it can affect your blood sugar level, and what 
action, if any, you need to take. 
 
Medicines that may cause your blood sugar level to fall (hypoglycaemia) include:  
- all other medicines to treat diabetes,  
- angiotensin converting enzyme (ACE) inhibitors (used to treat certain heart conditions or high 

blood pressure),  
- disopyramide (used to treat certain heart conditions),  
- fluoxetine (used to treat depression),  
- fibrates (used to lower high levels of blood lipids),  
- monoamine oxidase (MAO) inhibitors (used to treat depression),  
- pentoxifylline, propoxyphene, salicylates (such as aspirin, used to relieve pain and lower fever), 
- sulfonamide antibiotics. 
 
Medicines that may cause your blood sugar level to rise (hyperglycaemia) include:  
- corticosteroids (such as "cortisone", used to treat inflammation),  
- danazol (medicine acting on ovulation),  
- diazoxide (used to treat high blood pressure),  
- diuretics (used to treat high blood pressure or excessive fluid retention),  
- glucagon (pancreas hormone used to treat severe hypoglycaemia),  
- isoniazid (used to treat tuberculosis),  
- oestrogens and progestogens (such as in the contraceptive pill used for birth control),  
- phenothiazine derivatives (used to treat psychiatric disorders),  
- somatropin (growth hormone),  

 

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- sympathomimetic medicines (such as epinephrine [adrenaline] or salbutamol, terbutaline used to 
treat asthma), 

- thyroid hormones (used to treat the thyroid gland disorders), 
- protease inhibitors (used to treat HIV), 
- atypical antipsychotic medicines (such as olanzapine and clozapine). 
 
Your blood sugar level may either rise or fall if you take:  
- beta-blockers (used to treat high blood pressure),  
- clonidine (used to treat high blood pressure), 
- lithium salts (used to treat psychiatric disorders).  
Pentamidine (used to treat some infections caused by parasites) may cause hypoglycaemia which may 
sometimes be followed by hyperglycaemia. 
 
Beta-blockers like other sympatholytic medicines (such as clonidine, guanethidine, and reserpine) may 
weaken or suppress entirely the first warning symptoms which help you to recognise a 
hypoglycaemia. 
 
If you are not sure whether you are taking one of those medicines ask your doctor or pharmacist. 
 
Insulin Human Winthrop Basal with alcohol 
 
Your blood sugar levels may either rise or fall if you drink alcohol. 
 
Pregnancy and breast-feeding 
 
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor or pharmacist for advice before taking this medicine. 
 
Inform your doctor if you are planning to become pregnant, or if you are already pregnant. Your 
insulin dosage may need to be changed during pregnancy and after giving birth. Particularly careful 
control of your diabetes, and prevention of hypoglycaemia, is important for the health of your baby.  
 
If you are breast-feeding consult your doctor as you may require adjustments in your insulin doses and 
your diet. 
 
Driving and using machines 
 
Your ability to concentrate or react may be reduced if: 
- you have hypoglycaemia (low blood sugar levels), 
- you have hyperglycaemia (high blood sugar levels), 
- you have problems with your sight.  
Keep this possible problem in mind in all situations where you might put yourself and others at risk 
(such as driving a car or using machines). You should contact your doctor for advice on driving if: 
- you have frequent episodes of hypoglycaemia, 
- the first warning symptoms which help you to recognise hypoglycaemia are reduced or absent. 
 
Important information about some of the ingredients of Insulin Human Winthrop Basal  
 
This medicine contains less than 1 mmol (23 mg) sodium per dose, i.e. it is essentially ‘sodium-free’. 
 
 

 

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3. How to use Insulin Human Winthrop Basal 
 
Dose 
 
Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor 
or pharmacist if you are not sure. 
 
Based on your life-style and the results of your blood sugar (glucose) tests, your doctor will 
- determine how much Insulin Human Winthrop Basal per day you will need, 
- tell you when to check your blood sugar level, and whether you need to carry out urine tests, 
- tell you when you may need to inject a higher or lower dose of Insulin Human Winthrop Basal. 
 
Many factors may influence your blood sugar level. You should know these factors so that you are 
able to react correctly to changes in your blood sugar level and to prevent it from becoming too high 
or too low. See the box at the end of this leaflet for further information. 
 
Frequency of administration 
 
Insulin Human Winthrop Basal is injected under the skin 45 to 60 minutes before a meal.  
 
Method of administration 
 
Insulin Human Winthrop Basal is a fluid (suspension) for injection under the skin. 
 
Do NOT inject Insulin Human Winthrop Basal into a vein (blood vessel). 
 
Your doctor will show you in which area of the skin you should inject your insulin. With each 
injection, change the puncture site within the particular area of skin that you are using. 
 
Do not use it in insulin pumps or other infusion pumps - special insulin preparations are available for 
use in such devices. 
 
How to handle the vials 
 
Insulin Human Winthrop Basal contains 40 IU insulin per ml. Only injection syringes designed for 
this insulin concentration (40 IU per ml) must be used. The injection syringes must not contain any 
other medicines or traces of medicines (such as traces of heparin). 
 
Before the first withdrawal of insulin you must remove the safety tear-off cap on the vial. 
 
Mix the insulin well immediately before each injection. This is best done by rolling the vial tilted 
between the palms of the hands. Do not shake the vial vigorously as this could damage the insulin and 
cause froth to form. Froth can make it difficult for you to measure the correct dose. 
 
After mixing, the suspension must have a uniform milky-white appearance. It must not be used if it 
remains clear or if, for example, clumps, flakes, particles or anything similar are in the suspension or 
on the sides or bottom of the vial. A new vial with a uniform suspension on mixing must then be used. 
 
Always use a new vial if you notice that your blood sugar control is unexpectedly getting worse. This 
is because the insulin may have lost some of its effectiveness. If you think you may have a problem 
with your insulin, have it checked by your doctor or pharmacist. 
 
Special care before injection 
 
Before injection remove any air bubbles. Make sure that neither alcohol nor other disinfectants or 
other substances contaminate the insulin. Do not mix insulin with any other medicines except with 
insulin human preparations as detailed below. 

 

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Insulin Human Winthrop Basal may be mixed with all insulin human preparations, EXCEPT those 
specially designed for use in insulin pumps. Also, it must NOT be mixed with animal source insulins 
or insulin analogues. 
 
Your doctor will tell you if you have to mix insulin human preparations. If you need to inject a 
mixture, draw the other insulin into the injection syringe before Insulin Human Winthrop Basal. Inject 
as soon as you have mixed them. Do not mix insulins of different strengths (for example 100 IU per 
ml and 40 IU per ml). 
 
If you use more Insulin Human Winthrop Basal than you should 
- If you have injected too much Insulin Human Winthrop Basal, your blood sugar level may 

become too low (hypoglycaemia). Check your blood sugar frequently. In general, to prevent 
hypoglycaemia you must eat more food and monitor your blood sugar. For information on the 
treatment of hypoglycaemia, see box at the end of this leaflet. 

 
If you forget to use Insulin Human Winthrop Basal 
- If you have missed a dose of Insulin Human Winthrop Basal or if you have not injected 

enough insulin, your blood sugar level may become too high (hyperglycaemia). Check your 
blood sugar frequently. For information on the treatment of hyperglycaemia, see box at the end 
of this leaflet. 

 
- Do not take a double dose to make up for a forgotten dose. 
 
If you stop using Insulin Human Winthrop Basal 
This could lead to severe hyperglycaemia (very high blood sugar) and ketoacidosis (build-up of acid 
in the blood because the body is breaking down fat instead of sugar). Do not stop Insulin Human 
Winthrop Basal without speaking to a doctor, who will tell you what needs to be done. 
 
If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse. 
 
Insulin Mix-ups 
 
You must always check the insulin label before each injection to avoid mix-ups between Insulin 
Human Winthrop Basal and other insulins.  
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
The most frequent side effect is hypoglycaemia (low blood sugar). The specific frequency cannot be 
estimated from available data (frequency not known). Serious hypoglycaemia may cause a heart attack 
or brain damage and may be life-threatening. For further information on the side effects of low blood 
sugar or high blood sugar, see the box at the end of this leaflet. 
 
Severe allergic reactions to insulin may occur which may become life-threatening. Such reactions to 
insulin or to the excipients can cause large-scale skin reactions (rash and itching all over the body); 
severe swelling of skin or mucous membranes (angiooedema), shortness of breath, a fall in blood 
pressure with rapid heart beat and sweating. Frequency of these reactions cannot be estimated from 
available data. 
 
Side effects reported commonly (may affect up to 1 in 10 people) 
• Oedema 
Insulin treatment may cause temporary build-up of water in the body with swelling in the calves and 
ankles. 
• Injection site reactions 

 

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Side effects reported uncommonly (may affect up to 1 in 100 people) 
• Severe allergic reaction with low blood pressure (shock) 
• Injection site urticaria (itchy rash) 
 
Other side effects include (frequency cannot be estimated from the available data) 
• Sodium retention 
• Eye reactions 
A marked change (improvement or worsening) in your blood sugar control can disturb your vision 
temporarily. If you have proliferative retinopathy (an eye disease related to diabetes) severe 
hypoglycaemic attacks may cause temporary loss of vision.  
• Skin changes at the injection site (lipodystrophy) 
If you inject your insulin too often at the same skin site, fatty tissue under the skin at this site may 
either shrink or thicken. Insulin that you inject in such a site may not work very well. Changing the 
injection site with each injection may help to prevent such skin changes. 
• Skin and allergic reactions 
Other mild reactions at the injection site (such as injection site redness, unusually intense pain on 
injection site, itching, injection site swelling or injection site inflammation) may occur. They can also 
spread around the injection site. Most minor reactions to insulins usually resolve in a few days to a 
few weeks. 
 
Insulin treatment can cause the body to produce antibodies to insulin (substances that act against 
insulin). However, only very rarely, this will require a change to your insulin dosage. 
 
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any side effects not 
listed in this leaflet. 
 
 
5. How to store Insulin Human Winthrop Basal 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date which is stated on the carton and on the label of the vial 
after “EXP”. The expiry date refers to the last day of that month. 
 
Unopened vials 
Store in a refrigerator (2°C – 8°C). Do not freeze. Do not put Insulin Human Winthrop Basal next to 
the freezer compartment or a freezer pack. Keep the vial in the outer carton in order to protect from 
light. 
 
Opened vials 
Once in-use, the vial may be stored for a maximum of 4 weeks in the outer carton not above 25°C and 
away from direct heat (for example next to a heating unit) or direct light (direct sunlight or next to a 
lamp). Do not use the vial after this time period. It is recommended that the date of the first use be 
noted on the label. 
 
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Insulin Human Winthrop Basal contains 
- The active substance is insulin human. One ml of Insulin Human Winthrop Basal contains 

40 IU (International Units) of the active substance insulin human. 
- The other ingredients are: protamine sulphate, metacresol, phenol, zinc chloride, sodium 

dihydrogen phosphate dihydrate, glycerol, sodium hydroxide (see section 2 under “Important 

 

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information about some of the ingredients of Insulin Human Winthrop Basal”), hydrochloric 
acid (for pH adjustment) and water for injections. 

 
What Insulin Human Winthrop Basal looks like and contents of the pack 
After mixing, Insulin Human Winthrop Basal is a uniformly milky fluid (suspension for injection), 
with no clumps, particles or flocculation visible. 
 
Insulin Human Winthrop Basal is supplied in vials containing 10 ml suspension (400 IU). Packs of 
1 and 5 vials of 10 ml are available. Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder and Manufacturer 
Sanofi-Aventis Deutschland GmbH 
D-65926 Frankfurt am Main 
Germany 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
Sanofi Belgium 
Tél/Tel: +32 (0)2 710 54 00 
 

Lietuva 
UAB «SANOFI-AVENTIS LIETUVA» 
Tel: +370 5 2755224 
 

България 
sanofi-aventis Bulgaria EOOD 
Тел.: +359 (0)2 970 53 00 
 

Luxembourg/Luxemburg 
Sanofi Belgium  
Tél/Tel: +32 (0)2 710 54 00 (Belgique/Belgien) 
 

Česká republika 
sanofi-aventis, s.r.o. 
Tel: +420 233 086 111 
 

Magyarország 
SANOFI-AVENTIS Zrt. 
Tel.: +36 1 505 0050 
 

Danmark 
sanofi-aventis Denmark A/S 
Tlf: +45 45 16 70 00 
 

Malta 
Sanofi Malta Ltd. 
Tel: +356 21493022 
 

Deutschland 
Zentiva Pharma GmbH 
Tel: +49 (0)180 20 200 10 
 

Nederland 
sanofi-aventis Netherlands B.V. 
Tel: +31 (0)182 557 755 
 

Eesti 
sanofi-aventis Estonia OÜ 
Tel: +372 627 34 88 
 

Norge 
Aventis Pharma Norge AS 
Tlf: +47 67 10 71 00 
 

Ελλάδα 
sanofi-aventis AEBE 
Τηλ: +30 210 900 16 00 
 

Österreich 
sanofi-aventis GmbH 
Tel: +43 1 80 185 – 0 
 

España 
sanofi-aventis, S.A. 
Tel: +34 93 485 94 00 
 

Polska 
sanofi-aventis Sp . z o.o. 
Tel.: +48 22 280 00 00 
 

France 
sanofi-aventis France 
Tél: 0 800 222 555 
Appel depuis l’étranger : +33 1 57 63 23 23 
 

Portugal 
Sanofi - Produtos Farmacêuticos, Lda. 
Tel: +351 21 35 89 400 
 

 

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Hrvatska 
sanofi-aventis Croatia d.o.o. 
Tel: +385 1 600 34 00 

România 
Sanofi Romania SRL 
Tel: +40 (0) 21 317 31 36 
 

Ireland 
sanofi-aventis Ireland Ltd. T/A SANOFI 
Tel: +353 (0) 1 403 56 00 
 

Slovenija 
sanofi-aventis d.o.o. 
Tel: +386 1 560 48 00 
 

Ísland 
Vistor hf. 
Sími: +354 535 7000 
 

Slovenská republika 
sanofi-aventis Pharma Slovakia s.r.o. 
Tel: +421 2 33 100 100 
 

Italia 
Sanofi S.p.A. 
Tel: 800 13 12 12 (domande di tipo tecnico)  
800 536389 (altre domande) 
 

Suomi/Finland 
Sanofi Oy 
Puh/Tel: +358 (0) 201 200 300 
 

Κύπρος 
sanofi-aventis Cyprus Ltd. 
Τηλ: +357 22 871600 
 

Sverige 
Sanofi AB 
Tel: +46 (0)8 634 50 00 
 

Latvija 
sanofi-aventis Latvia SIA 
Tel: +371 67 33 24 51 
 

United Kingdom 
Sanofi 
Tel: +44 (0) 845 372 7101 
 

 
This leaflet was last revised in {date} 
 
 
Other source of information 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu/ 
 
 
 
 

HYPERGLYCAEMIA AND HYPOGLYCAEMIA 
 

Always carry some sugar (at least 20 grams) with you. 
Carry some information with you to show you are diabetic. 

 
HYPERGLYCAEMIA (high blood sugar levels) 

 
If your blood sugar is too high (hyperglycaemia), you may not have injected enough insulin. 
 
Why does hyperglycaemia occur? 
 
Examples include: 
- you have not injected your insulin or not injected enough, or if it has become less effective, for 

example through incorrect storage, 
- you are doing less exercise than usual, you are under stress (emotional distress, excitement), or 

you have an injury, operation, infection or fever, 
- you are taking or have taken certain other medicines (see section 2, "Other medicines and 

Insulin Human Winthrop Basal"). 
 
Warning symptoms of hyperglycaemia 
 

 

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Thirst, increased need to urinate, tiredness, dry skin, reddening of the face, loss of appetite, low blood 
pressure, fast heart beat, and glucose and ketone bodies in urine. Stomach pain, fast and deep 
breathing, sleepiness or even loss of consciousness may be signs of a serious condition (ketoacidosis) 
resulting from lack of insulin. 
 
What should you do if you experience hyperglycaemia 
 
Test your blood sugar level and your urine for ketones as soon as any of the above symptoms 
occur. Severe hyperglycaemia or ketoacidosis must always be treated by a doctor, normally in a 
hospital. 
 

HYPOGLYCAEMIA (low blood sugar levels) 
 
If your blood sugar level falls too much you may become unconscious. Serious hypoglycaemia may 
cause a heart attack or brain damage and may be life-threatening. You normally should be able to 
recognise when your blood sugar is falling too much so that you can take the right actions. 
 
Why does hypoglycaemia occur? 
 
Examples include: 
- you inject too much insulin, 
- you miss meals or delay them, 
- you do not eat enough, or eat food containing less carbohydrate than normal (sugar and 

substances similar to sugar are called carbohydrates; however, artificial sweeteners are NOT 
carbohydrates), 

- you lose carbohydrates due to vomiting or diarrhoea, 
- you drink alcohol, particularly if you are not eating much, 
- you are doing more exercise than usual or a different type of physical activity, 
- you are recovering from an injury or operation or other stress, 
- you are recovering from an illness or from fever, 
- you are taking or have stopped taking certain other medicines (see section 2, "Other medicines 

and Insulin Human Winthrop Basal"). 
 
Hypoglycaemia is also more likely to occur if: 
- you have just begun insulin treatment or changed to another insulin preparation, 
- your blood sugar levels are almost normal or are unstable, 
- you change the area of skin where you inject insulin (for example from the thigh to the upper 

arm), 
- you suffer from severe kidney or liver disease, or some other disease such as hypothyroidism. 
 
Warning symptoms of hypoglycaemia 
 
- In your body 
Examples of symptoms that tell you that your blood sugar level is falling too much or too fast: 
sweating, clammy skin, anxiety, fast heart beat, high blood pressure, palpitations and irregular 
heartbeat. These symptoms often develop before the symptoms of a low sugar level in the brain. 
 
- In your brain 
Examples of symptoms that indicate a low sugar level in the brain: headaches, intense hunger, nausea, 
vomiting, tiredness, sleepiness, sleep disturbances, restlessness, aggressive behaviour, lapses in 
concentration, impaired reactions, depression, confusion, speech disturbances (sometimes total loss of 
speech), visual disorders, trembling, paralysis, tingling sensations (paraesthesia), numbness and 
tingling sensations in the area of the mouth, dizziness, loss of self-control, inability to look after 
yourself, convulsions, loss of consciousness. 
 
The first symptoms which alert you to hypoglycaemia ("warning symptoms") may change, be weaker 
or may be missing altogether if 

 

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- you are elderly, if you have had diabetes for a long time or if you suffer from a certain type of 
nervous disease (diabetic autonomic neuropathy), 

- you have recently suffered hypoglycaemia (for example the day before) or if it develops slowly, 
- you have almost normal or, at least, greatly improved blood sugar levels, 
- you have recently changed from an animal insulin to a human insulin such as Insulin Human 

Winthrop, 
- you are taking or have taken certain other medicines (see section 2, "Other medicines and 
Insulin Human Winthrop Basal"). 
 
In such a case, you may develop severe hypoglycaemia (and even faint) before you are aware of the 
problem. Be familiar with your warning symptoms. If necessary, more frequent blood sugar testing 
can help to identify mild hypoglycaemic episodes that may otherwise be overlooked. If you are not 
confident about recognising your warning symptoms, avoid situations (such as driving a car) in which 
you or others would be put at risk by hypoglycaemia. 
 
What should you do if you experience hypoglycaemia 
 
1. Do not inject insulin. Immediately take about 10 to 20 g sugar, such as glucose, sugar cubes or a 

sugar-sweetened beverage. Caution: Artificial sweeteners and foods with artificial sweeteners 
(such as diet drinks) are of no help in treating hypoglycaemia. 

2. Then eat something that has a long-acting effect in raising your blood sugar (such as bread or 
pasta). Your doctor or nurse should have discussed this with you previously. 

3. If the hypoglycaemia comes back again take another 10 to 20 g sugar. 
4. Speak to a doctor immediately if you are not able to control the hypoglycaemia or if it recurs. 
 
Tell your relatives, friends and close colleagues the following: 
If you are not able to swallow or if you are unconscious, you will require an injection of glucose or 
glucagon (a medicine which increases blood sugar). These injections are justified even if it is not 
certain that you have hypoglycaemia. 
 
It is advisable to test your blood sugar immediately after taking glucose to check that you really have 
hypoglycaemia. 
 
 

 

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Package leaflet: Information for the user 

 
Insulin Human Winthrop Basal 100 IU/ml suspension for injection in a cartridge 

Insulin human 
 
 
Read all of this leaflet carefully before you start using this medicine because it contains 
important information for you. The instructions for using the insulin pen are provided with 
your insulin pen. Refer to them before using your medicine. 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor, pharmacist or nurse. 
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours. 
- If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible 

side effects not listed in this leaflet. 
 
What is in this leaflet: 
1. What Insulin Human Winthrop Basal is and what it is used for 
2. What you need to know before you use Insulin Human Winthrop Basal 
3. How to use Insulin Human Winthrop Basal 
4. Possible side effects 
5. How to store Insulin Human Winthrop Basal 
6. Contents of the pack and other information 
 
 
1. What Insulin Human Winthrop Basal is and what it is used for 
 
Insulin Human Winthrop Basal contains the active substance insulin human which is made by a 
biotechnology process and is identical with the body's own insulin. 
 
Insulin Human Winthrop Basal is an insulin preparation with a gradual onset and long duration of 
action. The insulin is present as tiny crystals of insulin protamine.  
 
Insulin Human Winthrop Basal is used to reduce high blood sugar in patients with diabetes mellitus 
who need treatment with insulin. Diabetes mellitus is a disease where your body does not produce 
enough insulin to control the level of blood sugar. 
 
 
2. What you need to know before you use Insulin Human Winthrop Basal 
 
Do not use Insulin Human Winthrop Basal 
 
If you are allergic to insulin or any of the other ingredients of this medicine (listed in section 6).  
 
Warnings and precautions 
 
Talk to your doctor, pharmacist or nurse before using Insulin Human Winthrop Basal.  
Follow closely the instructions for dosage, monitoring (blood and urine tests), diet and physical 
activity (physical work and exercise) as discussed with your doctor. 
 
If you are allergic to this medicine or to animal insulins, talk to your doctor. 
 
Special patient groups 
If you have liver or kidneys problems or if you are elderly, speak to your doctor as you may need a 
lower dose. 
 

 

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Travel 
Before travelling, consult your doctor. You may need to talk about 
- the availability of your insulin in the country you are visiting, 
- supplies of insulin, injection syringes etc., 
- correct storage of your insulin while travelling, 
- timing of meals and insulin administration while travelling, 
- the possible effects of changing to different time zones, 
- possible new health risks in the countries to be visited, 
- what you should do in emergency situations when you feel unwell or become ill. 
 
Illnesses and injuries 
In the following situations, the management of your diabetes may require a lot of care: 
- If you are ill or have a major injury then your blood sugar level may increase (hyperglycaemia).  
- If you are not eating enough, your blood sugar level may become too low (hypoglycaemia).  
In most cases you will need a doctor. Make sure that you contact a doctor early.  
 
If you have type 1 diabetes (insulin dependent diabetes mellitus), do not stop your insulin and 
continue to get enough carbohydrates. Always tell people who are caring for you or treating you that 
you require insulin. 
 
Some patients with long-standing type 2 diabetes mellitus and heart disease or previous stroke who 
were treated with pioglitazone and insulin experienced the development of heart failure. Inform your 
doctor as soon as possible if you experience signs of heart failure such as unusual shortness of breath 
or rapid increase in weight or localised swelling (oedema). 
 
Other medicines and Insulin Human Winthrop Basal 
 
Some medicines cause changes in the blood sugar level (decrease, increase or both depending on the 
situation). In each case, it may be necessary to adjust your insulin dosage to avoid blood sugar levels 
that are either too low or too high. Be careful when you start or stop taking another medicine. 
 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines. Before taking a medicine ask your doctor if it can affect your blood sugar level, and what 
action, if any, you need to take. 
 
Medicines that may cause your blood sugar level to fall (hypoglycaemia) include:  
- all other medicines to treat diabetes,  
- angiotensin converting enzyme (ACE) inhibitors (used to treat certain heart conditions or high 

blood pressure),  
- disopyramide (used to treat certain heart conditions),  
- fluoxetine (used to treat depression),  
- fibrates (used to lower high levels of blood lipids),  
- monoamine oxidase (MAO) inhibitors (used to treat depression),  
- pentoxifylline, propoxyphene, salicylates (such as aspirin, used to relieve pain and lower fever), 
- sulfonamide antibiotics. 
 
Medicines that may cause your blood sugar level to rise (hyperglycaemia) include:  
- corticosteroids (such as "cortisone", used to treat inflammation),  
- danazol (medicine acting on ovulation),  
- diazoxide (used to treat high blood pressure),  
- diuretics (used to treat high blood pressure or excessive fluid retention),  
- glucagon (pancreas hormone used to treat severe hypoglycaemia),  
- isoniazid (used to treat tuberculosis),  
- oestrogens and progestogens (such as in the contraceptive pill used for birth control),  
- phenothiazine derivatives (used to treat psychiatric disorders),  
- somatropin (growth hormone),  

 

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- sympathomimetic medicines (such as epinephrine [adrenaline] or salbutamol, terbutaline used to 
treat asthma), 

- thyroid hormones (used to treat the thyroid gland disorders), 
- protease inhibitors (used to treat HIV), 
- atypical antipsychotic medicines (such as olanzapine and clozapine). 
 
Your blood sugar level may either rise or fall if you take:  
- beta-blockers (used to treat high blood pressure),  
- clonidine (used to treat high blood pressure), 
- lithium salts (used to treat psychiatric disorders).  
Pentamidine (used to treat some infections caused by parasites) may cause hypoglycaemia which may 
sometimes be followed by hyperglycaemia. 
 
Beta-blockers like other sympatholytic medicines (such as clonidine, guanethidine, and reserpine) may 
weaken or suppress entirely the first warning symptoms which help you to recognise a 
hypoglycaemia. 
 
If you are not sure whether you are taking one of those medicines ask your doctor or pharmacist. 
 
Insulin Human Winthrop Basal with alcohol. 
 
Your blood sugar levels may either rise or fall if you drink alcohol. 
 
Pregnancy and breast-feeding 
 
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor or pharmacist for advice before taking this medicine. 
 
Inform your doctor if you are planning to become pregnant, or if you are already pregnant. Your 
insulin dosage may need to be changed during pregnancy and after giving birth. Particularly careful 
control of your diabetes, and prevention of hypoglycaemia, is important for the health of your baby.  
 
If you are breast-feeding consult your doctor as you may require adjustments in your insulin doses and 
your diet. 
 
Driving and using machines 
 
Your ability to concentrate or react may be reduced if: 
- you have hypoglycaemia (low blood sugar levels), 
- you have hyperglycaemia (high blood sugar levels), 
- you have problems with your sight.  
Keep this possible problem in mind in all situations where you might put yourself and others at risk 
(such as driving a car or using machines). You should contact your doctor for advice on driving if: 
- you have frequent episodes of hypoglycaemia, 
- the first warning symptoms which help you to recognise hypoglycaemia are reduced or absent. 
 
Important information about some of the ingredients of Insulin Human Winthrop Basal 
 
 
This medicine contains less than 1 mmol (23 mg) sodium per dose, i.e. it is essentially ‘sodium-free’. 
 
 

 

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3. How to use Insulin Human Winthrop Basal 
 
Dose 
 
Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor 
or pharmacist if you are not sure. 
 
Based on your life-style and the results of your blood sugar (glucose) tests, your doctor will 
- determine how much Insulin Human Winthrop Basal per day you will need, 
- tell you when to check your blood sugar level, and whether you need to carry out urine tests, 
- tell you when you may need to inject a higher or lower dose of Insulin Human Winthrop Basal. 
 
Many factors may influence your blood sugar level. You should know these factors so that you are 
able to react correctly to changes in your blood sugar level and to prevent it from becoming too high 
or too low. See the box at the end of this leaflet for further information. 
 
Frequency of administration 
 
Insulin Human Winthrop Basal is injected under the skin 45 to 60 minutes before a meal.  
 
Method of administration 
 
Insulin Human Winthrop Basal is a fluid (suspension) for injection under the skin. 
 
Do NOT inject Insulin Human Winthrop Basal into a vein (blood vessel). 
 
Your doctor will show you in which area of the skin you should inject your insulin. With each 
injection, change the puncture site within the particular area of skin that you are using. 
 
Do not use it in insulin pumps or other infusion pumps – special insulin preparations are available for 
use in such devices. 
 
How to handle the cartridges 
 
To ensure you get the accurate dose, the Insulin Human Winthrop Basal cartridges are to be used only 
with the following pens: 
- JuniorSTAR which delivers doses in steps of 0.5 units  
- OptiPen, ClikSTAR, Tactipen, Autopen 24 or AllStar which deliver doses in steps of 1 unit. 
Not all of these pens may be marketed in your country.  
 
The pen should be used as recommended in the information provided by the device manufacturer. The 
manufacturer’s instructions for using the pen must be followed carefully for loading the cartridge, 
attaching the injection needle, and administering the insulin injection. 
 
Keep the cartridge at room temperature for 1 or 2 hours before inserting it into the pen. Mix the 
insulin well and check it before you insert it into the pen. Later, you must mix the insulin well again 
immediately before each injection. 
 
Mixing is best done by gently tilting the cartridge or pen (with the cartridge in it) back and forth at 
least 10 times. To assist in mixing, three tiny metal balls are present in the cartridge. 
 
After mixing, the suspension must have a uniform milky-white appearance. It must not be used if it 
remains clear or if, for example, clumps, flakes, particles or anything similar are in the suspension or 
on the sides or bottom of the cartridge. A new cartridge with a uniform suspension on mixing must 
then be used. 
 

 

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Always use a new cartridge if you notice that your blood sugar control is unexpectedly getting worse. 
This is because the insulin may have lost some of its effectiveness. If you think you may have a 
problem with your insulin, have it checked by your doctor or pharmacist. 
 
Special care before injection 
 
Before injection remove any air bubbles (see instructions for using the pen). Make sure that neither 
alcohol nor other disinfectants or other substances contaminate the insulin. 
- Do not re-fill and re-use empty cartridges. 
- Do not add any other insulin to the cartridge. 
- Do not mix insulin with any other medicines. 
 
Problems with the pen? 
 
Refer to the manufacturer’s instructions for using the pen. 
If the insulin pen is damaged or not working properly (due to mechanical defects) it has to be 
discarded, and a new insulin pen has to be used. 
 
If the pen does not function well, you can draw the insulin from the cartridge into an injection syringe. 
Therefore, keep injection syringes and needles as well. However, use only those injection syringes 
which are designed for an insulin concentration of 100 IU (International Units) per ml. 
 
If you use more Insulin Human Winthrop Basal than you should 
- If you have injected too much Insulin Human Winthrop Basal, your blood sugar level may 

become too low (hypoglycaemia). Check your blood sugar frequently. In general, to prevent 
hypoglycaemia you must eat more food and monitor your blood sugar. For information on the 
treatment of hypoglycaemia, see box at the end of this leaflet. 

 
If you forget to use Insulin Hun Winthrop Basal 
- If you have missed a dose of Insulin Human Winthrop Basal or if you have not injected 

enough insulin, your blood sugar level may become too high (hyperglycaemia). Check your 
blood sugar frequently. For information on the treatment of hyperglycaemia, see box at the end of 
this leaflet. 

 
- Do not take a double dose to make up for a forgotten dose. 
 
If you stop using Insulin Human Winthrop Basal 
This could lead to severe hyperglycaemia (very high blood sugar) and ketoacidosis (build-up of acid 
in the blood because the body is breaking down fat instead of sugar). Do not stop Insulin Human 
Winthrop Basal without speaking to a doctor, who will tell you what needs to be done. 
 
If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse. 
 
Insulin Mix-ups 
 
You must always check the insulin label before each injection to avoid mix-ups between Insulin 
Human Winthrop Basal and other insulins.  
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
The most frequent side effect is hypoglycaemia (low blood sugar). The specific frequency cannot be 
estimated from available data (frequency not known). Serious hypoglycaemia may cause a heart attack 
or brain damage and may be life-threatening. For further information on the side effects of low blood 
sugar or high blood sugar, see the box at the end of this leaflet. 

 

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Severe allergic reactions to insulin may occur which may become life-threatening. Such reactions to 
insulin or to the excipients can cause large-scale skin reactions (rash and itching all over the body); 
severe swelling of skin or mucous membranes (angiooedema), shortness of breath, a fall in blood 
pressure with rapid heart beat and sweating. Frequency of these reactions cannot be estimated from 
available data. 
 
Side effects reported commonly (may affect up to 1 in 10 people) 
• Oedema 
Insulin treatment may cause temporary build-up of water in the body with swelling in the calves and 
ankles. 
• Injection site reactions 
 
Side effects reported uncommonly (may affect up to 1 in 100 people) 
• Severe allergic reaction with low blood pressure (shock) 
• Injection site urticaria (itchy rash) 
 
Other side effects include (frequency cannot be estimated from the available data) 
• Sodium retention 
• Eye reactions 
A marked change (improvement or worsening) in your blood sugar control can disturb your vision 
temporarily. If you have proliferative retinopathy (an eye disease related to diabetes) severe 
hypoglycaemic attacks may cause temporary loss of vision. 
• Skin changes at the injection site (lipodystrophy) 
If you inject your insulin too often at the same skin site, fatty tissue under the skin at this site may 
either shrink or thicken. Insulin that you inject in such a site may not work very well. Changing the 
injection site with each injection may help to prevent such skin changes. 
• Skin and allergic reactions 
Other mild reactions at the injection site (such as injection site redness, unusually intense pain on 
injection site, itching, injection site swelling or injection site inflammation) may occur. They can also 
spread around the injection site. Most minor reactions to insulins usually resolve in a few days to a 
few weeks. 
 
Insulin treatment can cause the body to produce antibodies to insulin (substances that act against 
insulin). However, only very rarely, this will require a change to your insulin dosage. 
 
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side 
effects not listed in this leaflet. 
 
 
5. How to store Insulin Human Winthrop Basal 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date which is stated on the carton and on the label of the 
cartridge after “EXP”. The expiry date refers to the last day of that month. 
 
Unopened cartridges 
Store in a refrigerator (2°C - 8°C). Do not freeze. Do not put Insulin Human Winthrop Basal next to 
the freezer compartment or a freezer pack. Keep the cartridge in the outer carton in order to protect 
from light. 
 
In-use cartridges 
Cartridges in-use (in the insulin pen) or carried as a spare may be stored for a maximum of 4 weeks 
not above 25°C and away from direct heat (for example next to a heating unit) or direct light (direct 
sunlight or next to a lamp). The cartridge in-use must not be stored in a refrigerator. Do not use the 
cartridge after this time period. 

 

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Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Insulin Human Winthrop Basal contains 
- The active substance is insulin human. One ml of Insulin Human Winthrop Basal contains 

100 IU (International Units) of the active substance insulin human. 
- The other ingredients are: protamine sulphate, metacresol, phenol, zinc chloride, sodium 

dihydrogen phosphate dihydrate, glycerol, sodium hydroxide (see section 2 under “Important 
information about some of the ingredients of Insulin Human Winthrop Basal”), hydrochloric 
acid (for pH adjustment) and water for injections. 

 
What Insulin Human Winthrop Basal looks like and contents of the pack 
After mixing, Insulin Human Winthrop Basal is a uniformly milky fluid (suspension for injection), 
with no clumps, particles or flocculation visible. 
 
Insulin Human Winthrop Basal is supplied in cartridges containing 3 ml suspension (300 IU). Packs of 
3, 4, 5, 6, 9 and 10 cartridges of 3 ml are available. Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder and Manufacturer 
Sanofi-Aventis Deutschland GmbH 
D-65926 Frankfurt am Main 
Germany 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
Sanofi Belgium 
Tél/Tel: +32 (0)2 710 54 00 
 

Lietuva 
UAB «SANOFI-AVENTIS LIETUVA» 
Tel: +370 5 2755224 
 

България 
sanofi-aventis Bulgaria EOOD 
Тел.: +359 (0)2 970 53 00 
 

Luxembourg/Luxemburg 
Sanofi Belgium  
Tél/Tel: +32 (0)2 710 54 00 (Belgique/Belgien) 
 

Česká republika 
sanofi-aventis, s.r.o. 
Tel: +420 233 086 111 
 

Magyarország 
SANOFI-AVENTIS Zrt. 
Tel.: +36 1 505 0050 
 

Danmark 
sanofi-aventis Denmark A/S 
Tlf: +45 45 16 70 00 
 

Malta 
Sanofi Malta Ltd. 
Tel: +356 21493022 
 

Deutschland 
Zentiva Pharma GmbH 
Tel: +49 (0)180 20 200 10 
 

Nederland 
sanofi-aventis Netherlands B.V. 
Tel: +31 (0)182 557 755 
 

Eesti 
sanofi-aventis Estonia OÜ 
Tel: +372 627 34 88 
 

Norge 
Aventis Pharma Norge AS 
Tlf: +47 67 10 71 00 
 

 

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Ελλάδα 
sanofi-aventis AEBE 
Τηλ: +30 210 900 16 00 
 

Österreich 
sanofi-aventis GmbH 
Tel: +43 1 80 185 – 0 
 

España 
sanofi-aventis, S.A. 
Tel: +34 93 485 94 00 
 

Polska 
sanofi-aventis Sp. z o.o. 
Tel.: +48 22 280 00 00 
 

France 
sanofi-aventis France 
Tél: 0 800 222 555 
Appel depuis l’étranger : +33 1 57 63 23 23 
 

Portugal 
Sanofi - Produtos Farmacêuticos, Lda. 
Tel: +351 21 35 89 400 
 

Hrvatska 
sanofi-aventis Croatia d.o.o. 
Tel: +385 1 600 34 00 

România 
Sanofi Romania SRL 
Tel: +40 (0) 21 317 31 36 
 

Ireland 
sanofi-aventis Ireland Ltd. T/A SANOFI 
Tel: +353 (0) 1 403 56 00 
 

Slovenija 
sanofi-aventis d.o.o. 
Tel: +386 1 560 48 00 
 

Ísland 
Vistor hf. 
Sími: +354 535 7000 
 

Slovenská republika 
sanofi-aventis Pharma Slovakia s.r.o. 
Tel: +421 2 33 100 100 
 

Italia 
Sanofi S.p.A. 
Tel: 800 13 12 12 (domande di tipo tecnico)  
800 536389 (altre domande) 
 

Suomi/Finland 
Sanofi Oy 
Puh/Tel: +358 (0) 201 200 300 
 

Κύπρος 
sanofi-aventis Cyprus Ltd. 
Τηλ: +357 22 871600 
 

Sverige 
Sanofi AB 
Tel: +46 (0)8 634 50 00 
 

Latvija 
sanofi-aventis Latvia SIA 
Tel: +371 67 33 24 51 
 

United Kingdom 
Sanofi 
Tel: +44 (0) 845 372 7101 
 

 
This leaflet was last revised in {date} 
 
 
Other source of information 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu/ 
 
 
 

 
HYPERGLYCAEMIA AND HYPOGLYCAEMIA 

 
Always carry some sugar (at least 20 grams) with you. 

Carry some information with you to show you are diabetic. 
 

HYPERGLYCAEMIA (high blood sugar levels) 
 

If your blood sugar is too high (hyperglycaemia), you may not have injected enough insulin. 

 

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Why does hyperglycaemia occur? 
 
Examples include: 
- you have not injected your insulin or not injected enough, or if it has become less effective, for 

example through incorrect storage, 
- your insulin pen does not work properly, 
- you are doing less exercise than usual, you are under stress (emotional distress, excitement), or 

you have an injury, operation, infection or fever, 
- you are taking or have taken certain other medicines (see section 2, "Other medicines and 

Insulin Human Winthrop Basal"). 
 
Warning symptoms of hyperglycaemia 
 
Thirst, increased need to urinate, tiredness, dry skin, reddening of the face, loss of appetite, low blood 
pressure, fast heart beat, and glucose and ketone bodies in urine. Stomach pain, fast and deep 
breathing, sleepiness or even loss of consciousness may be signs of a serious condition (ketoacidosis) 
resulting from lack of insulin. 
 
What should you do if you experience hyperglycaemia 
 
Test your blood sugar level and your urine for ketones as soon as any of the above symptoms 
occur. Severe hyperglycaemia or ketoacidosis must always be treated by a doctor, normally in a 
hospital. 
 

HYPOGLYCAEMIA (low blood sugar levels) 
 
If your blood sugar level falls too much you may become unconscious. Serious hypoglycaemia may 
cause a heart attack or brain damage and may be life-threatening. You normally should be able to 
recognise when your blood sugar is falling too much so that you can take the right actions. 
 
Why does hypoglycaemia occur? 
 
Examples include: 
- you inject too much insulin, 
- you miss meals or delay them, 
- you do not eat enough, or eat food containing less carbohydrate than normal (sugar and 

substances similar to sugar are called carbohydrates; however, artificial sweeteners are NOT 
carbohydrates), 

- you lose carbohydrates due to vomiting or diarrhoea, 
- you drink alcohol, particularly if you are not eating much, 
- you are doing more exercise than usual or a different type of physical activity, 
- you are recovering from an injury or operation or other stress, 
- you are recovering from an illness or from fever, 
- you are taking or have stopped taking certain other medicines (see section 2, "Other medicines 

and Insulin Human Winthrop Basal"). 
 
Hypoglycaemia is also more likely to occur if: 
- you have just begun insulin treatment or changed to another insulin preparation, 
- your blood sugar levels are almost normal or are unstable, 
- you change the area of skin where you inject insulin (for example from the thigh to the upper 

arm), 
- you suffer from severe kidney or liver disease, or some other disease such as hypothyroidism. 
 
Warning symptoms of hypoglycaemia 
 
- In your body 

 

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Examples of symptoms that tell you that your blood sugar level is falling too much or too fast: 
sweating, clammy skin, anxiety, fast heart beat, high blood pressure, palpitations and irregular 
heartbeat. These symptoms often develop before the symptoms of a low sugar level in the brain. 
 
- In your brain 
Examples of symptoms that indicate a low sugar level in the brain: headaches, intense hunger, nausea, 
vomiting, tiredness, sleepiness, sleep disturbances, restlessness, aggressive behaviour, lapses in 
concentration, impaired reactions, depression, confusion, speech disturbances (sometimes total loss of 
speech), visual disorders, trembling, paralysis, tingling sensations (paraesthesia), numbness and 
tingling sensations in the area of the mouth, dizziness, loss of self-control, inability to look after 
yourself, convulsions, loss of consciousness. 
 
The first symptoms which alert you to hypoglycaemia ("warning symptoms") may change, be weaker 
or may be missing altogether if 
- you are elderly, if you have had diabetes for a long time or if you suffer from a certain type of 

nervous disease (diabetic autonomic neuropathy), 
- you have recently suffered hypoglycaemia (for example the day before) or if it develops slowly, 
- you have almost normal or, at least, greatly improved blood sugar levels, 
- you have recently changed from an animal insulin to a human insulin such as Insulin Human 

Winthrop, 
- you are taking or have taken certain other medicines (see section 2, "Other medicines and 

Insulin Human Winthrop Basal"). 
 
In such a case, you may develop severe hypoglycaemia (and even faint) before you are aware of the 
problem. Be familiar with your warning symptoms. If necessary, more frequent blood sugar testing 
can help to identify mild hypoglycaemic episodes that may otherwise be overlooked. If you are not 
confident about recognising your warning symptoms, avoid situations (such as driving a car) in which 
you or others would be put at risk by hypoglycaemia. 
 
What should you do if you experience hypoglycaemia 
 
1. Do not inject insulin. Immediately take about 10 to 20 g sugar, such as glucose, sugar cubes or a 

sugar-sweetened beverage. Caution: Artificial sweeteners and foods with artificial sweeteners 
(such as diet drinks) are of no help in treating hypoglycaemia. 

2. Then eat something that has a long-acting effect in raising your blood sugar (such as bread or 
pasta). Your doctor or nurse should have discussed this with you previously. 

3. If the hypoglycaemia comes back again take another 10 to 20 g sugar. 
4. Speak to a doctor immediately if you are not able to control the hypoglycaemia or if it recurs. 
 
Tell your relatives, friends and close colleagues the following: 
If you are not able to swallow or if you are unconscious, you will require an injection of glucose or 
glucagon (a medicine which increases blood sugar). These injections are justified even if it is not 
certain that you have hypoglycaemia. 
 
It is advisable to test your blood sugar immediately after taking glucose to check that you really have 
hypoglycaemia. 
 
 

 

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Package leaflet: Information for the user 

 
Insulin Human Winthrop Basal SoloStar 100 IU/ml suspension for injection in a pre-filled pen 

Insulin human 
 
 
Read all of this leaflet carefully, including the Instructions for Use of Insulin Human Winthrop 
Basal SoloStar, pre-filled pen, before you start using this medicine because it contains important 
information for you. 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor, pharmacist or nurse. 
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours. 
- If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible 

side effects not listed in this leaflet. 
 
What is in this leaflet: 
1. What Insulin Human Winthrop Basal is and what it is used for 
2. What you need to know before you use Insulin Human Winthrop Basal 
3. How to use Insulin Human Winthrop Basal 
4. Possible side effects 
5. How to store Insulin Human Winthrop Basal 
6. Contents of the pack and other information 
 
 
1. What Insulin Human Winthrop Basal is and what it is used for 
 
Insulin Human Winthrop Basal contains the active substance insulin human which is made by a 
biotechnology process and is identical with the body's own insulin. 
 
Insulin Human Winthrop Basal is an insulin preparation with a gradual onset and long duration of 
action. The insulin is present as tiny crystals of insulin protamine. It comes in cartridges sealed in 
disposable pen injectors, SoloStar. 
 
Insulin Human Winthrop Basal is used to reduce high blood sugar in patients with diabetes mellitus 
who need treatment with insulin. Diabetes mellitus is a disease where your body does not produce 
enough insulin to control the level of blood sugar. 
 
 
2. What you need to know before you use Insulin Human Winthrop Basal 
 
Do not use Insulin Human Winthrop Basal 
 
If you are allergic to insulin or any of the other ingredients of this medicine (listed in section 6).  
 
Warnings and precautions 
 
Talk to your doctor, pharmacist or nurse before using Insulin Human Winthrop Basal 
Follow closely the instructions for dosage, monitoring (blood and urine tests), diet and physical 
activity (physical work and exercise), injection technique as discussed with your doctor. 
 
If you are allergic to this medicine or to animal insulins, talk to your doctor. 
 
Special patient groups 
If you have liver or kidneys problems or if you are elderly, speak to your doctor as you may need a 
lower dose. 

 

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Travel 
Before travelling, consult your doctor. You may need to talk about 
- the availability of your insulin in the country you are visiting, 
- supplies of insulin, injection syringes etc., 
- correct storage of your insulin while travelling, 
- timing of meals and insulin administration while travelling, 
- the possible effects of changing to different time zones, 
- possible new health risks in the countries to be visited, 
- what you should do in emergency situations when you feel unwell or become ill. 
 
Illnesses and injuries 
In the following situations, the management of your diabetes may require a lot of care: 
- If you are ill or have a major injury then your blood sugar level may increase (hyperglycaemia).  
- If you are not eating enough, your blood sugar level may become too low (hypoglycaemia).  
In most cases you will need a doctor. Make sure that you contact a doctor early.  
 
If you have type 1 diabetes (insulin dependent diabetes mellitus), do not stop your insulin and 
continue to get enough carbohydrates. Always tell people who are caring for you or treating you that 
you require insulin. 
 
Some patients with long-standing type 2 diabetes mellitus and heart disease or previous stroke who 
were treated with pioglitazone and insulin experienced the development of heart failure. Inform your 
doctor as soon as possible if you experience signs of heart failure such as unusual shortness of breath 
or rapid increase in weight or localised swelling (oedema). 
 
Other medicines and Insulin Human Winthrop Basal 
 
Some medicines cause changes in the blood sugar level (decrease, increase or both depending on the 
situation). In each case, it may be necessary to adjust your insulin dosage to avoid blood sugar levels 
that are either too low or too high. Be careful when you start or stop taking another medicine. 
 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines. Before taking a medicine ask your doctor if it can affect your blood sugar level, and what 
action, if any, you need to take. 
 
Medicines that may cause your blood sugar level to fall (hypoglycaemia) include:  
- all other medicines to treat diabetes,  
- angiotensin converting enzyme (ACE) inhibitors (used to treat certain heart conditions or high 

blood pressure),  
- disopyramide (used to treat certain heart conditions),  
- fluoxetine (used to treat depression),  
- fibrates (used to lower high levels of blood lipids),  
- monoamine oxidase (MAO) inhibitors (used to treat depression),  
- pentoxifylline, propoxyphene, salicylates (such as aspirin, used to relieve pain and lower fever), 
- sulfonamide antibiotics. 
 
Medicines that may cause your blood sugar level to rise (hyperglycaemia) include:  
- corticosteroids (such as "cortisone", used to treat inflammation),  
- danazol (medicine acting on ovulation),  
- diazoxide (used to treat high blood pressure),  
- diuretics (used to treat high blood pressure or excessive fluid retention),  
- glucagon (pancreas hormone used to treat severe hypoglycaemia),  
- isoniazid (used to treat tuberculosis),  
- oestrogens and progestogens (such as in the contraceptive pill used for birth control),  
- phenothiazine derivatives (used to treat psychiatric disorders),  
- somatropin (growth hormone),  

 

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- sympathomimetic medicines (such as epinephrine [adrenaline] or salbutamol, terbutaline used to 
treat asthma), 

- thyroid hormones (used to treat the thyroid gland disorders), 
- protease inhibitors (used to treat HIV), 
- atypical antipsychotic medicines (such as olanzapine and clozapine). 
 
Your blood sugar level may either rise or fall if you take:  
- beta-blockers (used to treat high blood pressure),  
- clonidine (used to treat high blood pressure),  
- lithium salts (used to treat psychiatric disorders).  
Pentamidine (used to treat some infections caused by parasites) may cause hypoglycaemia which may 
sometimes be followed by hyperglycaemia. 
 
Beta-blockers like other sympatholytic medicines (such as clonidine, guanethidine, and reserpine) may 
weaken or suppress entirely the first warning symptoms which help you to recognise a 
hypoglycaemia. 
 
If you are not sure whether you are taking one of those medicines ask your doctor or pharmacist. 
 
Insulin Human Winthrop Basal with alcohol 
 
Your blood sugar levels may either rise or fall if you drink alcohol. 
 
Pregnancy and breast-feeding 
 
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor or pharmacist for advice before taking this medicine. 
 
Inform your doctor if you are planning to become pregnant, or if you are already pregnant. Your 
insulin dosage may need to be changed during pregnancy and after giving birth. Particularly careful 
control of your diabetes, and prevention of hypoglycaemia, is important for the health of your baby.  
 
If you are breast-feeding consult your doctor as you may require adjustments in your insulin doses and 
your diet. 
 
Driving and using machines 
 
Your ability to concentrate or react may be reduced if: 
- you have hypoglycaemia (low blood sugar levels), 
- you have hyperglycaemia (high blood sugar levels), 
- you have problems with your sight.  
Keep this possible problem in mind in all situations where you might put yourself and others at risk 
(such as driving a car or using machines). You should contact your doctor for advice on driving if: 
- you have frequent episodes of hypoglycaemia, 
- the first warning symptoms which help you to recognise hypoglycaemia are reduced or absent. 
 
Important information about some of the ingredients of Insulin Human Winthrop Basal  
 
This medicine contains less than 1 mmol (23 mg) sodium per dose, i.e. it is essentially ‘sodium-free’. 
 
 

 

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3. How to use Insulin Human Winthrop Basal 
 
Dose 
 
Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor 
or pharmacist if you are not sure. 
 
Based on your life-style and the results of your blood sugar (glucose) tests, your doctor will 
- determine how much Insulin Human Winthrop Basal per day you will need, 
- tell you when to check your blood sugar level, and whether you need to carry out urine tests, 
- tell you when you may need to inject a higher or lower dose of Insulin Human Winthrop Basal. 
 
Many factors may influence your blood sugar level. You should know these factors so that you are 
able to react correctly to changes in your blood sugar level and to prevent it from becoming too high 
or too low. See the box at the end of this leaflet for further information. 
 
Frequency of administration 
 
Insulin Human Winthrop Basal is injected under the skin 45 to 60 minutes before a meal.  
 
Method of administration 
 
Insulin Human Winthrop Basal is a fluid (suspension) for injection under the skin. 
 
Do NOT inject Insulin Human Winthrop Basal into a vein (blood vessel). 
 
SoloStar delivers insulin in doses from 1 to 80 units in steps of 1 unit. Each pen contains multiple 
doses. 
 
Your doctor will show you in which area of the skin you should inject your insulin. With each 
injection, change the puncture site within the particular area of skin that you are using. 
 
How to handle SoloStar 
 
SoloStar is a pre-filled disposable pen containing human insulin. 
 
Read carefully the "SoloStar Instructions for Use" included in this package leaflet. You must 
use the pen as described in these Instructions for Use. 
 
A new injection needle must be attached before each use. Only use needles that have been approved 
for use with SoloStar. 
A safety test must be performed before each injection. 
 
Mix the insulin well and check it before first use. Later, you must mix the insulin well again 
immediately before each injection. 
 
Mixing is best done by gently tilting the pen back and forth at least 10 times. To assist in mixing, three 
tiny metal balls are present in the cartridge. 
 
After mixing, the suspension must have a uniform milky-white appearance. It must not be used if it 
remains clear or if, for example, clumps, flakes, particles or anything similar are in the suspension or 
on the sides or bottom of the cartridge in the pen. A new pen with a uniform suspension on mixing 
must then be used. 
 
Always use a new pen if you notice that your blood sugar control is unexpectedly getting worse. If 
you think you have a problem with SoloStar, consult your doctor, pharmacist or nurse. 
 

 

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To prevent the possible transmission of disease, each pen must be used by one patient only. 
 
Special care before injection 
 
Make sure that neither alcohol nor other disinfectants or other substances contaminate the insulin. 
 
Do not mix insulin with any other medicines. Insulin Human Winthrop Basal SoloStar pre-filled pen, 
is not designed to allow any other insulin to be mixed in the cartridge. 
 
Empty pens must not be re-filled and must be properly discarded. 
 
Do not use SoloStar if it is damaged or not working properly (due to mechanical defects), it has to be 
discarded and a new SoloStar has to be used. 
 
If you use more Insulin Human Winthrop Basal than you should 
- If you have injected too much Insulin Human Winthrop Basal, your blood sugar level may 

become too low (hypoglycaemia). Check your blood sugar frequently. In general, to prevent 
hypoglycaemia you must eat more food and monitor your blood sugar. For information on the 
treatment of hypoglycaemia, see box at the end of this leaflet. 

 
If you forget to use Insulin Human Winthrop Basal 
- If you have missed a dose of Insulin Human Winthrop Basal or if you have not injected 

enough insulin, your blood sugar level may become too high (hyperglycaemia). Check your 
blood sugar frequently. For information on the treatment of hyperglycaemia, see box at the end 
of this leaflet. 

 
- Do not take a double dose to make up for a forgotten dose. 
 
If you stop using Insulin Human Winthrop Basal 
This could lead to severe hyperglycaemia (very high blood sugar) and ketoacidosis (build-up of acid 
in the blood because the body is breaking down fat instead of sugar). Do not stop Insulin Human 
Winthrop Basal without speaking to a doctor, who will tell you what needs to be done. 
 
If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse. 
 
Insulin Mix-ups 
 
You must always check the insulin label before each injection to avoid mix-ups between Insulin 
Human Winthrop Basal and other insulins.  
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
The most frequent side effect is hypoglycaemia (low blood sugar). The specific frequency cannot be 
estimated from available data (frequency not known). Serious hypoglycaemia may cause a heart attack 
or brain damage and may be life-threatening. For further information on the side effects of low blood 
sugar or high blood sugar, see the box at the end of this leaflet. 
 
Severe allergic reactions to insulin may occur which may become life-threatening. Such reactions to 
insulin or to the excipients can cause large-scale skin reactions (rash and itching all over the body); 
severe swelling of skin or mucous membranes (angiooedema), shortness of breath, a fall in blood 
pressure with rapid heart beat and sweating. Frequency of these reactions cannot be estimated from 
available data. 
 

 

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Side effects reported commonly (may affect up to 1 in 10 people) 
• Oedema 
Insulin treatment may cause temporary build-up of water in the body with swelling in the calves and 
ankles. 
• Injection site reactions 
 
Side effects reported uncommonly (may affect up to 1 in 100 people) 
• Severe allergic reaction with low blood pressure (shock) 
• Injection site urticaria (itchy rash) 
 
Other side effects include (frequency cannot be estimated from the available data) 
• Sodium retention 
• Eye reactions 
A marked change (improvement or worsening) in your blood sugar control can disturb your vision 
temporarily. If you have proliferative retinopathy (an eye disease related to diabetes) severe 
hypoglycaemic attacks may cause temporary loss of vision. 
• Skin changes at the injection site (lipodystrophy) 
If you inject your insulin too often at the same skin site, fatty tissue under the skin at this site may 
either shrink or thicken. Insulin that you inject in such a site may not work very well. Changing the 
injection site with each injection may help to prevent such skin changes. 
• Skin and allergic reactions 
Other mild reactions at the injection site (such as injection site redness, unusually intense pain on 
injection site, itching, injection site swelling or injection site inflammation) may occur. They can also 
spread around the injection site. Most minor reactions to insulins usually resolve in a few days to a 
few weeks. 
 
Insulin treatment can cause the body to produce antibodies to insulin (substances that act against 
insulin). However, only very rarely, this will require a change to your insulin dosage. 
 
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side 
effects not listed in this leaflet. 
 
 
5. How to store Insulin Human Winthrop Basal 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date which is stated on the carton and on the label of the pen 
after “EXP”. The expiry date refers to the last day of that month. 
 
Not in-use pens 
Store in a refrigerator (2°C - 8°C). Do not freeze. Do not put the pre-filled pen next to the freezer 
compartment or a freezer pack. Keep the pre-filled pen in the outer carton in order to protect from 
light. 
 
In-use pens 
Pre-filled pens in-use or carried as a spare may be stored for a maximum of 4 weeks not above 25°C 
and away from direct heat (for example next to a heating unit) or direct light (direct sunlight or next to 
a lamp). The pen in-use must not be stored in a refrigerator. Do not use the pen after this time period.  
 
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment. 
 
 

 

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6. Contents of the pack and other information 
 
What Insulin Human Winthrop Basal contains 
- The active substance is insulin human. One ml of Insulin Human Winthrop Basal contains 

100 IU (International Units) of the active substance insulin human. 
- The other ingredients are: protamine sulphate, metacresol, phenol, zinc chloride, sodium 

dihydrogen phosphate dihydrate, glycerol, sodium hydroxide (see section 2 under “Important 
information about some of the ingredients of Insulin Human Winthrop Basal”), hydrochloric 
acid (for pH adjustment) and water for injections. 

 
What Insulin Human Winthrop Basal looks like and contents of the pack 
After mixing, Insulin Human Winthrop Basal is a uniformly milky fluid (suspension for injection), 
with no clumps, particles or flocculation visible. 
 
Insulin Human Winthrop Basal is supplied in pre-filled pens, SoloStar, containing 3 ml suspension 
(300 IU). Packs of 3, 4, 5, 6, 9 and 10 pens of 3 ml are available. Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder and Manufacturer 
Sanofi-Aventis Deutschland GmbH 
D-65926 Frankfurt am Main 
Germany 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
Sanofi Belgium 
Tél/Tel: +32 (0)2 710 54 00 
 

Lietuva 
UAB «SANOFI-AVENTIS LIETUVA» 
Tel: +370 5 2755224 
 

България 
sanofi-aventis Bulgaria EOOD 
Тел.: +359 (0)2 970 53 00 
 

Luxembourg/Luxemburg 
Sanofi Belgium  
Tél/Tel: +32 (0)2 710 54 00 (Belgique/Belgien) 
 

Česká republika 
sanofi-aventis, s.r.o. 
Tel: +420 233 086 111 
 

Magyarország 
SANOFI-AVENTIS Zrt. 
Tel.: +36 1 505 0050 
 

Danmark 
sanofi-aventis Denmark A/S 
Tlf: +45 45 16 70 00 
 

Malta 
Sanofi Malta Ltd. 
Tel: +356 21493022 
 

Deutschland 
Zentiva Pharma GmbH 
Tel: +49 (0)180 20 200 10 
 

Nederland 
sanofi-aventis Netherlands B.V. 
Tel: +31 (0)182 557 755 
 

Eesti 
sanofi-aventis Estonia OÜ 
Tel: +372 627 34 88 
 

Norge 
Aventis Pharma Norge AS 
Tlf: +47 67 10 71 00 
 

Ελλάδα 
sanofi-aventis AEBE 
Τηλ: +30 210 900 16 00 
 

Österreich 
sanofi-aventis GmbH 
Tel: +43 1 80 185 – 0 
 

España 
sanofi-aventis, S.A. 
Tel: +34 93 485 94 00 
 

Polska 
sanofi-aventis Sp. z o.o. 
Tel.: +48 22 280 00 00 
 

 

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France 
sanofi-aventis France 
Tél: 0 800 222 555 
Appel depuis l’étranger : +33 1 57 63 23 23 
 

Portugal 
Sanofi - Produtos Farmacêuticos, Lda. 
Tel: +351 21 35 89 400 
 

Hrvatska 
sanofi-aventis Croatia d.o.o. 
Tel: +385 1 600 34 00 

România 
Sanofi Romania SRL 
Tel: +40 (0) 21 317 31 36 
 

Ireland 
sanofi-aventis Ireland Ltd. T/A SANOFI 
Tel: +353 (0) 1 403 56 00 
 

Slovenija 
sanofi-aventis d.o.o. 
Tel: +386 1 560 48 00 
 

Ísland 
Vistor hf. 
Sími: +354 535 7000 
 

Slovenská republika 
sanofi-aventis Pharma Slovakia s.r.o. 
Tel: +421 2 33 100 100 
 

Italia 
Sanofi S.p.A. 
Tel: 800 13 12 12 (domande di tipo tecnico)  
800 536389 (altre domande) 
 

Suomi/Finland 
Sanofi Oy 
Puh/Tel: +358 (0) 201 200 300 
 

Κύπρος 
sanofi-aventis Cyprus Ltd. 
Τηλ: +357 22 871600 
 

Sverige 
Sanofi AB 
Tel: +46 (0)8 634 50 00 
 

Latvija 
sanofi-aventis Latvia SIA 
Tel: +371 67 33 24 51 
 

United Kingdom 
Sanofi 
Tel: +44 (0) 845 372 7101 
 

 
This leaflet was last revised in {date} 
 
 
Other source of information 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu/ 
 
 
 
 

HYPERGLYCAEMIA AND HYPOGLYCAEMIA 
 

Always carry some sugar (at least 20 grams) with you. 
Carry some information with you to show you are diabetic. 

 
HYPERGLYCAEMIA (high blood sugar levels) 

 
If your blood sugar is too high (hyperglycaemia), you may not have injected enough insulin. 
 
Why does hyperglycaemia occur? 
 
Examples include: 
- you have not injected your insulin or not injected enough, or if it has become less effective, for 

example through incorrect storage, 
- your insulin pen does not work properly, 

 

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- you are doing less exercise than usual, you are under stress (emotional distress, excitement), or 
you have an injury, operation, infection or fever, 

- you are taking or have taken certain other medicines (see section 2, "Other medicines and 
Insulin Human Winthrop Basal"). 

 
Warning symptoms of hyperglycaemia 
 
Thirst, increased need to urinate, tiredness, dry skin, reddening of the face, loss of appetite, low blood 
pressure, fast heart beat, and glucose and ketone bodies in urine. Stomach pain, fast and deep 
breathing, sleepiness or even loss of consciousness may be signs of a serious condition (ketoacidosis) 
resulting from lack of insulin. 
 
What should you do if you experience hyperglycaemia 
 
Test your blood sugar level and your urine for ketones as soon as any of the above symptoms 
occur. Severe hyperglycaemia or ketoacidosis must always be treated by a doctor, normally in a 
hospital. 
 

HYPOGLYCAEMIA (low blood sugar levels) 
 
If your blood sugar level falls too much you may become unconscious. Serious hypoglycaemia may 
cause a heart attack or brain damage and may be life-threatening. You normally should be able to 
recognise when your blood sugar is falling too much so that you can take the right actions. 
 
Why does hypoglycaemia occur? 
 
Examples include: 
- you inject too much insulin, 
- you miss meals or delay them, 
- you do not eat enough, or eat food containing less carbohydrate than normal (sugar and 

substances similar to sugar are called carbohydrates; however, artificial sweeteners are NOT 
carbohydrates), 

- you lose carbohydrates due to vomiting or diarrhoea, 
- you drink alcohol, particularly if you are not eating much, 
- you are doing more exercise than usual or a different type of physical activity, 
- you are recovering from an injury or operation or other stress, 
- you are recovering from an illness or from fever, 
- you are taking or have stopped taking certain other medicines (see section 2, "Other medicines 

and Insulin Human Winthrop Basal"). 
 
Hypoglycaemia is also more likely to occur if: 
- you have just begun insulin treatment or changed to another insulin preparation, 
- your blood sugar levels are almost normal or are unstable, 
- you change the area of skin where you inject insulin (for example from the thigh to the upper 

arm), 
- you suffer from severe kidney or liver disease, or some other disease such as hypothyroidism. 
 
Warning symptoms of hypoglycaemia 
 
- In your body 
Examples of symptoms that tell you that your blood sugar level is falling too much or too fast: 
sweating, clammy skin, anxiety, fast heart beat, high blood pressure, palpitations and irregular 
heartbeat. These symptoms often develop before the symptoms of a low sugar level in the brain. 
 
- In your brain 
Examples of symptoms that indicate a low sugar level in the brain: headaches, intense hunger, nausea, 
vomiting, tiredness, sleepiness, sleep disturbances, restlessness, aggressive behaviour, lapses in 

 

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concentration, impaired reactions, depression, confusion, speech disturbances (sometimes total loss of 
speech), visual disorders, trembling, paralysis, tingling sensations (paraesthesia), numbness and 
tingling sensations in the area of the mouth, dizziness, loss of self-control, inability to look after 
yourself, convulsions, loss of consciousness. 
 
The first symptoms which alert you to hypoglycaemia ("warning symptoms") may change, be weaker 
or may be missing altogether if 
- you are elderly, if you have had diabetes for a long time or if you suffer from a certain type of 

nervous disease (diabetic autonomic neuropathy), 
- you have recently suffered hypoglycaemia (for example the day before) or if it develops slowly, 
- you have almost normal or, at least, greatly improved blood sugar levels, 
- you have recently changed from an animal insulin to a human insulin such as Insulin Human 

Winthrop, 
- you are taking or have taken certain other medicines (see section 2, "Other medicines and 
Insulin Human Winthrop Basal"). 
 
In such a case, you may develop severe hypoglycaemia (and even faint) before you are aware of the 
problem. Be familiar with your warning symptoms. If necessary, more frequent blood sugar testing 
can help to identify mild hypoglycaemic episodes that may otherwise be overlooked. If you are not 
confident about recognising your warning symptoms, avoid situations (such as driving a car) in which 
you or others would be put at risk by hypoglycaemia. 
 
What should you do if you experience hypoglycaemia 
 
1. Do not inject insulin. Immediately take about 10 to 20 g sugar, such as glucose, sugar cubes or a 

sugar-sweetened beverage. Caution: Artificial sweeteners and foods with artificial sweeteners 
(such as diet drinks) are of no help in treating hypoglycaemia. 

2. Then eat something that has a long-acting effect in raising your blood sugar (such as bread or 
pasta). Your doctor or nurse should have discussed this with you previously. 

3. If the hypoglycaemia comes back again take another 10 to 20 g sugar. 
4. Speak to a doctor immediately if you are not able to control the hypoglycaemia or if it recurs. 
 
Tell your relatives, friends and close colleagues the following: 
If you are not able to swallow or if you are unconscious, you will require an injection of glucose or 
glucagon (a medicine which increases blood sugar). These injections are justified even if it is not 
certain that you have hypoglycaemia. 
 
It is advisable to test your blood sugar immediately after taking glucose to check that you really have 
hypoglycaemia. 
 
 

 

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Insulin Human Winthrop Basal SoloStar suspension for injection in a pre-filled pen. 
Instructions for Use. 
 
SoloStar is a prefilled pen for the injection of insulin. Your doctor has decided that SoloStar is 
appropriate for you based on your ability to handle SoloStar. Talk with your doctor, pharmacist or 
nurse about proper injection technique before using SoloStar. 
 
Read these instructions carefully before using your SoloStar. If you are not able to use SoloStar or 
follow all the instructions completely on your own, you must use SoloStar only if you have help from 
a person who is able to follow the instructions completely. Hold the pen as shown in this leaflet. To 
ensure that you read the dose correctly, hold the pen horizontally, with the needle on the left and the 
dosage selector to the right as shown in the illustrations below. 
 
Follow these instructions completely each time you use SoloStar to ensure that you get an 
accurate dose. If you do not follow these instructions completely, you may get too much or too 
little insulin, which may affect your blood glucose. 
 
You can set doses from 1 to 80 units in steps of 1 unit. Each pen contains multiple doses. 
 
Keep this leaflet for future reference. 
 
If you have any questions about SoloStar or about diabetes, ask your doctor, pharmacist or nurse or 
call the local sanofi-aventis number on the front of this leaflet. 
 

 
Schematic diagram of the pen 

 
 
Important information for use of SoloStar: 
 
• Always attach a new needle before each use. Only use needles that have been approved for use 

with SoloStar. 
• Do not select a dose and/or press the injection button without a needle attached. 
• Always perform the safety test before each injection (see Step 3). 
• This pen is only for your use. Do not share it with anyone else.  
• If your injection is given by another person, special caution must be taken by this person to avoid 

accidental needle injury and transmission of infection. 
• Never use SoloStar if it is damaged or if you are not sure that it is working properly. 
• Always have a spare SoloStar in case your SoloStar is lost or damaged. 
 
 
Step 1. Check the insulin 
 
A. Check the label on your SoloStar to make sure you have the correct insulin. Insulin Human 

Winthrop SoloStar is white with a colour on the injection button. The injection button colour 
will vary based on the formulation of Insulin Human Winthrop insulin used. The pictures below 
are for illustrative purposes only. 

 
B. Take off the pen cap. 
 
C. Check the appearance of your insulin.  

 

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If you are using a suspension insulin (Insulin Human Winthrop Basal or Insulin Human 
Winthrop mixtures), turn the pen up and down at least 10 times to resuspend the insulin. Turn 
the pen gently to avoid foaming in the cartridge.  

 

   
 

After mixing check the appearance of your insulin. Insulin suspensions must have an 
evenly milky-white appearance.  

 
 
Step 2. Attach the needle 
 
Always use a new sterile needle for each injection. This helps prevent contamination, and potential 
needle blocks. 
 
Before use of needle, carefully read the “Instructions for Use” accompanying the needles.  
 
Please note: The needles shown are for illustrative purposes only. 

 
A. Remove the protective seal from a new needle.  
 
B. Line up the needle with the pen, and keep it straight as you attach it (screw or push on, 

depending on the needle type). 
 

 . 
 

• If the needle is not kept straight while you attach it, it can damage the rubber seal and cause 
leakage, or break the needle. 

 

   
 
 
Step 3. Perform a safety test  
 
Always perform the safety test before each injection. This ensures that you get an accurate dose by: 
• ensuring that pen and needle work properly 
• removing air bubbles 
 
A. Select a dose of 2 units by turning the dosage selector. 

 

 

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B. Take off the outer needle cap and keep it to remove the used needle after injection. Take off the 

inner needle cap and discard it.  
 

   
 
C. Hold the pen with the needle pointing upwards. 
 
D. Tap the insulin reservoir so that any air bubbles rise up towards the needle. 
 
E. Press the injection button all the way in. Check if insulin comes out of the needle tip. 

   
 
You may have to perform the safety test several times before insulin is seen.  
 
• If no insulin comes out, check for air bubbles and repeat the safety test two more times to 

remove them. 
• If still no insulin comes out, the needle may be blocked. Change the needle and try again. 
• If no insulin comes out after changing the needle, your SoloStar may be damaged. Do not use 

this SoloStar. 
 
Step 4. Select the dose 
 
You can set the dose in steps of 1 unit, from a minimum of 1 unit to a maximum of 80 units. If you 
need a dose greater than 80 units, you should give it as two or more injections. 
 
A. Check that the dose window shows “0” following the safety test. 
 
B. Select your required dose (in the example below, the selected dose is 30 units). If you turn past 

your dose, you can turn back down. 
 

  
 
 

 

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• Do not push the injection button while turning, as insulin will come out. 
 
• You cannot turn the dosage selector past the number of units left in the pen. Do not force the 

dosage selector to turn. In this case, either you can inject what is remaining in the pen and 
complete your dose with a new SoloStar or use a new SoloStar for your full dose. 

 
 
Step 5. Inject the dose 
 
A. Use the injection method as instructed by your doctor, pharmacist or nurse.  
 
B. Insert the needle into the skin. 
 

   
 
C. Deliver the dose by pressing the injection button in all the way. The number in the dose window 

will return to “0” as you inject.  

   
 

D. Keep the injection button pressed all the way in. Slowly count to 10 before you withdraw the 
needle from the skin. This ensures that the full dose will be delivered. 
 
The pen plunger moves with each dose. The plunger will reach the end of the cartridge when 
the total of 300 units of insulin have been used. 

 
 
Step 6. Remove and discard the needle 
 
Always remove the needle after each injection and store SoloStar without a needle attached.  
This helps prevent: 
• Contamination and/or infection  
• Entry of air into the insulin reservoir and leakage of insulin, which can cause inaccurate dosing. 
 
A. Put the outer needle cap back on the needle, and use it to unscrew the needle from the pen. To 

reduce the risk of accidental needle injury, never replace the inner needle cap.  
 

• If your injection is given by another person, or if you are giving an injection to another person, 
special caution must be taken by this person when removing and disposing of the needle. Follow 
recommended safety measures for removal and disposal of needles (e.g. contact your doctor, 
pharmacist or nurse) in order to reduce the risk of accidental needle injury and transmission of 
infectious diseases. 

 
B. Dispose of the needle safely.  
 
C. Always put the pen cap back on the pen, then store the pen until your next injection. 
 
 

 

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Storage instructions  
 
Please check the reverse (insulin) side of this leaflet for instructions on how to store SoloStar. 
 
If your SoloStar is in cool storage, take it out 1 to 2 hours before you inject to allow it to warm up. 
Cold insulin is more painful to inject. 
 
Discard your used SoloStar as required by your local authorities. 
 
 
Maintenance 
 
Protect your SoloStar from dust and dirt. 
 
You can clean the outside of your SoloStar by wiping it with a damp cloth.  
 
Do not soak, wash or lubricate the pen as this may damage it.  
 
Your SoloStar is designed to work accurately and safely. It should be handled with care. Avoid 
situations where SoloStar might be damaged. If you are concerned that your SoloStar may be 
damaged, use a new one. 
 
 

 

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Package leaflet: Information for the user 

 
Insulin Human Winthrop Comb 15 100 IU/ml suspension for injection in a vial 

Insulin human 
 
 
Read all of this leaflet carefully before you start using this medicine because it contains 
important information for you. 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor, pharmacist or nurse. 
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours. 
- If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible 

side effects not listed in this leaflet. 
 
What is in this leaflet: 
1. What Insulin Human Winthrop Comb 15 is and what it is used for 
2. What you need to know before you use Insulin Human Winthrop Comb 15 
3. How to use Insulin Human Winthrop Comb 15 
4. Possible side effects 
5. How to store Insulin Human Winthrop Comb 15 
6. Contents of the pack and other information 
 
 
1. What Insulin Human Winthrop Comb 15 is and what it is used for 
 
Insulin Human Winthrop Comb 15 contains the active substance insulin human which is made by a 
biotechnology process and is identical with the body's own insulin. 
 
Insulin Human Winthrop Comb 15 is an insulin preparation with a gradual onset and long duration of 
action. 
 
Insulin Human Winthrop Comb 15 is used to reduce high blood sugar in patients with diabetes 
mellitus who need treatment with insulin. Diabetes mellitus is a disease where your body does not 
produce enough insulin to control the level of blood sugar. 
 
 
2. What you need to know before you use Insulin Human Winthrop Comb 15 
 
Do not use Insulin Human Winthrop Comb 15 
 
If you are allergic to insulin or any of the other ingredients of this medicine (listed in section 6).  
 
Warnings and precautions 
 
Talk to you doctor, pharmacist or nurse before using Insulin Human Winthrop Comb 15. 
Follow closely the instructions for dosage, monitoring (blood and urine tests), diet and physical 
activity (physical work and exercise) as discussed with your doctor. 
 
If you are allergic to this medicine or to animal insulins, talk to your doctor. 
 
Special patient groups 
If you have liver or kidneys problems or if you are elderly, speak to your doctor as you may need a 
lower dose. 
 

 

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Travel 
Before travelling, consult your doctor. You may need to talk about 
- the availability of your insulin in the country you are visiting, 
- supplies of insulin, injection syringes etc., 
- correct storage of your insulin while travelling, 
- timing of meals and insulin administration while travelling, 
- the possible effects of changing to different time zones, 
- possible new health risks in the countries to be visited, 
- what you should do in emergency situations when you feel unwell or become ill. 
 
Illnesses and injuries 
In the following situations, the management of your diabetes may require a lot of care: 
- If you are ill or have a major injury then your blood sugar level may increase (hyperglycaemia).  
- If you are not eating enough, your blood sugar level may become too low (hypoglycaemia).  
In most cases you will need a doctor. Make sure that you contact a doctor early.  
 
If you have type 1 diabetes (insulin dependent diabetes mellitus), do not stop your insulin and 
continue to get enough carbohydrates. Always tell people who are caring for you or treating you that 
you require insulin. 
 
Some patients with long-standing type 2 diabetes mellitus and heart disease or previous stroke who 
were treated with pioglitazone and insulin experienced the development of heart failure. Inform your 
doctor as soon as possible if you experience signs of heart failure such as unusual shortness of breath 
or rapid increase in weight or localised swelling (oedema). 
 
Other medicines and Insulin Human Winthrop Comb 15 
 
Some medicines cause changes in the blood sugar level (decrease, increase or both depending on the 
situation). In each case, it may be necessary to adjust your insulin dosage to avoid blood sugar levels 
that are either too low or too high. Be careful when you start or stop taking another medicine. 
 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines. Before taking a medicine ask your doctor if it can affect your blood sugar level, and what 
action, if any, you need to take. 
 
Medicines that may cause your blood sugar level to fall (hypoglycaemia) include:  
- all other medicines to treat diabetes,  
- angiotensin converting enzyme (ACE) inhibitors (used to treat certain heart conditions or high 

blood pressure),  
- disopyramide (used to treat certain heart conditions),  
- fluoxetine (used to treat depression),  
- fibrates (used to lower high levels of blood lipids),  
- monoamine oxidase (MAO) inhibitors (used to treat depression),  
- pentoxifylline, propoxyphene, salicylates (such as aspirin, used to relieve pain and lower fever), 
- sulfonamide antibiotics. 
 
Medicines that may cause your blood sugar level to rise (hyperglycaemia) include:  
- corticosteroids (such as "cortisone", used to treat inflammation),  
- danazol (medicine acting on ovulation),  
- diazoxide (used to treat high blood pressure),  
- diuretics (used to treat high blood pressure or excessive fluid retention),  
- glucagon (pancreas hormone used to treat severe hypoglycaemia),  
- isoniazid (used to treat tuberculosis),  
- oestrogens and progestogens (such as in the contraceptive pill used for birth control),  
- phenothiazine derivatives (used to treat psychiatric disorders),  
- somatropin (growth hormone),  

 

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- sympathomimetic medicines (such as epinephrine [adrenaline] or salbutamol, terbutaline used to 
treat asthma), 

- thyroid hormones (used to treat the thyroid gland disorders), 
- protease inhibitors (used to treat HIV), 
- atypical antipsychotic medicines (such as olanzapine and clozapine). 
 
Your blood sugar level may either rise or fall if you take:  
- beta-blockers (used to treat high blood pressure),  
- clonidine (used to treat high blood pressure), 
- lithium salts (used to treat psychiatric disorders).  
Pentamidine (used to treat some infections caused by parasites) may cause hypoglycaemia which may 
sometimes be followed by hyperglycaemia. 
 
Beta-blockers like other sympatholytic medicines (such as clonidine, guanethidine, and reserpine) may 
weaken or suppress entirely the first warning symptoms which help you to recognise a 
hypoglycaemia. 
 
If you are not sure whether you are taking one of those medicines ask your doctor or pharmacist. 
 
Insulin Human Winthrop Comb 15 with alcohol 
 
Your blood sugar levels may either rise or fall if you drink alcohol. 
 
Pregnancy and breast-feeding 
 
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor or pharmacist for advice before taking this medicine. 
 
Inform your doctor if you are planning to become pregnant, or if you are already pregnant. Your 
insulin dosage may need to be changed during pregnancy and after giving birth. Particularly careful 
control of your diabetes, and prevention of hypoglycaemia, is important for the health of your baby.  
 
If you are breast-feeding consult your doctor as you may require adjustments in your insulin doses and 
your diet. 
 
Driving and using machines 
 
Your ability to concentrate or react may be reduced if: 
- you have hypoglycaemia (low blood sugar levels), 
- you have hyperglycaemia (high blood sugar levels), 
- you have problems with your sight.  
Keep this possible problem in mind in all situations where you might put yourself and others at risk 
(such as driving a car or using machines). You should contact your doctor for advice on driving if: 
- you have frequent episodes of hypoglycaemia, 
- the first warning symptoms which help you to recognise hypoglycaemia are reduced or absent. 
 
Important information about some of the ingredients of Insulin Human Winthrop Comb 15 
 
This medicine contains less than 1 mmol (23 mg) sodium per dose, i.e. it is essentially ‘sodium-free’. 
 
 

 

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3. How to use Insulin Human Winthrop Comb 15 
 
Dose 
 
Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor 
or pharmacist if you are not sure. 
 
Based on your life-style and the results of your blood sugar (glucose) tests, your doctor will 
- determine how much Insulin Human Winthrop Comb 15 per day you will need, 
- tell you when to check your blood sugar level, and whether you need to carry out urine tests, 
- tell you when you may need to inject a higher or lower dose of Insulin Human Winthrop 

Comb 15. 
 
Many factors may influence your blood sugar level. You should know these factors so that you are 
able to react correctly to changes in your blood sugar level and to prevent it from becoming too high 
or too low. See the box at the end of this leaflet for further information. 
 
Frequency of administration 
 
Insulin Human Winthrop Comb 15 is injected under the skin 30 to 45 minutes before a meal.  
 
Method of administration 
 
Insulin Human Winthrop Comb 15 is a fluid (suspension) for injection under the skin. 
 
Do NOT inject Insulin Human Winthrop Comb 15 into a vein (blood vessel). 
 
Your doctor will show you in which area of the skin you should inject your insulin. With each 
injection, change the puncture site within the particular area of skin that you are using. 
 
Do not use it in insulin pumps or other infusion pumps - special insulin preparations are available for 
use in such devices. 
 
How to handle the vials 
 
Insulin Human Winthrop Comb 15 contains 100 IU insulin per ml. Only injection syringes designed 
for this insulin concentration (100 IU per ml) must be used. The injection syringes must not contain 
any other medicines or traces of medicines (such as traces of heparin). 
 
Before the first withdrawal of insulin you must remove the safety tear-off cap on the vial. 
 
Mix the insulin well immediately before each injection. This is best done by rolling the vial tilted 
between the palms of the hands. Do not shake the vial vigorously as this could damage the insulin and 
cause froth to form. Froth can make it difficult for you to measure the correct dose. 
 
After mixing, the suspension must have a uniform milky-white appearance. It must not be used if it 
remains clear or if, for example, clumps, flakes, particles or anything similar are in the suspension or 
on the sides or bottom of the vial. A new vial with a uniform suspension on mixing must then be used. 
 
Always use a new vial if you notice that your blood sugar control is unexpectedly getting worse. This 
is because the insulin may have lost some of its effectiveness. If you think you may have a problem 
with your insulin, have it checked by your doctor or pharmacist. 
 

 

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Special care before injection 
 
Before injection remove any air bubbles. Make sure that neither alcohol nor other disinfectants or 
other substances contaminate the insulin. Do not mix insulin with any other medicines except with 
insulin human preparations as detailed below. 
 
Insulin Human Winthrop Comb 15 may be mixed with all insulin human preparations, EXCEPT those 
specially designed for use in insulin pumps. Also, it must NOT be mixed with animal source insulins 
or insulin analogues. 
 
Your doctor will tell you if you have to mix insulin human preparations. If you need to inject a 
mixture, draw the other insulin into the injection syringe before Insulin Human Winthrop Comb 15. 
Inject as soon as you have mixed them. Do not mix insulins of different strengths (for example 100 IU 
per ml and 40 IU per ml). 
 
If you use more Insulin Human Winthrop Comb 15 than you should 
- If you have injected too much Insulin Human Winthrop Comb 15, your blood sugar level 

may become too low (hypoglycaemia). Check your blood sugar frequently. In general, to 
prevent hypoglycaemia you must eat more food and monitor your blood sugar. For information 
on the treatment of hypoglycaemia, see box at the end of this leaflet. 

 
If you forget to use Insulin Human Winthrop Comb 15 
- If you have missed a dose of Insulin Human Winthrop Comb 15 or if you have not injected 

enough insulin, your blood sugar level may become too high (hyperglycaemia). Check your 
blood sugar frequently. For information on the treatment of hyperglycaemia, see box at the end of 
this leaflet. 

 
- Do not take a double dose to make up for a forgotten dose. 
 
If you stop using Insulin Human Winthrop Comb 15 
This could lead to severe hyperglycaemia (very high blood sugar) and ketoacidosis (build-up of acid 
in the blood because the body is breaking down fat instead of sugar). Do not stop Insulin Human 
Winthrop Comb 15 without speaking to a doctor, who will tell you what needs to be done. 
 
If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse. 
 
Insulin Mix-ups 
 
You must always check the insulin label before each injection to avoid mix-ups between Insulin 
Human Winthrop Comb 15 and other insulins.  
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
The most frequent side effect is hypoglycaemia (low blood sugar). The specific frequency cannot be 
estimated from available data (frequency not known). Serious hypoglycaemia may cause a heart attack 
or brain damage and may be life-threatening. For further information on the side effects of low blood 
sugar or high blood sugar, see the box at the end of this leaflet. 
 
Severe allergic reactions to insulin may occur which may become life-threatening. Such reactions to 
insulin or to the excipients can cause large-scale skin reactions (rash and itching all over the body); 
severe swelling of skin or mucous membranes (angiooedema), shortness of breath, a fall in blood 
pressure with rapid heart beat and sweating.Frequency of these reactions cannot be estimated from 
available data. 
 

 

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Side effects reported commonly (may affect up to 1 in 10 people) 
• Oedema 
Insulin treatment may cause temporary build-up of water in the body with swelling in the calves and 
ankles. 
• Injection site reactions 
 
Side effects reported uncommonly (may affect up to 1 in 100 people) 
• Severe allergic reaction with low blood pressure (shock) 
• Injection site urticaria (itchy rash) 
 
Other side effects include (frequency cannot be estimated from the available data) 
• Sodium retention 
• Eye reactions 
A marked change (improvement or worsening) in your blood sugar control can disturb your vision 
temporarily. If you have proliferative retinopathy (an eye disease related to diabetes) severe 
hypoglycaemic attacks may cause temporary loss of vision.  
• Skin changes at the injection site (lipodystrophy) 
If you inject your insulin too often at the same skin site, fatty tissue under the skin at this site may 
either shrink or thicken. Insulin that you inject in such a site may not work very well. Changing the 
injection site with each injection may help to prevent such skin changes. 
• Skin and allergic reactions 
Other mild reactions at the injection site (such as injection site redness, unusually intense pain on 
injection site, itching, injection site swelling or injection site inflammation) may occur. They can also 
spread around the injection site. Most minor reactions to insulins usually resolve in a few days to a 
few weeks. 
 
Insulin treatment can cause the body to produce antibodies to insulin (substances that act against 
insulin). However, only very rarely, this will require a change to your insulin dosage. 
 
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side 
effects not listed in this leaflet. 
 
 
5. How to store Insulin Human Winthrop Comb 15 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date which is stated on the carton after “EXP” and on the 
label of the vial after “EXP”. The expiry date refers to the last day of that month. 
 
Unopened vials 
Store in a refrigerator (2°C - 8°C). Do not freeze. Do not put Insulin Human Winthrop Comb 15 next 
to the freezer compartment or a freezer pack. Keep the vial in the outer carton in order to protect from 
light. 
 
Opened vials 
Once in-use, the vial may be stored for a maximum of 4 weeks in the outer carton not above 25°C and 
away from direct heat (for example next to a heating unit) or direct light (direct sunlight or next to a 
lamp). Do not use the vial after this time period. It is recommended that the date of the first use be 
noted on the label. 
 
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment. 
 
 

 

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6. Contents of the pack and other information 
 
What Insulin Human Winthrop Comb 15 contains 
- The active substance is insulin human. One ml of Insulin Human Winthrop Comb 15 contains 

100 IU (International Units) of the active substance insulin human. 15% of the insulin is 
dissolved in water; the other 85% is present as tiny crystals of insulin protamine. 

- The other ingredients are: protamine sulphate, metacresol, phenol, zinc chloride, sodium 
dihydrogen phosphate dihydrate, glycerol, sodium hydroxide (see section 2 under “Important 
information about some of the ingredients of Insulin Human Winthrop Comb 15”), hydrochloric 
acid (for pH adjustment) and water for injections. 

 
What Insulin Human Winthrop Comb 15 looks like and contents of the pack 
After mixing, Insulin Human Winthrop Comb 15 is a uniformly milky fluid (suspension for injection), 
with no clumps, particles or flocculation visible. 
 
Insulin Human Winthrop Comb 15 is supplied in vials containing 5 ml suspension (500 IU). Packs of 
1 and 5 vials of 5 ml are available. Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder and Manufacturer 
Sanofi-Aventis Deutschland GmbH 
D-65926 Frankfurt am Main 
Germany 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
Sanofi Belgium 
Tél/Tel: +32 (0)2 710 54 00 
 

Lietuva 
UAB «SANOFI-AVENTIS LIETUVA» 
Tel: +370 5 2755224 
 

България 
sanofi-aventis Bulgaria EOOD 
Тел.: +359 (0)2 970 53 00 
 

Luxembourg/Luxemburg 
Sanofi Belgium  
Tél/Tel: +32 (0)2 710 54 00 (Belgique/Belgien) 
 

Česká republika 
sanofi-aventis, s.r.o. 
Tel: +420 233 086 111 
 

Magyarország 
SANOFI-AVENTIS Zrt. 
Tel.: +36 1 505 0050 
 

Danmark 
sanofi-aventis Denmark A/S 
Tlf: +45 45 16 70 00 
 

Malta 
Sanofi Malta Ltd. 
Tel: +356 21493022 
 

Deutschland 
Zentiva Pharma GmbH 
Tel: +49 (0)180 20 200 10 
 

Nederland 
sanofi-aventis Netherlands B.V. 
Tel: +31 (0)182 557 755 
 

Eesti 
sanofi-aventis Estonia OÜ 
Tel: +372 627 34 88 
 

Norge 
Aventis Pharma Norge AS 
Tlf: +47 67 10 71 00 
 

Ελλάδα 
sanofi-aventis AEBE 
Τηλ: +30 210 900 16 00 
 

Österreich 
sanofi-aventis GmbH 
Tel: +43 1 80 185 – 0 
 

 

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España 
sanofi-aventis, S.A. 
Tel: +34 93 485 94 00 
 

Polska 
sanofi-aventis Sp. z o.o. 
Tel.: +48 22 280 00 00 
 

France 
sanofi-aventis France 
Tél: 0 800 222 555 
Appel depuis l’étranger : +33 1 57 63 23 23 
 

Portugal 
Sanofi - Produtos Farmacêuticos, Lda. 
Tel: +351 21 35 89 400 
 

Hrvatska 
sanofi-aventis Croatia d.o.o. 
Tel: +385 1 600 34 00 

România 
Sanofi Romania SRL 
Tel: +40 (0) 21 317 31 36 
 

Ireland 
sanofi-aventis Ireland Ltd. T/A SANOFI 
Tel: +353 (0) 1 403 56 00 
 

Slovenija 
sanofi-aventis d.o.o. 
Tel: +386 1 560 48 00 
 

Ísland 
Vistor hf. 
Sími: +354 535 7000 
 

Slovenská republika 
sanofi-aventis Pharma Slovakia s.r.o. 
Tel: +421 2 33 100 100 
 

Italia 
Sanofi S.p.A. 
Tel: 800 13 12 12 (domande di tipo tecnico)  
800 536389 (altre domande) 
 

Suomi/Finland 
Sanofi Oy 
Puh/Tel: +358 (0) 201 200 300 
 

Κύπρος 
sanofi-aventis Cyprus Ltd. 
Τηλ: +357 22 871600 
 

Sverige 
Sanofi AB 
Tel: +46 (0)8 634 50 00 
 

Latvija 
sanofi-aventis Latvia SIA 
Tel: +371 67 33 24 51 
 

United Kingdom 
Sanofi 
Tel: +44 (0) 845 372 7101 
 

 
This leaflet was last revised in {date} 
 
 
Other source of information 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu/ 
 
 
 
 

HYPERGLYCAEMIA AND HYPOGLYCAEMIA 
 

Always carry some sugar (at least 20 grams) with you. 
Carry some information with you to show you are diabetic. 

 
HYPERGLYCAEMIA (high blood sugar levels) 

 
If your blood sugar is too high (hyperglycaemia), you may not have injected enough insulin. 
 
Why does hyperglycaemia occur? 
 
Examples include: 

 

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- you have not injected your insulin or not injected enough, or if it has become less effective, for 
example through incorrect storage, 

- you are doing less exercise than usual, you are under stress (emotional distress, excitement), or 
you have an injury, operation, infection or fever, 

- you are taking or have taken certain other medicines (see section 2, "Other medicines and 
Insulin Human Winthrop Comb 15"). 

 
Warning symptoms of hyperglycaemia 
 
Thirst, increased need to urinate, tiredness, dry skin, reddening of the face, loss of appetite, low blood 
pressure, fast heart beat, and glucose and ketone bodies in urine. Stomach pain, fast and deep 
breathing, sleepiness or even loss of consciousness may be signs of a serious condition (ketoacidosis) 
resulting from lack of insulin. 
 
What should you do if you experience hyperglycaemia 
 
Test your blood sugar level and your urine for ketones as soon as any of the above symptoms 
occur. Severe hyperglycaemia or ketoacidosis must always be treated by a doctor, normally in a 
hospital. 
 

HYPOGLYCAEMIA (low blood sugar levels) 
 
If your blood sugar level falls too much you may become unconscious. Serious hypoglycaemia may 
cause a heart attack or brain damage and may be life-threatening. You normally should be able to 
recognise when your blood sugar is falling too much so that you can take the right actions. 
 
Why does hypoglycaemia occur? 
 
Examples include: 
- you inject too much insulin, 
- you miss meals or delay them, 
- you do not eat enough, or eat food containing less carbohydrate than normal (sugar and 

substances similar to sugar are called carbohydrates; however, artificial sweeteners are NOT 
carbohydrates), 

- you lose carbohydrates due to vomiting or diarrhoea, 
- you drink alcohol, particularly if you are not eating much, 
- you are doing more exercise than usual or a different type of physical activity, 
- you are recovering from an injury or operation or other stress, 
- you are recovering from an illness or from fever, 
- you are taking or have stopped taking certain other medicines (see section 2, "Other medicines 

and Insulin Human Winthrop Comb 15"). 
 
Hypoglycaemia is also more likely to occur if: 
- you have just begun insulin treatment or changed to another insulin preparation, 
- your blood sugar levels are almost normal or are unstable, 
- you change the area of skin where you inject insulin (for example from the thigh to the upper 

arm), 
- you suffer from severe kidney or liver disease, or some other disease such as hypothyroidism. 
 
Warning symptoms of hypoglycaemia 
 
- In your body 
Examples of symptoms that tell you that your blood sugar level is falling too much or too fast: 
sweating, clammy skin, anxiety, fast heart beat, high blood pressure, palpitations and irregular 
heartbeat. These symptoms often develop before the symptoms of a low sugar level in the brain. 
 
- In your brain 

 

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Examples of symptoms that indicate a low sugar level in the brain: headaches, intense hunger, nausea, 
vomiting, tiredness, sleepiness, sleep disturbances, restlessness, aggressive behaviour, lapses in 
concentration, impaired reactions, depression, confusion, speech disturbances (sometimes total loss of 
speech), visual disorders, trembling, paralysis, tingling sensations (paraesthesia), numbness and 
tingling sensations in the area of the mouth, dizziness, loss of self-control, inability to look after 
yourself, convulsions, loss of consciousness. 
 
The first symptoms which alert you to hypoglycaemia ("warning symptoms") may change, be weaker 
or may be missing altogether if 
- you are elderly, if you have had diabetes for a long time or if you suffer from a certain type of 

nervous disease (diabetic autonomic neuropathy), 
- you have recently suffered hypoglycaemia (for example the day before) or if it develops slowly, 
- you have almost normal or, at least, greatly improved blood sugar levels, 
- you have recently changed from an animal insulin to a human insulin such as Insulin Human 

Winthrop, 
- you are taking or have taken certain other medicines (see section 2, "Other medicines and 

Insulin Human Winthrop Comb 15"). 
 
In such a case, you may develop severe hypoglycaemia (and even faint) before you are aware of the 
problem. Be familiar with your warning symptoms. If necessary, more frequent blood sugar testing 
can help to identify mild hypoglycaemic episodes that may otherwise be overlooked. If you are not 
confident about recognising your warning symptoms, avoid situations (such as driving a car) in which 
you or others would be put at risk by hypoglycaemia. 
 
What should you do if you experience hypoglycaemia 
 
1. Do not inject insulin. Immediately take about 10 to 20 g sugar, such as glucose, sugar cubes or a 

sugar-sweetened beverage. Caution: Artificial sweeteners and foods with artificial sweeteners 
(such as diet drinks) are of no help in treating hypoglycaemia. 

2. Then eat something that has a long-acting effect in raising your blood sugar (such as bread or 
pasta). Your doctor or nurse should have discussed this with you previously. 

3. If the hypoglycaemia comes back again take another 10 to 20 g sugar. 
4. Speak to a doctor immediately if you are not able to control the hypoglycaemia or if it recurs. 
 
Tell your relatives, friends and close colleagues the following: 
If you are not able to swallow or if you are unconscious, you will require an injection of glucose or 
glucagon (a medicine which increases blood sugar). These injections are justified even if it is not 
certain that you have hypoglycaemia. 
 
It is advisable to test your blood sugar immediately after taking glucose to check that you really have 
hypoglycaemia. 
 
 

 

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Package leaflet: Information for the user 

 
Insulin Human Winthrop Comb 15 40 IU/ml suspension for injection in a vial 

Insulin human 
 
 
Read all of this leaflet carefully before you start using this medicine because it contains 
important information for you. 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor, pharmacist or nurse. 
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours. 
- If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible 

side effects not listed in this leaflet. 
 
What is in this leaflet: 
1. What Insulin Human Winthrop Comb 15 is and what it is used for 
2. What you need to know before you use Insulin Human Winthrop Comb 15 
3. How to use Insulin Human Winthrop Comb 15 
4. Possible side effects 
5. How to store Insulin Human Winthrop Comb 15 
6. Contents of the pack and other information 
 
 
1. What Insulin Human Winthrop Comb 15 is and what it is used for 
 
Insulin Human Winthrop Comb 15 contains the active substance insulin human which is made by a 
biotechnology process and is identical with the body's own insulin. 
 
Insulin Human Winthrop Comb 15 is an insulin preparation with a gradual onset and long duration of 
action.  
 
Insulin Human Winthrop Comb 15 is used to reduce high blood sugar in patients with diabetes 
mellitus who need treatment with insulin. Diabetes mellitus is a disease where your body does not 
produce enough insulin to control the level of blood sugar. 
 
 
2. What you need to know before you use Insulin Human Winthrop Comb 15 
 
Do not use Insulin Human Winthrop Comb 15 
 
If you are allergic to insulin or any of the other ingredients of this medicine (listed in section 6).  
 
Warnings and precautions 
 
Talk to your doctor, pharmacist or nurse before using Insulin Human Winthrop Comb 15. 
Follow closely the instructions for dosage, monitoring (blood and urine tests), diet and physical 
activity (physical work and exercise) as discussed with your doctor. 
 
If you are allergic to this medicine or to animal insulins, talk to your doctor. 
 
Special patient groups 
If you have liver or kidneys problems or if you are elderly, speak to your doctor as you may need a 
lower dose. 
 

 

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Travel 
Before travelling, consult your doctor. You may need to talk about 
- the availability of your insulin in the country you are visiting, 
- supplies of insulin, injection syringes etc., 
- correct storage of your insulin while travelling, 
- timing of meals and insulin administration while travelling, 
- the possible effects of changing to different time zones, 
- possible new health risks in the countries to be visited, 
- what you should do in emergency situations when you feel unwell or become ill. 
 
Illnesses and injuries 
In the following situations, the management of your diabetes may require a lot of care: 
- If you are ill or have a major injury then your blood sugar level may increase (hyperglycaemia).  
- If you are not eating enough, your blood sugar level may become too low (hypoglycaemia).  
In most cases you will need a doctor. Make sure that you contact a doctor early.  
 
If you have type 1 diabetes (insulin dependent diabetes mellitus), do not stop your insulin and 
continue to get enough carbohydrates. Always tell people who are caring for you or treating you that 
you require insulin. 
 
Some patients with long-standing type 2 diabetes mellitus and heart disease or previous stroke who 
were treated with pioglitazone and insulin experienced the development of heart failure. Inform your 
doctor as soon as possible if you experience signs of heart failure such as unusual shortness of breath 
or rapid increase in weight or localised swelling (oedema). 
 
Other medicines and Insulin Human Winthrop Comb 15 
 
Some medicines cause changes in the blood sugar level (decrease, increase or both depending on the 
situation). In each case, it may be necessary to adjust your insulin dosage to avoid blood sugar levels 
that are either too low or too high. Be careful when you start or stop taking another medicine. 
 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines. Before taking a medicine ask your doctor if it can affect your blood sugar level, and what 
action, if any, you need to take. 
 
Medicines that may cause your blood sugar level to fall (hypoglycaemia) include:  
- all other medicines to treat diabetes,  
- angiotensin converting enzyme (ACE) inhibitors (used to treat certain heart conditions or high 

blood pressure),  
- disopyramide (used to treat certain heart conditions),  
- fluoxetine (used to treat depression),  
- fibrates (used to lower high levels of blood lipids),  
- monoamine oxidase (MAO) inhibitors (used to treat depression),  
- pentoxifylline, propoxyphene, salicylates (such as aspirin, used to relieve pain and lower fever), 
- sulfonamide antibiotics. 
 
Medicines that may cause your blood sugar level to rise (hyperglycaemia) include:  
- corticosteroids (such as "cortisone", used to treat inflammation),  
- danazol (medicine acting on ovulation),  
- diazoxide (used to treat high blood pressure),  
- diuretics (used to treat high blood pressure or excessive fluid retention),  
- glucagon (pancreas hormone used to treat severe hypoglycaemia),  
- isoniazid (used to treat tuberculosis),  
- oestrogens and progestogens (such as in the contraceptive pill used for birth control),  
- phenothiazine derivatives (used to treat psychiatric disorders),  
- somatropin (growth hormone),  

 

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- sympathomimetic medicines (such as epinephrine [adrenaline] or salbutamol, terbutaline used to 
treat asthma), 

- thyroid hormones (used to treat the thyroid gland disorders), 
- protease inhibitors (used to treat HIV), 
- atypical antipsychotic medicines (such as olanzapine and clozapine). 
 
Your blood sugar level may either rise or fall if you take:  
- beta-blockers (used to treat high blood pressure),  
- clonidine (used to treat high blood pressure),  
- lithium salts (used to treat psychiatric disorders).  
Pentamidine (used to treat some infections caused by parasites) may cause hypoglycaemia which may 
sometimes be followed by hyperglycaemia. 
 
Beta-blockers like other sympatholytic medicines (such as clonidine, guanethidine, and reserpine) may 
weaken or suppress entirely the first warning symptoms which help you to recognise a 
hypoglycaemia. 
 
If you are not sure whether you are taking one of those medicines ask your doctor or pharmacist. 
 
Insulin Human Winthrop Comb 15 with alcohol 
 
Your blood sugar levels may either rise or fall if you drink alcohol. 
 
Pregnancy and breast-feeding 
 
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor or pharmacist for advice before taking this medicine. 
 
Inform your doctor if you are planning to become pregnant, or if you are already pregnant. Your 
insulin dosage may need to be changed during pregnancy and after giving birth. Particularly careful 
control of your diabetes, and prevention of hypoglycaemia, is important for the health of your baby.  
 
If you are breast-feeding consult your doctor as you may require adjustments in your insulin doses and 
your diet. 
 
Driving and using machines 
 
Your ability to concentrate or react may be reduced if: 
- you have hypoglycaemia (low blood sugar levels), 
- you have hyperglycaemia (high blood sugar levels), 
- you have problems with your sight.  
Keep this possible problem in mind in all situations where you might put yourself and others at risk 
(such as driving a car or using machines). You should contact your doctor for advice on driving if: 
- you have frequent episodes of hypoglycaemia, 
- the first warning symptoms which help you to recognise hypoglycaemia are reduced or absent. 
 
Important information about some of the ingredients of Insulin Human Winthrop Comb 15 
 
This medicine contains less than 1 mmol (23 mg) sodium per dose, i.e. it is essentially ‘sodium-free’. 
 
 

 

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3. How to use Insulin Human Winthrop Comb 15 
 
Dose 
 
Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor 
or pharmacist if you are not sure. 
 
Based on your life-style and the results of your blood sugar (glucose) tests, your doctor will 
- determine how much Insulin Human Winthrop Comb 15 per day you will need, 
- tell you when to check your blood sugar level, and whether you need to carry out urine tests, 
- tell you when you may need to inject a higher or lower dose of Insulin Human Winthrop 

Comb 15. 
 
Many factors may influence your blood sugar level. You should know these factors so that you are 
able to react correctly to changes in your blood sugar level and to prevent it from becoming too high 
or too low. See the box at the end of this leaflet for further information. 
 
Frequency of administration 
 
Insulin Human Winthrop Comb 15 is injected under the skin 30 to 45 minutes before a meal.  
 
Method of administration 
 
Insulin Human Winthrop Comb 15 is a fluid (suspension) for injection under the skin. 
 
Do NOT inject Insulin Human Winthrop Comb 15 into a vein (blood vessel). 
 
Your doctor will show you in which area of the skin you should inject your insulin. With each 
injection, change the puncture site within the particular area of skin that you are using. 
 
Do not use it in insulin pumps or other infusion pumps - special insulin preparations are available for 
use in such devices. 
 
How to handle the vials 
 
Insulin Human Winthrop Comb 15 contains 40 IU insulin per ml. Only injection syringes designed for 
this insulin concentration (40 IU per ml) must be used. The injection syringes must not contain any 
other medicines or traces of medicines (such as traces of heparin). 
 
Before the first withdrawal of insulin you must remove the safety tear-off capon the vial. 
 
Mix the insulin well immediately before each injection. This is best done by rolling the vial tilted 
between the palms of the hands. Do not shake the vial vigorously as this could damage the insulin and 
cause froth to form. Froth can make it difficult for you to measure the correct dose. 
 
After mixing, the suspension must have a uniform milky-white appearance. It must not be used if it 
remains clear or if, for example, clumps, flakes, particles or anything similar are in the suspension or 
on the sides or bottom of the vial. A new vial with a uniform suspension on mixing must then be used. 
 
Always use a new vial if you notice that your blood sugar control is unexpectedly getting worse. This 
is because the insulin may have lost some of its effectiveness. If you think you may have a problem 
with your insulin, have it checked by your doctor or pharmacist. 
 

 

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Special care before injection 
 
Before injection remove any air bubbles. Make sure that neither alcohol nor other disinfectants or 
other substances contaminate the insulin. Do not mix insulin with any other medicines except with 
insulin human preparations as detailed below. 
 
Insulin Human Winthrop Comb 15 may be mixed with all insulin human preparations, EXCEPT those 
specially designed for use in insulin pumps. Also, it must NOT be mixed with animal source insulins 
or insulin analogues. 
 
Your doctor will tell you if you have to mix insulin human preparations. If you need to inject a 
mixture, draw the other insulin into the injection syringe before Insulin Human Winthrop Comb 15. 
Inject as soon as you have mixed them. Do not mix insulins of different strengths (for example 100 IU 
per ml and 40 IU per ml). 
 
If you use more Insulin Human Winthrop Comb 15 than you should 
- If you have injected too much Insulin Human Winthrop Comb 15, your blood sugar level 

may become too low (hypoglycaemia). Check your blood sugar frequently. In general, to 
prevent hypoglycaemia you must eat more food and monitor your blood sugar. For information 
on the treatment of hypoglycaemia, see box at the end of this leaflet. 

 
If you forget to use Insulin Human Winthrop Comb 15 
- If you have missed a dose of Insulin Human Winthrop Comb 15 or if you have not injected 

enough insulin, your blood sugar level may become too high (hyperglycaemia). Check your 
blood sugar frequently. For information on the treatment of hyperglycaemia, see box at the end 
of this leaflet. 

 
- Do not take a double dose to make up for a forgotten dose. 
 
If you stop using Insulin Human Winthrop Comb 15 
This could lead to severe hyperglycaemia (very high blood sugar) and ketoacidosis (build-up of acid 
in the blood because the body is breaking down fat instead of sugar). Do not stop Insulin Human 
Winthrop Comb 15 without speaking to a doctor, who will tell you what needs to be done. 
 
If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse. 
 
Insulin Mix-ups 
 
You must always check the insulin label before each injection to avoid mix-ups between Insulin 
Human Winthrop Comb 15 and other insulins.  
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
The most frequent side effect is hypoglycaemia (low blood sugar). The specific frequency cannot be 
estimated from available data (frequency not known). Serious hypoglycaemia may cause a heart attack 
or brain damage and may be life-threatening. For further information on the side effects of low blood 
sugar or high blood sugar, see the box at the end of this leaflet. 
 
Severe allergic reactions to insulin may occur which may become life-threatening. Such reactions to 
insulin or to the excipients can cause large-scale skin reactions (rash and itching all over the body); 
severe swelling of skin or mucous membranes (angiooedema), shortness of breath, a fall in blood 
pressure with rapid heart beat and sweating. Frequency of these reactions cannot be estimated from 
available data. 
 

 

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Side effects reported commonly (may affect up to 1 in 10 people) 
• Oedema 
Insulin treatment may cause temporary build-up of water in the body with swelling in the calves and 
ankles. 
• Injection site reactions 
 
Side effects reported uncommonly (may affect up to 1 in 100 people) 
• Severe allergic reaction with low blood pressure (shock) 
• Injection site urticaria (itchy rash) 
 
Other side effects include (frequency cannot be estimated from the available data) 
• Sodium retention 
• Eye reactions 
A marked change (improvement or worsening) in your blood sugar control can disturb your vision 
temporarily. If you have proliferative retinopathy (an eye disease related to diabetes) severe 
hypoglycaemic attacks may cause temporary loss of vision.  
• Skin changes at the injection site (lipodystrophy) 
If you inject your insulin too often at the same skin site, fatty tissue under the skin at this site may 
either shrink or thicken. Insulin that you inject in such a site may not work very well. Changing the 
injection site with each injection may help to prevent such skin changes. 
• Skin and allergic reactions 
Other mild reactions at the injection site (such as injection site redness, unusually intense pain on 
injection site, itching, injection site swelling or injection site inflammation) may occur. They can also 
spread around the injection site. Most minor reactions to insulins usually resolve in a few days to a 
few weeks. 
 
Insulin treatment can cause the body to produce antibodies to insulin (substances that act against 
insulin). However, only very rarely, this will require a change to your insulin dosage. 
 
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side 
effects not listed in this leaflet. 
 
 
5. How to store Insulin Human Winthrop Comb 15 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date which is stated on the carton and on the label of the vial 
after “EXP”. The expiry date refers to the last day of that month. 
 
Unopened vials 
Store in a refrigerator (2°C - 8°C). Do not freeze. Do not put Insulin Human Winthrop Comb 15 next 
to the freezer compartment or a freezer pack. Keep the vial in the outer carton in order to protect from 
light. 
 
Opened vials 
Once in-use, the vial may be stored for a maximum of 4 weeks in the outer carton not above 25°C and 
away from direct heat (for example next to a heating unit) or direct light (direct sunlight or next to a 
lamp). Do not use the vial after this time period. It is recommended that the date of the first use be 
noted on the label. 
 
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment. 
 
 

 

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6. Contents of the pack and other information 
 
What Insulin Human Winthrop Comb 15 contains 
- The active substance is insulin human. One ml of Insulin Human Winthrop Comb 15 contains 

40 IU (International Units) of the active substance insulin human. 15% of the insulin is 
dissolved in water; the other 85% is present as tiny crystals of insulin protamine. 

- The other ingredients are: protamine sulphate, metacresol, phenol, zinc chloride, sodium 
dihydrogen phosphate dihydrate, glycerol, sodium hydroxide (see section 2 under “Important 
information about some of the ingredients of Insulin Human Winthrop Comb 15”), hydrochloric 
acid (for pH adjustment) and water for injections. 

 
What Insulin Human Winthrop Comb 15 looks like and contents of the pack 
After mixing, Insulin Human Winthrop Comb 15 is a uniformly milky fluid (suspension for injection), 
with no clumps, particles or flocculation visible. 
 
Insulin Human Winthrop Comb 15 is supplied in vials containing 10 ml suspension (400 IU). Packs of 
1 and 5 vials of 10 ml are available. Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder and Manufacturer 
Sanofi-Aventis Deutschland GmbH 
D-65926 Frankfurt am Main 
Germany 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
Sanofi Belgium 
Tél/Tel: +32 (0)2 710 54 00 
 

Lietuva 
UAB «SANOFI-AVENTIS LIETUVA» 
Tel: +370 5 2755224 
 

България 
sanofi-aventis Bulgaria EOOD 
Тел.: +359 (0)2 970 53 00 
 

Luxembourg/Luxemburg 
Sanofi Belgium  
Tél/Tel: +32 (0)2 710 54 00 (Belgique/Belgien) 
 

Česká republika 
sanofi-aventis, s.r.o. 
Tel: +420 233 086 111 
 

Magyarország 
SANOFI-AVENTIS Zrt. 
Tel.: +36 1 505 0050 
 

Danmark 
sanofi-aventis Denmark A/S 
Tlf: +45 45 16 70 00 
 

Malta 
Sanofi Malta Ltd. 
Tel: +356 21493022 
 

Deutschland 
Zentiva Pharma GmbH 
Tel: +49 (0)180 20 200 10 
 

Nederland 
sanofi-aventis Netherlands B.V. 
Tel: +31 (0)182 557 755 
 

Eesti 
sanofi-aventis Estonia OÜ 
Tel: +372 627 34 88 
 

Norge 
Aventis Pharma Norge AS 
Tlf: +47 67 10 71 00 
 

Ελλάδα 
sanofi-aventis AEBE 
Τηλ: +30 210 900 16 00 
 

Österreich 
sanofi-aventis GmbH 
Tel: +43 1 80 185 – 0 
 

 

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España 
sanofi-aventis, S.A. 
Tel: +34 93 485 94 00 
 

Polska 
sanofi-aventis Sp . z o.o. 
Tel.: +48 22 280 00 00 
 

France 
sanofi-aventis France 
Tél: 0 800 222 555 
Appel depuis l’étranger : +33 1 57 63 23 23 
 

Portugal 
Sanofi - Produtos Farmacêuticos, Lda. 
Tel: +351 21 35 89 400 
 

Hrvatska 
sanofi-aventis Croatia d.o.o. 
Tel: +385 1 600 34 00 

România 
Sanofi Romania SRL 
Tel: +40 (0) 21 317 31 36 
 

Ireland 
sanofi-aventis Ireland Ltd. T/A SANOFI 
Tel: +353 (0) 1 403 56 00 
 

Slovenija 
sanofi-aventis d.o.o. 
Tel: +386 1 560 48 00 
 

Ísland 
Vistor hf. 
Sími: +354 535 7000 
 

Slovenská republika 
sanofi-aventis Pharma Slovakia s.r.o. 
Tel: +421 2 33 100 100 
 

Italia 
Sanofi S.p.A. 
Tel: 800 13 12 12 (domande di tipo tecnico)  
800 536389 (altre domande) 
 

Suomi/Finland 
Sanofi Oy 
Puh/Tel: +358 (0) 201 200 300 
 

Κύπρος 
sanofi-aventis Cyprus Ltd. 
Τηλ: +357 22 871600 
 

Sverige 
Sanofi AB 
Tel: +46 (0)8 634 50 00 
 

Latvija 
sanofi-aventis Latvia SIA 
Tel: +371 67 33 24 51 
 

United Kingdom 
Sanofi 
Tel: +44 (0) 845 372 7101 
 

 
This leaflet was last revised in {date} 
 
 
Other source of information 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu/ 
 
 
 
 

HYPERGLYCAEMIA AND HYPOGLYCAEMIA 
 

Always carry some sugar (at least 20 grams) with you. 
Carry some information with you to show you are diabetic. 

 
HYPERGLYCAEMIA (high blood sugar levels) 

 
If your blood sugar is too high (hyperglycaemia), you may not have injected enough insulin. 
 
Why does hyperglycaemia occur? 
 
Examples include: 

 

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- you have not injected your insulin or not injected enough, or if it has become less effective, for 
example through incorrect storage, 

- you are doing less exercise than usual, you are under stress (emotional distress, excitement), or 
you have an injury, operation, infection or fever, 

- you are taking or have taken certain other medicines (see section 2, "Other medicines and 
Insulin Human Winthrop Comb 15"). 

 
Warning symptoms of hyperglycaemia 
 
Thirst, increased need to urinate, tiredness, dry skin, reddening of the face, loss of appetite, low blood 
pressure, fast heart beat, and glucose and ketone bodies in urine. Stomach pain, fast and deep 
breathing, sleepiness or even loss of consciousness may be signs of a serious condition (ketoacidosis) 
resulting from lack of insulin. 
 
What should you do if you experience hyperglycaemia 
 
Test your blood sugar level and your urine for ketones as soon as any of the above symptoms 
occur. Severe hyperglycaemia or ketoacidosis must always be treated by a doctor, normally in a 
hospital. 
 

HYPOGLYCAEMIA (low blood sugar levels) 
 
If your blood sugar level falls too much you may become unconscious. Serious hypoglycaemia may 
cause a heart attack or brain damage and may be life-threatening. You normally should be able to 
recognise when your blood sugar is falling too much so that you can take the right actions. 
 
Why does hypoglycaemia occur? 
 
Examples include: 
- you inject too much insulin, 
- you miss meals or delay them, 
- you do not eat enough, or eat food containing less carbohydrate than normal (sugar and 

substances similar to sugar are called carbohydrates; however, artificial sweeteners are NOT 
carbohydrates), 

- you lose carbohydrates due to vomiting or diarrhoea, 
- you drink alcohol, particularly if you are not eating much, 
- you are doing more exercise than usual or a different type of physical activity, 
- you are recovering from an injury or operation or other stress, 
- you are recovering from an illness or from fever, 
- you are taking or have stopped taking certain other medicines (see section 2, "Other medicines 

and Insulin Human Winthrop Comb 15"). 
 
Hypoglycaemia is also more likely to occur if: 
- you have just begun insulin treatment or changed to another insulin preparation, 
- your blood sugar levels are almost normal or are unstable, 
- you change the area of skin where you inject insulin (for example from the thigh to the upper 

arm), 
- you suffer from severe kidney or liver disease, or some other disease such as hypothyroidism. 
 
Warning symptoms of hypoglycaemia 
 
- In your body 
Examples of symptoms that tell you that your blood sugar level is falling too much or too fast: 
sweating, clammy skin, anxiety, fast heart beat, high blood pressure, palpitations and irregular 
heartbeat. These symptoms often develop before the symptoms of a low sugar level in the brain. 
 
- In your brain 

 

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Examples of symptoms that indicate a low sugar level in the brain: headaches, intense hunger, nausea, 
vomiting, tiredness, sleepiness, sleep disturbances, restlessness, aggressive behaviour, lapses in 
concentration, impaired reactions, depression, confusion, speech disturbances (sometimes total loss of 
speech), visual disorders, trembling, paralysis, tingling sensations (paraesthesia), numbness and 
tingling sensations in the area of the mouth, dizziness, loss of self-control, inability to look after 
yourself, convulsions, loss of consciousness. 
 
The first symptoms which alert you to hypoglycaemia ("warning symptoms") may change, be weaker 
or may be missing altogether if 
- you are elderly, if you have had diabetes for a long time or if you suffer from a certain type of 

nervous disease (diabetic autonomic neuropathy), 
- you have recently suffered hypoglycaemia (for example the day before) or if it develops slowly, 
- you have almost normal or, at least, greatly improved blood sugar levels, 
- you have recently changed from an animal insulin to a human insulin such as Insulin Human 

Winthrop, 
- you are taking or have taken certain other medicines (see section 2, "Other medicines and 

Insulin Human Winthrop Comb 15."). 
 
In such a case, you may develop severe hypoglycaemia (and even faint) before you are aware of the 
problem. Be familiar with your warning symptoms. If necessary, more frequent blood sugar testing 
can help to identify mild hypoglycaemic episodes that may otherwise be overlooked. If you are not 
confident about recognising your warning symptoms, avoid situations (such as driving a car) in which 
you or others would be put at risk by hypoglycaemia. 
 
What should you do if you experience hypoglycaemia 
 
1. Do not inject insulin. Immediately take about 10 to 20 g sugar, such as glucose, sugar cubes or a 

sugar-sweetened beverage. Caution: Artificial sweeteners and foods with artificial sweeteners 
(such as diet drinks) are of no help in treating hypoglycaemia. 

2. Then eat something that has a long-acting effect in raising your blood sugar (such as bread or 
pasta). Your doctor or nurse should have discussed this with you previously. 

3. If the hypoglycaemia comes back again take another 10 to 20 g sugar. 
4. Speak to a doctor immediately if you are not able to control the hypoglycaemia or if it recurs. 
 
Tell your relatives, friends and close colleagues the following: 
If you are not able to swallow or if you are unconscious, you will require an injection of glucose or 
glucagon (a medicine which increases blood sugar). These injections are justified even if it is not 
certain that you have hypoglycaemia. 
 
It is advisable to test your blood sugar immediately after taking glucose to check that you really have 
hypoglycaemia. 
 
 

 

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Package leaflet: Information for the user 

 
Insulin Human Winthrop Comb 15 100 IU/ml suspension for injection in a cartridge 

Insulin human 
 
 
Read all of this leaflet carefully before you start using this medicine because it contains 
important information for you. The instructions for using the insulin pen are provided with 
your insulin pen. Refer to them before using your medicine. 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor, pharmacist or nurse. 
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours. 
- If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible 

side effects not listed in this leaflet. 
 
What is in this leaflet: 
1. What Insulin Human Winthrop Comb 15 is and what it is used for 
2. What you need to know before you use Insulin Human Winthrop Comb 15 
3. How to use Insulin Human Winthrop Comb 15 
4. Possible side effects 
5. How to store Insulin Human Winthrop Comb 15 
6. Contents of the pack and other information 
 
 
1. What Insulin Human Winthrop Comb 15 is and what it is used for 
 
Insulin Human Winthrop Comb 15 contains the active substance insulin human which is made by a 
biotechnology process and is identical with the body's own insulin. 
 
Insulin Human Winthrop Comb 15 is an insulin preparation with a gradual onset and long duration of 
action.  
 
Insulin Human Winthrop Comb 15 is used to reduce high blood sugar in patients with diabetes 
mellitus who need treatment with insulin. Diabetes mellitus is a disease where your body does not 
produce enough insulin to control the level of blood sugar. 
 
 
2. What you need to know before you use Insulin Human Winthrop Comb 15 
 
Do not use Insulin Human Winthrop Comb 15 
 
If you are allergic to insulin or any of the other ingredients of this medicine (listed in section 6).  
 
Warnings and precautions 
 
Talk to your doctor, pharmacist or nurse before using Insulin Human Winthrop Comb 15. 
Follow closely the instructions for dosage, monitoring (blood and urine tests), diet and physical 
activity (physical work and exercise) as discussed with your doctor. 
 
If you are allergic to this medicine or to animal insulins, talk to your doctor. 
 
Special patient groups 
If you have liver or kidneys problems or if you are elderly, speak to your doctor as you may need a 
lower dose. 
 

 

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Travel 
Before travelling, consult your doctor. You may need to talk about 
- the availability of your insulin in the country you are visiting, 
- supplies of insulin, injection syringes etc., 
- correct storage of your insulin while travelling, 
- timing of meals and insulin administration while travelling, 
- the possible effects of changing to different time zones, 
- possible new health risks in the countries to be visited, 
- what you should do in emergency situations when you feel unwell or become ill. 
 
Illnesses and injuries 
In the following situations, the management of your diabetes may require a lot of care: 
- If you are ill or have a major injury then your blood sugar level may increase (hyperglycaemia). 
- If you are not eating enough, your blood sugar level may become too low (hypoglycaemia).  
In most cases you will need a doctor. Make sure that you contact a doctor early. 
 
If you have type 1 diabetes (insulin dependent diabetes mellitus), do not stop your insulin and 
continue to get enough carbohydrates. Always tell people who are caring for you or treating you that 
you require insulin. 
 
Some patients with long-standing type 2 diabetes mellitus and heart disease or previous stroke who 
were treated with pioglitazone and insulin experienced the development of heart failure. Inform your 
doctor as soon as possible if you experience signs of heart failure such as unusual shortness of breath 
or rapid increase in weight or localised swelling (oedema). 
 
Oother medicines and Insulin Human Winthrop Comb 15 
 
Some medicines cause changes in the blood sugar level (decrease, increase or both depending on the 
situation). In each case, it may be necessary to adjust your insulin dosage to avoid blood sugar levels 
that are either too low or too high. Be careful when you start or stop taking another medicine. 
 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines. Before taking a medicine ask your doctor if it can affect your blood sugar level, and what 
action, if any, you need to take. 
 
Medicines that may cause your blood sugar level to fall (hypoglycaemia) include:  
- all other medicines to treat diabetes, 
- angiotensin converting enzyme (ACE) inhibitors (used to treat certain heart conditions or high 

blood pressure), 
- disopyramide (used to treat certain heart conditions), 
- fluoxetine (used to treat depression), 
- fibrates (used to lower high levels of blood lipids), 
- monoamine oxidase (MAO) inhibitors (used to treat depression), 
- pentoxifylline, propoxyphene, salicylates (such as aspirin, used to relieve pain and lower fever), 
- sulfonamide antibiotics. 
 
Medicines that may cause your blood sugar level to rise (hyperglycaemia) include:  
- corticosteroids (such as "cortisone", used to treat inflammation), 
- danazol (medicine acting on ovulation), 
- diazoxide (used to treat high blood pressure),  
- diuretics (used to treat high blood pressure or excessive fluid retention), 
- glucagon (pancreas hormone used to treat severe hypoglycaemia), 
- isoniazid (used to treat tuberculosis), 
- oestrogens and progestogens (such as in the contraceptive pill used for birth control), 
- phenothiazine derivatives (used to treat psychiatric disorders), 
- somatropin (growth hormone), 

 

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- sympathomimetic medicines (such as epinephrine [adrenaline] or salbutamol, terbutaline used to 
treat asthma), 

- thyroid hormones (used to treat the thyroid gland disorders), 
- protease inhibitors (used to treat HIV), 
- atypical antipsychotic medicines (such as olanzapine and clozapine). 
 
Your blood sugar level may either rise or fall if you take:  
- beta-blockers (used to treat high blood pressure), 
- clonidine (used to treat high blood pressure), 
- lithium salts (used to treat psychiatric disorders). 
Pentamidine (used to treat some infections caused by parasites) may cause hypoglycaemia which may 
sometimes be followed by hyperglycaemia. 
 
Beta-blockers like other sympatholytic medicines (such as clonidine, guanethidine, and reserpine) may 
weaken or suppress entirely the first warning symptoms which help you to recognise a 
hypoglycaemia. 
 
If you are not sure whether you are taking one of those medicines ask your doctor or pharmacist. 
 
Insulin Human Winthrop Comb 15 with alcohol 
 
Your blood sugar levels may either rise or fall if you drink alcohol. 
 
Pregnancy and breast-feeding 
 
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor or pharmacist for advice before taking this medicine. 
 
Inform your doctor if you are planning to become pregnant, or if you are already pregnant. Your 
insulin dosage may need to be changed during pregnancy and after giving birth. Particularly careful 
control of your diabetes, and prevention of hypoglycaemia, is important for the health of your baby.  
 
If you are breast-feeding consult your doctor as you may require adjustments in your insulin doses and 
your diet. 
 
Driving and using machines 
 
Your ability to concentrate or react may be reduced if: 
- you have hypoglycaemia (low blood sugar levels), 
- you have hyperglycaemia (high blood sugar levels), 
- you have problems with your sight.  
Keep this possible problem in mind in all situations where you might put yourself and others at risk 
(such as driving a car or using machines). You should contact your doctor for advice on driving if: 
- you have frequent episodes of hypoglycaemia, 
- the first warning symptoms which help you to recognise hypoglycaemia are reduced or absent. 
 
Important information about some of the ingredients of Insulin Human Winthrop Comb 15  
 
This medicine contains less than 1 mmol (23 mg) sodium per dose, i.e. it is essentially ‘sodium-free’. 
 
 

 

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3. How to use Insulin Human Winthrop Comb 15 
 
Dose 
 
Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor 
or pharmacist if you are not sure. 
 
Based on your life-style and the results of your blood sugar (glucose) tests, your doctor will 
- determine how much Insulin Human Winthrop Comb 15 per day you will need, 
- tell you when to check your blood sugar level, and whether you need to carry out urine tests, 
- tell you when you may need to inject a higher or lower dose of Insulin Human Winthrop 

Comb 15. 
 
Many factors may influence your blood sugar level. You should know these factors so that you are 
able to react correctly to changes in your blood sugar level and to prevent it from becoming too high 
or too low. See the box at the end of this leaflet for further information. 
 
Frequency of administration 
 
Insulin Human Winthrop Comb 15 is injected under the skin 30 to 45 minutes before a meal.  
 
Method of administration 
 
Insulin Human Winthrop Comb 15 is a fluid (suspension) for injection under the skin. 
 
Do NOT inject Insulin Human Winthrop Comb 15 into a vein (blodd vessel). 
 
Your doctor will show you in which area of the skin you should inject your insulin. With each 
injection, change the puncture site within the particular area of skin that you are using. 
 
Do not use it in insulin pumps or other infusion pumps - special insulin preparations are available for 
use in such devices. 
 
How to handle the cartridges 
 
To ensure you get the accurate dose, the Insulin Human Winthrop Comb 15 cartridges are to be used 
only with the following pens: 
- JuniorSTAR which delivers doses in steps of 0.5 units  
- OptiPen, ClikSTAR, Tactipen, Autopen 24 or AllStar which deliver doses in steps of 1 unit. 
Not all of these pens may be marketed in your country.  
 
The pen should be used as recommended in the information provided by the device manufacturer. The 
manufacturer’s instructions for using the pen must be followed carefully for loading the cartridge, 
attaching the injection needle, and administering the insulin injection. 
 
Keep the cartridge at room temperature for 1 or 2 hours before inserting it into the pen. Mix the 
insulin well and check it before you insert it into the pen. Later, you must mix the insulin well again 
immediately before each injection. 
 
Mixing is best done by gently tilting the cartridge or pen (with the cartridge in it) back and forth at 
least 10 times. To assist in mixing, three tiny metal balls are present in the cartridge. 
 
After mixing, the suspension must have a uniform milky-white appearance. It must not be used if it 
remains clear or if, for example, clumps, flakes, particles or anything similar are in the suspension or 
on the sides or bottom of the cartridge. A new cartridge with a uniform suspension on mixing must 
then be used. 
 

 

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Always use a new cartridge must also be used if you notice that your blood sugar control is 
unexpectedly getting worse. This is because the insulin may have lost some of its effectiveness. If you 
think you may have a problem with your insulin, have it checked by your doctor or pharmacist. 
 
Special care before injection 
 
Before injection remove any air bubbles (see instructions for using the pen). Make sure that neither 
alcohol nor other disinfectants or other substances contaminate the insulin. 
- Do not re-fill and re-use empty cartridges. 
- Do not add any other insulin to the cartridge. 
- Do not mix insulin with any other medicines. 
 
Problems with the pen? 
 
Refer to the manufacturer’s instructions for using the pen. 
If the insulin pen is damaged or not working properly (due to mechanical defects) it has to be 
discarded, and a new insulin pen has to be used. 
 
If the pen does not function well, you can draw the insulin from the cartridge into an injection syringe. 
Therefore, keep injection syringes and needles as well. However, use only those injection syringes 
which are designed for an insulin concentration of 100 IU (International Units) per ml. 
 
If you use more Insulin Human Winthrop Comb 15 than you should 
- If you have injected too much Insulin Human Winthrop Comb 15, your blood sugar level 

may become too low (hypoglycaemia). Check your blood sugar frequently. In general, to 
prevent hypoglycaemia you must eat more food and monitor your blood sugar. For information 
on the treatment of hypoglycaemia, see box at the end of this leaflet. 

 
If you forget to use Insulin Human Winthrop Comb 15 
- If you have missed a dose of Insulin Human Winthrop Comb 15 or if you have not injected 

enough insulin, your blood sugar level may become too high (hyperglycaemia). Check your 
blood sugar frequently. For information on the treatment of hyperglycaemia, see box at the end 
of this leaflet. 

 
- Do not take a double dose to make up for a forgotten dose. 
 
If you stop using Insulin Human Winthrop Comb 15 
This could lead to severe hyperglycaemia (very high blood sugar) and ketoacidosis (build-up of acid 
in the blood because the body is breaking down fat instead of sugar). Do not stop Insulin Human 
Winthrop Comb 15 without speaking to a doctor, who will tell you what needs to be done. 
 
If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse. 
 
Insulin Mix-ups 
 
You must always check the insulin label before each injection to avoid mix-ups between Insulin 
Human Winthrop Comb 15 and other insulins.  
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
The most frequent side effect is hypoglycaemia (low blood sugar). The specific frequency cannot be 
estimated from available data (frequency not known). Serious hypoglycaemia may cause a heart attack 
or brain damage and may be life-threatening. For further information on the side effects of low blood 
sugar or high blood sugar, see the box at the end of this leaflet. 

 

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Severe allergic reactions to insulin may occur which may become life-threatening. Such reactions to 
insulin or to the excipients can cause large-scale skin reactions (rash and itching all over the body); 
severe swelling of skin or mucous membranes (angiooedema), shortness of breath, a fall in blood 
pressure with rapid heart beat and sweating. Frequency of these reactions cannot be estimated from 
available data. 
 
Side effects reported commonly (may affect up to 1 in 10 people) 
• Oedema 
Insulin treatment may cause temporary build-up of water in the body with swelling in the calves and 
ankles. 
• Injection site reactions 
 
Side effects reported uncommonly (may affect up to 1 in 100 people) 
• Severe allergic reaction with low blood pressure (shock) 
• Injection site urticaria (itchy rash) 
 
Other side effects include (frequency cannot be estimated from the available data) 
• Sodium retention 
• Eye reactions 
A marked change (improvement or worsening) in your blood sugar control can disturb your vision 
temporarily. If you have proliferative retinopathy (an eye disease related to diabetes) severe 
hypoglycaemic attacks may cause temporary loss of vision.  
• Skin changes at the injection site (lipodystrophy) 
If you inject your insulin too often at the same skin site, fatty tissue under the skin at this site may 
either shrink or thicken. Insulin that you inject in such a site may not work very well. Changing the 
injection site with each injection may help to prevent such skin changes. 
• Skin and allergic reactions 
Other mild reactions at the injection site (such as injection site redness, unusually intense pain on 
injection site, itching, injection site swelling or injection site inflammation) may occur. They can also 
spread around the injection site. Most minor reactions to insulins usually resolve in a few days to a 
few weeks. 
 
Insulin treatment can cause the body to produce antibodies to insulin (substances that act against 
insulin). However, only very rarely, this will require a change to your insulin dosage. 
 
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side 
effects not listed in this leaflet. 
 
 
5. How to store Insulin Human Winthrop Comb 15 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date which is stated on the carton and on the label of the 
cartridge after “EXP”. The expiry date refers to the last day of that month. 
 
Unopened cartridges 
Store in a refrigerator (2°C - 8°C). Do not freeze. Do not put Insulin Human Winthrop Comb 15 next 
to the freezer compartment or a freezer pack. Keep the cartridge in the outer carton in order to protect 
from light. 
 
In-use cartridges 
Cartridges in-use (in the insulin pen) or carried as a spare may be stored for a maximum of 4 weeks 
not above 25°C and away from direct heat (for example next to a heating unit) or direct light (direct 
sunlight or next to a lamp). The cartridge in-use must not be stored in a refrigerator. Do not use the 
cartridge after this time period. 

 

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Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Insulin Human Winthrop Comb 15 contains 
- The active substance is insulin human. One ml of Insulin Human Winthrop Comb 15 contains 

100 IU (International Units) of the active substance insulin human. 15% of the insulin is 
dissolved in water; the other 85% is present as tiny crystals of insulin protamine. 

- The other ingredients are: protamine sulphate, metacresol, phenol, zinc chloride, sodium 
dihydrogen phosphate dihydrate, glycerol, sodium hydroxide (see section 2 “Important 
information about some of the ingredients of Insulin Human Winthrop Comb 15”), hydrochloric 
acid (for pH adjustment) and water for injections. 

 
What Insulin Human Winthrop Comb 15 looks like and contents of the pack 
After mixing, Insulin Human Winthrop Comb 15 is a uniformly milky-fluid (suspension for injection), 
with no clumps, particles or flocculation visible. 
 
Insulin Human Winthrop Comb 15 is supplied in cartridges containing 3 ml suspension (300 IU). 
Packs of 3, 4, 5, 6, 9 and 10 cartridges of 3 ml are available. Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder and Manufacturer 
Sanofi-Aventis Deutschland GmbH 
D-65926 Frankfurt am Main 
Germany 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
Sanofi Belgium 
Tél/Tel: +32 (0)2 710 54 00 
 

Lietuva 
UAB «SANOFI-AVENTIS LIETUVA» 
Tel: +370 5 2755224 
 

България 
sanofi-aventis Bulgaria EOOD 
Тел.: +359 (0)2 970 53 00 
 

Luxembourg/Luxemburg 
Sanofi Belgium  
Tél/Tel: +32 (0)2 710 54 00 (Belgique/Belgien) 
 

Česká republika 
sanofi-aventis, s.r.o. 
Tel: +420 233 086 111 
 

Magyarország 
SANOFI-AVENTIS Zrt. 
Tel.: +36 1 505 0050 
 

Danmark 
sanofi-aventis Denmark A/S 
Tlf: +45 45 16 70 00 
 

Malta 
Sanofi Malta Ltd. 
Tel: +356 21493022 
 

Deutschland 
Zentiva Pharma GmbH 
Tel: +49 (0)180 20 200 10 
 

Nederland 
sanofi-aventis Netherlands B.V. 
Tel: +31 (0)182 557 755 
 

Eesti 
sanofi-aventis Estonia OÜ 
Tel: +372 627 34 88 
 

Norge 
Aventis Pharma Norge AS 
Tlf: +47 67 10 71 00 
 

 

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Ελλάδα 
sanofi-aventis AEBE 
Τηλ: +30 210 900 16 00 
 

Österreich 
sanofi-aventis GmbH 
Tel: +43 1 80 185 – 0 
 

España 
sanofi-aventis, S.A. 
Tel: +34 93 485 94 00 
 

Polska 
sanofi-aventis Sp. z o.o. 
Tel.: +48 22 280 00 00 
 

France 
sanofi-aventis France 
Tél: 0 800 222 555 
Appel depuis l’étranger : +33 1 57 63 23 23 
 

Portugal 
Sanofi - Produtos Farmacêuticos, Lda. 
Tel: +351 21 35 89 400 
 

Hrvatska 
sanofi-aventis Croatia d.o.o. 
Tel: +385 1 600 34 00 

România 
Sanofi Romania SRL 
Tel: +40 (0) 21 317 31 36 
 

Ireland 
sanofi-aventis Ireland Ltd. T/A SANOFI 
Tel: +353 (0) 1 403 56 00 
 

Slovenija 
sanofi-aventis d.o.o. 
Tel: +386 1 560 48 00 
 

Ísland 
Vistor hf. 
Sími: +354 535 7000 
 

Slovenská republika 
sanofi-aventis Pharma Slovakia s.r.o. 
Tel: +421 2 33 100 100 
 

Italia 
Sanofi S.p.A. 
Tel: 800 13 12 12 (domande di tipo tecnico)  
800 536389 (altre domande) 
 

Suomi/Finland 
Sanofi Oy 
Puh/Tel: +358 (0) 201 200 300 
 

Κύπρος 
sanofi-aventis Cyprus Ltd. 
Τηλ: +357 22 871600 
 

Sverige 
Sanofi AB 
Tel: +46 (0)8 634 50 00 
 

Latvija 
sanofi-aventis Latvia SIA 
Tel: +371 67 33 24 51 
 

United Kingdom 
Sanofi 
Tel: +44 (0) 845 372 7101 
 

 
This leaflet was last revised in {date} 
 
 
Other source of information 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu/ 
 
 
 
 

HYPERGLYCAEMIA AND HYPOGLYCAEMIA 
 

Always carry some sugar (at least 20 grams) with you. 
Carry some information with you to show you are diabetic. 

 
HYPERGLYCAEMIA (high blood sugar levels) 

 
If your blood sugar is too high (hyperglycaemia), you may not have injected enough insulin. 

 

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Why does hyperglycaemia occur? 
 
Examples include: 
- you have not injected your insulin or not injected enough, or if it has become less effective, for 

example through incorrect storage, 
- your insulin pen does not work properly, 
- you are doing less exercise than usual, you are under stress (emotional distress, excitement), or 

you have an injury, operation, infection or fever, 
- you are taking or have taken certain other medicines (see section 2, "Other medicines and 

Insulin Human Winthrop comb 15"). 
 
Warning symptoms of hyperglycaemia 
 
Thirst, increased need to urinate, tiredness, dry skin, reddening of the face, loss of appetite, low blood 
pressure, fast heart beat, and glucose and ketone bodies in urine. Stomach pain, fast and deep 
breathing, sleepiness or even loss of consciousness may be signs of a serious condition (ketoacidosis) 
resulting from lack of insulin. 
 
What should you do if you experience hyperglycaemia 
 
Test your blood sugar level and your urine for ketones as soon as any of the above symptoms 
occur. Severe hyperglycaemia or ketoacidosis must always be treated by a doctor, normally in a 
hospital. 
 

HYPOGLYCAEMIA (low blood sugar levels) 
 
If your blood sugar level falls too much you may become unconscious. Serious hypoglycaemia may 
cause a heart attack or brain damage and may be life-threatening. You normally should be able to 
recognise when your blood sugar is falling too much so that you can take the right actions. 
 
Why does hypoglycaemia occur? 
 
Examples include: 
- you inject too much insulin, 
- you miss meals or delay them, 
- you do not eat enough, or eat food containing less carbohydrate than normal (sugar and 

substances similar to sugar are called carbohydrates; however, artificial sweeteners are NOT 
carbohydrates), 

- you lose carbohydrates due to vomiting or diarrhoea, 
- you drink alcohol, particularly if you are not eating much, 
- you are doing more exercise than usual or a different type of physical activity, 
- you are recovering from an injury or operation or other stress, 
- you are recovering from an illness or from fever, 
- you are taking or have stopped taking certain other medicines (see section 2, "Other medicines 

and Insulin Human Winthrop Comb 15"). 
 
Hypoglycaemia is also more likely to occur if: 
- you have just begun insulin treatment or changed to another insulin preparation, 
- your blood sugar levels are almost normal or are unstable, 
- you change the area of skin where you inject insulin (for example from the thigh to the upper 

arm), 
- you suffer from severe kidney or liver disease, or some other disease such as hypothyroidism. 
 
Warning symptoms of hypoglycaemia 
 
- In your body 

 

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Examples of symptoms that tell you that your blood sugar level is falling too much or too fast: 
sweating, clammy skin, anxiety, fast heart beat, high blood pressure, palpitations and irregular 
heartbeat. These symptoms often develop before the symptoms of a low sugar level in the brain. 
 
- In your brain 
Examples of symptoms that indicate a low sugar level in the brain: headaches, intense hunger, nausea, 
vomiting, tiredness, sleepiness, sleep disturbances, restlessness, aggressive behaviour, lapses in 
concentration, impaired reactions, depression, confusion, speech disturbances (sometimes total loss of 
speech), visual disorders, trembling, paralysis, tingling sensations (paraesthesia), numbness and 
tingling sensations in the area of the mouth, dizziness, loss of self-control, inability to look after 
yourself, convulsions, loss of consciousness. 
 
The first symptoms which alert you to hypoglycaemia ("warning symptoms") may change, be weaker 
or may be missing altogether if 
- you are elderly, if you have had diabetes for a long time or if you suffer from a certain type of 

nervous disease (diabetic autonomic neuropathy), 
- you have recently suffered hypoglycaemia (for example the day before) or if it develops slowly, 
- you have almost normal or, at least, greatly improved blood sugar levels, 
- you have recently changed from an animal insulin to a human insulin such as Insulin Human 

Winthrop, 
- you are taking or have taken certain other medicines (see section 2, "Other medicines and 

Insulin Human Winthrop Comb 15"). 
 
In such a case, you may develop severe hypoglycaemia (and even faint) before you are aware of the 
problem. Be familiar with your warning symptoms. If necessary, more frequent blood sugar testing 
can help to identify mild hypoglycaemic episodes that may otherwise be overlooked. If you are not 
confident about recognising your warning symptoms, avoid situations (such as driving a car) in which 
you or others would be put at risk by hypoglycaemia. 
 
What should you do if you experience hypoglycaemia 
 
1. Do not inject insulin. Immediately take about 10 to 20 g sugar, such as glucose, sugar cubes or a 

sugar-sweetened beverage. Caution: Artificial sweeteners and foods with artificial sweeteners 
(such as diet drinks) are of no help in treating hypoglycaemia. 

2. Then eat something that has a long-acting effect in raising your blood sugar (such as bread or 
pasta). Your doctor or nurse should have discussed this with you previously. 

3. If the hypoglycaemia comes back again take another 10 to 20 g sugar. 
4. Speak to a doctor immediately if you are not able to control the hypoglycaemia or if it recurs. 
 
Tell your relatives, friends and close colleagues the following: 
If you are not able to swallow or if you are unconscious, you will require an injection of glucose or 
glucagon (a medicine which increases blood sugar). These injections are justified even if it is not 
certain that you have hypoglycaemia. 
 
It is advisable to test your blood sugar immediately after taking glucose to check that you really have 
hypoglycaemia. 
 
 

 

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Package leaflet: Information for the user 

 
Insulin Human Winthrop Comb 15 SoloStar 100 IU/ml suspension for injection in a pre-filled 

pen 
Insulin human 

 
 
Read all of this leaflet carefully, including the Instructions for Use of Insulin Human Winthrop 
Comb 15 SoloStar, pre-filled pen, before you start using this medicine because it contains 
important information for you. 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor, pharmacist or nurse. 
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours. 
- If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible 

side effects not listed in this leaflet. 
 
What is in this leaflet: 
1. What Insulin Human Winthrop Comb 15 is and what it is used for 
2. What you need to know before you use Insulin Human Winthrop Comb 15 
3. How to use Insulin Human Winthrop Comb 15 
4. Possible side effects 
5. How to store Insulin Human Winthrop Comb 15 
6. Contents of the pack and other information 
 
 
1. What Insulin Human Winthrop Comb 15 is and what it is used for 
 
Insulin Human Winthrop Comb 15 contains the active substance insulin human which is made by a 
biotechnology process and is identical with the body's own insulin. 
 
Insulin Human Winthrop Comb 15 is an insulin preparation with a gradual onset and long duration of 
action. It comes in cartridges sealed in disposable pen injectors, SoloStar. 
 
Insulin Human Winthrop Comb 15 is used to reduce high blood sugar in patients with diabetes 
mellitus who need treatment with insulin. Diabetes mellitus is a disease where your body does not 
produce enough insulin to control the level of blood sugar. 
 
 
2. What you need to know before you use Insulin Human Winthrop Comb 15 
 
Do not use Insulin Human Winthrop Comb 15  
 
If you are allergic to insulin or any of the other ingredients of this medicine (listed in section 6).  
 
Warnings and precautions 
 
Talk to your doctor, pharmacist or nurse before using Insulin Human Winthrop Comb 15. 
Follow closely the instructions for dosage, monitoring (blood and urine tests), diet and physical 
activity (physical work and exercise), injection technique as discussed with your doctor. 
 
If you are allergic to this medicine or to animal insulins, talk to your doctor. 
 
Special patient groups 
If you have liver or kidneys problems or if you are elderly, speak to your doctor as you may need a 
lower dose. 

 

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Travel 
Before travelling, consult your doctor. You may need to talk about 
- the availability of your insulin in the country you are visiting, 
- supplies of insulin, injection syringes etc., 
- correct storage of your insulin while travelling, 
- timing of meals and insulin administration while travelling, 
- the possible effects of changing to different time zones, 
- possible new health risks in the countries to be visited, 
- what you should do in emergency situations when you feel unwell or become ill. 
 
Illnesses and injuries 
In the following situations, the management of your diabetes may require a lot of care: 
- If you are ill or have a major injury then your blood sugar level may increase (hyperglycaemia).  
- If you are not eating enough, your blood sugar level may become too low (hypoglycaemia).  
In most cases you will need a doctor. Make sure that you contact a doctor early.  
 
If you have type 1 diabetes (insulin dependent diabetes mellitus), do not stop your insulin and 
continue to get enough carbohydrates. Always tell people who are caring for you or treating you that 
you require insulin. 
 
Some patients with long-standing type 2 diabetes mellitus and heart disease or previous stroke who 
were treated with pioglitazone and insulin experienced the development of heart failure. Inform your 
doctor as soon as possible if you experience signs of heart failure such as unusual shortness of breath 
or rapid increase in weight or localised swelling (oedema). 
 
Other medicines and Insulin Human Winthrop Comb 15 
 
Some medicines cause changes in the blood sugar level (decrease, increase or both depending on the 
situation). In each case, it may be necessary to adjust your insulin dosage to avoid blood sugar levels 
that are either too low or too high. Be careful when you start or stop taking another medicine. 
 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines. Before taking a medicine ask your doctor if it can affect your blood sugar level, and what 
action, if any, you need to take. 
 
Medicines that may cause your blood sugar level to fall (hypoglycaemia) include:  
- all other medicines to treat diabetes,  
- angiotensin converting enzyme (ACE) inhibitors (used to treat certain heart conditions or high 

blood pressure),  
- disopyramide (used to treat certain heart conditions),  
- fluoxetine (used to treat depression),  
- fibrates (used to lower high levels of blood lipids),  
- monoamine oxidase (MAO) inhibitors (used to treat depression),  
- pentoxifylline, propoxyphene, salicylates (such as aspirin, used to relieve pain and lower fever), 
- sulfonamide antibiotics. 
 
Medicines that may cause your blood sugar level to rise (hyperglycaemia) include:  
- corticosteroids (such as "cortisone", used to treat inflammation),  
- danazol (medicine acting on ovulation),  
- diazoxide (used to treat high blood pressure),  
- diuretics (used to treat high blood pressure or excessive fluid retention),  
- glucagon (pancreas hormone used to treat severe hypoglycaemia),  
- isoniazid (used to treat tuberculosis),  
- oestrogens and progestogens (such as in the contraceptive pill used for birth control),  
- phenothiazine derivatives (used to treat psychiatric disorders),  
- somatropin (growth hormone),  

 

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- sympathomimetic medicines (such as epinephrine [adrenaline] or salbutamol, terbutaline used to 
treat asthma), 

- thyroid hormones (used to treat the thyroid gland disorders), 
- protease inhibitors (used to treat HIV), 
- atypical antipsychotic medicines (such as olanzapine and clozapine). 
 
Your blood sugar level may either rise or fall if you take:  
- beta-blockers (used to treat high blood pressure),  
- clonidine (used to treat high blood pressure), 
- lithium salts (used to treat psychiatric disorders).  
Pentamidine (used to treat some infections caused by parasites) may cause hypoglycaemia which may 
sometimes be followed by hyperglycaemia. 
 
Beta-blockers like other sympatholytic medicines (such as clonidine, guanethidine, and reserpine) may 
weaken or suppress entirely the first warning symptoms which help you to recognise a 
hypoglycaemia. 
 
If you are not sure whether you are taking one of those medicines ask your doctor or pharmacist. 
 
Insulin Human Winthrop Comb 15 with alcohol 
 
Your blood sugar levels may either rise or fall if you drink alcohol. 
 
Pregnancy and breast-feeding 
 
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor or pharmacist for advice before taking this medicine. 
 
Inform your doctor if you are planning to become pregnant, or if you are already pregnant. Your 
insulin dosage may need to be changed during pregnancy and after giving birth. Particularly careful 
control of your diabetes, and prevention of hypoglycaemia, is important for the health of your baby.. 
 
If you are breast-feeding consult your doctor as you may require adjustments in your insulin doses and 
your diet. 
 
Driving and using machines 
 
Your ability to concentrate or react may be reduced if: 
- you have hypoglycaemia (low blood sugar levels), 
- you have hyperglycaemia (high blood sugar levels), 
- you have problems with your sight.  
Keep this possible problem in mind in all situations where you might put yourself and others at risk 
(such as driving a car or using machines). You should contact your doctor for advice on driving if: 
- you have frequent episodes of hypoglycaemia, 
- the first warning symptoms which help you to recognise hypoglycaemia are reduced or absent. 
 
Important information about some of the ingredients of Insulin Human Winthrop Comb 15  
 
This medicine contains less than 1 mmol (23 mg) sodium per dose, i.e. it is essentially ‘sodium-free’. 
 
 

 

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3. How to use Insulin Human Winthrop Comb 15 
 
Dose 
 
Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor 
or pharmacist if you are not sure. 
 
Based on your life-style and the results of your blood sugar (glucose) tests, your doctor will 
- determine how much Insulin Human Winthrop Comb 15 per day you will need, 
- tell you when to check your blood sugar level, and whether you need to carry out urine tests, 
- tell you when you may need to inject a higher or lower dose of Insulin Human Winthrop 

Comb 15. 
 
Many factors may influence your blood sugar level. You should know these factors so that you are 
able to react correctly to changes in your blood sugar level and to prevent it from becoming too high 
or too low. See the box at the end of this leaflet for further information. 
 
Frequency of administration 
 
Insulin Human Winthrop Comb 15 is injected under the skin 30 to 45 minutes before a meal.  
 
Method of administration 
 
Insulin Human Winthrop Comb 15 is a fluid (suspension) for injection under the skin. 
 
Do NOT inject Insulin Human Winthrop Comb 15 into a vein (blood vessel). 
 
SoloStar delivers insulin in doses from 1 to 80 units in steps of 1 unit. Each pen contains multiple 
doses. 
 
Your doctor will show you in which area of the skin you should inject your insulin. With each 
injection, change the puncture site within the particular area of skin that you are using. 
 
How to handle SoloStar 
 
SoloStar is a pre-filled disposable pen containing human insulin. 
 
Read carefully the "SoloStar Instructions for Use" included in this package leaflet. You must 
use the pen as described in these Instructions for Use. 
 
A new injection needle must be attached before each use. Only use needles that have been approved 
for use with SoloStar. 
A safety test must be performed before each injection. 
 
Mix the insulin well and check it before first use. Later, you must mix the insulin well again 
immediately before each injection. 
 
Mixing is best done by gently tilting the pen back and forth at least 10 times. To assist in mixing, three 
tiny metal balls are present in the cartridge. 
 
After mixing, the suspension must have a uniform milky-white appearance. It must not be used if it 
remains clear or if, for example, clumps, flakes, particles or anything similar are in the suspension or 
on the sides or bottom of the cartridge in the pen. A new pen with a uniform suspension on mixing 
must then be used. 
 
Always use a new pen if you notice that your blood sugar control is unexpectedly getting worse. If 
you think you have a problem with SoloStar, consult your doctor, pharmacist or nurse. 

 

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To prevent the possible transmission of disease, each pen must be used by one patient only. 
 
Special care before injection 
 
Make sure that neither alcohol nor other disinfectants or other substances contaminate the insulin. 
 
Do not mix insulin with any other medicines. Insulin Human Winthrop Comb 15 SoloStar, pre-filled 
pen, is not designed to allow any other insulin to be mixed in the cartridge. 
 
Empty pens must not be re-filled and must be properly discarded. 
 
Do not use SoloStar if it is damaged or not working properly (due to mechanical defects), it has to be 
discarded and a new SoloStar has to be used. 
 
If you use more Insulin Human Winthrop Comb 15 than you should 
- If you have injected too much Insulin Human Winthrop Comb 15, your blood sugar level 

may become too low (hypoglycaemia). Check your blood sugar frequently. In general, to 
prevent hypoglycaemia you must eat more food and monitor your blood sugar. For information 
on the treatment of hypoglycaemia, see box at the end of this leaflet. 

 
If you forget to use Insulin Human Winthrop Comb 15 
- If you have missed a dose of Insulin Human Winthrop Comb 15 or if you have not injected 

enough insulin, your blood sugar level may become too high (hyperglycaemia). Check your 
blood sugar frequently. For information on the treatment of hyperglycaemia, see box at the end 
of this leaflet. 

 
- Do not take a double dose to make up for a forgotten dose. 
 
If you stop using Insulin Human Winthrop Comb 15 
 
This could lead to severe hyperglycaemia (very high blood sugar) and ketoacidosis (build-up of acid 
in the blood because the body is breaking down fat instead of sugar). Do not stop Insulin Human 
Winthrop Comb 15 without speaking to a doctor, who will tell you what needs to be done. 
 
If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse. 
 
Insulin Mix-ups 
 
You must always check the insulin label before each injection to avoid mix-ups between Insulin 
Human Winthrop Comb 15 and other insulins.  
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
The most frequent side effect is hypoglycaemia (low blood sugar). The specific frequency cannot be 
estimated from available data (frequency not know). Serious hypoglycaemia may cause a heart attack 
or brain damage and may be life-threatening. For further information on the side effects of low blood 
sugar or high blood sugar, see the box at the end of this leaflet. 
 
Severe allergic reactions to insulin may occur which may become life-threatening. Such reactions to 
insulin or to the excipients can cause large-scale skin reactions (rash and itching all over the body); 
severe swelling of skin or mucous membranes (angiooedema), shortness of breath, a fall in blood 
pressure with rapid heart beat and sweating. Frequency of these reactions cannot be estimated from 
available data. 

 

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Side effects reported commonly (may affect 1 in 10 people) 
• Oedema 
Insulin treatment may cause temporary build-up of water in the body with swelling in the calves and 
ankles. 
• Injection site reactions 
 
Side effects reported uncommonly (may affect up to 1 in 100 people) 
• Severe allergic reaction with low blood pressure (shock) 
• Injection site urticaria (itchy rash) 
 
Other side effects include (frequency cannot be estimated from the available data) 
• Sodium retention 
• Eye reactions 
A marked change (improvement or worsening) in your blood sugar control can disturb your vision 
temporarily. If you have proliferative retinopathy (an eye disease related to diabetes) severe 
hypoglycaemic attacks may cause temporary loss of vision.  
• Skin changes at the injection site (lipodystrophy) 
If you inject your insulin too often at the same skin site, fatty tissue under the skin at this site may 
either shrink or thicken. Insulin that you inject in such a site may not work very well. Changing the 
injection site with each injection may help to prevent such skin changes. 
• Skin and allergic reactions 
Other mild reactions at the injection site (such as injection site redness, unusually intense pain on 
injection site, itching, injection site swelling or injection site inflammation) may occur. They can also 
spread around the injection site. Most minor reactions to insulins usually resolve in a few days to a 
few weeks. 
 
Insulin treatment can cause the body to produce antibodies to insulin (substances that act against 
insulin). However, only very rarely, this will require a change to your insulin dosage. 
 
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side 
effects not listed in this leaflet. 
 
 
5. How to store Insulin Human Winthrop Comb 15  
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date which is stated on the carton and on the label of the pen 
after “EXP”. The expiry date refers to the last day of that month. 
 
Not in-use pens 
Store in a refrigerator (2°C - 8°C). Do not freeze. Do not put the pre-filled pen next to the freezer 
compartment or a freezer pack. Keep the pre-filled pen in the outer carton in order to protect from 
light. 
 
In-use pens 
Pre-filled pens in-use or carried as a spare may be stored for a maximum of 4 weeks not above 25°C 
and away from direct heat (for example next to a heating unit) or direct light (direct sunlight or next to 
a lamp). The pen in-use must not be stored in a refrigerator. Do not use the pen after this time period. 
 
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment. 
 
 

 

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6. Contents of the pack and other information 
 
What Insulin Human Winthrop Comb 15 contains 
- The active substance is insulin human. One ml of Insulin Human Winthrop Comb 15 contains 

100 IU (International Units) of the active substance insulin human. 15% of the insulin is 
dissolved in water; the other 85% is present as tiny crystals of insulin protamine. 

- The other ingredients are: protamine sulphate, metacresol, phenol, zinc chloride, sodium 
dihydrogen phosphate dihydrate, glycerol, sodium hydroxide (see section 2 under “Important 
information about some of the ingredients of Insulin Human Winthrop Comb 15”), hydrochloric 
acid (for pH adjustment) and water for injections. 

 
What Insulin Human Winthrop Comb 15 looks like and contents of the pack 
After mixing, Insulin Human Winthrop Comb 15 is a uniformly milky fluid (suspension for injection), 
with no clumps, particles or flocculation visible. 
 
Insulin Human Winthrop Comb 15 is supplied in pre-filled pens, SoloStar, containing 3 ml 
suspension, (300 IU). Packs of 3, 4, 5, 6, 9 and 10 pens of 3 ml are available. Not all pack sizes may 
be marketed. 
 
Marketing Authorisation Holder and Manufacturer 
Sanofi-Aventis Deutschland GmbH 
D-65926 Frankfurt am Main 
Germany 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
Sanofi Belgium 
Tél/Tel: +32 (0)2 710 54 00 
 

Lietuva 
UAB «SANOFI-AVENTIS LIETUVA» 
Tel: +370 5 2755224 
 

България 
sanofi-aventis Bulgaria EOOD 
Тел.: +359 (0)2 970 53 00 
 

Luxembourg/Luxemburg 
Sanofi Belgium  
Tél/Tel: +32 (0)2 710 54 00 (Belgique/Belgien) 
 

Česká republika 
sanofi-aventis, s.r.o. 
Tel: +420 233 086 111 
 

Magyarország 
SANOFI-AVENTIS Zrt. 
Tel.: +36 1 505 0050 
 

Danmark 
sanofi-aventis Denmark A/S 
Tlf: +45 45 16 70 00 
 

Malta 
Sanofi Malta Ltd. 
Tel: +356 21493022 
 

Deutschland 
Zentiva Pharma GmbH 
Tel: +49 (0)180 20 200 10 
 

Nederland 
sanofi-aventis Netherlands B.V. 
Tel: +31 (0)182 557 755 
 

Eesti 
sanofi-aventis Estonia OÜ 
Tel: +372 627 34 88 
 

Norge 
Aventis Pharma Norge AS 
Tlf: +47 67 10 71 00 
 

Ελλάδα 
sanofi-aventis AEBE 
Τηλ: +30 210 900 16 00 
 

Österreich 
sanofi-aventis GmbH 
Tel: +43 1 80 185 – 0 
 

 

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España 
sanofi-aventis, S.A. 
Tel: +34 93 485 94 00 
 

Polska 
sanofi-aventis Sp . z o.o. 
Tel.: +48 22 280 00 00 
 

France 
sanofi-aventis France 
Tél: 0 800 222 555 
Appel depuis l’étranger : +33 1 57 63 23 23 
 

Portugal 
Sanofi - Produtos Farmacêuticos, Lda. 
Tel: +351 21 35 89 400 
 

Hrvatska 
sanofi-aventis Croatia d.o.o. 
Tel: +385 1 600 34 00 

România 
Sanofi Romania SRL 
Tel: +40 (0) 21 317 31 36 
 

Ireland 
sanofi-aventis Ireland Ltd. T/A SANOFI 
Tel: +353 (0) 1 403 56 00 
 

Slovenija 
sanofi-aventis d.o.o. 
Tel: +386 1 560 48 00 
 

Ísland 
Vistor hf. 
Sími: +354 535 7000 
 

Slovenská republika 
sanofi-aventis Pharma Slovakia s.r.o. 
Tel: +421 2 33 100 100 
 

Italia 
Sanofi S.p.A. 
Tel: 800 13 12 12 (domande di tipo tecnico)  
800 536389 (altre domande) 
 

Suomi/Finland 
Sanofi Oy 
Puh/Tel: +358 (0) 201 200 300 
 

Κύπρος 
sanofi-aventis Cyprus Ltd. 
Τηλ: +357 22 871600 
 

Sverige 
Sanofi AB 
Tel: +46 (0)8 634 50 00 
 

Latvija 
sanofi-aventis Latvia SIA 
Tel: +371 67 33 24 51 
 

United Kingdom 
Sanofi 
Tel: +44 (0) 845 372 7101 
 

 
This leaflet was last revised in {date} 
 
 
Other source of information 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu/ 
 
 
 
 

HYPERGLYCAEMIA AND HYPOGLYCAEMIA 
 

Always carry some sugar (at least 20 grams) with you. 
Carry some information with you to show you are diabetic. 

 
HYPERGLYCAEMIA (high blood sugar levels) 

 
If your blood sugar is too high (hyperglycaemia), you may not have injected enough insulin. 
 
Why does hyperglycaemia occur? 
 
Examples include: 

 

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- you have not injected your insulin or not injected enough, or if it has become less effective, for 
example through incorrect storage, 

- your insulin pen does not work properly, 
- you are doing less exercise than usual, you are under stress (emotional distress, excitement), or 

you have an injury, operation, infection or fever, 
- you are taking or have taken certain other medicines (see section 2, "Other medicines and 

Insulin Human Winthrop Comb 15"). 
 
Warning symptoms of hyperglycaemia 
 
Thirst, increased need to urinate, tiredness, dry skin, reddening of the face, loss of appetite, low blood 
pressure, fast heart beat, and glucose and ketone bodies in urine. Stomach pain, fast and deep 
breathing, sleepiness or even loss of consciousness may be signs of a serious condition (ketoacidosis) 
resulting from lack of insulin. 
 
What should you do if you experience hyperglycaemia 
 
Test your blood sugar level and your urine for ketones as soon as any of the above symptoms 
occur. Severe hyperglycaemia or ketoacidosis must always be treated by a doctor, normally in a 
hospital. 
 

HYPOGLYCAEMIA (low blood sugar levels) 
 
If your blood sugar level falls too much you may become unconscious. Serious hypoglycaemia may 
cause a heart attack or brain damage and may be life-threatening. You normally should be able to 
recognise when your blood sugar is falling too much so that you can take the right actions. 
 
Why does hypoglycaemia occur? 
 
Examples include: 
- you inject too much insulin, 
- you miss meals or delay them, 
- you do not eat enough, or eat food containing less carbohydrate than normal (sugar and 

substances similar to sugar are called carbohydrates; however, artificial sweeteners are NOT 
carbohydrates), 

- you lose carbohydrates due to vomiting or diarrhoea, 
- you drink alcohol, particularly if you are not eating much, 
- you are doing more exercise than usual or a different type of physical activity, 
- you are recovering from an injury or operation or other stress, 
- you are recovering from an illness or from fever, 
- you are taking or have stopped taking certain other medicines (see section 2, "Other medicines 

and Insulin Human Winthrop Comb 15"). 
 
Hypoglycaemia is also more likely to occur if: 
- you have just begun insulin treatment or changed to another insulin preparation, 
- your blood sugar levels are almost normal or are unstable, 
- you change the area of skin where you inject insulin (for example from the thigh to the upper 

arm), 
- you suffer from severe kidney or liver disease, or some other disease such as hypothyroidism. 
 
Warning symptoms of hypoglycaemia 
 
- In your body 
Examples of symptoms that tell you that your blood sugar level is falling too much or too fast: 
sweating, clammy skin, anxiety, fast heart beat, high blood pressure, palpitations and irregular 
heartbeat. These symptoms often develop before the symptoms of a low sugar level in the brain. 
 

 

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- In your brain 
Examples of symptoms that indicate a low sugar level in the brain: headaches, intense hunger, nausea, 
vomiting, tiredness, sleepiness, sleep disturbances, restlessness, aggressive behaviour, lapses in 
concentration, impaired reactions, depression, confusion, speech disturbances (sometimes total loss of 
speech), visual disorders, trembling, paralysis, tingling sensations (paraesthesia), numbness and 
tingling sensations in the area of the mouth, dizziness, loss of self-control, inability to look after 
yourself, convulsions, loss of consciousness. 
 
The first symptoms which alert you to hypoglycaemia ("warning symptoms") may change, be weaker 
or may be missing altogether if 
- you are elderly, if you have had diabetes for a long time or if you suffer from a certain type of 

nervous disease (diabetic autonomic neuropathy), 
- you have recently suffered hypoglycaemia (for example the day before) or if it develops slowly, 
- you have almost normal or, at least, greatly improved blood sugar levels, 
- you have recently changed from an animal insulin to a human insulin such as Insulin Human 

Winthrop, 
- you are taking or have taken certain other medicines (see section 2, "Other medicines and 

Insulin Human Winthrop Comb 15"). 
 
In such a case, you may develop severe hypoglycaemia (and even faint) before you are aware of the 
problem. Be familiar with your warning symptoms. If necessary, more frequent blood sugar testing 
can help to identify mild hypoglycaemic episodes that may otherwise be overlooked. If you are not 
confident about recognising your warning symptoms, avoid situations (such as driving a car) in which 
you or others would be put at risk by hypoglycaemia. 
 
What should you do if you experience hypoglycaemia 
 
1. Do not inject insulin. Immediately take about 10 to 20 g sugar, such as glucose, sugar cubes or a 

sugar-sweetened beverage. Caution: Artificial sweeteners and foods with artificial sweeteners 
(such as diet drinks) are of no help in treating hypoglycaemia. 

2. Then eat something that has a long-acting effect in raising your blood sugar (such as bread or 
pasta). Your doctor or nurse should have discussed this with you previously. 

3. If the hypoglycaemia comes back again take another 10 to 20 g sugar. 
4. Speak to a doctor immediately if you are not able to control the hypoglycaemia or if it recurs. 
 
Tell your relatives, friends and close colleagues the following: 
If you are not able to swallow or if you are unconscious, you will require an injection of glucose or 
glucagon (a medicine which increases blood sugar). These injections are justified even if it is not 
certain that you have hypoglycaemia. 
 
It is advisable to test your blood sugar immediately after taking glucose to check that you really have 
hypoglycaemia. 
 
 

 

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Insulin Human Winthrop Comb 15 SoloStar suspension for injection in a pre-filled pen. 
Instructions for Use. 
 
SoloStar is a prefilled pen for the injection of insulin. Your doctor has decided that SoloStar is 
appropriate for you based on your ability to handle SoloStar. Talk with your doctor, pharmacist or 
nurse about proper injection technique before using SoloStar. 
 
Read these instructions carefully before using your SoloStar. If you are not able to use SoloStar or 
follow all the instructions completely on your own, you must use SoloStar only if you have help from 
a person who is able to follow the instructions completely. Hold the pen as shown in this leaflet. To 
ensure that you read the dose correctly, hold the pen horizontally, with the needle on the left and the 
dosage selector to the right as shown in the illustrations below. 
 
Follow these instructions completely each time you use SoloStar to ensure that you get an 
accurate dose. If you do not follow these instructions completely, you may get too much or too 
little insulin, which may affect your blood glucose. 
 
You can set doses from 1 to 80 units in steps of 1 unit. Each pen contains multiple doses. 
 
Keep this leaflet for future reference. 
 
If you have any questions about SoloStar or about diabetes, ask your doctor, pharmacist or nurse or 
call the local sanofi-aventis number on the front of this leaflet. 
 

 
Schematic diagram of the pen 

 
 
Important information for use of SoloStar: 
 
• Always attach a new needle before each use. Only use needles that have been approved for use 

with SoloStar. 
• Do not select a dose and/or press the injection button without a needle attached. 
• Always perform the safety test before each injection (see Step 3). 
• This pen is only for your use. Do not share it with anyone else.  
• If your injection is given by another person, special caution must be taken by this person to avoid 

accidental needle injury and transmission of infection. 
• Never use SoloStar if it is damaged or if you are not sure that it is working properly. 
• Always have a spare SoloStar in case your SoloStar is lost or damaged. 
 
 
Step 1. Check the insulin 
 
A. Check the label on your SoloStar to make sure you have the correct insulin. Insulin Human 

Winthrop SoloStar is white with a colour on the injection button. The injection button colour 
will vary based on the formulation of Insulin Human Winthrop insulin used. The pictures below 
are for illustrative purposes only. 

 
B. Take off the pen cap. 
 
C. Check the appearance of your insulin.  

 

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If you are using a suspension insulin (Insulin Human Winthrop Basal or Insulin Human 
Winthrop mixtures), turn the pen up and down at least 10 times to resuspend the insulin. Turn 
the pen gently to avoid foaming in the cartridge.  

 

   
 

After mixing check the appearance of your insulin. Insulin suspensions must have an 
evenly milky-white appearance.  

 
 
Step 2. Attach the needle 
 
Always use a new sterile needle for each injection. This helps prevent contamination, and potential 
needle blocks. 
 
Before use of needle, carefully read the “Instructions for Use” accompanying the needles.  
 
Please note: The needles shown are for illustrative purposes only. 

 
A. Remove the protective seal from a new needle.  
 
B. Line up the needle with the pen, and keep it straight as you attach it (screw or push on, 

depending on the needle type). 
 

 . 
 

• If the needle is not kept straight while you attach it, it can damage the rubber seal and cause 
leakage, or break the needle. 

 

   
 
 
Step 3. Perform a safety test  
 
Always perform the safety test before each injection. This ensures that you get an accurate dose by: 
• ensuring that pen and needle work properly 
• removing air bubbles 
 
A. Select a dose of 2 units by turning the dosage selector. 

 

 

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B. Take off the outer needle cap and keep it to remove the used needle after injection. Take off the 

inner needle cap and discard it.  
 

   
 
C. Hold the pen with the needle pointing upwards. 
 
D. Tap the insulin reservoir so that any air bubbles rise up towards the needle. 
 
E. Press the injection button all the way in. Check if insulin comes out of the needle tip. 

   
 
You may have to perform the safety test several times before insulin is seen.  
 
• If no insulin comes out, check for air bubbles and repeat the safety test two more times to 

remove them. 
• If still no insulin comes out, the needle may be blocked. Change the needle and try again. 
• If no insulin comes out after changing the needle, your SoloStar may be damaged. Do not use 

this SoloStar. 
 
Step 4. Select the dose 
 
You can set the dose in steps of 1 unit, from a minimum of 1 unit to a maximum of 80 units. If you 
need a dose greater than 80 units, you should give it as two or more injections. 
 
A. Check that the dose window shows “0” following the safety test. 
 
B. Select your required dose (in the example below, the selected dose is 30 units). If you turn past 

your dose, you can turn back down. 
 

  
 

 

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• Do not push the injection button while turning, as insulin will come out. 
 
• You cannot turn the dosage selector past the number of units left in the pen. Do not force the 

dosage selector to turn. In this case, either you can inject what is remaining in the pen and 
complete your dose with a new SoloStar or use a new SoloStar for your full dose. 

 
 
Step 5. Inject the dose 
 
A. Use the injection method as instructed by your doctor, pharmacist or nurse.  
 
B. Insert the needle into the skin. 
 

   
 
C. Deliver the dose by pressing the injection button in all the way. The number in the dose window 

will return to “0” as you inject.  

   
 

D. Keep the injection button pressed all the way in. Slowly count to 10 before you withdraw the 
needle from the skin. This ensures that the full dose will be delivered. 
 
The pen plunger moves with each dose. The plunger will reach the end of the cartridge when 
the total of 300 units of insulin have been used. 

 
 
Step 6. Remove and discard the needle 
 
Always remove the needle after each injection and store SoloStar without a needle attached.  
This helps prevent: 
• Contamination and/or infection  
• Entry of air into the insulin reservoir and leakage of insulin, which can cause inaccurate dosing. 
 
A. Put the outer needle cap back on the needle, and use it to unscrew the needle from the pen. To 

reduce the risk of accidental needle injury, never replace the inner needle cap.  
 

• If your injection is given by another person, or if you are giving an injection to another person, 
special caution must be taken by this person when removing and disposing of the needle. Follow 
recommended safety measures for removal and disposal of needles (e.g. contact your doctor, 
pharmacist or nurse) in order to reduce the risk of accidental needle injury and transmission of 
infectious diseases. 

 
B. Dispose of the needle safely.  
 
C. Always put the pen cap back on the pen, then store the pen until your next injection. 
 
 

 

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Storage instructions  
 
Please check the reverse (insulin) side of this leaflet for instructions on how to store SoloStar. 
 
If your SoloStar is in cool storage, take it out 1 to 2 hours before you inject to allow it to warm up. 
Cold insulin is more painful to inject. 
 
Discard your used SoloStar as required by your local authorities. 
 
 
Maintenance 
 
Protect your SoloStar from dust and dirt. 
 
You can clean the outside of your SoloStar by wiping it with a damp cloth.  
 
Do not soak, wash or lubricate the pen as this may damage it.  
 
Your SoloStar is designed to work accurately and safely. It should be handled with care. Avoid 
situations where SoloStar might be damaged. If you are concerned that your SoloStar may be 
damaged, use a new one. 
 
 
 

 

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Package leaflet: Information for the user 

 
Insulin Human Winthrop Comb 25 100 IU/ml suspension for injection in a vial 

Insulin human 
 
 
Read all of this leaflet carefully before you start using this medicine because it contains 
important information for you. 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor, pharmacist or nurse. 
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours. 
- If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible 

side effects not listed in this leaflet. 
 
What is in this leaflet: 
1. What Insulin Human Winthrop Comb 25 is and what it is used for 
2. What you need to know before you use Insulin Human Winthrop Comb 25 
3. How to use Insulin Human Winthrop Comb 25 
4. Possible side effects 
5. How to store Insulin Human Winthrop Comb 25 
6. Contents of the pack and other information 
 
 
1. What Insulin Human Winthrop Comb 25 is and what it is used for 
 
Insulin Human Winthrop Comb 25 contains the active substance insulin human which is made by a 
biotechnology process and is identical with the body's own insulin. 
 
Insulin Human Winthrop Comb 25 is an insulin preparation with a gradual onset and long duration of 
action.  
 
Insulin Human Winthrop Comb 25 is used to reduce high blood sugar in patients with diabetes 
mellitus who need treatment with insulin. Diabetes mellitus is a disease where your body does not 
produce enough insulin to control the level of blood sugar. 
 
 
2. What you need to know before you use Insulin Human Winthrop Comb 25 
 
Do not use Insulin Human Winthrop Comb 25 
 
If you are allergic to insulin or any of the other ingredients of this medicine (listed in section 6).  
 
Warnings and precautions 
 
Talk to your doctor, pharmacist or nurse before using Insulin Human Winthrop Comb 25. 
Follow closely the instructions for dosage, monitoring (blood and urine tests), diet and physical 
activity (physical work and exercise) as discussed with your doctor. 
 
If you are allergic to this medicine or to animal insulins, talk to your doctor. 
 
Special patient groups 
If you have liver or kidneys problems or if you are elderly, speak to your doctor as you may need a 
lower dose. 
 

 

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Travel 
Before travelling, consult your doctor. You may need to talk about 
- the availability of your insulin in the country you are visiting, 
- supplies of insulin, injection syringes etc., 
- correct storage of your insulin while travelling, 
- timing of meals and insulin administration while travelling, 
- the possible effects of changing to different time zones, 
- possible new health risks in the countries to be visited, 
- what you should do in emergency situations when you feel unwell or become ill. 
 
Illnesses and injuries 
In the following situations, the management of your diabetes may require a lot of care: 
- If you are ill or have a major injury then your blood sugar level may increase (hyperglycaemia).  
- If you are not eating enough, your blood sugar level may become too low (hypoglycaemia).  
In most cases you will need a doctor. Make sure that you contact a doctor early.  
 
If you have type 1 diabetes (insulin dependent diabetes mellitus), do not stop your insulin and 
continue to get enough carbohydrates. Always tell people who are caring for you or treating you that 
you require insulin. 
 
Some patients with long-standing type 2 diabetes mellitus and heart disease or previous stroke who 
were treated with pioglitazone and insulin experienced the development of heart failure. Inform your 
doctor as soon as possible if you experience signs of heart failure such as unusual shortness of breath 
or rapid increase in weight or localised swelling (oedema). 
 
Other medicines and Insulin Human Winthrop Comb 25 
 
Some medicines cause changes in the blood sugar level (decrease, increase or both depending on the 
situation). In each case, it may be necessary to adjust your insulin dosage to avoid blood sugar levels 
that are either too low or too high. Be careful when you start or stop taking another medicine. 
 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines. Before taking a medicine ask your doctor if it can affect your blood sugar level, and what 
action, if any, you need to take. 
 
Medicines that may cause your blood sugar level to fall (hypoglycaemia) include:  
- all other medicines to treat diabetes,  
- angiotensin converting enzyme (ACE) inhibitors (used to treat certain heart conditions or high 

blood pressure),  
- disopyramide (used to treat certain heart conditions),  
- fluoxetine (used to treat depression),  
- fibrates (used to lower high levels of blood lipids),  
- monoamine oxidase (MAO) inhibitors (used to treat depression),  
- pentoxifylline, propoxyphene, salicylates (such as aspirin, used to relieve pain and lower fever), 
- sulfonamide antibiotics. 
 
Medicines that may cause your blood sugar level to rise (hyperglycaemia) include:  
- corticosteroids (such as "cortisone", used to treat inflammation),  
- danazol (medicine acting on ovulation),  
- diazoxide (used to treat high blood pressure),  
- diuretics (used to treat high blood pressure or excessive fluid retention),  
- glucagon (pancreas hormone used to treat severe hypoglycaemia),  
- isoniazid (used to treat tuberculosis),  
- oestrogens and progestogens (such as in the contraceptive pill used for birth control),  
- phenothiazine derivatives (used to treat psychiatric disorders),  
- somatropin (growth hormone),  

 

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- sympathomimetic medicines (such as epinephrine [adrenaline] or salbutamol, terbutaline used to 
treat asthma), 

- thyroid hormones (used to treat the thyroid gland disorders), 
- protease inhibitors (used to treat HIV), 
- atypical antipsychotic medicines (such as olanzapine and clozapine). 
 
Your blood sugar level may either rise or fall if you take:  
- beta-blockers (used to treat high blood pressure),  
- clonidine (used to treat high blood pressure), 
- lithium salts (used to treat psychiatric disorders).  
Pentamidine (used to treat some infections caused by parasites) may cause hypoglycaemia which may 
sometimes be followed by hyperglycaemia. 
 
Beta-blockers like other sympatholytic medicines (such as clonidine, guanethidine, and reserpine) may 
weaken or suppress entirely the first warning symptoms which help you to recognise a 
hypoglycaemia. 
 
If you are not sure whether you are taking one of those medicines ask your doctor or pharmacist. 
 
Insulin Human Winthrop Comb 25 with alcohol 
 
Your blood sugar levels may either rise or fall if you drink alcohol. 
 
Pregnancy and breast-feeding 
 
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor or pharmacist for advice before taking this medicine. 
 
Inform your doctor if you are planning to become pregnant, or if you are already pregnant. Your 
insulin dosage may need to be changed during pregnancy and after giving birth. Particularly careful 
control of your diabetes, and prevention of hypoglycaemia, is important for the health of your baby.  
 
If you are breast-feeding consult your doctor as you may require adjustments in your insulin doses and 
your diet. 
 
Driving and using machines 
 
Your ability to concentrate or react may be reduced if: 
- you have hypoglycaemia (low blood sugar levels), 
- you have hyperglycaemia (high blood sugar levels), 
- you have problems with your sight.  
Keep this possible problem in mind in all situations where you might put yourself and others at risk 
(such as driving a car or using machines). You should contact your doctor for advice on driving if: 
- you have frequent episodes of hypoglycaemia, 
- the first warning symptoms which help you to recognise hypoglycaemia are reduced or absent. 
 
Important information about some of the ingredients of Insulin Human Winthrop Comb 25  
 
This medicine contains less than 1 mmol (23 mg) sodium per dose, i.e. it is essentially ‘sodium-free’. 
 
 

 

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3. How to use Insulin Human Winthrop Comb 25 
 
Dose 
 
Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor 
or pharmacist if you are not sure. 
 
Based on your life-style and the results of your blood sugar (glucose) tests, your doctor will 
- determine how much Insulin Human Winthrop Comb 25 per day you will need, 
- tell you when to check your blood sugar level, and whether you need to carry out urine tests, 
- tell you when you may need to inject a higher or lower dose of Insulin Human Winthrop 

Comb 25. 
 
Many factors may influence your blood sugar level. You should know these factors so that you are 
able to react correctly to changes in your blood sugar level and to prevent it from becoming too high 
or too low. See the box at the end of this leaflet for further information. 
 
Frequency of administration 
 
Insulin Human Winthrop Comb 25 is injected under the skin 30 to 45 minutes before a meal.  
 
Method of administration 
 
Insulin Human Winthrop Comb 25 is a fluid (suspension) for injection under the skin. 
 
Do NOT inject Insulin Human Winthrop Comb 25 into a vein (blood vessel). 
 
Your doctor will show you in which area of the skin you should inject your insulin. With each 
injection, change the puncture site within the particular area of skin that you are using. 
 
Do not use it in insulin pumps or other infusion pumps - special insulin preparations are available for 
use in such devices. 
 
How to handle the vials 
 
Insulin Human Winthrop Comb 25 contains 100 IU insulin per ml. Only injection syringes designed 
for this insulin concentration (100 IU per ml) must be used. The injection syringes must not contain 
any other medicines or traces of medicines (such as traces of heparin). 
 
Before the first withdrawal of insulin you must remove the safety tear-off cap on the vial. 
 
Mix the insulin well immediately before each injection. This is best done by rolling the vial tilted 
between the palms of the hands. Do not shake the vial vigorously as this could damage the insulin and 
cause froth to form. Froth can make it difficult for you to measure the correct dose. 
 
After mixing, the suspension must have a uniform milky-white appearance. It must not be used if it 
remains clear or if, for example, clumps, flakes, particles or anything similar are in the suspension or 
on the sides or bottom of the vial. A new vial with a uniform suspension on mixing must then be used. 
 
Always use a new vial must also be used if you notice that your blood sugar control is unexpectedly 
getting worse. This is because the insulin may have lost some of its effectiveness. If you think you 
may have a problem with your insulin, have it checked by your doctor or pharmacist. 
 

 

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Special care before injection 
 
Before injection remove any air bubbles. Make sure that neither alcohol nor other disinfectants or 
other substances contaminate the insulin. Do not mix insulin with any other medicine except with 
insulin human preparations as detailed below. 
 
Insulin Human Winthrop Comb 25 may be mixed with all insulin human preparations, EXCEPT those 
specially designed for use in insulin pumps. Also, it must NOT be mixed with animal source insulins 
or insulin analogues. 
 
Your doctor will tell you if you have to mix insulin human preparations. If you need to inject a 
mixture, draw the other insulin into the injection syringe before Insulin Human Winthrop Comb 25. 
Inject as soon as you have mixed them. Do not mix insulins of different strengths (for example 100 IU 
per ml and 40 IU per ml). 
 
If you use more Insulin Human Winthrop Comb 25 than you should 
- If you have injected too much Insulin Human Winthrop Comb 25, your blood sugar level 

may become too low (hypoglycaemia). Check your blood sugar frequently. In general, to 
prevent hypoglycaemia you must eat more food and monitor your blood sugar. For information 
on the treatment of hypoglycaemia, see box at the end of this leaflet. 

 
If you forget to use Insulin Human Winthrop Comb 25 
- If you have missed a dose of Insulin Human Winthrop Comb 25 or if you have not injected 

enough insulin, your blood sugar level may become too high (hyperglycaemia). Check your 
blood sugar frequently. For information on the treatment of hyperglycaemia, see box at the end 
of this leaflet. 

 
- Do not take a double dose to make up for a forgotten dose. 
 
If you stop using Insulin Human Winthrop Comb 25 
This could lead to severe hyperglycaemia (very high blood sugar) and ketoacidosis (build-up of acid 
in the blood because the body is breaking down fat instead of sugar). Do not stop Insulin Human 
Winthrop Comb 25 without speaking to a doctor, who will tell you what needs to be done. 
 
If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse. 
 
Insulin Mix-ups 
 
You must always check the insulin label before each injection to avoid mix-ups between Insulin 
Human Winthrop Comb 25 and other insulins.  
 
 
4. Possible side effects 
 
Like all medicines, Insulin Human Winthrop Comb 25 can cause side effects, although not everybody 
gets them. 
 
The most frequent side effect is hypoglycaemia (low blood sugar). The specific frequency cannot be 
estimated from available data (frequency not known). Serious hypoglycaemia may cause a heart attack 
or brain damage and may be life-threatening. For further information on the side effects of low blood 
sugar or high blood sugar, see the box at the end of this leaflet. 
 
Severe allergic reactions to insulin may occur which may become life-threatening. Such reactions to 
insulin or to the excipients can cause large-scale skin reactions (rash and itching all over the body); 
severe swelling of skin or mucous membranes (angiooedema), shortness of breath, a fall in blood 
pressure with rapid heart beat and sweating. Frequency of these reactions caanot be estimated from 
available data. 

 

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Side effects reported commonly (may affect up to 1 in 10 people) 
• Oedema 
Insulin treatment may cause temporary build-up of water in the body with swelling in the calves and 
ankles. 
• Injection site reactions 
 
Side effects reported uncommonly (may affect up to 1 in 100 people) 
• Severe allergic reaction with low blood pressure (shock) 
• Injection site urticaria (itchy rash) 
 
Other side effects include (frequency cannot be estimated from the available data) 
• Sodium retention 
• Eye reactions 
A marked change (improvement or worsening) in your blood sugar control can disturb your vision 
temporarily. If you have proliferative retinopathy (an eye disease related to diabetes) severe 
hypoglycaemic attacks may cause temporary loss of vision.  
• Skin changes at the injection site (lipodystrophy) 
If you inject your insulin too often at the same skin site, fatty tissue under the skin at this site may 
either shrink or thicken. Insulin that you inject in such a site may not work very well. Changing the 
injection site with each injection may help to prevent such skin changes. 
• Skin and allergic reactions 
Other mild reactions at the injection site (such as injection site redness, unusually intense pain on 
injection site, itching, injection site swelling or injection site inflammation) may occur. They can also 
spread around the injection site. Most minor reactions to insulins usually resolve in a few days to a 
few weeks. 
 
Insulin treatment can cause the body to produce antibodies to insulin (substances that act against 
insulin). However, only very rarely, this will require a change to your insulin dosage. 
 
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side 
effects not listed in this leaflet. 
 
 
5. How to store Insulin Human Winthrop Comb 25 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date which is stated on the carton and on the label of the vial 
after “EXP”. The expiry date refers to the last day of that month. 
 
Unopened vials 
Store in a refrigerator (2°C – 8°C). Do not freeze. Do not put Insulin Human Winthrop Comb 25 next 
to the freezer compartment or a freezer pack. Keep the vial in the outer carton in order to protect from 
light. 
 
Opened vials 
Once in-use, the vial may be stored for a maximum of 4 weeks in the outer carton not above 25°C and 
away from direct heat (for example next to a heating unit) or direct light (direct sunlight or next to a 
lamp). Do not use the vial after this time period. It is recommended that the date of the first use be 
noted on the label. 
 
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment. 
 
 

 

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6. Contents of the pack and other information 
 
What Insulin Human Winthrop Comb 25 contains 
- The active substance is insulin human. One ml of Insulin Human Winthrop Comb 25 contains 

100 IU (International Units) of the active substance insulin human. 25% of the insulin is 
dissolved in water; the other 75% is present as tiny crystals of insulin protamine. 

- The other ingredients are: protamine sulphate, metacresol, phenol, zinc chloride, sodium 
dihydrogen phosphate dihydrate, glycerol, sodium hydroxide (see section 2 under “Important 
information about some of the ingredients of Insulin Human Winthrop Comb 25”), hydrochloric 
acid (for pH adjustment) and water for injections. 

 
What Insulin Human Winthrop Comb 25 looks like and contents of the pack 
After mixing, Insulin Human Winthrop Comb 25 is a uniformly milky fluid (suspension for injection), 
with no clumps, particles or flocculation visible. 
 
Insulin Human Winthrop Comb 25 is supplied in vials containing 5 ml suspension (500 IU). Packs of 
1 and 5 vials of 5 ml are available. Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder and Manufacturer 
Sanofi-Aventis Deutschland GmbH 
D-65926 Frankfurt am Main 
Germany 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
Sanofi Belgium 
Tél/Tel: +32 (0)2 710 54 00 
 

Lietuva 
UAB «SANOFI-AVENTIS LIETUVA» 
Tel: +370 5 2755224 
 

България 
sanofi-aventis Bulgaria EOOD 
Тел.: +359 (0)2 970 53 00 
 

Luxembourg/Luxemburg 
Sanofi Belgium  
Tél/Tel: +32 (0)2 710 54 00 (Belgique/Belgien) 
 

Česká republika 
sanofi-aventis, s.r.o. 
Tel: +420 233 086 111 
 

Magyarország 
SANOFI-AVENTIS Zrt. 
Tel.: +36 1 505 0050 
 

Danmark 
sanofi-aventis Denmark A/S 
Tlf: +45 45 16 70 00 
 

Malta 
Sanofi Malta Ltd. 
Tel: +356 21493022 
 

Deutschland 
Zentiva Pharma GmbH 
Tel: +49 (0)180 20 200 10 
 

Nederland 
sanofi-aventis Netherlands B.V. 
Tel: +31 (0)182 557 755 
 

Eesti 
sanofi-aventis Estonia OÜ 
Tel: +372 627 34 88 
 

Norge 
Aventis Pharma Norge AS 
Tlf: +47 67 10 71 00 
 

Ελλάδα 
sanofi-aventis AEBE 
Τηλ: +30 210 900 16 00 
 

Österreich 
sanofi-aventis GmbH 
Tel: +43 1 80 185 – 0 
 

 

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España 
sanofi-aventis, S.A. 
Tel: +34 93 485 94 00 
 

Polska 
sanofi-aventis Sp . z o.o. 
Tel.: +48 22 280 00 00 
 

France 
sanofi-aventis France 
Tél: 0 800 222 555 
Appel depuis l’étranger : +33 1 57 63 23 23 
 

Portugal 
Sanofi - Produtos Farmacêuticos, Lda. 
Tel: +351 21 35 89 400 
 

Hrvatska 
sanofi-aventis Croatia d.o.o. 
Tel: +385 1 600 34 00 

România 
Sanofi Romania SRL 
Tel: +40 (0) 21 317 31 36 
 

Ireland 
sanofi-aventis Ireland Ltd. T/A SANOFI 
Tel: +353 (0) 1 403 56 00 
 

Slovenija 
sanofi-aventis d.o.o. 
Tel: +386 1 560 48 00 
 

Ísland 
Vistor hf. 
Sími: +354 535 7000 
 

Slovenská republika 
sanofi-aventis Pharma Slovakia s.r.o. 
Tel: +421 2 33 100 100 
 

Italia 
Sanofi S.p.A. 
Tel: 800 13 12 12 (domande di tipo tecnico)  
800 536389 (altre domande) 
 

Suomi/Finland 
Sanofi Oy 
Puh/Tel: +358 (0) 201 200 300 
 

Κύπρος 
sanofi-aventis Cyprus Ltd. 
Τηλ: +357 22 871600 
 

Sverige 
Sanofi AB 
Tel: +46 (0)8 634 50 00 
 

Latvija 
sanofi-aventis Latvia SIA 
Tel: +371 67 33 24 51 
 

United Kingdom 
Sanofi 
Tel: +44 (0) 845 372 7101 
 

 
This leaflet was last revised in {date} 
 
 
Other source of information 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu/ 
 
 
 
 

HYPERGLYCAEMIA AND HYPOGLYCAEMIA 
 

Always carry some sugar (at least 20 grams) with you. 
Carry some information with you to show you are diabetic. 

 
HYPERGLYCAEMIA (high blood sugar levels) 

 
If your blood sugar is too high (hyperglycaemia), you may not have injected enough insulin. 
 
Why does hyperglycaemia occur? 
 
Examples include: 

 

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- you have not injected your insulin or not injected enough, or if it has become less effective, for 
example through incorrect storage, 

- you are doing less exercise than usual, you are under stress (emotional distress, excitement), or 
you have an injury, operation, infection or fever, 

- you are taking or have taken certain other medicines (see section 2, "Other medicines and 
Insulin Human Winthrop Comb 25"). 

 
Warning symptoms of hyperglycaemia 
 
Thirst, increased need to urinate, tiredness, dry skin, reddening of the face, loss of appetite, low blood 
pressure, fast heart beat, and glucose and ketone bodies in urine. Stomach pain, fast and deep 
breathing, sleepiness or even loss of consciousness may be signs of a serious condition (ketoacidosis) 
resulting from lack of insulin. 
 
What should you do if you experience hyperglycaemia 
 
Test your blood sugar level and your urine for ketones as soon as any of the above symptoms 
occur. Severe hyperglycaemia or ketoacidosis must always be treated by a doctor, normally in a 
hospital. 
 

HYPOGLYCAEMIA (low blood sugar levels) 
 
If your blood sugar level falls too much you may become unconscious. Serious hypoglycaemia may 
cause a heart attack or brain damage and may be life-threatening. You normally should be able to 
recognise when your blood sugar is falling too much so that you can take the right actions. 
 
Why does hypoglycaemia occur? 
 
Examples include: 
- you inject too much insulin, 
- you miss meals or delay them, 
- you do not eat enough, or eat food containing less carbohydrate than normal (sugar and 

substances similar to sugar are called carbohydrates; however, artificial sweeteners are NOT 
carbohydrates), 

- you lose carbohydrates due to vomiting or diarrhoea, 
- you drink alcohol, particularly if you are not eating much, 
- you are doing more exercise than usual or a different type of physical activity, 
- you are recovering from an injury or operation or other stress, 
- you are recovering from an illness or from fever, 
- you are taking or have stopped taking certain other medicines (see section 2, "Other medicines 

and Insulin Human Winthrop Comb 25"). 
 
Hypoglycaemia is also more likely to occur if: 
- you have just begun insulin treatment or changed to another insulin preparation, 
- your blood sugar levels are almost normal or are unstable, 
- you change the area of skin where you inject insulin (for example from the thigh to the upper 

arm), 
- you suffer from severe kidney or liver disease, or some other disease such as hypothyroidism. 
 
Warning symptoms of hypoglycaemia 
 
- In your body 
Examples of symptoms that tell you that your blood sugar level is falling too much or too fast: 
sweating, clammy skin, anxiety, fast heart beat, high blood pressure, palpitations and irregular 
heartbeat. These symptoms often develop before the symptoms of a low sugar level in the brain. 
 
- In your brain 

 

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Examples of symptoms that indicate a low sugar level in the brain: headaches, intense hunger, nausea, 
vomiting, tiredness, sleepiness, sleep disturbances, restlessness, aggressive behaviour, lapses in 
concentration, impaired reactions, depression, confusion, speech disturbances (sometimes total loss of 
speech), visual disorders, trembling, paralysis, tingling sensations (paraesthesia), numbness and 
tingling sensations in the area of the mouth, dizziness, loss of self-control, inability to look after 
yourself, convulsions, loss of consciousness. 
 
The first symptoms which alert you to hypoglycaemia ("warning symptoms") may change, be weaker 
or may be missing altogether if 
- you are elderly, if you have had diabetes for a long time or if you suffer from a certain type of 

nervous disease (diabetic autonomic neuropathy), 
- you have recently suffered hypoglycaemia (for example the day before) or if it develops slowly, 
- you have almost normal or, at least, greatly improved blood sugar levels, 
- you have recently changed from an animal insulin to a human insulin such as Insulin Human 

Winthrop, 
- you are taking or have taken certain other medicines (see section 2, "Other medicines and 

Insulin Human Winthrop Comb 25"). 
 
In such a case, you may develop severe hypoglycaemia (and even faint) before you are aware of the 
problem. Be familiar with your warning symptoms. If necessary, more frequent blood sugar testing 
can help to identify mild hypoglycaemic episodes that may otherwise be overlooked. If you are not 
confident about recognising your warning symptoms, avoid situations (such as driving a car) in which 
you or others would be put at risk by hypoglycaemia. 
 
What should you do if you experience hypoglycaemia 
 
1. Do not inject insulin. Immediately take about 10 to 20 g sugar, such as glucose, sugar cubes or a 

sugar-sweetened beverage. Caution: Artificial sweeteners and foods with artificial sweeteners 
(such as diet drinks) are of no help in treating hypoglycaemia. 

2. Then eat something that has a long-acting effect in raising your blood sugar (such as bread or 
pasta). Your doctor or nurse should have discussed this with you previously. 

3. If the hypoglycaemia comes back again take another 10 to 20 g sugar. 
4. Speak to a doctor immediately if you are not able to control the hypoglycaemia or if it recurs. 
 
Tell your relatives, friends and close colleagues the following: 
If you are not able to swallow or if you are unconscious, you will require an injection of glucose or 
glucagon (a medicine which increases blood sugar). These injections are justified even if it is not 
certain that you have hypoglycaemia. 
 
It is advisable to test your blood sugar immediately after taking glucose to check that you really have 
hypoglycaemia. 

 
 

 

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Package leaflet: Information for the user 

 
Insulin Human Winthrop Comb 25 40 IU/ml suspension for injection in a vial 

Insulin human 
 
 
Read all of this leaflet carefully before you start using this medicine because it contains 
important information for you. 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor, pharmacist or nurse. 
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours. 
- If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible 

side effects not listed in this leaflet. 
 
What is in this leaflet: 
1. What Insulin Human Winthrop Comb 25 is and what it is used for 
2. What you need to know before you use Insulin Human Winthrop Comb 25 
3. How to use Insulin Human Winthrop Comb 25 
4. Possible side effects 
5. How to store Insulin Human Winthrop Comb 25 
6. Contents of the pack and other information 
 
 
1. What Insulin Human Winthrop Comb 25 is and what it is used for 
 
Insulin Human Winthrop Comb 25 contains the active substance insulin human which is made by a 
biotechnology process and is identical with the body's own insulin. 
 
Insulin Human Winthrop Comb 25 is an insulin preparation with a gradual onset and long duration of 
action.  
 
Insulin Human Winthrop Comb 25 is used to reduce high blood sugar in patients with diabetes 
mellitus who need treatment with insulin. Diabetes mellitus is a disease where your body does not 
produce enough insulin to control the level of blood sugar. 
 
 
2. What you need to know before you use Insulin Human Winthrop Comb 25 
 
Do not use Insulin Human Winthrop Comb 25 
 
If you are allergic to insulin or any of the other ingredients of this medicine (listed in section 6). 
 
Warnings and precautions 
 
Talk to your doctor, pharmacist or nurse before using Insulin Human Winthrop Comb 25. 
Follow closely the instructions for dosage, monitoring (blood and urine tests), diet and physical 
activity (physical work and exercise) as discussed with your doctor. 
 
If you are allergic to this medicine or to animal insulins, talk to your doctor. 
 
Special patient groups 
If you have liver or kidneys problems or if you are elderly, speak to your doctor as you may need a 
lower dose. 
 

 

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Travel 
Before travelling, consult your doctor. You may need to talk about 
- the availability of your insulin in the country you are visiting, 
- supplies of insulin, injection syringes etc., 
- correct storage of your insulin while travelling, 
- timing of meals and insulin administration while travelling, 
- the possible effects of changing to different time zones, 
- possible new health risks in the countries to be visited, 
- what you should do in emergency situations when you feel unwell or become ill. 
 
Illnesses and injuries 
In the following situations, the management of your diabetes may require a lot of care: 
- If you are ill or have a major injury then your blood sugar level may increase (hyperglycaemia).  
- If you are not eating enough, your blood sugar level may become too low (hypoglycaemia).  
In most cases you will need a doctor. Make sure that you contact a doctor early.  
 
If you have type 1 diabetes (insulin dependent diabetes mellitus), do not stop your insulin and 
continue to get enough carbohydrates. Always tell people who are caring for you or treating you that 
you require insulin. 
 
Some patients with long-standing type 2 diabetes mellitus and heart disease or previous stroke who 
were treated with pioglitazone and insulin experienced the development of heart failure. Inform your 
doctor as soon as possible if you experience signs of heart failure such as unusual shortness of breath 
or rapid increase in weight or localised swelling (oedema). 
 
Other medicines and Insulin Human Winthrop Comb 25 
 
Some medicines cause changes in the blood sugar level (decrease, increase or both depending on the 
situation). In each case, it may be necessary to adjust your insulin dosage to avoid blood sugar levels 
that are either too low or too high. Be careful when you start or stop taking another medicine. 
 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines. Before taking a medicine ask your doctor if it can affect your blood sugar level, and what 
action, if any, you need to take. 
 
Medicines that may cause your blood sugar level to fall (hypoglycaemia) include:  
- all other medicines to treat diabetes,  
- angiotensin converting enzyme (ACE) inhibitors (used to treat certain heart conditions or high 

blood pressure),  
- disopyramide (used to treat certain heart conditions),  
- fluoxetine (used to treat depression),  
- fibrates (used to lower high levels of blood lipids),  
- monoamine oxidase (MAO) inhibitors (used to treat depression),  
- pentoxifylline, propoxyphene, salicylates (such as aspirin, used to relieve pain and lower fever), 
- sulfonamide antibiotics. 
 
Medicines that may cause your blood sugar level to rise (hyperglycaemia) include:  
- corticosteroids (such as "cortisone", used to treat inflammation),  
- danazol (medicine acting on ovulation),  
- diazoxide (used to treat high blood pressure),  
- diuretics (used to treat high blood pressure or excessive fluid retention),  
- glucagon (pancreas hormone used to treat severe hypoglycaemia),  
- isoniazid (used to treat tuberculosis),  
- oestrogens and progestogens (such as in the contraceptive pill used for birth control),  
- phenothiazine derivatives (used to treat psychiatric disorders),  
- somatropin (growth hormone),  

 

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- sympathomimetic medicines (such as epinephrine [adrenaline] or salbutamol, terbutaline used to 
treat asthma), 

- thyroid hormones (used to treat the thyroid gland disorders), 
- protease inhibitors (used to treat HIV), 
- atypical antipsychotic medicines (such as olanzapine and clozapine). 
 
Your blood sugar level may either rise or fall if you take:  
- beta-blockers (used to treat high blood pressure),  
- clonidine (used to treat high blood pressure), 
- lithium salts (used to treat psychiatric disorders).  
Pentamidine (used to treat some infections caused by parasites) may cause hypoglycaemia which may 
sometimes be followed by hyperglycaemia. 
 
Beta-blockers like other sympatholytic medicines (such as clonidine, guanethidine, and reserpine) may 
weaken or suppress entirely the first warning symptoms which help you to recognise a 
hypoglycaemia. 
 
If you are not sure whether you are taking one of those medicines ask your doctor or pharmacist. 
 
Insulin Human Winthrop Comb 25 alcohol 
 
Your blood sugar levels may either rise or fall if you drink alcohol. 
 
Pregnancy and breast-feeding 
 
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor or pharmacist for advice before taking this medicine. 
 
Inform your doctor if you are planning to become pregnant, or if you are already pregnant. Your 
insulin dosage may need to be changed during pregnancy and after giving birth. Particularly careful 
control of your diabetes, and prevention of hypoglycaemia, is important for the health of your baby.  
 
If you are breast-feeding consult your doctor as you may require adjustments in your insulin doses and 
your diet. 
 
Driving and using machines 
 
Your ability to concentrate or react may be reduced if: 
- you have hypoglycaemia (low blood sugar levels), 
- you have hyperglycaemia (high blood sugar levels), 
- you have problems with your sight.  
Keep this possible problem in mind in all situations where you might put yourself and others at risk 
(such as driving a car or using machines). You should contact your doctor for advice on driving if: 
- you have frequent episodes of hypoglycaemia, 
- the first warning symptoms which help you to recognise hypoglycaemia are reduced or absent. 
 
Important information about some of the ingredients of Insulin Human Winthrop Comb 25  
 
This medicine contains less than 1 mmol (23 mg) sodium per dose, i.e. it is essentially ‘sodium-free’. 
 
 

 

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3. How to use Insulin Human Winthrop Comb 25 
 
Dose 
 
Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor 
or pharmacist if you are not sure. 
 
Based on your life-style and the results of your blood sugar (glucose) tests, your doctor will 
- determine how much Insulin Human Winthrop Comb 25 per day you will need, 
- tell you when to check your blood sugar level, and whether you need to carry out urine tests, 
- tell you when you may need to inject a higher or lower dose of Insulin Human Winthrop 

Comb 25. 
 
Many factors may influence your blood sugar level. You should know these factors so that you are 
able to react correctly to changes in your blood sugar level and to prevent it from becoming too high 
or too low. See the box at the end of this leaflet for further information. 
 
Frequency of administration 
 
Insulin Human Winthrop Comb 25 is injected under the skin 30 to 45 minutes before a meal.  
 
Method of administration 
 
Insulin Human Winthrop Comb 25 is a fluid (suspension) for injection under the skin. 
 
Do NOT inject Insulin Human Winthrop Comb 25 into a vein (blood vessel). 
 
Your doctor will show you in which area of the skin you should inject your insulin. With each 
injection, change the puncture site within the particular area of skin that you are using. 
 
Do not use it in insulin pumps or other infusion pumps – special insulin preparations are available for 
use in such devices. 
 
How to handle the vials 
 
Insulin Human Winthrop Comb 25 contains 40 IU insulin per ml. Only injection syringes designed for 
this insulin concentration (40 IU per ml) must be used. The injection syringes must not contain any 
other medicines or traces of medicines (such as traces of heparin). 
 
Before the first withdrawal of insulin you must remove the safety tear-off cap on the vial. 
 
Mix the insulin well immediately before each injection. This is best done by rolling the vial tilted 
between the palms of the hands. Do not shake the vial vigorously as this could damage the insulin and 
cause froth to form. Froth can make it difficult for you to measure the correct dose. 
 
After mixing, the suspension must have a uniform milky-white appearance. It must not be used if it 
remains clear or if, for example, clumps, flakes, particles or anything similar are in the suspension or 
on the sides or bottom of the vial. A new vial with a uniform suspension on mixing must then be used. 
 
Always use a new vial must also be used if you notice that your blood sugar control is unexpectedly 
getting worse. This is because the insulin may have lost some of its effectiveness. If you think you 
may have a problem with your insulin, have it checked by your doctor or pharmacist. 
 

 

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Special care before injection 
 
Before injection remove any air bubbles. Make sure that neither alcohol nor other disinfectants or 
other substances contaminate the insulin. Do not mix insulin with any other medicines except with 
insulin human preparations as detailed below. 
 
Insulin Human Winthrop Comb 25 may be mixed with all insulin human preparations, EXCEPT those 
specially designed for use in insulin pumps. Also, it must NOT be mixed with animal source insulins 
or insulin analogues. 
 
Your doctor will tell you if you have to mix insulin human preparations. If you need to inject a 
mixture, draw the other insulin into the injection syringe before Insulin Human Winthrop Comb 25. 
Inject as soon as you have mixed them. Do not mix insulins of different strengths (for example 100 IU 
per ml and 40 IU per ml). 
 
If you use more Insulin Human Winthrop Comb 25 than you should 
- If you have injected too much Insulin Human Winthrop Comb 25, your blood sugar level 

may become too low (hypoglycaemia). Check your blood sugar frequently. In general, to 
prevent hypoglycaemia you must eat more food and monitor your blood sugar. For information 
on the treatment of hypoglycaemia, see box at the end of this leaflet. 

 
If you forget to use Insulin HumaWinthrop Comb 25 
- If you have missed a dose of Insulin Human Winthrop Comb 25 or if you have not injected 

enough insulin, your blood sugar level may become too high (hyperglycaemia). Check your 
blood sugar frequently. For information on the treatment of hyperglycaemia, see box at the end of 
this leaflet. 

 
- Do not take a double dose to make up for a forgotten dose. 
 
If you stop using Insulin Human Winthrop Comb 25 
This could lead to severe hyperglycaemia (very high blood sugar) and ketoacidosis (build-up of acid 
in the blood because the body is breaking down fat instead of sugar). Do not stop Insulin Human 
Winthrop Comb 25 without speaking to a doctor, who will tell you what needs to be done. 
 
If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse. 
 
Insulin Mix-ups 
 
You must always check the insulin label before each injection to avoid mix-ups between Insulin 
Human Winthrop Comb 25 and other insulins.  
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
The most frequent side effect is hypoglycaemia (low blood sugar). The specific frequency cannot be 
estimated from available data (frequency not known). Serious hypoglycaemia may cause a heart attack 
or brain damage and may be life-threatening. For further information on the side effects of low blood 
sugar or high blood sugar, see the box at the end of this leaflet. 
 
Severe allergic reactions to insulin may occur which may become life-threatening. Such reactions to 
insulin or to the excipients can cause large-scale skin reactions (rash and itching all over the body); 
severe swelling of skin or mucous membranes (angiooedema), shortness of breath, a fall in blood 
pressure with rapid heart beat and sweating. Frequency of these reactions cannot be estimated from 
availabla data. 
 

 

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Side effects reported commonly (may affect up to 1 in 10 people) 
• Oedema 
Insulin treatment may cause temporary build-up of water in the body with swelling in the calves and 
ankles. 
• Injection site reactions 
 
Side effects reported uncommonly (may affect up to 1 in 100 people) 
• Severe allergic reaction with low blood pressure (shock) 
• Injection site urticaria (itchy rash) 
 
Other side effects include (frequency cannot be estimated from the available data) 
• Sodium retention 
• Eye reactions 
A marked change (improvement or worsening) in your blood sugar control can disturb your vision 
temporarily. If you have proliferative retinopathy (an eye disease related to diabetes) severe 
hypoglycaemic attacks may cause temporary loss of vision. 
• Skin changes at the injection site (lipodystrophy) 
If you inject your insulin too often at the same skin site, fatty tissue under the skin at this site may 
either shrink or thicken. Insulin that you inject in such a site may not work very well. Changing the 
injection site with each injection may help to prevent such skin changes. 
• Skin and allergic reactions 
Other mild reactions at the injection site (such as injection site redness, unusually intense pain on 
injection site, itching, injection site swelling or injection site inflammation) may occur. They can also 
spread around the injection site. Most minor reactions to insulins usually resolve in a few days to a 
few weeks. 
 
Insulin treatment can cause the body to produce antibodies to insulin (substances that act against 
insulin). However, only very rarely, this will require a change to your insulin dosage. 
 
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side 
effects not listed in this leaflet. 
 
 
5. How to store Insulin Human Winthrop Comb 25 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date which is stated on the carton and on the label of the vial 
after “EXP”. The expiry date refers to the last day of that month. 
 
Unopened vials 
Store in a refrigerator (2°C - 8°C). Do not freeze. Do not put Insulin Human Winthrop Comb 25 next 
to the freezer compartment or a freezer pack. Keep the vial in the outer carton in order to protect from 
light. 
 
Opened vials 
Once in-use, the vial may be stored for a maximum of 4 weeks in the outer carton not above 25°C and 
away from direct heat (for example next to a heating unit) or direct light (direct sunlight or next to a 
lamp). Do not use the vial after this time period. It is recommended that the date of the first use be 
noted on the label. 
 
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment. 
 
 

 

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6. Contents of the pack and other information 
 
What Insulin Human Winthrop Comb 25 contains 
- The active substance is insulin human. One ml of Insulin Human Winthrop Comb 25 contains 

40 IU (International Units) of the active substance insulin human. 25% of the insulin is 
dissolved in water; the other 75% is present as tiny crystals of insulin protamine. 

- The other ingredients are: protamine sulphate, metacresol, phenol, zinc chloride, sodium 
dihydrogen phosphate dihydrate, glycerol, sodium hydroxide (see section 2 under “Important 
information about some of the ingredients of Insulin Human Winthrop Comb 25”), hydrochloric 
acid (for pH adjustment) and water for injections. 

 
What Insulin Human Winthrop Comb 25 looks like and contents of the pack 
After mixing, Insulin Human Winthrop Comb 25 is a uniformly milky fluid (suspension for injection), 
with no clumps, particles or flocculation visible. 
 
Insulin Human Winthrop Comb 25 is supplied in vials containing 10 ml suspension (400 IU). Packs of 
1 and 5 vials of 10 ml are available. Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder and Manufacturer 
Sanofi-Aventis Deutschland GmbH 
D-65926 Frankfurt am Main 
Germany 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
Sanofi Belgium 
Tél/Tel: +32 (0)2 710 54 00 
 

Lietuva 
UAB «SANOFI-AVENTIS LIETUVA» 
Tel: +370 5 2755224 
 

България 
sanofi-aventis Bulgaria EOOD 
Тел.: +359 (0)2 970 53 00 
 

Luxembourg/Luxemburg 
Sanofi Belgium  
Tél/Tel: +32 (0)2 710 54 00 (Belgique/Belgien) 
 

Česká republika 
sanofi-aventis, s.r.o. 
Tel: +420 233 086 111 
 

Magyarország 
SANOFI-AVENTIS Zrt. 
Tel.: +36 1 505 0050 
 

Danmark 
sanofi-aventis Denmark A/S 
Tlf: +45 45 16 70 00 
 

Malta 
Sanofi Malta Ltd. 
Tel: +356 21493022 
 

Deutschland 
Zentiva Pharma GmbH 
Tel: +49 (0)180 20 200 10 
 

Nederland 
sanofi-aventis Netherlands B.V. 
Tel: +31 (0)182 557 755 
 

Eesti 
sanofi-aventis Estonia OÜ 
Tel: +372 627 34 88 
 

Norge 
Aventis Pharma Norge AS 
Tlf: +47 67 10 71 00 
 

Ελλάδα 
sanofi-aventis AEBE 
Τηλ: +30 210 900 16 00 
 

Österreich 
sanofi-aventis GmbH 
Tel: +43 1 80 185 – 0 
 

 

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España 
sanofi-aventis, S.A. 
Tel: +34 93 485 94 00 
 

Polska 
sanofi-aventis Sp. z o.o. 
Tel.: +48 22 280 00 00 
 

France 
sanofi-aventis France 
Tél: 0 800 222 555 
Appel depuis l’étranger : +33 1 57 63 23 23 
 

Portugal 
Sanofi - Produtos Farmacêuticos, Lda. 
Tel: +351 21 35 89 400 
 

Hrvatska 
sanofi-aventis Croatia d.o.o. 
Tel: +385 1 600 34 00 

România 
Sanofi Romania SRL 
Tel: +40 (0) 21 317 31 36 
 

Ireland 
sanofi-aventis Ireland Ltd. T/A SANOFI 
Tel: +353 (0) 1 403 56 00 
 

Slovenija 
sanofi-aventis d.o.o. 
Tel: +386 1 560 48 00 
 

Ísland 
Vistor hf. 
Sími: +354 535 7000 
 

Slovenská republika 
sanofi-aventis Pharma Slovakia s.r.o. 
Tel: +421 2 33 100 100 
 

Italia 
Sanofi S.p.A. 
Tel: 800 13 12 12 (domande di tipo tecnico)  
800 536389 (altre domande) 
 

Suomi/Finland 
Sanofi Oy 
Puh/Tel: +358 (0) 201 200 300 
 

Κύπρος 
sanofi-aventis Cyprus Ltd. 
Τηλ: +357 22 871600 
 

Sverige 
Sanofi AB 
Tel: +46 (0)8 634 50 00 
 

Latvija 
sanofi-aventis Latvia SIA 
Tel: +371 67 33 24 51 
 

United Kingdom 
Sanofi 
Tel: +44 (0) 845 372 7101 
 

 
This leaflet was last revised in {date} 
 
 
Other source of information 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu/ 
 
 
 
 

HYPERGLYCAEMIA AND HYPOGLYCAEMIA 
 

Always carry some sugar (at least 20 grams) with you. 
Carry some information with you to show you are diabetic. 

 
HYPERGLYCAEMIA (high blood sugar levels) 

 
If your blood sugar is too high (hyperglycaemia), you may not have injected enough insulin. 
 
Why does hyperglycaemia occur? 
 
Examples include: 

 

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- you have not injected your insulin or not injected enough, or if it has become less effective, for 
example through incorrect storage, 

- you are doing less exercise than usual, you are under stress (emotional distress, excitement), or 
you have an injury, operation, infection or fever, 

- you are taking or have taken certain other medicines (see section 2, "Other medicines and 
Insulin Human Winthrop comb 25"). 

 
Warning symptoms of hyperglycaemia 
 
Thirst, increased need to urinate, tiredness, dry skin, reddening of the face, loss of appetite, low blood 
pressure, fast heart beat, and glucose and ketone bodies in urine. Stomach pain, fast and deep 
breathing, sleepiness or even loss of consciousness may be signs of a serious condition (ketoacidosis) 
resulting from lack of insulin. 
 
What should you do if you experience hyperglycaemia 
 
Test your blood sugar level and your urine for ketones as soon as any of the above symptoms 
occur. Severe hyperglycaemia or ketoacidosis must always be treated by a doctor, normally in a 
hospital. 
 

HYPOGLYCAEMIA (low blood sugar levels) 
 
If your blood sugar level falls too much you may become unconscious. Serious hypoglycaemia may 
cause a heart attack or brain damage and may be life-threatening. You normally should be able to 
recognise when your blood sugar is falling too much so that you can take the right actions. 
 
Why does hypoglycaemia occur? 
 
Examples include: 
- you inject too much insulin, 
- you miss meals or delay them, 
- you do not eat enough, or eat food containing less carbohydrate than normal (sugar and 

substances similar to sugar are called carbohydrates; however, artificial sweeteners are NOT 
carbohydrates), 

- you lose carbohydrates due to vomiting or diarrhoea, 
- you drink alcohol, particularly if you are not eating much, 
- you are doing more exercise than usual or a different type of physical activity, 
- you are recovering from an injury or operation or other stress, 
- you are recovering from an illness or from fever, 
- you are taking or have stopped taking certain other medicines (see section 2, "Other medicines 

and Insulin Human Winthrop Comb 25"). 
 
Hypoglycaemia is also more likely to occur if: 
- you have just begun insulin treatment or changed to another insulin preparation, 
- your blood sugar levels are almost normal or are unstable, 
- you change the area of skin where you inject insulin (for example from the thigh to the upper 

arm), 
- you suffer from severe kidney or liver disease, or some other disease such as hypothyroidism. 
 
Warning symptoms of hypoglycaemia 
 
- In your body 
Examples of symptoms that tell you that your blood sugar level is falling too much or too fast: 
sweating, clammy skin, anxiety, fast heart beat, high blood pressure, palpitations and irregular 
heartbeat. These symptoms often develop before the symptoms of a low sugar level in the brain. 
 
- In your brain 

 

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Examples of symptoms that indicate a low sugar level in the brain: headaches, intense hunger, nausea, 
vomiting, tiredness, sleepiness, sleep disturbances, restlessness, aggressive behaviour, lapses in 
concentration, impaired reactions, depression, confusion, speech disturbances (sometimes total loss of 
speech), visual disorders, trembling, paralysis, tingling sensations (paraesthesia), numbness and 
tingling sensations in the area of the mouth, dizziness, loss of self-control, inability to look after 
yourself, convulsions, loss of consciousness. 
 
The first symptoms which alert you to hypoglycaemia ("warning symptoms") may change, be weaker 
or may be missing altogether if 
- you are elderly, if you have had diabetes for a long time or if you suffer from a certain type of 

nervous disease (diabetic autonomic neuropathy), 
- you have recently suffered hypoglycaemia (for example the day before) or if it develops slowly, 
- you have almost normal or, at least, greatly improved blood sugar levels, 
- you have recently changed from an animal insulin to a human insulin such as Insulin Human 

Winthrop, 
- you are taking or have taken certain other medicines (see section 2, "Other medicines and 

Insulin Human Winthrop Comb 25"). 
 
In such a case, you may develop severe hypoglycaemia (and even faint) before you are aware of the 
problem. Be familiar with your warning symptoms. If necessary, more frequent blood sugar testing 
can help to identify mild hypoglycaemic episodes that may otherwise be overlooked. If you are not 
confident about recognising your warning symptoms, avoid situations (such as driving a car) in which 
you or others would be put at risk by hypoglycaemia. 
 
What should you do if you experience hypoglycaemia 
 
1. Do not inject insulin. Immediately take about 10 to 20 g sugar, such as glucose, sugar cubes or a 

sugar-sweetened beverage. Caution: Artificial sweeteners and foods with artificial sweeteners 
(such as diet drinks) are of no help in treating hypoglycaemia. 

2. Then eat something that has a long-acting effect in raising your blood sugar (such as bread or 
pasta). Your doctor or nurse should have discussed this with you previously. 

3. If the hypoglycaemia comes back again take another 10 to 20 g sugar. 
4. Speak to a doctor immediately if you are not able to control the hypoglycaemia or if it recurs. 
 
Tell your relatives, friends and close colleagues the following: 
If you are not able to swallow or if you are unconscious, you will require an injection of glucose or 
glucagon (a medicine which increases blood sugar). These injections are justified even if it is not 
certain that you have hypoglycaemia. 
 
It is advisable to test your blood sugar immediately after taking glucose to check that you really have 
hypoglycaemia. 
 
 

 

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Package leaflet: Information for the user 

 
Insulin Human Winthrop Comb 25 100 IU/ml suspension for injection in a cartridge 

Insulin human 
 
 
Read all of this leaflet carefully before you start using this medicine because it contains 
important information for you. The instructions for using the insulin pen are provided with 
your insulin pen. Refer to them before using your medicine. 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor, pharmacist or nurse. 
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours. 
- If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible 

side effects not listed in this leaflet. 
 
What is in this leaflet: 
1. What Insulin Human Winthrop Comb 25 is and what it is used for 
2. What you need to know before you use Insulin Human Winthrop Comb 25 
3. How to use Insulin Human Winthrop Comb 25 
4. Possible side effects 
5. How to store Insulin Human Winthrop Comb 25 
6. Contents of the pack and other information 
 
 
1. What Insulin Human Winthrop Comb 25 is and what it is used for 
 
Insulin Human Winthrop Comb 25 contains the active substance insulin human which is made by a 
biotechnology process and is identical with the body's own insulin. 
 
Insulin Human Winthrop Comb 25 is an insulin preparation with a gradual onset and long duration of 
action.  
 
Insulin Human Winthrop Comb 25 is used to reduce high blood sugar in patients with diabetes 
mellitus who need treatment with insulin. Diabetes mellitus is a disease where your body does not 
produce enough insulin to control the level of blood sugar. 
 
 
2. What you need to know before you use Insulin Human Winthrop Comb 25 
 
Do not use Insulin Human Winthrop Comb 25 
 

If you are allergic to insulin or any of the other ingredients of this medicine (listed in section 6).  
 
Warnings and precautions 
 
Talk to your doctor, pharmacist or nurse before using Insulin Human Winthrop Comb 25. 
Follow closely the instructions for dosage, monitoring (blood and urine tests), diet and physical 
activity (physical work and exercise) as discussed with your doctor. 
 
If you are allergic to this medicine or to animal insulins, talk to your doctor. 
 
Special patient groups 
If you have liver or kidneys problems or if you are elderly, speak to your doctor as you may need a 
lower dose. 
 

 

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Travel 
Before travelling, consult your doctor. You may need to talk about 
- the availability of your insulin in the country you are visiting, 
- supplies of insulin, injection syringes etc., 
- correct storage of your insulin while travelling, 
- timing of meals and insulin administration while travelling, 
- the possible effects of changing to different time zones, 
- possible new health risks in the countries to be visited, 
- what you should do in emergency situations when you feel unwell or become ill. 
 
Illnesses and injuries 
In the following situations, the management of your diabetes may require a lot of care: 
- If you are ill or have a major injury then your blood sugar level may increase (hyperglycaemia).  
- If you are not eating enough, your blood sugar level may become too low (hypoglycaemia).  
In most cases you will need a doctor. Make sure that you contact a doctor early.  
 
If you have type 1 diabetes (insulin dependent diabetes mellitus), do not stop your insulin and 
continue to get enough carbohydrates. Always tell people who are caring for you or treating you that 
you require insulin. 
 
Some patients with long-standing type 2 diabetes mellitus and heart disease or previous stroke who 
were treated with pioglitazone and insulin experienced the development of heart failure. Inform your 
doctor as soon as possible if you experience signs of heart failure such as unusual shortness of breath 
or rapid increase in weight or localised swelling (oedema). 
 
Other medicines and Insulin Human Winthrop Comb 25 
 
Some medicines cause changes in the blood sugar level (decrease, increase or both depending on the 
situation). In each case, it may be necessary to adjust your insulin dosage to avoid blood sugar levels 
that are either too low or too high. Be careful when you start or stop taking another medicine. 
 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines. Before taking a medicine ask your doctor if it can affect your blood sugar level, and what 
action, if any, you need to take. 
 
Medicines that may cause your blood sugar level to fall (hypoglycaemia) include:  
- all other medicines to treat diabetes,  
- angiotensin converting enzyme (ACE) inhibitors (used to treat certain heart conditions or high 

blood pressure),  
- disopyramide (used to treat certain heart conditions),  
- fluoxetine (used to treat depression),  
- fibrates (used to lower high levels of blood lipids),  
- monoamine oxidase (MAO) inhibitors (used to treat depression),  
- pentoxifylline, propoxyphene, salicylates (such as aspirin, used to relieve pain and lower fever), 
- sulfonamide antibiotics. 
 
Medicines that may cause your blood sugar level to rise (hyperglycaemia) include:  
- corticosteroids (such as "cortisone", used to treat inflammation),  
- danazol (medicine acting on ovulation),  
- diazoxide (used to treat high blood pressure),  
- diuretics (used to treat high blood pressure or excessive fluid retention),  
- glucagon (pancreas hormone used to treat severe hypoglycaemia),  
- isoniazid (used to treat tuberculosis),  
- oestrogens and progestogens (such as in the contraceptive pill used for birth control),  
- phenothiazine derivatives (used to treat psychiatric disorders),  
- somatropin (growth hormone),  

 

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- sympathomimetic medicines (such as epinephrine [adrenaline] or salbutamol, terbutaline used to 
treat asthma), 

- thyroid hormones (used to treat the thyroid gland disorders), 
- protease inhibitors (used to treat HIV), 
- atypical antipsychotic medicines (such as olanzapine and clozapine). 
 
Your blood sugar level may either rise or fall if you take:  
- beta-blockers (used to treat high blood pressure),  
- clonidine (used to treat high blood pressure), 
- lithium salts (used to treat psychiatric disorders).  
Pentamidine (used to treat some infections caused by parasites) may cause hypoglycaemia which may 
sometimes be followed by hyperglycaemia. 
 
Beta-blockers like other sympatholytic medicines (such as clonidine, guanethidine, and reserpine) may 
weaken or suppress entirely the first warning symptoms which help you to recognise a 
hypoglycaemia. 
 
If you are not sure whether you are taking one of those medicines ask your doctor or pharmacist. 
 
Insulin Human Winthrop Comb 25 with alcohol 
 
Your blood sugar levels may either rise or fall if you drink alcohol. 
 
Pregnancy and breast-feeding 
 
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor or pharmacist for advice before taking this medicine. 
 
Inform your doctor if you are planning to become pregnant, or if you are already pregnant. Your 
insulin dosage may need to be changed during pregnancy and after giving birth. Particularly careful 
control of your diabetes, and prevention of hypoglycaemia, is important for the health of your baby.  
 
If you are breast-feeding consult your doctor as you may require adjustments in your insulin doses and 
your diet. 
 
Driving and using machines 
 
Your ability to concentrate or react may be reduced if: 
- you have hypoglycaemia (low blood sugar levels), 
- you have hyperglycaemia (high blood sugar levels), 
- you have problems with your sight.  
Keep this possible problem in mind in all situations where you might put yourself and others at risk 
(such as driving a car or using machines). You should contact your doctor for advice on driving if: 
- you have frequent episodes of hypoglycaemia, 
- the first warning symptoms which help you to recognise hypoglycaemia are reduced or absent. 
 
Important information about some of the ingredients of Insulin Human Winthrop Comb 25  
 
This medicine contains less than 1 mmol (23 mg) sodium per dose, i.e. it is essentially ‘sodium-free’. 
 
 

 

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3. How to use Insulin Human Winthrop Comb 25 
 
Dose 
 
Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor 
or pharmacist if you are not sure. 
 
Based on your life-style and the results of your blood sugar (glucose) tests, your doctor will 
- determine how much Insulin Human Winthrop Comb 25 per day you will need, 
- tell you when to check your blood sugar level, and whether you need to carry out urine tests, 
- tell you when you may need to inject a higher or lower dose of Insulin Human Winthrop 

Comb 25. 
 
Many factors may influence your blood sugar level. You should know these factors so that you are 
able to react correctly to changes in your blood sugar level and to prevent it from becoming too high 
or too low. See the box at the end of this leaflet for further information. 
 
Frequency of administration 
 
Insulin Human Winthrop Comb 25 is injected under the skin 30 to 45 minutes before a meal.  
 
Method of administration 
 
Insulin Human Winthrop Comb 25 is a fluid (suspension) for injection under the skin. 
 
Do NOT inject Insulin Human Winthrop Comb 25 into a vein (blood vessel). 
 
Your doctor will show you in which area of the skin you should inject your insulin. With each 
injection, change the puncture site within the particular area of skin that you are using. 
 
Do not use it in insulin pumps or other infusion pumps - special insulin preparations are available for 
use in such devices. 
 
How to handle the cartridges 
 
To ensure you get the accurate dose, the Insulin Human Winthrop Comb 25 cartridges are to be used 
only with the following pens: 
- JuniorSTAR which delivers doses in steps of 0.5 units  
- OptiPen, ClikSTAR, Tactipen, Autopen 24 or AllStar which deliver doses in steps of 1 unit. 
Not all of these pens may be marketed in your country.  
 
The pen should be used as recommended in the information provided by the device manufacturer. The 
manufacturer’s instructions for using the pen must be followed carefully for loading the cartridge, 
attaching the injection needle, and administering the insulin injection. 
 
Keep the cartridge at room temperature for 1 or 2 hours before inserting it into the pen. Mix the 
insulin well and check it before you insert it into the pen. Later, you must mix the insulin well again 
immediately before each injection. 
 
Mixing is best done by gently tilting the cartridge or pen (with the cartridge in it) back and forth at 
least 10 times. To assist in mixing, three tiny metal balls are present in the cartridge. 
 
After mixing, the suspension must have a uniform milky-white appearance. It must not be used if it 
remains clear or if, for example, clumps, flakes, particles or anything similar are in the suspension or 
on the sides or bottom of the cartridge. A new cartridge with a uniform suspension on mixing must 
then be used. 
 

 

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Always use a new cartridge if you notice that your blood sugar control is unexpectedly getting worse. 
This is because the insulin may have lost some of its effectiveness. If you think you may have a 
problem with your insulin, have it checked by your doctor or pharmacist. 
 
Special care before injection 
 
Before injection remove any air bubbles (see instructions for using the pen). Make sure that neither 
alcohol nor other disinfectants or other substances contaminate the insulin. 
- Do not re-fill and re-use empty cartridges. 
- Do not add any other insulin to the cartridge. 
- Do not mix insulin with any other medicines. 
 
Problems with the pen? 
 
Refer to the manufacturer’s instructions for using the pen. 
If the insulin pen is damaged or not working properly (due to mechanical defects) it has to be 
discarded, and a new insulin pen has to be used. 
 
If the pen does not function well, you can draw the insulin from the cartridge into an injection syringe. 
Therefore, keep injection syringes and needles as well. However, use only those injection syringes 
which are designed for an insulin concentration of 100 IU (International Units) per ml. 
 
If you use more Insulin Human Winthrop Comb 25 than you should 
- If you have injected too much Insulin Human Winthrop Comb 25, your blood sugar level 

may become too low (hypoglycaemia). Check your blood sugar frequently. In general, to 
prevent hypoglycaemia you must eat more food and monitor your blood sugar. For information 
on the treatment of hypoglycaemia, see box at the end of this leaflet. 

 
If you forget to use Insulin Human Winthrop Comb 25 
- If you have missed a dose of Insulin Human Winthrop Comb 25 or if you have not injected 

enough insulin, your blood sugar level may become too high (hyperglycaemia). Check your 
blood sugar frequently. For information on the treatment of hyperglycaemia, see box at the end 
of this leaflet. 

 
- Do not take a double dose to make up for a forgotten dose. 
 
If you stop using Insulin Human Winthrop Comb 25 
This could lead to severe hyperglycaemia (very high blood sugar) and ketoacidosis (build-up of acid 
in the blood because the body is breaking down fat instead of sugar). Do not stop Insulin Human 
Winthrop Comb 25 without speaking to a doctor, who will tell you what needs to be done. 
 
If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse. 
 
Insulin Mix-ups 
 
You must always check the insulin label before each injection to avoid mix-ups between Insulin 
Human Winthrop Comb 25 and other insulins.  
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
The most frequent side effect is hypoglycaemia (low blood sugar). The specific frequency cannot be 
estimated from available data (frequency not known). Serious hypoglycaemia may cause a heart attack 
or brain damage and may be life-threatening. For further information on the side effects of low blood 
sugar or high blood sugar, see the box at the end of this leaflet. 

 

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Severe allergic reactions to insulin may occur which may become life-threatening. Such reactions to 
insulin or to the excipients can cause large-scale skin reactions (rash and itching all over the body); 
severe swelling of skin or mucous membranes (angiooedema), shortness of breath, a fall in blood 
pressure with rapid heart beat and sweating. Frequency of these reactions cannot be estimated from 
available data. 
 
Side effects reported commonly (may affect up to 1 in 10 people) 
• Oedema 
Insulin treatment may cause temporary build-up of water in the body with swelling in the calves and 
ankles. 
• Injection site reactions 
 
Side effects reported uncommonly (may affect up to 1 in 100 people) 
• Severe allergic reaction with low blood pressure (shock) 
• Injection site urticaria (itchy rash) 
 
Other side effects include (frequency cannot be estimated from the available data) 
• Sodium retention 
• Eye reactions 
A marked change (improvement or worsening) in your blood sugar control can disturb your vision 
temporarily. If you have proliferative retinopathy (an eye disease related to diabetes) severe 
hypoglycaemic attacks may cause temporary loss of vision.  
• Skin changes at the injection site (lipodystrophy) 
If you inject your insulin too often at the same skin site, fatty tissue under the skin at this site may 
either shrink or thicken. Insulin that you inject in such a site may not work very well. Changing the 
injection site with each injection may help to prevent such skin changes. 
• Skin and allergic reactions 
Other mild reactions at the injection site (such as injection site redness, unusually intense pain on 
injection site, itching, injection site swelling or injection site inflammation) may occur. They can also 
spread around the injection site. Most minor reactions to insulins usually resolve in a few days to a 
few weeks. 
 
Insulin treatment can cause the body to produce antibodies to insulin (substances that act against 
insulin). However, only very rarely, this will require a change to your insulin dosage. 
 
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side 
effects not listed in this leaflet. 
 
 
5. How to store Insulin Human Winthrop Comb 25 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date which is stated on the carton and on the label of the 
cartridge after “EXP”. The expiry date refers to the last day of that month. 
 
Unopened cartridges 
Store in a refrigerator (2°C - 8°C). Do not freeze. Do not put Insulin Human Winthrop Comb 25 next 
to the freezer compartment or a freezer pack. Keep the cartridge in the outer carton in order to protect 
from light. 
 
In-use cartridges 
Cartridges in-use (in the insulin pen) or carried as a spare may be stored for a maximum of 4 weeks 
not above 25°C and away from direct heat (for example next to a heating unit) or direct light (direct 
sunlight or next to a lamp). The cartridge in-use must not be stored in a refrigerator. Do not use the 
cartridge after this time period. 

 

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Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Insulin Human Winthrop Comb 25 contains 
- The active substance is insulin human. One ml of Insulin Human Winthrop Comb 25 contains 

100 IU (International Units) of the active substance insulin human. 25% of the insulin is 
dissolved in water; the other 75% is present as tiny crystals of insulin protamine. 

- The other ingredients are: protamine sulphate, metacresol, phenol, zinc chloride, sodium 
dihydrogen phosphate dihydrate, glycerol, sodium hydroxide (see section 2 under “Important 
information about some of the ingredients of Insulin Human Winthrop Comb 25”), hydrochloric 
acid (for pH adjustment) and water for injections. 

 
What Insulin Human Winthrop Comb 25 looks like and contents of the pack 
After mixing, Insulin Human Winthrop Comb 25 is a uniformly milky fluid (suspension for injection), 
with no clumps, particles or flocculation visible. 
 
Insulin Human Winthrop Comb 25 is supplied in cartridge containing 3 ml suspension (300 IU). Packs 
of 3, 4, 5, 6, 9 and 10 cartridges of 3 ml are available. Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder and Manufacturer 
Sanofi-Aventis Deutschland GmbH 
D-65926 Frankfurt am Main 
Germany 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
Sanofi Belgium 
Tél/Tel: +32 (0)2 710 54 00 
 

Lietuva 
UAB «SANOFI-AVENTIS LIETUVA» 
Tel: +370 5 2755224 
 

България 
sanofi-aventis Bulgaria EOOD 
Тел.: +359 (0)2 970 53 00 
 

Luxembourg/Luxemburg 
Sanofi Belgium  
Tél/Tel: +32 (0)2 710 54 00 (Belgique/Belgien) 
 

Česká republika 
sanofi-aventis, s.r.o. 
Tel: +420 233 086 111 
 

Magyarország 
SANOFI-AVENTIS Zrt. 
Tel.: +36 1 505 0050 
 

Danmark 
sanofi-aventis Denmark A/S 
Tlf: +45 45 16 70 00 
 

Malta 
Sanofi Malta Ltd. 
Tel: +356 21493022 
 

Deutschland 
Zentiva Pharma GmbH 
Tel: +49 (0)180 20 200 10 
 

Nederland 
sanofi-aventis Netherlands B.V. 
Tel: +31 (0)182 557 755 
 

Eesti 
sanofi-aventis Estonia OÜ 
Tel: +372 627 34 88 
 

Norge 
Aventis Pharma Norge AS 
Tlf: +47 67 10 71 00 
 

 

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Ελλάδα 
sanofi-aventis AEBE 
Τηλ: +30 210 900 16 00 
 

Österreich 
sanofi-aventis GmbH 
Tel: +43 1 80 185 – 0 
 

España 
sanofi-aventis, S.A. 
Tel: +34 93 485 94 00 
 

Polska 
sanofi-aventis Sp. z o.o. 
Tel.: +48 22 280 00 00 
 

France 
sanofi-aventis France 
Tél: 0 800 222 555 
Appel depuis l’étranger : +33 1 57 63 23 23 
 

Portugal 
Sanofi - Produtos Farmacêuticos, Lda. 
Tel: +351 21 35 89 400 
 

Hrvatska 
sanofi-aventis Croatia d.o.o. 
Tel: +385 1 600 34 00 

România 
Sanofi Romania SRL 
Tel: +40 (0) 21 317 31 36 
 

Ireland 
sanofi-aventis Ireland Ltd. T/A SANOFI 
Tel: +353 (0) 1 403 56 00 
 

Slovenija 
sanofi-aventis d.o.o. 
Tel: +386 1 560 48 00 
 

Ísland 
Vistor hf. 
Sími: +354 535 7000 
 

Slovenská republika 
sanofi-aventis Pharma Slovakia s.r.o. 
Tel: +421 2 33 100 100 
 

Italia 
Sanofi S.p.A. 
Tel: 800 13 12 12 (domande di tipo tecnico)  
800 536389 (altre domande) 
 

Suomi/Finland 
Sanofi Oy 
Puh/Tel: +358 (0) 201 200 300 
 

Κύπρος 
sanofi-aventis Cyprus Ltd. 
Τηλ: +357 22 871600 
 

Sverige 
Sanofi AB 
Tel: +46 (0)8 634 50 00 
 

Latvija 
sanofi-aventis Latvia SIA 
Tel: +371 67 33 24 51 
 

United Kingdom 
Sanofi 
Tel: +44 (0) 845 372 7101 
 

 
This leaflet was last revised in {date}  
 
 
Other source of information 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu/ 
 
 
 
 

HYPERGLYCAEMIA AND HYPOGLYCAEMIA 
 

Always carry some sugar (at least 20 grams) with you. 
Carry some information with you to show you are diabetic. 

 
HYPERGLYCAEMIA (high blood sugar levels) 

 
If your blood sugar is too high (hyperglycaemia), you may not have injected enough insulin. 

 

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Why does hyperglycaemia occur? 
 
Examples include: 
- you have not injected your insulin or not injected enough, or if it has become less effective, for 

example through incorrect storage, 
- your insulin pen does not work properly, 
- you are doing less exercise than usual, you are under stress (emotional distress, excitement), or 

you have an injury, operation, infection or fever, 
- you are taking or have taken certain other medicines (see section 2, "Other medicines and 

Insulin Human Winthrop Comb 25"). 
 
Warning symptoms of hyperglycaemia 
 
Thirst, increased need to urinate, tiredness, dry skin, reddening of the face, loss of appetite, low blood 
pressure, fast heart beat, and glucose and ketone bodies in urine. Stomach pain, fast and deep 
breathing, sleepiness or even loss of consciousness may be signs of a serious condition (ketoacidosis) 
resulting from lack of insulin. 
 
What should you do if you experience hyperglycaemia 
 
Test your blood sugar level and your urine for ketones as soon as any of the above symptoms 
occur. Severe hyperglycaemia or ketoacidosis must always be treated by a doctor, normally in a 
hospital. 
 

HYPOGLYCAEMIA (low blood sugar levels) 
 
If your blood sugar level falls too much you may become unconscious. Serious hypoglycaemia may 
cause a heart attack or brain damage and may be life-threatening. You normally should be able to 
recognise when your blood sugar is falling too much so that you can take the right actions. 
 
Why does hypoglycaemia occur? 
 
Examples include: 
- you inject too much insulin, 
- you miss meals or delay them, 
- you do not eat enough, or eat food containing less carbohydrate than normal (sugar and 

substances similar to sugar are called carbohydrates; however, artificial sweeteners are NOT 
carbohydrates), 

- you lose carbohydrates due to vomiting or diarrhoea, 
- you drink alcohol, particularly if you are not eating much, 
- you are doing more exercise than usual or a different type of physical activity, 
- you are recovering from an injury or operation or other stress, 
- you are recovering from an illness or from fever, 
- you are taking or have stopped taking certain other medicines (see section 2, "Other medicines 

and Insulin Human Winthrop Comb 25"). 
 
Hypoglycaemia is also more likely to occur if: 
- you have just begun insulin treatment or changed to another insulin preparation, 
- your blood sugar levels are almost normal or are unstable, 
- you change the area of skin where you inject insulin (for example from the thigh to the upper 

arm), 
- you suffer from severe kidney or liver disease, or some other disease such as hypothyroidism. 
 
Warning symptoms of hypoglycaemia 
 
- In your body 

 

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Examples of symptoms that tell you that your blood sugar level is falling too much or too fast: 
sweating, clammy skin, anxiety, fast heart beat, high blood pressure, palpitations and irregular 
heartbeat. These symptoms often develop before the symptoms of a low sugar level in the brain. 
 
- In your brain 
Examples of symptoms that indicate a low sugar level in the brain: headaches, intense hunger, nausea, 
vomiting, tiredness, sleepiness, sleep disturbances, restlessness, aggressive behaviour, lapses in 
concentration, impaired reactions, depression, confusion, speech disturbances (sometimes total loss of 
speech), visual disorders, trembling, paralysis, tingling sensations (paraesthesia), numbness and 
tingling sensations in the area of the mouth, dizziness, loss of self-control, inability to look after 
yourself, convulsions, loss of consciousness. 
 
The first symptoms which alert you to hypoglycaemia ("warning symptoms") may change, be weaker 
or may be missing altogether if 
- you are elderly, if you have had diabetes for a long time or if you suffer from a certain type of 

nervous disease (diabetic autonomic neuropathy), 
- you have recently suffered hypoglycaemia (for example the day before) or if it develops slowly, 
- you have almost normal or, at least, greatly improved blood sugar levels, 
- you have recently changed from an animal insulin to a human insulin such as Insulin Human 

Winthrop, 
- you are taking or have taken certain other medicines (see section 2, "Other medicines and 

Insulin Human Winthrop Comb 25"). 
 
In such a case, you may develop severe hypoglycaemia (and even faint) before you are aware of the 
problem. Be familiar with your warning symptoms. If necessary, more frequent blood sugar testing 
can help to identify mild hypoglycaemic episodes that may otherwise be overlooked. If you are not 
confident about recognising your warning symptoms, avoid situations (such as driving a car) in which 
you or others would be put at risk by hypoglycaemia. 
 
What should you do if you experience hypoglycaemia 
 
1. Do not inject insulin. Immediately take about 10 to 20 g sugar, such as glucose, sugar cubes or a 

sugar-sweetened beverage. Caution: Artificial sweeteners and foods with artificial sweeteners 
(such as diet drinks) are of no help in treating hypoglycaemia. 

2. Then eat something that has a long-acting effect in raising your blood sugar (such as bread or 
pasta). Your doctor or nurse should have discussed this with you previously. 

3. If the hypoglycaemia comes back again take another 10 to 20 g sugar. 
4. Speak to a doctor immediately if you are not able to control the hypoglycaemia or if it recurs. 
 
Tell your relatives, friends and close colleagues the following: 
If you are not able to swallow or if you are unconscious, you will require an injection of glucose or 
glucagon (a medicine which increases blood sugar). These injections are justified even if it is not 
certain that you have hypoglycaemia. 
 
It is advisable to test your blood sugar immediately after taking glucose to check that you really have 
hypoglycaemia. 
 
 

 

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Package leaflet: Information for the user 

 
Insulin Human Winthrop Comb 25 SoloStar 100 IU/ml suspension for injection in a pre-filled 

pen 
Insulin human 

 
 
Read all of this leaflet carefully, including the Instructions for Use of Insulin Human Winthrop 
Comb 25 SoloStar, pre-filled pen, before you start using this medicine because it contains 
important information for you. 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor, pharmacist or nurse. 
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours. 
- If you get any side effects, talk to your doctor, pharmacist or nurse? This includes any possible 

side effects not listed in this leaflet,. 
 
What is in this leaflet: 
1. What Insulin Human Winthrop Comb 25 is and what it is used for 
2. What you need to know before you use Insulin Human Winthrop Comb 25 
3. How to use Insulin Human Winthrop Comb 25 
4. Possible side effects 
5. How to store Insulin Human Winthrop Comb 25 
6. Contents of the pack and other information 
 
 
1. What Insulin Human Winthrop Comb 25 is and what it is used for 
 
Insulin Human Winthrop Comb 25 contains the active substance insulin human which is made by a 
biotechnology process and is identical with the body's own insulin. 
 
Insulin Human Winthrop Comb 25 is an insulin preparation with a gradual onset and long duration of 
action. It comes in cartridges sealed in disposable pen injectors, SoloStar. 
 
Insulin Human Winthrop Comb 25 is used to reduce high blood sugar in patients with diabetes 
mellitus who need treatment with insulin. Diabetes mellitus is a disease where your body does not 
produce enough insulin to control the level of blood sugar. 
 
 
2. What you need to know before you use Insulin Human Winthrop Comb 25 
 
Do not use Insulin Human Winthrop Comb 25  
 
If you are allergic to insulin or any of the other ingredients of this medicine (listed in section 6).  
 
Warnings and precautions 
 
Talk to your doctor, pharmacist or nurse before using Insulin Human Winthrop Comb 25. 
Follow closely the instructions for dosage, monitoring (blood and urine tests), diet and physical 
activity (physical work and exercise), injection technique as discussed with your doctor. 
 
If you are allergic to this medicine or to animal insulins, talk to your doctor. 
 
Special patient groups 
If you have liver or kidneys problems or if you are elderly, speak to your doctor as you may need a 
lower dose. 

 

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Travel 
Before travelling, consult your doctor. You may need to talk about 
- the availability of your insulin in the country you are visiting, 
- supplies of insulin, injection syringes etc., 
- correct storage of your insulin while travelling, 
- timing of meals and insulin administration while travelling, 
- the possible effects of changing to different time zones, 
- possible new health risks in the countries to be visited, 
- what you should do in emergency situations when you feel unwell or become ill. 
 
Illnesses and injuries 
In the following situations, the management of your diabetes may require a lot of care: 
- If you are ill or have a major injury then your blood sugar level may increase (hyperglycaemia).  
- If you are not eating enough, your blood sugar level may become too low (hypoglycaemia).  
In most cases you will need a doctor. Make sure that you contact a doctor early.  
 
If you have type 1 diabetes (insulin dependent diabetes mellitus), do not stop your insulin and 
continue to get enough carbohydrates. Always tell people who are caring for you or treating you that 
you require insulin. 
 
Some patients with long-standing type 2 diabetes mellitus and heart disease or previous stroke who 
were treated with pioglitazone and insulin experienced the development of heart failure. Inform your 
doctor as soon as possible if you experience signs of heart failure such as unusual shortness of breath 
or rapid increase in weight or localised swelling (oedema). 
 
Other medicines and Insulin Human Winthrop Comb 25 
 
Some medicines cause changes in the blood sugar level (decrease, increase or both depending on the 
situation). In each case, it may be necessary to adjust your insulin dosage to avoid blood sugar levels 
that are either too low or too high. Be careful when you start or stop taking another medicine. 
 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines. Before taking a medicine ask your doctor if it can affect your blood sugar level, and what 
action, if any, you need to take. 
 
Medicines that may cause your blood sugar level to fall (hypoglycaemia) include:  
- all other medicines to treat diabetes,  
- angiotensin converting enzyme (ACE) inhibitors (used to treat certain heart conditions or high 

blood pressure),  
- disopyramide (used to treat certain heart conditions),  
- fluoxetine (used to treat depression),  
- fibrates (used to lower high levels of blood lipids),  
- monoamine oxidase (MAO) inhibitors (used to treat depression),  
- pentoxifylline, propoxyphene, salicylates (such as aspirin, used to relieve pain and lower fever), 
- sulfonamide antibiotics. 
 
Medicines that may cause your blood sugar level to rise (hyperglycaemia) include:  
- corticosteroids (such as "cortisone", used to treat inflammation),  
- danazol (medicine acting on ovulation),  
- diazoxide (used to treat high blood pressure),  
- diuretics (used to treat high blood pressure or excessive fluid retention),  
- glucagon (pancreas hormone used to treat severe hypoglycaemia),  
- isoniazid (used to treat tuberculosis),  
- oestrogens and progestogens (such as in the contraceptive pill used for birth control),  
- phenothiazine derivatives (used to treat psychiatric disorders),  
- somatropin (growth hormone),  

 

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- sympathomimetic medicines (such as epinephrine [adrenaline] or salbutamol, terbutaline used to 
treat asthma), 

- thyroid hormones (used to treat the thyroid gland disorders), 
- protease inhibitors (used to treat HIV), 
- atypical antipsychotic medicines (such as olanzapine and clozapine). 
 
Your blood sugar level may either rise or fall if you take:  
- beta-blockers (used to treat high blood pressure),  
- clonidine (used to treat high blood pressure), 
- lithium salts (used to treat psychiatric disorders).  
Pentamidine (used to treat some infections caused by parasites) may cause hypoglycaemia which may 
sometimes be followed by hyperglycaemia. 
 
Beta-blockers like other sympatholytic medicines (such as clonidine, guanethidine, and reserpine) may 
weaken or suppress entirely the first warning symptoms which help you to recognise a 
hypoglycaemia. 
 
If you are not sure whether you are taking one of those medicines ask your doctor or pharmacist. 
 
Insulin Human Winthrop Comb 25 with alcohol 
 
Your blood sugar levels may either rise or fall if you drink alcohol. 
 
Pregnancy and breast-feeding 
 
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor or pharmacist for advice before taking this medicine. 
 
Inform your doctor if you are planning to become pregnant, or if you are already pregnant. Your 
insulin dosage may need to be changed during pregnancy and after giving birth. Particularly careful 
control of your diabetes, and prevention of hypoglycaemia, is important for the health of your baby.  
 
If you are breast-feeding consult your doctor as you may require adjustments in your insulin doses and 
your diet. 
 
Driving and using machines 
 
Your ability to concentrate or react may be reduced if: 
- you have hypoglycaemia (low blood sugar levels), 
- you have hyperglycaemia (high blood sugar levels), 
- you have problems with your sight.  
Keep this possible problem in mind in all situations where you might put yourself and others at risk 
(such as driving a car or using machines). You should contact your doctor for advice on driving if: 
- you have frequent episodes of hypoglycaemia, 
- the first warning symptoms which help you to recognise hypoglycaemia are reduced or absent. 
 
Important information about some of the ingredients of Insulin Human Winthrop Comb 25  
 
This medicine contains less than 1 mmol (23 mg) sodium per dose, i.e. it is essentially ‘sodium-free’. 
 
 

 

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3. How to use Insulin Human Winthrop Comb 25 
 
Dose 
 
Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor 
or pharmacist if you are not sure. 
 
Based on your life-style and the results of your blood sugar (glucose) tests, your doctor will 
- determine how much Insulin Human Winthrop Comb 25 per day you will need, 
- tell you when to check your blood sugar level, and whether you need to carry out urine tests, 
- tell you when you may need to inject a higher or lower dose of Insulin Human Winthrop 

Comb 25. 
 
Many factors may influence your blood sugar level. You should know these factors so that you are 
able to react correctly to changes in your blood sugar level and to prevent it from becoming too high 
or too low. See the box at the end of this leaflet for further information. 
 
Frequency of administration 
 
Insulin Human Winthrop Comb 25 is injected under the skin 30 to 45 minutes before a meal.  
 
Method of administration 
 
Insulin Human Winthrop Comb 25 is a fluid (suspension) for injection under the skin. 
 
Do NOT inject Insulin Human Winthrop Comb 25 into a vein (blood vessel).  
 
SoloStar delivers insulin in doses from 1 to 80 units in steps of 1 unit. Each pen contains multiple 
doses. 
 
Your doctor will show you in which area of the skin you should inject your insulin. With each 
injection, change the puncture site within the particular area of skin that you are using. 
 
How to handle SoloStar 
 
SoloStar is a pre-filled disposable pen containing human insulin. 
 
Read carefully the "SoloStar Instructions for Use" included in this package leaflet. You must 
use the pen as described in these Instructions for Use. 
 
A new injection needle must be attached before each use. Only use needles that have been approved 
for use with SoloStar. 
A safety test must be performed before each injection. 
 
Mix the insulin well and check it before first use. Later, you must mix the insulin well again 
immediately before each injection. 
 
Mixing is best done by gently tilting the pen back and forth at least 10 times. To assist in mixing, three 
tiny metal balls are present in the cartridge. 
 
After mixing, the suspension must have a uniform milky-white appearance. It must not be used if it 
remains clear or if, for example, clumps, flakes, particles or anything similar are in the suspension or 
on the sides or bottom of the cartridge in the pen. A new pen with a uniform suspension on mixing 
must then be used. 
 
Always use a new pen if you notice that your blood sugar control is unexpectedly getting worse. If 
you think you have a problem with SoloStar, consult your doctor, pharmacist or nurse. 

 

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To prevent the possible transmission of disease, each pen must be used by one patient only. 
 
Special care before injection 
 
Make sure that neither alcohol nor other disinfectants or other substances contaminate the insulin. 
 
Do not mix insulin with any other medicines. Insulin Human Winthrop Comb 25 SoloStar, pre-filled 
pen, is not designed to allow any other insulin to be mixed in the cartridge. 
 
Empty pens must not be re-filled and must be properly discarded. 
 
Do not use SoloStar if it is damaged or not working properly (due to mechanical defects), it has to be 
discarded and a new SoloStar has to be used. 
 
If you use more Insulin Human Winthrop Comb 25 than you should 
- If you have injected too much Insulin Human Winthrop Comb 25, your blood sugar level 

may become too low (hypoglycaemia). Check your blood sugar frequently. In general, to 
prevent hypoglycaemia you must eat more food and monitor your blood sugar. For information 
on the treatment of hypoglycaemia, see box at the end of this leaflet. 

 
If you forget to use Insulin Human Winthrop Comb 25 
- If you have missed a dose of Insulin Human Winthrop Comb 25 or if you have not injected 

enough insulin, your blood sugar level may become too high (hyperglycaemia). Check your 
blood sugar frequently. For information on the treatment of hyperglycaemia, see box at the end 
of this leaflet. 

 
- Do not take a double dose to make up for a forgotten dose. 
 
If you stop using Insulin Human Winthrop Comb 25 
This could lead to severe hyperglycaemia (very high blood sugar) and ketoacidosis (build-up of acid 
in the blood because the body is breaking down fat instead of sugar). Do not stop Insulin Human 
Winthrop Comb 25 without speaking to a doctor, who will tell you what needs to be done. 
 
If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse. 
 
Insulin Mix-ups 
 
You must always check the insulin label before each injection to avoid mix-ups between Insulin 
Human Winthrop Comb 25 and other insulins.  
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
The most frequent side effect is hypoglycaemia (low blood sugar). The specific frequency cannot be 
estimated from available data (frequency not known). Serious hypoglycaemia may cause a heart attack 
or brain damage and may be life-threatening. For further information on the side effects of low blood 
sugar or high blood sugar, see the box at the end of this leaflet. 
 
Severe allergic reactions to insulin may occur which may become life-threatening. Such reactions to 
insulin or to the excipients can cause large-scale skin reactions (rash and itching all over the body); 
severe swelling of skin or mucous membranes (angiooedema), shortness of breath, a fall in blood 
pressure with rapid heart beat and sweating. Frequency of these reactions cannot be estimated from 
available data. 
 

 

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Side effects reported commonly (may affect up to 1 in 10 people) 
• Oedema 
Insulin treatment may cause temporary build-up of water in the body with swelling in the calves and 
ankles. 
• Injection site reactions 
 
Side effects reported uncommonly (may affect up to 1 in 100 people) 
• Severe allergic reaction with low blood pressure (shock) 
• Injection site urticaria (itchy rash) 
 
Other side effects include (frequency cannot be estimated from the available data) 
• Sodium retention 
• Eye reactions 
A marked change (improvement or worsening) in your blood sugar control can disturb your vision 
temporarily. If you have proliferative retinopathy (an eye disease related to diabetes) severe 
hypoglycaemic attacks may cause temporary loss of vision. 
• Skin changes at the injection site (lipodystrophy) 
If you inject your insulin too often at the same skin site, fatty tissue under the skin at this site may 
either shrink or thicken. Insulin that you inject in such a site may not work very well. Changing the 
injection site with each injection may help to prevent such skin changes. 
• Skin and allergic reactions 
Other mild reactions at the injection site (such as injection site redness, unusually intense pain on 
injection site, itching, injection site swelling or injection site inflammation) may occur. They can also 
spread around the injection site. Most minor reactions to insulins usually resolve in a few days to a 
few weeks. 
 
Insulin treatment can cause the body to produce antibodies to insulin (substances that act against 
insulin). However, only very rarely, this will require a change to your insulin dosage. 
 
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side 
effects not listed in this leaflet. 
 
 
5. How to store Insulin Human Winthrop Comb 25 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date which is stated on the carton and on the label of the pen 
after “EXP”. The expiry date refers to the last day of that month. 
 
Not in-use pens 
Store in a refrigerator (2°C – 8°C). Do not freeze. Do not put the pre-filled pen next to the freezer 
compartment or a freezer pack. Keep the pen in the outer carton in order to protect from light. 
 
In-use pens 
Pre-filled pens in-use or carried as a spare may be stored for a maximum of 4 weeks not above 25°C 
and away from direct heat (for example next to a heating unit) or direct light (direct sunlight or next to 
a lamp). The pen in-use must not be stored in a refrigerator. Do not use the pen after this time period. 
 
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment. 
 
 

 

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6. Contents of the pack and other information 
 
What Insulin Human Winthrop Comb 25 contains 
- The active substance is insulin human. One ml of Insulin Human Winthrop Comb 25 contains 

100 IU (International Units) of the active substance insulin human. 25% of the insulin is 
dissolved in water; the other 75% is present as tiny crystals of insulin protamine. 

- The other ingredients are: protamine sulphate, metacresol, phenol, zinc chloride, sodium 
dihydrogen phosphate dihydrate, glycerol, sodium hydroxide (see section 2 under “Important 
information about some of the ingredients of Insulin Human Winthrop Comb 25”), hydrochloric 
acid (for pH adjustment) and water for injections. 

 
What Insulin Human Winthrop Comb 25 looks like and contents of the pack 
After mixing, Insulin Human Winthrop Comb 25 is a uniformly milky fluid (suspension for injection), 
with no clumps, particles or flocculation visible. 
 
Insulin Human Winthrop Comb 25 is supplied in pre-filled pens, SoloStar, containing 3 ml 
suspension, (300 IU). Packs of 3, 4, 5, 6, 9 and 10 pens of 3 ml are available. Not all pack sizes may 
be marketed. 
 
Marketing Authorisation Holder and Manufacturer 
Sanofi-Aventis Deutschland GmbH 
D-65926 Frankfurt am Main 
Germany 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
Sanofi Belgium 
Tél/Tel: +32 (0)2 710 54 00 
 

Lietuva 
UAB «SANOFI-AVENTIS LIETUVA» 
Tel: +370 5 2755224 
 

България 
sanofi-aventis Bulgaria EOOD 
Тел.: +359 (0)2 970 53 00 
 

Luxembourg/Luxemburg 
Sanofi Belgium  
Tél/Tel: +32 (0)2 710 54 00 (Belgique/Belgien) 
 

Česká republika 
sanofi-aventis, s.r.o. 
Tel: +420 233 086 111 
 

Magyarország 
SANOFI-AVENTIS Zrt. 
Tel.: +36 1 505 0050 
 

Danmark 
sanofi-aventis Denmark A/S 
Tlf: +45 45 16 70 00 
 

Malta 
Sanofi Malta Ltd. 
Tel: +356 21493022 
 

Deutschland 
Zentiva Pharma GmbH 
Tel: +49 (0)180 20 200 10 
 

Nederland 
sanofi-aventis Netherlands B.V. 
Tel: +31 (0)182 557 755 
 

Eesti 
sanofi-aventis Estonia OÜ 
Tel: +372 627 34 88 
 

Norge 
Aventis Pharma Norge AS 
Tlf: +47 67 10 71 00 
 

Ελλάδα 
sanofi-aventis AEBE 
Τηλ: +30 210 900 16 00 
 

Österreich 
sanofi-aventis GmbH 
Tel: +43 1 80 185 – 0 
 

 

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España 
sanofi-aventis, S.A. 
Tel: +34 93 485 94 00 
 

Polska 
sanofi-aventis Sp . z o.o. 
Tel.: +48 22 280 00 00 
 

France 
sanofi-aventis France 
Tél: 0 800 222 555 
Appel depuis l’étranger : +33 1 57 63 23 23 
 

Portugal 
Sanofi - Produtos Farmacêuticos, Lda. 
Tel: +351 21 35 89 400 
 

Hrvatska 
sanofi-aventis Croatia d.o.o. 
Tel: +385 1 600 34 00 

România 
Sanofi Romania SRL 
Tel: +40 (0) 21 317 31 36 
 

Ireland 
sanofi-aventis Ireland Ltd. T/A SANOFI 
Tel: +353 (0) 1 403 56 00 
 

Slovenija 
sanofi-aventis d.o.o. 
Tel: +386 1 560 48 00 
 

Ísland 
Vistor hf. 
Sími: +354 535 7000 
 

Slovenská republika 
sanofi-aventis Pharma Slovakia s.r.o. 
Tel: +421 2 33 100 100 
 

Italia 
Sanofi S.p.A. 
Tel: 800 13 12 12 (domande di tipo tecnico)  
800 536389 (altre domande) 
 

Suomi/Finland 
Sanofi Oy 
Puh/Tel: +358 (0) 201 200 300 
 

Κύπρος 
sanofi-aventis Cyprus Ltd. 
Τηλ: +357 22 871600 
 

Sverige 
Sanofi AB 
Tel: +46 (0)8 634 50 00 
 

Latvija 
sanofi-aventis Latvia SIA 
Tel: +371 67 33 24 51 
 

United Kingdom 
Sanofi 
Tel: +44 (0) 845 372 7101 
 

 
This leaflet was last revised in {date} 
 
 
Other source of information 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu/ 
 
 
 
 

HYPERGLYCAEMIA AND HYPOGLYCAEMIA 
 

Always carry some sugar (at least 20 grams) with you. 
Carry some information with you to show you are diabetic. 

 
HYPERGLYCAEMIA (high blood sugar levels) 

 
If your blood sugar is too high (hyperglycaemia), you may not have injected enough insulin. 
 
Why does hyperglycaemia occur? 
 
Examples include: 

 

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- you have not injected your insulin or not injected enough, or if it has become less effective, for 
example through incorrect storage, 

- your insulin pen does not work properly, 
- you are doing less exercise than usual, you are under stress (emotional distress, excitement), or 

you have an injury, operation, infection or fever, 
- you are taking or have taken certain other medicines (see section 2, "Other medicines and 

Insulin Human Winthrop Comb 25"). 
 
Warning symptoms of hyperglycaemia 
 
Thirst, increased need to urinate, tiredness, dry skin, reddening of the face, loss of appetite, low blood 
pressure, fast heart beat, and glucose and ketone bodies in urine. Stomach pain, fast and deep 
breathing, sleepiness or even loss of consciousness may be signs of a serious condition (ketoacidosis) 
resulting from lack of insulin. 
 
What should you do if you experience hyperglycaemia 
 
Test your blood sugar level and your urine for ketones as soon as any of the above symptoms 
occur. Severe hyperglycaemia or ketoacidosis must always be treated by a doctor, normally in a 
hospital. 
 

HYPOGLYCAEMIA (low blood sugar levels) 
 
If your blood sugar level falls too much you may become unconscious. Serious hypoglycaemia may 
cause a heart attack or brain damage and may be life-threatening. You normally should be able to 
recognise when your blood sugar is falling too much so that you can take the right actions. 
 
Why does hypoglycaemia occur? 
 
Examples include: 
- you inject too much insulin, 
- you miss meals or delay them, 
- you do not eat enough, or eat food containing less carbohydrate than normal (sugar and 

substances similar to sugar are called carbohydrates; however, artificial sweeteners are NOT 
carbohydrates), 

- you lose carbohydrates due to vomiting or diarrhoea, 
- you drink alcohol, particularly if you are not eating much, 
- you are doing more exercise than usual or a different type of physical activity, 
- you are recovering from an injury or operation or other stress, 
- you are recovering from an illness or from fever, 
- you are taking or have stopped taking certain other medicines (see section 2, "Other medicines 

and Insulin Human Winthrop Comb 25"). 
 
Hypoglycaemia is also more likely to occur if: 
- you have just begun insulin treatment or changed to another insulin preparation, 
- your blood sugar levels are almost normal or are unstable, 
- you change the area of skin where you inject insulin (for example from the thigh to the upper 

arm), 
- you suffer from severe kidney or liver disease, or some other disease such as hypothyroidism. 
 
Warning symptoms of hypoglycaemia 
 
- In your body 
Examples of symptoms that tell you that your blood sugar level is falling too much or too fast: 
sweating, clammy skin, anxiety, fast heart beat, high blood pressure, palpitations and irregular 
heartbeat. These symptoms often develop before the symptoms of a low sugar level in the brain. 
 

 

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- In your brain 
Examples of symptoms that indicate a low sugar level in the brain: headaches, intense hunger, nausea, 
vomiting, tiredness, sleepiness, sleep disturbances, restlessness, aggressive behaviour, lapses in 
concentration, impaired reactions, depression, confusion, speech disturbances (sometimes total loss of 
speech), visual disorders, trembling, paralysis, tingling sensations (paraesthesia), numbness and 
tingling sensations in the area of the mouth, dizziness, loss of self-control, inability to look after 
yourself, convulsions, loss of consciousness. 
 
The first symptoms which alert you to hypoglycaemia ("warning symptoms") may change, be weaker 
or may be missing altogether if 
- you are elderly, if you have had diabetes for a long time or if you suffer from a certain type of 

nervous disease (diabetic autonomic neuropathy), 
- you have recently suffered hypoglycaemia (for example the day before) or if it develops slowly, 
- you have almost normal or, at least, greatly improved blood sugar levels, 
- you have recently changed from an animal insulin to a human insulin such as Insulin Human 

Winthrop, 
- you are taking or have taken certain other medicines (see section 2, "Other medicines and 

Insulin Human Winthrop Comb 25"). 
 
In such a case, you may develop severe hypoglycaemia (and even faint) before you are aware of the 
problem. Be familiar with your warning symptoms. If necessary, more frequent blood sugar testing 
can help to identify mild hypoglycaemic episodes that may otherwise be overlooked. If you are not 
confident about recognising your warning symptoms, avoid situations (such as driving a car) in which 
you or others would be put at risk by hypoglycaemia. 
 
What should you do if you experience hypoglycaemia 
 
1. Do not inject insulin. Immediately take about 10 to 20 g sugar, such as glucose, sugar cubes or a 

sugar-sweetened beverage. Caution: Artificial sweeteners and foods with artificial sweeteners 
(such as diet drinks) are of no help in treating hypoglycaemia. 

2. Then eat something that has a long-acting effect in raising your blood sugar (such as bread or 
pasta). Your doctor or nurse should have discussed this with you previously. 

3. If the hypoglycaemia comes back again take another 10 to 20 g sugar. 
4. Speak to a doctor immediately if you are not able to control the hypoglycaemia or if it recurs. 
 
Tell your relatives, friends and close colleagues the following: 
If you are not able to swallow or if you are unconscious, you will require an injection of glucose or 
glucagon (a medicine which increases blood sugar). These injections are justified even if it is not 
certain that you have hypoglycaemia. 
 
It is advisable to test your blood sugar immediately after taking glucose to check that you really have 
hypoglycaemia. 
 
 

 

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Insulin Human Winthrop Comb 25 Solostar suspension for injection in a pre-filled pen. 
Instructions for Use. 
 
SoloStar is a prefilled pen for the injection of insulin. Your doctor has decided that SoloStar is 
appropriate for you based on your ability to handle SoloStar. Talk with your doctor, pharmacist or 
nurse about proper injection technique before using SoloStar. 
 
Read these instructions carefully before using your SoloStar. If you are not able to use SoloStar or 
follow all the instructions completely on your own, you must use SoloStar only if you have help from 
a person who is able to follow the instructions completely. Hold the pen as shown in this leaflet. To 
ensure that you read the dose correctly, hold the pen horizontally, with the needle on the left and the 
dosage selector to the right as shown in the illustrations below. 
 
Follow these instructions completely each time you use SoloStar to ensure that you get an 
accurate dose. If you do not follow these instructions completely, you may get too much or too 
little insulin, which may affect your blood glucose. 
 
You can set doses from 1 to 80 units in steps of 1 unit. Each pen contains multiple doses. 
 
Keep this leaflet for future reference. 
 
If you have any questions about SoloStar or about diabetes, ask your doctor, pharmacist or nurse or 
call the local sanofi-aventis number on the front of this leaflet. 
 

 
Schematic diagram of the pen 

 
 
Important information for use of SoloStar: 
 
• Always attach a new needle before each use. Only use needles that have been approved for use 

with SoloStar. 
• Do not select a dose and/or press the injection button without a needle attached. 
• Always perform the safety test before each injection (see Step 3). 
• This pen is only for your use. Do not share it with anyone else.  
• If your injection is given by another person, special caution must be taken by this person to avoid 

accidental needle injury and transmission of infection. 
• Never use SoloStar if it is damaged or if you are not sure that it is working properly. 
• Always have a spare SoloStar in case your SoloStar is lost or damaged. 
 
 
Step 1. Check the insulin 
 
A. Check the label on your SoloStar to make sure you have the correct insulin. Insulin Human 

Winthrop SoloStar is white with a colour on the injection button. The injection button colour 
will vary based on the formulation of Insulin Human Winthrop insulin used. The pictures below 
are for illustrative purposes only. 

 
B. Take off the pen cap. 
 
C. Check the appearance of your insulin.  

 

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If you are using a suspension insulin (Insulin Human Winthrop Basal or Insulin Human 
Winthrop mixtures), turn the pen up and down at least 10 times to resuspend the insulin. Turn 
the pen gently to avoid foaming in the cartridge.  

 

   
 

After mixing check the appearance of your insulin. Insulin suspensions must have an 
evenly milky-white appearance.  

 
 
Step 2. Attach the needle 
 
Always use a new sterile needle for each injection. This helps prevent contamination, and potential 
needle blocks. 
 
Before use of needle, carefully read the “Instructions for Use” accompanying the needles.  
 
Please note: The needles shown are for illustrative purposes only. 

 
A. Remove the protective seal from a new needle.  
 
B. Line up the needle with the pen, and keep it straight as you attach it (screw or push on, 

depending on the needle type). 
 

 . 
 

• If the needle is not kept straight while you attach it, it can damage the rubber seal and cause 
leakage, or break the needle. 

 

   
 
 
Step 3. Perform a safety test  
 
Always perform the safety test before each injection. This ensures that you get an accurate dose by: 
• ensuring that pen and needle work properly 
• removing air bubbles 
 
A. Select a dose of 2 units by turning the dosage selector. 

 

 

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B. Take off the outer needle cap and keep it to remove the used needle after injection. Take off the 

inner needle cap and discard it.  
 

   
 
C. Hold the pen with the needle pointing upwards. 
 
D. Tap the insulin reservoir so that any air bubbles rise up towards the needle. 
 
E. Press the injection button all the way in. Check if insulin comes out of the needle tip. 

   
 
You may have to perform the safety test several times before insulin is seen.  
 
• If no insulin comes out, check for air bubbles and repeat the safety test two more times to 

remove them. 
• If still no insulin comes out, the needle may be blocked. Change the needle and try again. 
• If no insulin comes out after changing the needle, your SoloStar may be damaged. Do not use 

this SoloStar. 
 
Step 4. Select the dose 
 
You can set the dose in steps of 1 unit, from a minimum of 1 unit to a maximum of 80 units. If you 
need a dose greater than 80 units, you should give it as two or more injections. 
 
A. Check that the dose window shows “0” following the safety test. 
 
B. Select your required dose (in the example below, the selected dose is 30 units). If you turn past 

your dose, you can turn back down. 
 

  
 

 

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• Do not push the injection button while turning, as insulin will come out. 
 
• You cannot turn the dosage selector past the number of units left in the pen. Do not force the 

dosage selector to turn. In this case, either you can inject what is remaining in the pen and 
complete your dose with a new SoloStar or use a new SoloStar for your full dose. 

 
 
Step 5. Inject the dose 
 
A. Use the injection method as instructed by your doctor, pharmacist or nurse.  
 
B. Insert the needle into the skin. 
 

   
 
C. Deliver the dose by pressing the injection button in all the way. The number in the dose window 

will return to “0” as you inject.  

   
 

D. Keep the injection button pressed all the way in. Slowly count to 10 before you withdraw the 
needle from the skin. This ensures that the full dose will be delivered. 
 
The pen plunger moves with each dose. The plunger will reach the end of the cartridge when 
the total of 300 units of insulin have been used. 

 
 
Step 6. Remove and discard the needle 
 
Always remove the needle after each injection and store SoloStar without a needle attached.  
This helps prevent: 
• Contamination and/or infection  
• Entry of air into the insulin reservoir and leakage of insulin, which can cause inaccurate dosing. 
 
A. Put the outer needle cap back on the needle, and use it to unscrew the needle from the pen. To 

reduce the risk of accidental needle injury, never replace the inner needle cap.  
 

• If your injection is given by another person, or if you are giving an injection to another person, 
special caution must be taken by this person when removing and disposing of the needle. Follow 
recommended safety measures for removal and disposal of needles (e.g. contact your doctor, 
pharmacist or nurse) in order to reduce the risk of accidental needle injury and transmission of 
infectious diseases. 

 
B. Dispose of the needle safely.  
 
C. Always put the pen cap back on the pen, then store the pen until your next injection. 
 
 

 

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Storage instructions  
 
Please check the reverse (insulin) side of this leaflet for instructions on how to store SoloStar. 
 
If your SoloStar is in cool storage, take it out 1 to 2 hours before you inject to allow it to warm up. 
Cold insulin is more painful to inject. 
 
Discard your used SoloStar as required by your local authorities. 
 
 
Maintenance 
 
Protect your SoloStar from dust and dirt. 
 
You can clean the outside of your SoloStar by wiping it with a damp cloth.  
 
Do not soak, wash or lubricate the pen as this may damage it.  
 
Your SoloStar is designed to work accurately and safely. It should be handled with care. Avoid 
situations where SoloStar might be damaged. If you are concerned that your SoloStar may be 
damaged, use a new one. 
 
 

 

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Package leaflet: Information for the user 

 
Insulin Human Winthrop Comb 30 100 IU/ml suspension for injection in a vial 

Insulin human 
 
 
Read all of this leaflet carefully before you start using this medicine because it contains 
important information for you. 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor, pharmacist or nurse. 
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours. 
- If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible 

side effects not listed in this leaflet. 
 
What is in this leaflet: 
1. What Insulin Human Winthrop Comb 30 is and what it is used for 
2. What you need to know before you use Insulin Human Winthrop Comb 30 
3. How to use Insulin Human Winthrop Comb 30 
4. Possible side effects 
5. How to store Insulin Human Winthrop Comb 30 
6. Contents of the pack and other information 
 
 
1. What Insulin Human Winthrop Comb 30 is and what it is used for 
 
Insulin Human Winthrop Comb 30 contains the active substance insulin human which is made by a 
biotechnology process and is identical with the body's own insulin. 
 
Insulin Human Winthrop Comb 30 is an insulin preparation with a gradual onset and long duration of 
action.  
 
Insulin Human Winthrop Comb 30 is used to reduce high blood sugar in patients with diabetes 
mellitus who need treatment with insulin. Diabetes mellitus is a disease where your body does not 
produce enough insulin to control the level of blood sugar. 
 
 
2. What you need to know before you use Insulin Human Winthrop Comb 30 
 
Do not use Insulin Human Winthrop Comb 30 
 
If you are allergic to insulin or any of the other ingredients of this medicine (listed in section 6).  
 
Warnings and precautions 
 
Talk to your doctor, pharmacist or nurse before using Insulin Human Winthrop Comb 30. 
Follow closely the instructions for dosage, monitoring (blood and urine tests), diet and physical 
activity (physical work and exercise) as discussed with your doctor. 
 
If you are allergic to this medicine or to animal insulins, talk to your doctor. 
 
Special patient groups 
If you have liver or kidneys problems or if you are elderly, speak to your doctor as you may need a 
lower dose. 
 

 

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Travel 
Before travelling, consult your doctor. You may need to talk about 
- the availability of your insulin in the country you are visiting, 
- supplies of insulin, injection syringes etc., 
- correct storage of your insulin while travelling, 
- timing of meals and insulin administration while travelling, 
- the possible effects of changing to different time zones, 
- possible new health risks in the countries to be visited, 
- what you should do in emergency situations when you feel unwell or become ill. 
 
Illnesses and injuries 
In the following situations, the management of your diabetes may require a lot of care: 
- If you are ill or have a major injury then your blood sugar level may increase (hyperglycaemia).  
- If you are not eating enough, your blood sugar level may become too low (hypoglycaemia).  
In most cases you will need a doctor. Make sure that you contact a doctor early.  
 
If you have type 1 diabetes (insulin dependent diabetes mellitus), do not stop your insulin and 
continue to get enough carbohydrates. Always tell people who are caring for you or treating you that 
you require insulin. 
 
Some patients with long-standing type 2 diabetes mellitus and heart disease or previous stroke who 
were treated with pioglitazone and insulin experienced the development of heart failure. Inform your 
doctor as soon as possible if you experience signs of heart failure such as unusual shortness of breath 
or rapid increase in weight or localised swelling (oedema). 
 
Other medicines and Insulin Human Winthrop Comb 30 
 
Some medicines cause changes in the blood sugar level (decrease, increase or both depending on the 
situation). In each case, it may be necessary to adjust your insulin dosage to avoid blood sugar levels 
that are either too low or too high. Be careful when you start or stop taking another medicine. 
 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines. Before taking a medicine ask your doctor if it can affect your blood sugar level, and what 
action, if any, you need to take. 
 
Medicines that may cause your blood sugar level to fall (hypoglycaemia) include:  
- all other medicines to treat diabetes,  
- angiotensin converting enzyme (ACE) inhibitors (used to treat certain heart conditions or high 

blood pressure),  
- disopyramide (used to treat certain heart conditions),  
- fluoxetine (used to treat depression),  
- fibrates (used to lower high levels of blood lipids),  
- monoamine oxidase (MAO) inhibitors (used to treat depression),  
- pentoxifylline, propoxyphene, salicylates (such as aspirin, used to relieve pain and lower fever), 
- sulfonamide antibiotics. 
 
Medicines that may cause your blood sugar level to rise (hyperglycaemia) include:  
- corticosteroids (such as "cortisone", used to treat inflammation),  
- danazol (medicine acting on ovulation),  
- diazoxide (used to treat high blood pressure),  
- diuretics (used to treat high blood pressure or excessive fluid retention),  
- glucagon (pancreas hormone used to treat severe hypoglycaemia),  
- isoniazid (used to treat tuberculosis),  
- oestrogens and progestogens (such as in the contraceptive pill used for birth control),  
- phenothiazine derivatives (used to treat psychiatric disorders),  
- somatropin (growth hormone),  

 

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- sympathomimetic medicines (such as epinephrine [adrenaline] or salbutamol, terbutaline used to 
treat asthma), 

- thyroid hormones (used to treat the thyroid gland disorders), 
- protease inhibitors (used to treat HIV), 
- atypical antipsychotic medicines (such as olanzapine and clozapine). 
 
Your blood sugar level may either rise or fall if you take:  
- beta-blockers (used to treat high blood pressure),  
- clonidine (used to treat high blood pressure), 
- lithium salts (used to treat psychiatric disorders).  
Pentamidine (used to treat some infections caused by parasites) may cause hypoglycaemia which may 
sometimes be followed by hyperglycaemia. 
 
Beta-blockers like other sympatholytic medicines (such as clonidine, guanethidine, and reserpine) may 
weaken or suppress entirely the first warning symptoms which help you to recognise a 
hypoglycaemia. 
 
If you are not sure whether you are taking one of those medicines ask your doctor or pharmacist. 
 
Insulin Human Winthrop Comb 30 with alcohol 
 
Your blood sugar levels may either rise or fall if you drink alcohol. 
 
Pregnancy and breast-feeding 
 
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor or pharmacist for advice before taking this medicine. 
 
Inform your doctor if you are planning to become pregnant, or if you are already pregnant. Your 
insulin dosage may need to be changed during pregnancy and after giving birth. Particularly careful 
control of your diabetes, and prevention of hypoglycaemia, is important for the health of your baby.  
 
If you are breast-feeding consult your doctor as you may require adjustments in your insulin doses and 
your diet. 
 
Driving and using machines 
 
Your ability to concentrate or react may be reduced if: 
- you have hypoglycaemia (low blood sugar levels), 
- you have hyperglycaemia (high blood sugar levels), 
- you have problems with your sight.  
Keep this possible problem in mind in all situations where you might put yourself and others at risk 
(such as driving a car or using machines). You should contact your doctor for advice on driving if: 
- you have frequent episodes of hypoglycaemia, 
- the first warning symptoms which help you to recognise hypoglycaemia are reduced or absent. 
 
Important information about some of the ingredients of Insulin Human Winthrop Comb 30  
 
This medicine contains less than 1 mmol (23 mg) sodium per dose, i.e. it is essentially ‘sodium-free’. 
 
 

 

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3. How to use Insulin Human Winthrop Comb 30 
 
Dose 
 
Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor 
or pharmacist if you are not sure. 
 
Based on your life-style and the results of your blood sugar (glucose) tests, your doctor will 
- determine how much Insulin Human Winthrop Comb 30 per day you will need, 
- tell you when to check your blood sugar level, and whether you need to carry out urine tests, 
- tell you when you may need to inject a higher or lower dose of Insulin Human Winthrop 

Comb 30. 
 
Many factors may influence your blood sugar level. You should know these factors so that you are 
able to react correctly to changes in your blood sugar level and to prevent it from becoming too high 
or too low. See the box at the end of this leaflet for further information. 
 
Frequency of administration 
 
Insulin Human Winthrop Comb 30 is injected under the skin 30 to 45 minutes before a meal.  
 
Method of administration 
 
Insulin Human Winthrop Comb 30 is a fluid (suspension) for injection under the skin. 
 
Do NOT inject Insulin Human Winthrop Comb 30 into a vein (blood vessel). 
 
Your doctor will show you in which area of the skin you should inject your insulin. With each 
injection, change the puncture site within the particular area of skin that you are using. 
 
Do not use it in insulin pumps or other infusion pumps - special insulin preparations are available for 
use in such devices. 
 
How to handle the vials 
 
Insulin Human Winthrop Comb 30 contains 100 IU insulin per ml. Only injection syringes designed 
for this insulin concentration (100 IU per ml) must be used. The injection syringes must not contain 
any other medicines or traces of medicines (such as traces of heparin). 
 
Before the first withdrawal of insulin you must remove the safety tear-off cap on the vial. 
 
Mix the insulin well immediately before each injection. This is best done by rolling the vial tilted 
between the palms of the hands. Do not shake the vial vigorously as this could damage the insulin and 
cause froth to form. Froth can make it difficult for you to measure the correct dose. 
 
After mixing, the suspension must have a uniform milky-white appearance. It must not be used if it 
remains clear or if, for example, clumps, flakes, particles or anything similar are in the suspension or 
on the sides or bottom of the vial. A new vial with a uniform suspension on mixing must then be used. 
 
Always use a new vial must also be used if you notice that your blood sugar control is unexpectedly 
getting worse. This is because the insulin may have lost some of its effectiveness. If you think you 
may have a problem with your insulin, have it checked by your doctor or pharmacist. 
 

 

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Special care before injection 
 
Before injection remove any air bubbles. Make sure that neither alcohol nor other disinfectants or 
other substances contaminate the insulin. Do not mix insulin with any other medicines except with 
insulin human preparations as detailed below. 
 
Insulin Human Winthrop Comb 30 may be mixed with all insulin human preparations, EXCEPT those 
specially designed for use in insulin pumps. Also, it must NOT be mixed with animal source insulins 
or insulin analogues. 
 
Your doctor will tell you if you have to mix insulin human preparations. If you need to inject a 
mixture, draw the other insulin into the injection syringe before Insulin Human Winthrop Comb 30. 
Inject as soon as you have mixed them. Do not mix insulins of different strengths (for example 100 IU 
per ml and 40 IU per ml). 
 
If you use more Insulin Human Winthrop Comb 30 than you should 
- If you have injected too much Insulin Human Winthrop Comb 30, your blood sugar level 

may become too low (hypoglycaemia). Check your blood sugar frequently. In general, to 
prevent hypoglycaemia you must eat more food and monitor your blood sugar. For information 
on the treatment of hypoglycaemia, see box at the end of this leaflet. 

 
If you forget to use Insulin Human Winthrop Comb 30 
- If you have missed a dose of Insulin Human Winthrop Comb 30 or if you have not injected 

enough insulin, your blood sugar level may become too high (hyperglycaemia). Check your 
blood sugar frequently. For information on the treatment of hyperglycaemia, see box at the end 
of this leaflet. 

 
- Do not take a double dose to make up for a forgotten dose. 
 
If you stop using Insulin Human Winthrop Comb 30 
This could lead to severe hyperglycaemia (very high blood sugar) and ketoacidosis (build-up of acid 
in the blood because the body is breaking down fat instead of sugar). Do not stop Insulin Human 
Winthrop Comb 30 without speaking to a doctor, who will tell you what needs to be done. 
 
If you have any further questions on the use of this medicine, ask your doctor or pharmacist or nurse. 
 
Insulin Mix-ups 
 
You must always check the insulin label before each injection to avoid mix-ups between Insulin 
Human Winthrop Comb 30 and other insulins.  
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
The most frequent side effect is hypoglycaemia (low blood sugar). The specific frequency cannot be 
estimated from available data (frequency not known). Serious hypoglycaemia may cause a heart attack 
or brain damage and may be life-threatening. For further information on the side effects of low blood 
sugar or high blood sugar, see the box at the end of this leaflet. 
 
Severe allergic reactions to insulin may occur which may become life-threatening. Such reactions to 
insulin or to the excipients can cause large-scale skin reactions (rash and itching all over the body); 
severe swelling of skin or mucous membranes (angiooedema), shortness of breath, a fall in blood 
pressure with rapid heart beat and sweating. Frequency of these reactions cannot be estimated from 
available data. 
 

 

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Side effects reported commonly (may affect up to 1 in 10 people) 
• Oedema 
Insulin treatment may cause temporary build-up of water in the body with swelling in the calves and 
ankles. 
• Injection site reactions 
 
Side effects reported uncommonly (may affect up to 1 in 100 people) 
• Severe allergic reaction with low blood pressure (shock) 
• Injection site urticaria (itchy rash) 
 
Other side effects include (frequency cannot be estimated from the available data) 
• Sodium retention 
• Eye reactions 
A marked change (improvement or worsening) in your blood sugar control can disturb your vision 
temporarily. If you have proliferative retinopathy (an eye disease related to diabetes) severe 
hypoglycaemic attacks may cause temporary loss of vision. 
• Skin changes at the injection site (lipodystrophy) 
If you inject your insulin too often at the same skin site, fatty tissue under the skin at this site may 
either shrink or thicken. Insulin that you inject in such a site may not work very well. Changing the 
injection site with each injection may help to prevent such skin changes. 
• Skin and allergic reactions 
Other mild reactions at the injection site (such as injection site redness, unusually intense pain on 
injection site, itching, injection site swelling or injection site inflammation) may occur. They can also 
spread around the injection site. Most minor reactions to insulins usually resolve in a few days to a 
few weeks. 
 
Insulin treatment can cause the body to produce antibodies to insulin (substances that act against 
insulin). However, only very rarely, this will require a change to your insulin dosage. 
 
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side 
effects not listed in this leaflet. 
 
 
5. How to store Insulin Human Winthrop Comb 30 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date which is stated on the carton and on the label of the vial 
after “EXP”. The expiry date refers to the last day of that month. 
 
Unopened vials 
Store in a refrigerator (2°C – 8°C). Do not freeze. Do not put Insulin Human Winthrop Comb 30 next 
to the freezer compartment or a freezer pack. Keep the vial in the outer carton in order to protect from 
light. 
 
Opened vials 
Once in-use, the vial may be stored for a maximum of 4 weeks in the outer carton not above 25°C and 
away from direct heat (for example next to a heating unit) or direct light (direct sunlight or next to a 
lamp). Do not use the vial after this time period. It is recommended that the date of the first use be 
noted on the label. 
 
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment. 
 
 

 

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6. Contents of the pack and other information 
 
What Insulin Human Winthrop Comb 30 contains 
- The active substance is insulin human. One ml of Insulin Human Winthrop Comb 30 contains 

100 IU (International Units) of the active substance insulin human. 30% of the insulin is 
dissolved in water; the other 70% is present as tiny crystals of insulin protamine. 

- The other ingredients are: protamine sulphate, metacresol, phenol, zinc chloride, sodium 
dihydrogen phosphate dihydrate, glycerol, sodium hydroxide (see section 2 under “Important 
information about some of the ingredients of Insulin Human Winthrop Comb 30”), hydrochloric 
acid (for pH adjustment) and water for injections. 

 
What Insulin Human Winthrop Comb 30 looks like and contents of the pack 
After mixing, Insulin Human Winthrop Comb 30 is a uniformly milky fluid (suspension for injection), 
with no clumps, particles or flocculation visible. 
 
Insulin Human Winthrop Comb 30 is supplied in vials containing 5 ml of suspension for injection 
(equivalent to 500 IU) or 10 ml of suspension for injection (equivalent to 1000 IU). Packs of 1 and 
5 vials of 5 ml or 10 ml are available. Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder and Manufacturer 
Sanofi-Aventis Deutschland GmbH 
D-65926 Frankfurt am Main 
Germany 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
Sanofi Belgium 
Tél/Tel: +32 (0)2 710 54 00 
 

Lietuva 
UAB «SANOFI-AVENTIS LIETUVA» 
Tel: +370 5 2755224 
 

България 
sanofi-aventis Bulgaria EOOD 
Тел.: +359 (0)2 970 53 00 
 

Luxembourg/Luxemburg 
Sanofi Belgium  
Tél/Tel: +32 (0)2 710 54 00 (Belgique/Belgien) 
 

Česká republika 
sanofi-aventis, s.r.o. 
Tel: +420 233 086 111 
 

Magyarország 
SANOFI-AVENTIS Zrt. 
Tel.: +36 1 505 0050 
 

Danmark 
sanofi-aventis Denmark A/S 
Tlf: +45 45 16 70 00 
 

Malta 
Sanofi Malta Ltd. 
Tel: +356 21493022 
 

Deutschland 
Zentiva Pharma GmbH 
Tel: +49 (0)180 20 200 10 
 

Nederland 
sanofi-aventis Netherlands B.V. 
Tel: +31 (0)182 557 755 
 

Eesti 
sanofi-aventis Estonia OÜ 
Tel: +372 627 34 88 
 

Norge 
Aventis Pharma Norge AS 
Tlf: +47 67 10 71 00 
 

Ελλάδα 
sanofi-aventis AEBE 
Τηλ: +30 210 900 16 00 
 

Österreich 
sanofi-aventis GmbH 
Tel: +43 1 80 185 – 0 
 

 

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España 
sanofi-aventis, S.A. 
Tel: +34 93 485 94 00 
 

Polska 
sanofi-aventis Sp . z o.o. 
Tel.: +48 22 280 00 00 
 

France 
sanofi-aventis France 
Tél: 0 800 222 555 
Appel depuis l’étranger : +33 1 57 63 23 23 
 

Portugal 
Sanofi - Produtos Farmacêuticos, Lda. 
Tel: +351 21 35 89 400 
 

Hrvatska 
sanofi-aventis Croatia d.o.o. 
Tel: +385 1 600 34 00 

România 
Sanofi Romania SRL 
Tel: +40 (0) 21 317 31 36 
 

Ireland 
sanofi-aventis Ireland Ltd. T/A SANOFI 
Tel: +353 (0) 1 403 56 00 
 

Slovenija 
sanofi-aventis d.o.o. 
Tel: +386 1 560 48 00 
 

Ísland 
Vistor hf. 
Sími: +354 535 7000 
 

Slovenská republika 
sanofi-aventis Pharma Slovakia s.r.o. 
Tel: +421 2 33 100 100 
 

Italia 
Sanofi S.p.A. 
Tel: 800 13 12 12 (domande di tipo tecnico)  
800 536389 (altre domande) 
 

Suomi/Finland 
Sanofi Oy 
Puh/Tel: +358 (0) 201 200 300 
 

Κύπρος 
sanofi-aventis Cyprus Ltd. 
Τηλ: +357 22 871600 
 

Sverige 
Sanofi AB 
Tel: +46 (0)8 634 50 00 
 

Latvija 
sanofi-aventis Latvia SIA 
Tel: +371 67 33 24 51 
 

United Kingdom 
Sanofi 
Tel: +44 (0) 845 372 7101 
 

 
This leaflet was last revised in {date} 
 
 
Other source of information 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu/ 
 
 
 
 

HYPERGLYCAEMIA AND HYPOGLYCAEMIA 
 

Always carry some sugar (at least 20 grams) with you. 
Carry some information with you to show you are diabetic. 

 
HYPERGLYCAEMIA (high blood sugar levels) 

 
If your blood sugar is too high (hyperglycaemia), you may not have injected enough insulin. 
 
Why does hyperglycaemia occur? 
 
Examples include: 

 

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- you have not injected your insulin or not injected enough, or if it has become less effective, for 
example through incorrect storage, 

- you are doing less exercise than usual, you are under stress (emotional distress, excitement), or 
you have an injury, operation, infection or fever, 

- you are taking or have taken certain other medicines (see section 2, "Other medicines and 
Insulin Human Winthrop Comb 30"). 

 
Warning symptoms of hyperglycaemia 
 
Thirst, increased need to urinate, tiredness, dry skin, reddening of the face, loss of appetite, low blood 
pressure, fast heart beat, and glucose and ketone bodies in urine. Stomach pain, fast and deep 
breathing, sleepiness or even loss of consciousness may be signs of a serious condition (ketoacidosis) 
resulting from lack of insulin. 
 
What should you do if you experience hyperglycaemia 
 
Test your blood sugar level and your urine for ketones as soon as any of the above symptoms 
occur. Severe hyperglycaemia or ketoacidosis must always be treated by a doctor, normally in a 
hospital. 
 

HYPOGLYCAEMIA (low blood sugar levels) 
 
If your blood sugar level falls too much you may become unconscious. Serious hypoglycaemia may 
cause a heart attack or brain damage and may be life-threatening. You normally should be able to 
recognise when your blood sugar is falling too much so that you can take the right actions. 
 
Why does hypoglycaemia occur? 
 
Examples include: 
- you inject too much insulin, 
- you miss meals or delay them, 
- you do not eat enough, or eat food containing less carbohydrate than normal (sugar and 

substances similar to sugar are called carbohydrates; however, artificial sweeteners are NOT 
carbohydrates), 

- you lose carbohydrates due to vomiting or diarrhoea, 
- you drink alcohol, particularly if you are not eating much, 
- you are doing more exercise than usual or a different type of physical activity, 
- you are recovering from an injury or operation or other stress, 
- you are recovering from an illness or from fever, 
- you are taking or have stopped taking certain other medicines (see section 2, "Other medicines 

and Insulin Human Winthrop Comb 30"). 
 
Hypoglycaemia is also more likely to occur if: 
- you have just begun insulin treatment or changed to another insulin preparation, 
- your blood sugar levels are almost normal or are unstable, 
- you change the area of skin where you inject insulin (for example from the thigh to the upper 

arm), 
- you suffer from severe kidney or liver disease, or some other disease such as hypothyroidism. 
 
Warning symptoms of hypoglycaemia 
 
- In your body 
Examples of symptoms that tell you that your blood sugar level is falling too much or too fast: 
sweating, clammy skin, anxiety, fast heart beat, high blood pressure, palpitations and irregular 
heartbeat. These symptoms often develop before the symptoms of a low sugar level in the brain. 
 

 

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- In your brain 
Examples of symptoms that indicate a low sugar level in the brain: headaches, intense hunger, nausea, 
vomiting, tiredness, sleepiness, sleep disturbances, restlessness, aggressive behaviour, lapses in 
concentration, impaired reactions, depression, confusion, speech disturbances (sometimes total loss of 
speech), visual disorders, trembling, paralysis, tingling sensations (paraesthesia), numbness and 
tingling sensations in the area of the mouth, dizziness, loss of self-control, inability to look after 
yourself, convulsions, loss of consciousness. 
 
The first symptoms which alert you to hypoglycaemia ("warning symptoms") may change, be weaker 
or may be missing altogether if 
- you are elderly, if you have had diabetes for a long time or if you suffer from a certain type of 

nervous disease (diabetic autonomic neuropathy), 
- you have recently suffered hypoglycaemia (for example the day before) or if it develops slowly, 
- you have almost normal or, at least, greatly improved blood sugar levels, 
- you have recently changed from an animal insulin to a human insulin such as Insulin Human 

Winthrop, 
- you are taking or have taken certain other medicines (see section 2, "Other medicines and 

Insulin Human Winthrop Comb 30"). 
 
In such a case, you may develop severe hypoglycaemia (and even faint) before you are aware of the 
problem. Be familiar with your warning symptoms. If necessary, more frequent blood sugar testing 
can help to identify mild hypoglycaemic episodes that may otherwise be overlooked. If you are not 
confident about recognising your warning symptoms, avoid situations (such as driving a car) in which 
you or others would be put at risk by hypoglycaemia. 
 
What should you do if you experience hypoglycaemia 
 
1. Do not inject insulin. Immediately take about 10 to 20 g sugar, such as glucose, sugar cubes or a 

sugar-sweetened beverage. Caution: Artificial sweeteners and foods with artificial sweeteners 
(such as diet drinks) are of no help in treating hypoglycaemia. 

2. Then eat something that has a long-acting effect in raising your blood sugar (such as bread or 
pasta). Your doctor or nurse should have discussed this with you previously. 

3. If the hypoglycaemia comes back again take another 10 to 20 g sugar. 
4. Speak to a doctor immediately if you are not able to control the hypoglycaemia or if it recurs. 
 
Tell your relatives, friends and close colleagues the following: 
If you are not able to swallow or if you are unconscious, you will require an injection of glucose or 
glucagon (a medicine which increases blood sugar). These injections are justified even if it is not 
certain that you have hypoglycaemia. 
 
It is advisable to test your blood sugar immediately after taking glucose to check that you really have 
hypoglycaemia. 

 
 

 

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Package leaflet: Information for the user 

 
Insulin Human Winthrop Comb 30 100 IU/ml suspension for injection in a cartridge 

Insulin human 
 
 
Read all of this leaflet carefully before you start using this medicine because it contains 
important information for you. The instructions for using the insulin pen are provided with 
your insulin pen. Refer to them before using your medicine. 
 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor, pharmacist or nurse. 
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours. 
- If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible 

side effects not listed in this leaflet. 
 
What is in this leaflet: 
1. What Insulin Human Winthrop Comb 30 is and what it is used for 
2. What you need to know before you use Insulin Human Winthrop Comb 30 
3. How to use Insulin Human Winthrop Comb 30 
4. Possible side effects 
5. How to store Insulin Human Winthrop Comb 30 
6. Contents of the pack and other information 
 
 
1. What Insulin Human Winthrop Comb 30 is and what it is used for 
 
Insulin Human Winthrop Comb 30 contains the active substance insulin human which is made by a 
biotechnology process and is identical with the body's own insulin. 
 
Insulin Human Winthrop Comb 30 is an insulin preparation with a gradual onset and long duration of 
action.  
 
Insulin Human Winthrop Comb 30 is used to reduce high blood sugar in patients with diabetes 
mellitus who need treatment with insulin. Diabetes mellitus is a disease where your body does not 
produce enough insulin to control the level of blood sugar. 
 
 
2. What you need to know before you use Insulin Human Winthrop Comb 30 
 
Do not use Insulin Human Winthrop Comb 30 
 

If you are allergic to insulin or any of the other ingredients of this medicine (listed in section 6).  
 
Warnings and precautions 
 
Talk to your doctor, pharmacist or nurse before using Insulin Human Winthrop Comb 30. 
Follow closely the instructions for dosage, monitoring (blood and urine tests), diet and physical 
activity (physical work and exercise) as discussed with your doctor. 
 
If you are allergic to this medicine or to animal insulins, talk to your doctor. 
 
Special patient groups 
If you have liver or kidneys problems or if you are elderly, speak to your doctor as you may need a 
lower dose. 

 

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Travel 
Before travelling, consult your doctor. You may need to talk about 
- the availability of your insulin in the country you are visiting, 
- supplies of insulin, injection syringes etc., 
- correct storage of your insulin while travelling, 
- timing of meals and insulin administration while travelling, 
- the possible effects of changing to different time zones, 
- possible new health risks in the countries to be visited, 
- what you should do in emergency situations when you feel unwell or become ill. 
 
Illnesses and injuries 
In the following situations, the management of your diabetes may require a lot of care: 
- If you are ill or have a major injury then your blood sugar level may increase (hyperglycaemia).  
- If you are not eating enough, your blood sugar level may become too low (hypoglycaemia).  
In most cases you will need a doctor. Make sure that you contact a doctor early.  
 
If you have type 1 diabetes (insulin dependent diabetes mellitus), do not stop your insulin and 
continue to get enough carbohydrates. Always tell people who are caring for you or treating you that 
you require insulin. 
 
Some patients with long-standing type 2 diabetes mellitus and heart disease or previous stroke who 
were treated with pioglitazone and insulin experienced the development of heart failure. Inform your 
doctor as soon as possible if you experience signs of heart failure such as unusual shortness of breath 
or rapid increase in weight or localised swelling (oedema). 
 
Other medicines and Insulin Human Winthrop Comb 30 
 
Some medicines cause changes in the blood sugar level (decrease, increase or both depending on the 
situation). In each case, it may be necessary to adjust your insulin dosage to avoid blood sugar levels 
that are either too low or too high. Be careful when you start or stop taking another medicine. 
 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines. Before taking a medicine ask your doctor if it can affect your blood sugar level, and what 
action, if any, you need to take. 
 
Medicines that may cause your blood sugar level to fall (hypoglycaemia) include:  
- all other medicines to treat diabetes,  
- angiotensin converting enzyme (ACE) inhibitors (used to treat certain heart conditions or high 

blood pressure),  
- disopyramide (used to treat certain heart conditions),  
- fluoxetine (used to treat depression),  
- fibrates (used to lower high levels of blood lipids),  
- monoamine oxidase (MAO) inhibitors (used to treat depression),  
- pentoxifylline, propoxyphene, salicylates (such as aspirin, used to relieve pain and lower fever), 
- sulfonamide antibiotics. 
 
Medicines that may cause your blood sugar level to rise (hyperglycaemia) include:  
- corticosteroids (such as "cortisone", used to treat inflammation),  
- danazol (medicine acting on ovulation),  
- diazoxide (used to treat high blood pressure),  
- diuretics (used to treat high blood pressure or excessive fluid retention),  
- glucagon (pancreas hormone used to treat severe hypoglycaemia),  
- isoniazid (used to treat tuberculosis),  
- oestrogens and progestogens (such as in the contraceptive pill used for birth control),  
- phenothiazine derivatives (used to treat psychiatric disorders),  
- somatropin (growth hormone),  

 

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- sympathomimetic medicines (such as epinephrine [adrenaline] or salbutamol, terbutaline used to 
treat asthma), 

- thyroid hormones (used to treat the thyroid gland disorders), 
- protease inhibitors (used to treat HIV), 
- atypical antipsychotic medicines (such as olanzapine and clozapine). 
 
Your blood sugar level may either rise or fall if you take:  
- beta-blockers (used to treat high blood pressure),  
- clonidine (used to treat high blood pressure), 
- lithium salts (used to treat psychiatric disorders).  
Pentamidine (used to treat some infections caused by parasites) may cause hypoglycaemia which may 
sometimes be followed by hyperglycaemia. 
 
Beta-blockers like other sympatholytic medicines (such as clonidine, guanethidine, and reserpine) may 
weaken or suppress entirely the first warning symptoms which help you to recognise a 
hypoglycaemia. 
 
If you are not sure whether you are taking one of those medicines ask your doctor or pharmacist. 
 
Insulin Human Winthrop Comb 30 with alcohol 
 
Your blood sugar levels may either rise or fall if you drink alcohol. 
 
Pregnancy and breast-feeding 
 
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor or pharmacist for advice before taking this medicine. 
 
Inform your doctor if you are planning to become pregnant, or if you are already pregnant. Your 
insulin dosage may need to be changed during pregnancy and after giving birth. Particularly careful 
control of your diabetes, and prevention of hypoglycaemia, is important for the health of your baby.  
 
If you are breast-feeding consult your doctor as you may require adjustments in your insulin doses and 
your diet. 
 
Driving and using machines 
 
Your ability to concentrate or react may be reduced if: 
- you have hypoglycaemia (low blood sugar levels), 
- you have hyperglycaemia (high blood sugar levels), 
- you have problems with your sight.  
Keep this possible problem in mind in all situations where you might put yourself and others at risk 
(such as driving a car or using machines). You should contact your doctor for advice on driving if: 
- you have frequent episodes of hypoglycaemia, 
- the first warning symptoms which help you to recognise hypoglycaemia are reduced or absent. 
 
Important information about some of the ingredients of Insulin Human Winthrop Comb 30  
 
This medicine contains less than 1 mmol (23 mg) sodium per dose, i.e. it is essentially ‘sodium-free’. 
 
 

 

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3. How to use Insulin Human Winthrop Comb 30 
 
Dose 
 
Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor 
or pharmacist if you are not sure. 
 
Based on your life-style and the results of your blood sugar (glucose) tests, your doctor will 
- determine how much Insulin Human Winthrop Comb 30 per day you will need, 
- tell you when to check your blood sugar level, and whether you need to carry out urine tests, 
- tell you when you may need to inject a higher or lower dose of Insulin Human Winthrop 

Comb 30. 
 
Many factors may influence your blood sugar level. You should know these factors so that you are 
able to react correctly to changes in your blood sugar level and to prevent it from becoming too high 
or too low. See the box at the end of this leaflet for further information. 
 
Frequency of administration 
 
Insulin Human Winthrop Comb 30 is injected under the skin 30 to 45 minutes before a meal.  
 
Method of administration 
 
Insulin Human Winthrop Comb 30 is a fluid (suspension) for injection under the skin. 
 
Do NOT inject Insulin Human Winthrop Comb 30 into a vein (blood vessel). 
 
Your doctor will show you in which area of the skin you should inject your insulin. With each 
injection, change the puncture site within the particular area of skin that you are using. 
 
Do not use it in insulin pumps or other infusion pumps - special insulin preparations are available for 
use in such devices. 
 
How to handle the cartridges 
 
To ensure you get the accurate dose, the Insulin Human Winthrop Comb 30 cartridges are to be used 
only with the following pens: 
- JuniorSTAR which delivers doses in steps of 0.5 units  
- OptiPen, ClikSTAR, Tactipen, Autopen 24 or AllStar which deliver doses in steps of 1 unit. 
Not all of these pens may be marketed in your country.  
 
The pen should be used as recommended in the information provided by the device manufacturer. The 
manufacturer’s instructions for using the pen must be followed carefully for loading the cartridge, 
attaching the injection needle, and administering the insulin injection. 
 
Keep the cartridge at room temperature for 1 or 2 hours before inserting it into the pen. Mix the 
insulin well and check it before you insert it into the pen. Later, you must mix the insulin well again 
immediately before each injection. 
 
Mixing is best done by gently tilting the cartridge or pen (with the cartridge in it) back and forth at 
least 10 times. To assist in mixing, three tiny metal balls are present in the cartridge. 
 
After mixing, the suspension must have a uniform milky-white appearance. It must not be used if it 
remains clear or if, for example, clumps, flakes, particles or anything similar are in the suspension or 
on the sides or bottom of the cartridge. A new cartridge with a uniform suspension on mixing must 
then be used. 
 

 

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Always use a new cartridge if you notice that your blood sugar control is unexpectedly getting worse. 
This is because the insulin may have lost some of its effectiveness. If you think you may have a 
problem with your insulin, have it checked by your doctor or pharmacist. 
 
Special care before injection 
 
Before injection remove any air bubbles (see instructions for using the pen). Make sure that neither 
alcohol nor other disinfectants or other substances contaminate the insulin. 
- Do not re-fill and re-use empty cartridges. 
- Do not add any other insulin to the cartridge. 
- Do not mix insulin with any other medicines. 
 
Problems with the pen? 
 
Refer to the manufacturer’s instructions for using the pen. 
If the insulin pen is damaged or not working properly (due to mechanical defects) it has to be 
discarded, and a new insulin pen has to be used. 
 
If the pen does not function well, you can draw the insulin from the cartridge into an injection syringe. 
Therefore, keep injection syringes and needles as well. However, use only those injection syringes 
which are designed for an insulin concentration of 100 IU (International Units) per ml. 
 
If you use more Insulin Human Winthrop Comb 30 than you should 
- If you have injected too much Insulin Human Winthrop Comb 30, your blood sugar level 

may become too low (hypoglycaemia). Check your blood sugar frequently. In general, to 
prevent hypoglycaemia you must eat more food and monitor your blood sugar. For information 
on the treatment of hypoglycaemia, see box at the end of this leaflet. 

 
If you forget to use Insulin Human Winthrop Comb 30 
- If you have missed a dose of Insulin Human Winthrop Comb 30 or if you have not injected 

enough insulin, your blood sugar level may become too high (hyperglycaemia). Check your 
blood sugar frequently. For information on the treatment of hyperglycaemia, see box at the end 
of this leaflet. 

 
- Do not take a double dose to make up for a forgotten dose. 
 
If you stop using Insulin Human Winthrop Comb 30 
This could lead to severe hyperglycaemia (very high blood sugar) and ketoacidosis (build-up of acid 
in the blood because the body is breaking down fat instead of sugar). Do not stop Insulin Human 
Winthrop Comb 30 without speaking to a doctor, who will tell you what needs to be done. 
 
If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse. 
 
Insulin Mix-ups 
 
You must always check the insulin label before each injection to avoid mix-ups between Insulin 
Human Winthrop Comb 30 and other insulins.  
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
The most frequent side effect is hypoglycaemia (low blood sugar). The specific frequency cannot be 
estimated from available data (frequency not known). Serious hypoglycaemia may cause a heart attack 
or brain damage and may be life-threatening. For further information on the side effects of low blood 
sugar or high blood sugar, see the box at the end of this leaflet. 

 

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Severe allergic reactions to insulin may occur which may become life-threatening. Such reactions to 
insulin or to the excipients can cause large-scale skin reactions (rash and itching all over the body); 
severe swelling of skin or mucous membranes (angiooedema), shortness of breath, a fall in blood 
pressure with rapid heart beat and sweating. Frequency of these reactions cannot be estimated from 
available data. 
 
Side effects reported commonly (may affect up to 1 in 10 people) 
• Oedema 
Insulin treatment may cause temporary build-up of water in the body with swelling in the calves and 
ankles. 
• Injection site reactions 
 
Side effects reported uncommonly (may affect up to 1 in 100 people) 
• Severe allergic reaction with low blood pressure (shock) 
• Injection site urticaria (itchy rash) 
 
Other side effects include (frequency cannot be estimated from the available data) 
• Sodium retention 
• Eye reactions 
A marked change (improvement or worsening) in your blood sugar control can disturb your vision 
temporarily. If you have proliferative retinopathy (an eye disease related to diabetes) severe 
hypoglycaemic attacks may cause temporary loss of vision. 
• Skin changes at the injection site (lipodystrophy) 
If you inject your insulin too often at the same skin site, fatty tissue under the skin at this site may 
either shrink or thicken. Insulin that you inject in such a site may not work very well. Changing the 
injection site with each injection may help to prevent such skin changes. 
• Skin and allergic reactions 
Other mild reactions at the injection site (such as injection site redness, unusually intense pain on 
injection site, itching, injection site swelling or injection site inflammation) may occur. They can also 
spread around the injection site. Most minor reactions to insulins usually resolve in a few days to a 
few weeks. 
 
Insulin treatment can cause the body to produce antibodies to insulin (substances that act against 
insulin). However, only very rarely, this will require a change to your insulin dosage. 
 
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side 
effects not listed in this leaflet. 
 
 
5. How to store Insulin Human Winthrop Comb 30 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date which is stated on the carton and on the label of the 
cartridge after “EXP”. The expiry date refers to the last day of that month. 
 
Unopened cartridges 
Store in a refrigerator (2°C - 8°C). Do not freeze. Do not put Insulin Human Winthrop Comb 30 next 
to the freezer compartment or a freezer pack. Keep the cartridge in the outer carton in order to protect 
from light. 
 
In-use cartridges 
Cartridges in-use (in the insulin pen) or carried as a spare may be stored for a maximum of 4 weeks 
not above 25°C and away from direct heat (for example next to a heating unit) or direct light (direct 
sunlight or next to a lamp). The cartridge in-use must not be stored in a refrigerator. Do not use the 
cartridge after this time period. 

 

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Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Insulin Human Winthrop Comb 30 contains 
- The active substance is insulin human. One ml of Insulin Human Winthrop Comb 30 contains 

100 IU (International Units) of the active substance insulin human. 30% of the insulin is 
dissolved in water; the other 70% is present as tiny crystals of insulin protamine. 

- The other ingredients are: protamine sulphate, metacresol, phenol, zinc chloride, sodium 
dihydrogen phosphate dihydrate, glycerol, sodium hydroxide (see section 2 under “Important 
information about some of the ingredients of Insulin Human Winthrop Comb 30”), hydrochloric 
acid (for pH adjustment) and water for injections. 

 
What Insulin Human Winthrop Comb 30 looks like and contents of the pack 
After mixing, Insulin Human Winthrop Comb 30 is a uniformly milky fluid (suspension for injection), 
with no clumps, particles or flocculation visible. 
 
Insulin Human Winthrop Comb 30 is supplied in cartridge containing 3 ml suspension (300 IU). Packs 
of 3, 4, 5, 6, 9 and 10 cartridges of 3 ml are available. Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder and Manufacturer 
Sanofi-Aventis Deutschland GmbH 
D-65926 Frankfurt am Main 
Germany 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
Sanofi Belgium 
Tél/Tel: +32 (0)2 710 54 00 
 

Lietuva 
UAB «SANOFI-AVENTIS LIETUVA» 
Tel: +370 5 2755224 
 

България 
sanofi-aventis Bulgaria EOOD 
Тел.: +359 (0)2 970 53 00 
 

Luxembourg/Luxemburg 
Sanofi Belgium  
Tél/Tel: +32 (0)2 710 54 00 (Belgique/Belgien) 
 

Česká republika 
sanofi-aventis, s.r.o. 
Tel: +420 233 086 111 
 

Magyarország 
SANOFI-AVENTIS Zrt. 
Tel.: +36 1 505 0050 
 

Danmark 
sanofi-aventis Denmark A/S 
Tlf: +45 45 16 70 00 
 

Malta 
Sanofi Malta Ltd. 
Tel: +356 21493022 
 

Deutschland 
Zentiva Pharma GmbH 
Tel: +49 (0)180 20 200 10 
 

Nederland 
sanofi-aventis Netherlands B.V. 
Tel: +31 (0)182 557 755 
 

Eesti 
sanofi-aventis Estonia OÜ 
Tel: +372 627 34 88 
 

Norge 
Aventis Pharma Norge AS 
Tlf: +47 67 10 71 00 
 

 

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Ελλάδα 
sanofi-aventis AEBE 
Τηλ: +30 210 900 16 00 
 

Österreich 
sanofi-aventis GmbH 
Tel: +43 1 80 185 – 0 
 

España 
sanofi-aventis, S.A. 
Tel: +34 93 485 94 00 
 

Polska 
sanofi-aventis Sp. z o.o. 
Tel.: +48 22 280 00 00 
 

France 
sanofi-aventis France 
Tél: 0 800 222 555 
Appel depuis l’étranger : +33 1 57 63 23 23 
 

Portugal 
Sanofi - Produtos Farmacêuticos, Lda. 
Tel: +351 21 35 89 400 
 

Hrvatska 
sanofi-aventis Croatia d.o.o. 
Tel: +385 1 600 34 00 

România 
Sanofi Romania SRL 
Tel: +40 (0) 21 317 31 36 
 

Ireland 
sanofi-aventis Ireland Ltd. T/A SANOFI 
Tel: +353 (0) 1 403 56 00 
 

Slovenija 
sanofi-aventis d.o.o. 
Tel: +386 1 560 48 00 
 

Ísland 
Vistor hf. 
Sími: +354 535 7000 
 

Slovenská republika 
sanofi-aventis Pharma Slovakia s.r.o. 
Tel: +421 2 33 100 100 
 

Italia 
Sanofi S.p.A. 
Tel: 800 13 12 12 (domande di tipo tecnico)  
800 536389 (altre domande) 
 

Suomi/Finland 
Sanofi Oy 
Puh/Tel: +358 (0) 201 200 300 
 

Κύπρος 
sanofi-aventis Cyprus Ltd. 
Τηλ: +357 22 871600 
 

Sverige 
Sanofi AB 
Tel: +46 (0)8 634 50 00 
 

Latvija 
sanofi-aventis Latvia SIA 
Tel: +371 67 33 24 51 
 

United Kingdom 
Sanofi 
Tel: +44 (0) 845 372 7101 
 

 
This leaflet was last revised in {date}  
 
 
Other source of information 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu/ 
 
 
 
 

HYPERGLYCAEMIA AND HYPOGLYCAEMIA 
 

Always carry some sugar (at least 20 grams) with you. 
Carry some information with you to show you are diabetic. 

 
HYPERGLYCAEMIA (high blood sugar levels) 

 
If your blood sugar is too high (hyperglycaemia), you may not have injected enough insulin. 

 

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Why does hyperglycaemia occur? 
 
Examples include: 
- you have not injected your insulin or not injected enough, or if it has become less effective, for 

example through incorrect storage, 
- your insulin pen does not work properly, 
- you are doing less exercise than usual, you are under stress (emotional distress, excitement), or 

you have an injury, operation, infection or fever, 
- you are taking or have taken certain other medicines (see section 2, "Other medicines and 

Insulin Human Winthrop Comb 30"). 
 
Warning symptoms of hyperglycaemia 
 
Thirst, increased need to urinate, tiredness, dry skin, reddening of the face, loss of appetite, low blood 
pressure, fast heart beat, and glucose and ketone bodies in urine. Stomach pain, fast and deep 
breathing, sleepiness or even loss of consciousness may be signs of a serious condition (ketoacidosis) 
resulting from lack of insulin. 
 
What should you do if you experience hyperglycaemia 
 
Test your blood sugar level and your urine for ketones as soon as any of the above symptoms 
occur. Severe hyperglycaemia or ketoacidosis must always be treated by a doctor, normally in a 
hospital. 
 

HYPOGLYCAEMIA (low blood sugar levels) 
 
If your blood sugar level falls too much you may become unconscious. Serious hypoglycaemia may 
cause a heart attack or brain damage and may be life-threatening. You normally should be able to 
recognise when your blood sugar is falling too much so that you can take the right actions. 
 
Why does hypoglycaemia occur? 
 
Examples include: 
- you inject too much insulin, 
- you miss meals or delay them, 
- you do not eat enough, or eat food containing less carbohydrate than normal (sugar and 

substances similar to sugar are called carbohydrates; however, artificial sweeteners are NOT 
carbohydrates), 

- you lose carbohydrates due to vomiting or diarrhoea, 
- you drink alcohol, particularly if you are not eating much, 
- you are doing more exercise than usual or a different type of physical activity, 
- you are recovering from an injury or operation or other stress, 
- you are recovering from an illness or from fever, 
- you are taking or have stopped taking certain other medicines (see section 2, "Other medicines 

and Insulin Human Winthrop Comb 30"). 
 
Hypoglycaemia is also more likely to occur if: 
- you have just begun insulin treatment or changed to another insulin preparation, 
- your blood sugar levels are almost normal or are unstable, 
- you change the area of skin where you inject insulin (for example from the thigh to the upper 

arm), 
- you suffer from severe kidney or liver disease, or some other disease such as hypothyroidism. 
 

 

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Warning symptoms of hypoglycaemia 
 
- In your body 
Examples of symptoms that tell you that your blood sugar level is falling too much or too fast: 
sweating, clammy skin, anxiety, fast heart beat, high blood pressure, palpitations and irregular 
heartbeat. These symptoms often develop before the symptoms of a low sugar level in the brain. 
 
- In your brain 
Examples of symptoms that indicate a low sugar level in the brain: headaches, intense hunger, nausea, 
vomiting, tiredness, sleepiness, sleep disturbances, restlessness, aggressive behaviour, lapses in 
concentration, impaired reactions, depression, confusion, speech disturbances (sometimes total loss of 
speech), visual disorders, trembling, paralysis, tingling sensations (paraesthesia), numbness and 
tingling sensations in the area of the mouth, dizziness, loss of self-control, inability to look after 
yourself, convulsions, loss of consciousness. 
 
The first symptoms which alert you to hypoglycaemia ("warning symptoms") may change, be weaker 
or may be missing altogether if 
- you are elderly, if you have had diabetes for a long time or if you suffer from a certain type of 

nervous disease (diabetic autonomic neuropathy), 
- you have recently suffered hypoglycaemia (for example the day before) or if it develops slowly, 
- you have almost normal or, at least, greatly improved blood sugar levels, 
- you have recently changed from an animal insulin to a human insulin such as Insulin Human 

Winthrop, 
-  you are taking or have taken certain other medicines (see section 2, "Other medicines and 

Insulin Human Winthrop Comb 30"). 
 
In such a case, you may develop severe hypoglycaemia (and even faint) before you are aware of the 
problem. Be familiar with your warning symptoms. If necessary, more frequent blood sugar testing 
can help to identify mild hypoglycaemic episodes that may otherwise be overlooked. If you are not 
confident about recognising your warning symptoms, avoid situations (such as driving a car) in which 
you or others would be put at risk by hypoglycaemia. 
 
What should you do if you experience hypoglycaemia 
 
1. Do not inject insulin. Immediately take about 10 to 20 g sugar, such as glucose, sugar cubes or a 

sugar-sweetened beverage. Caution: Artificial sweeteners and foods with artificial sweeteners 
(such as diet drinks) are of no help in treating hypoglycaemia. 

2. Then eat something that has a long-acting effect in raising your blood sugar (such as bread or 
pasta). Your doctor or nurse should have discussed this with you previously. 

3. If the hypoglycaemia comes back again take another 10 to 20 g sugar. 
4. Speak to a doctor immediately if you are not able to control the hypoglycaemia or if it recurs. 
 
Tell your relatives, friends and close colleagues the following: 
If you are not able to swallow or if you are unconscious, you will require an injection of glucose or 
glucagon (a medicine which increases blood sugar). These injections are justified even if it is not 
certain that you have hypoglycaemia. 
 
It is advisable to test your blood sugar immediately after taking glucose to check that you really have 
hypoglycaemia. 
 
 

 

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Package leaflet: Information for the user 

 
Insulin Human Winthrop Comb 30 SoloStar 100 IU/ml suspension for injection in a pre-filled 

pen 
Insulin human 

 
 
Read all of this leaflet carefully, including the Instructions for Use of Insulin Human Winthrop 
Comb 30 SoloStar, pre-filled pen, before you start using this medicine because it contains 
important information for you. 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor, pharmacist or nurse. 
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours. 
- If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible 

side effects not listed in this leaflet. 
 
What is in this leaflet: 
1. What Insulin Human Winthrop Comb 30 is and what it is used for 
2. What you need to know before you use Insulin Human Winthrop Comb 30 
3. How to use Insulin Human Winthrop Comb 30 
4. Possible side effects 
5. How to store Insulin Human Winthrop Comb 30 
6. Contents of the pack and other information 
 
 
1. What Insulin Human Winthrop Comb 30 is and what it is used for 
 
Insulin Human Winthrop Comb 30 contains the active substance insulin human which is made by a 
biotechnology process and is identical with the body's own insulin. 
 
Insulin Human Winthrop Comb 30 is an insulin preparation with a gradual onset and long duration of 
action. It comes in cartridges sealed in disposable pen injectors, SoloStar. 
 
Insulin Human Winthrop Comb 30 is used to reduce high blood sugar in patients with diabetes 
mellitus who need treatment with insulin. Diabetes mellitus is a disease where your body does not 
produce enough insulin to control the level of blood sugar. 
 
 
2. What you need to know before you use Insulin Human Winthrop Comb 30 
 
Do not use Insulin Human Winthrop Comb 30  
 
If you are allergic to insulin or any of the other ingredients of this medicine (listed in section 6).  
 
Warnings and precautions 
 
Talk to your doctor, pharmacist or nurse before using Insulin Human Winthrop Comb 30. 
Follow closely the instructions for dosage, monitoring (blood and urine tests), diet and physical 
activity (physical work and exercise), injection technique as discussed with your doctor. 
 
If you are allergic to this medicine or to animal insulins, talk to your doctor. 
 
Special patient groups 
If you have liver or kidneys problems or if you are elderly, speak to your doctor as you may need a 
lower dose. 

 

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Travel 
Before travelling, consult your doctor. You may need to talk about 
- the availability of your insulin in the country you are visiting, 
- supplies of insulin, injection syringes etc., 
- correct storage of your insulin while travelling, 
- timing of meals and insulin administration while travelling, 
- the possible effects of changing to different time zones, 
- possible new health risks in the countries to be visited, 
- what you should do in emergency situations when you feel unwell or become ill. 
 
Illnesses and injuries 
In the following situations, the management of your diabetes may require a lot of care: 
- If you are ill or have a major injury then your blood sugar level may increase (hyperglycaemia).  
- If you are not eating enough, your blood sugar level may become too low (hypoglycaemia).  
In most cases you will need a doctor. Make sure that you contact a doctor early.  
 
If you have type 1 diabetes (insulin dependent diabetes mellitus), do not stop your insulin and 
continue to get enough carbohydrates. Always tell people who are caring for you or treating you that 
you require insulin. 
 
Some patients with long-standing type 2 diabetes mellitus and heart disease or previous stroke who 
were treated with pioglitazone and insulin experienced the development of heart failure. Inform your 
doctor as soon as possible if you experience signs of heart failure such as unusual shortness of breath 
or rapid increase in weight or localised swelling (oedema). 
 
Other medicines and Insulin Human Winthrop Comb 30 
 
Some medicines cause changes in the blood sugar level (decrease, increase or both depending on the 
situation). In each case, it may be necessary to adjust your insulin dosage to avoid blood sugar levels 
that are either too low or too high. Be careful when you start or stop taking another medicine. 
 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines. Before taking a medicine ask your doctor if it can affect your blood sugar level, and what 
action, if any, you need to take. 
 
Medicines that may cause your blood sugar level to fall (hypoglycaemia) include:  
- all other medicines to treat diabetes,  
- angiotensin converting enzyme (ACE) inhibitors (used to treat certain heart conditions or high 

blood pressure),  
- disopyramide (used to treat certain heart conditions),  
- fluoxetine (used to treat depression),  
- fibrates (used to lower high levels of blood lipids),  
- monoamine oxidase (MAO) inhibitors (used to treat depression),  
- pentoxifylline, propoxyphene, salicylates (such as aspirin, used to relieve pain and lower fever), 
- sulfonamide antibiotics. 
 
Medicines that may cause your blood sugar level to rise (hyperglycaemia) include:  
- corticosteroids (such as "cortisone", used to treat inflammation),  
- danazol (medicine acting on ovulation),  
- diazoxide (used to treat high blood pressure),  
- diuretics (used to treat high blood pressure or excessive fluid retention),  
- glucagon (pancreas hormone used to treat severe hypoglycaemia),  
- isoniazid (used to treat tuberculosis),  
- oestrogens and progestogens (such as in the contraceptive pill used for birth control),  
- phenothiazine derivatives (used to treat psychiatric disorders),  
- somatropin (growth hormone),  

 

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- sympathomimetic medicines (such as epinephrine [adrenaline] or salbutamol, terbutaline used to 
treat asthma), 

- thyroid hormones (used to treat the thyroid gland disorders), 
- protease inhibitors (used to treat HIV), 
- atypical antipsychotic medicines (such as olanzapine and clozapine). 
 
Your blood sugar level may either rise or fall if you take:  
- beta-blockers (used to treat high blood pressure),  
- clonidine (used to treat high blood pressure), 
- lithium salts (used to treat psychiatric disorders).  
Pentamidine (used to treat some infections caused by parasites) may cause hypoglycaemia which may 
sometimes be followed by hyperglycaemia. 
 
Beta-blockers like other sympatholytic medicines (such as clonidine, guanethidine, and reserpine) may 
weaken or suppress entirely the first warning symptoms which help you to recognise a 
hypoglycaemia. 
 
If you are not sure whether you are taking one of those medicines ask your doctor or pharmacist. 
 
Insulin Human Winthrop Comb 30 with alcohol 
 
Your blood sugar levels may either rise or fall if you drink alcohol. 
 
Pregnancy and breast-feeding 
 
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor or pharmacist for advice before taking this medicine. 
 
Inform your doctor if you are planning to become pregnant, or if you are already pregnant. Your 
insulin dosage may need to be changed during pregnancy and after giving birth. Particularly careful 
control of your diabetes, and prevention of hypoglycaemia, is important for the health of your baby.  
 
If you are breast-feeding consult your doctor as you may require adjustments in your insulin doses and 
your diet. 
 
Driving and using machines 
 
Your ability to concentrate or react may be reduced if: 
- you have hypoglycaemia (low blood sugar levels), 
- you have hyperglycaemia (high blood sugar levels), 
- you have problems with your sight.  
Keep this possible problem in mind in all situations where you might put yourself and others at risk 
(such as driving a car or using machines). You should contact your doctor for advice on driving if: 
- you have frequent episodes of hypoglycaemia, 
- the first warning symptoms which help you to recognise hypoglycaemia are reduced or absent. 
 
Important information about some of the ingredients of Insulin Human Winthrop Comb 30  
 
This medicine contains less than 1 mmol (23 mg) sodium per dose, i.e. it is essentially ‘sodium-free’. 
 
 

 

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3. How to use Insulin Human Winthrop Comb 30 
 
Dose 
 
Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor 
or pharmacist if you are not sure. 
 
Based on your life-style and the results of your blood sugar (glucose) tests, your doctor will 
- determine how much Insulin Human Winthrop Comb 30 per day you will need, 
- tell you when to check your blood sugar level, and whether you need to carry out urine tests, 
- tell you when you may need to inject a higher or lower dose of Insulin Human Winthrop 

Comb 30. 
 
Many factors may influence your blood sugar level. You should know these factors so that you are 
able to react correctly to changes in your blood sugar level and to prevent it from becoming too high 
or too low. See the box at the end of this leaflet for further information. 
 
Frequency of administration 
 
Insulin Human Winthrop Comb 30 is injected under the skin 30 to 45 minutes before a meal.  
 
Method of administration 
 
Insulin Human Winthrop Comb 30 is a fluid (suspension) for injection under the skin. 
 
Do NOT inject Insulin Human Winthrop Comb 30 into a vein (blood vessel).  
 
SoloStar delivers insulin in doses from 1 to 80 units in steps of 1 unit. Each pen contains multiple 
doses. 
 
Your doctor will show you in which area of the skin you should inject your insulin. With each 
injection, change the puncture site within the particular area of skin that you are using. 
 
How to handle SoloStar 
 
SoloStar is a pre-filled disposable pen containing human insulin. 
 
Read carefully the "SoloStar Instructions for Use" included in this package leaflet. You must 
use the pen as described in these Instructions for Use. 
 
A new injection needle must be attached before each use. Only use needles that have been approved 
for use with SoloStar. 
A safety test must be performed before each injection. 
 
Mix the insulin well and check it before first use. Later, you must mix the insulin well again 
immediately before each injection. 
 
Mixing is best done by gently tilting the pen back and forth at least 10 times. To assist in mixing, three 
tiny metal balls are present in the cartridge. 
 
After mixing, the suspension must have a uniform milky-white appearance. It must not be used if it 
remains clear or if, for example, clumps, flakes, particles or anything similar are in the suspension or 
on the sides or bottom of the cartridge in the pen. A new pen with a uniform suspension on mixing 
must then be used. 
 
Always use a new pen if you notice that your blood sugar control is unexpectedly getting worse. If 
you think you have a problem with SoloStar, consult your doctor, pharmacist or nurse. 

 

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To prevent the possible transmission of disease, each pen must be used by one patient only. 
 
Special care before injection 
 
Make sure that neither alcohol nor other disinfectants or other substances contaminate the insulin. 
 
Do not mix insulin with any other medicines. Insulin Human Winthrop Comb 30 SoloStar, pre-filled 
pen, is not designed to allow any other insulin to be mixed in the cartridge. 
 
Empty pens must not be re-filled and must be properly discarded. 
 
Do not use SoloStar if it is damaged or not working properly (due to mechanical defects), it has to be 
discarded and a new SoloStar has to be used. 
 
If you use more Insulin Human Winthrop Comb 30 than you should 
- If you have injected too much Insulin Human Winthrop Comb 30, your blood sugar level 

may become too low (hypoglycaemia). Check your blood sugar frequently. In general, to 
prevent hypoglycaemia you must eat more food and monitor your blood sugar. For information 
on the treatment of hypoglycaemia, see box at the end of this leaflet. 

 
If you forget to use Insulin Human Winthrop Comb 30 
- If you have missed a dose of Insulin Human Winthrop Comb 30 or if you have not injected 

enough insulin, your blood sugar level may become too high (hyperglycaemia). Check your 
blood sugar frequently. For information on the treatment of hyperglycaemia, see box at the end 
of this leaflet. 

 
- Do not take a double dose to make up for a forgotten dose. 
 
If you stop using Insulin Human Winthrop Comb 30 
This could lead to severe hyperglycaemia (very high blood sugar) and ketoacidosis (build-up of acid 
in the blood because the body is breaking down fat instead of sugar). Do not stop Insulin Human 
Winthrop Comb 30 without speaking to a doctor, who will tell you what needs to be done. 
 
If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse. 
 
Insulin Mix-ups 
 
You must always check the insulin label before each injection to avoid mix-ups between Insulin 
Human Winthrop Comb 30 and other insulins.  
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
The most frequent side effect is hypoglycaemia (low blood sugar). The specific frequency cannot be 
estimated from available data (frequency not known). Serious hypoglycaemia may cause a heart attack 
or brain damage and may be life-threatening. For further information on the side effects of low blood 
sugar or high blood sugar, see the box at the end of this leaflet. 
 
Severe allergic reactions to insulin may occur which may become life-threatening. Such reactions to 
insulin or to the excipients can cause large-scale skin reactions (rash and itching all over the body); 
severe swelling of skin or mucous membranes (angiooedema), shortness of breath, a fall in blood 
pressure with rapid heart beat and sweating. Frequency of these reactions cannot be estimated from 
available data. 
 

 

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Side effects reported commonly (may affect up to 1 in 10 people) 
• Oedema 
Insulin treatment may cause temporary build-up of water in the body with swelling in the calves and 
ankles. 
• Injection site reactions 
 
Side effects reported uncommonly (may affect up to 1 in 100 people) 
• Severe allergic reaction with low blood pressure (shock) 
• Injection site urticaria (itchy rash) 
 
Other side effects include (frequency cannot be estimated from the available data) 
• Sodium retention 
• Eye reactions 
A marked change (improvement or worsening) in your blood sugar control can disturb your vision 
temporarily. If you have proliferative retinopathy (an eye disease related to diabetes) severe 
hypoglycaemic attacks may cause temporary loss of vision. 
• Skin changes at the injection site (lipodystrophy) 
If you inject your insulin too often at the same skin site, fatty tissue under the skin at this site may 
either shrink or thicken. Insulin that you inject in such a site may not work very well. Changing the 
injection site with each injection may help to prevent such skin changes. 
• Skin and allergic reactions 
Other mild reactions at the injection site (such as injection site redness, unusually intense pain on 
injection site, itching, injection site swelling or injection site inflammation) may occur. They can also 
spread around the injection site. Most minor reactions to insulins usually resolve in a few days to a 
few weeks. 
 
Insulin treatment can cause the body to produce antibodies to insulin (substances that act against 
insulin). However, only very rarely, this will require a change to your insulin dosage. 
 
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side 
effects not listed in this leaflet. 
 
 
5. How to store Insulin Human Winthrop Comb 30 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date which is stated on the carton and on the label of the pen 
after “EXP”. The expiry date refers to the last day of that month. 
 
Not in-use pens 
Store in a refrigerator (2°C – 8°C). Do not freeze. Do not put the pre-filled pen next to the freezer 
compartment or a freezer pack. Keep the pre-filled pen in the outer carton in order to protect from 
light. 
 
In-use pens 
Pre-filled pens in-use or carried as a spare may be stored for a maximum of 4 weeks not above 25°C 
and away from direct heat (for example next to a heating unit) or direct light (direct sunlight or next to 
a lamp). The pen in-use must not be stored in a refrigerator. Do not use the pen after this time period. 
 
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment. 
 
 

 

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6. Contents of the pack and other information 
 
What Insulin Human Winthrop Comb 30 contains 
- The active substance is insulin human. One ml of Insulin Human Winthrop Comb 30 contains 

100 IU (International Units) of the active substance insulin human. 30% of the insulin is 
dissolved in water; the other 70% is present as tiny crystals of insulin protamine. 

- The other ingredients are: protamine sulphate, metacresol, phenol, zinc chloride, sodium 
dihydrogen phosphate dihydrate, glycerol, sodium hydroxide (see section 2 under “Important 
information about some of the ingredients of Insulin Human Winthrop Comb 30”), hydrochloric 
acid (for pH adjustment) and water for injections. 

 
What Insulin Human Winthrop Comb 30 looks like and contents of the pack 
After mixing, Insulin Human Winthrop Comb 30is a uniformly milky fluid (suspension for injection), 
with no clumps, particles or flocculation visible. 
 
Insulin Human Winthrop Comb 30 is supplied in pre-filled pens, SoloStar, containing 3 ml 
suspension, (300 IU). Packs of 3, 4, 5, 6, 9 and 10 pens of 3 ml are available. Not all pack sizes may 
be marketed. 
 
Marketing Authorisation Holder and Manufacturer 
Sanofi-Aventis Deutschland GmbH 
D-65926 Frankfurt am Main 
Germany 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
Sanofi Belgium 
Tél/Tel: +32 (0)2 710 54 00 
 

Lietuva 
UAB «SANOFI-AVENTIS LIETUVA» 
Tel: +370 5 2755224 
 

България 
sanofi-aventis Bulgaria EOOD 
Тел.: +359 (0)2 970 53 00 
 

Luxembourg/Luxemburg 
Sanofi Belgium  
Tél/Tel: +32 (0)2 710 54 00 (Belgique/Belgien) 
 

Česká republika 
sanofi-aventis, s.r.o. 
Tel: +420 233 086 111 
 

Magyarország 
SANOFI-AVENTIS Zrt. 
Tel.: +36 1 505 0050 
 

Danmark 
sanofi-aventis Denmark A/S 
Tlf: +45 45 16 70 00 
 

Malta 
Sanofi Malta Ltd. 
Tel: +356 21493022 
 

Deutschland 
Zentiva Pharma GmbH 
Tel: +49 (0)180 20 200 10 
 

Nederland 
sanofi-aventis Netherlands B.V. 
Tel: +31 (0)182 557 755 
 

Eesti 
sanofi-aventis Estonia OÜ 
Tel: +372 627 34 88 
 

Norge 
Aventis Pharma Norge AS 
Tlf: +47 67 10 71 00 
 

Ελλάδα 
sanofi-aventis AEBE 
Τηλ: +30 210 900 16 00 
 

Österreich 
sanofi-aventis GmbH 
Tel: +43 1 80 185 – 0 
 

 

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España 
sanofi-aventis, S.A. 
Tel: +34 93 485 94 00 
 

Polska 
sanofi-aventis Sp . z o.o. 
Tel.: +48 22 280 00 00 
 

France 
sanofi-aventis France 
Tél: 0 800 222 555 
Appel depuis l’étranger : +33 1 57 63 23 23 
 

Portugal 
Sanofi - Produtos Farmacêuticos, Lda. 
Tel: +351 21 35 89 400 
 

Hrvatska 
sanofi-aventis Croatia d.o.o. 
Tel: +385 1 600 34 00 

România 
Sanofi Romania SRL 
Tel: +40 (0) 21 317 31 36 
 

Ireland 
sanofi-aventis Ireland Ltd. T/A SANOFI 
Tel: +353 (0) 1 403 56 00 
 

Slovenija 
sanofi-aventis d.o.o. 
Tel: +386 1 560 48 00 
 

Ísland 
Vistor hf. 
Sími: +354 535 7000 
 

Slovenská republika 
sanofi-aventis Pharma Slovakia s.r.o. 
Tel: +421 2 33 100 100 
 

Italia 
Sanofi S.p.A. 
Tel: 800 13 12 12 (domande di tipo tecnico)  
800 536389 (altre domande) 
 

Suomi/Finland 
Sanofi Oy 
Puh/Tel: +358 (0) 201 200 300 
 

Κύπρος 
sanofi-aventis Cyprus Ltd. 
Τηλ: +357 22 871600 
 

Sverige 
Sanofi AB 
Tel: +46 (0)8 634 50 00 
 

Latvija 
sanofi-aventis Latvia SIA 
Tel: +371 67 33 24 51 
 

United Kingdom 
Sanofi 
Tel: +44 (0) 845 372 7101 
 

 
This leaflet was last revised in {date} 
 
 
Other source of information 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu/ 
 
 

 

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537 

 
 

HYPERGLYCAEMIA AND HYPOGLYCAEMIA 
 

Always carry some sugar (at least 20 grams) with you. 
Carry some information with you to show you are diabetic. 

 
HYPERGLYCAEMIA (high blood sugar levels) 

 
If your blood sugar is too high (hyperglycaemia), you may not have injected enough insulin. 
 
Why does hyperglycaemia occur? 
 
Examples include: 
- you have not injected your insulin or not injected enough, or if it has become less effective, for 

example through incorrect storage, 
- your insulin pen does not work properly, 
- you are doing less exercise than usual, you are under stress (emotional distress, excitement), or 

you have an injury, operation, infection or fever, 
- you are taking or have taken certain other medicines (see section 2, "Other medicines and 

Insulin Human Winthrop Comb 30"). 
 
Warning symptoms of hyperglycaemia 
 
Thirst, increased need to urinate, tiredness, dry skin, reddening of the face, loss of appetite, low blood 
pressure, fast heart beat, and glucose and ketone bodies in urine. Stomach pain, fast and deep 
breathing, sleepiness or even loss of consciousness may be signs of a serious condition (ketoacidosis) 
resulting from lack of insulin. 
 
What should you do if you experience hyperglycaemia 
 
Test your blood sugar level and your urine for ketones as soon as any of the above symptoms 
occur. Severe hyperglycaemia or ketoacidosis must always be treated by a doctor, normally in a 
hospital. 
 

HYPOGLYCAEMIA (low blood sugar levels) 
 
If your blood sugar level falls too much you may become unconscious. Serious hypoglycaemia may 
cause a heart attack or brain damage and may be life-threatening. You normally should be able to 
recognise when your blood sugar is falling too much so that you can take the right actions. 
 
Why does hypoglycaemia occur? 
 
Examples include: 
- you inject too much insulin, 
- you miss meals or delay them, 
- you do not eat enough, or eat food containing less carbohydrate than normal (sugar and 

substances similar to sugar are called carbohydrates; however, artificial sweeteners are NOT 
carbohydrates), 

- you lose carbohydrates due to vomiting or diarrhoea, 
- you drink alcohol, particularly if you are not eating much, 
- you are doing more exercise than usual or a different type of physical activity, 
- you are recovering from an injury or operation or other stress, 
- you are recovering from an illness or from fever, 
- you are taking or have stopped taking certain other medicines (see section 2, "Other medicines 

and Insulin Human Winthrop Comb 30"). 
 

 

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Hypoglycaemia is also more likely to occur if: 
- you have just begun insulin treatment or changed to another insulin preparation, 
- your blood sugar levels are almost normal or are unstable, 
- you change the area of skin where you inject insulin (for example from the thigh to the upper 

arm), 
- you suffer from severe kidney or liver disease, or some other disease such as hypothyroidism. 
 
Warning symptoms of hypoglycaemia 
 
- In your body 
Examples of symptoms that tell you that your blood sugar level is falling too much or too fast: 
sweating, clammy skin, anxiety, fast heart beat, high blood pressure, palpitations and irregular 
heartbeat. These symptoms often develop before the symptoms of a low sugar level in the brain. 
 
- In your brain 
Examples of symptoms that indicate a low sugar level in the brain: headaches, intense hunger, nausea, 
vomiting, tiredness, sleepiness, sleep disturbances, restlessness, aggressive behaviour, lapses in 
concentration, impaired reactions, depression, confusion, speech disturbances (sometimes total loss of 
speech), visual disorders, trembling, paralysis, tingling sensations (paraesthesia), numbness and 
tingling sensations in the area of the mouth, dizziness, loss of self-control, inability to look after 
yourself, convulsions, loss of consciousness. 
 
The first symptoms which alert you to hypoglycaemia ("warning symptoms") may change, be weaker 
or may be missing altogether if 
- you are elderly, if you have had diabetes for a long time or if you suffer from a certain type of 

nervous disease (diabetic autonomic neuropathy), 
- you have recently suffered hypoglycaemia (for example the day before) or if it develops slowly, 
- you have almost normal or, at least, greatly improved blood sugar levels, 
- you have recently changed from an animal insulin to a human insulin such as Insulin Human 

Winthrop, 
- you are taking or have taken certain other medicines (see section 2, "Other medicines and 

Insulin Human Winthrop Comb 30"). 
 
In such a case, you may develop severe hypoglycaemia (and even faint) before you are aware of the 
problem. Be familiar with your warning symptoms. If necessary, more frequent blood sugar testing 
can help to identify mild hypoglycaemic episodes that may otherwise be overlooked. If you are not 
confident about recognising your warning symptoms, avoid situations (such as driving a car) in which 
you or others would be put at risk by hypoglycaemia. 
 
What should you do if you experience hypoglycaemia 
 
2. Do not inject insulin. Immediately take about 10 to 20 g sugar, such as glucose, sugar cubes or a 

sugar-sweetened beverage. Caution: Artificial sweeteners and foods with artificial sweeteners 
(such as diet drinks) are of no help in treating hypoglycaemia. 

2. Then eat something that has a long-acting effect in raising your blood sugar (such as bread or 
pasta). Your doctor or nurse should have discussed this with you previously. 

3. If the hypoglycaemia comes back again take another 10 to 20 g sugar. 
4. Speak to a doctor immediately if you are not able to control the hypoglycaemia or if it recurs. 
 
Tell your relatives, friends and close colleagues the following: 
If you are not able to swallow or if you are unconscious, you will require an injection of glucose or 
glucagon (a medicine which increases blood sugar). These injections are justified even if it is not 
certain that you have hypoglycaemia. 
 
It is advisable to test your blood sugar immediately after taking glucose to check that you really have 
hypoglycaemia. 
 

 

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Insulin Human Winthrop Comb 30 SoloStar suspension for injection in a pre-filled pen. 
Instructions for Use. 
 
SoloStar is a prefilled pen for the injection of insulin. Your doctor has decided that SoloStar is 
appropriate for you based on your ability to handle SoloStar. Talk with your doctor, pharmacist or 
nurse about proper injection technique before using SoloStar. 
 
Read these instructions carefully before using your SoloStar. If you are not able to use SoloStar or 
follow all the instructions completely on your own, you must use SoloStar only if you have help from 
a person who is able to follow the instructions completely. Hold the pen as shown in this leaflet. To 
ensure that you read the dose correctly, hold the pen horizontally, with the needle on the left and the 
dosage selector to the right as shown in the illustrations below. 
 
Follow these instructions completely each time you use SoloStar to ensure that you get an 
accurate dose. If you do not follow these instructions completely, you may get too much or too 
little insulin, which may affect your blood glucose. 
 
You can set doses from 1 to 80 units in steps of 1 unit. Each pen contains multiple doses. 
 
Keep this leaflet for future reference. 
 
If you have any questions about SoloStar or about diabetes, ask your doctor, pharmacist or nurseor 
call the local sanofi-aventis number on the front of this leaflet. 
 

 
Schematic diagram of the pen 

 
 
Important information for use of SoloStar: 
 
• Always attach a new needle before each use. Only use needles that have been approved for use 

with SoloStar. 
• Do not select a dose and/or press the injection button without a needle attached. 
• Always perform the safety test before each injection (see Step 3). 
• This pen is only for your use. Do not share it with anyone else.  
• If your injection is given by another person, special caution must be taken by this person to avoid 

accidental needle injury and transmission of infection. 
• Never use SoloStar if it is damaged or if you are not sure that it is working properly. 
• Always have a spare SoloStar in case your SoloStar is lost or damaged. 
 
 
Step 1. Check the insulin 
 
A Check the label on your SoloStar to make sure you have the correct insulin. Insulin Human 
Winthrop SoloStar is white with a colour on the injection button. The injection button colour will vary 
based on the formulation of Insulin Human Winthrop insulin used. The pictures below are for 
illustrative purposes only. 
 
B Take off the pen cap. 
 
C Check the appearance of your insulin.  

 

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If you are using a suspension insulin (Insulin Human Winthrop Basal or Insulin Human 
Winthrop mixtures), turn the pen up and down at least 10 times to resuspend the insulin. Turn 
the pen gently to avoid foaming in the cartridge.  

 

   
 

After mixing check the appearance of your insulin. Insulin suspensions must have an 
evenly milky-white appearance.  

 
 
Step 2. Attach the needle 
 
Always use a new sterile needle for each injection. This helps prevent contamination, and potential 
needle blocks. 
 
Before use of needle, carefully read the “Instructions for Use” accompanying the needles.  
 
Please note: The needles shown are for illustrative purposes only. 

 
A Remove the protective seal from a new needle.  
 
B Line up the needle with the pen, and keep it straight as you attach it (screw or push on, 
depending on the needle type). 
 

 . 
 

• If the needle is not kept straight while you attach it, it can damage the rubber seal and cause 
leakage, or break the needle. 

 

   
 
 
Step 3. Perform a safety test  
 
Always perform the safety test before each injection. This ensures that you get an accurate dose by: 
• ensuring that pen and needle work properly 
• removing air bubbles 
 
A Select a dose of 2 units by turning the dosage selector. 

 

 

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541 

   
 
B Take off the outer needle cap and keep it to remove the used needle after injection. Take off 
the inner needle cap and discard it.  
 

   
 
C Hold the pen with the needle pointing upwards. 
 
D Tap the insulin reservoir so that any air bubbles rise up towards the needle. 
 
E Press the injection button all the way in. Check if insulin comes out of the needle tip. 

   
 
You may have to perform the safety test several times before insulin is seen.  
 
• If no insulin comes out, check for air bubbles and repeat the safety test two more times to 

remove them. 
• If still no insulin comes out, the needle may be blocked. Change the needle and try again. 
• If no insulin comes out after changing the needle, your SoloStar may be damaged. Do not use 

this SoloStar. 
 
Step 4. Select the dose 
 
You can set the dose in steps of 1 unit, from a minimum of 1 unit to a maximum of 80 units. If you 
need a dose greater than 80 units, you should give it as two or more injections. 
 
A Check that the dose window shows “0” following the safety test. 
 
B Select your required dose (in the example below, the selected dose is 30 units). If you turn 
past your dose, you can turn back down. 
 

  
 

 

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• Do not push the injection button while turning, as insulin will come out. 
 
• You cannot turn the dosage selector past the number of units left in the pen. Do not force the 

dosage selector to turn. In this case, either you can inject what is remaining in the pen and 
complete your dose with a new SoloStar or use a new SoloStar for your full dose. 

 
 
Step 5. Inject the dose 
 
A Use the injection method as instructed by your doctor, pharmacist or nurse.  
 
B Insert the needle into the skin. 
 

   
 
C Deliver the dose by pressing the injection button in all the way. The number in the dose 
window will return to “0” as you inject.  

   
 

D Keep the injection button pressed all the way in. Slowly count to 10 before you withdraw the 
needle from the skin. This ensures that the full dose will be delivered. 

 
The pen plunger moves with each dose. The plunger will reach the end of the cartridge when 
the total of 300 units of insulin have been used. 

 
 
Step 6. Remove and discard the needle 
 
Always remove the needle after each injection and store SoloStar without a needle attached.  
This helps prevent: 
• Contamination and/or infection  
• Entry of air into the insulin reservoir and leakage of insulin, which can cause inaccurate dosing. 
 
A Put the outer needle cap back on the needle, and use it to unscrew the needle from the pen. To 
reduce the risk of accidental needle injury, never replace the inner needle cap.  

 
• If your injection is given by another person, or if you are giving an injection to another person, 

special caution must be taken by this person when removing and disposing of the needle. Follow 
recommended safety measures for removal and disposal of needles (e.g. contact your doctor, 
pharmacist or nurse) in order to reduce the risk of accidental needle injury and transmission of 
infectious diseases. 

 
B Dispose of the needle safely.  
 
C Always put the pen cap back on the pen, then store the pen until your next injection. 
 
 

 

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Storage instructions  
 
Please check the reverse (insulin) side of this leaflet for instructions on how to store SoloStar. 
 
If your SoloStar is in cool storage, take it out 1 to 2 hours before you inject to allow it to warm up. 
Cold insulin is more painful to inject. 
 
Discard your used SoloStar as required by your local authorities. 
 
 
Maintenance 
 
Protect your SoloStar from dust and dirt. 
 
You can clean the outside of your SoloStar by wiping it with a damp cloth.  
 
Do not soak, wash or lubricate the pen as this may damage it.  
 
Your SoloStar is designed to work accurately and safely. It should be handled with care. Avoid 
situations where SoloStar might be damaged. If you are concerned that your SoloStar may be 
damaged, use a new one. 
 

 

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Package leaflet: Information for the user 

 
Insulin Human Winthrop Comb 50 100 IU/ml suspension for injection in a vial 

Insulin human 
 

 
Read all of this leaflet carefully before you start using this medicine because it contains 
important information for you. 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor, pharmacist or nurse. 
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours. 
- If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible 

side effects not listed in this leaflet. 
 
What is in this leaflet: 
1. What Insulin Human Winthrop Comb 50 is and what it is used for 
2. What you need to know before you use Insulin Human Winthrop Comb 50 
3. How to use Insulin Human Winthrop Comb 50 
4. Possible side effects 
5. How to store Insulin Human Winthrop Comb 50 
6. Contents of the pack and other information 
 
 
1. What Insulin Human Winthrop Comb  50 is and what it is used for 
 
Insulin Human Winthrop Comb 50 contains the active substance insulin human which is made by a 
biotechnology process and is identical with the body's own insulin. 
 
Insulin Human Winthrop Comb 50 is an insulin preparation with a rapid onset and moderately long 
duration of action.  
 
Insulin Human Winthrop Comb 50 is used to reduce high blood sugar in patients with diabetes 
mellitus who need treatment with insulin. Diabetes mellitus is a disease where your body does not 
produce enough insulin to control the level of blood sugar. 
 
 
2. What you need to know before you use Insulin Human Winthrop Comb  50 
 
Do not use Insulin Human Winthrop Comb 50 
 
If you are allergic to insulin or any of the other ingredients of this medicine (listed in section 6).  
 
Warnings and precautions 
 
Talk to your doctor, pharmacist or nurse before using Insulin Human Winthrop Comb 50. 
Follow closely the instructions for dosage, monitoring (blood and urine tests), diet and physical 
activity (physical work and exercise) as discussed with your doctor. 
 
If you are allergic to this medicine or to animal insulins, talk to your doctor. 
 
Special patient groups 
If you have liver or kidneys problems or if you are elderly, speak to your doctor as you may need a 
lower dose. 
 

 

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Travel 
Before travelling, consult your doctor. You may need to talk about 
- the availability of your insulin in the country you are visiting, 
- supplies of insulin, injection syringes etc., 
- correct storage of your insulin while travelling, 
- timing of meals and insulin administration while travelling, 
- the possible effects of changing to different time zones, 
- possible new health risks in the countries to be visited, 
- what you should do in emergency situations when you feel unwell or become ill. 
 
Illnesses and injuries 
In the following situations, the management of your diabetes may require a lot of care: 
- If you are ill or have a major injury then your blood sugar level may increase (hyperglycaemia).  
- If you are not eating enough, your blood sugar level may become too low (hypoglycaemia).  
In most cases you will need a doctor. Make sure that you contact a doctor early.  
 
If you have type 1 diabetes (insulin dependent diabetes mellitus), do not stop your insulin and 
continue to get enough carbohydrates. Always tell people who are caring for you or treating you that 
you require insulin. 
 
Some patients with long-standing type 2 diabetes mellitus and heart disease or previous stroke who 
were treated with pioglitazone and insulin experienced the development of heart failure. Inform your 
doctor as soon as possible if you experience signs of heart failure such as unusual shortness of breath 
or rapid increase in weight or localised swelling (oedema). 
 
Other medicines and Insulin Human Winthrop Comb  50 
 
Some medicines cause changes in the blood sugar level (decrease, increase or both depending on the 
situation). In each case, it may be necessary to adjust your insulin dosage to avoid blood sugar levels 
that are either too low or too high. Be careful when you start or stop taking another medicine. 
 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines. Before taking a medicine ask your doctor if it can affect your blood sugar level, and what 
action, if any, you need to take. 
 
Medicines that may cause your blood sugar level to fall (hypoglycaemia) include:  
- all other medicines to treat diabetes,  
- angiotensin converting enzyme (ACE) inhibitors (used to treat certain heart conditions or high 

blood pressure),  
- disopyramide (used to treat certain heart conditions),  
- fluoxetine (used to treat depression),  
- fibrates (used to lower high levels of blood lipids),  
- monoamine oxidase (MAO) inhibitors (used to treat depression),  
- pentoxifylline, propoxyphene, salicylates (such as aspirin, used to relieve pain and lower fever), 
- sulfonamide antibiotics. 
 
Medicines that may cause your blood sugar level to rise (hyperglycaemia) include:  
- corticosteroids (such as "cortisone", used to treat inflammation),  
- danazol (medicine acting on ovulation),  
- diazoxide (used to treat high blood pressure),  
- diuretics (used to treat high blood pressure or excessive fluid retention),  
- glucagon (pancreas hormone used to treat severe hypoglycaemia),  
- isoniazid (used to treat tuberculosis),  
- oestrogens and progestogens (such as in the contraceptive pill used for birth control),  
- phenothiazine derivatives (used to treat psychiatric disorders),  
- somatropin (growth hormone),  

 

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- sympathomimetic medicines (such as epinephrine [adrenaline] or salbutamol, terbutaline used to 
treat asthma), 

- thyroid hormones (used to treat the thyroid gland disorders), 
- protease inhibitors (used to treat HIV), 
- atypical antipsychotic medicines (such as olanzapine and clozapine). 
 
Your blood sugar level may either rise or fall if you take:  
- beta-blockers (used to treat high blood pressure),  
- clonidine (used to treat high blood pressure), 
- lithium salts (used to treat psychiatric disorders).  
Pentamidine (used to treat some infections caused by parasites) may cause hypoglycaemia which may 
sometimes be followed by hyperglycaemia. 
 
Beta-blockers like other sympatholytic medicines (such as clonidine, guanethidine, and reserpine) may 
weaken or suppress entirely the first warning symptoms which help you to recognise a 
hypoglycaemia. 
 
If you are not sure whether you are taking one of those medicines ask your doctor or pharmacist. 
 
Insulin Human Winthrop Comb 50 with alcohol 
 
Your blood sugar levels may either rise or fall if you drink alcohol. 
 
Pregnancy and breast-feeding 
 
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor or pharmacist for advice before taking this medicine. 
 
Inform your doctor if you are planning to become pregnant, or if you are already pregnant. Your 
insulin dosage may need to be changed during pregnancy and after giving birth. Particularly careful 
control of your diabetes, and prevention of hypoglycaemia, is important for the health of your baby.  
 
If you are breast-feeding consult your doctor as you may require adjustments in your insulin doses and 
your diet. 
 
Driving and using machines 
 
Your ability to concentrate or react may be reduced if:  
- you have hypoglycaemia (low blood sugar levels), 
- you have hyperglycaemia (high blood sugar levels), 
- you have problems with your sight.  
Keep this possible problem in mind in all situations where you might put yourself and others at risk 
(such as driving a car or using machines). You should contact your doctor for advice on driving if: 
- you have frequent episodes of hypoglycaemia, 
- the first warning symptoms which help you to recognise hypoglycaemia are reduced or absent. 
 
Important information about some of the ingredients of Insulin Human Winthrop Comb 50  
 
This medicine contains less than 1 mmol (23 mg) sodium per dose, i.e. it is essentially ‘sodium-free’. 
 
 

 

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3. How to use Insulin Human Winthrop Comb  50 
 
Dose 
 
Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor 
or pharmacist if you are not sure. 
 
Based on your life-style and the results of your blood sugar (glucose) tests, your doctor will 
- determine how much Insulin Human Winthrop Comb 50 per day you will need, 
- tell you when to check your blood sugar level, and whether you need to carry out urine tests, 
- tell you when you may need to inject a higher or lower dose of Insulin Human Winthrop 

Comb 50. 
 
Many factors may influence your blood sugar level. You should know these factors so that you are 
able to react correctly to changes in your blood sugar level and to prevent it from becoming too high 
or too low. See the box at the end of this leaflet for further information. 
 
Frequency of administration 
 
Insulin Human Winthrop Comb 50 is injected under the skin 20 to 30 minutes before a meal.  
 
Method of administration 
 
Insulin Human Winthrop Comb 50 is a fluid (suspension) for injection under the skin. 
 
Do NOT inject Insulin Human Winthrop Comb 50 into a vein (blood vessel). 
 
Your doctor will show you in which area of the skin you should inject your insulin. With each 
injection, change the puncture site within the particular area of skin that you are using. 
 
Do not use it in insulin pumps or other infusion pumps – special insulin preparations are available for 
use in such devices. 
 
How to handle the vials 
 
Insulin Human Winthrop Comb 50 contains 100 IU insulin per ml. Only injection syringes designed 
for this insulin concentration (100 IU per ml) must be used. The injection syringes must not contain 
any other medicines or traces of medicines (such as traces of heparin). 
 
Before the first withdrawal of insulin you must remove the safety tear-off cap on the vial. 
 
Mix the insulin well immediately before each injection. This is best done by rolling the vial tilted 
between the palms of the hands. Do not shake the vial vigorously as this could damage the insulin and 
cause froth to form. Froth can make it difficult for you to measure the correct dose. 
 
After mixing, the suspension must have a uniform milky-white appearance. It must not be used if it 
remains clear or if, for example, clumps, flakes, particles or anything similar are in the suspension or 
on the sides or bottom of the vial. A new vial with a uniform suspension on mixing must then be used. 
 
Always use a new vial if you notice that your blood sugar control is unexpectedly getting worse. This 
is because the insulin may have lost some of its effectiveness. If you think you may have a problem 
with your insulin, have it checked by your doctor or pharmacist. 
 

 

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Special care before injection 
 
Before injection remove any air bubbles. Make sure that neither alcohol nor other disinfectants or 
other substances contaminate the insulin. Do not mix insulin with any other medicines except with 
insulin human preparations as detailed below. 
 
Insulin Human Winthrop Comb 50 may be mixed with all insulin human preparations, EXCEPT those 
specially designed for use in insulin pumps. Also, it must NOT be mixed with animal source insulins 
or insulin analogues. 
 
Your doctor will tell you if you have to mix insulin human preparations. If you need to inject a 
mixture, draw the other insulin into the injection syringe before Insulin Human Winthrop Comb 50. 
Inject as soon as you have mixed them. Do not mix insulins of different strengths (for example 100 IU 
per ml and 40 IU per ml). 
 
If you use more Insulin Human Winthrop Comb 50 than you should 
- If you have injected too much Insulin Human Winthrop Comb 50, your blood sugar level 

may become too low (hypoglycaemia). Check your blood sugar frequently. In general, to 
prevent hypoglycaemia you must eat more food and monitor your blood sugar. For information 
on the treatment of hypoglycaemia, see box at the end of this leaflet. 

 
If you forget to use Insulin Human Winthrop Comb 50 
- If you have missed a dose of Insulin Human Winthrop Comb 50 or if you have not injected 

enough insulin, your blood sugar level may become too high (hyperglycaemia). Check your 
blood sugar frequently. For information on the treatment of hyperglycaemia, see box at the end 
of this leaflet. 

 
- Do not take a double dose to make up for a forgotten dose. 
 
If you stop using Insulin Human Winthrop Comb 50 
This could lead to severe hyperglycaemia (very high blood sugar) and ketoacidosis (build-up of acid 
in the blood because the body is breaking down fat instead of sugar). Do not stop Insulin Human 
Winthrop Comb 50 without speaking to a doctor, who will tell you what needs to be done. 
 
If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse. 
 
Insulin Mix-ups 
 
You must always check the insulin label before each injection to avoid mix-ups between Insulin 
Human Winthrop Comb 50 and other insulins.  
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
The most frequent side effect is hypoglycaemia (low blood sugar). The specific frequency cannot be 
estimated from available data (frequency not known). Serious hypoglycaemia may cause a heart attack 
or brain damage and may be life-threatening. For further information on the side effects of low blood 
sugar or high blood sugar, see the box at the end of this leaflet. 
 
Severe allergic reactions to insulin may occur which may become life-threatening. Such reactions to 
insulin or to the excipients can cause large-scale skin reactions (rash and itching all over the body); 
severe swelling of skin or mucous membranes (angiooedema), shortness of breath, a fall in blood 
pressure with rapid heart beat and sweating. Frequency of these reactions cannot be estimated from 
available data. 
 

 

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Side effects reported commonly (may affect up to 1 in 100 people) 
• Oedema 
Insulin treatment may cause temporary build-up of water in the body with swelling in the calves and 
ankles. 
• Injection site reactions 
 
Side effects reported uncommonly (may affect up to 1 in 100 people) 
• Severe allergic reaction with low blood pressure (shock) 
• Injection site urticaria (itchy rash) 
 
Other side effects include (frequency cannot be estimated from the available data) 
• Sodium retention 
• Eye reactions 
A marked change (improvement or worsening) in your blood sugar control can disturb your vision 
temporarily. If you have proliferative retinopathy (an eye disease related to diabetes) severe 
hypoglycaemic attacks may cause temporary loss of vision. 
• Skin changes at the injection site (lipodystrophy) 
If you inject your insulin too often at the same skin site, fatty tissue under the skin at this site may 
either shrink or thicken. Insulin that you inject in such a site may not work very well. Changing the 
injection site with each injection may help to prevent such skin changes. 
• Skin and allergic reactions 
Other mild reactions at the injection site (such as injection site redness, unusually intense pain on 
injection site, itching, injection site swelling or injection site inflammation) may occur. They can also 
spread around the injection site. Most minor reactions to insulins usually resolve in a few days to a 
few weeks. 
 
Insulin treatment can cause the body to produce antibodies to insulin (substances that act against 
insulin). However, only very rarely, this will require a change to your insulin dosage. 
 
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side 
effects not listed in this leaflet. 
 
 
5. How to store Insulin Human Winthrop Comb  50 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date which is stated on the carton and on the label of the vial 
after “EXP”. The expiry date refers to the last day of that month. 
 
Unopened vials 
Store in a refrigerator (2°C - 8°C). Do not freeze. Do not put Insulin Human Winthrop Comb 50 next 
to the freezer compartment or a freezer pack. Keep the vial in the outer carton in order to protect from 
light. 
 
Opened vials 
Once in-use, the vial may be stored for a maximum of 4 weeks in the outer carton not above 25°C and 
away from direct heat (for example next to a heating unit) or direct light (direct sunlight or next to a 
lamp). Do not use the vial after this time period. It is recommended that the date of the first use be 
noted on the label. 
 
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment. 
 
 

 

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6. Contents of the pack and other information 
 
What Insulin Human Winthrop Comb 50 contains 
- The active substance is insulin human. One ml of Insulin Human Winthrop Comb 50 contains 

100 IU (International Units) of the active substance insulin human. 50% of the insulin is 
dissolved in water; the other 50% is present as tiny crystals of insulin protamine. 

- The other ingredients are: protamine sulphate, metacresol, phenol, zinc chloride, sodium 
dihydrogen phosphate dihydrate, glycerol, sodium hydroxide (see section 2 under “Important 
information about some of the ingredients of Insulin Human Winthrop Comb 50”), hydrochloric 
acid (for pH adjustment) and water for injections. 

 
What Insulin Human Winthrop Comb 50 looks like and contents of the pack 
After mixing, Insulin Human Winthrop Comb 50 is a uniformly milky fluid (suspension for injection), 
with no clumps, particles or flocculation visible. 
 
Insulin Human Winthrop Comb 50 is supplied in vials containing 5 ml suspension (500 IU). Packs of 
1 and 5 vials of 5 ml are available. Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder and Manufacturer 
Sanofi-Aventis Deutschland GmbH 
D-65926 Frankfurt am Main 
Germany 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
Sanofi Belgium 
Tél/Tel: +32 (0)2 710 54 00 
 

Lietuva 
UAB «SANOFI-AVENTIS LIETUVA» 
Tel: +370 5 2755224 
 

България 
sanofi-aventis Bulgaria EOOD 
Тел.: +359 (0)2 970 53 00 
 

Luxembourg/Luxemburg 
Sanofi Belgium  
Tél/Tel: +32 (0)2 710 54 00 (Belgique/Belgien) 
 

Česká republika 
sanofi-aventis, s.r.o. 
Tel: +420 233 086 111 
 

Magyarország 
SANOFI-AVENTIS Zrt. 
Tel.: +36 1 505 0050 
 

Danmark 
sanofi-aventis Denmark A/S 
Tlf: +45 45 16 70 00 
 

Malta 
Sanofi Malta Ltd. 
Tel: +356 21493022 
 

Deutschland 
Zentiva Pharma GmbH 
Tel: +49 (0)180 20 200 10 
 

Nederland 
sanofi-aventis Netherlands B.V. 
Tel: +31 (0)182 557 755 
 

Eesti 
sanofi-aventis Estonia OÜ 
Tel: +372 627 34 88 
 

Norge 
Aventis Pharma Norge AS 
Tlf: +47 67 10 71 00 
 

Ελλάδα 
sanofi-aventis AEBE 
Τηλ: +30 210 900 16 00 
 

Österreich 
sanofi-aventis GmbH 
Tel: +43 1 80 185 – 0 
 

 

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España 
sanofi-aventis, S.A. 
Tel: +34 93 485 94 00 
 

Polska 
sanofi-aventis Sp. z o.o. 
Tel.: +48 22 280 00 00 
 

France 
sanofi-aventis France 
Tél: 0 800 222 555 
Appel depuis l’étranger : +33 1 57 63 23 23 
 

Portugal 
Sanofi - Produtos Farmacêuticos, Lda. 
Tel: +351 21 35 89 400 
 

Hrvatska 
sanofi-aventis Croatia d.o.o. 
Tel: +385 1 600 34 00 

România 
Sanofi Romania SRL 
Tel: +40 (0) 21 317 31 36 
 

Ireland 
sanofi-aventis Ireland Ltd. T/A SANOFI 
Tel: +353 (0) 1 403 56 00 
 

Slovenija 
sanofi-aventis d.o.o. 
Tel: +386 1 560 48 00 
 

Ísland 
Vistor hf. 
Sími: +354 535 7000 
 

Slovenská republika 
sanofi-aventis Pharma Slovakia s.r.o. 
Tel: +421 2 33 100 100 
 

Italia 
Sanofi S.p.A. 
Tel: 800 13 12 12 (domande di tipo tecnico)  
800 536389 (altre domande) 
 

Suomi/Finland 
Sanofi Oy 
Puh/Tel: +358 (0) 201 200 300 
 

Κύπρος 
sanofi-aventis Cyprus Ltd. 
Τηλ: +357 22 871600 
 

Sverige 
Sanofi AB 
Tel: +46 (0)8 634 50 00 
 

Latvija 
sanofi-aventis Latvia SIA 
Tel: +371 67 33 24 51 
 

United Kingdom 
Sanofi 
Tel: +44 (0) 845 372 7101 
 

 
This leaflet was last revised in {date} 
 
 
Other source of information 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu/ 
 
 
 
 

HYPERGLYCAEMIA AND HYPOGLYCAEMIA 
 

Always carry some sugar (at least 20 grams) with you. 
Carry some information with you to show you are diabetic. 

 
HYPERGLYCAEMIA (high blood sugar levels) 

 
If your blood sugar is too high (hyperglycaemia), you may not have injected enough insulin. 
 
Why does hyperglycaemia occur? 
 
Examples include: 

 

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- you have not injected your insulin or not injected enough, or if it has become less effective, for 
example through incorrect storage, 

- you are doing less exercise than usual, you are under stress (emotional distress, excitement), or 
you have an injury, operation, infection or fever, 

- you are taking or have taken certain other medicines (see section 2, "Other medicines and 
Insulin Human Winthrop Comb 50"). 

 
Warning symptoms of hyperglycaemia 
 
Thirst, increased need to urinate, tiredness, dry skin, reddening of the face, loss of appetite, low blood 
pressure, fast heart beat, and glucose and ketone bodies in urine. Stomach pain, fast and deep 
breathing, sleepiness or even loss of consciousness may be signs of a serious condition (ketoacidosis) 
resulting from lack of insulin. 
 
What should you do if you experience hyperglycaemia 
 
Test your blood sugar level and your urine for ketones as soon as any of the above symptoms 
occur. Severe hyperglycaemia or ketoacidosis must always be treated by a doctor, normally in a 
hospital. 
 

HYPOGLYCAEMIA (low blood sugar levels) 
 
If your blood sugar level falls too much you may become unconscious. Serious hypoglycaemia may 
cause a heart attack or brain damage and may be life-threatening. You normally should be able to 
recognise when your blood sugar is falling too much so that you can take the right actions. 
 
Why does hypoglycaemia occur? 
 
Examples include: 
- you inject too much insulin, 
- you miss meals or delay them, 
- you do not eat enough, or eat food containing less carbohydrate than normal (sugar and 

substances similar to sugar are called carbohydrates; however, artificial sweeteners are NOT 
carbohydrates), 

- you lose carbohydrates due to vomiting or diarrhoea, 
- you drink alcohol, particularly if you are not eating much, 
- you are doing more exercise than usual or a different type of physical activity, 
- you are recovering from an injury or operation or other stress, 
- you are recovering from an illness or from fever, 
- you are taking or have stopped taking certain other medicines (see section 2, "Other medicines 

and Insulin Human Winthrop Comb 50"). 
 
Hypoglycaemia is also more likely to occur if: 
- you have just begun insulin treatment or changed to another insulin preparation, 
- your blood sugar levels are almost normal or are unstable, 
- you change the area of skin where you inject insulin (for example from the thigh to the upper 

arm), 
- you suffer from severe kidney or liver disease, or some other disease such as hypothyroidism. 
 
Warning symptoms of hypoglycaemia 
 
- In your body 
Examples of symptoms that tell you that your blood sugar level is falling too much or too fast: 
sweating, clammy skin, anxiety, fast heart beat, high blood pressure, palpitations and irregular 
heartbeat. These symptoms often develop before the symptoms of a low sugar level in the brain. 
 
- In your brain 

 

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Examples of symptoms that indicate a low sugar level in the brain: headaches, intense hunger, nausea, 
vomiting, tiredness, sleepiness, sleep disturbances, restlessness, aggressive behaviour, lapses in 
concentration, impaired reactions, depression, confusion, speech disturbances (sometimes total loss of 
speech), visual disorders, trembling, paralysis, tingling sensations (paraesthesia), numbness and 
tingling sensations in the area of the mouth, dizziness, loss of self-control, inability to look after 
yourself, convulsions, loss of consciousness. 
 
The first symptoms which alert you to hypoglycaemia ("warning symptoms") may change, be weaker 
or may be missing altogether if 
- you are elderly, if you have had diabetes for a long time or if you suffer from a certain type of 

nervous disease (diabetic autonomic neuropathy), 
- you have recently suffered hypoglycaemia (for example the day before) or if it develops slowly, 
- you have almost normal or, at least, greatly improved blood sugar levels, 
- you have recently changed from an animal insulin to a human insulin such as Insulin Human 

Winthrop, 
- you are taking or have taken certain other medicines (see section 2, "Other medicines and 

Insulin Human Winthrop Comb 50"). 
 
In such a case, you may develop severe hypoglycaemia (and even faint) before you are aware of the 
problem. Be familiar with your warning symptoms. If necessary, more frequent blood sugar testing 
can help to identify mild hypoglycaemic episodes that may otherwise be overlooked. If you are not 
confident about recognising your warning symptoms, avoid situations (such as driving a car) in which 
you or others would be put at risk by hypoglycaemia. 
 
What should you do if you experience hypoglycaemia 
 
1. Do not inject insulin. Immediately take about 10 to 20 g sugar, such as glucose, sugar cubes or a 

sugar-sweetened beverage. Caution: Artificial sweeteners and foods with artificial sweeteners 
(such as diet drinks) are of no help in treating hypoglycaemia. 

2. Then eat something that has a long-acting effect in raising your blood sugar (such as bread or 
pasta). Your doctor or nurse should have discussed this with you previously. 

3. If the hypoglycaemia comes back again take another 10 to 20 g sugar. 
4. Speak to a doctor immediately if you are not able to control the hypoglycaemia or if it recurs. 
 
Tell your relatives, friends and close colleagues the following: 
If you are not able to swallow or if you are unconscious, you will require an injection of glucose or 
glucagon (a medicine which increases blood sugar). These injections are justified even if it is not 
certain that you have hypoglycaemia. 
 
It is advisable to test your blood sugar immediately after taking glucose to check that you really have 
hypoglycaemia. 
 
 

 

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Package leaflet: Information for the user 

 
Insulin Human Winthrop Comb 50 40 IU/ml suspension for injection in a vial 

Insulin human 
 
 
Read all of this leaflet carefully before you start using this medicine because it contains 
important information for you. 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor, pharmacist or nurse. 
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours. 
- If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible 

side effects not listed in this leaflet. 
 
What is in this leaflet: 
1. What Insulin Human Winthrop Comb 50 is and what it is used for 
2. What you need to know before you use Insulin Human Winthrop Comb 50 
3. How to use Insulin Human Winthrop Comb 50 
4. Possible side effects 
5. How to store Insulin Human Winthrop Comb 50 
6. Contents of the pack and other information 
 
 
1. What Insulin Human Winthrop Comb  50 is and what it is used for 
 
Insulin Human Winthrop Comb 50 contains the active substance insulin human which is made by a 
biotechnology process and is identical with the body's own insulin. 
 
Insulin Human Winthrop Comb 50 is an insulin preparation with a rapid onset and moderately long 
duration of action.  
 
Insulin Human Winthrop Comb 50 is used to reduce high blood sugar in patients with diabetes 
mellitus who need treatment with insulin. Diabetes mellitus is a disease where your body does not 
produce enough insulin to control the level of blood sugar. 
 
 
2. What you need to know before you use Insulin Human Winthrop Comb  50 
 
Do not use Insulin Human Winthrop Comb 50 
 
If you are allergic to insulin or any of the other ingredients of this medicine (listed in section 6). 
 
Warnings and precautions 
 
Talk to your doctor, pharmacist or nurse before using Insulin Human Winthrop Comb 50. 
Follow closely the instructions for dosage, monitoring (blood and urine tests), diet and physical 
activity (physical work and exercise) as discussed with your doctor. 
 
If you are allergic to this medicine or to animal insulins, talk to your doctor. 
 
Special patient groups 
If you have liver or kidneys problems or if you are elderly, speak to your doctor as you may need a 
lower dose. 
 

 

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Travel 
Before travelling, consult your doctor. You may need to talk about 
- the availability of your insulin in the country you are visiting, 
- supplies of insulin, injection syringes etc., 
- correct storage of your insulin while travelling, 
- timing of meals and insulin administration while travelling, 
- the possible effects of changing to different time zones, 
- possible new health risks in the countries to be visited, 
- what you should do in emergency situations when you feel unwell or become ill. 
 
Illnesses and injuries 
In the following situations, the management of your diabetes may require a lot of care: 
- If you are ill or have a major injury then your blood sugar level may increase (hyperglycaemia).  
- If you are not eating enough, your blood sugar level may become too low (hypoglycaemia).  
In most cases you will need a doctor. Make sure that you contact a doctor early.  
 
If you have type 1 diabetes (insulin dependent diabetes mellitus), do not stop your insulin and 
continue to get enough carbohydrates. Always tell people who are caring for you or treating you that 
you require insulin. 
 
Some patients with long-standing type 2 diabetes mellitus and heart disease or previous stroke who 
were treated with pioglitazone and insulin experienced the development of heart failure. Inform your 
doctor as soon as possible if you experience signs of heart failure such as unusual shortness of breath 
or rapid increase in weight or localised swelling (oedema). 
 
Other medicines and Insulin Human Winthrop Comb  50 
 
Some medicines cause changes in the blood sugar level (decrease, increase or both depending on the 
situation). In each case, it may be necessary to adjust your insulin dosage to avoid blood sugar levels 
that are either too low or too high. Be careful when you start or stop taking another medicine. 
 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines. Before taking a medicine ask your doctor if it can affect your blood sugar level, and what 
action, if any, you need to take. 
 
Medicines that may cause your blood sugar level to fall (hypoglycaemia) include:  
- all other medicines to treat diabetes,  
- angiotensin converting enzyme (ACE) inhibitors (used to treat certain heart conditions or high 

blood pressure),  
- disopyramide (used to treat certain heart conditions),  
- fluoxetine (used to treat depression),  
- fibrates (used to lower high levels of blood lipids),  
- monoamine oxidase (MAO) inhibitors (used to treat depression),  
- pentoxifylline, propoxyphene, salicylates (such as aspirin, used to relieve pain and lower fever), 
- sulfonamide antibiotics. 
 
Medicines that may cause your blood sugar level to rise (hyperglycaemia) include:  
- corticosteroids (such as "cortisone", used to treat inflammation),  
- danazol (medicine acting on ovulation),  
- diazoxide (used to treat high blood pressure),  
- diuretics (used to treat high blood pressure or excessive fluid retention),  
- glucagon (pancreas hormone used to treat severe hypoglycaemia),  
- isoniazid (used to treat tuberculosis),  
- oestrogens and progestogens (such as in the contraceptive pill used for birth control),  
- phenothiazine derivatives (used to treat psychiatric disorders),  
- somatropin (growth hormone),  

 

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- sympathomimetic medicines (such as epinephrine [adrenaline] or salbutamol, terbutaline used to 
treat asthma), 

- thyroid hormones (used to treat the thyroid gland disorders), 
- protease inhibitors (used to treat HIV), 
- atypical antipsychotic medicines (such as olanzapine and clozapine). 
 
Your blood sugar level may either rise or fall if you take:  
- beta-blockers (used to treat high blood pressure),  
- clonidine (used to treat high blood pressure), 
- lithium salts (used to treat psychiatric disorders).  
Pentamidine (used to treat some infections caused by parasites) may cause hypoglycaemia which may 
sometimes be followed by hyperglycaemia. 
 
Beta-blockers like other sympatholytic medicines (such as clonidine, guanethidine, and reserpine) may 
weaken or suppress entirely the first warning symptoms which help you to recognise a 
hypoglycaemia. 
 
If you are not sure whether you are taking one of those medicines ask your doctor or pharmacist. 
 
Insulin Human Winthrop Comb 50 with alcohol 
 
Your blood sugar levels may either rise or fall if you drink alcohol. 
 
Pregnancy and breast-feeding 
 
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor or pharmacist for advice before taking this medicine. 
 
Inform your doctor if you are planning to become pregnant, or if you are already pregnant. Your 
insulin dosage may need to be changed during pregnancy and after giving birth. Particularly careful 
control of your diabetes, and prevention of hypoglycaemia, is important for the health of your baby.  
 
If you are breast-feeding consult your doctor as you may require adjustments in your insulin doses and 
your diet. 
 
Driving and using machines 
 
Your ability to concentrate or react may be reduced if:  
- you have hypoglycaemia (low blood sugar levels), 
- you have hyperglycaemia (high blood sugar levels), 
- you have problems with your sight.  
Keep this possible problem in mind in all situations where you might put yourself and others at risk 
(such as driving a car or using machines). You should contact your doctor for advice on driving if: 
- you have frequent episodes of hypoglycaemia, 
- the first warning symptoms which help you to recognise hypoglycaemia are reduced or absent. 
 
Important information about some of the ingredients of Insulin Human Winthrop Comb 50  
 
This medicine contains less than 1 mmol (23 mg) sodium per dose, i.e. it is essentially ‘sodium-free’. 
 
 

 

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3. How to use Insulin Human Winthrop Comb  50 
 
Dose 
 
Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor 
or pharmacist if you are not sure. 
 
Based on your life-style and the results of your blood sugar (glucose) tests, your doctor will 
- determine how much Insulin Human Winthrop Comb 50 per day you will need, 
- tell you when to check your blood sugar level, and whether you need to carry out urine tests, 
- tell you when you may need to inject a higher or lower dose of Insulin Human Winthrop 

Comb 50. 
 
Many factors may influence your blood sugar level. You should know these factors so that you are 
able to react correctly to changes in your blood sugar level and to prevent it from becoming too high 
or too low. See the box at the end of this leaflet for further information. 
 
Frequency of administration 
 
Insulin Human Winthrop Comb 50 is injected under the skin 20 to 30 minutes before a meal.  
 
Method of administration 
 
Insulin Human Winthrop Comb 50 is a fluid (suspension) for injection under the skin. 
 
Do NOT inject Insulin Human Winthrop Comb 50 into a vein (blood vessel). 
 
Your doctor will show you in which area of the skin you should inject your insulin. With each 
injection, change the puncture site within the particular area of skin that you are using. 
 
Do not use it in insulin pumps or other infusion pumps – special insulin preparations are available for 
use in such devices. 
 
How to handle the vials 
 
Insulin Human Winthrop Comb 50 contains 40 IU insulin per ml. Only injection syringes designed for 
this insulin concentration (40 IU per ml) must be used. The injection syringes must not contain any 
other medicines or traces of medicines (such as traces of heparin). 
 
Before the first withdrawal of insulin you must remove the safety tear-off cap on the vial. 
 
Mix the insulin well immediately before each injection. This is best done by rolling the vial tilted 
between the palms of the hands. Do not shake the vial vigorously as this could damage the insulin and 
cause froth to form. Froth can make it difficult for you to measure the correct dose. 
 
After mixing, the suspension must have a uniform milky-white appearance. It must not be used if it 
remains clear or if, for example, clumps, flakes, particles or anything similar are in the suspension or 
on the sides or bottom of the vial. A new vial with a uniform suspension on mixing must then be used. 
 
Always use a new vial if you notice that your blood sugar control is unexpectedly getting worse. This 
is because the insulin may have lost some of its effectiveness. If you think you may have a problem 
with your insulin, have it checked by your doctor or pharmacist. 
 

 

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Special care before injection 
 
Before injection remove any air bubbles. Make sure that neither alcohol nor other disinfectants or 
other substances contaminate the insulin. Do not mix insulin with any other medicines except with 
insulin human preparations as detailed below. 
 
Insulin Human Winthrop Comb 50 may be mixed with all insulin human preparations, EXCEPT those 
specially designed for use in insulin pumps. Also, it must NOT be mixed with animal source insulins 
or insulin analogues. 
 
Your doctor will tell you if you have to mix insulin human preparations. If you need to inject a 
mixture, draw the other insulin into the injection syringe before Insulin Human Winthrop Comb 50. 
Inject as soon as you have mixed them. Do not mix insulins of different strengths (for example 100 IU 
per ml and 40 IU per ml). 
 
If you use more Insulin Human Winthrop Comb 50 than you should 
- If you have injected too much Insulin Human Winthrop Comb 50, your blood sugar level 

may become too low (hypoglycaemia). Check your blood sugar frequently. In general, to 
prevent hypoglycaemia you must eat more food and monitor your blood sugar. For information 
on the treatment of hypoglycaemia, see box at the end of this leaflet. 

 
If you forget to use Insulin Human Winthrop Comb 50 
- If you have missed a dose of Insulin Human Winthrop Comb 50 or if you have not injected 

enough insulin, your blood sugar level may become too high (hyperglycaemia). Check your 
blood sugar frequently. For information on the treatment of hyperglycaemia, see box at the end 
of this leaflet. 

 
- Do not take a double dose to make up for a forgotten dose. 
 
If you stop using Insulin Human Winthrop Comb 50 
This could lead to severe hyperglycaemia (very high blood sugar) and ketoacidosis (build-up of acid 
in the blood because the body is breaking down fat instead of sugar). Do not stop Insulin Human 
Winthrop Comb 50 without speaking to a doctor, who will tell you what needs to be done. 
 
If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse. 
 
Insulin Mix-ups 
 
You must always check the insulin label before each injection to avoid mix-ups between Insulin 
Human Winthrop Comb 50 and other insulins.  
 
 
4. Possible side effects 
 
Like all medicines, this medicine cause side effects, although not everybody gets them. 
 
The most frequent side effect is hypoglycaemia (low blood sugar). The specific frequency cannot be 
estimated from available data (frequency not known). Serious hypoglycaemia may cause a heart attack 
or brain damage and may be life-threatening. For further information on the side effects of low blood 
sugar or high blood sugar, see the box at the end of this leaflet. 
 
Severe allergic reactions to insulin may occur which may become life-threatening. Such reactions to 
insulin or to the excipients can cause large-scale skin reactions (rash and itching all over the body); 
severe swelling of skin or mucous membranes (angiooedema), shortness of breath, a fall in blood 
pressure with rapid heart beat and sweating. Frequency of these reactions cannot be estimated from 
available data. 
 

 

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Side effects reported commonly (may affect up to 1 in 10 people) 
• Oedema 
Insulin treatment may cause temporary build-up of water in the body with swelling in the calves and 
ankles. 
• Injection site reactions 
 
Side effects reported uncommonly (may affect up to 1 in 100 people) 
• Severe allergic reaction with low blood pressure (shock) 
• Injection site urticaria (itchy rash) 
 
Other side effects include (frequency cannot be estimated from the available data) 
• Sodium retention 
• Eye reactions 
A marked change (improvement or worsening) in your blood sugar control can disturb your vision 
temporarily. If you have proliferative retinopathy (an eye disease related to diabetes) severe 
hypoglycaemic attacks may cause temporary loss of vision. 
• Skin changes at the injection site (lipodystrophy) 
If you inject your insulin too often at the same skin site, fatty tissue under the skin at this site may 
either shrink or thicken. Insulin that you inject in such a site may not work very well. Changing the 
injection site with each injection may help to prevent such skin changes. 
• Skin and allergic reactions 
Other mild reactions at the injection site (such as injection site redness, unusually intense pain on 
injection site, itching, injection site swelling or injection site inflammation) may occur. They can also 
spread around the injection site. Most minor reactions to insulins usually resolve in a few days to a 
few weeks. 
 
Insulin treatment can cause the body to produce antibodies to insulin (substances that act against 
insulin). However, only very rarely, this will require a change to your insulin dosage. 
 
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side 
effects not listed in this leaflet. 
 
 
5. How to store Insulin Human Winthrop Comb  50 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date which is stated on the carton and on the label of the vial 
after “EXP”. The expiry date refers to the last day of that month. 
 
Unopened vials 
Store in a refrigerator (2°C – 8°C). Do not freeze. Do not put Insulin Human Winthrop Comb 50 next 
to the freezer compartment or a freezer pack. Keep the vial in the outer carton in order to protect from 
light. 
 
Opened vials 
Once in-use, the vial may be stored for a maximum of 4 weeks in the outer carton not above 25°Cand 
away from direct heat (for example next to a heating unit) or direct light (direct sunlight or next to a 
lamp). Do not use the vial after this time period. It is recommended that the date of the first use be 
noted on the label. 
 
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment. 
 
 

 

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6. Contents of the pack and other information 
 
What Insulin Human Winthrop Comb 50 contains 
- The active substance is insulin human. One ml of Insulin Human Winthrop Comb 50 contains 

40 IU (International Units) of the active substance insulin human. 50% of the insulin is 
dissolved in water; the other 50% is present as tiny crystals of insulin protamine. 

- The other ingredients are: protamine sulphate, metacresol, phenol, zinc chloride, sodium 
dihydrogen phosphate dihydrate, glycerol, sodium hydroxide (see section 2 under “Important 
information about some of the ingredients of Insulin Human Winthrop Comb 50”), hydrochloric 
acid (for pH adjustment) and water for injections. 

 
What Insulin Human Winthrop Comb 50 looks like and contents of the pack 
After mixing, Insulin Human Winthrop Comb 50 is a uniformly milky fluid (suspension for injection), 
with no clumps, particles or flocculation visible. 
 
Insulin Human Winthrop Comb 50 is supplied in vials contains 10 ml suspension (400 IU). Packs of 
1 and 5 vials of 10 ml are available. Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder and Manufacturer 
Sanofi-Aventis Deutschland GmbH 
D-65926 Frankfurt am Main 
Germany 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
Sanofi Belgium 
Tél/Tel: +32 (0)2 710 54 00 
 

Lietuva 
UAB «SANOFI-AVENTIS LIETUVA» 
Tel: +370 5 2755224 
 

България 
sanofi-aventis Bulgaria EOOD 
Тел.: +359 (0)2 970 53 00 
 

Luxembourg/Luxemburg 
Sanofi Belgium  
Tél/Tel: +32 (0)2 710 54 00 (Belgique/Belgien) 
 

Česká republika 
sanofi-aventis, s.r.o. 
Tel: +420 233 086 111 
 

Magyarország 
SANOFI-AVENTIS Zrt. 
Tel.: +36 1 505 0050 
 

Danmark 
sanofi-aventis Denmark A/S 
Tlf: +45 45 16 70 00 
 

Malta 
Sanofi Malta Ltd. 
Tel: +356 21493022 
 

Deutschland 
Zentiva Pharma GmbH 
Tel: +49 (0)180 20 200 10 
 

Nederland 
sanofi-aventis Netherlands B.V. 
Tel: +31 (0)182 557 755 
 

Eesti 
sanofi-aventis Estonia OÜ 
Tel: +372 627 34 88 
 

Norge 
Aventis Pharma Norge AS 
Tlf: +47 67 10 71 00 
 

Ελλάδα 
sanofi-aventis AEBE 
Τηλ: +30 210 900 16 00 
 

Österreich 
sanofi-aventis GmbH 
Tel: +43 1 80 185 – 0 
 

 

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España 
sanofi-aventis, S.A. 
Tel: +34 93 485 94 00 
 

Polska 
sanofi-aventis Sp . z o.o. 
Tel.: +48 22 280 00 00 
 

France 
sanofi-aventis France 
Tél: 0 800 222 555 
Appel depuis l’étranger : +33 1 57 63 23 23 
 

Portugal 
Sanofi - Produtos Farmacêuticos, Lda. 
Tel: +351 21 35 89 400 
 

Hrvatska 
sanofi-aventis Croatia d.o.o. 
Tel: +385 1 600 34 00 

România 
Sanofi Romania SRL 
Tel: +40 (0) 21 317 31 36 
 

Ireland 
sanofi-aventis Ireland Ltd. T/A SANOFI 
Tel: +353 (0) 1 403 56 00 
 

Slovenija 
sanofi-aventis d.o.o. 
Tel: +386 1 560 48 00 
 

Ísland 
Vistor hf. 
Sími: +354 535 7000 
 

Slovenská republika 
sanofi-aventis Pharma Slovakia s.r.o. 
Tel: +421 2 33 100 100 
 

Italia 
Sanofi S.p.A. 
Tel: 800 13 12 12 (domande di tipo tecnico)  
800 536389 (altre domande) 
 

Suomi/Finland 
Sanofi Oy 
Puh/Tel: +358 (0) 201 200 300 
 

Κύπρος 
sanofi-aventis Cyprus Ltd. 
Τηλ: +357 22 871600 
 

Sverige 
Sanofi AB 
Tel: +46 (0)8 634 50 00 
 

Latvija 
sanofi-aventis Latvia SIA 
Tel: +371 67 33 24 51 
 

United Kingdom 
Sanofi 
Tel: +44 (0) 845 372 7101 
 

 
This leaflet was last revised in {date} 
 
 
Other source of information 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu/ 
 
 

 

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HYPERGLYCAEMIA AND HYPOGLYCAEMIA 
 

Always carry some sugar (at least 20 grams) with you. 
Carry some information with you to show you are diabetic. 

 
HYPERGLYCAEMIA (high blood sugar levels) 

 
If your blood sugar is too high (hyperglycaemia), you may not have injected enough insulin. 
 
Why does hyperglycaemia occur? 
 
Examples include: 
- you have not injected your insulin or not injected enough, or if it has become less effective, for 

example through incorrect storage, 
- you are doing less exercise than usual, you are under stress (emotional distress, excitement), or 

you have an injury, operation, infection or fever, 
- you are taking or have taken certain other medicines (see section 2, "Other medicines and 

Insulin Human Winthrop Comb 50"). 
 
Warning symptoms of hyperglycaemia 
 
Thirst, increased need to urinate, tiredness, dry skin, reddening of the face, loss of appetite, low blood 
pressure, fast heart beat, and glucose and ketone bodies in urine. Stomach pain, fast and deep 
breathing, sleepiness or even loss of consciousness may be signs of a serious condition (ketoacidosis) 
resulting from lack of insulin. 
 
What should you do if you experience hyperglycaemia 
 
Test your blood sugar level and your urine for ketones as soon as any of the above symptoms 
occur. Severe hyperglycaemia or ketoacidosis must always be treated by a doctor, normally in a 
hospital. 
 

HYPOGLYCAEMIA (low blood sugar levels) 
 
If your blood sugar level falls too much you may become unconscious. Serious hypoglycaemia may 
cause a heart attack or brain damage and may be life-threatening. You normally should be able to 
recognise when your blood sugar is falling too much so that you can take the right actions. 
 
Why does hypoglycaemia occur? 
 
Examples include: 
- you inject too much insulin, 
- you miss meals or delay them, 
- you do not eat enough, or eat food containing less carbohydrate than normal (sugar and 

substances similar to sugar are called carbohydrates; however, artificial sweeteners are NOT 
carbohydrates), 

- you lose carbohydrates due to vomiting or diarrhoea, 
- you drink alcohol, particularly if you are not eating much, 
- you are doing more exercise than usual or a different type of physical activity, 
- you are recovering from an injury or operation or other stress, 
- you are recovering from an illness or from fever, 
- you are taking or have stopped taking certain other medicines (see section 2, "Other medicines 

and Insulin Human Winthrop Comb 50"). 
 

 

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Hypoglycaemia is also more likely to occur if: 
- you have just begun insulin treatment or changed to another insulin preparation, 
- your blood sugar levels are almost normal or are unstable, 
- you change the area of skin where you inject insulin (for example from the thigh to the upper 

arm), 
- you suffer from severe kidney or liver disease, or some other disease such as hypothyroidism. 
 
Warning symptoms of hypoglycaemia 
 
- In your body 
Examples of symptoms that tell you that your blood sugar level is falling too much or too fast: 
sweating, clammy skin, anxiety, fast heart beat, high blood pressure, palpitations and irregular 
heartbeat. These symptoms often develop before the symptoms of a low sugar level in the brain. 
 
- In your brain 
Examples of symptoms that indicate a low sugar level in the brain: headaches, intense hunger, nausea, 
vomiting, tiredness, sleepiness, sleep disturbances, restlessness, aggressive behaviour, lapses in 
concentration, impaired reactions, depression, confusion, speech disturbances (sometimes total loss of 
speech), visual disorders, trembling, paralysis, tingling sensations (paraesthesia), numbness and 
tingling sensations in the area of the mouth, dizziness, loss of self-control, inability to look after 
yourself, convulsions, loss of consciousness. 
 
The first symptoms which alert you to hypoglycaemia ("warning symptoms") may change, be weaker 
or may be missing altogether if 
- you are elderly, if you have had diabetes for a long time or if you suffer from a certain type of 

nervous disease (diabetic autonomic neuropathy), 
- you have recently suffered hypoglycaemia (for example the day before) or if it develops slowly, 
- you have almost normal or, at least, greatly improved blood sugar levels, 
- you have recently changed from an animal insulin to a human insulin such as Insulin Human 

Winthrop, 
- you are taking or have taken certain other medicines (see section 2, "Other medicines and 

Insulin Human Winthrop Comb 50"). 
 
In such a case, you may develop severe hypoglycaemia (and even faint) before you are aware of the 
problem. Be familiar with your warning symptoms. If necessary, more frequent blood sugar testing 
can help to identify mild hypoglycaemic episodes that may otherwise be overlooked. If you are not 
confident about recognising your warning symptoms, avoid situations (such as driving a car) in which 
you or others would be put at risk by hypoglycaemia. 
 
What should you do if you experience hypoglycaemia 
 
1. Do not inject insulin. Immediately take about 10 to 20 g sugar, such as glucose, sugar cubes or a 

sugar-sweetened beverage. Caution: Artificial sweeteners and foods with artificial sweeteners 
(such as diet drinks) are of no help in treating hypoglycaemia. 

2. Then eat something that has a long-acting effect in raising your blood sugar (such as bread or 
pasta). Your doctor or nurse should have discussed this with you previously. 

3. If the hypoglycaemia comes back again take another 10 to 20 g sugar. 
4. Speak to a doctor immediately if you are not able to control the hypoglycaemia or if it recurs. 
 
Tell your relatives, friends and close colleagues the following: 
If you are not able to swallow or if you are unconscious, you will require an injection of glucose or 
glucagon (a medicine which increases blood sugar). These injections are justified even if it is not 
certain that you have hypoglycaemia. 
 
It is advisable to test your blood sugar immediately after taking glucose to check that you really have 
hypoglycaemia. 
 

 

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Package leaflet: Information for the user 

 
Insulin Human Winthrop Comb 50 100 IU/ml suspension for injection in a cartridge 

Insulin human 
 
 
Read all of this leaflet carefully before you start using this medicine because it contains 
important information for you. The instructions for using the insulin pen are provided with 
your insulin pen. Refer to them before using your medicine. 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor, pharmacist or nurse. 
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours. 
- If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible 

side effects not listed in this leaflet. 
 
What is in this leaflet: 
1. What Insulin Human Winthrop Comb 50 is and what it is used for 
2. What you need to know before you use Insulin Human Winthrop Comb 50 
3. How to use Insulin Human Winthrop Comb 50 
4. Possible side effects 
5. How to store Insulin Human Winthrop Comb 50 
6. Contents of the pack and other information 
 
 
1. What Insulin Human Winthrop Comb  50 is and what it is used for 
 
Insulin Human Winthrop Comb 50 contains the active substance insulin human which is made by a 
biotechnology process and is identical with the body's own insulin. 
 
Insulin Human Winthrop Comb 50 is an insulin preparation with a rapid onset and moderately long 
duration of action.  
 
Insulin Human Winthrop Comb 50 is used to reduce high blood sugar in patients with diabetes 
mellitus who need treatment with insulin. Diabetes mellitus is a disease where your body does not 
produce enough insulin to control the level of blood sugar. 
 
 
2. What you need to know before you use Insulin Human Winthrop Comb  50 
 
Do not use Insulin Human Winthrop Comb 50 
 
If you are allergic to insulin or any of the other ingredients of this medicine (listed in section 6).  
 
Warnings and precautions 
 
Talk to your doctor, pharmacist or nurse before using Insulin Human Winthrop Comb 50. 
Follow closely the instructions for dosage, monitoring (blood and urine tests), diet and physical 
activity (physical work and exercise) as discussed with your doctor. 
 
If you are allergic to this medicine or to animal insulins, talk to your doctor. 
 
Special patient groups 
If you have liver or kidneys problems or if you are elderly, speak to your doctor as you may need a 
lower dose. 
 

 

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Travel 
Before travelling, consult your doctor. You may need to talk about 
- the availability of your insulin in the country you are visiting, 
- supplies of insulin, injection syringes etc., 
- correct storage of your insulin while travelling, 
- timing of meals and insulin administration while travelling, 
- the possible effects of changing to different time zones, 
- possible new health risks in the countries to be visited, 
- what you should do in emergency situations when you feel unwell or become ill. 
 
Illnesses and injuries 
In the following situations, the management of your diabetes may require a lot of care: 
- If you are ill or have a major injury then your blood sugar level may increase (hyperglycaemia).  
- If you are not eating enough, your blood sugar level may become too low (hypoglycaemia).  
In most cases you will need a doctor. Make sure that you contact a doctor early.  
 
If you have type 1 diabetes (insulin dependent diabetes mellitus), do not stop your insulin and 
continue to get enough carbohydrates. Always tell people who are caring for you or treating you that 
you require insulin. 
 
Some patients with long-standing type 2 diabetes mellitus and heart disease or previous stroke who 
were treated with pioglitazone and insulin experienced the development of heart failure. Inform your 
doctor as soon as possible if you experience signs of heart failure such as unusual shortness of breath 
or rapid increase in weight or localised swelling (oedema). 
 
Other medicines and Insulin Human Winthrop Comb  50 
 
Some medicines cause changes in the blood sugar level (decrease, increase or both depending on the 
situation). In each case, it may be necessary to adjust your insulin dosage to avoid blood sugar levels 
that are either too low or too high. Be careful when you start or stop taking another medicine. 
 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines. Before taking a medicine ask your doctor if it can affect your blood sugar level, and what 
action, if any, you need to take. 
 
Medicines that may cause your blood sugar level to fall (hypoglycaemia) include:  
- all other medicines to treat diabetes,  
- angiotensin converting enzyme (ACE) inhibitors (used to treat certain heart conditions or high 

blood pressure),  
- disopyramide (used to treat certain heart conditions),  
- fluoxetine (used to treat depression),  
- fibrates (used to lower high levels of blood lipids),  
- monoamine oxidase (MAO) inhibitors (used to treat depression),  
- pentoxifylline, propoxyphene, salicylates (such as aspirin, used to relieve pain and lower fever), 
- sulfonamide antibiotics. 
 
Medicines that may cause your blood sugar level to rise (hyperglycaemia) include:  
- corticosteroids (such as "cortisone", used to treat inflammation),  
- danazol (medicine acting on ovulation),  
- diazoxide (used to treat high blood pressure),  
- diuretics (used to treat high blood pressure or excessive fluid retention),  
- glucagon (pancreas hormone used to treat severe hypoglycaemia),  
- isoniazid (used to treat tuberculosis),  
- oestrogens and progestogens (such as in the contraceptive pill used for birth control),  
- phenothiazine derivatives (used to treat psychiatric disorders),  
- somatropin (growth hormone),  

 

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- sympathomimetic medicines (such as epinephrine [adrenaline] or salbutamol, terbutaline used to 
treat asthma), 

- thyroid hormones (used to treat the thyroid gland disorders), 
- protease inhibitors (used to treat HIV), 
- atypical antipsychotic medicines (such as olanzapine and clozapine). 
 
Your blood sugar level may either rise or fall if you take:  
- beta-blockers (used to treat high blood pressure),  
- clonidine (used to treat high blood pressure),  
- lithium salts (used to treat psychiatric disorders).  
Pentamidine (used to treat some infections caused by parasites) may cause hypoglycaemia which may 
sometimes be followed by hyperglycaemia. 
 
Beta-blockers like other sympatholytic medicines (such as clonidine, guanethidine, and reserpine) may 
weaken or suppress entirely the first warning symptoms which help you to recognise a 
hypoglycaemia. 
 
If you are not sure whether you are taking one of those medicines ask your doctor or pharmacist. 
 
Insulin Human Winthrop Comb 50 with alcohol 
 
Your blood sugar levels may either rise or fall if you drink alcohol. 
 
Pregnancy and breast-feeding 
 
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor or pharmacist for advice before taking this medicine. 
 
Inform your doctor if you are planning to become pregnant, or if you are already pregnant. Your 
insulin dosage may need to be changed during pregnancy and after giving birth. Particularly careful 
control of your diabetes, and prevention of hypoglycaemia, is important for the health of your baby.  
If you are breast-feeding consult your doctor as you may require adjustments in your insulin doses and 
your diet. 
 
Driving and using machines 
 
Your ability to concentrate or react may be reduced if:  
- you have hypoglycaemia (low blood sugar levels), 
- you have hyperglycaemia (high blood sugar levels), 
- you have problems with your sight.  
Keep this possible problem in mind in all situations where you might put yourself and others at risk 
(such as driving a car or using machines). You should contact your doctor for advice on driving if: 
- you have frequent episodes of hypoglycaemia, 
- the first warning symptoms which help you to recognise hypoglycaemia are reduced or absent. 
 
Important information about some of the ingredients of Insulin Human Winthrop Comb 50  
 
This medicine contains less than 1 mmol (23 mg) sodium per dose, i.e. it is essentially ‘sodium-free’. 
 
 
3. How to use Insulin Human Winthrop Comb  50 
 
Dose 
 
Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor 
or pharmacist if you are not sure. 
 

 

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Based on your life-style and the results of your blood sugar (glucose) tests, your doctor will 
- determine how much Insulin Human Winthrop Comb 50 per day you will need, 
- tell you when to check your blood sugar level, and whether you need to carry out urine tests, 
- tell you when you may need to inject a higher or lower dose of Insulin Human Winthrop 

Comb 50. 
 
Many factors may influence your blood sugar level. You should know these factors so that you are 
able to react correctly to changes in your blood sugar level and to prevent it from becoming too high 
or too low. See the box at the end of this leaflet for further information. 
 
Frequency of administration 
 
Insulin Human Winthrop Comb 50 is injected under the skin 20 to 30 minutes before a meal.  
 
Method of administration 
 
Insulin Human Winthrop Comb 50 is a fluid (suspension) for injection under the skin. 
 
Do NOT inject Insulin Human Winthrop Comb 50 into a vein (blood vessel). 
 
Your doctor will show you in which area of the skin you should inject your insulin. With each 
injection, change the puncture site within the particular area of skin that you are using. 
 
Do not use it in insulin pumps or other infusion pumps - special insulin preparations are available for 
use in such devices. 
 
How to handle the cartridges 
 
To ensure you get the accurate dose, the Insulin Human Winthrop Comb 50 cartridges are to be used 
only with the following pens: 
- JuniorSTAR which delivers doses in steps of 0.5 units  
- OptiPen, ClikSTAR, Tactipen, Autopen 24 or AllStar which deliver doses in steps of 1 unit. 
Not all of these pens may be marketed in your country.  
 
The pen should be used as recommended in the information provided by the device manufacturer. The 
manufacturer’s instructions for using the pen must be followed carefully for loading the cartridge, 
attaching the injection needle, and administering the insulin injection. 
 
Keep the cartridge at room temperature for 1 or 2 hours before inserting it into the pen. Mix the 
insulin well and check it before you insert it into the pen. Later, you must mix the insulin well again 
immediately before each injection. 
 
Mixing is best done by gently tilting the cartridge or pen (with the cartridge in it) back and forth at 
least 10 times. To assist in mixing, three tiny metal balls are present in the cartridge. 
 
After mixing, the suspension must have a uniform milky-white appearance. It must not be used if it 
remains clear or if, for example, clumps, flakes, particles or anything similar are in the suspension or 
on the sides or bottom of the cartridge. A new cartridge with a uniform suspension on mixing must 
then be used. 
 
Always use a new cartridge if you notice that your blood sugar control is unexpectedly getting worse. 
This is because the insulin may have lost some of its effectiveness. If you think you may have a 
problem with your insulin, have it checked by your doctor or pharmacist. 
 
Special care before injection 
 

 

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Before injection remove any air bubbles (see instructions for using the pen). Make sure that neither 
alcohol nor other disinfectants or other substances contaminate the insulin. 
- Do not re-fill and re-use empty cartridges. 
- Do not add any other insulin to the cartridge. 
- Do not mix insulin with any other medicines. 
-  
-  
 
Problems with the pen? 
 
Refer to the manufacturer’s instructions for using the pen. 
If the insulin pen is damaged or not working properly (due to mechanical defects) it has to be 
discarded, and a new insulin pen has to be used. 
 
If the pen does not function well, you can draw the insulin from the cartridge into an injection syringe. 
Therefore, keep injection syringes and needles as well. However, use only those injection syringes 
which are designed for an insulin concentration of 100 IU (International Units) per ml. 
 
If you use more Insulin Human Winthrop Comb 50 than you should 
- If you have injected too much Insulin Human Winthrop Comb 50, your blood sugar level 

may become too low (hypoglycaemia). Check your blood sugar frequently. In general, to 
prevent hypoglycaemia you must eat more food and monitor your blood sugar. For information 
on the treatment of hypoglycaemia, see box at the end of this leaflet. 

 
If you forget to use Insulin HumaWinthrop Comb 50 
- If you have missed a dose of Insulin Human Winthrop Comb 50 or if you have not injected 

enough insulin, your blood sugar level may become too high (hyperglycaemia). Check your 
blood sugar frequently. For information on the treatment of hyperglycaemia, see box at the end 
of this leaflet. 

 
- Do not take a double dose to make up for a forgotten dose. 
 
If you stop using Insulin Human Winthrop Comb 50 
This could lead to severe hyperglycaemia (very high blood sugar) and ketoacidosis (build-up of acid 
in the blood because the body is breaking down fat instead of sugar). Do not stop Insulin Human 
Winthrop Comb 50 without speaking to a doctor, who will tell you what needs to be done. 
 
If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse. 
 
Insulin Mix-ups 
 
You must always check the insulin label before each injection to avoid mix-ups between Insulin 
Human Winthrop Comb 50 and other insulins.  
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
The most frequent side effect is hypoglycaemia (low blood sugar). The specific frequency cannot be 
estimated from available data (frequency not known). Serious hypoglycaemia may cause a heart attack 
or brain damage and may be life-threatening. For further information on the side effects of low blood 
sugar or high blood sugar, see the box at the end of this leaflet. 
 
Severe allergic reactions to insulin may occur which may become life-threatening. Such reactions to 
insulin or to the excipients can cause large-scale skin reactions (rash and itching all over the body); 
severe swelling of skin or mucous membranes (angiooedema), shortness of breath, a fall in blood 

 

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pressure with rapid heart beat and sweating. Frequency of these reactions cannot be estimated from 
available data. 
 
Side effects reported commonly (may affect up to 1 in 10 people) 
• Oedema 
Insulin treatment may cause temporary build-up of water in the body with swelling in the calves and 
ankles. 
• Injection site reactions 
 
Side effects reported uncommonly (may affect up to 1 in 100 people) 
• Severe allergic reaction with low blood pressure (shock) 
• Injection site urticaria (itchy rash) 
 
Other side effects include (frequency cannot be estimated from the available data) 
• Sodium retention 
• Eye reactions 
A marked change (improvement or worsening) in your blood sugar control can disturb your vision 
temporarily. If you have proliferative retinopathy (an eye disease related to diabetes) severe 
hypoglycaemic attacks may cause temporary loss of vision. 
• Skin changes at the injection site (lipodystrophy) 
If you inject your insulin too often at the same skin site, fatty tissue under the skin at this site may 
either shrink or thicken. Insulin that you inject in such a site may not work very well. Changing the 
injection site with each injection may help to prevent such skin changes. 
• Skin and allergic reactions 
Other mild reactions at the injection site (such as injection site redness, unusually intense pain on 
injection site, itching, injection site swelling or injection site inflammation) may occur. They can also 
spread around the injection site. Most minor reactions to insulins usually resolve in a few days to a 
few weeks. 
 
Insulin treatment can cause the body to produce antibodies to insulin (substances that act against 
insulin). However, only very rarely, this will require a change to your insulin dosage. 
 
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side 
effects not listed in this leaflet. 
 
 
5. How to store Insulin Human Winthrop Comb  50 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date which is stated on the carton and on the label of the 
cartridge after “EXP”. The expiry date refers to the last day of that month. 
 
Unopened cartridges 
Store in a refrigerator (2°C - 8°C). Do not freeze. Do not put Insulin Human Winthrop Comb 50 next 
to the freezer compartment or a freezer pack. Keep the cartridge in the outer carton in order to protect 
from light. 
 
In-use cartridges 
Cartridges in-use (in the insulin pen) or carried as a spare may be stored for a maximum of 4 weeks 
not above 25°C and away from direct heat (for example next to a heating unit) or direct light (direct 
sunlight or next to a lamp). The cartridge in-use must not be stored in a refrigerator. Do not use the 
cartridge after this time period. 
 
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment. 
 

 

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6. Contents of the pack and other information 
 
What Insulin Human Winthrop Comb 50 contains 
- The active substance is insulin human. One ml of Insulin Human Winthrop Comb 50 contains 

100 IU (International Units) of the active substance insulin human. 50% of the insulin is 
dissolved in water; the other 50% is present as tiny crystals of insulin protamine. 

- The other ingredients are: protamine sulphate, metacresol, phenol, zinc chloride, sodium 
dihydrogen phosphate dihydrate, glycerol, sodium hydroxide (see section 2 under “Important 
information about some of the ingredients of Insulin Human Winthrop Comb 50”), hydrochloric 
acid (for pH adjustment) and water for injections. 

 
What Insulin Human Winthrop Comb 50 looks like and contents of the pack 
After mixing, Insulin Human Winthrop Comb 50 is a uniformly milky fluid (suspension for injection), 
with no clumps, particles or flocculation visible. 
 
Insulin Human Winthrop Comb 50 is supplied in cartridges containing 3 ml suspension (300 IU). 
Packs of 3, 4, 5, 6, 9 and 10 cartridges of 3 ml are available. Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder and Manufacturer 
Sanofi-Aventis Deutschland GmbH 
D-65926 Frankfurt am Main 
Germany 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
Sanofi Belgium 
Tél/Tel: +32 (0)2 710 54 00 
 

Lietuva 
UAB «SANOFI-AVENTIS LIETUVA» 
Tel: +370 5 2755224 
 

България 
sanofi-aventis Bulgaria EOOD 
Тел.: +359 (0)2 970 53 00 
 

Luxembourg/Luxemburg 
Sanofi Belgium  
Tél/Tel: +32 (0)2 710 54 00 (Belgique/Belgien) 
 

Česká republika 
sanofi-aventis, s.r.o. 
Tel: +420 233 086 111 
 

Magyarország 
SANOFI-AVENTIS Zrt. 
Tel.: +36 1 505 0050 
 

Danmark 
sanofi-aventis Denmark A/S 
Tlf: +45 45 16 70 00 
 

Malta 
Sanofi Malta Ltd. 
Tel: +356 21493022 
 

Deutschland 
Zentiva Pharma GmbH 
Tel: +49 (0)180 20 200 10 
 

Nederland 
sanofi-aventis Netherlands B.V. 
Tel: +31 (0)182 557 755 
 

Eesti 
sanofi-aventis Estonia OÜ 
Tel: +372 627 34 88 
 

Norge 
Aventis Pharma Norge AS 
Tlf: +47 67 10 71 00 
 

Ελλάδα 
sanofi-aventis AEBE 
Τηλ: +30 210 900 16 00 
 

Österreich 
sanofi-aventis GmbH 
Tel: +43 1 80 185 – 0 
 

 

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España 
sanofi-aventis, S.A. 
Tel: +34 93 485 94 00 
 

Polska 
sanofi-aventis Sp. z o.o. 
Tel.: +48 22 280 00 00 
 

France 
sanofi-aventis France 
Tél: 0 800 222 555 
Appel depuis l’étranger : +33 1 57 63 23 23 
 

Portugal 
Sanofi - Produtos Farmacêuticos, Lda. 
Tel: +351 21 35 89 400 
 

Hrvatska 
sanofi-aventis Croatia d.o.o. 
Tel: +385 1 600 34 00 

România 
Sanofi Romania SRL 
Tel: +40 (0) 21 317 31 36 
 

Ireland 
sanofi-aventis Ireland Ltd. T/A SANOFI 
Tel: +353 (0) 1 403 56 00 
 

Slovenija 
sanofi-aventis d.o.o. 
Tel: +386 1 560 48 00 
 

Ísland 
Vistor hf. 
Sími: +354 535 7000 
 

Slovenská republika 
sanofi-aventis Pharma Slovakia s.r.o. 
Tel: +421 2 33 100 100 
 

Italia 
Sanofi S.p.A. 
Tel: 800 13 12 12 (domande di tipo tecnico)  
800 536389 (altre domande) 
 

Suomi/Finland 
Sanofi Oy 
Puh/Tel: +358 (0) 201 200 300 
 

Κύπρος 
sanofi-aventis Cyprus Ltd. 
Τηλ: +357 22 871600 
 

Sverige 
Sanofi AB 
Tel: +46 (0)8 634 50 00 
 

Latvija 
sanofi-aventis Latvia SIA 
Tel: +371 67 33 24 51 
 

United Kingdom 
Sanofi 
Tel: +44 (0) 845 372 7101 
 

 
This leaflet was last revised in {date} 
 
 
Other source of information 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu/ 
 
 
 
 

HYPERGLYCAEMIA AND HYPOGLYCAEMIA 
 

Always carry some sugar (at least 20 grams) with you. 
Carry some information with you to show you are diabetic. 

 
HYPERGLYCAEMIA (high blood sugar levels) 

 
If your blood sugar is too high (hyperglycaemia), you may not have injected enough insulin. 
 
Why does hyperglycaemia occur? 
 
Examples include: 

 

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- you have not injected your insulin or not injected enough, or if it has become less effective, for 
example through incorrect storage, 

- your insulin pen does not work properly, 
- you are doing less exercise than usual, you are under stress (emotional distress, excitement), or 

you have an injury, operation, infection or fever, 
- you are taking or have taken certain other medicines (see section 2, "Other medicines and 

Insulin Human Winthrop Comb 50"). 
 
Warning symptoms of hyperglycaemia 
 
Thirst, increased need to urinate, tiredness, dry skin, reddening of the face, loss of appetite, low blood 
pressure, fast heart beat, and glucose and ketone bodies in urine. Stomach pain, fast and deep 
breathing, sleepiness or even loss of consciousness may be signs of a serious condition (ketoacidosis) 
resulting from lack of insulin. 
 
What should you do if you experience hyperglycaemia 
 
Test your blood sugar level and your urine for ketones as soon as any of the above symptoms 
occur. Severe hyperglycaemia or ketoacidosis must always be treated by a doctor, normally in a 
hospital. 
 

HYPOGLYCAEMIA (low blood sugar levels) 
 
If your blood sugar level falls too much you may become unconscious. Serious hypoglycaemia may 
cause a heart attack or brain damage and may be life-threatening. You normally should be able to 
recognise when your blood sugar is falling too much so that you can take the right actions. 
 
Why does hypoglycaemia occur? 
 
Examples include: 
- you inject too much insulin, 
- you miss meals or delay them, 
- you do not eat enough, or eat food containing less carbohydrate than normal (sugar and 

substances similar to sugar are called carbohydrates; however, artificial sweeteners are NOT 
carbohydrates), 

- you lose carbohydrates due to vomiting or diarrhoea, 
- you drink alcohol, particularly if you are not eating much, 
- you are doing more exercise than usual or a different type of physical activity, 
- you are recovering from an injury or operation or other stress, 
- you are recovering from an illness or from fever, 
- you are taking or have stopped taking certain other medicines (see section 2, "Other medicines 

and Insulin Human Winthrop Comb 50"). 
 
Hypoglycaemia is also more likely to occur if: 
- you have just begun insulin treatment or changed to another insulin preparation, 
- your blood sugar levels are almost normal or are unstable, 
- you change the area of skin where you inject insulin (for example from the thigh to the upper 

arm), 
- you suffer from severe kidney or liver disease, or some other disease such as hypothyroidism. 
 
Warning symptoms of hypoglycaemia 
 
- In your body 
Examples of symptoms that tell you that your blood sugar level is falling too much or too fast: 
sweating, clammy skin, anxiety, fast heart beat, high blood pressure, palpitations and irregular 
heartbeat. These symptoms often develop before the symptoms of a low sugar level in the brain. 
 

 

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- In your brain 
Examples of symptoms that indicate a low sugar level in the brain: headaches, intense hunger, nausea, 
vomiting, tiredness, sleepiness, sleep disturbances, restlessness, aggressive behaviour, lapses in 
concentration, impaired reactions, depression, confusion, speech disturbances (sometimes total loss of 
speech), visual disorders, trembling, paralysis, tingling sensations (paraesthesia), numbness and 
tingling sensations in the area of the mouth, dizziness, loss of self-control, inability to look after 
yourself, convulsions, loss of consciousness. 
 
The first symptoms which alert you to hypoglycaemia ("warning symptoms") may change, be weaker 
or may be missing altogether if 
- you are elderly, if you have had diabetes for a long time or if you suffer from a certain type of 

nervous disease (diabetic autonomic neuropathy), 
- you have recently suffered hypoglycaemia (for example the day before) or if it develops slowly, 
- you have almost normal or, at least, greatly improved blood sugar levels, 
- you have recently changed from an animal insulin to a human insulin such as Insulin Human 

Winthrop, 
- you are taking or have taken certain other medicines (see section 2, "Other medicines and 

Insulin Human Winthrop Comb 50"). 
 
In such a case, you may develop severe hypoglycaemia (and even faint) before you are aware of the 
problem. Be familiar with your warning symptoms. If necessary, more frequent blood sugar testing 
can help to identify mild hypoglycaemic episodes that may otherwise be overlooked. If you are not 
confident about recognising your warning symptoms, avoid situations (such as driving a car) in which 
you or others would be put at risk by hypoglycaemia. 
 
What should you do if you experience hypoglycaemia 
 
1. Do not inject insulin. Immediately take about 10 to 20 g sugar, such as glucose, sugar cubes or a 

sugar-sweetened beverage. Caution: Artificial sweeteners and foods with artificial sweeteners 
(such as diet drinks) are of no help in treating hypoglycaemia. 

2. Then eat something that has a long-acting effect in raising your blood sugar (such as bread or 
pasta). Your doctor or nurse should have discussed this with you previously. 

3. If the hypoglycaemia comes back again take another 10 to 20 g sugar. 
4. Speak to a doctor immediately if you are not able to control the hypoglycaemia or if it recurs. 
 
Tell your relatives, friends and close colleagues the following: 
If you are not able to swallow or if you are unconscious, you will require an injection of glucose or 
glucagon (a medicine which increases blood sugar). These injections are justified even if it is not 
certain that you have hypoglycaemia. 
 
It is advisable to test your blood sugar immediately after taking glucose to check that you really have 
hypoglycaemia. 
 
 

 

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Package leaflet: Information for the user 

 
Insulin Human Winthrop Comb 50 SoloStar 100 IU/ml suspension for injection in a pre-filled 

pen 
Insulin human 

 
 
Read all of this leaflet carefully, including the Instructions for Use of Insulin Human Winthrop 
Comb 50 SoloStar, pre-filled pen, before you start using this medicine because it contains 
important information for you. 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor, pharmacist or nurse. 
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours. 
- If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible 

side effects not listed in this leaflet. 
 
What is in this leaflet: 
1. What Insulin Human Winthrop Comb 50 is and what it is used for 
2. What you need to know before you use Insulin Human Winthrop Comb 50 
3. How to use Insulin Human Winthrop Comb 50 
4. Possible side effects 
5. How to store Insulin Human Winthrop Comb 50 
6. Contents of the pack and other information 
 
 
1. What Insulin Human Winthrop Comb  50 is and what it is used for 
 
Insulin Human Winthrop Comb 50 contains the active substance insulin human which is made by a 
biotechnology process and is identical with the body's own insulin. 
 
Insulin Human Winthrop Comb 50 is an insulin preparation with a rapid onset and moderately long 
duration of action. It comes in cartridges sealed in disposable pen injectors, SoloStar. 
 
Insulin Human Winthrop Comb 50 is used to reduce high blood sugar in patients with diabetes 
mellitus who need treatment with insulin. Diabetes mellitus is a disease where your body does not 
produce enough insulin to control the level of blood sugar. 
 
 
2. What you need to know before you use Insulin Human Winthrop Comb  50 
 
Do not use Insulin Human Winthrop Comb 50 
 
If you are allergic to insulin or any of the other ingredients of this medicine (listed in section 6).  
 
Warnings and precautions 
 
Talk to your doctor, pharmacist or nurse befor using Insulin Human Winthrop Comb 50. 
Follow closely the instructions for dosage, monitoring (blood and urine tests), diet and physical 
activity (physical work and exercise), injection technique as discussed with your doctor. 
 
If you are allergic to this medicine or to animal insulins, talk to your doctor. 
 
Special patient groups 
If you have liver or kidneys problems or if you are elderly, speak to your doctor as you may need a 
lower dose. 

 

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Travel 
Before travelling, consult your doctor. You may need to talk about 
- the availability of your insulin in the country you are visiting, 
- supplies of insulin, injection syringes etc., 
- correct storage of your insulin while travelling, 
- timing of meals and insulin administration while travelling, 
- the possible effects of changing to different time zones, 
- possible new health risks in the countries to be visited, 
- what you should do in emergency situations when you feel unwell or become ill. 
 
Illnesses and injuries 
In the following situations, the management of your diabetes may require a lot of care: 
- If you are ill or have a major injury then your blood sugar level may increase (hyperglycaemia).  
- If you are not eating enough, your blood sugar level may become too low (hypoglycaemia).  
In most cases you will need a doctor. Make sure that you contact a doctor early.  
 
If you have type 1 diabetes (insulin dependent diabetes mellitus), do not stop your insulin and 
continue to get enough carbohydrates. Always tell people who are caring for you or treating you that 
you require insulin. 
 
Some patients with long-standing type 2 diabetes mellitus and heart disease or previous stroke who 
were treated with pioglitazone and insulin experienced the development of heart failure. Inform your 
doctor as soon as possible if you experience signs of heart failure such as unusual shortness of breath 
or rapid increase in weight or localised swelling (oedema). 
 
Other medicines and Insulin Human Winthrop Comb  50 
 
Some medicines cause changes in the blood sugar level (decrease, increase or both depending on the 
situation). In each case, it may be necessary to adjust your insulin dosage to avoid blood sugar levels 
that are either too low or too high. Be careful when you start or stop taking another medicine. 
 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines. Before taking a medicine ask your doctor if it can affect your blood sugar level, and what 
action, if any, you need to take. 
 
Medicines that may cause your blood sugar level to fall (hypoglycaemia) include:  
- all other medicines to treat diabetes,  
- angiotensin converting enzyme (ACE) inhibitors (used to treat certain heart conditions or high 

blood pressure),  
- disopyramide (used to treat certain heart conditions),  
- fluoxetine (used to treat depression),  
- fibrates (used to lower high levels of blood lipids),  
- monoamine oxidase (MAO) inhibitors (used to treat depression),  
- pentoxifylline, propoxyphene, salicylates (such as aspirin, used to relieve pain and lower fever), 
- sulfonamide antibiotics. 
 
Medicines that may cause your blood sugar level to rise (hyperglycaemia) include:  
- corticosteroids (such as "cortisone", used to treat inflammation),  
- danazol (medicine acting on ovulation),  
- diazoxide (used to treat high blood pressure),  
- diuretics (used to treat high blood pressure or excessive fluid retention),  
- glucagon (pancreas hormone used to treat severe hypoglycaemia),  
- isoniazid (used to treat tuberculosis),  
- oestrogens and progestogens (such as in the contraceptive pill used for birth control),  
- phenothiazine derivatives (used to treat psychiatric disorders),  
- somatropin (growth hormone),  

 

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- sympathomimetic medicines (such as epinephrine [adrenaline] or salbutamol, terbutaline used to 
treat asthma), 

- thyroid hormones (used to treat the thyroid gland disorders), 
- protease inhibitors (used to treat HIV), 
- atypical antipsychotic medicines (such as olanzapine and clozapine). 
 
Your blood sugar level may either rise or fall if you take:  
- beta-blockers (used to treat high blood pressure),  
- clonidine (used to treat high blood pressure), 
- lithium salts (used to treat psychiatric disorders).  
Pentamidine (used to treat some infections caused by parasites) may cause hypoglycaemia which may 
sometimes be followed by hyperglycaemia. 
 
Beta-blockers like other sympatholytic medicines (such as clonidine, guanethidine, and reserpine) may 
weaken or suppress entirely the first warning symptoms which help you to recognise a 
hypoglycaemia. 
 
If you are not sure whether you are taking one of those medicines ask your doctor or pharmacist. 
 
Insulin Human Winthrop Comb 50 with alcohol 
 
Your blood sugar levels may either rise or fall if you drink alcohol. 
 
Pregnancy and breast-feeding 
 
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor or pharmacist for advice before taking this medicine. 
 
Inform your doctor if you are planning to become pregnant, or if you are already pregnant. Your 
insulin dosage may need to be changed during pregnancy and after giving birth. Particularly careful 
control of your diabetes, and prevention of hypoglycaemia, is important for the health of your baby.  
 
If you are breast-feeding consult your doctor as you may require adjustments in your insulin doses and 
your diet. 
 
Driving and using machines 
 
Your ability to concentrate or react may be reduced if:  
- you have hypoglycaemia (low blood sugar levels), 
- you have hyperglycaemia (high blood sugar levels), 
- you have problems with your sight.  
Keep this possible problem in mind in all situations where you might put yourself and others at risk 
(such as driving a car or using machines). You should contact your doctor for advice on driving if: 
- you have frequent episodes of hypoglycaemia, 
- the first warning symptoms which help you to recognise hypoglycaemia are reduced or absent. 
 
Important information about some of the ingredients of Insulin Human Winthrop Comb 50  
 
This medicine contains less than 1 mmol (23 mg) sodium per dose, i.e. it is essentially ‘sodium-free’. 
 
 

 

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3. How to use Insulin Human Winthrop Comb 50 
 
Dose 
 
Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor 
or pharmacist if you are not sure. 
 
Based on your life-style and the results of your blood sugar (glucose) tests, your doctor will 
- determine how much Insulin Human Winthrop Comb 50 per day you will need, 
- tell you when to check your blood sugar level, and whether you need to carry out urine tests, 
- tell you when you may need to inject a higher or lower dose of Insulin Human Winthrop 

Comb 50. 
 
Many factors may influence your blood sugar level. You should know these factors so that you are 
able to react correctly to changes in your blood sugar level and to prevent it from becoming too high 
or too low. See the box at the end of this leaflet for further information. 
 
Frequency of administration 
 
Insulin Human Winthrop Comb 50 is injected under the skin 20 to 30 minutes before a meal. 
 
Method of administration 
 
Insulin Human Winthrop Comb 50 is a fluid (suspension) for injection under the skin. 
 
Do NOT inject Insulin Human Winthrop Comb 50 into a vein. 
 
SoloStar delivers insulin in doses from 1 to 80 units in steps of 1 unit. Each pen contains multiple 
doses. 
 
Your doctor will show you in which area of the skin you should inject your insulin. With each 
injection, change the puncture site within the particular area of skin that you are using. 
 
How to handle SoloStar 
 
SoloStar is a pre-filled disposable pen containing human insulin. 
 
Read carefully the "SoloStar Instructions for Use" included in this package leaflet. You must 
use the pen as described in these Instructions for Use. 
 
A new injection needle must be attached before each use. Only use needles that have been approved 
for use with SoloStar. 
A safety test must be performed before each injection. 
 
Mix the insulin well and check it before first use. Later, you must mix the insulin well again 
immediately before each injection. 
 
Mixing is best done by gently tilting the pen back and forth at least 10 times. To assist in mixing, three 
tiny metal balls are present in the cartridge. 
 
After mixing, the suspension must have a uniform milky-white appearance. It must not be used if it 
remains clear or if, for example, clumps, flakes, particles or anything similar are in the suspension or 
on the sides or bottom of the cartridge in the pen. A new pen with a uniform suspension on mixing 
must then be used. 
 
Always use a new pen if you notice that your blood sugar control is unexpectedly getting worse. If 
you think you have a problem with SoloStar, consult your doctor, pharmacist or nurse. 

 

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To prevent the possible transmission of disease, each pen must be used by one patient only. 
 
Special care before injection 
 
Make sure that neither alcohol nor other disinfectants or other substances contaminate the insulin. 
 
Do not mix insulin with any other medicines. Insulin Human Winthrop Comb 50 SoloStar, pre-filled 
pen, is not designed to allow any other insulin to be mixed in the cartridge. 
 
Empty pens must not be re-filled and must be properly discarded. 
 
Do not use SoloStar if it is damaged or not working properly (due to mechanical defects), it has to be 
discarded and a new SoloStar has to be used. 
 
If you use more Insulin Human Winthrop Comb 50 than you should 
- If you have injected too much Insulin Human Winthrop Comb 50, your blood sugar level 

may become too low (hypoglycaemia). Check your blood sugar frequently. In general, to 
prevent hypoglycaemia you must eat more food and monitor your blood sugar. For information 
on the treatment of hypoglycaemia, see box at the end of this leaflet. 

 
If you forget to use Insulin Human Winthrop Comb 50 
- If you have missed a dose of Insulin Human Winthrop Comb 50 or if you have not injected 

enough insulin, your blood sugar level may become too high (hyperglycaemia). Check your 
blood sugar frequently. For information on the treatment of hyperglycaemia, see box at the end 
of this leaflet. 

 
- Do not take a double dose to make up for a forgotten dose. 
 
If you stop using Insulin Human Winthrop Comb 50 
This could lead to severe hyperglycaemia (very high blood sugar) and ketoacidosis (build-up of acid 
in the blood because the body is breaking down fat instead of sugar). Do not stop Insulin Human 
Winthrop Comb 50 without speaking to a doctor, who will tell you what needs to be done. 
 
If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse. 
 
Insulin Mix-ups 
 
You must always check the insulin label before each injection to avoid mix-ups between Insulin 
Human Winthrop Comb 50 and other insulins.  
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
The most frequent side effect is hypoglycaemia (low blood sugar). The specific frequency cannot be 
estimated from available data (frequency not known). Serious hypoglycaemia may cause a heart attack 
or brain damage and may be life-threatening. For further information on the side effects of low blood 
sugar or high blood sugar, see the box at the end of this leaflet. 
 
Severe allergic reactions to insulin may occur which may become life-threatening. Such reactions to 
insulin or to the excipients can cause large-scale skin reactions (rash and itching all over the body); 
severe swelling of skin or mucous membranes (angiooedema), shortness of breath, a fall in blood 
pressure with rapid heart beat and sweating. Frequency of these reactions cannot be estimated from 
available data. 
 

 

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Side effects reported commonly (may affect up to 1 in 10 people) 
• Oedema 
Insulin treatment may cause temporary build-up of water in the body with swelling in the calves and 
ankles. 
• Injection site reactions 
 
Side effects reported uncommonly (may affect up to 1 in 100 peopel) 
• Severe allergic reaction with low blood pressure (shock) 
• Injection site urticaria (itchy rash) 
 
Other side effects include (frequency cannot be estimated from the available data) 
• Sodium retention 
• Eye reactions 
A marked change (improvement or worsening) in your blood sugar control can disturb your vision 
temporarily. If you have proliferative retinopathy (an eye disease related to diabetes) severe 
hypoglycaemic attacks may cause temporary loss of vision. 
• Skin changes at the injection site (lipodystrophy) 
If you inject your insulin too often at the same skin site, fatty tissue under the skin at this site may 
either shrink or thicken. Insulin that you inject in such a site may not work very well. Changing the 
injection site with each injection may help to prevent such skin changes. 
• Skin and allergic reactions 
Other mild reactions at the injection site (such as injection site redness, unusually intense pain on 
injection site, itching, injection site swelling or injection site inflammation) may occur. They can also 
spread around the injection site. Most minor reactions to insulins usually resolve in a few days to a 
few weeks. 
 
Insulin treatment can cause the body to produce antibodies to insulin (substances that act against 
insulin). However, only very rarely, this will require a change to your insulin dosage. 
 
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side 
effects not listed in this leaflet. 
 
 
5. How to store Insulin Human Winthrop Comb 50 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date which isstated on the carton and on the label of the pen 
after “EXP”. The expiry date refers to the last day of that month. 
 
Not in-use pens 
Store in a refrigerator (2°C – 8°C). Do not freeze. Do not put the pre-filled pen next to the freezer 
compartment or a freezer pack. Keep the pre-filled pen in the outer carton in order to protect from 
light. 
 
In-use pens 
Pre-filled pens in-use or carried as a spare may be stored for a maximum of 4 weeks not above 25°C 
and away from direct heat (for example next to a heating unit) or direct light (direct sunlight or next to 
a lamp). The pen in-use must not be stored in a refrigerator. Do not use the pen after this time period.  
 
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment. 
 
 

 

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6. Contents of the pack and other information 
 
What Insulin Human Winthrop Comb 50 contains 
- The active substance is insulin human. One ml of Insulin Human Winthrop Comb 50 contains 

100 IU (International Units) of the active substance insulin human. 50% of the insulin is 
dissolved in water; the other 50% is present as tiny crystals of insulin protamine. 

- The other ingredients are: protamine sulphate, metacresol, phenol, zinc chloride, sodium 
dihydrogen phosphate dihydrate, glycerol, sodium hydroxide (see section 2 under “Important 
information about some of the ingredients of Insulin Human Winthrop Comb 50”), hydrochloric 
acid (for pH adjustment) and water for injections. 

 
What Insulin Human Winthrop Comb 50 looks like and contents of the pack 
After mixing, Insulin Human Winthrop Comb 50 is a uniformly milky fluid (suspension for injection), 
with no clumps, particles or flocculation visible. 
 
Insulin Human Winthrop Comb 50 is supplied in pre-filled pens, SoloStar, containing 3 ml 
suspension, (300 IU). Packs of 3, 4, 5, 6, 9 and 10 pens of 3 ml are available. Not all pack sizes may 
be marketed. 
 
Marketing Authorisation Holder and Manufacturer 
Sanofi-Aventis Deutschland GmbH 
D-65926 Frankfurt am Main 
Germany 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
Sanofi Belgium 
Tél/Tel: +32 (0)2 710 54 00 
 

Lietuva 
UAB «SANOFI-AVENTIS LIETUVA» 
Tel: +370 5 2755224 
 

България 
sanofi-aventis Bulgaria EOOD 
Тел.: +359 (0)2 970 53 00 
 

Luxembourg/Luxemburg 
Sanofi Belgium  
Tél/Tel: +32 (0)2 710 54 00 (Belgique/Belgien) 
 

Česká republika 
sanofi-aventis, s.r.o. 
Tel: +420 233 086 111 
 

Magyarország 
SANOFI-AVENTIS Zrt. 
Tel.: +36 1 505 0050 
 

Danmark 
sanofi-aventis Denmark A/S 
Tlf: +45 45 16 70 00 
 

Malta 
Sanofi Malta Ltd. 
Tel: +356 21493022 
 

Deutschland 
Zentiva Pharma GmbH 
Tel: +49 (0)180 20 200 10 
 

Nederland 
sanofi-aventis Netherlands B.V. 
Tel: +31 (0)182 557 755 
 

Eesti 
sanofi-aventis Estonia OÜ 
Tel: +372 627 34 88 
 

Norge 
Aventis Pharma Norge AS 
Tlf: +47 67 10 71 00 
 

Ελλάδα 
sanofi-aventis AEBE 
Τηλ: +30 210 900 16 00 
 

Österreich 
sanofi-aventis GmbH 
Tel: +43 1 80 185 – 0 
 

 

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España 
sanofi-aventis, S.A. 
Tel: +34 93 485 94 00 
 

Polska 
sanofi-aventis Sp . z o.o. 
Tel.: +48 22 280 00 00 
 

France 
sanofi-aventis France 
Tél: 0 800 222 555 
Appel depuis l’étranger : +33 1 57 63 23 23 
 

Portugal 
Sanofi - Produtos Farmacêuticos, Lda. 
Tel: +351 21 35 89 400 
 

Hrvatska 
sanofi-aventis Croatia d.o.o. 
Tel: +385 1 600 34 00 

România 
Sanofi Romania SRL 
Tel: +40 (0) 21 317 31 36 
 

Ireland 
sanofi-aventis Ireland Ltd. T/A SANOFI 
Tel: +353 (0) 1 403 56 00 
 

Slovenija 
sanofi-aventis d.o.o. 
Tel: +386 1 560 48 00 
 

Ísland 
Vistor hf. 
Sími: +354 535 7000 
 

Slovenská republika 
sanofi-aventis Pharma Slovakia s.r.o. 
Tel: +421 2 33 100 100 
 

Italia 
Sanofi S.p.A. 
Tel: 800 13 12 12 (domande di tipo tecnico)  
800 536389 (altre domande) 
 

Suomi/Finland 
Sanofi Oy 
Puh/Tel: +358 (0) 201 200 300 
 

Κύπρος 
sanofi-aventis Cyprus Ltd. 
Τηλ: +357 22 871600 
 

Sverige 
Sanofi AB 
Tel: +46 (0)8 634 50 00 
 

Latvija 
sanofi-aventis Latvia SIA 
Tel: +371 67 33 24 51 
 

United Kingdom 
Sanofi 
Tel: +44 (0) 845 372 7101 
 

 
This leaflet was last revised in {date} 
 
 
Other source of information 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu/ 
 
 
 
 

HYPERGLYCAEMIA AND HYPOGLYCAEMIA 
 

Always carry some sugar (at least 20 grams) with you. 
Carry some information with you to show you are diabetic. 

 
HYPERGLYCAEMIA (high blood sugar levels) 

 
If your blood sugar is too high (hyperglycaemia), you may not have injected enough insulin. 
 
Why does hyperglycaemia occur? 
 
Examples include: 

 

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- you have not injected your insulin or not injected enough, or if it has become less effective, for 
example through incorrect storage, 

- your insulin pen does not work properly, 
- you are doing less exercise than usual, you are under stress (emotional distress, excitement), or 

you have an injury, operation, infection or fever, 
- you are taking or have taken certain other medicines (see section 2, " Other medicines and 

Insulin Human Winthrop Comb 50"). 
 
Warning symptoms of hyperglycaemia 
 
Thirst, increased need to urinate, tiredness, dry skin, reddening of the face, loss of appetite, low blood 
pressure, fast heart beat, and glucose and ketone bodies in urine. Stomach pain, fast and deep 
breathing, sleepiness or even loss of consciousness may be signs of a serious condition (ketoacidosis) 
resulting from lack of insulin. 
 
What should you do if you experience hyperglycaemia 
 
Test your blood sugar level and your urine for ketones as soon as any of the above symptoms 
occur. Severe hyperglycaemia or ketoacidosis must always be treated by a doctor, normally in a 
hospital. 
 

HYPOGLYCAEMIA (low blood sugar levels) 
 
If your blood sugar level falls too much you may become unconscious. Serious hypoglycaemia may 
cause a heart attack or brain damage and may be life-threatening. You normally should be able to 
recognise when your blood sugar is falling too much so that you can take the right actions. 
 
Why does hypoglycaemia occur? 
 
Examples include: 
- you inject too much insulin, 
- you miss meals or delay them, 
- you do not eat enough, or eat food containing less carbohydrate than normal (sugar and 

substances similar to sugar are called carbohydrates; however, artificial sweeteners are NOT 
carbohydrates), 

- you lose carbohydrates due to vomiting or diarrhoea, 
- you drink alcohol, particularly if you are not eating much, 
- you are doing more exercise than usual or a different type of physical activity, 
- you are recovering from an injury or operation or other stress, 
- you are recovering from an illness or from fever, 
- you are taking or have stopped taking certain other medicines (see section 2, " Other medicines 

and Insulin Human Winthrop Comb 50"). 
 
Hypoglycaemia is also more likely to occur if: 
- you have just begun insulin treatment or changed to another insulin preparation, 
- your blood sugar levels are almost normal or are unstable, 
- you change the area of skin where you inject insulin (for example from the thigh to the upper 

arm), 
- you suffer from severe kidney or liver disease, or some other disease such as hypothyroidism. 
 
Warning symptoms of hypoglycaemia 
 
- In your body 
Examples of symptoms that tell you that your blood sugar level is falling too much or too fast: 
sweating, clammy skin, anxiety, fast heart beat, high blood pressure, palpitations and irregular 
heartbeat. These symptoms often develop before the symptoms of a low sugar level in the brain. 
 

 

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- In your brain 
Examples of symptoms that indicate a low sugar level in the brain: headaches, intense hunger, nausea, 
vomiting, tiredness, sleepiness, sleep disturbances, restlessness, aggressive behaviour, lapses in 
concentration, impaired reactions, depression, confusion, speech disturbances (sometimes total loss of 
speech), visual disorders, trembling, paralysis, tingling sensations (paraesthesia), numbness and 
tingling sensations in the area of the mouth, dizziness, loss of self-control, inability to look after 
yourself, convulsions, loss of consciousness. 
 
The first symptoms which alert you to hypoglycaemia ("warning symptoms") may change, be weaker 
or may be missing altogether if 
- you are elderly, if you have had diabetes for a long time or if you suffer from a certain type of 

nervous disease (diabetic autonomic neuropathy), 
- you have recently suffered hypoglycaemia (for example the day before) or if it develops slowly, 
- you have almost normal or, at least, greatly improved blood sugar levels, 
- you have recently changed from an animal insulin to a human insulin such as Insulin Human 

Winthrop, 
- you are taking or have taken certain other medicines (see section 2, " Other medicines and 

Insulin Human Winthrop Comb 50"). 
 
In such a case, you may develop severe hypoglycaemia (and even faint) before you are aware of the 
problem. Be familiar with your warning symptoms. If necessary, more frequent blood sugar testing 
can help to identify mild hypoglycaemic episodes that may otherwise be overlooked. If you are not 
confident about recognising your warning symptoms, avoid situations (such as driving a car) in which 
you or others would be put at risk by hypoglycaemia. 
 
What should you do if you experience hypoglycaemia 
 
1. Do not inject insulin. Immediately take about 10 to 20 g sugar, such as glucose, sugar cubes or a 

sugar-sweetened beverage. Caution: Artificial sweeteners and foods with artificial sweeteners 
(such as diet drinks) are of no help in treating hypoglycaemia. 

2. Then eat something that has a long-acting effect in raising your blood sugar (such as bread or 
pasta). Your doctor or nurse should have discussed this with you previously. 

3. If the hypoglycaemia comes back again take another 10 to 20 g sugar. 
4. Speak to a doctor immediately if you are not able to control the hypoglycaemia or if it recurs. 
 
Tell your relatives, friends and close colleagues the following: 
If you are not able to swallow or if you are unconscious, you will require an injection of glucose or 
glucagon (a medicine which increases blood sugar). These injections are justified even if it is not 
certain that you have hypoglycaemia. 
 
It is advisable to test your blood sugar immediately after taking glucose to check that you really have 
hypoglycaemia. 
 
 

 

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Insulin Human Winthrop Comb 50 SoloStar suspension for injection in a pre-filled pen. 
Instructions for Use. 
 
SoloStar is a prefilled pen for the injection of insulin. Your doctor has decided that SoloStar is 
appropriate for you based on your ability to handle SoloStar. Talk with your doctor, pharmacist or 
nurse about proper injection technique before using SoloStar. 
 
Read these instructions carefully before using your SoloStar. If you are not able to use SoloStar or 
follow all the instructions completely on your own, you must use SoloStar only if you have help from 
a person who is able to follow the instructions completely. Hold the pen as shown in this leaflet. To 
ensure that you read the dose correctly, hold the pen horizontally, with the needle on the left and the 
dosage selector to the right as shown in the illustrations below. 
 
Follow these instructions completely each time you use SoloStar to ensure that you get an 
accurate dose. If you do not follow these instructions completely, you may get too much or too 
little insulin, which may affect your blood glucose. 
 
You can set doses from 1 to 80 units in steps of 1 unit. Each pen contains multiple doses. 
 
Keep this leaflet for future reference. 
 
If you have any questions about SoloStar or about diabetes, ask your doctor, pharmacist or nurse or 
call the local sanofi-aventis number on the front of this leaflet. 
 

 
Schematic diagram of the pen 

 
 
Important information for use of SoloStar: 
 
• Always attach a new needle before each use. Only use needles that have been approved for use 

with SoloStar. 
• Do not select a dose and/or press the injection button without a needle attached. 
• Always perform the safety test before each injection (see Step 3). 
• This pen is only for your use. Do not share it with anyone else.  
• If your injection is given by another person, special caution must be taken by this person to avoid 

accidental needle injury and transmission of infection. 
• Never use SoloStar if it is damaged or if you are not sure that it is working properly. 
• Always have a spare SoloStar in case your SoloStar is lost or damaged. 
 
 
Step 1. Check the insulin 
 
A. Check the label on your SoloStar to make sure you have the correct insulin. Insulin Human 

Winthrop SoloStar is white with a colour on the injection button. The injection button colour 
will vary based on the formulation of Insulin Human Winthrop insulin used. The pictures below 
are for illustrative purposes only. 

 
B. Take off the pen cap. 
 
C. Check the appearance of your insulin.  

 

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If you are using a suspension insulin (Insulin Human Winthrop Basal or Insulin Human 
Winthrop mixtures), turn the pen up and down at least 10 times to resuspend the insulin. Turn 
the pen gently to avoid foaming in the cartridge. 

 

   
 

After mixing check the appearance of your insulin. Insulin suspensions must have an 
evenly milky-white appearance.  

 
 
Step 2. Attach the needle 
 
Always use a new sterile needle for each injection. This helps prevent contamination, and potential 
needle blocks. 
 
Before use of needle, carefully read the “Instructions for Use” accompanying the needles. 
 
Please note: The needles shown are for illustrative purposes only. 

 
A. Remove the protective seal from a new needle. 
 
B. Line up the needle with the pen, and keep it straight as you attach it (screw or push on, 

depending on the needle type). 
 

  
 
• If the needle is not kept straight while you attach it, it can damage the rubber seal and cause 

leakage, or break the needle. 
 

   
 
 
Step 3. Perform a safety test 
 
Always perform the safety test before each injection. This ensures that you get an accurate dose by: 
• ensuring that pen and needle work properly 
• removing air bubbles 
 
A. Select a dose of 2 units by turning the dosage selector. 

 

 

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B. Take off the outer needle cap and keep it to remove the used needle after injection. Take off the 

inner needle cap and discard it.  
 

   
 
C. Hold the pen with the needle pointing upwards. 
 
D. Tap the insulin reservoir so that any air bubbles rise up towards the needle. 
 
E. Press the injection button all the way in. Check if insulin comes out of the needle tip. 

   
 
You may have to perform the safety test several times before insulin is seen. 
 
• If no insulin comes out, check for air bubbles and repeat the safety test two more times to 

remove them. 
• If still no insulin comes out, the needle may be blocked. Change the needle and try again. 
• If no insulin comes out after changing the needle, your SoloStar may be damaged. Do not use 

this SoloStar. 
 
Step 4. Select the dose 
 
You can set the dose in steps of 1 unit, from a minimum of 1 unit to a maximum of 80 units. If you 
need a dose greater than 80 units, you should give it as two or more injections. 
 
A. Check that the dose window shows “0” following the safety test. 
 
B. Select your required dose (in the example below, the selected dose is 30 units). If you turn past 

your dose, you can turn back down. 
 

  
 

 

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• Do not push the injection button while turning, as insulin will come out. 
 
• You cannot turn the dosage selector past the number of units left in the pen. Do not force the 

dosage selector to turn. In this case, either you can inject what is remaining in the pen and 
complete your dose with a new SoloStar or use a new SoloStar for your full dose. 

 
 
Step 5. Inject the dose 
 
A. Use the injection method as instructed by your doctor, pharmacist or nurse. 
 
B. Insert the needle into the skin. 
 

   
 
C. Deliver the dose by pressing the injection button in all the way. The number in the dose window 

will return to “0” as you inject.  

   
 

D. Keep the injection button pressed all the way in. Slowly count to 10 before you withdraw the 
needle from the skin. This ensures that the full dose will be delivered. 
 
The pen plunger moves with each dose. The plunger will reach the end of the cartridge when 
the total of 300 units of insulin have been used. 

 
 
Step 6. Remove and discard the needle 
 
Always remove the needle after each injection and store SoloStar without a needle attached. 
This helps prevent: 
• Contamination and/or infection 
• Entry of air into the insulin reservoir and leakage of insulin, which can cause inaccurate dosing. 
 
A. Put the outer needle cap back on the needle, and use it to unscrew the needle from the pen. To 

reduce the risk of accidental needle injury, never replace the inner needle cap. 
 

• If your injection is given by another person, or if you are giving an injection to another person, 
special caution must be taken by this person when removing and disposing of the needle. Follow 
recommended safety measures for removal and disposal of needles (e.g. contact your doctor, 
pharmacist or nurse) in order to reduce the risk of accidental needle injury and transmission of 
infectious diseases. 

 
B. Dispose of the needle safely.  
 
C. Always put the pen cap back on the pen, then store the pen until your next injection. 
 
 

 

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Storage instructions  
 
Please check the reverse (insulin) side of this leaflet for instructions on how to store SoloStar. 
 
If your SoloStar is in cool storage, take it out 1 to 2 hours before you inject to allow it to warm up. 
Cold insulin is more painful to inject. 
 
Discard your used SoloStar as required by your local authorities. 
 
 
Maintenance 
 
Protect your SoloStar from dust and dirt. 
 
You can clean the outside of your SoloStar by wiping it with a damp cloth. 
 
Do not soak, wash or lubricate the pen as this may damage it. 
 
Your SoloStar is designed to work accurately and safely. It should be handled with care. Avoid 
situations where SoloStar might be damaged. If you are concerned that your SoloStar may be 
damaged, use a new one. 
 
 

 

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Package leaflet: Information for the user 

 
Insulin Human Winthrop Infusat 100 IU/ml solution for injection in a vial 

Insulin human 
 
 
Read all of this leaflet carefully before you start using this medicine because it contains 
important information for you. 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor, pharmacist or nurse. 
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours. 
- If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible 

side effects not listed in this leaflet. 
 
What is in this leaflet 
1. What Insulin Human Winthrop Infusat is and what it is used for 
2. What you need to know before you use Insulin Human Winthrop Infusat 
3. How to use Insulin Human Winthrop Infusat 
4. Possible side effects 
5. How to store Insulin Human Winthrop Infusat 
6. Contents of the pack and other information 
 
 
1. What Insulin Human Winthrop Infusat is and what it is used for 
 
Insulin Human Winthrop Infusat contains the active substance insulin human which is made by a 
biotechnology process and is identical with the body's own insulin. 
 
Insulin Human Winthrop Infusat is an insulin solution with a rapid onset and short duration of action. 
 
Insulin Human Winthrop Infusat must only be used in insulin pumps suitable for this insulin. 
 
Insulin Human Winthrop Infusat is used to reduce high blood sugar in patients with diabetes mellitus 
who need treatment with insulin. Diabetes mellitus is a disease where your body does not produce 
enough insulin to control the level of blood sugar. 
 
 
2. What you need to know before you use Insulin Human Winthrop Infusat 
 
Do not use Insulin Human Winthrop Infusat 
 
If you are allergic to insulin or any of the other ingredients of this medicine (listed in section 6). 
 
Warnings and precautions 
 
Talk to your doctor, pharmacist or nurse before using Insulin Human Winthrop Infusat. 
Follow closely the instructions for dosage, monitoring (blood and urine tests), diet and physical 
activity (physical work and exercise) as discussed with your doctor. 
 
If you are allergic to this medicine or to animal insulins, talk to your doctor. 
 
Special patient groups 
If you have liver or kidneys problems or if you are elderly, speak to your doctor as you may need a 
lower dose. 
 

 

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Travel 
Before travelling, consult your doctor. You may need to talk about 
- the availability of your insulin in the country you are visiting, 
- supplies of insulin, injection syringes etc., 
- correct storage of your insulin while travelling, 
- whom to contact in the event of technical problems with your pump, 
- timing of meals and insulin administration while travelling, 
- the possible effects of changing to different time zones, 
- possible new health risks in the countries to be visited, 
- what you should do in emergency situations when you feel unwell or become ill. 
 
Illnesses and injuries 
In the following situations, the management of your diabetes may require a lot of care: 
- If you are ill or have a major injury then your blood sugar level may increase (hyperglycaemia). 
- If you are not eating enough, your blood sugar level may become too low (hypoglycaemia). 
In most cases you will need a doctor. Make sure that you contact a doctor early. 
 
If you have type 1 diabetes (insulin dependent diabetes mellitus), do not stop your insulin and 
continue to get enough carbohydrates. Always tell people who are caring for you or treating you that 
you require insulin. 
 
Some patients with long-standing type 2 diabetes mellitus and heart disease or previous stroke who 
were treated with pioglitazone and insulin experienced the development of heart failure. Inform your 
doctor as soon as possible if you experience signs of heart failure such as unusual shortness of breath 
or rapid increase in weight or localised swelling (oedema). 
 
Other medicines and Insulin Human Winthrop Infusat 
 
Some medicines cause changes in the blood sugar level (decrease, increase or both depending on the 
situation). In each case, it may be necessary to adjust your insulin dosage to avoid blood sugar levels 
that are either too low or too high. Be careful when you start or stop taking another medicine. 
 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines. Before taking a medicine ask your doctor if it can affect your blood sugar level, and what 
action, if any, you need to take. 
 
Medicines that may cause your blood sugar level to fall (hypoglycaemia) include:  
- all other medicines to treat diabetes, 
- angiotensin converting enzyme (ACE) inhibitors (used to treat certain heart conditions or high 

blood pressure), 
- disopyramide (used to treat certain heart conditions), 
- fluoxetine (used to treat depression), 
- fibrates (used to lower high levels of blood lipids), 
- monoamine oxidase (MAO) inhibitors (used to treat depression), 
- pentoxifylline, propoxyphene, salicylates (such as aspirin, used to relieve pain and lower fever), 
- sulfonamide antibiotics. 
 
Medicines that may cause your blood sugar level to rise (hyperglycaemia) include:  
- corticosteroids (such as "cortisone", used to treat inflammation), 
- danazol (medicine acting on ovulation), 
- diazoxide (used to treat high blood pressure), 
- diuretics (used to treat high blood pressure or excessive fluid retention), 
- glucagon (pancreas hormone used to treat severe hypoglycaemia), 
- isoniazid (used to treat tuberculosis), 
- oestrogens and progestogens (such as in the contraceptive pill used for birth control), 
- phenothiazine derivatives (used to treat psychiatric disorders), 
- somatropin (growth hormone), 

 

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- sympathomimetic medicines (such as epinephrine [adrenaline] or salbutamol, terbutaline used to 
treat asthma), 

- thyroid hormones (used to treat the thyroid gland disorders), 
- protease inhibitors (used to treat HIV), 
- atypical antipsychotic medicines (such as olanzapine and clozapine). 
 
Your blood sugar level may either rise or fall if you take:  
- beta-blockers (used to treat high blood pressure), 
- clonidine (used to treat high blood pressure), 
- lithium salts (used to treat psychiatric disorders). 
Pentamidine (used to treat some infections caused by parasites) may cause hypoglycaemia which may 
sometimes be followed by hyperglycaemia. 
 
Beta-blockers like other sympatholytic medicines (such as clonidine, guanethidine, and reserpine) may 
weaken or suppress entirely the first warning symptoms which help you to recognise a 
hypoglycaemia. 
 
If you are not sure whether you are taking one of those medicines ask your doctor or pharmacist. 
 
Insulin Human Winthrop Infusat with alcohol 
 
Your blood sugar levels may either rise or fall if you drink alcohol. 
 
Pregnancy and breast-feeding 
 
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor or pharmacist for advice before taking this medicine. 
 
Inform your doctor if you are planning to become pregnant, or if you are already pregnant. Your 
insulin dosage may need to be changed during pregnancy and after giving birth. Particularly careful 
control of your diabetes, and prevention of hypoglycaemia, is important for the health of your baby.  
 
If you are breast-feeding consult your doctor as you may require adjustments in your insulin doses and 
your diet. 
 
Driving and using machines 
 
Your ability to concentrate or react may be reduced if: 
- you have hypoglycaemia (low blood sugar levels), 
- you have hyperglycaemia (high blood sugar levels), 
- you have problems with your sight.  
Keep this possible problem in mind in all situations where you might put yourself and others at risk 
(such as driving a car or using machines). You should contact your doctor for advice on driving if: 
- you have frequent episodes of hypoglycaemia, 
- the first warning symptoms which help you to recognise hypoglycaemia are reduced or absent. 
 
 
3. How to use Insulin Human Winthrop Infusat 
 
Dose 
 
Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor 
or pharmacist if you are not sure. 
 

 

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Based on your life-style and the results of your blood sugar (glucose) tests, your doctor will 
- determine how much Insulin Human Winthrop Infusat per day you will need, how much of this 

is infused continuously ("basal rate") and how much and when you need additional insulin as an 
"insulin boost" ("bolus dose"), 

- tell you when to check your blood sugar level, and whether you need to carry out urine tests, 
- tell you when you may need to use a higher or lower dose of Insulin Human Winthrop Infusat. 
 
Many factors may influence your blood sugar level. You should know these factors so that you are 
able to react correctly to changes in your blood sugar level and to prevent it from becoming too high 
or too low. See the box at the end of this leaflet for further information. 
 
Method of administration 
 
Insulin Human Winthrop Infusat is a solution to be given under the skin. 
 
Your doctor will show you how and in which area of the skin you should infuse your insulin and how 
often you must change the puncture site within the particular area of skin where you are infusing the 
insulin. Speak to your doctor before you change the area of skin that you are infusing. 
 
Do not use Insulin Human Winthrop Infusat in peristaltic pumps with silicone tubing. Situations in 
which you must not start or continue to use insulin pumps are described in the operating manuals for 
these pumps. 
 
How to handle the vials 
 
Insulin Human Winthrop Infusat has been developed for use in Hoechst Infusor and H-Tron. It must 
only be used in insulin pumps suitable for this insulin. Only tetrafluoroethylene or polyethylene 
catheters must be used for infusion. The operating manual provided with the pump will tell you how 
to use it. 
 
Insulin Human Winthrop Infusat must only be used if the solution is clear, colourless, with no solid 
particles visible, and has a water-like consistency. 
 
The insulin cartridge of the pump must be sterile and must be used once only. After filling the 
cartridge of the pump keep it at room temperature for 1 to 2 hours before using it, so that you can see 
and remove any air bubbles which form during warming-up. 
 
Special care before injection 
 
Before starting the infusion remove any air bubbles. Make sure that neither alcohol nor other 
disinfectants or other substances contaminate the insulin. 
 
Do not mix insulin with any other medicines. Insulin Human Winthrop Infusat must NOT be mixed 
with any other insulin preparations. 
 
Insulin pump faults 
 
You should always consider the possibility of a technical problem if, in order to achieve the desired 
blood sugar levels, 
- you need additional insulin ("bolus doses") at larger doses or more often than usual, or 
- you need additional insulin ("bolus doses") at smaller doses or less often than usual. 
 
For details on safety precautions in the use of insulin pumps see the operating manual. 
 
If the pump does not function well, you can draw the insulin from the cartridge into an injection 
syringe for injection. Therefore, keep injection syringes and injection needles as well. However, use 

 

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only those injection syringes which are designed for an insulin concentration of 100 IU (International 
Units) per ml. 
 
If you use more Insulin Human Winthrop Infusat than you should 
- If you have injected too much Insulin Human Winthrop Infusat, your blood sugar level may 

become too low (hypoglycaemia). Check your blood sugar frequently. In general, to prevent 
hypoglycaemia you must eat more food and monitor your blood sugar. For information on the 
treatment of hypoglycaemia, see box at the end of this leaflet. 

 
If you forget to use Insulin Human Winthrop Infusat 
- If you have missed a dose of Insulin Human Winthrop Infusat or if you have not injected 

enough insulin, your blood sugar level may become too high (hyperglycaemia). Check your 
blood sugar frequently. For information on the treatment of hyperglycaemia, see box at the end 
of this leaflet. 

 
- Do not take a double dose to make up for a forgotten dose. 
 
If you stop using Insulin Human Winthrop Infusat 
This could lead to severe hyperglycaemia (very high blood sugar) and ketoacidosis (build-up of acid 
in the blood because the body is breaking down fat instead of sugar). Do not stop Insulin Human 
Winthrop Infusat without speaking to a doctor, who will tell you what needs to be done. 
 
If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse. 
 
Insulin Mix-ups 
 
You must always check the insulin label before each injection to avoid mix-ups between Insulin 
Human Winthrop Infusat and other insulins.  
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
The most frequent side effect is hypoglycaemia (low blood sugar). The specific frequency cannot be 
estimated from available data (frequency not known). Serious hypoglycaemia may cause a heart attack 
or brain damage and may be life-threatening. For further information on the side effects of low blood 
sugar or high blood sugar, see the box at the end of this leaflet. 
 
Severe allergic reactions to insulin may occur which may become life-threatening. Such reactions to 
insulin or to the excipients can cause large-scale skin reactions (rash and itching all over the body); 
severe swelling of skin or mucous membranes (angiooedema), shortness of breath, a fall in blood 
pressure with rapid heart beat and sweating. Frequency of these reactions cannot be estimated from 
available data. 
 
Side effects reported commonly (may affect up to 1 in 10 people) 
• Oedema 
Insulin treatment may cause temporary build-up of water in the body with swelling in the calves and 
ankles. 
• Injection site reactions 
 
Side effects reported uncommonly (may affect up to 1 in 100 people) 
• Severe allergic reaction with low blood pressure (shock) 
• Injection site urticaria (itchy rash) 
 

 

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Other side effects include (frequency cannot be estimated from the available data) 
• Sodium retention 
• Eye reactions 
A marked change (improvement or worsening) in your blood sugar control can disturb your vision 
temporarily. If you have proliferative retinopathy (an eye disease related to diabetes) severe 
hypoglycaemic attacks may cause temporary loss of vision. 
• Skin changes at the injection site (lipodystrophy) 
If you inject your insulin too often at the same skin site, fatty tissue under the skin at this site may 
either shrink or thicken. Insulin that you inject in such a site may not work very well. Changing the 
injection site with each injection may help to prevent such skin changes. 
• Skin and allergic reactions 
Other mild reactions at the injection site (such as injection site redness, unusually intense pain on 
injection site, itching, injection site swelling or injection site inflammation) may occur. They can also 
spread around the injection site. Most minor reactions to insulins usually resolve in a few days to a 
few weeks. 
 
Insulin treatment can cause the body to produce antibodies to insulin (substances that act against 
insulin). However, only very rarely, this will require a change to your insulin dosage. 
 
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side 
effects not listed in this leaflet. 
 
 
5. How to store Insulin Human Winthrop Infusat 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date which is stated on the carton and on the label of the vial 
afetr “EXP”. The expiry date refers to the last day of that month. 
 
Unopened vials 
Store in a refrigerator (2°C - 8°C). Do not freeze. Do not put Insulin Human Winthrop Infusat next to 
the freezer compartment or a freezer pack. Keep the vial in the outer carton in order to protect from 
light. 
 
Opened vials 
Once in-use, the vial may be stored for a maximum of 4 weeks in the outer carton not above 25°C and 
away from direct heat (for example next to a heating unit) or direct light (direct sunlight or next to a 
lamp). Do not use the vial after this time period. It is recommended that the date of the first use be 
noted on the label. 
 
Once in the pump, Insulin Human Winthrop Infusat may be kept for up to 2 weeks. 
 
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Insulin Human Winthrop Infusat contains 
- The active substance is insulin human. One ml of Insulin Human Winthrop Infusat contains 

100 IU (International Units) of the active substance insulin human. 
- The other ingredients are: phenol, zinc chloride, trometamol, poloxamer 171, glycerol, 

hydrochloric acid (for pH adjustment) and water for injections. 
 

 

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What Insulin Human Winthrop Infusat looks like and contents of the pack 
Insulin Human Winthrop Infusat is a clear, colourless solution for injection, with no solid particles 
visible, and of water-like consistency. 
 
Insulin Human Winthrop Infusat is supplied in vials containing 10 ml solution (1000 IU). Pack of 
3 vials of 10 ml is available. 
 
Marketing Authorisation Holder and Manufacturer 
Sanofi-Aventis Deutschland GmbH 
D-65926 Frankfurt am Main 
Germany 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
Sanofi Belgium 
Tél/Tel: +32 (0)2 710 54 00 
 

Lietuva 
UAB «SANOFI-AVENTIS LIETUVA» 
Tel: +370 5 2755224 
 

България 
sanofi-aventis Bulgaria EOOD 
Тел.: +359 (0)2 970 53 00 
 

Luxembourg/Luxemburg 
Sanofi Belgium  
Tél/Tel: +32 (0)2 710 54 00 (Belgique/Belgien) 
 

Česká republika 
sanofi-aventis, s.r.o. 
Tel: +420 233 086 111 
 

Magyarország 
SANOFI-AVENTIS Zrt. 
Tel.: +36 1 505 0050 
 

Danmark 
sanofi-aventis Denmark A/S 
Tlf: +45 45 16 70 00 
 

Malta 
Sanofi Malta Ltd. 
Tel: +356 21493022 
 

Deutschland 
Zentiva Pharma GmbH 
Tel: +49 (0)180 20 200 10 
 

Nederland 
sanofi-aventis Netherlands B.V. 
Tel: +31 (0)182 557 755 
 

Eesti 
sanofi-aventis Estonia OÜ 
Tel: +372 627 34 88 
 

Norge 
Aventis Pharma Norge AS 
Tlf: +47 67 10 71 00 
 

Ελλάδα 
sanofi-aventis AEBE 
Τηλ: +30 210 900 16 00 
 

Österreich 
sanofi-aventis GmbH 
Tel: +43 1 80 185 – 0 
 

España 
sanofi-aventis, S.A. 
Tel: +34 93 485 94 00 
 

Polska 
sanofi-aventis Sp. z o.o. 
Tel.: +48 22 280 00 00 
 

France 
sanofi-aventis France 
Tél: 0 800 222 555 
Appel depuis l’étranger : +33 1 57 63 23 23 
 

Portugal 
Sanofi - Produtos Farmacêuticos, Lda. 
Tel: +351 21 35 89 400 
 

 

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Hrvatska 
sanofi-aventis Croatia d.o.o. 
Tel: +385 1 600 34 00 

România 
Sanofi Romania SRL 
Tel: +40 (0) 21 317 31 36 
 

Ireland 
sanofi-aventis Ireland Ltd. T/A SANOFI 
Tel: +353 (0) 1 403 56 00 
 

Slovenija 
sanofi-aventis d.o.o. 
Tel: +386 1 560 48 00 
 

Ísland 
Vistor hf. 
Sími: +354 535 7000 
 

Slovenská republika 
sanofi-aventis Pharma Slovakia s.r.o. 
Tel: +421 2 33 100 100 
 

Italia 
Sanofi S.p.A. 
Tel: 800 13 12 12 (domande di tipo tecnico)  
800 536389 (altre domande) 
 

Suomi/Finland 
Sanofi Oy 
Puh/Tel: +358 (0) 201 200 300 
 

Κύπρος 
sanofi-aventis Cyprus Ltd. 
Τηλ: +357 22 871600 
 

Sverige 
Sanofi AB 
Tel: +46 (0)8 634 50 00 
 

Latvija 
sanofi-aventis Latvia SIA 
Tel: +371 67 33 24 51 
 

United Kingdom 
Sanofi 
Tel: +44 (0) 845 372 7101 
 

 
This leaflet was last revised in {date} 
 
 
Other source of information 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu/ 
 
 
 
 

HYPERGLYCAEMIA AND HYPOGLYCAEMIA 
 

Always carry some sugar (at least 20 grams) with you. 
Carry some information with you to show you are diabetic. 

 
HYPERGLYCAEMIA (high blood sugar levels) 

 
If your blood sugar is too high (hyperglycaemia), you may not have injected enough insulin. 
 
Why does hyperglycaemia occur? 
 
Examples include: 
- you have not injected your insulin or not injected enough, or if it has become less effective, for 

example through incorrect storage, 
- your insulin pump does not work properly, 
- you are doing less exercise than usual, you are under stress (emotional distress, excitement), or 

you have an injury, operation, infection or fever, 
- you are taking or have taken certain other medicines (see section 2, "Other medicines and 

Insulin Human Winthrop Infusat"). 
 
Warning symptoms of hyperglycaemia 

 

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Thirst, increased need to urinate, tiredness, dry skin, reddening of the face, loss of appetite, low blood 
pressure, fast heart beat, and glucose and ketone bodies in urine. Stomach pain, fast and deep 
breathing, sleepiness or even loss of consciousness may be signs of a serious condition (ketoacidosis) 
resulting from lack of insulin. 
 
What should you do if you experience hyperglycaemia 
 
Test your blood sugar level and your urine for ketones as soon as any of the above symptoms 
occur. Severe hyperglycaemia or ketoacidosis must always be treated by a doctor, normally in a 
hospital. 
 

HYPOGLYCAEMIA (low blood sugar levels) 
 
If your blood sugar level falls too much you may become unconscious. Serious hypoglycaemia may 
cause a heart attack or brain damage and may be life-threatening. You normally should be able to 
recognise when your blood sugar is falling too much so that you can take the right actions. 
 
Why does hypoglycaemia occur? 
 
Examples include: 
- you inject too much insulin, 
- you miss meals or delay them, 
- you do not eat enough, or eat food containing less carbohydrate than normal (sugar and 

substances similar to sugar are called carbohydrates; however, artificial sweeteners are NOT 
carbohydrates), 

- you lose carbohydrates due to vomiting or diarrhoea, 
- you drink alcohol, particularly if you are not eating much, 
- you are doing more exercise than usual or a different type of physical activity, 
- you are recovering from an injury or operation or other stress, 
- you are recovering from an illness or from fever, 
- you are taking or have stopped taking certain other medicines (see section 2, "Other medicines 

and Insulin Human Winthrop Infusat"). 
 
Hypoglycaemia is also more likely to occur if: 
- you have just begun insulin treatment or changed to another insulin preparation, 
- your blood sugar levels are almost normal or are unstable, 
- you change the area of skin where you inject insulin (for example from the thigh to the upper 

arm), 
- you suffer from severe kidney or liver disease, or some other disease such as hypothyroidism. 
 
Warning symptoms of hypoglycaemia 
 
- In your body 
Examples of symptoms that tell you that your blood sugar level is falling too much or too fast: 
sweating, clammy skin, anxiety, fast heart beat, high blood pressure, palpitations and irregular 
heartbeat. These symptoms often develop before the symptoms of a low sugar level in the brain. 
 
- In your brain 
Examples of symptoms that indicate a low sugar level in the brain: headaches, intense hunger, nausea, 
vomiting, tiredness, sleepiness, sleep disturbances, restlessness, aggressive behaviour, lapses in 
concentration, impaired reactions, depression, confusion, speech disturbances (sometimes total loss of 
speech), visual disorders, trembling, paralysis, tingling sensations (paraesthesia), numbness and 
tingling sensations in the area of the mouth, dizziness, loss of self-control, inability to look after 
yourself, convulsions, loss of consciousness. 
 

 

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The first symptoms which alert you to hypoglycaemia ("warning symptoms") may change, be weaker 
or may be missing altogether if 
- you are elderly, if you have had diabetes for a long time or if you suffer from a certain type of 

nervous disease (diabetic autonomic neuropathy), 
- you have recently suffered hypoglycaemia (for example the day before) or if it develops slowly, 
- you have almost normal or, at least, greatly improved blood sugar levels, 
- you have recently changed from an animal insulin to a human insulin such as Insulin Human 

Winthrop, 
- you are taking or have taken certain other medicines (see section 2, "Other medicines and 

Insulin Human Winthrop Infusat"). 
 
In such a case, you may develop severe hypoglycaemia (and even faint) before you are aware of the 
problem. Be familiar with your warning symptoms. If necessary, more frequent blood sugar testing 
can help to identify mild hypoglycaemic episodes that may otherwise be overlooked. If you are not 
confident about recognising your warning symptoms, avoid situations (such as driving a car) in which 
you or others would be put at risk by hypoglycaemia. 
 
What should you do if you experience hypoglycaemia 
 
1. Stop your insulin infusion (if necessary, by withdrawing the needle) at least until you feel that 

you are fully alert again. Immediately take about 10 to 20 g sugar, such as glucose, sugar cubes 
or a sugar-sweetened beverage. Caution: Artificial sweeteners and foods with artificial 
sweeteners (such as diet drinks) are of no help in treating hypoglycaemia. 

2. Then eat something that has a long-acting effect in raising your blood sugar (such as bread or 
pasta). Your doctor or nurse should have discussed this with you previously. 

3. If the hypoglycaemia comes back again take another 10 to 20 g sugar. 
4. Speak to a doctor immediately if you are not able to control the hypoglycaemia or if it recurs. 
 
Tell your relatives, friends and close colleagues the following: 
If you are not able to swallow or if you are unconscious, you will require an injection of glucose or 
glucagon (a medicine which increases blood sugar). These injections are justified even if it is not 
certain that you have hypoglycaemia. 
 
It is advisable to test your blood sugar immediately after taking glucose to check that you really have 
hypoglycaemia. 
 
 

 

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Package leaflet: Information for the user 

 
Insulin Human Winthrop Infusat 100 IU/ml solution for injection in a cartridge 

Insulin human 
 
 
Read all of this leaflet carefully before you start using this medicine because it contains 
important information for you. 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor, pharmacist or nurse. 
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours. 
- If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible 

side effects not listed in this leaflet. 
 
What is in this leaflet: 
1. What Insulin Human Winthrop Infusat is and what it is used for 
2. What you need to know before you use Insulin Human Winthrop Infusat 
3. How to use Insulin Human Winthrop Infusat 
4. Possible side effects 
5. How to store Insulin Human Winthrop Infusat 
6. Contents of the pack and other information 
 
 
1. What Insulin Human Winthrop Infusat is and what it is used for 
 
Insulin Human Winthrop Infusat contains the active substance insulin human which is made by a 
biotechnology process and is identical with the body's own insulin. 
 
Insulin Human Winthrop Infusat is an insulin solution with a rapid onset and short duration of action. 
It comes in cartridges designed for use in Hoechst Infusor and H-Tron (insulin pumps). 
 
Insulin Human Winthrop Infusat must only be used in insulin pumps suitable for this insulin. 
 
Insulin Human Winthrop Infusat is used to reduce high blood sugar in patients with diabetes mellitus 
who need treatment with insulin. Diabetes mellitus is a disease where your body does not produce 
enough insulin to control the level of blood sugar. 
 
 
2. What you need to know before you use Insulin Human Winthrop Infusat 
 
Do not use Insulin Human Winthrop Infusat 
 
If you are allergic to insulin or any of the other ingredients of this medicine (listed in section 6).  
 
Warnings and precautions 
 
Talk to your doctor, pharmacist or nurse beforing using Insulin Human Winthrop Infusat 
Follow closely the instructions for dosage, monitoring (blood and urine tests), diet and physical 
activity (physical work and exercise) as discussed with your doctor. 
 
If you are allergic to this medicine or to animal insulins, talk to your doctor. 
 
Special patient groups 
If you have liver or kidneys problems or if you are elderly, speak to your doctor as you may need a 
lower dose. 

 

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Travel 
Before travelling, consult your doctor. You may need to talk about 
- the availability of your insulin in the country you are visiting, 
- supplies of insulin, injection syringes etc., 
- correct storage of your insulin while travelling, 
- whom to contact in the event of technical problems with your pump, 
- timing of meals and insulin administration while travelling, 
- the possible effects of changing to different time zones, 
- possible new health risks in the countries to be visited, 
- what you should do in emergency situations when you feel unwell or become ill. 
 
Illnesses and injuries 
In the following situations, the management of your diabetes may require a lot of care: 
- If you are ill or have a major injury then your blood sugar level may increase (hyperglycaemia).  
- If you are not eating enough, your blood sugar level may become too low (hypoglycaemia).  
In most cases you will need a doctor. Make sure that you contact a doctor early.  
 
If you have type 1 diabetes (insulin dependent diabetes mellitus), do not stop your insulin and 
continue to get enough carbohydrates. Always tell people who are caring for you or treating you that 
you require insulin. 
 
Some patients with long-standing type 2 diabetes mellitus and heart disease or previous stroke who 
were treated with pioglitazone and insulin experienced the development of heart failure. Inform your 
doctor as soon as possible if you experience signs of heart failure such as unusual shortness of breath 
or rapid increase in weight or localised swelling (oedema). 
 
Other medicines and Insulin Human Winthrop Infusat 
 
Some medicines cause changes in the blood sugar level (decrease, increase or both depending on the 
situation). In each case, it may be necessary to adjust your insulin dosage to avoid blood sugar levels 
that are either too low or too high. Be careful when you start or stop taking another medicine. 
 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines. Before taking a medicine ask your doctor if it can affect your blood sugar level, and what 
action, if any, you need to take. 
 
Medicines that may cause your blood sugar level to fall (hypoglycaemia) include:  
- all other medicines to treat diabetes,  
- angiotensin converting enzyme (ACE) inhibitors (used to treat certain heart conditions or high 

blood pressure),  
- disopyramide (used to treat certain heart conditions),  
- fluoxetine (used to treat depression),  
- fibrates (used to lower high levels of blood lipids),  
- monoamine oxidase (MAO) inhibitors (used to treat depression),  
- pentoxifylline, propoxyphene, salicylates (such as aspirin, used to relieve pain and lower fever), 
- sulfonamide antibiotics. 
 
Medicines that may cause your blood sugar level to rise (hyperglycaemia) include:  
- corticosteroids (such as "cortisone", used to treat inflammation),  
- danazol (medicine acting on ovulation),  
- diazoxide (used to treat high blood pressure),  
- diuretics (used to treat high blood pressure or excessive fluid retention),  
- glucagon (pancreas hormone used to treat severe hypoglycaemia),  
- isoniazid (used to treat tuberculosis),  
- oestrogens and progestogens (such as in the contraceptive pill used for birth control),  
- phenothiazine derivatives (used to treat psychiatric disorders),  

 

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- somatropin (growth hormone),  
- sympathomimetic medicines (such as epinephrine [adrenaline] or salbutamol, terbutaline used to 

treat asthma), 
- thyroid hormones (used to treat the thyroid gland disorders), 
- protease inhibitors (used to treat HIV), 
- atypical antipsychotic medicines (such as olanzapine and clozapine). 
 
Your blood sugar level may either rise or fall if you take:  
- beta-blockers (used to treat high blood pressure),  
- clonidine (used to treat high blood pressure),  
- lithium salts (used to treat psychiatric disorders).  
Pentamidine (used to treat some infections caused by parasites) may cause hypoglycaemia which may 
sometimes be followed by hyperglycaemia. 
 
Betablockers like other sympatholytic medicines (such as clonidine, guanethidine, and reserpine) may 
weaken or suppress entirely the first warning symptoms which help you to recognise a 
hypoglycaemia. 
 
If you are not sure whether you are taking one of those medicines ask your doctor or pharmacist. 
 
Insulin Human Winthrop Infusat with alcohol 
 
Your blood sugar levels may either rise or fall if you drink alcohol. 
 
Pregnancy and breast-feeding 
 
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor or pharmacist for advice before taking this medicine. 
 
Inform your doctor if you are planning to become pregnant, or if you are already pregnant. Your 
insulin dosage may need to be changed during pregnancy and after giving birth. Particularly careful 
control of your diabetes, and prevention of hypoglycaemia, is important for the health of your baby.  
 
If you are breast-feeding consult your doctor as you may require adjustments in your insulin doses and 
your diet. 
 
Driving and using machines 
 
Your ability to concentrate or react may be reduced if:  
- you have hypoglycaemia (low blood sugar levels), 
- you have hyperglycaemia (high blood sugar levels), 
- you have problems with your sight.  
Keep this possible problem in mind in all situations where you might put yourself and others at risk 
(such as driving a car or using machines). You should contact your doctor for advice on driving if: 
- you have frequent episodes of hypoglycaemia, 
- the first warning symptoms which help you to recognise hypoglycaemia are reduced or absent. 
 
 
3. How to use Insulin Human Winthrop Infusat 
 
Dose 
 
Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor 
or pharmacist if you are not sure. 
 

 

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Based on your life-style and the results of your blood sugar (glucose) tests, your doctor will 
- determine how much Insulin Human Winthrop Infusat per day you will need, how much of this 

is infused continuously ("basal rate") and how much and when you need additional insulin as an 
"insulin boost" ("bolus dose"), 

- tell you when to check your blood sugar level, and whether you need to carry out urine tests, 
- tell you when you may need to use a higher or lower dose of Insulin Human Winthrop Infusat. 
 
Many factors may influence your blood sugar level. You should know these factors so that you are 
able to react correctly to changes in your blood sugar level and to prevent it from becoming too high 
or too low. See the box at the end of this leaflet for further information. 
 
Method of administration 
 
Insulin Human Winthrop Infusat is a solution to be given under the skin. 
 
Your doctor will show you how and in which area of the skin you should infuse your insulin and how 
often you must change the puncture site within the particular area of skin where you are infusing the 
insulin. Speak to your doctor before you change the area of skin that you are infusing. 
 
Do not use Insulin Human Winthrop Infusat in peristaltic pumps with silicone tubing. Situations in 
which you must not start or continue to use insulin pumps are described in the operating manuals for 
these pumps. 
 
How to handle the cartridges 
 
Insulin Human Winthrop Infusat comes in cartridges designed for use in Hoechst Infusor and H-Tron. 
It must only be used in insulin pumps suitable for this insulin. Only tetrafluoroethylene or 
polyethylene catheters must be used for infusion. The operating manual provided with the pump will 
tell you how to use it. 
 
Insulin Human Winthrop Infusat must only be used if the solution is clear, colourless, with no solid 
particles visible, and has a water-like consistency. 
 
Keep the cartridge at room temperature 1 to 2 hours before inserting it in the pump so that you can see 
and remove any air bubbles which form during warming-up. 
 
Special care before injection 
 
Before starting the infusion remove any air bubbles. Make sure that neither alcohol nor other 
disinfectants or other substances contaminate the insulin. 
 
Do not mix insulin with any other medicines. Insulin Human Winthrop Infusat must NOT be mixed 
with any other insulin preparations. 
 
Do not re-fill and re-use empty cartridges. 
 
Insulin pump faults 
 
You should always consider the possibility of a technical problem if, in order to achieve the desired 
blood sugar levels, 
- you need additional insulin ("bolus doses") at larger doses or more often than usual, or 
- you need additional insulin ("bolus doses") at smaller doses or less often than usual. 
 
For details on safety precautions in the use of insulin pumps see the operating manual. 
 
If the pump does not function well, you can draw the insulin from the cartridge into an injection 
syringe for injection. Therefore, keep injection syringes and injection needles as well. However, use 

 

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only those injection syringes which are designed for an insulin concentration of 100 IU (International 
Units) per ml. 
 
If you use more Insulin Human Winthrop Infusat than you should 
- If you have injected too much Insulin Human Winthrop Infusat, your blood sugar level may 

become too low (hypoglycaemia). Check your blood sugar frequently. In general, to prevent 
hypoglycaemia you must eat more food and monitor your blood sugar. For information on the 
treatment of hypoglycaemia, see box at the end of this leaflet. 

 
If you forget to use Insulin Human Winthrop Infusat 
- If you have missed a dose of Insulin Human Winthrop Infusat or if you have not injected 

enough insulin, your blood sugar level may become too high (hyperglycaemia). Check your 
blood sugar frequently. For information on the treatment of hyperglycaemia, see box at the end 
of this leaflet. 

 
- Do not take a double dose to make up for a forgotten dose. 
 
If you stop using Insulin Human Winthrop Infusat 
This could lead to severe hyperglycaemia (very high blood sugar) and ketoacidosis (build-up of acid 
in the blood because the body is breaking down fat instead of sugar). Do not stop Insulin Human 
Winthrop Infusat without speaking to a doctor, who will tell you what needs to be done. 
 
If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse. 
 
Insulin Mix-ups 
 
You must always check the insulin label before each injection to avoid mix-ups between Insulin 
Human Winthrop Infusat and other insulins.  
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
The most frequent side effect is hypoglycaemia (low blood sugar). The specific frequency cannot be 
estimated from available data (frequency not known). Serious hypoglycaemia may cause a heart attack 
or brain damage and may be life-threatening. For further information on the side effects of low blood 
sugar or high blood sugar, see the box at the end of this leaflet. 
 
Severe allergic reactions to insulin may occur which may become life-threatening. Such reactions to 
insulin or to the excipients can cause large-scale skin reactions (rash and itching all over the body); 
severe swelling of skin or mucous membranes (angiooedema), shortness of breath, a fall in blood 
pressure with rapid heart beat and sweating. Frequency of these reactions cannot be estimated from 
available data. 
 
Side effects reported commonly (may affect up to 1 in 10 people) 
• Oedema 
Insulin treatment may cause temporary build-up of water in the body with swelling in the calves and 
ankles. 
• Injection site reactions 
 
Side effects reported uncommonly (may affect up to 1 in 100 people) 
• Severe allergic reaction with low blood pressure (shock) 
• Injection site urticaria (itchy rash) 
 

 

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Other side effects include (frequency cannot be estimated from the available data)  
• Sodium retention 
• Eye reactions 
A marked change (improvement or worsening) in your blood sugar control can disturb your vision 
temporarily. If you have proliferative retinopathy (an eye disease related to diabetes) severe 
hypoglycaemic attacks may cause temporary loss of vision. 
• Skin changes at the injection site (lipodystrophy) 
If you inject your insulin too often at the same skin site, fatty tissue under the skin at this site may 
either shrink or thicken. Insulin that you inject in such a site may not work very well. Changing the 
injection site with each injection may help to prevent such skin changes. 
• Skin and allergic reactions 
Other mild reactions at the injection site (such as injection site redness, unusually intense pain on 
injection site, itching, injection site swelling or injection site inflammation) may occur. They can also 
spread around the injection site. Most minor reactions to insulins usually resolve in a few days to a 
few weeks. 
 
Insulin treatment can cause the body to produce antibodies to insulin (substances that act against 
insulin). However, only very rarely, this will require a change to your insulin dosage. 
 
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side 
effects not listed in this leaflet. 
 
 
5. How to store Insulin Human Winthrop Infusat 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date which is stated on the carton and on the label of the 
cartridge after “EXP”. The expiry date refers to the last day of that month. 
 
Unopened cartridges 
Store in a refrigerator (2°C - 8°C). Do not freeze. Do not put Insulin Human Winthrop Infusat next to 
the freezer compartment or a freezer pack. Keep the cartridge in the outer carton in order to protect 
from light. 
 
Once in the pump, Insulin Human Winthrop Infusat may be kept for up to 2 weeks. 
 
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Insulin Human Winthrop Infusat contains 
- The active substance is insulin human. One ml of Insulin Human Winthrop Infusat contains 

100 IU (International Units) of the active substance insulin human. 
- The other ingredients are: phenol, zinc chloride, trometamol, poloxamer 171, glycerol, 

hydrochloric acid (for pH adjustment) and water for injections. 
 
What Insulin Human Winthrop Infusat looks like and contents of the pack 
Insulin Human Winthrop Infusat is a clear, colourless solution for injection, with no solid particles 
visible, and of water-like consistency. 
 
Insulin Human Winthrop Infusat is supplied in cartridges containing 3.15 ml solution (315 IU). Pack 
of 5 cartridges of 3.15 ml is available. 
 

 

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Marketing Authorisation Holder and Manufacturer 
Sanofi-Aventis Deutschland GmbH 
D-65926 Frankfurt am Main 
Germany 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
Sanofi Belgium 
Tél/Tel: +32 (0)2 710 54 00 
 

Lietuva 
UAB «SANOFI-AVENTIS LIETUVA» 
Tel: +370 5 2755224 
 

България 
sanofi-aventis Bulgaria EOOD 
Тел.: +359 (0)2 970 53 00 
 

Luxembourg/Luxemburg 
Sanofi Belgium  
Tél/Tel: +32 (0)2 710 54 00 (Belgique/Belgien) 
 

Česká republika 
sanofi-aventis, s.r.o. 
Tel: +420 233 086 111 
 

Magyarország 
SANOFI-AVENTIS Zrt. 
Tel.: +36 1 505 0050 
 

Danmark 
sanofi-aventis Denmark A/S 
Tlf: +45 45 16 70 00 
 

Malta 
Sanofi Malta Ltd. 
Tel: +356 21493022 
 

Deutschland 
Zentiva Pharma GmbH 
Tel: +49 (0)180 20 200 10 
 

Nederland 
sanofi-aventis Netherlands B.V. 
Tel: +31 (0)182 557 755 
 

Eesti 
sanofi-aventis Estonia OÜ 
Tel: +372 627 34 88 
 

Norge 
Aventis Pharma Norge AS 
Tlf: +47 67 10 71 00 
 

Ελλάδα 
sanofi-aventis AEBE 
Τηλ: +30 210 900 16 00 
 

Österreich 
sanofi-aventis GmbH 
Tel: +43 1 80 185 – 0 
 

España 
sanofi-aventis, S.A. 
Tel: +34 93 485 94 00 
 

Polska 
sanofi-aventis Sp. z o.o. 
Tel.: +48 22 280 00 00 
 

France 
sanofi-aventis France 
Tél: 0 800 222 555 
Appel depuis l’étranger : +33 1 57 63 23 23 
 

Portugal 
Sanofi - Produtos Farmacêuticos, Lda. 
Tel: +351 21 35 89 400 
 

Hrvatska 
sanofi-aventis Croatia d.o.o. 
Tel: +385 1 600 34 00 

România 
Sanofi Romania SRL 
Tel: +40 (0) 21 317 31 36 
 

Ireland 
sanofi-aventis Ireland Ltd. T/A SANOFI 
Tel: +353 (0) 1 403 56 00 
 

Slovenija 
sanofi-aventis d.o.o. 
Tel: +386 1 560 48 00 
 

Ísland 
Vistor hf. 
Sími: +354 535 7000 
 

Slovenská republika 
sanofi-aventis Pharma Slovakia s.r.o. 
Tel: +421 2 33 100 100 
 

 

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Italia 
Sanofi S.p.A. 
Tel: 800 13 12 12 (domande di tipo tecnico)  
800 536389 (altre domande) 
 

Suomi/Finland 
Sanofi Oy 
Puh/Tel: +358 (0) 201 200 300 
 

Κύπρος 
sanofi-aventis Cyprus Ltd. 
Τηλ: +357 22 871600 
 

Sverige 
Sanofi AB 
Tel: +46 (0)8 634 50 00 
 

Latvija 
sanofi-aventis Latvia SIA 
Tel: +371 67 33 24 51 
 

United Kingdom 
Sanofi 
Tel: +44 (0) 845 372 7101 
 

 
This leaflet was last revised in {date} 
 
 
Other source of information 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu/ 
 
 
 
 

HYPERGLYCAEMIA AND HYPOGLYCAEMIA 
 

Always carry some sugar (at least 20 grams) with you. 
Carry some information with you to show you are diabetic. 

 
HYPERGLYCAEMIA (high blood sugar levels) 

 
If your blood sugar is too high (hyperglycaemia), you may not have injected enough insulin. 
 
Why does hyperglycaemia occur? 
 
Examples include: 
- you have not injected your insulin or not injected enough, or if it has become less effective, for 

example through incorrect storage, 
- your insulin pump does not work properly, 
- you are doing less exercise than usual, you are under stress (emotional distress, excitement), or 

you have an injury, operation, infection or fever, 
- you are taking or have taken certain other medicines (see section 2, "Other medicines and 

Insulin Human Winthrop Infusat"). 
 
Warning symptoms of hyperglycaemia 
 
Thirst, increased need to urinate, tiredness, dry skin, reddening of the face, loss of appetite, low blood 
pressure, fast heart beat, and glucose and ketone bodies in urine. Stomach pain, fast and deep 
breathing, sleepiness or even loss of consciousness may be signs of a serious condition (ketoacidosis) 
resulting from lack of insulin. 
 
What should you do if you experience hyperglycaemia 
 
Test your blood sugar level and your urine for ketones as soon as any of the above symptoms 
occur. Severe hyperglycaemia or ketoacidosis must always be treated by a doctor, normally in a 
hospital. 
 

 

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HYPOGLYCAEMIA (low blood sugar levels) 
 
If your blood sugar level falls too much you may become unconscious. Serious hypoglycaemia may 
cause a heart attack or brain damage and may be life-threatening. You normally should be able to 
recognise when your blood sugar is falling too much so that you can take the right actions. 
 
Why does hypoglycaemia occur? 
 
Examples include: 
- you inject too much insulin, 
- you miss meals or delay them, 
- you do not eat enough, or eat food containing less carbohydrate than normal (sugar and 

substances similar to sugar are called carbohydrates; however, artificial sweeteners are NOT 
carbohydrates), 

- you lose carbohydrates due to vomiting or diarrhoea, 
- you drink alcohol, particularly if you are not eating much, 
- you are doing more exercise than usual or a different type of physical activity, 
- you are recovering from an injury or operation or other stress, 
- you are recovering from an illness or from fever, 
- you are taking or have stopped taking certain other medicines (see section 2, "Other medicines 

and Insulin Human Winthrop Infusat"). 
 
Hypoglycaemia is also more likely to occur if: 
- you have just begun insulin treatment or changed to another insulin preparation, 
- your blood sugar levels are almost normal or are unstable, 
- you change the area of skin where you inject insulin (for example from the thigh to the upper 

arm), 
- you suffer from severe kidney or liver disease, or some other disease such as hypothyroidism. 
 
Warning symptoms of hypoglycaemia 
 
- In your body 
Examples of symptoms that tell you that your blood sugar level is falling too much or too fast: 
sweating, clammy skin, anxiety, fast heart beat, high blood pressure, palpitations and irregular 
heartbeat. These symptoms often develop before the symptoms of a low sugar level in the brain. 
 
- In your brain 
Examples of symptoms that indicate a low sugar level in the brain: headaches, intense hunger, nausea, 
vomiting, tiredness, sleepiness, sleep disturbances, restlessness, aggressive behaviour, lapses in 
concentration, impaired reactions, depression, confusion, speech disturbances (sometimes total loss of 
speech), visual disorders, trembling, paralysis, tingling sensations (paraesthesia), numbness and 
tingling sensations in the area of the mouth, dizziness, loss of self-control, inability to look after 
yourself, convulsions, loss of consciousness. 
 
The first symptoms which alert you to hypoglycaemia ("warning symptoms") may change, be weaker 
or may be missing altogether if 
- you are elderly, if you have had diabetes for a long time or if you suffer from a certain type of 

nervous disease (diabetic autonomic neuropathy), 
- you have recently suffered hypoglycaemia (for example the day before) or if it develops slowly, 
- you have almost normal or, at least, greatly improved blood sugar levels, 
- you have recently changed from an animal insulin to a human insulin such as Insulin Human 

Winthrop, 
- you are taking or have taken certain other medicines (see section 2, "Other medicines and 

Insulin Human Winthrop Infusat"). 
 
In such a case, you may develop severe hypoglycaemia (and even faint) before you are aware of the 
problem. Be familiar with your warning symptoms. If necessary, more frequent blood sugar testing 

 

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can help to identify mild hypoglycaemic episodes that may otherwise be overlooked. If you are not 
confident about recognising your warning symptoms, avoid situations (such as driving a car) in which 
you or others would be put at risk by hypoglycaemia. 
 
What should you do if you experience hypoglycaemia 
 
1. Stop your insulin infusion (if necessary, by withdrawing the needle) at least until you feel that 

you are fully alert again. Immediately take about 10 to 20 g sugar, such as glucose, sugar cubes 
or a sugar-sweetened beverage. Caution: Artificial sweeteners and foods with artificial 
sweeteners (such as diet drinks) are of no help in treating hypoglycaemia. 

2. Then eat something that has a long-acting effect in raising your blood sugar (such as bread or 
pasta). Your doctor or nurse should have discussed this with you previously. 

3. If the hypoglycaemia comes back again take another 10 to 20 g sugar. 
4. Speak to a doctor immediately if you are not able to control the hypoglycaemia or if it recurs. 
 
Tell your relatives, friends and close colleagues the following: 
If you are not able to swallow or if you are unconscious, you will require an injection of glucose or 
glucagon (a medicine which increases blood sugar). These injections are justified even if it is not 
certain that you have hypoglycaemia. 
 
It is advisable to test your blood sugar immediately after taking glucose to check that you really have 
hypoglycaemia. 
 
 

 

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	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER(S) OF THE BIOLOGICAL ACTIVE SUBSTANCE(S) AND MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET