Apidra

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ANNEX I 

 

SUMMARY OF PRODUCT CHARACTERISTICS 

 

 



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1. NAME OF THE MEDICINAL PRODUCT 

 

Apidra 100 Units/ml solution for injection in a vial 

Apidra 100 Units/ml solution for injection in a cartridge 

Apidra SoloStar 100 Units/ml solution for injection in a pre-filled pen 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 

 

Each ml contains 100 Units insulin glulisine (equivalent to 3.49 mg). 

 

Apidra 100 Units/ml solution for injection in a vial 

Each vial contains 10 ml of solution for injection, equivalent to 1000 Units. 

 

Apidra 100 Units/ml solution for injection in a cartridge 

Each cartridge contains 3 ml of solution for injection, equivalent to 300 Units. 

 

Apidra SoloStar 100 Units/ml solution for injection in a pre-filled pen 

Each pen contains 3 ml of solution for injection, equivalent to 300 Units. 

 

Insulin glulisine is produced by recombinant DNA technology in Escherichia coli. 

For the full list of excipients, see section 6.1. 

 

 

3. PHARMACEUTICAL FORM 

 

Apidra 100 Units/ml solution for injection in a vial 

Solution for injection in a vial. 

 

Apidra 100 Units/ml solution for injection in a cartridge 

Solution for injection in a cartridge. 

 

Apidra SoloStar 100 Units/ml solution for injection in a pre-filled pen 

Solution for injection in a pre-filled pen. 

 

Clear, colourless, aqueous solution. 

 

 

4. CLINICAL PARTICULARS 

 

4.1 Therapeutic indications 

 

Treatment of adults, adolescents and children 6 years or older, with diabetes mellitus, where treatment 

with insulin is required. 

 

4.2 Posology and method of administration 

 

Posology 

The potency of this preparation is stated in units. These units are exclusive to Apidra and are not the 

same as IU or the units used to express the potency of other insulin analogues (see section 5.1). 

Apidra should be used in regimens that include an intermediate or long acting insulin or basal insulin 

analogue and can be used with oral hypoglycaemic agents. 

The dose of Apidra should be individually adjusted. 

 

 



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Special populations 

Renal impairment 

The pharmacokinetic properties of insulin glulisine are generally maintained in patients with renal 

impairment. However, insulin requirements may be reduced in the presence of renal impairment (see 

section 5.2). 

 

Hepatic impairment 

The pharmacokinetic properties of insulin glulisine have not been investigated in patients with decreased 

liver function. In patients with hepatic impairment, insulin requirements may be diminished due to 

reduced capacity for gluconeogenesis and reduced insulin metabolism. 

 

Elderly 

Limited pharmacokinetic data are available in elderly patients with diabetes mellitus. Deterioration of 

renal function may lead to a decrease in insulin requirements. 

 

Paediatric population 

There is insufficient clinical information on the use of Apidra in children younger than the age of 

6 years. 

 

Method of administration 

 

Apidra 100 Units/ml solution for injection in a vial 

Intravenous use 

Apidra can be administered intravenously. This should be carried out by healthcare professionals. 

Apidra must not be mixed with glucose or Ringer’s solution or with any other insulin. 

 

Continuous subcutaneous insulin infusion 

Apidra may be used for Continuous Subcutaneous Insulin Infusion (CSII) in pump systems suitable for 

insulin infusion with the appropriate catheters and reservoirs. Patients using CSII should be 

comprehensively instructed on the use of the pump system. 

The infusion set and reservoir used with Apidra must be changed at least every 48 hours using aseptic 

technique. These instructions may differ from general pump manual instructions. It is important that 

patients follow the Apidra specific instructions when using Apidra. Failure to follow Apidra specific 

instructions may lead to serious adverse events. 

When used with a subcutaneous insulin infusion pump, Apidra must not be mixed with diluents or any 

other insulin. 

Patients administering Apidra by CSII must have an alternative insulin delivery system available in case 

of pump system failure (see section 4.4 and 4.8). 

 

Apidra 100 Units/ml solution for injection in a vial 

For further details on handling, see section 6.6. 

 

Apidra 100 Units/ml solution for injection in a cartridge 

Apidra 100 Units/ml in cartridges is only suitable for subcutaneous injections from a reusable pen. If 

administration by syringe, intravenous injection or infusion pump is necessary, a vial should be used 

(see section 4.4). For further details on handling, see section 6.6. 

 

Apidra SoloStar 100 Units/ml solution for injection in a pre-filled pen 

Apidra SoloStar 100 Units/ml in pre-filled pen is only suitable for subcutaneous injections. If 

administration by syringe, intravenous injection or infusion pump is necessary, a vial should be used 

(see section 4.4). 



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Subcutaneous use 

Apidra should be given by subcutaneous injection shortly (0-15 min) before or soon after meals or by 

continuous subcutaneous pump infusion. 

Apidra should be administered subcutaneously in the abdominal wall, thigh or deltoid or by continuous 

infusion in the abdominal wall. Injection sites and infusion sites within an injection area (abdomen, thigh 

or deltoid) should be rotated from one injection to the next. The rate of absorption, and consequently the 

onset and duration of action, may be affected by the injection site, exercise and other variables. 

Subcutaneous injection in the abdominal wall ensures a slightly faster absorption than other injection 

sites (see section 5.2). 

Care should be taken to ensure that a blood vessel has not been entered. After injection, the site of 

injection should not be massaged. Patients must be educated to use proper injection techniques. 

 

Mixing with insulins 

When administered as a subcutaneous injection, Apidra must not be mixed with other medicinal 

products except NPH human insulin. 

For further details on handling, see section 6.6. 

Before using SoloStar, the Instructions for use included in the Package leaflet must be read carefully 

(see section 6.6). 

 

4.3 Contraindications 

 

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 

Hypoglycaemia. 

 

4.4 Special warnings and precautions for use 

 

Transferring a patient to another type or brand of insulin should be done under strict medical 

supervision. Changes in strength, brand (manufacturer), type (regular, neutral protamine Hagedorn 

[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 dose. Concomitant oral antidiabetic treatment may 

need to be adjusted. 

 

Hyperglycaemia 

The use of inadequate doses or discontinuation of treatment, especially in insulin-dependent diabetic, 

may lead to hyperglycaemia and diabetic ketoacidosis; conditions which are potentially lethal. 

 

Hypoglycaemia 

The time of occurrence of hypoglycaemia depends on the action profile of the insulins used and may, 

therefore, change when the treatment regimen is changed. 

Conditions which may make the early warning symptoms of hypoglycaemia different or less pronounced 

include long duration of diabetes, intensified insulin therapy, diabetic nerve disease, medicinal products 

such as beta blockers or after transfer from animal-source insulin to human insulin. 

Adjustment of dose may be also necessary if patients undertake increased physical activity or change 

their usual meal plan. Exercise taken immediately after a meal may increase the risk of hypoglycaemia. 

When compared with soluble human insulin, if hypoglycaemia occurs after an injection with rapid 

acting analogues, it may occur earlier. 

Uncorrected hypoglycaemic or hyperglycaemic reactions can cause loss of consciousness, coma, or 

death. 

Insulin requirements may be altered during illness or emotional disturbances. 

 



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Apidra 100 Units/ml solution for injection in a cartridge 

Pens to be used with Apidra 100 units/ml solution for injection in a cartridge 

Apidra 100 units/ml in cartridges is only suitable for subcutaneous injections from a reusable pen. If 

administration by syringe, intravenous injection or infusion pump is necessary, a vial should be used. 

The Apidra cartridges should only be used with the following pens: 

− JuniorSTAR which delivers Apidra in 0.5 unit dose increments 
− ClikSTAR, Tactipen, Autopen 24, AllStar and AllStar PRO which all deliver Apidra 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 (see section 4.2 and 6.6). 

Not all of these pens may be marketed in your country. 

 

Medication errors 

Medication errors have been reported in which other insulins, particularly long-acting insulins, have 

been accidentally administered instead of insulin glulisine. Insulin label must always be checked before 

each injection to avoid medication errors between insulin glulisine and other insulins. 

 

Apidra 100 Units/ml solution for injection in a vial 

Continuous subcutaneous insulin infusion 

Malfunction of the insulin pump or infusion set or handling errors can rapidly lead to hyperglycaemia, 

ketosis and diabetic ketoacidosis. Prompt identification and correction of the cause of hyperglycaemia or 

ketosis or diabetic ketoacidosis is necessary. 

Cases of diabetic ketoacidosis have been reported when Apidra has been given in continuous 

subcutaneous insulin infusion in pump systems. Most of the cases were related to handling errors or 

pump system failure. 

Interim subcutaneous injections with Apidra may be required. Patients using continuous subcutaneous 

insulin infusion pump therapy must be trained to administer insulin by injection and have alternative 

insulin delivery system available in case of pump system failure (see section 4.2 and 4.8). 

 

Excipients 

This medicinal product contains less than 1 mmol (23 mg) sodium per dose, i.e. it is essentially 

‘sodium-free’. 

Apidra contains metacresol, which may cause allergic reactions. 

 

Combination of Apidra 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 Apidra 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. 

 

Apidra SoloStar 100 Units/ml solution for injection in a pre-filled pen 

Handling of the SoloStar pre-filled pen 

Apidra SoloStar 100 units/ml in pre-filled pen is only suitable for subcutaneous injections. If 

administration by syringe, intravenous injection or infusion pump is necessary, a vial should be used. 

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). 

 

4.5 Interaction with other medicinal products and other forms of interaction 

 

Studies on pharmacokinetic interactions have not been performed. Based on empirical knowledge from 

similar medicinal products, clinically relevant pharmacokinetic interactions are unlikely to occur. 

A number of substances affect glucose metabolism and may require dose adjustment of insulin glulisine 

and particularly close monitoring. 



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Substances that may enhance the blood-glucose-lowering activity and increase susceptibility to 

hypoglycaemia include oral antidiabetic medicinal products, angiotensin converting enzyme (ACE) 

inhibitors, disopyramide, fibrates, fluoxetine, monoamine oxidase inhibitors (MAOIs), pentoxifylline, 

propoxyphene, salicylates and sulphonamide antibiotics. 

Substances that may reduce the blood-glucose-lowering activity include corticosteroids, danazol, 

diazoxide, diuretics, glucagon, isoniazid, phenothiazine derivatives, somatropin, sympathomimetic 

medicinal products (e.g. epinephrine [adrenaline], salbutamol, terbutaline), thyroid hormones, 

oestrogens, progestins (e.g. in oral contraceptives), 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 activity 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 Pregnancy and lactation 

 

Pregnancy 

There are no or limited amount of data (less than 300 pregnancy outcomes) from the use of insulin 

glulisine in pregnant women. 

Animal reproduction studies have not revealed any differences between insulin glulisine and human 

insulin regarding pregnancy, embryonal/foetal development, parturition or postnatal development (see 

section 5.3). 

Caution should be exercised when prescribing to pregnant women. Careful monitoring of glucose 

control is essential. 

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. 

 

Breast-feeding 

It is unknown whether insulin glulisine is excreted in human milk, but in general insulin does not pass 

into breast milk and is not absorbed after oral administration. 

Breast-feeding mothers may require adjustments in insulin dose and diet. 

 

Fertility 

Animal reproduction studies with insulin glulisine have not revealed any adverse effects on fertility. 

 

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 operating 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. The advisability of driving should be 

considered in these circumstances. 

 

4.8 Undesirable effects 

 

Summary of the safety profile 

Hypoglycaemia, the most frequent adverse reaction of insulin therapy, may occur if the insulin dose is 

too high in relation to the insulin requirement. 

 



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Tabulated list of adverse reactions 

The following related adverse reactions from clinical studies were 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 

Organ system 

classes 

Very common 

 

Common 

 

Uncommon 

 

Rare  

 

Unknown 

Metabolism 

and nutrition 

disorders 

Hypoglycaemia    Hyperglycaemia 

(potentially 

leading to 

Diabetic 

ketoacidosis(1)) 

Skin and 

subcutaneous 

tissue 

disorders 

 

 Injection site 

reactions  

Local 

hypersensitivity 

reactions 

 Lipodystrophy  

General 

disorders and 

administration 

site conditions 

 

  Systemic 

hypersensitivity 

reactions  

  

(1) Apidra 100 Units/ml solution for injection in a vial: Most of the cases were related to handling errors or 
pump system failure when Apidra was used with CSII. 

 

Description of selected adverse reactions 

• Metabolism and nutrition disorders 

Symptoms of hypoglycaemia usually occur suddenly. They may include cold sweats, cool pale skin, 

fatigue, nervousness or tremor, anxiousness, unusual tiredness or weakness, confusion, difficulty in 

concentration, drowsiness, excessive hunger, vision changes, headache, nausea and palpitation. 

Hypoglycaemia can become severe and may lead to unconsciousness and/or convulsions and may result 

in temporary or permanent impairment of brain function or even death. 

 

Apidra 100 Units/ml solution for injection in a vial 

Cases of hyperglycaemia have been reported with Apidra when used with CSII (see section 4.4) that has 

led to Diabetic Ketoacidosis (DKA); most of the cases were related to handling errors or pump system 

failure. The patient should always follow the Apidra specific instructions and always have access to 

alternative insulin delivery system in case of pump system failure. 

 

• Skin and subcutaneous tissue disorders 

Local hypersensitivity reactions (redness, swelling and itching at the injection site) may occur during 

treatment with insulin. These reactions are usually transitory and normally they disappear during 

continued treatment. 

Lipodystrophy may occur at the injection site as a consequence of failure to rotate injection sites within 

an area. 

 

• General disorders and administration site conditions 

Systemic hypersensitivity reactions may include urticaria, chest tightness, dyspnoea, allergic dermatitis 

and pruritus. Severe cases of generalized allergy, including anaphylactic reaction, may be 

life-threatening. 

 

Reporting of suspected adverse reactions 

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 

allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 



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professionals are asked to report any suspected adverse reactions via the national reporting system listed 

in Appendix V. 

4.9 Overdose 

 

Symptoms 

Hypoglycaemia may occur as a result of an excess of insulin activity relative to food intake and energy 

expenditure. 

There are no specific data available concerning overdoses with insulin glulisine. However, 

hypoglycaemia may develop over sequential stages. 

 

Management 

Mild hypoglycaemic episodes can be treated by oral administration of glucose or sugary products. It is 

therefore recommended that the diabetic patient constantly carries some sugar lumps, sweets, biscuits or 

sugary fruit juice. 

Severe hypoglycaemic episodes, where the patient has become unconscious, can be treated by glucagon 

(0.5 mg to 1 mg) given intramuscularly or subcutaneously by a person who has received appropriate 

instruction, or by glucose given intravenously by a healthcare professional. Glucose must also be given 

intravenously, if the patient does not respond to glucagon within 10 to 15 minutes. 

Upon regaining consciousness, administration of oral carbohydrate is recommended for the patient in 

order to prevent relapse. 

After an injection of glucagon, the patient should be monitored in a hospital in order to find the reason 

for this severe hypoglycaemia and prevent other similar episodes. 

 

 

5. PHARMACOLOGICAL PROPERTIES 

 

5.1  Pharmacodynamic properties 

 

Pharmacotherapeutic group: Drugs used in diabetes, insulins and analogues for injection, fast-acting. 

ATC code: A10AB06 

 

Mechanism of action 

Insulin glulisine is a recombinant human insulin analogue that is equipotent to regular human insulin. 

Insulin glulisine has a more rapid onset of action and a shorter duration of action than regular human 

insulin. 

The primary activity of insulins and insulin analogues, including insulin glulisine, is regulation of 

glucose metabolism. Insulins lower blood glucose levels by stimulating peripheral glucose uptake, 

especially by skeletal muscle and fat, and by inhibiting hepatic glucose production. Insulin inhibits 

lipolysis in the adipocyte, inhibits proteolysis and enhances protein synthesis. 

Studies in healthy volunteers and patients with diabetes demonstrated that insulin glulisine is more rapid 

in onset of action and of shorter duration of action than regular human insulin when given 

subcutaneously. When insulin glulisine is injected subcutaneously, the glucose lowering activity will 

begin within 10-20 minutes. After intravenous administration, a faster onset and shorter duration of 

action, as well as a greater peak response were observed as compared with subcutaneous 

administration. The glucose-lowering activities of insulin glulisine and regular human insulin are 

equipotent when administered by intravenous route. 

One unit of insulin glulisine has the same glucose-lowering activity as one unit of regular human insulin. 

 

Dose proportionality 

In a study with 18 male subjects with diabetes mellitus type 1 aged 21 to 50 years, insulin glulisine 

displayed dose-proportional glucose lowering effect in the therapeutic relevant dose range 0.075 to 

0.15 Units/kg, and less than proportional increase in glucose lowering effect with 0.3 Units/kg or higher, 

like human insulin. 

Insulin glulisine takes effect about twice as fast as regular human insulin and completes the glucose 

lowering effect about 2 hours earlier than regular human insulin. 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc
http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


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A phase I study in patients with type 1 diabetes mellitus assessed the glucose lowering profiles of 

insulin glulisine and regular human insulin administered subcutaneously at a dose of 0.15 Units/kg, at 

different times in relation to a 15-minute standard meal. Data indicated that insulin glulisine 

administered 2 minutes before the meal gives similar postprandial glycaemic control compared to 

regular human insulin given 30 minutes before the meal. When given 2 minutes prior to meal, insulin 

glulisine provided better postprandial control than regular human insulin given 2 minutes before the 

meal. Insulin glulisine administered 15 minutes after starting the meal gives similar glycaemic control as 

regular human insulin given 2 minutes before the meal (see figure 1). 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

                  Figure 1A                                    Figure 1B                                        Figure 1C     

 

Figure 1: Average glucose-lowering effect over 6 hours in 20 patients with type 1 diabetes mellitus. 

Insulin glulisine given 2 minutes (GLULISINE pre) before the start of a meal compared to regular 

human insulin given 30 minutes (REGULAR 30 min) before the start of the meal (figure 1A) and 

compared to regular human insulin given 2 minutes (REGULAR pre) before a meal (figure 1B). Insulin 

glulisine given 15 minutes (GLULISINE post) after start of a meal compared to regular human insulin 

given 2 minutes (REGULAR pre) before start of the meal (figure 1C). On the x-axis, zero (arrow) is the 

start of a 15-minute meal. 

 

Obesity 

A phase I study carried out with insulin glulisine, lispro and regular human insulin in an obese 

population has demonstrated that insulin glulisine maintains its rapid-acting properties. In this study, the 

time to 20% of total AUC and the AUC (0-2h) representing the early glucose lowering activity were 

respectively of 114 minutes and 427 mg/kg for insulin glulisine, 121 minutes and 354 mg/kg for lispro, 

150 minutes and 197 mg/kg for regular human insulin (see figure 2). 

 

-1 0 1 2 3 4 5 6 7

TIME - hour

60

80

100

120

140

160

180

200

220

G
L
U

C
O

S
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 -
 m

g
/d

L

REGULAR  - pre
GLULISINE - post

-1 0 1 2 3 4 5 6 7

TIME - hour

60

80

100

120

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160

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200

220

G
L
U

C
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 -
 m

g
/d

L

REGULAR  - pre
GLULISINE - pre

-1 0 1 2 3 4 5 6 7

TIME - hour

60

80

100

120

140

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200

220

G
L
U

C
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 -
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REGULAR  - 30 min
GLULISINE - pre



10 

0 2 4 6 8 10

TIME - hour

0

2

4

6

8

10

12

G
IR

 -
 m

g
/k

g
/m

in

REGULAR
LISPRO
GLULISINE

 
Figure 2: Glucose infusion rates (GIR) after subcutaneous injection of 0.3 Units/kg of insulin glulisine 

(GLULISINE) or insulin lispro (LISPRO) or regular human insulin (REGULAR) in an obese 

population. 

 

Another phase I study with insulin glulisine and insulin lispro in a non-diabetic population in 

80 subjects with a wide range of body mass indices (18-46 kg/m²) has demonstrated that rapid action is 

generally maintained across a wide range of body mass indices (BMI), while total glucose lowering 

effect decreases with increasing obesity. 

The average total GIR AUC between 0-1 hour was 102 ± 75 mg/kg and 158 ± 100 mg/kg with 0.2 and 

0.4 Units/kg insulin glulisine, respectively, and was 83.1 ± 72.8 mg/kg and 112.3 ± 70.8 mg/kg with 

0.2 and 0.4 Units/kg insulin lispro, respectively.  

A phase I study in 18 obese patients with type 2 diabetes mellitus (BMI between 35 and 40 kg/m2) with 

insulin glulisine and insulin lispro [90% CI: 0.81, 0.95 (p=<0.01)] has shown that insulin glulisine 

effectively controls diurnal postprandial blood glucose excursions. 

 

Clinical efficacy and safety 

 

Type 1 diabetes mellitus–Adults 

In a 26-week phase III clinical study comparing insulin glulisine with insulin lispro both injected 

subcutaneously shortly (0-15 minutes) before a meal in patients with type 1 diabetes mellitus using 

insulin glargine as basal insulin, insulin glulisine was comparable to insulin lispro for glycaemic control 

as reflected by changes in glycated haemoglobin (expressed as HbA1c equivalent) from baseline to 

endpoint. Comparable self-monitored blood glucose values were observed. No increase in the basal 

insulin dose was needed with insulin glulisine, in contrast to insulin lispro. 

A 12-week phase III clinical study performed in patients with type 1 diabetes mellitus receiving insulin 

glargine as basal therapy indicate that the immediate post-meal administration of insulin glulisine 

provides efficacy that was comparable to immediate pre-meal insulin glulisine (0-15 minutes) or regular 

insulin (30-45 minutes). 



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In the per-protocol population there was a significantly larger observed reduction in GHb in the 

pre-meal glulisine group compared with the regular insulin group. 

 

Type 1 diabetes mellitus–Paediatric 

A 26-week phase III clinical study compared insulin glulisine with insulin lispro both injected 

subcutaneously shortly (0-15 minutes) before a meal in children (4-5 years: n=9; 6-7 years: n=32 and 

8-11 years: n=149) and adolescents (12-17 years: n=382) with type 1 diabetes mellitus using insulin 

glargine or NPH as basal insulin. Insulin glulisine was comparable to insulin lispro for glycaemic 

control as reflected by changes in glycated haemoglobin (GHb expressed as HbA1c equivalent) from 

baseline to endpoint and by self-monitored blood glucose values. 

There is insufficient clinical information on the use of Apidra in children younger than the age of 

6 years. 

 

Type 2 diabetes mellitus–Adults 

A 26-week phase III clinical study followed by a 26-week extension safety study was conducted to 

compare insulin glulisine (0-15 minutes before a meal) with regular human insulin (30-45 minutes 

before a meal) injected subcutaneously in patients with type 2 diabetes mellitus also using NPH insulin 

as basal insulin. The average body mass index (BMI) of patients was 34.55 kg/m2. Insulin glulisine was 

shown to be comparable to regular human insulin with regard to glycated haemoglobin (expressed as 

HbA1c equivalent) changes from baseline to the 6-month endpoint (-0.46% for insulin glulisine and -

0.30% for regular human insulin, p=0.0029) and from baseline to the 12-month endpoint (-0.23% for 

insulin glulisine and -0.13% for regular human insulin, difference not significant). In this study, the 

majority of patients (79%) mixed their short acting insulin with NPH insulin immediately prior to 

injection and 58% of subjects used oral hypoglycaemic agents at randomization and were instructed to 

continue to use them at the same dose. 

 

Race and gender 

In controlled clinical studies in adults, insulin glulisine did not show differences in safety and efficacy in 

subgroup analyses based on race and gender. 

 

5.2 Pharmacokinetic properties 

 

In insulin glulisine the replacement of the human insulin amino acid asparagine in position B3 by lysine 

and the lysine in position B29 by glutamic acid favours more rapid absorption. 

In a study with 18 male subjects with diabetes mellitus type 1, aged 21 to 50 years, insulin glulisine 

displays dose-proportionality for early, maximum and total exposure in the dose range 

0.075 to 0.4 Units/kg. 

 

Absorption and bioavailability 

Pharmacokinetic profiles in healthy volunteers and diabetes patients (type 1 or 2) demonstrated that 

absorption of insulin glulisine was about twice as fast with a peak concentration approximately twice as 

high as compared to regular human insulin. 

In a study in patients with type 1 diabetes mellitus after subcutaneous administration of 0.15 Units/kg, 

for insulin glulisine the Tmax was 55 minutes and Cmax was 82 ± 1.3 µUnits/ml compared to a Tmax of 

82 minutes and a Cmax of 46 ± 1.3 µUnits/ml for regular human insulin. The mean residence time of 

insulin glulisine was shorter (98 min) than for regular human insulin (161 min) (see figure 3). 



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Figure 3: Pharmacokinetic profile of insulin glulisine and regular human insulin in type 1 diabetes 

mellitus patients after a dose of 0.15 Units/kg. 

 

In a study in patients with type 2 diabetes mellitus after subcutaneous administration of 0.2 Units/kg 

insulin glulisine, the Cmax was 91 µUnits/ml with the interquartile range from 78 to 104 µUnits/ml. 

When insulin glulisine was injected subcutaneously into abdomen, deltoid and thigh, the 

concentration-time profiles were similar with a slightly faster absorption when administered in the 

abdomen compared to the thigh. Absorption from deltoid sites was in-between (see section 4.2). The 

absolute bioavailability (70%) of insulin glulisine was similar between injection sites and of low 

intra-subject variability (11% CV). Intravenous bolus administration of insulin glulisine resulted in a 

higher systemic exposure when compared to subcutaneous injection, with a Cmax approximately 40-fold 

higher. 

 

Obesity 

Another phase I study with insulin glulisine and insulin lispro in a non-diabetic population in 

80 subjects with a wide range of body mass indices (18-46 kg/m²) has demonstrated that rapid 

absorption and total exposure is generally maintained across a wide range of body mass indices. 

The time to 10% of total INS exposure was reached earlier by approximately 5-6 min with insulin 

glulisine. 

 

Distribution and elimination 

The distribution and elimination of insulin glulisine and regular human insulin after intravenous 

administration is similar with volumes of distribution of 13 l and 22 l and half-lives of 13 and 

18 minutes, respectively. 

After subcutaneous administration, insulin glulisine is eliminated more rapidly than regular human 

insulin with an apparent half-life of 42 minutes compared to 86 minutes. In an across study analysis of 

insulin glulisine in either healthy subjects or subjects with type 1 or type 2 diabetes mellitus the 

apparent half-life ranged from 37 to 75 minutes (interquartile range). 

Insulin glulisine shows low plasma protein binding, similar to human insulin. 

 

Special populations 

 

Renal impairment 

In a clinical study performed in non-diabetic subjects covering a wide range of renal function 

(CrCl >80 ml/min, 30-50 ml/min, <30 ml/min), the rapid-acting properties of insulin glulisine were 

generally maintained. However, insulin requirements may be reduced in the presence of renal 

impairment. 

 



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Hepatic impairment 

The pharmacokinetic properties have not been investigated in patients with impaired liver function. 

 

Elderly 

Very limited pharmacokinetic data are available for elderly patients with diabetes mellitus. 

 

Children and adolescents 

The pharmacokinetic and pharmacodynamic properties of insulin glulisine were investigated in children 

(7-11 years) and adolescents (12-16 years) with type 1 diabetes mellitus. Insulin glulisine was rapidly 

absorbed in both age groups, with similar Tmax and Cmax as in adults (see section 4.2). Administered 

immediately before a test meal, insulin glulisine provided better postprandial control than regular human 

insulin, as in adults (see section 5.1). The glucose excursion (AUC 0-6h) was 641 mg.h.dl
-1 for insulin 

glulisine and 801 mg.h.dl-1 for regular human insulin. 

 

5.3 Preclinical safety data 

 

Non-clinical data did not reveal toxicity findings others than those linked to the blood glucose lowering 

pharmacodynamic activity (hypoglycaemia), different from regular human insulin or of clinical 

relevance for humans. 

 

 

6. PHARMACEUTICAL PARTICULARS 

 

6.1 List of excipients 

 

Metacresol 

Sodium chloride 

Trometamol 

Polysorbate 20 

Hydrochloric acid, concentrated 

Sodium hydroxide 

Water for injections 

 

6.2 Incompatibilities 

 

Apidra 100 Units/ml solution for injection in a vial 

Subcutaneous use 

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal 

products except NPH human insulin. 

When used with an insulin infusion pump, Apidra must not be mixed with other medicinal products. 

 

Intravenous use 

Apidra was found to be incompatible with Glucose 5% solution and Ringer’s solution and, therefore, 

must not be used with these solution fluids. The use of other solutions has not been studied. 

 

6.3 Shelf life 

 

2 years. 

 

Apidra 100 Units/ml solution for injection in a vial 

Shelf life after first use of the vial 

The product may be stored for a maximum of 4 weeks below 25°C 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 from the vial be noted on the label. 

 



14 

Shelf life for intravenous use 

Insulin glulisine for intravenous use at a concentration of 1 Unit/ml is stable between 15°C and 25°C 

for 48 hours (see section 6.6). 

 

Apidra 100 Units/ml solution for injection in a cartridge 

Shelf life after first use of the cartridge 

The product may be stored for a maximum of 4 weeks below 25°C 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. 

 

Apidra SoloStar 100 Units/ml solution for injection in a pre-filled pen 

Shelf life after first use of the pen 

The product may be stored for a maximum of 4 weeks below 25°C 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 

 

Apidra 100 Units/ml solution for injection in a vial 

Unopened vials 

Store in a refrigerator (2°C - 8°C). 

Do not freeze. 

Do not put Apidra 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. 

 

Apidra 100 Units/ml solution for injection in a cartridge 

Unopened cartridges 

Store in a refrigerator (2°C - 8°C). 

Do not freeze. 

Do not put Apidra 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. 

 

Apidra SoloStar 100 Units/ml solution for injection in a pre-filled pen 

Not in-use pens 

Store in a refrigerator (2°C-8°C). 

Do not freeze. 

Do not put Apidra 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 

 

Apidra 100 Units/ml solution for injection in a vial 

10 ml solution in a vial (type I colourless glass) with a stopper (flanged aluminium overseal, elastomeric 

chlorobutyl rubber) and a polypropylene tear-off cap. Packs of 1, 2, 4 and 5 vials are available. 

Not all pack sizes may be marketed. 



15 

 

Apidra 100 Units/ml solution for injection in a cartridge 

3 ml solution in a cartridge (type I colourless glass) with a plunger (elastomeric bromobutyl rubber) and 

a flanged cap (aluminium) with a stopper (elastomeric bromobutyl rubber). Packs of 1, 3, 4, 5, 6, 8, 9 

and 10 cartridges are available. 

Not all pack sizes may be marketed. 

 

Apidra SoloStar 100 Units/ml solution for injection in a pre-filled pen 

3 ml solution in a cartridge (colourless glass) with a plunger (elastomeric bromobutyl rubber) and a 

flanged cap (aluminium) with a stopper (elastomeric bromobutyl rubber). The cartridge is sealed in a 

disposable pre-filled pen. Packs of 1, 3, 4, 5, 6, 8, 9 and 10 pens are available. 

Not all pack sizes may be marketed. 

 

6.6 Special precautions for disposal and other handling 

 

Apidra 100 Units/ml solution for injection in a vial 

Subcutaneous use 

Apidra vials are for use with insulin syringes with the corresponding unit scale and for use with an 

insulin pump system (see section 4.2). 

Inspect the vial before use. It must only be used if the solution is clear, colourless, with no solid 

particles visible. Since Apidra is a solution, it does not require resuspension before use. 

Insulin label must always be checked before each injection to avoid medication errors between insulin 

glulisine and other insulins (see section 4.4). 

 

Mixing with insulins 

When mixed with NPH human insulin, Apidra should be drawn into the syringe first. Injection should 

be given immediately after mixing as no data are available regarding the mixtures made up a significant 

time before injection. 

 

Continuous subcutaneous infusion pump 

Refer to section 4.2 and 4.4 for advice. 

 

Intravenous use 

Apidra should be used at a concentration of 1 Unit/ml insulin glulisine in infusion systems with sodium 

chloride 9 mg/ml (0.9%) solution for infusion with or without 40 mmol/l potassium chloride using 

coextruded polyolefin/polyamide plastic infusion bags with a dedicated infusion line. Insulin glulisine 

for intravenous use at a concentration of 1 Unit/ml is stable at room temperature for 48 hours. 

After dilution for intravenous use, the solution should be inspected visually for particulate matter prior 

to administration. It must only be used if the solution is clear and colourless, not when cloudy or with 

visible particles. 

Apidra was found to be incompatible with Glucose 5% solution and Ringer’s solution and, therefore, 

must not be used with these solution fluids. The use of other solutions has not been studied. 

 

Apidra 100 Units/ml solution for injection in a cartridge 

Apidra 100 units/ml in a cartridge is only suitable for subcutaneous injections from a reusable pen. If 

administration by syringe, intravenous injection or infusion pump is necessary, a vial should be used. 

The Apidra cartridges are to be used only in conjunction with the pens: ClikSTAR, Autopen 24, 

Tactipen, AllStar, AllStar PRO or JuniorSTAR (see section 4.2 and 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 needle, and administering the insulin injection. Inspect the cartridge before use. It must 

only be used if the solution is clear, colourless, with no solid particles visible. Before insertion of the 

cartridge into the reusable pen, the cartridge must be stored at room temperature for 1 to 2 hours. Air 



16 

bubbles must be removed from the cartridge before injection (see instruction for using pen). Empty 

cartridges must not be refilled. 

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. 

To prevent any kind of contamination, the re-usable pen should be used by a single patient only. 

Insulin label must always be checked before each injection to avoid medication errors between insulin 

glulisine and other insulins (see section 4.4). 

 

Apidra SoloStar 100 Units/ml solution for injection in a pre-filled pen 

Apidra SoloStar 100 units/ml in a pre-filled pen is only suitable for subcutaneous injections. If 

administration by syringe, intravenous injection or infusion pump is necessary, a vial should be used. 

Before first use, the pen must be stored at room temperature for 1 to 2 hours. 

Inspect the cartridge before use. It must only be used if the solution is clear, colourless, with no solid 

particles visible, and if it is of water-like consistency. Since Apidra is a solution, it does not require 

resuspension before use. 

Empty pens must never be reused and must be properly discarded. 

To prevent any kind of contamination, the use of the pre-filled pen should remain strictly for a single 

patient use. 

Insulin label must always be checked before each injection to avoid medication errors between insulin 

glulisine and other insulins (see section 4.4). 

 

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 of this SPC for instructions on how to store SoloStar. 

 

If SoloStar is in cool storage, it should be taken out 1 to 2 hours before you inject 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. 

 

Pen needle (not included) Pen body Pen cap 

Outer 

needle 

cap 

Inner 

needle 

cap 

 

Needle 

 

Protective seal 

Rubber seal 

Insulin reservoir 

Dosage 

selector 

Dose 

window 

Injection 

button 



17 

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. The Apidra SoloStar 

is blue. It has a dark blue injection button with a raised ring on the top. After removing the pen cap, the 

appearance of insulin should also be checked: the insulin solution must be clear, colourless, with no 

solid particles visible, and must have a water-like consistency. 

 

Step 2 Attach the needle 

 

Only needles that are compatible for use with SoloStar should be used. 

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. 



18 

 

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 

must not be reused. 

 

Special caution must be taken when removing and disposing 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) 

 

Apidra 100 Units/ml solution for injection in a vial 

EU/1/04/285/001-004 

 

Apidra 100 Units/ml solution for injection in a cartridge 

EU/1/04/285/005-012 

 

Apidra SoloStar 100 Units/ml solution for injection in a pre-filled pen 

EU/1/04/285/029-036 

 

 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 

 

Date of first authorisation: 27 September 2004 

Date of latest renewal: 20 August 2009 

 

 

10. DATE OF REVISION OF THE TEXT 

 

Detailed information on this product is available on the website of the European Medicines Agency 

http://www.ema.europa.eu/ 



19 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX II 

 

A. MANUFACTURER(S) OF THE BIOLOGICAL ACTIVE 

SUBSTANCE 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 

 



20 

A. MANUFACTURER(S) OF THE BIOLOGICAL ACTIVE SUBSTANCE AND 

MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 

 

Name and address of the manufacturer(s) of the biological active substance 

 

Sanofi-Aventis Deutschland GmbH 

Industriepark Höchst, D-65926 Frankfurt 

Germany 

 

Name and address of the manufacturer(s) responsible for batch release 

 

Sanofi-Aventis Deutschland GmbH 

Industriepark Höchst, D-65926 Frankfurt 

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 dates for submission of a PSUR and the update of a RMP coincide, they can be submitted at the 

same time. 



21 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX III 

 

LABELLING AND PACKAGE LEAFLET 



22 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

A. LABELLING 

 

 



23 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

OUTER CARTON (10 ml vial) 

 

 

1. NAME OF THE MEDICINAL PRODUCT  

 

Apidra 100 Units/ml, solution for injection in a vial 

Insulin glulisine 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each ml contains 100 Units insulin glulisine (equivalent to 3.49 mg). 

Each vial contains 10 ml of solution for injection, equivalent to 1000 Units. 

 

 

3. LIST OF EXCIPIENTS 

 

Also contains: metacresol, sodium chloride, trometamol, polysorbate 20, concentrated hydrochloric 

acid, sodium hydroxide, water for injections (see leaflet for further information). 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Solution for injection in a vial. 

1 vial of 10ml. 

2 vials of 10ml. 

4 vials of 10ml. 

5 vials of 10ml. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

Subcutaneous or intravenous 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 

 



24 

 

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. 

 

After first use: The product may be stored for a maximum of 4 weeks below 25°C. 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/1/04/285/001 1 vial of 10ml 

EU/1/04/285/002 2 vials of 10ml. 

EU/1/04/285/003 4 vials of 10ml 

EU/1/04/285/004 5 vials of 10ml. 

 

 

13. BATCH NUMBER 

 

BN  

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Apidra 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC: 



25 

SN: 

NN: 



26 

 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 

 

LABEL (10 ml vial) 

 

 

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 

 

Apidra 100 Units/ml solution for injection 

 

Insulin glulisine 

 

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 



27 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

OUTER CARTON (cartridge) 

 

 

1. NAME OF THE MEDICINAL PRODUCT  

 

Apidra 100 Units/ml, solution for injection in a cartridge 

Insulin glulisine 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each ml contains 100 Units insulin glulisine (equivalent to 3.49 mg). 

 

 

3. LIST OF EXCIPIENTS 

 

Also contains: metacresol, sodium chloride, trometamol, polysorbate 20, concentrated hydrochloric 

acid, sodium hydroxide, water for injections (see leaflet for further information). 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Solution for injection in a cartridge. 

1 cartridge of 3ml. 

3 cartridges of 3ml. 

4 cartridges of 3ml. 

5 cartridges of 3ml. 

6 cartridges of 3ml. 

8 cartridges of 3ml. 

9 cartridges of 3ml. 

10 cartridges of 3ml. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

The Apidra cartridges are to be used only with the pens: ClikSTAR, Tactipen, Autopen 24, AllStar, 

AllStar PRO, JuniorSTAR.  

Not all of these pens may be marketed in your country. 

 

Read the package leaflet before use. 

Subcutaneous 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. 

 

 



28 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

Use only clear and colourless solutions. 

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 

 

 

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. 

 

After first use: 

The product may be stored for a maximum of 4 weeks below 25°C. Do not refrigerate. Keep the 

cartridge inserted in the pen protected 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/1/04/285/005 1 cartridge of 3ml 

EU/1/04/285/006 3 cartridges of 3ml. 

EU/1/04/285/007 4 cartridges of 3ml. 

EU/1/04/285/008 5 cartridges of 3ml. 

EU/1/04/285/009 6 cartridges of 3ml. 

EU/1/04/285/010 8 cartridges of 3ml. 

EU/1/04/285/011 9 cartridges of 3ml. 

EU/1/04/285/012 10 cartridges of 3ml. 

 

 

13. BATCH NUMBER 

 

BN 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 



29 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Apidra 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC: 

SN: 

NN: 

 

 



30 

 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 

 

LABEL (cartridge) 

 

 

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 

 

Apidra 100 Units/ml solution for injection 

 

Insulin glulisine 

 

Subcutaneous use Abbreviation authorised for multilingual pack 

 

 

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 



31 

 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

ALUMINIUM FOIL USED FOR SEALING TRANSPARENT PLASTIC TRAY 

CONTAINING THE CARTRIDGE 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Apidra 100 Units/ml solution for injection in a cartridge 

Insulin glulisine 

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Sanofi-Aventis Deutschland GmbH 

 

 

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. 



32 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

OUTER CARTON (PRE-FILLED PEN for SoloStar) 

 

 

1. NAME OF THE MEDICINAL PRODUCT  

 

Apidra SoloStar 100 Units/ml solution for injection in a pre-filled pen 

 

Insulin glulisine 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each ml contains 100 Units insulin glulisine (equivalent to 3.49 mg). 

 

 

3. LIST OF EXCIPIENTS 

 

Also contains: metacresol, sodium chloride, trometamol, polysorbate 20, concentrated hydrochloric 

acid, sodium hydroxide, water for injections (see leaflet for further information). 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Solution for injection in a pre-filled pen. 

1 pen of 3 ml. 

3 pens of 3 ml. 

4 pens of 3 ml. 

5 pens of 3 ml. 

6 pens of 3 ml. 

8 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. 

 

 

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. 

 

 



33 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

Use only clear and colourless solutions. 

 

Only use needles that are compatible for use with SoloStar. 

 

8. EXPIRY DATE 

 

EXP 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

Unopened 

Store in a refrigerator. 

Do not freeze. 

Keep the pre-filled pen in the outer carton in order to protect from light. 

 

After its first use, the product may be stored for a maximum of 4 weeks below 25°C. Do not refrigerate. 

Keep the pen protected 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/1/04/285/029 1 pen of 3 ml. 

EU/1/04/285/030 3 pens of 3 ml. 

EU/1/04/285/031 4 pens of 3 ml. 

EU/1/04/285/032 5 pens of 3 ml. 

EU/1/04/285/033 6 pens of 3 ml. 

EU/1/04/285/034 8 pens of 3 ml. 

EU/1/04/285/035 9 pens of 3 ml. 

EU/1/04/285/036 10 pens of 3 ml. 

 

 

13. BATCH NUMBER 

 

BN 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 



34 

 

Open here 

 

 

16. INFORMATION IN BRAILLE 

 

Apidra SoloStar 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC: 

SN: 

NN: 

 



35 

 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 

 

PEN LABEL (pre-filled pen SoloStar) 

 

 

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 

 

Apidra SoloStar 100 Units/ml solution for injection 

 

Insulin glulisine 

 

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 

 

 



36 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

B. PACKAGE LEAFLET 

 



37 

Package leaflet: Information for the user 

 

Apidra 100 Units/ml solution for injection in a vial 

Insulin glulisine 

 

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. See section 4. 

 

What is in this leaflet 

1. What Apidra is and what it is used for 

2. What you need to know before you use Apidra 

3. How to use Apidra 

4. Possible side effects 

5. How to store Apidra 

6. Contents of the pack and other information 

 

 

1. What Apidra is and what it is used for 

 

Apidra is an antidiabetic agent, used to reduce high blood sugar in patients with diabetes mellitus; it 

may be given to adults, adolescents and children, 6 years of age and older. Diabetes mellitus is a disease 

where your body does not produce enough insulin to control the level of blood sugar. 

 

It is made by biotechnology. It has a rapid onset within 10-20 minutes and a short duration, about 4 

hours. 

 

 

2. What you need to know before you use Apidra 

 

Do not use Apidra 

 

- If you are allergic to insulin glulisine or any of the other ingredients of this medicine (listed in 

section 6). 

- If your blood sugar is too low (hypoglycaemia), follow the guidance for hypoglycaemia (see box 

at the end of this leaflet). 

 

Warnings and precautions 

 

Talk to your doctor, pharmacist or nurse before using Apidra. 

Follow closely the instructions for dose, monitoring (blood tests), diet and physical activity (physical 

work and exercise) as discussed with your doctor. 

 

Special patient groups 

If you have liver or kidney problems, speak to your doctor as you may need a lower dose. 

 

There is insufficient clinical information on the use of Apidra in children younger than the age of 

6 years. 

 



38 

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 extra 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 Apidra 

 

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 dose 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), 

- sulphonamide 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), 



39 

- somatropin (growth hormone), 

- sympathomimetic medicines (such as epinephrine [adrenaline], salbutamol, terbutaline used to 

treat asthma), 

- thyroid hormones (used to treat 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. 

 

Apidra 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 

dose may need to be changed during pregnancy and after giving birth. Careful control of your diabetes, 

and prevention of hypoglycaemia, is important for the health of your baby. 

 

There are no or limited data on the use of Apidra in pregnant women. 

 

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). 

 

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 Apidra 

 

This medicine contains less than 1 mmol (23 mg) sodium per dose, i.e. it is essentially ‘sodium-free’. 

 



40 

Apidra contains metacresol 

 

Apidra contains metacresol, which may cause allergic reactions. 

 

 

3. How to use Apidra 

 

Dose 

 

Always use this medicine exactly as your doctor 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 and your previous insulin 

usage, your doctor will determine how much Apidra you will need. 

 

Apidra is a short-acting insulin. Your doctor may tell you to use it in combination with an intermediate, 

long-acting insulin, a basal insulin or with tablets used to treat high blood sugar levels. 

 

If you switch from another insulin to insulin glulisine, your dosage may have to be adjusted by your 

doctor. 

 

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 

 

Apidra is injected under the skin (subcutaneously). It may also be given intravenously by healthcare 

professionals under close supervision by a doctor. 

 

Your doctor will show you in which area of the skin you should inject Apidra. Apidra can be injected in 

the abdominal wall, the thigh or upper arm or by continuous infusion in the abdominal wall. The effect 

will be slightly quicker if the insulin is injected into your abdomen. As for all insulins, injection sites and 

infusion sites within an-injection area (abdomen, thigh or upper arm) must be rotated from one injection 

to the next. 

 

Frequency of administration 

 

Apidra should be taken shortly (0-15 minutes) before or soon after meals. 

 

Instructions for proper use 

 

How to handle the vials 

 

Apidra vials are for use with insulin syringes with the corresponding unit scale and for use with an 

insulin pump system. 

 

Look at the vial before you use it. Only use it if the solution is clear, colourless and has no visible 

particles in it. 

Do not shake or mix it before use. 

 

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 

Apidra, have it checked by your doctor or pharmacist. 

 



41 

If you have to mix two types of insulin 

 

Apidra must not be mixed with any preparation other than NPH human insulin. 

 

If Apidra is mixed with NPH human insulin, Apidra should be drawn into the syringe first. Injection 

should be given immediately after mixing. 

 

How to handle an infusion pump system 

 

Before using Apidra in the pump system you should have been given detailed instructions on how to use 

the pump system. In addition, you should have been provided with information about what to do if you 

become ill or if your blood sugar levels get too high or too low, or if the pump system fails.  

Use the pump system recommended by your doctor. Read and follow the instructions that come with 

your insulin infusion pump. Follow your doctor’s instructions about the basal infusion rate and the 

mealtime insulin boluses to be taken. Measure your blood sugar level regularly to make sure you get the 

benefit of the insulin infusion and to make sure that the pump is working properly. 

 

Change the infusion set and reservoir at least every 48 hours using aseptic technique. These instructions 

may differ from the instructions that come with your insulin infusion pump. When you use Apidra in the 

pump system, it is important that you always follow these specific instructions. Failure to follow these 

specific instructions may lead to serious adverse events. 

 

Apidra must never be mixed with diluents or any other insulin when used in a pump. 

 

What to do if the pump system fails or when the pump is used incorrectly 

 

Pump or infusion set problems or using the pump incorrectly can result in you not getting enough 

insulin. This can quickly cause you to have high blood sugar and diabetic ketoacidosis (build-up of acid 

in the blood because the body is breaking down fat instead of sugar).  

If your blood sugar level starts to rise, contact your doctor, pharmacist or nurse as soon as possible. 

They will tell you what needs to be done. 

You may need to use Apidra with syringes or pens. You should always have an alternative insulin 

delivery system available for injection under the skin in case the pump system fails. 

 

If you use more Apidra than you should 

 

- If you have injected too much Apidra, 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 Apidra 

 

- If you have missed a dose of Apidra 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 Apidra 

 

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 Apidra without speaking 

to a doctor, who will tell you what needs to be done. 

 



42 

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 Apidra and 

other insulins. 

 

 

4. Possible side effects 

 

Like all medicines, this medicine can cause side effects, although not everybody gets them. 

 

Serious side effects 

 

Hypoglycaemia (low blood sugar) can be very serious. Hypoglycaemia is a very commonly reported 

side effect (may affect more than 1 in 10 people). Hypoglycaemia (low blood sugar) means that there 

is not enough sugar in the blood. If your blood sugar level falls too much you may become 

unconscious. Serious hypoglycaemia may cause brain damage and may be life-threatening. If you have 

symptoms of low blood sugar, take actions to increase your blood sugar level immediately. See the box 

at the end of this leaflet for important further information about hypoglycaemia and its treatment. 

 

If you experience the following symptoms, contact your doctor immediately: 

Systemic allergic reactions are side effects reported uncommonly (may affect up to 1 in 100 people) 

Generalised allergy to insulin: Associated symptoms may include large-scale skin reactions (rash and 

itching all over the body), severe swelling of skin or mucous membranes (angioedema), shortness of 

breath, a fall in blood pressure with rapid heartbeat and sweating. These could be symptoms of severe 

cases of generalised allergy to insulin, including anaphylactic reaction, which may be 

life-threatening. 

 

Hyperglycaemia (high blood sugar) means that there is too much sugar in the blood. The frequency 

of hyperglycaemia cannot be estimated. If your blood sugar level is too high, this tells you that you may 

need more insulin than you have injected.  

Hyperglycaemia can cause diabetic ketoacidosis (build-up of acid in the blood because the body is 

breaking down fat instead of sugar). 

These are serious side effects. 

These conditions can happen when there are problems with the infusion pump or when the pump 

system is used incorrectly. 

This means you may not always get enough insulin to treat your diabetes. 

If this happens you must seek urgent medical help. 

Always have available an alternative insulin delivery system for injection under the skin (see 

section 3 under “How to handle an infusion pump system” and “What to do if the pump system fails or 

when the pump is used incorrectly”). 

For more information on signs and symptoms of hyperglycaemia refer to the box at the end of this 

leaflet. 

 

Other side effects 

Common reported side effects (may affect up to 1 in 10 people) 

• Skin and allergic reactions at the injection site 

Reactions at the injection site may occur (such as reddening, unusually intense pain on injection, itching, 

hives, swelling or inflammation). They can also spread around the injection site. Most minor reactions 

to insulins usually resolve in a few days to a few weeks. 

 

Rare reported side effect (may affect up to 1 in 1,000 people) 

• Skin changes at the injection site (lipodystrophy) 



43 

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. 

 

Side effects where the frequency cannot be estimated from the available data 

• 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. 

 

Reporting of side effects 

 

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side 

effects not listed in this leaflet. You can also report side effects directly via the national reporting system 

listed in Appendix V. By reporting side effects you can help provide more information on the safety of 

this medicine. 

 

 

5. How to store Apidra 

 

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 Apidra 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 below 25°C away 

from direct heat or direct light. 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 use this medicine if it does not appear clear and colourless. 

 

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 Apidra contains 

 

- The active substance is insulin glulisine. Each ml of the solution contains 100 Units of insulin 

glulisine (equivalent to 3.49 mg). Each vial contains 10 ml of solution for injection, equivalent to 

1000 Units. 

- The other ingredients are: metacresol (see section 2 under “Apidra contains metacresol”), sodium 

chloride (see section 2 under “Important information about some of the ingredients of Apidra”), 

trometamol, polysorbate 20, concentrated hydrochloric acid, sodium hydroxide, water for 

injections. 

 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc
http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


44 

What Apidra looks like and contents of the pack 

 

Apidra 100 Units/ml solution for injection in a vial is a clear, colourless, aqueous solution with no 

particles visible. 

 

Each vial contains 10 ml solution (1000 Units). Packs of 1, 2, 4 and 5 vials are available. Not all pack 

sizes may be marketed. 

 

Marketing Authorisation Holder and Manufacturer 

 

Marketing Authorisation Holder: 

Sanofi-Aventis Deutschland GmbH 

D-65926 Frankfurt am Main 

Germany 

 

Manufacturer: 

Sanofi-Aventis Deutschland GmbH 

Industriepark Höchst, D-65926 Frankfurt 

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 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 A/S 

Tlf: +45 45 16 70 00 

 

Malta 

Sanofi S.p.A. 

Tel: +39 02 39394275 

 

Deutschland 

Sanofi-Aventis Deutschland GmbH 

Tel.: 0800 52 52 010 

Tel. aus dem Ausland: +49 69 305 21 131 

 

Nederland 

sanofi-aventis Netherlands B.V. 

Tel: +31 20 245 4000 

 

 

Eesti 

sanofi-aventis Estonia OÜ 

Tel: +372 627 34 88 

 

Norge 

sanofi-aventis 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 

 



45 

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  

 

 

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 a person with diabetes. 

 

 

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, 



46 

- 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 

Apidra"). 

 

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 Apidra"). 

 

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 

 



47 

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 and 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, 

- you have had diabetes for a long time, 

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

Apidra). 

 

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. 

 



48 

THE FOLLOWING INFORMATION IS INTENDED FOR HEALTHCARE 

PROFESSIONALS ONLY: 

 

Apidra can be administered intravenously, which should be carried out by healthcare professionals. 

Instruction for intravenous administration 

Apidra should be used at a concentration of 1 Unit/ml insulin glulisine in infusion systems with sodium 

chloride 9 mg/ml (0.9%) solution for infusion with or without 40 mmol/l potassium chloride using 

coextruded polyolefin/polyamide plastic infusion bags with a dedicated infusion line. Insulin glulisine 

for intravenous use at a concentration of 1 Unit/ml is stable at room temperature for 48 hours. 

 

After dilution for intravenous use, the solution should be inspected visually for particulate matter prior 

to administration. Never use the solution if it has become cloudy or contains particles; use it only if it is 

clear and colourless. 

 

Apidra was found to be incompatible with Glucose 5% solution and Ringer’s solution and, therefore, 

must not be used with these solution fluids. The use of other solutions has not been studied. 

 



49 

Package leaflet: Information for the user 

 

Apidra 100 Units/ml solution for injection in a cartridge 

Insulin glulisine 

 

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. See section 4. 

 

What is in this leaflet 

1. What Apidra is and what it is used for 

2. What you need to know before you use Apidra 

3. How to use Apidra 

4. Possible side effects 

5. How to store Apidra 

6. Contents of the pack and other information 

 

 

1. What Apidra is and what it is used for 

 

Apidra is an antidiabetic agent, used to reduce high blood sugar in patients with diabetes mellitus; it 

may be given to adults, adolescents and children, 6 years of age and older. Diabetes mellitus is a disease 

where your body does not produce enough insulin to control the level of blood sugar. 

 

It is made by biotechnology. It has a rapid onset within 10-20 minutes and a short duration, about 4 

hours. 

 

 

2. What you need to know before you use Apidra 

 

Do not use Apidra 

 

- If you are allergic to insulin glulisine or any of the other ingredients of this medicine (listed in 

section 6). 

- If your blood sugar is too low (hypoglycaemia), follow the guidance for hypoglycaemia (see box 

at the end of this leaflet). 

 

Warnings and precautions 

 

Apidra in cartridges is only suitable for injecting just under the skin using a reusable pen (see also 

section 3). Speak to your doctor if you need to inject your insulin by another method. 

 

Talk to your doctor, pharmacist or nurse before using Apidra. 

Follow closely the instructions for dose, monitoring (blood tests), diet and physical activity (physical 

work and exercise) as discussed with your doctor. 

 

Special patient groups 

If you have liver or kidney problems, speak to your doctor as you may need a lower dose. 

 



50 

There is insufficient clinical information on the use of Apidra in children younger than the age of 

6 years. 

 

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, needles, 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 extra 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 Apidra 

 

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 dose 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), 

- sulphonamide 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), 



51 

- 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), 

- sympathomimetic medicines (such as epinephrine [adrenaline], salbutamol, terbutaline used to 

treat asthma), 

- thyroid hormones (used to treat 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. 

 

Apidra 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 

dose may need to be changed during pregnancy and after giving birth. Careful control of your diabetes, 

and prevention of hypoglycaemia, is important for the health of your baby. 

 

There are no or limited data on the use of Apidra in pregnant women. 

 

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).  

 

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. 

 



52 

Important information about some of the ingredients of Apidra 

 

This medicine contains less than 1 mmol (23 mg) sodium per dose, i.e. it is essentially ‘sodium-free’. 

 

Apidra contains metacresol 

 

Apidra contains metacresol, which may cause allergic reactions. 

 

 

3. How to use Apidra 

 

Dose 

 

Always use this medicine exactly as your doctor 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 and your previous insulin 

usage, your doctor will determine how much Apidra you will need. 

 

Apidra is a short-acting insulin. Your doctor may tell you to use it in combination with an intermediate, 

long acting insulin, a basal insulin or with tablets used to treat high blood sugar levels. 

 

If you switch from another insulin to insulin glulisine, your dosage may have to be adjusted by your 

doctor. 

 

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 

 

Apidra is injected under the skin (subcutaneously). 

 

Your doctor will show you in which area of the skin you should inject Apidra. Apidra can be injected in 

the abdominal wall, the thigh or upper arm or by continuous infusion in the abdominal wall. The effect 

will be slightly quicker if the insulin is injected into your abdomen. As for all insulins, injection sites and 

infusion sites within an-injection area (abdomen, thigh or upper arm) must be rotated from one injection 

to the next. 

 

Frequency of administration 

 

Apidra should be taken shortly (0-15 minutes) before or soon after meals. 

 

Instructions for proper use  

 

How to handle the cartridges 

 

Apidra in cartridges is only suitable for injecting just under the skin using a reusable pen. Speak to your 

doctor if you need to inject your insulin by another method. 

To ensure you get the accurate dose, the Apidra cartridges are to be used only with the following pens: 

- JuniorSTAR which delivers doses in steps of 0.5 units  

- ClikSTAR, Tactipen, Autopen 24, AllStar or AllStar PRO 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. 



53 

 

The manufacturer’s instructions for using the pen must be followed carefully for loading the cartridge, 

attaching the needle, and administering the insulin injection. 

 

Before insertion of the cartridge into the reusable pen, the cartridge must be stored at room temperature 

for 1 to 2 hours. 

 

Look at the cartridge before you use it. Only use it if the solution is clear, colourless and has no visible 

particles in it. 

 

Do not shake or mix it before use. 

 

Special care before injection 

 

Air bubbles must be removed from the cartridge before injection (see instructions for using the pen). 

Empty cartridges must not be refilled. 

 

To prevent any kind of contamination, the reusable pen should be used only by you. 

 

Problems with the insulin 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 you use more Apidra than you should 

 

- If you have injected too much Apidra, 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 Apidra 

 

- If you have missed a dose of Apidra 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 Apidra 

 

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 Apidra 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 Apidra and 

other insulins.  

 

 



54 

4. Possible side effects 

 

Like all medicines, this medicine can cause side effects, although not everybody gets them. 

 

Serious side effects 

 

Hypoglycaemia (low blood sugar) can be very serious. Hypoglycaemia is a very commonly reported 

side effect (may affect more than 1 in 10 people). Hypoglycaemia (low blood sugar) means that there 

is not enough sugar in the blood. If your blood sugar level falls too much you may become 

unconscious. Serious hypoglycaemia may cause brain damage and may be life-threatening. If you have 

symptoms of low blood sugar, take actions to increase your blood sugar level immediately. See the box 

at the end of this leaflet for important further information about hypoglycaemia and its treatment. 

 

If you experience the following symptoms, contact your doctor immediately: 

Systemic allergic reactions are side effects reported uncommonly (may affect up to 1 in 100 people). 

Generalised allergy to insulin: Associated symptoms may include large-scale skin reactions (rash and 

itching all over the body), severe swelling of skin or mucous membranes (angioedema), shortness of 

breath, a fall in blood pressure with rapid heartbeat and sweating. These could be symptoms of severe 

cases of generalised allergy to insulin, including anaphylactic reaction, which may be 

life-threatening. 

 

Hyperglycaemia (high blood sugar) means that there is too much sugar in the blood. The frequency 

of hyperglycaemia cannot be estimated. If your blood sugar level is too high, this tells you that you may 

need more insulin than you have injected. This can be serious if your blood glucose level becomes very 

high. 

For more information on signs and symptoms of hyperglycaemia refer to the box at the end of this 

leaflet. 

 

Other side effects 

 

Common reported side effects (may affect up to 1 in 10 people) 

• Skin and allergic reactions at the injection site 

Reactions at the injection site may occur (such as reddening, unusually intense pain on injection, itching, 

hives, swelling or inflammation). They can also spread around the injection site. Most minor reactions 

to insulins usually resolve in a few days to a few weeks. 

 

Rare reported side effect (may affect up to 1 in 1,000 people) 

• 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. 

 

Side effects where the frequency cannot be estimated from the available data 

• 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. 

 

Reporting of side effects 

 

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side 

effects not listed in this leaflet. You can also report side effects directly via the national reporting system 

listed in Appendix V. By reporting side effects you can help provide more information on the safety of 

this medicine. 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc
http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


55 

 

 

5. How to store Apidra 

 

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 Apidra 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) may be stored for a maximum of 4 weeks below 25°C, away from 

direct heat or direct light and must not be stored in a refrigerator. Do not use it after this time period. 

Do not use this medicine if it does not appear clear and colourless. 

 

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 Apidra contains 

 

− The active substance is insulin glulisine. Each ml of the solution contains 100 Units of insulin 
glulisine (equivalent to 3.49 mg). Each cartridge contains 3 ml of solution for injection, equivalent 

to 300 Units. 

− The other ingredients are: metacresol (see section 2 under “Apidra contains metacresol”), sodium 
chloride (see section 2 under “Important information about some of the ingredients of Apidra”), 

trometamol, polysorbate 20, concentrated hydrochloric acid, sodium hydroxide, water for 

injections 

 

What Apidra looks like and contents of the pack 

 

Apidra 100 Units/ml solution for injection in a cartridge is a clear, colourless, aqueous solution with no 

particles visible. 

 

Each cartridge contains 3 ml solution (300 Units). Packs of 1, 3, 4, 5, 6, 8, 9 and 10 cartridges are 

available. Not all pack sizes may be marketed. 

 

Marketing Authorisation Holder and Manufacturer 

 

Marketing Authorisation Holder: 

Sanofi-Aventis Deutschland GmbH 

D-65926 Frankfurt am Main 

Germany. 

 

Manufacturer: 

Sanofi-Aventis Deutschland GmbH 

Industriepark Höchst, D-65926 Frankfurt 

Germany 



56 

 

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 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 A/S 

Tlf: +45 45 16 70 00 

 

Malta 

Sanofi S.p.A. 

Tel: +39 02 39394275 

 

Deutschland 

Sanofi-Aventis Deutschland GmbH 

Tel.: 0800 52 52 010 

Tel. aus dem Ausland: +49 69 305 21 131 

 

Nederland 

sanofi-aventis Netherlands B.V. 

Tel: +31 20 245 4000 

 

 

Eesti 

sanofi-aventis Estonia OÜ 

Tel: +372 627 34 88 

 

Norge 

sanofi-aventis 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 

 



57 

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 

 

 

Other source of information 

Detailed information on this medicine is available on the European Medicines Agency web site: 

http://www.ema.europa.eu/ 



58 

 

HYPERGLYCAEMIA AND HYPOGLYCAEMIA 

 

Always carry some sugar (at least 20 grams) with you. 

Carry some information with you to show you are a person with diabetes. 

 

 

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 

Apidra"). 

 

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 Apidra"). 

 

Hypoglycaemia is also more likely to occur if: 

- you have just begun insulin treatment or changed to another insulin preparation, 



59 

- 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 and 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,  

- you have had diabetes for a long time,  

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

Apidra”). 

 

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. 



60 

 Package leaflet: Information for the user 

 

Apidra SoloStar 100 Units/ml solution for injection in a pre-filled pen 

Insulin glulisine 

 

Read carefully all of this leaflet including the Instructions for Use of Apidra SoloStar, pre-filled 

pen, before 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. See section 4. 

 

What is in this leaflet 

1. What Apidra is and what it is used for 

2. What you need to know before you use Apidra 

3. How to use Apidra 

4. Possible side effects 

5. How to store Apidra 

6. Contents of the pack and other information 

 

 

1. What Apidra is and what it used for 

 

Apidra is an antidiabetic agent, used to reduce high blood sugar in patients with diabetes mellitus; it 

may be given to adults, adolescents and children, 6 years of age and older. Diabetes mellitus is a disease 

where your body does not produce enough insulin to control the level of blood sugar. 

 

It is made by biotechnology. It has a rapid onset within 10-20 minutes and a short duration, about 4 

hours. 

 

 

2. What you need to know before you use Apidra 

 

Do not use Apidra 

 

- If you are allergic to insulin glulisine or any of the other ingredients of this medicine (listed in 

section 6). 

- If your blood sugar is too low (hypoglycaemia), follow the guidance for hypoglycaemia (see box 

at the end of this leaflet). 

 

Warnings and precautions 

 

Apidra in a pre-filled pen is only suitable for injecting just under the skin (see also section 3). Speak to 

your doctor if you need to inject your insulin by another method. 

 

Talk to your doctor, pharmacist or nurse before using Apidra. 

Follow closely the instructions for dose, monitoring (blood tests), diet and physical activity (physical 

work and exercise) as discussed with your doctor. 

 

Special patient groups 

If you have liver or kidney problems, speak to your doctor as you may need a lower dose. 

 



61 

There is insufficient clinical information on the use of Apidra in children younger than the age of 

6 years. 

 

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, needles, 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 extra 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 Apidra 

 

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 dose 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), 

- sulphonamide 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), 



62 

- 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), 

- sympathomimetic medicines (such as epinephrine [adrenaline], salbutamol, terbutaline used to 

treat asthma), 

- thyroid hormones (used to treat 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. 

 

Apidra 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 

dose may need to be changed during pregnancy and after giving birth. Careful control of your diabetes, 

and prevention of hypoglycaemia, is important for the health of your baby. 

 

There are no or limited data on the use of Apidra in pregnant women. 

 

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).  

 

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. 

 



63 

Important information about some of the ingredients of Apidra 

 

This medicine contains less than 1 mmol (23 mg) sodium per dose, i.e. it is essentially ‘sodium-free’. 

 

Apidra contains metacresol 

 

Apidra contains metacresol, which may cause allergic reactions. 

 

 

3. How to use Apidra 

 

Dose 

 

Always use this medicine exactly as your doctor 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 and your previous insulin 

usage, your doctor will determine how much Apidra you will need. 

 

 

Apidra is a short-acting insulin. Your doctor may tell you to use it in combination with an intermediate, 

long acting insulin, a basal insulin or with tablets used to treat high blood sugar levels. 

 

If you switch from another insulin to insulin glulisine, your dosage may have to be adjusted by your 

doctor. 

 

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 

 

Apidra is injected under the skin (subcutaneously). 

 

Your doctor will show you in which area of the skin you should inject Apidra. Apidra can be injected in 

the abdominal wall, the thigh or upper arm or by continuous infusion in the abdominal wall. The effect 

will be slightly quicker if the insulin is injected into your abdomen. As for all insulins, injection sites and 

infusion sites within an-injection area (abdomen, thigh or upper arm) must be rotated from one injection 

to the next. 

 

Frequency of administration 

 

Apidra should be taken shortly (0-15 minutes) before or soon after meals. 

 

Instructions for proper use 

 

How to handle SoloStar 

 

SoloStar is a pre-filled disposable pen containing insulin glulisine. Apidra in a pre-filled pen is only 

suitable for injecting just under the skin. Speak to your doctor if you need to inject your insulin by 

another method. 

 

Read carefully the "SoloStar Instructions for use" included in this package leaflet. You must use 

the pen as described in these Instructions for use. 

 



64 

To prevent the possible transmission of disease, each pen must be used by one patient only. 

 

Before use always attach a new needle, and perform a safety test. Only use needles that are compatible 

for use with SoloStar (see “SoloStar Instructions for use”). 

 

Look at the cartridge sealed in the disposable pen injector before you use it. Only use it if the solution is 

clear, colourless and has no visible particles in it. Do not shake or mix it before use. 

 

Always use a new pen if you notice that your blood sugar control is unexpectedly getting worse. If you 

think you may have a problem with SoloStar, please consult your Health Care Professional. 

 

If you use more Apidra than you should 

 

- If you have injected too much Apidra, 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 Apidra 

 

- If you have missed a dose of Apidra 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 Apidra 

 

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 Apidra 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 Apidra and 

other insulins. 

 

 

4. Possible side effects 

 

Like all medicines, this medicine can cause side effects, although not everybody gets them. 

 

Serious side effects 

 

Hypoglycaemia (low blood sugar) can be very serious. Hypoglycaemia is a very commonly reported 

side effect (may affect more than 1 on 10 people). Hypoglycaemia (low blood sugar) means that 

there is not enough sugar in the blood. If your blood sugar level falls too much you may become 

unconscious. Serious hypoglycaemia may cause brain damage and may be life-threatening. If you have 

symptoms of low blood sugar, take actions to increase your blood sugar level immediately. See the box 

at the end of this leaflet for important further information about hypoglycaemia and its treatment. 

 

If you experience the following symptoms, contact your doctor immediately: 

Systemic allergic reactions are side effects reported uncommonly (may affect up to 1 in 100 people). 



65 

Generalised allergy to insulin: Associated symptoms may include large-scale skin reactions (rash and 

itching all over the body), severe swelling of skin or mucous membranes (angioedema), shortness of 

breath, a fall in blood pressure with rapid heartbeat and sweating. These could be symptoms of severe 

cases of generalised allergy to insulin, including anaphylactic reaction, which may be 

life-threatening. 

 

Hyperglycaemia (high blood sugar) means that there is too much sugar in the blood. The frequency 

of hyperglycaemia cannot be estimated. If your blood sugar level is too high, this tells you that you may 

need more insulin than you have injected. This can be serious if your blood glucose level becomes very 

high. 

For more information on signs and symptoms of hyperglycaemia refer to the box at the end of this 

leaflet. 

 

Other side effects 

 

Common reported side effects (may affect up to 1 in 10 people) 

• Skin and allergic reactions at the injection site 

Reactions at the injection site may occur (such as reddening, unusually intense pain on injection, itching, 

hives, swelling or inflammation). They can also spread around the injection site. Most minor reactions 

to insulins usually resolve in a few days to a few weeks. 

 

Rare reported side effect (may affect up to 1 in 1,000 people) 

• 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. 

 

Side effects where the frequency cannot be estimated from the available data 

• 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. 

 

Reporting of side effects 

 

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side 

effects not listed in this leaflet. You can also report side effects directly via the national reporting system 

listed in Appendix V. By reporting side effects you can help provide more information on the safety of 

this medicine. 

 

 

5. How to store Apidra 

 

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 SoloStar 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 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc
http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


66 

Pre-filled pens in use (or carried as a spare) may be stored for a maximum of 4 weeks below 25°C and 

away from direct heat or direct light. The pen in use must not be stored in a refrigerator. 

Do not use it after this time period. 

 

Do not use this medicine if it does not appear clear and colourless. 

 

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 Apidra contains 

 

- The active substance is insulin glulisine. Each ml of the solution contains 100 Units of insulin 

glulisine (equivalent to 3.49 mg). 

- The other ingredients are: metacresol (see section 2 under “Apidra contains metacresol”), sodium 

chloride (see section 2 under “Important information about some of the ingredients of Apidra”), 

trometamol, polysorbate 20, concentrated hydrochloric acid, sodium hydroxide, water for 

injections 

 

What Apidra looks like and contents of the pack 

 

Apidra SoloStar 100 Units/ml solution for injection in a pre-filled pen. It is a clear, colourless, aqueous 

solution with no particles visible. 

 

Each pen contains 3 ml solution, equivalent to 300 Units. Packs of 1, 3, 4, 5, 6, 8, 9 and 10 pre-filled 

pens are available. Not all pack sizes may be marketed. 

 

Marketing Authorisation Holder and Manufacturer 

 

Marketing Authorisation Holder: 

Sanofi-Aventis Deutschland GmbH 

D-65926 Frankfurt am Main 

Germany 

 

Manufacturer: 

Sanofi-Aventis Deutschland GmbH 

Industriepark Höchst, D- 65926 Frankfurt 

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 BULGARIA EOOD 

Тел.: +359 (0)2 970 53 00 

 

Luxembourg/Luxemburg 

Sanofi Belgium  

Tél/Tel: +32 (0)2 710 54 00 (Belgique/Belgien) 

 



67 

Česká republika 

sanofi-aventis, s.r.o. 

Tel: +420 233 086 111 

 

Magyarország 

SANOFI-AVENTIS Zrt. 

Tel.: +36 1 505 0050 

 

Danmark 

Sanofi A/S 

Tlf: +45 45 16 70 00 

 

Malta 

Sanofi S.p.A. 

Tel: +39 02 39394275 

 

Deutschland 

Sanofi-Aventis Deutschland GmbH 

Tel.: 0800 52 52 010 

Tel. aus dem Ausland: +49 69 305 21 131 

 

Nederland 

sanofi-aventis Netherlands B.V. 

Tel: +31 20 245 4000 

 

 

Eesti 

sanofi-aventis Estonia OÜ 

Tel: +372 627 34 88 

 

Norge 

sanofi-aventis 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 

 

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 

 

 



68 

This leaflet was last revised in 

 

 

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 a person with diabetes. 

 

 

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 

Apidra"). 

 

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, 



69 

- 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 Apidra"). 

 

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 and 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,  

- you have had diabetes for a long time,  

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

Apidra”). 

 

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. 

 



70 

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. 



71 

 

Apidra SoloStar solution for injection in a pre-filled pen. INSTRUCTIONS FOR USE 

 

SoloStar is a pre-filled 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. 

 

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 are compatible 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. The Apidra SoloStar 

is blue. It has a dark blue injection button with a raised ring on the top. 

 

B. Take off the pen cap. 

 

C. Check the appearance of your insulin. Apidra is a clear insulin. Do not use this SoloStar if the 

insulin is cloudy, coloured or has particles. 

 

Pen cap Pen needle (not included) Pen body 

Outer  

needle 

cap 

Inner 

needle 

cap Rubber seal 

Protective seal 

Needle 

Insulin reservoir 

Dosage 

selector 

Dose  

window 

Injection 

button 



72 

Step 2.  Attach the needle 

 

Always use a new sterile needle for each injection. This helps prevent contamination, and potential 

needle blocks. 

 

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. 

 

 

 
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. 

 

Keep Discard 



73 

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. 

 

 
• 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. 

 

 



74 

 

 
 

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 has 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 (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, as instructed by your doctor, pharmacist or nurse. 

 

C. Always put the pen cap back on the pen, then store the pen until your next injection. 

 

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 to 

room temperature. Cold insulin is more painful to inject. 

 

Discard your used SoloStar as required by your local authorities. 

10 secs 



75 

 

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. 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER(S) OF THE BIOLOGICAL ACTIVE SUBSTANCE 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