natgillin/translations-raw huggingface dataset:
NovoMix 30
The influence of different injection sites on the absorption of NovoMix 30 has not been investigated.
NovoMix 30
NovoMix 30 should never be administered intravenously.
. (
Renal or hepatic impairment may reduce the patient’ s insulin requirements.
10
No studies have been performed in children under the age of 6 years.
5. 1).
Dose recommendation:
NovoMix 30.
Dosage of NovoMix 30 is individual and determined in accordance with the needs of the patient.
$2, NovoMix 30,,
For patients with type 2 diabetes, the recommended starting dose of NovoMix 30 is 6 U at breakfast and 6 U at dinner (evening meal).
NovoMix 30 6 U
NovoMix 30 can also be initiated once daily with 12 U at dinner (evening meal).
6U
When using
(
2 NovoMix 30 once daily, it is generally recommended to move to twice-daily when reaching 30 units by splitting the dose into equal breakfast and dinner doses.
(NovoMix 30
If twice daily dosing with NovoMix 30 results in recurrent daytime hypoglycaemic episodes, the morning dose can be split into morning and lunchtime doses (thrice daily dosing).
,
The following titration guideline is recommended for dose adjustments:
30 U, NovoMix 30
Pre-meal blood glucose level
NovoMix 30.%
NovoMix 30 dose adjustment
< 4, 4 mmol/ l
< 4.4 mmol/ l
< 80 mg/ dL
< 80 mg/ dL
NovoMix
4.4 – 6.1 mmol/ l
30 - 2U
80 – 110 mg/ dL
4, 4 – 6, 1 mmol/ l 6, 2 – 7, 8 mmol/ l 7, 9 – 10 mmol/ l > 10 mmol/ l
6.2 – 7.8 mmol/ l 7.9 – 10 mmol/ l > 10 mmol/ l
80 – 110 mg/ dL 111 – 140 mg/ dL 141 – 180 mg/ dL > 180 mg/ dL
111 – 140 mg/ dL 141 – 180 mg/ dL > 180 mg/ dL
+2U +4U +6U
+2U +4U +6U
)
The dose should not be increased if hypoglycaemia occurred within these days.
% HbA1c. *.
Dose adjustments can be made once a week until target HbA1c is reached.
NovoMix 30
The combination of NovoMix 30 with pioglitazone should only be considered following clinical evaluation of the patient’ s risk of developing signs or symptoms of fluid-related adverse events.
NovoMix 30
The initiation of NovoMix 30 should be undertaken cautiously titrating to the lowest dose required to achieve glycaemic control (see section 4.4)
0, 5
In patients with type 1 diabetes the individual insulin requirement is usually between 0.5 and 1.0 Units/ kg/ day.
NovoMix 30
NovoMix 30 may fully or partially meet this requirement.
NovoMix 30
When transferring a patient from biphasic human insulin to NovoMix 30, start with the same dose and regimen.
NovoMix 30
NovoMix 30 can be used in elderly patients; however there is limited experience with the use of NovoMix 30 in combination with OADs in patients older than 75 years.
• (•
4.3 Contraindications
+
• Hypersensitivity to the active substance or to any of the excipients • Hypoglycaemia.
3
The use of dosages which are inadequate or discontinuation of treatment, especially in insulin- dependent diabetics, may lead to hyperglycaemia and diabetic ketoacidosis; conditions which are potentially lethal.
4. 4
This may have to be compensated for in the individual patient, through adjustment of insulin dose and/ or food intake.
+ $
Patients, whose blood glucose control is greatly improved, e. g. by intensified insulin therapy, may experience a change in their usual warning symptoms of hypoglycaemia, and should be advised accordingly.
'
3 Tighter control of glucose levels can increase the potential for hypoglycaemic episodes and therefore require special attention during dose intensification as outlined in section 4.2.
NovoMix 30
NovoMix 30 should be administered in immediate relation to a meal.
.)
Concomitant illness, especially infections, usually increases the patient’ s insulin requirements.
(
When patients are transferred between different types of insulin products, the early warning symptoms of hypoglycaemia may change or become less pronounced than those experienced with their previous insulin.
4. 8 -
Changes in strength, brand (manufacturer), type, origin (animal, human, human insulin analogue), and/ or method of manufacture (recombinant DNA versus animal source insulin) may result in the need for a change in dosage.
NovoMix 30 "
Patients taking NovoMix 30 may need a change in dosage from that used with their usual insulin.
.,
Exercise taken immediately after a meal may increase the risk of hypoglycaemia.
,
Insulin suspensions are not to be used in insulin infusion pumps.
.
Reactions usually resolve in a few days to a few weeks.
NovoMix 30,
On rare occasions, injection site reactions may require discontinuation of NovoMix 30.
NovoMix 30
Combination of NovoMix 30 with pioglitazone:
NovoMix 30
Patients should be observed for signs and symptoms of heart failure, weight gain and oedema when NovoMix 30 is used in combination with pioglitazone.
.
4.5 Interaction with other medicinal products and other forms of interaction
,
A number of medicinal products are known to interact with the glucose metabolism.
.
Oral antidiabetic drugs (OAD), octreotide, monoamine oxidase inhibitors (MAOIs), non-selective beta-adrenergic blocking agents, angiotensin converting enzyme (ACE) inhibitors, salicylates, alcohol, anabolic steroids and sulphonamides.
,
Oral contraceptives, thiazides, glucocorticoids, thyroid hormones, sympathomimetics and danazol.
,
Beta-blocking agents may mask the symptoms of hypoglycaemia.
-
Alcohol may intensify and prolong the glucose lowering effect of insulin.
0
4 4.6 Pregnancy and lactation
NovoMix 30
There is limited clinical experience with NovoMix 30 in pregnancy.
.
Animal reproduction studies have not revealed any differences between insulin aspart and human insulin regarding embryotoxicity or teratogenicity.
.
After delivery, insulin requirements return rapidly to pre-pregnancy levels.
NovoMix 30
There are no restrictions on treatment with NovoMix 30 during lactation.
NovoMix 30.
However, the NovoMix 30 dosage may need to be adjusted.
4. 7
4.7 Effects on ability to drive and use machines
1!
This may constitute a risk in situations where these abilities are of special importance (e. g. driving a car or operating machinery).
& * 0
The advisability of driving should be considered in these circumstances.
NovoMix,
4.8 Undesirable effects
,
Severe hypoglycaemia may lead to unconsciousness and/ or convulsions and may result in temporary or permanent impairment of brain function or even death.
.
During clinical trials the overall rates of hypoglycaemia did not differ between patients treated with insulin aspart compared to human insulin.
4. 2.)
Frequencies of adverse drug reactions from clinical trials, which by an overall judgement are considered related to insulin aspart are listed below.
(> 1/ 1 000, < 1/ 100)
The frequencies are defined as:
(> 1/ 10 000,
Uncommon (> 1/ 1,000 ,< 1/100) and rare (> 1/10 ,000, < 1/1,000).
(< 1/ 10 000),
Isolated spontaneous cases are presented as very rare defined as (< 1/ 10,000), including isolated reports.
*
Immune system disorders Uncommon - Urticaria, rash, eruptions
- 0
Generalised hypersensitivity reactions are potentially life threatening.
,
5 Nervous system disorders Rare - Peripheral neuropathy Fast improvement in blood glucose control may be associated with a condition termed acute painful neuropathy, which is usually reversible.
,
These symptoms are usually of transitory nature.
& (
However, intensification of insulin therapy with abrupt improvement in glycaemic control may be associated with worsening of diabetic retinopathy.
-% #
Skin and subcutaneous tissue disorders Uncommon - Lipodystrophy Lipodystrophy may occur at the injection site as a consequence of failure to rotate injection sites within an area.
*
These reactions are usually transitory and normally they disappear during continued treatment.
NovoMix 30
Oedema and weight increase may occur when NovoMix 30 is used in combination with OADs.
mg), *
4.9 Overdose
*
A specific overdose for insulin cannot be defined, however, hypoglycaemia may develop over sequential stages if too high doses relative to the patient’ s requirement are administered:
. 1 *
Upon regaining consciousness administration of oral carbohydrate is recommended for the patient in order to prevent relapse.
5. 1
5.
-! '-
5.1 Pharmacodynamic properties
/ 0
Insulins and analogues for injection, intermediate-acting combined with fast-acting.
% 10% D05.
A10AD05.
NovoMix 30
NovoMix 30 is a biphasic suspension of insulin aspart (rapid-acting human insulin analogue) and protamine-crystallised insulin aspart (intermediate-acting human insulin analogue).
"
6 The blood glucose lowering effect of insulin occurs when the molecules facilitate the uptake of glucose by binding to insulin receptors on muscle and fat cells - and simultaneously inhibit the output of glucose from the liver.
30%
NovoMix 30 is a biphasic insulin, which contains 30% soluble insulin aspart.
"
The maximum effect is exerted between 1 and 4 hours after injection.
"24
The duration of action is up to 24 hours.
NovoMix *
Glucose infusion rate
7 (# *
Hours
30 (---)
Figure 1:
30.
Activity profile of NovoMix 30 (___) and biphasic human insulin 30 (---) in healthy subjects.
,
In a 3 month trial in patients with type 1 and type 2 diabetes NovoMix 30 showed equal control of glycosylated haemoglobin compared to treatment with biphasic human insulin 30.
2, NovoMix 30 #. '
Insulin aspart is equipotent to human insulin on a molar basis.
30,
Compared to biphasic human insulin 30, administration of NovoMix 30 before breakfast and dinner resulted in lower postprandial blood glucose after both meals (breakfast and dinner).
NovoMix 30
A meta-analysis including nine trials in patients with type 1 and type 2 diabetes showed that fasting blood glucose was higher in patients treated with NovoMix 30, than in patients treated with biphasic human insulin 30.
-
In one study, 341 patients with type 2 diabetes were randomised to treatment with NovoMix 30 either alone or in combination with metformin, or to metformin together with sulfonylurea.
16
The primary efficacy variable - HbA1c after 16 weeks of treatment - did not differ between patients with NovoMix 30 combined with metformin and patients with metformin plus sulfonylurea.
(116
In one study, patients with type 2 diabetes, insufficiently controlled on oral hypoglycaemic agents alone, were randomised to treatment with twice daily NovoMix 30 (117 patients) or once daily insulin glargine (116 patients).
28
After 28 weeks treatment following the dosing guideline outlined in section 4.2, the mean reduction in HbA1c was 2.8% with NovoMix 30 (mean at baseline = 9.7%).
30.
With NovoMix 30, 66% and 42% of the patients reached HbA1c levels below 7% and 6.5%, respectively, and mean FPG was reduced by about 7 mmol/ L (from 14.0 mmol/ L at baseline to 7.1 mmol/ L).
NovoMix 30
The risk of overall daytime hypoglycaemic episodes was increased in patients treated with NovoMix 30
NovoMix 30.
Children and adolescents:
NovoMix 30
Mean HbA1c remained similar to baseline throughout the trial in both treatment groups, and there was no difference in hypoglycaemia rate with NovoMix 30 or biphasic human insulin 30.
30
Final HbA1c was significantly lower in the biphasic human insulin 30 treated group compared with NovoMix 30.
#
5.2 Pharmacokinetic properties
HbA1c NovoMix 30
In insulin aspart substitution of amino acid proline with aspartic acid at position B28 reduces the tendency to form hexamers in the soluble fraction of NovoMix 30, as compared with soluble human insulin.
30
The insulin aspart in the soluble phase of NovoMix 30 comprises 30% of the total insulin; this is absorbed more rapidly from the subcutaneous layer than the soluble insulin component of biphasic human insulin.
30%
The maximum serum insulin concentration is, on average, 50% higher with NovoMix 30 than with biphasic human insulin 30.
NovoMix 30
The mean half life (t½) of NovoMix 30, reflecting the absorption rate of the protamine bound fraction, was about 8-9 hours.
(t1/ 2) NovoMix 30,
Children and adolescents:
NovoMix 30
The pharmacokinetics of NovoMix 30 has not been investigated in children or adolescents.
NovoMix 30
The pharmacokinetics of NovoMix 30 has not been investigated in elderly, or patients with impaired renal or liver function.
in vitro,, "
5.3 Preclinical safety data
*
Non-clinical data with insulin aspart reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity and toxicity to reproduction.
IGF- 1
Studies also demonstrate that the dissociation of binding to the insulin receptor of insulin aspart is equivalent to human insulin.
6
8 6.
30° ().
6.1 List of excipients
6. 4
Glycerol Phenol Metacresol Zinc (as chloride) Sodium chloride Disodium phosphate dihydrate Protamine sulphate Sodium hydroxide (for pH adjustment) Hydrochloric acid (for pH adjustment) Water for injections
(2° (-
6.2 Incompatibilities
8° ()
In absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.
NovoMix 30 Penfill,
6.3 Shelf life
".
2 years.
30°C)
The in-use shelf life is 4 weeks (not above 30°C).
4
6.4 Special precautions for storage
,
Store in a refrigerator (2°C – 8°C) away from the freezing compartment.
.
Do not freeze.
30º (.
Do not refrigerate.
$, NovoMix 30 Penfill
Do not store above 30°C.
"
After removing NovoMix 30 Penfill from the refrigerator it is recommended to allow NovoMix 30 Penfill to reach room temperature before resuspending the insulin as instructed for the first time use.
6. 5
A glass (Type 1) cartridge which is closed with a latex-free (bromobutyl) rubber piston at one end and a latex-free (bromobutyl/ polyisoprene) rubber closure at the other.
NovoNordisk
Each cartridge contains 3 ml suspension.
NovoFine. $
Cartons of 5 or 10 cartridges.
10 NovoMix 30 Penfill
Not all pack sizes may be marketed.
. $
6.6 Special precautions for disposal and other handling
.
Detailed instruction accompanying the cartridge and delivery system must be followed.
NovoMix 30
NovoMix 30 Penfill is for use by one person only.
.
The resuspended liquid must appear uniformly white and cloudy.
NovoMix 30, "
NovoMix 30 which has been frozen must not be used.
.
The patient should be advised to discard the needle after each injection.
$.
Any unused product or waste material should be disposed of in accordance with local requirements.
Novo Nordisk A/ S Novo Allé DK- 2880 Bagsværd
Novo Nordisk A/ S Novo Allé DK-2880 Bagsværd Denmark
() 8 9 8
MARKETING AUTHORISATION NUMBERS
EU/ 1/ 00/ 142/ 004 EU/ 1/ 00/ 142/ 005
EU/ 1/ 00/ 142/ 004 EU/ 1/ 00/ 142/ 005
8 9 / 8 9
Date of first authorisation:
: 1% 2005
1 August 2005
2000
10.
8
DATE OF REVISION OF THE TEXT
NovoMix 50 Penfill 100 U/ ml,
NovoMix 50 Penfill 100 U/ ml, suspension for injection in a cartridge.
50/ 50
Soluble insulin aspart*/ protamine-crystallised insulin aspart*…… ..100 U/ ml in the ratio of 50/ 50
3 ml
3.
300 U.
PHARMACEUTICAL FORM
,
Suspension for injection in a cartridge.
NovoMix 50
NovoMix 50 is a white suspension.
! "
4.1 Therapeutic indications
#
Treatment of diabetes mellitus.
!
4.2 Posology and method of administration
NovoMix 50
The rapid onset of action and early peak of activity of insulin aspart allows NovoMix 50 to be given immediately before a meal.
NovoMix 50
When necessary, NovoMix 50 can be given soon after start of a meal.
:
Dosage:
NovoMix 50
Dosage of NovoMix 50 is individual and determined on the basis of the physician’ s advice in accordance with the patient’ s needs.
.
In patients with type 2 diabetes, NovoMix 50 can be given in monotherapy or in combination with metformin, when the blood glucose is inadequately controlled with metformin alone.
NovoMix 50.
Transfer to NovoMix 50 from other insulin preparations may require adjustment of dose and timing of administration.
(
Physical activity may reduce the patients’ insulin requirements.
.
Optimised metabolic control, including glucose monitoring, is therefore recommended.
.
Renal or hepatic impairment may reduce the patient’ s insulin requirements.
18
No studies have been performed with NovoMix 50 in children and adolescents under the age of 18 years.
.
Administration:
NovoMix 50
NovoMix 50 is administered subcutaneously by injection in the thigh or in the abdominal wall.
50
The influence of different injection sites on the absorption of NovoMix 50 has not been investigated.
NovoMix 50
NovoMix 50 should never be administered intravenously.
NovoMix 50 "
4.3 Contraindications
.,
• Hypersensitivity to the active substance or to any of the excipients • Hypoglycaemia.
,
4.4 Special warnings and precautions for use
.
The use of dosages which are inadequate or discontinuation of treatment, especially in insulin- dependent diabetics, may lead to hyperglycaemia and diabetic ketoacidosis; conditions which are potentially lethal.
(
Omission of a meal or unplanned, strenuous physical exercise may lead to hypoglycaemia (see section 4.8 and section 4.9).
.
Patients, whose blood glucose control is greatly improved, e. g. by intensified insulin therapy, may experience a change in their usual warning symptoms of hypoglycaemia, and should be advised accordingly.
NovoMix 50,
NovoMix 50 should be administered in immediate relation to a meal.
13
Concomitant illness, especially infections, usually increases the patient’ s insulin requirements.
,
When patients are transferred between different types of insulin products, the early warning symptoms of hypoglycaemia may change or become less pronounced than those experienced with their previous insulin.
.
Changes in strength, brand (manufacturer), type, origin (animal, human, human insulin analogue), and/ or method of manufacture (recombinant DNA versus animal source insulin) may result in the need for a change in dosage.
NovoMix 50
Patients taking NovoMix 50 may need a change in dosage from that used with their usual insulin.
"
On rare occasions, injection site reactions may require discontinuation of NovoMix 50.
.
12 NovoMix 50 contains metacresol, which may cause allergic reactions.
4. 5
4.5 Interaction with other medicinal products and other forms of interaction
"- '/
A number of medicinal products are known to interact with the glucose metabolism.
0 ', ($!
Oral antidiabetic drugs (OAD), octreotide, monoamine oxidase inhibitors (MAOIs), non-selective beta-adrenergic blocking agents, angiotensin converting enzyme (ACE) inhibitors, salicylates, alcohol, anabolic steroids and sulphonamides.
',!
Oral contraceptives, thiazides, glucocorticoids, thyroid hormones, sympathomimetics and danazol.
', (1 -
Beta-blocking agents may mask the symptoms of hypoglycaemia.
"-
Alcohol may intensify and prolong the glucose lowering effect of insulin.
($%!),
4.6 Pregnancy and lactation
NovoMix 50
There is limited clinical experience with NovoMix 50 in pregnancy.
NovoMix 50
There are no restrictions on treatment with NovoMix 50 during lactation.
NovoMix 50.
However, the NovoMix 50 dosage may need to be adjusted.
NovoMix, /
4.8 Undesirable effects
',,. $,.
Severe hypoglycaemia may lead to unconsciousness and/ or convulsions and may result in temporary or permanent impairment of brain function or even death.
/,
In clinical trials and during marketed use the frequency varies with patient population and dose
,
During clinical trials the overall rates of hypoglycaemia did not differ between patients treated with insulin aspart compared to human insulin.
-
Frequencies of adverse drug reactions from clinical trials, which by an overall judgement are considered related to insulin aspart are listed below.
,
Immune system disorders Uncommon - Urticaria, rash, eruptions
& (
Generalised hypersensitivity reactions are potentially life threatening.
-% #
Nervous system disorders Rare - Peripheral neuropathy Fast improvement in blood glucose control may be associated with a condition termed acute painful neuropathy, which is usually reversible.
*
These symptoms are usually of transitory nature.
-
However, intensification of insulin therapy with abrupt improvement in glycaemic control may be associated with worsening of diabetic retinopathy.
. '
Skin and subcutaneous tissue disorders Uncommon - Lipodystrophy Lipodystrophy may occur at the injection site as a consequence of failure to rotate injection sites within an area.
,
These reactions are usually transitory and normally they disappear during continued treatment.
#
These symptoms are usually of transitory nature.
- 2 $...
4.9 Overdose
4. 9 '"
A specific overdose for insulin cannot be defined, however, hypoglycaemia may develop over sequential stages if too high doses relative to the patient’ s requirement are administered:
$,
It is therefore recommended that the diabetic patient always carry sugar-containing products • Severe hypoglycaemic episodes, where the patient has become unconscious, can be treated by
5.
14 glucagon (0.5 to 1 mg) given intramuscularly or subcutaneously by a trained person or glucose given intravenously by a medical professional.
NovoMix 50 NPH
NovoMix 50 is a biphasic suspension of insulin aspart (rapid-acting human insulin analogue) and protamine-crystallised insulin aspart (intermediate-acting human insulin analogue).
#
The blood glucose lowering effect of insulin occurs when the molecules facilitate the uptake of glucose by binding to insulin receptors on muscle and fat cells - and simultaneously inhibit the output of glucose from the liver.
50%
NovoMix 50 is a biphasic insulin, which contains 50% soluble insulin aspart.
(50%)
The crystalline phase (50%) consists of protamine-crystallised insulin aspart, which has an activity profile that is similar to that of human NPH insulin.
,
Glucose Infusion Rate
NovoMix 50 * 1
Hours NovoMix 50
14 - 24
Figure 1:
/ NovoMix 50
Activity Profile for NovoMix 50 in Healthy Caucasian Subjects.
1:
15 5.2 Pharmacokinetic properties
NovoMix 50
In insulin aspart substitution of amino acid proline with aspartic acid at position B28 reduces the tendency to form hexamers in the soluble fraction of NovoMix 50, as compared with soluble human insulin.
NovoMix 50, # NovoMix 50,
The insulin aspart in the soluble phase of NovoMix 50 comprises 50% of the total insulin; this is absorbed more rapidly from the subcutaneous layer than the soluble insulin component of biphasic human insulin.
50%
The remaining 50% is in crystalline form as protamine-crystallised insulin aspart; this has a prolonged absorption profile similar to human NPH insulin.
445 ± 135 pmol/ l
In healthy volunteers a mean maximum serum concentration of 445 ± 135 pmol/ l was reached about 60 minutes after a subcutaneous dose of 0.30 U/ kg body weight.
NovoMix 50
The pharmacokinetics of NovoMix 50 has not been investigated in elderly, children or patients with impaired renal or liver function.
6
PHARMACEUTICAL PARTICULARS
NovoMix 50 Penfill,
6.3 Shelf life
(
After removing NovoMix 50 Penfill from the refrigerator it is recommended to allow NovoMix 50 Penfill to reach room temperature before resuspending the insulin as instructed for the first time use.
$, NovoMix 50 Penfill ".
6.5 Nature and contents of container
1, 5
Cartons of 1, 5 or 10 cartridges.
NovoFine. $
Not all pack sizes may be marketed.
.
6.6 Special precautions for disposal and other handling
,
Detailed instruction accompanying the cartridge and delivery system must be followed.
NovoMix 50 Penfill
NovoMix 50 Penfill is for use by one person only.
NovoMix 50
The necessity of resuspending the NovoMix 50 suspension immediately before use is to be stressed to the patient.
NovoMix 50, "
NovoMix 50 which has been frozen must not be used.
EU/ 1/ 00/ 142/ 011 EU/ 1/ 00/ 142/ 012 EU/ 1/ 00/ 142/ 013
EU/ 1/ 00/ 142/ 011 EU/ 1/ 00/ 142/ 012 EU/ 1/ 00/ 142/ 013
NovoMix 70 Penfill 100 U/ ml,
NovoMix 70 Penfill 100 U/ ml, suspension for injection in a cartridge.
70/ 30
Soluble insulin aspart*/ protamine-crystallised insulin aspart*…… ..100 U/ ml in the ratio of 70/ 30
NovoMix 70
NovoMix 70 is a white suspension.
NovoMix 70
The rapid onset of action and early peak of activity of insulin aspart allows NovoMix 70 to be given immediately before a meal.
NovoMix 70
When necessary, NovoMix 70 can be given soon after start of a meal.
NovoMix 70
Dosage of NovoMix 70 is individual and determined on the basis of the physician’ s advice in accordance with the patient’ s needs.
.
In patients with type 2 diabetes, NovoMix 70 can be given in monotherapy or in combination with metformin, when the blood glucose is inadequately controlled with metformin alone.