natgillin/translations-raw huggingface dataset:
. "
Exercise taken immediately after a meal may increase the risk of hypoglycaemia.
!
Insulin suspensions are not to be used in insulin infusion pumps.
.
On rare occasions, injection site reactions may require discontinuation of NovoMix 30.
NovoMix 30.
Combination of NovoMix 30 with pioglitazone:
:
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.
4
4 4.6 Pregnancy and lactation
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
However, the NovoMix 30 dosage may need to be adjusted.
. '!
4.7 Effects on ability to drive and use machines
. "
This may constitute a risk in situations where these abilities are of special importance (e. g. driving a car or operating machinery).
NovoMix 30.
4.8 Undesirable effects
4. 7
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.
% +
Frequencies of adverse drug reactions from clinical trials, which by an overall judgement are considered related to insulin aspart are listed below.
NovoMix
The frequencies are defined as:
(> 1/ 1. 000, <
Uncommon (> 1/ 1,000 ,< 1/100) and rare (> 1/10 ,000, < 1/1,000).
(> 1/ 10. 000, < 1/ 1. 000). # (< 1/ 10. 000),
Immune system disorders Uncommon - Urticaria, rash, eruptions
(
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.
.
These reactions are usually transitory and normally they disappear during continued treatment.
&
These symptoms are usually of transitory nature.
30
Oedema and weight increase may occur when NovoMix 30 is used in combination with OADs.
4. 9 $% $&! $'
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:
:
Upon regaining consciousness administration of oral carbohydrate is recommended for the patient in order to prevent relapse.
/
5.1 Pharmacodynamic properties
$/
Pharmacotherapeutic group:
4 A10AD05.
Drugs used in diabetes.
# 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.
NovoMix 30
When NovoMix 30 is injected subcutaneously, the onset of action will occur within 10 to 20 minutes of injection.
24
The duration of action is up to 24 hours.
.
Glucose infusion rate
(---)
Hours
NovoMix 30 (___)
Figure 1:
30
Activity profile of NovoMix 30 (___) and biphasic human insulin 30 (---) in healthy subjects.
(
Insulin aspart is equipotent to human insulin on a molar basis.
(
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.
- HbA1c NovoMix 30. (
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.
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
Children and adolescents:
NovoMix 30
Final HbA1c was significantly lower in the biphasic human insulin 30 treated group compared with NovoMix 30.
NovoMix 30.
5.2 Pharmacokinetic properties
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.
70%
The remaining 70% is in crystalline form as protamine-crystallised insulin aspart; this has a prolonged absorption profile similar to human NPH insulin.
30
The maximum serum insulin concentration is, on average, 50% higher with NovoMix 30 than with biphasic human insulin 30.
140 ± 32 pmol/ l,
In healthy volunteers a mean maximum serum concentration of 140 ± 32 pmol/ l was reached about 60 minutes after a subcutaneous dose of 0.20 U/ kg body weight.
NovoMix 30,
The mean half life (t½) of NovoMix 30, reflecting the absorption rate of the protamine bound fraction, was about 8-9 hours.
30
The pharmacokinetics of NovoMix 30 has not been investigated in children or adolescents.
30
The pharmacokinetics of NovoMix 30 has not been investigated in elderly, or patients with impaired renal or liver function.
!
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.
%,
Studies also demonstrate that the dissociation of binding to the insulin receptor of insulin aspart is equivalent to human insulin.
7 8 $
8 6.
6. 2% / 0 (+
PHARMACEUTICAL PARTICULARS
"
6.1 List of excipients
-
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
!
6.2 Incompatibilities
1
In absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.
30°C).
6.3 Shelf life
, + 1. "$& +
2 years.
4
The in-use shelf life is 4 weeks (not above 30°C).
-
6.4 Special precautions for storage
(2°C– 8°C)
Store in a refrigerator (2°C – 8°C) away from the freezing compartment.
-%. -
Do not freeze.
NovoMix Penfill,
NovoMix 30 Penfill cartridges in use or carried as a spare: can be kept at ambient temperature (below 30°C) for up to 4 weeks, but any remainder must then be discarded.
30°C)
Do not refrigerate.
9.
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 Nature and contents of container
-
Each cartridge contains 3 ml suspension.
. 9
Cartons of 5 or 10 cartridges.
NovoMix 30 Penfill
Not all pack sizes may be marketed.
-
6.6 Special precautions for disposal and other handling
NovoMix 30 Penfill
NovoMix 30 Penfill is for use by one person only.
NovoFine. *
The cartridge must not be refilled.
# NovoMix 30 Penfill%
9 The necessity of resuspending the NovoMix 30 suspension immediately before use is to be stressed to the patient.
# NovoMix 30 Penfill
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.
7. #
7.
/
Date of first authorisation:
2000
1 August 2000 Date of last renewal:
2005
1 August 2005
* …….. 100 U/ ml
QUALITATIVE AND QUANTITATIVE COMPOSITION
* cerevisiae.
* produced by recombinant DNA technology in Saccharomyces cerevisiae.
DNA
One unit of insulin aspart corresponds to 6 nmol, 0.035 mg salt-free anhydrous insulin aspart.
Saccharomyces
1 cartridge contains 3 ml equivalent to 300 U.
To NovoMix 50
NovoMix 50 is a white suspension.
$) $* '+% +
4.1 Therapeutic indications
'NovoMix 50
Treatment of diabetes mellitus.
NovoMix 50,
When necessary, NovoMix 50 can be given soon after start of a meal.
NovoMix 50.)
Dosage:
%
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.
To NovoMix 50
NovoMix 50 is administered subcutaneously by injection in the thigh or in the abdominal wall.
To NovoMix
4.3 Contraindications
4. 3
• 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.
0 0
Omission of a meal or unplanned, strenuous physical exercise may lead to hypoglycaemia (see section 4.8 and section 4.9).
To NovoMix 50
NovoMix 50 should be administered in immediate relation to a meal.
-
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.
. "
Insulin suspensions are not to be used in insulin infusion pumps.
!
On rare occasions, injection site reactions may require discontinuation of NovoMix 50.
.
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.
,,
Alcohol may intensify and prolong the glucose lowering effect of insulin.
NovoMix 50.
There is limited clinical experience with NovoMix 50 in pregnancy.
# NovoMix 50
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 50. '!
Insulin treatment of the breast-feeding mother presents no risk to the baby.
14 4. 7
4.7 Effects on ability to drive and use machines
,%
This may constitute a risk in situations where these abilities are of special importance (e. g. driving a car or operating machinery).
% +
The advisability of driving should be considered in these circumstances.
% / $. / +)
4.8 Undesirable effects
3
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.
(> 1/ 1. 000, < 1/ 100),
Uncommon (> 1/ 1,000 ,< 1/100) and rare (> 1/10 ,000, < 1/1,000).
–,
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.
,,
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 symptoms are usually of transitory nature.
$% $&! $'
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:
!
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
,
Upon regaining consciousness administration of oral carbohydrate is recommended for the patient in order to prevent relapse.
.
A10AD05.
To NovoMix 50
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.
NovoMix 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
6 NovoMix 50
Hours NovoMix 50
NovoMix 50
Activity Profile for NovoMix 50 in Healthy Caucasian Subjects.
'
Insulin aspart is equipotent to human insulin on a molar basis.
.
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
The remaining 50% is in crystalline form as protamine-crystallised insulin aspart; this has a prolonged absorption profile similar to human NPH insulin.
6. 1, $'
PHARMACEUTICAL PARTICULARS
& $
6.1 List of excipients
() 6
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
30°C).
6.2 Incompatibilities
6. 4
In absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.
$1 & "
6.3 Shelf life
(2°C – 8°C)
Store in a refrigerator (2°C – 8°C) away from the freezing compartment.
!
16 NovoMix 50 Penfill cartridges in use or carried as a spare: can be kept at ambient temperature (below 30°C) for up to 4 weeks, but any remainder must then be discarded.
9
Keep the cartridges in the outer carton in order to protect from light.
%
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
NovoMix 50 Penfill -,
The cartridge contains a glass ball to facilitate resuspension.
NovoMix 50 Penfill
Each cartridge contains 3 ml suspension.
Novo Nordisk (
Cartons of 1, 5 or 10 cartridges.
NovoFine. *
Not all pack sizes may be marketed.
To NovoMix%
Detailed instruction accompanying the cartridge and delivery system must be followed.
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.
-
The patient should be advised to discard the needle after each injection.
Novo Nordisk A/ S Novo Allé DK- 2880 Bagsvaerd
Novo Nordisk A/ S Novo Allé DK-2880 Bagsværd Denmark
5
Date of first authorisation:
* cerevisiae
* produced by recombinant DNA technology in Saccharomyces cerevisiae.
6. 1
PHARMACEUTICAL FORM
To NovoMix 70
NovoMix 70 is a white suspension.
! "
4.
'NovoMix 70
Treatment of diabetes mellitus.
NovoMix 70,
When necessary, NovoMix 70 can be given soon after start of a meal.
NovoMix 70.)
Dosage:
%
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.
NovoMix 70
Transfer to NovoMix 70 from other insulin preparations may require adjustment of dose and timing of administration.
To NovoMix 70
NovoMix 70 is administered subcutaneously by injection in the thigh or in the abdominal wall.
• 0 •
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).
4. 4
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.
To NovoMix 70
NovoMix 70 should be administered in immediate relation to a meal.
!
On rare occasions, injection site reactions may require discontinuation of NovoMix 70.
NovoMix 70.
19 NovoMix 70 contains metacresol, which may cause allergic reactions.
# NovoMix 70
4.5 Interaction with other medicinal products and other forms of interaction
4. 5
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.
(OAD),,
4.6 Pregnancy and lactation
%
After delivery, insulin requirements return rapidly to pre-pregnancy levels.
22 4. 7
4.7 Effects on ability to drive and use machines
&
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.
,%
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.
1
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
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
. (
Upon regaining consciousness administration of oral carbohydrate is recommended for the patient in order to prevent relapse.
To NovoMix 70
NovoMix 70 is a biphasic suspension of insulin aspart (rapid-acting human insulin analogue) and protamine-crystallised insulin aspart (intermediate-acting human insulin analogue).
30%
The crystalline phase (30%) consists of protamine-crystallised insulin aspart, which has an activity profile that is similar to that of human NPH insulin.
)
The duration of action is up to 14 hours to 24 hours (Figure 1).
& 20: +
Glucose Infusion Rate
NovoMix 70
Hours NovoMix 70
6 NovoMix 70
Figure 1:
NovoMix 70
Activity Profile for NovoMix 70 in Healthy Caucasian Subjects.
NovoMix 70,
22 5.2 Pharmacokinetic properties
0, 30 U/ kg!
In type 2 patients with diabetes, the maximum concentration was reached about 75 minutes after dosing.
721 ± 184 pmol/ l.
In type 1 patients with diabetes a mean maximum serum concentration of 721 ± 184 pmol/ l was reached about 60 minutes after a subcutaneous dose of 0.30 U/ kg body weight.
$1 & ",
6.3 Shelf life
, + 1.
2 years.
-
23 6.4 Special precautions for storage
NovoMix 70 Penfill
NovoMix 70 Penfill cartridges in use or carried as a spare: can be kept at ambient temperature (below 30°C) for up to 4 weeks, but any remainder must then be discarded.
,
After removing NovoMix 70 Penfill from the refrigerator it is recommended to allow NovoMix 70 Penfill to reach room temperature before resuspending the insulin as instructed for the first time use.
NovoMix 70 Penfill
6.5 Nature and contents of container
-,
The cartridge contains a glass ball to facilitate resuspension.
50 Penfill
Each cartridge contains 3 ml suspension.
70 Penfill.
NovoMix 70 Penfill is for use by one person only.
'NovoMix 70
The necessity of resuspending the NovoMix 70 suspension immediately before use is to be stressed to the patient.
# NovoMix 70
NovoMix 70 which has been frozen must not be used.
:: 1,: 1,
Date of first authorisation:
2000 2005
1 August 2005
30/ 70
Soluble insulin aspart*/ protamine-crystallised insulin aspart*………… 100 U/ ml in the ratio of 30/ 70
*.........
* produced by recombinant DNA technology in Saccharomyces cerevisiae.
Saccharomyces cerevisiae.
1 pre-filled pen contains 3 ml equivalent to 300 U.
(!
No studies have been performed in children under the age of 6 years.
,
26 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.
+
The following titration guideline is recommended for dose adjustments:
# NovoMix 30
NovoMix 30 may fully or partially meet this requirement.
.
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.
NovoMix
4.3 Contraindications
. '
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.
%
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.
&,
27 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.
:
Exercise taken immediately after a meal may increase the risk of hypoglycaemia.
.)
Insulin suspensions are not to be used in insulin infusion pumps.
,
On rare occasions, injection site reactions may require discontinuation of NovoMix 30.
-
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.
!
Alcohol may intensify and prolong the glucose lowering effect of insulin.
%
28 4.6 Pregnancy and lactation
. '!
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.
(> 1/ 1. 000, < 1/ 100))
4.7 Effects on ability to drive and use machines