Medicines
Update of 01/03/2024
NOVOMIX®
biphasic insulin aspart
Forms and presentations
NovoMix 30 Penfill:
Injectable SC suspension at 100 units/ml (opaque, white and aqueous): Cartridges* of 3 ml, box of 5.
NovoMix 30 FlexPen:
Injectable SC suspension at 100 units/ml (opaque, white and aqueous): Cartridges* of 3 ml in disposable prefilled multidose pen, box of 5.
NovoMix 50 FlexPen:
Injectable SC suspension at 100 units/ml (opaque, white and aqueous): Cartridges* of 3 ml in disposable prefilled multidose pen, box of 5.
* The cartridge contains a glass bead that facilitates resuspension.
Composition
| per cartridge or per pen | |
| Insulin aspart*
|
300 units |
1 ml of suspension contains 100 units (i.e. 3,5 mg) of soluble insulin aspart/crystallised protamine insulin aspart, in a ratio of 30/70 (NovoMix 30) and 50/50 (NovoMix 50).
* Insulin aspart is produced on Saccharomyces cerevisiae by recombinant DNA technology.Indications
- NovoMix 30:
- NovoMix 30 is indicated for the treatment of diabetes in adults, adolescents and children from 10 years of age.
- NovoMix 50:
- NovoMix 50 is indicated for the treatment of diabetes in adults.
Dosage and administration
DosageThe insulin content of insulin analogues, including insulin aspart, is expressed in units, whereas the insulin content of human insulin is expressed in international units.
The dosage of NovoMix depends on each individual and is determined according to the patient's needs. Glycaemic monitoring and insulin dose adjustment are recommended in order to achieve optimal glycaemic control.
A dose adjustment may be necessary if the patient increases physical activity, changes their usual diet or in case of concomitant illness.
- NovoMix 30:
- In patients with type 2 diabetes, NovoMix 30 may be administered as monotherapy. NovoMix 30 may also be administered in combination with oral antidiabetics and/or a GLP-1 receptor agonist. For patients with type 2 diabetes, the recommended initial dose of NovoMix 30 is 6 units at breakfast and 6 units at dinner (evening meal). NovoMix 30 may also be initiated as one injection per day of 12 units at dinner (evening meal). When NovoMix 30 is used as one injection per day and the dose reaches 30 units, it is generally recommended to switch to two injections per day, dividing the breakfast and dinner (evening meal) doses equally. If recurrent episodes of hypoglycaemia occur during the day with two injections per day of NovoMix 30, the morning dose may be split into one dose in the morning and one dose at noon (i.e. 3 injections per day).
- It is advised to follow the following titration recommendations for dose adjustment:
-
Preprandial blood glucose Dose adjustment of NovoMix 30 < 4,4 mmol/l < 80 mg/dl - 2 units 4,4 - 6,1 mmol/l 80 - 110 mg/dl 0 6,2 - 7,8 mmol/l 111 - 140 mg/dl + 2 units 7,9 - 10 mmol/l 141 - 180 mg/dl + 4 units > 10 mmol/l > 180 mg/dl + 6 units - The lowest preprandial blood glucose of the last three days should be taken into account. The dose should not be increased if there has been a hypoglycaemic episode during these last three days.
- Dose adjustment can be performed once weekly until the HbA1c target is reached. Blood glucose measured before meals should be used to adjust the previous dose.
- In patients with type 2 diabetes, a dose reduction of 20 % is recommended for patients with an HbA1c level below 8 % when a GLP-1 receptor agonist is added to NovoMix 30, in order to minimise the risk of hypoglycaemia. For patients with an HbA1c level above 8 %, a dose reduction should be considered. Subsequently, the dose should be adjusted individually.
- In patients with type 1 diabetes, individual insulin requirements generally lie between 0,5 and 1 units/kg/day. These requirements may be partially or fully covered by NovoMix 30.
-
- Special populations:
-
- Elderly subjects (≥ 65 years):
NovoMix 30 may be used in elderly patients; however, experience with the use of NovoMix 30 in combination with oral antidiabetic agents in patients over 75 years of age is limited.
Intensified glycaemic control and individual dose adjustment of insulin aspart are necessary in elderly patients. - Subjects with renal or hepatic impairment:
Renal or hepatic impairment may reduce the patient's insulin requirements.
Intensified glycaemic control and individual dose adjustment of insulin aspart are necessary in patients with renal or hepatic impairment.
- Elderly subjects (≥ 65 years):
-
- Paediatric population:
- NovoMix 30 may be used in adolescents and children from 10 years of age when premixed insulin is preferred. Clinical experience with NovoMix 30 in children aged 6 to 9 years is limited (see Pharmacodynamics).
- No data are available with NovoMix 30 in children under 6 years of age.
-
- Replacing other insulins:
- Replacement of human biphasic insulin by NovoMix 30 in a patient should start with the same dose and the same administration regimen. The dose should then be adjusted according to individual needs (see the titration recommendations for dose adjustment in the table above).
- Close blood glucose monitoring is recommended during the change of treatment and during the first weeks (see Warnings and Precautions for Use).
- NovoMix 50:
- Individual insulin requirements generally range between 0,5 and 1 unit/kg/day. These requirements may be partially or fully covered by NovoMix 50.
- In patients with type 2 diabetes, NovoMix 50 may be administered alone or in combination with metformin when glycaemia is insufficiently controlled by metformin alone.
-
- Special populations:
- Intensification of glycaemic control and individual adjustment of the insulin aspart dose are necessary in elderly patients (≥ 65 years) and in patients with renal or hepatic impairment.
- Renal or hepatic impairment may reduce the patient's insulin requirements.
-
- Paediatric population:
- The safety and efficacy of NovoMix 50 in children under 18 years of age have not been established. No data are available.
-
- Replacing other insulins:
- Replacing an insulin with NovoMix 50 may require an adjustment of the dose and the timing of administration. It is recommended to closely monitor glycaemia during the change of treatment and during the first weeks (see Warnings and Precautions for Use).
Method of administration:
NovoMix is a biphasic suspension of an insulin analogue, insulin aspart. The suspension contains rapid-acting and intermediate-acting insulin aspart in a ratio of 30/70 (NovoMix 30) and of 50/50 (NovoMix 50).
NovoMix must be administered subcutaneously only.
NovoMix must be administered subcutaneously in the thigh or abdominal wall. If needed, the buttock or deltoid region may be used. Rotation of injection sites within the same region should always be performed in order to reduce the risk of developing lipodystrophy and cutaneous amyloidosis (see Warnings and Precautions for UseAdverse effects). The influence of the different injection sites on the absorption of NovoMix has not been studied. The duration of action varies depending on the dose, the injection site, blood flow, temperature and the intensity of physical activity.
NovoMix has a faster onset of action than human biphasic insulin and should generally be administered immediately before a meal. If necessary, NovoMix may be injected shortly after a meal.
For more detailed instructions for use, please refer to the package leaflet.
- NovoMix 30 Penfill:
-
- Administration with an insulin delivery system:
- NovoMix 30 Penfill is designed to be used with Novo Nordisk insulin delivery systems and NovoFine or NovoTwist needles. NovoMix 30 Penfill is suitable only for subcutaneous injections administered by means of a reusable pen. If administration by syringe is necessary, a vial should be used.
- NovoMix FlexPen:
-
- Administration with FlexPen:
- NovoMix FlexPen is a prefilled (colour-coded) pen designed to be used with NovoFine or NovoTwist needles. FlexPen allows injection of 1 to 60 units in steps of 1 unit. NovoMix FlexPen is suitable only for subcutaneous injections. If administration by syringe is necessary, a vial should be used.
Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in section Composition.Warnings and precautions
NovoMix must not be administered intravenously because of the risk of severe hypoglycaemia. Intramuscular administration should be avoided. NovoMix must not be used in insulin infusion pumps.
Before travelling to countries with different time zones, the patient should consult their doctor as they may need to take their insulin and meals at different times.
An inadequate dose or discontinuation of treatment, particularly in patients with type 1 diabetes, may lead to hyperglycaemia and diabetic ketoacidosis. Generally, the first symptoms of hyperglycaemia develop gradually, over a few hours or a few days. They include thirst, increased frequency of urination, nausea, vomiting, drowsiness, dry and red skin, dry mouth, loss of appetite and acetone-smelling breath. In type 1 diabetes, untreated hyperglycaemic episodes can lead to potentially fatal diabetic ketoacidosis.
Skipping a meal or unplanned strenuous physical exercise may lead to hypoglycaemia.
Hypoglycaemia may occur if the insulin dose is too high for the patient's needs. In case of hypoglycaemia or suspected hypoglycaemia, NovoMix must not be injected. After stabilisation of the patient's blood glucose, a dose adjustment should be considered (see Posology and Method of administrationAdverse effectsOverdose).
Patients whose glycaemic control is markedly improved, for example as part of intensified insulin therapy, may experience a change in the usual warning signs of hypoglycaemia and should be made aware of this possibility. The usual warning signs may disappear in patients with long-standing diabetes.
As NovoMix must be administered immediately before or after a meal, its rapid onset of action should be taken into account in patients with concomitant diseases or taking other medicinal products and in whom food absorption may be delayed.
Concomitant diseases, particularly infections and febrile conditions, generally increase the patient's insulin requirements. Concomitant diseases affecting the kidneys, liver, or adrenal, pituitary or thyroid glands may require adjustment of the insulin dose.
If the patient switches insulin type, the warning symptoms of hypoglycaemia may be altered or become less pronounced than those experienced with their previous insulin.
- NovoMix 30:
- Compared with human biphasic insulin, NovoMix 30 may have a stronger effect on lowering glucose within 6 hours after injection. This may need to be compensated for, depending on the patient, by an adjustment of the insulin dose and/or by food intake.
- Tighter glycaemic control may increase the risk of hypoglycaemic episodes and therefore requires particular attention when the dosage is intensified, as described in the section Dosage and administration.
In case of a change of insulin type or brand, the patient must be closely monitored medically. Changes in strength, brand (manufacturer), type, origin (animal insulin, human insulin or human insulin analogue) and/or manufacturing method (recombinant DNA or animal-derived insulin) may require a change in dose. Patients switching to NovoMix as a replacement for another type of insulin may require an increase in the number of injections or a change in dose compared with their usual insulins. If a dose adjustment proves necessary, it may be made with the first injection or during the first weeks or first months.
As with all insulin therapy, injection site reactions may occur, presenting as pain, redness, urticaria, inflammation, bruising, swelling and pruritus. Continuous rotation of injection sites within a given area reduces the risk of developing these reactions. These reactions usually resolve within a few days to a few weeks. In rare cases, injection site reactions may require discontinuation of NovoMix.
Patients must be instructed to continuously rotate injection sites in order to reduce the risk of developing lipodystrophy or cutaneous amyloidosis. There is a potential risk of delayed insulin absorption and worsening of glycaemic control following insulin injections at sites showing these reactions. Sudden switching of the injection site to an unaffected area has been reported to cause hypoglycaemia. Blood glucose monitoring is recommended after switching the injection site from an affected to an unaffected area, and an adjustment of the antidiabetic medicinal product dose may be considered.
Cases of cardiac failure have been reported when pioglitazone was used in combination with insulin, particularly in patients with risk factors for the development of cardiac failure. This should be taken into account if treatment combining pioglitazone and NovoMix is considered. If such a combination is initiated, these patients will need to be monitored for signs and symptoms of cardiac failure, weight gain and oedema. Pioglitazone should be discontinued if worsening of cardiac failure symptoms occurs.
Patients must be instructed to always check the insulin label before each injection in order to avoid accidental confusion between NovoMix and other insulins.
Insulin administration may cause the formation of anti-insulin antibodies. In rare cases, the presence of these anti-insulin antibodies may require an adjustment of the insulin dose to correct a tendency to hyper- or hypoglycaemia.
In order to improve the traceability of biological medicinal products, the name and batch number of the product administered must be clearly recorded.
Interactions
A number of medicinal products are known to interact with glucose metabolism.
The following substances may reduce the patient's insulin requirements: oral antidiabetic medicinal products, GLP-1 receptor agonists, monoamine oxidase inhibitors (MAOIs), beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, salicylates, anabolic steroids and sulphonamides.
The following substances may increase the patient's insulin requirements: oral contraceptives, thiazides, glucocorticoids, thyroid hormones, sympathomimetics, growth hormone and danazol.
Beta-blockers may mask the symptoms of hypoglycaemia.
Octreotide and lanreotide may either increase or decrease insulin requirements.
Alcohol may either intensify or reduce the hypoglycaemic effect of insulin.
Fertility, pregnancy and breastfeeding
Pregnancy:Clinical experience with NovoMix during pregnancy is limited.
Animal reproduction studies have not shown any difference between insulin aspart and human insulin in terms of embryotoxicity or teratogenic effects.
In diabetic pregnant women, intensified glycaemic control and monitoring are generally recommended throughout pregnancy as well as in cases of planned pregnancy. Insulin requirements usually decrease during the first trimester and then increase during the second and third trimesters. After delivery, insulin requirements quickly return to pre-pregnancy levels.
Breastfeeding:
Administration of NovoMix during breastfeeding is not subject to any restriction.
Insulin therapy in a breastfeeding mother presents no risk to the baby. However, it may be necessary to adjust the dose of NovoMix.
Fertility:Animal reproduction studies have not revealed any differences between insulin aspart and human insulin with regard to fertility.
Driving and using machines
The patient's concentration abilities and reflexes may be reduced in case of hypoglycaemia. This could pose a risk in situations where these abilities are essential (for example driving vehicles or using machines).Patients must be informed of the precautions to take in order to avoid any hypoglycaemia while driving vehicles or using machines. This is particularly important in patients who are little or poorly familiar with the warning signs of hypoglycaemia or who are prone to frequent hypoglycaemic episodes. In such circumstances, the ability to drive vehicles or use machines must be assessed.
Adverse effects
The adverse reactions observed in patients treated with NovoMix are most often due to the pharmacological action of insulin aspart.
The most frequently reported adverse reaction during treatment is hypoglycaemia. The frequency of hypoglycaemia varies depending on the patient population, the doses used and the level of glycaemic control, see 'Description of selected adverse reactions' below.
At the start of insulin treatment, refractive disorders, oedema and injection site reactions (pain, redness, urticaria, inflammation, bruising, swelling and pruritus at the injection site) may occur. These reactions are usually transient. A rapid improvement in glycaemic control may be associated with acute painful neuropathy, which is usually reversible. Intensification of insulin therapy with a sudden improvement in glycaemic control may be associated with a transient worsening of diabetic retinopathy, whereas improvement of long-term glycaemic control decreases the risk of progression of diabetic retinopathy.
The adverse reactions listed below are derived from clinical trial data and classified by MedDRA frequency and by system organ class. Frequency categories are defined according to the following conventions: very common (≥ 1/10); common (≥ 1/100, < 1/10); uncommon (≥ 1/1 000, < 1/100); rare (≥ 1/10 000, < 1/1 000); very rare (< 1/10 000); frequency not known (cannot be estimated from the available data).
| Immune system disorders | Uncommon: urticaria, rash, eruptions |
| Very rare: anaphylactic reactions* | |
| Metabolism and nutrition disorders | Very common: hypoglycaemia* |
| Nervous system disorders | Rare: peripheral neuropathy (painful neuropathy) |
| Eye disorders | Uncommon: refractive disorders, diabetic retinopathy |
| Skin and subcutaneous tissue disorders | Uncommon: lipodystrophy* |
| Not known: cutaneous amyloidosis(a) | |
| General disorders and administration site conditions | Uncommon: oedema, injection site reactions |
(a) ADRs derived from post-marketing data.
- Anaphylactic reactions:
- The occurrence of generalised hypersensitivity reactions (including generalised skin rash, pruritus, sweating, gastrointestinal disorders, angioneurotic oedema, respiratory difficulties, palpitations and decreased blood pressure) is very rare but these reactions may potentially be life-threatening.
- Hypoglycaemia:
- The most frequently reported adverse reaction is hypoglycaemia. This occurs when the insulin dose is too high in relation to the insulin requirement. Severe hypoglycaemia can cause loss of consciousness and/or convulsions and may lead to temporary or permanent impairment of brain function, or even death. Symptoms of hypoglycaemia usually occur suddenly. They may include: cold sweats, cold pale skin, fatigue, nervousness or tremor, anxiety, unusual asthenia or weakness, confusion, difficulty concentrating, drowsiness, excessive hunger, visual disturbances, headache, nausea and palpitations.
- During clinical trials, the frequency of hypoglycaemia varied depending on the patient population, the doses used and the level of glycaemic control. During the clinical trials, the overall rate of hypoglycaemia was not different between patients treated with insulin aspart and those treated with human insulin.
- Skin and subcutaneous tissue disorders:
- Lipodystrophy (including lipohypertrophy, lipoatrophy) and cutaneous amyloidosis may occur at the injection site and delay the local absorption of insulin. Continuous rotation of injection sites within a given area may help to reduce or avoid these reactions (see Warnings and Precautions for Use).
- NovoMix 30:
- Since marketing and during clinical trials, the frequency, type and severity of adverse effects observed in the paediatric population do not show any differences compared with greater experience acquired in the general population.
- NovoMix 50:
- The safety and efficacy of NovoMix 50 in children under 18 years of age have not been established. No data are available.
Since marketing and during clinical trials, the frequency, type and severity of adverse effects observed in elderly patients and in patients with renal or hepatic impairment do not show any differences compared with greater experience acquired in the general population.
Reporting of suspected adverse reactions:Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continuous monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals should report any suspected adverse reaction via the national reporting system: National Agency for the Safety of Medicines and Health Products (ANSM) and the network of Regional Pharmacovigilance Centres. Website: https://signalement.social-sante.gouv.fr.
Overdose
For insulins, there is no specific definition of overdose.
However, hypoglycaemia may develop in successive stages if doses that are too high are administered relative to the patient's needs:- Episodes of moderate hypoglycaemia can be treated by oral administration of glucose or sugary foods. Diabetic patients are therefore advised to always carry sugary foods with them.
- Episodes of severe hypoglycaemia, with loss of consciousness, can be treated by intramuscular or subcutaneous administration of glucagon (0,5 to 1 mg) by a person trained for this purpose, or by intravenous administration of glucose by healthcare professionals. If the patient does not respond to glucagon within 10 to 15 minutes, glucose should be administered intravenously. As soon as the patient has regained consciousness, oral intake of carbohydrates is recommended in order to prevent a relapse.
Pharmacodynamics
Pharmacotherapeutic class: drugs used in diabetes; insulins and analogues for injection, combination of an intermediate- or long-acting analogue and a rapid-acting analogue (ATC code: A10AD05).
- NovoMix 30:
- NovoMix 30 is a biphasic suspension of 30% soluble insulin aspart (a rapid-acting analogue of human insulin) and 70% crystallised protamine insulin aspart (an intermediate-acting analogue of human insulin).
- NovoMix 50:
- NovoMix 50 is a biphasic suspension of 50% soluble insulin aspart (a rapid-acting analogue of human insulin) and 50% crystallised protamine insulin aspart (an intermediate-acting analogue of human insulin).
The glucose-lowering effect of insulin aspart is due to the binding of insulin to receptors on muscle and fat cells, thereby facilitating glucose uptake, and to the simultaneous inhibition of hepatic glucose production.
- NovoMix 30:
- NovoMix 30 is a biphasic insulin that contains 30% soluble insulin aspart. Owing to its rapid onset of action, it can be administered closer to meals (from 0 to 10 minutes before/after the meal) than soluble human insulin. The crystalline phase (70%) consists of crystallised protamine insulin aspart, whose activity profile is similar to that of human NPH insulin.
- Administered subcutaneously, NovoMix 30 begins to act within 10 to 20 minutes after injection. Its maximum effect occurs 1 to 4 hours after injection. Its duration of action can reach 24 hours (figure 1).
-
- NovoMix 50:
- NovoMix 50 is a biphasic insulin that contains 50% soluble insulin aspart. Owing to its rapid onset of action, it can be administered closer to meals (from 0 to 10 minutes before/after the meal) than soluble human insulin. The crystalline phase (50%) consists of crystallised protamine insulin aspart, whose activity profile is similar to that of human NPH insulin.
- Administered subcutaneously, NovoMix 50 begins to act within 10 to 20 minutes after injection. Its maximum effect occurs 1 to 4 hours after injection. Its duration of action is 14 to 24 hours (figure 2).
-
- On a molar basis, insulin aspart is equipotent to human insulin.
- NovoMix 30:
- In a 3-month study conducted in patients with type 1 and type 2 diabetes, NovoMix 30 showed glycosylated haemoglobin control similar to that associated with treatment with biphasic human insulin 30. On a molar basis, insulin aspart is equipotent to human insulin. NovoMix 30, administered before breakfast and before dinner (evening meal), resulted in lower postprandial blood glucose compared with biphasic human insulin 30 administered before the 2 meals (breakfast and dinner).
- A meta-analysis of nine studies conducted 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 alone or in combination with metformin, or to treatment with metformin in combination with a sulfonylurea. The primary efficacy criterion - that is, the HbA1c after 16 weeks of treatment - was not different between patients treated with NovoMix 30 in combination with metformin and patients treated with metformin in combination with a sulfonylurea. In this study, 57 % of patients had a baseline HbA1c above 9 %. In this group of patients, the HbA1c was significantly lower after treatment with NovoMix 30 in combination with metformin than after treatment with metformin in combination with a sulfonylurea.
- In one study, patients with type 2 diabetes, inadequately controlled on oral antidiabetic agents alone, were randomised to treatment with NovoMix 30 twice daily (117 patients) or treatment with insulin glargine once daily (116 patients). After 28 weeks of treatment corresponding to the dose recommendations described in section Posology/Method of administration, the mean reduction in HbA1c was 2,8 % with NovoMix 30 (mean HbA1c at baseline = 9,7 %). 66 % and 42 % of patients treated with NovoMix 30 achieved an HbA1c below 7 % and 6,5 % respectively, and the mean fasting plasma glucose decreased by approximately 7 mmol/l (from 14,0 mmol/l at baseline to 7,1 mmol/l).
- A meta-analysis performed in patients with type 2 diabetes showed that NovoMix 30, compared with human biphasic insulin 30, reduced the overall risk of nocturnal hypoglycaemic episodes as well as major hypoglycaemia. The overall risk of daytime hypoglycaemic episodes was increased in patients treated with NovoMix 30.
- NovoMix 30:
- A 16-week clinical trial comparing postprandial glycaemic control with NovoMix 30 administered at meals versus human insulin/human biphasic insulin 30 administered at meals and NPH insulin at bedtime was conducted in 167 patients aged 10 years to 18 years. The mean HbA1c remained similar throughout the study in both treatment groups, and there was no difference in the rate of hypoglycaemia with NovoMix 30 or human biphasic insulin 30.
- In a double-blind, cross-over clinical trial (12 weeks of each treatment), conducted in a smaller (54 patients) and younger population (from 6 years to 12 years), the rate of hypoglycaemic episodes and the postprandial rise in glycaemia were significantly lower with NovoMix 30 compared with human biphasic insulin 30. The final HbA1c was significantly lower in the group treated with human biphasic insulin 30 than in the NovoMix 30 group.
Pharmacokinetics
The substitution of the amino acid proline by aspartic acid at position B28 of insulin aspart reduces the tendency to form hexamers, as observed with soluble human insulin.
- NovoMix 30:
- The insulin aspart in the soluble phase of NovoMix 30 represents 30 % of total insulin; it is absorbed more rapidly from subcutaneous tissue than the soluble fraction of human biphasic insulin. The remaining 70 % consists of crystallised insulin aspart protamine in crystal form, whose prolonged absorption profile is similar to that of NPH human insulin.
- With NovoMix 30, the maximum serum insulin concentration is on average 50 % higher than that observed with human biphasic insulin 30. On average, the time to reach maximum concentration is half that of human biphasic insulin 30. In healthy volunteers, a mean maximum serum concentration of 140 ± 32 pmol/l was reached approximately 60 minutes after subcutaneous injection of a dose of 0,20 unit/kg body weight. The mean half-life (t½) of NovoMix 30, which reflects the absorption rate of the protamine-bound fraction, was approximately 8 to 9 hours. Return to baseline serum concentrations occurred within 15 to 18 hours after subcutaneous injection of the dose. In patients with type 2 diabetes, the maximum concentration was reached approximately 95 minutes after injection of the dose, and concentrations well above zero were measured at least 14 hours after administration.
- NovoMix 50:
- The insulin aspart in the soluble phase of NovoMix 50 represents 50 % of total insulin; it is absorbed more rapidly from subcutaneous tissue than the soluble fraction of human biphasic insulin. The remaining 50 % consists of crystallised insulin aspart protamine in crystal form, whose prolonged absorption profile is similar to that of NPH human insulin.
- In healthy volunteers, a mean maximum serum concentration of 445 ± 135 pmol/l was reached approximately 60 minutes after subcutaneous injection of a dose of 0,30 unit/kg body weight. In patients with type 2 diabetes, the maximum concentration was reached approximately 95 minutes after injection of the dose.
The pharmacokinetic properties of NovoMix 30 have not been studied in elderly patients or in patients with renal or hepatic impairment.
The pharmacokinetic properties of NovoMix 50 have not been studied in children, elderly patients or in patients with renal or hepatic impairment.
- NovoMix 30:
- The pharmacokinetic properties of NovoMix 30 have not been studied in children or adolescents. However, the pharmacokinetic and pharmacodynamic properties of soluble insulin aspart have been studied in children (6 to 12 years) and adolescents (13 to 17 years) with type 1 diabetes. Insulin aspart was absorbed rapidly in both groups, with a Tmax equivalent to that of adults. However, a variation of Cmax was observed according to age, which underlines the importance of individual dose adjustment of insulin aspart.
Preclinical safety
Non-clinical data from conventional safety pharmacology, repeated-dose toxicity, genotoxicity, and reproductive and developmental studies did not reveal any particular risk for humans.
In in vitro studies assessing both binding to the insulin and IGF-1 receptors and effects on cell growth, insulin aspart behaved very similarly to human insulin. The studies also demonstrated that the dissociation of insulin aspart binding from the insulin receptor was equivalent to that of human insulin.
INCOMPATIBILITIES
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.
Storage conditions
- Shelf life before opening:
- 2 years.
- To be stored in a refrigerator (between 2 °C and 8 °C). Keep away from the cooling element. Do not freeze.
- During use or carried as a spare:
- The product may be kept for a maximum of 4 weeks.
- Store below 30 °C. Do not refrigerate. Do not freeze.
- Keep the Penfill cartridge in the outer carton in order to protect from light.
- Keep the cap on the FlexPen in order to protect from light.
HANDLING/DISPOSAL INSTRUCTIONS
After taking NovoMix out of the refrigerator, it is recommended to wait for NovoMix to reach room temperature before resuspending the insulin as described in the instructions for first use.
Do not use this medicine if you notice that the resuspended liquid is not uniformly white, opaque and watery. It is necessary to tell the patient that it is important to resuspend NovoMix immediately before using it.
NovoMix must not be used if it has been frozen.
The patient will be advised that they must discard the needle after each injection.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
Needles, cartridges and prefilled pens must not be shared.
The cartridge must not be refilled.
Prescription, supply and reimbursement
LIST II| Marketing authorisation (AMM) | EU/1/00/142/004 ; CIP 3400935495259 (SmPC rev 22.05.2023) NovoMix 30 Penfill. |
| EU/1/00/142/009 ; CIP 3400935676641 (SmPC rev 22.05.2023) NovoMix 30 FlexPen. | |
| EU/1/00/142/015 ; CIP 3400937024297 (SmPC rev 22.05.2023) NovoMix 50 FlexPen. |
| Price: | 26,69 euros (5 NovoMix 30 Penfill cartridges). |
| 31,28 euros (5 NovoMix 30 FlexPen pens). | |
| 31,28 euros (5 NovoMix 50 FlexPen pens). | |
| Reimbursed by Social Security at 65 %. Collective. | |
Marketing authorisation holder: Novo Nordisk A/S, Denmark.
Local representative:
NOVO NORDISK
12, cours Michelet. 92800 Puteaux
Medical and pharmaceutical information:
Tel:
or 01 41 97 65 00 (free service and calls)
Fax:
E-mail: infomed@novonordisk.com
http://www.novonordisk.fr
Source: VIDAL · Updated on 11/11/2026. This information does not replace advice from a healthcare professional.