NovoMix 30 FlexPen , 10x3ml, Novo Nordisk Pharma GmbH , NovoMix

NovoMix 30 FlexPen , 10x3ml, Novo Nordisk Pharma GmbH , NovoMix

Indication

  pharmacodynamics. NovoMix 30 FlexPen is a two-phase suspension consisting of a mixture of insulin analogues: insulin aspart (an analogue of short-acting human insulin) and protamine-insulin aspart (an analogue of medium-acting human insulin). A decrease in blood glucose levels under the influence of insulin aspart occurs after it binds to insulin receptors, which promotes the uptake of glucose into muscle and fat cells and at the same time inhibits the release of glucose from the liver.NovoMix 30 FlexPen is a two-phase suspension containing 30% soluble insulin aspart. This ensures a faster onset of action compared to soluble human insulin, which allows the drug to be administered immediately before meals (from 0 to 10 minutes). The crystalline phase (70%) consists of protamine insulin aspart, which has the same activity profile as human neutral protamine Hagedorn insulin (NPH).NovoMix 30 FlexPen begins to act 10–20 minutes after subcutaneous injection. The maximum effect is achieved 1–4 hours after administration. Duration of action — up to 24 hours.
  The level of glycosylated hemoglobin in patients with type I and II diabetes mellitus who were administered NovoMix 30 FlexPen for 3 months was the same as when administered biphasic human insulin. When administered in equal molar doses, insulin aspart is equipotential to human insulin.In a clinical study, patients with type II diabetes mellitus (341 people), divided into groups according to a randomized principle, received only NovoMix 30 FlexPen or NovoMix 30 FlexPen in combination with metformin, or metformin in combination with a sulfonylurea. After 16 weeks of treatment, HbA1c concentrations in patients receiving NovoMix 30 FlexPen in combination with metformin or metformin in combination with a sulfonylurea were the same. In this study, 57% of patients had HbA1c levels >9%. In these patients, combined treatment with NovoMix 30 FlexPen and metformin caused a more pronounced decrease in HbA1c levels compared to the combination of metformin and sulfonylurea.In the study, patients with type II diabetes mellitus, in whom glycemic control only with oral hypoglycemic drugs was ineffective, were administered NovoMix 30 FlexPen 2 times a day (117 patients) or insulin glargine 1 time a day (116 patients). After 28 weeks of treatment with NovoMix 30 FlexPen, accompanied by dose adjustment, the HbA1c level decreased by 2.8% (the average HbA1c value at inclusion in the study was 9.7%). When treated with NovoMix 30 FlexPen, HbA1c levels <7% were achieved by 66% of patients, and <6.5% by 42% of patients; at the same time, the fasting plasma glucose concentration decreased by approximately 7 mmol/l (from 14.0 mmol/l before treatment to 7.1 mmol/l).
A meta-analysis conducted in patients with type II diabetes mellitus showed a decrease in the risk of episodes of hypoglycemia at night and severe hypoglycemia during treatment with NovoMix 30 FlexPen compared with biphasic human insulin. At the same time, the risk of episodes of hypoglycemia during the day was higher in patients receiving NovoMix 30 FlexPen.
Pregnancy period.Novomix 30 has not been studied in pregnant women. However, in clinical studies comparing the safety and effectiveness of insulin aspart and soluble human insulin in the treatment of pregnant women with type I diabetes mellitus (a total of 322 pregnant women, insulin aspart — 157 people, soluble human insulin — 165 people), no side effects of insulin aspart on the fetus were detected or a newborn.
  In addition, in a clinical study of 27 women with gestational diabetes who received insulin aspart (14 people) or soluble human insulin (13 people), there were no differences in the safety of treatment with both drugs.
Children and teenagers. A 16-week study involving 167 patients aged 10–18 years compared the effectiveness of maintaining postprandial glycemic control with mealtime administration of NovoMix 30 FlexPen using human insulin/biphasic human insulin 30 with meals with NPH insulin injections at bedtime. Throughout the entire study period, in both groups, the HbA1c concentration remained at the level that was at inclusion in the study; however, there were no differences in the incidence of hypoglycemia episodes.
In a double-blind crossover study (12 weeks per treatment course) conducted in a relatively small group of children (54 people) aged 6–12 years, the increase in the number of episodes of hypoglycemia and the increase in glucose concentration were statistically significantly less during treatment with NovoMix 30 FlexPen compared with biphasic human insulin 30. The HbA1c level at the end of treatment was significantly lower in the group that received biphasic human insulin 30 than in the group that took NovoMix 30 FlexPen.Elderly persons. The pharmacodynamics of the drug NovoMix 30 FlexPen has not been studied in elderly and senile patients. However, a randomized, double-blind, crossover study was conducted that compared the pharmacokinetics and pharmacodynamics of insulin aspart and soluble human insulin in 19 patients with type II diabetes mellitus aged 65 years to 83 years. The relative differences in pharmacodynamic parameters (GIRmax, AUCgir0-120 min) after administration of insulin aspart or human insulin in these patients were the same as in practically healthy individuals or young patients with diabetes mellitus.
Pharmacokinetics. In insulin aspart, the amino acid proline at position 28 of the B-chain of the insulin molecule is replaced by aspartic acid, which reduces the formation of hexamers formed in soluble human insulin preparations. In the soluble phase of the drug NovoMix 30 FlexPen, the proportion of insulin aspart is 30% of total insulin. It is absorbed into the blood from subcutaneous tissue faster than soluble biphasic human insulin. The remaining 70% is the share of the crystalline form of protamine insulin aspart, the longer absorption intensity of which is the same as that of human NPH insulin.
  Cmax of insulin in the blood serum after administration of the drug NovoMix 30 FlexPen is 50% higher, and the time to achieve it is half as short compared to biphasic human insulin 30. In healthy volunteers after subcutaneous administration of the drug NovoMix 30 FlexPen at the rate of 0.20 U/kg body weight Cmax of insulin aspart in blood serum was achieved after 60 minutes and amounted to 140±32 pmol/l. T1/2 of NovoMix 30 FlexPen, which reflects the rate of absorption of the protamine fraction, was approximately 8–9 hours. The level of insulin in the blood serum returned to baseline 15–18 hours after subcutaneous administration. In patients with type II diabetes mellitus, Cmax was achieved 95 minutes after administration and remained above the initial concentration for at least 14 hours.
Children and teenagers

The pharmacokinetics of NovoMix 30 FlexPen have not been studied in children and adolescents. However, the pharmacokinetics and pharmacodynamics of soluble insulin aspart were studied in children (6–12 years) and adolescents (13–17 years) with type 1 diabetes mellitus. It was rapidly absorbed in patients from both groups, with tmax values ​​being the same as in adults. At the same time, Cmax values ​​in different groups differed significantly, which indicates the importance of individual selection of doses of insulin aspart.Elderly persons. The pharmacokinetics of NovoMix 30 FlexPen have not been studied in elderly patients. However, the relative discrepancies in the values ​​of pharmacodynamic parameters after the administration of insulin aspart or human insulin to patients with type II diabetes mellitus of elderly and senile age (65 years — 83 years, average age — 70 years) were the same as in practically healthy individuals or patients with diabetes mellitus more than young age. In elderly and senile patients, the rate of absorption decreases, as evidenced by a longer time to reach Cmax of insulin in the blood (tmax) (82 min with an interquartile range of 60–120 min). In this case, the value of Cmax was the same as and in patients with type II diabetes mellitus of younger age, and slightly lower than in patients with type I diabetes mellitus.
The pharmacokinetics of NovoMix 30 FlexPen have not been studied in patients with impaired renal or hepatic function.

Contraindication

  hypoglycemia; hypersensitivity to insulin aspart or any component of the drug.

Dosing

  Insulin dosage is individual and determined by the doctor in accordance with the patient’s needs. Since the effect of NovoMix 30 FlexPen occurs faster than biphasic human insulin, it should be administered immediately before meals. If necessary, NovoMix 30 FlexPen can be administered a short period of time after meals. On average, a patient’s need for insulin, depending on body weight, ranges from 0.5 to 1.0 IU/kg/day.It can be fully or partially achieved by administering the drug NovoMix 30 FlexPen. The daily need for insulin may increase in patients with insulin resistance (for example, obesity) and decrease in patients with remaining residual production of endogenous insulin.
NovoMix 30 FlexPen is usually injected subcutaneously into the thigh area. You can also give injections to the anterior abdominal wall, buttocks or deltoid muscle of the shoulder. To avoid lipodystrophy, the injection site should be changed even within the same body area.
Like other insulin medications, the duration of action may vary depending on the dose, injection site, blood flow rate, body temperature and level of physical activity. The dependence of the absorption rate on the site of drug administration has not been studied.
For patients with type II diabetes mellitus, NovoMix 30 FlexPen can be prescribed both as monotherapy and in combination with oral hypoglycemic agents in cases where blood glucose cannot be effectively controlled using only hypoglycemic drugs.
For patients with type II diabetes mellitus, the recommended initial dose of NovoMix 30 FlexPen is 6 units before breakfast and 6 units before dinner. You can begin its administration with a dose of 12 units before dinner. After reaching a dose of 30 units, it is usually recommended to switch from a single injection to 2 injections per day of 15 units before breakfast and dinner. Then you can safely switch to 3 injections per day and administer half the morning dose before breakfast and lunch.