Reduction in blood glucose levels due to an increase of intracellular transport of insulin aspart after binding to insulin receptors of muscle and fat tissue and the simultaneous inhibition of glucose production by the liver.
After subcutaneous administration nandrolone phenylpropionate dosage effect develops within 10-20 minutes. Maximum effect is observed in the range of 1 to 4 hours after injection. The duration of action of the drug is 24 hours. In the three-month comparative clinical study involving patients with diabetes mellitus type 1 and 2, who received and biphasic human insulin 30, twice daily before breakfast and dinner, it was shown that is greatly reduced postprandial blood glucose (after breakfast and dinner).
Meta-analysis of the data obtained in the course of nine clinical trials involving patients with diabetes mellitus type 1 and 2, showed that when administered before breakfast and dinner, provides better control of postprandial blood glucose levels (mean increase in glucose levels prandial after breakfast, lunch and dinner), as compared to biphasic human insulin 30. Although fasting glucose in patients using , was higher overall has the same effect on the concentration of glycated hemoglobin (HbA 1c ) as biphasic human insulin 30.
In a clinical study involving 341 patients with type 2 diabetes, patients were randomized to the treatment group only, in combination with metformin and metformin in combination with sulfonylurea. The concentration of HbA 1c after 16 weeks of treatment was not different in patients treated in combination with metformin in patients treated with metformin in combination with sulfonylureas. In this study, 57% of patients base concentration HbA 1c was higher than 9%; therapy in these patients, drug in combination with metformin, has led to a significant reduction in the concentration of HbA 1c than in patients treated with metformin in combination with sulfonylureas.
Children and adolescents: There were conducted 16-week clinical study that compared the blood glucose after a meal on the background of (before the meal), human insulin / biphasic human insulin 30 (before meals) and isophane insulin (administered before bedtime). The study involved 167 patients aged 10 to 18 years. The average values of HbA 1c in both groups remained close to the initial values throughout the study. Also, when applying or biphasic human insulin 30, there was no difference in the incidence of hypoglycemia.
It was also a double-blind crossover study of patients in a population aged 6 to 12 years (a total of 54 patients, 12 weeks on each treatment). The incidence of hypoglycemia and increasing glucose after meals in patients who used , were significantly lower compared with the values in the group of patients treated with biphasic human insulin 30. The values of HbA 1c at the end of the study group using a biphasic human insulin 30 were significantly lower than in the group of patients treated.
Nandrolone phenylpropionate dosage in patients with middle and old age has not been studied. However, in a randomized double-blind crossover study conducted on 19 patients with type 2 diabetes aged 65-83 years (mean age – 70 years) compared the pharmacokinetics and pharmacodynamics of insulin aspart and soluble human insulin. Relative differences values pharmacodynamic parameters (maximal glucose infusion rate – GIR max and the area under the curve of its infusion rate for 120 minutes following administration of insulin formulations – AUC GIR , 0-120 min) between insulin aspart and human insulin in elderly patients are similar to those in healthy volunteers and in younger patients with diabetes mellitus.
In insulin aspart substitution of amino acid proline at position B28 with Aspartic acid molecules reduces the tendency to form hexamers in the soluble fraction which is observed in the soluble human insulin. Therefore insulin aspart (30%) is absorbed from the subcutaneous fat faster than soluble insulin contained in the two-human insulin. The remaining 70% is the share of the crystalline form of insulin aspart protamine, the rate of absorption is the same as that of human NPH insulin.
The maximum concentration in serum insulin after administration to 50% higher than in two-phase human insulin 30, and the time to achieve shorter half compared to human insulin 30 biphasic.
In healthy volunteers after subcutaneous injection rate 0.20 IU / kg body weight of the maximum concentration of insulin aspart was achieved in serum 60 min and was 140 ± 32 pmol / L.Long half-life (t 1/2 ) of the which reflects the rate of absorption associated with protamine fraction was 8-9 hours. Insulin serum returned to baseline by 15-18 hours after subcutaneous administration. Patients maximum concentration of type 2 diabetes was achieved by 95 minutes after administration and remained above the initial at least 14 hours.
A study of the pharmacokinetics of the drug in elderly patients have been conducted. However, the relative differences in pharmacokinetic parameters values between insulin aspart and human soluble insulin in elderly patients with type 2 diabetes (ages 65-83 years old, average age – 70 years) were similar to those in healthy subjects and in younger patients with diabetes mellitus. In elderly patients, there was a decrease in the rate of absorption, resulting in a slowdown in t max (82 minutes (interquartile range: 60-120 minutes)), while the average maximum concentration C max was similar to that observed in younger patients with type 2 diabetes, and slightly less than in patients with type 1 diabetes.
Patients with impaired renal and hepatic function:
The study of the pharmacokinetics of the drug in patients with impaired renal and hepatic function have not been conducted. However, with increasing doses in patients with various degrees of renal impairment and liver changes were observed in the pharmacokinetics of insulin aspart soluble.
Children and adolescents:
The pharmacokinetic properties of the drug in children and adolescents have not been studied. 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. Patients in both age groups, insulin aspart was characterized by fast absorption and values of t max, similar to those in adults. However, the values of C max in two age groups were different, indicating the importance of individual selection of doses of insulin aspart.
Preclinical safety data
Preclinical studies did not reveal nandrolone phenylpropionate dosage any danger to humans, based on conventional pharmacological safety of these studies, the toxicity of repeated application, genotoxicity and reproductive toxicity.
In in vitro tests include binding to insulin and IGF-1 receptors and the effect on cell growth, it has been shown that the properties of insulin aspart properties similar to human insulin. The research results also show that the dissociation of binding to insulin aspart insulin receptors equivalent to that of human insulin.
Indications for use:
- Increased individual sensitivity to insulin aspart or any of the components of the drug
is not recommended for use in children under 6 years old because clinical studies NovoMiks® 30 Penfill® have not been conducted.
Pregnancy and lactation
Clinical experience with drug NovoMiks® 30 Penfill® during pregnancy is limited.
Research on the use NovoMiks® 30 Penfill® preparation were not carried out in pregnant women. However, data from two randomized controlled clinical trials (respectively, 157 and 14 pregnant women treated with insulin aspart in a basal-bolus regimen) did not reveal any adverse effect of insulin aspart on pregnancy or the fetus / newborn health compared to soluble human insulin. Furthermore, in a randomized clinical study of 27 women with gestational diabetes treated with insulin aspart and human soluble insulin (insulin aspart 14 women was obtained, the human insulin – 13) have been demonstrated similar safety profiles for both types of insulin.
During a possible pregnancy and throughout its life it is necessary to conduct careful monitoring of the patients with diabetes mellitus, and control the concentration of glucose in the blood. Insulin requirements usually decreases trimester I and II gradually increases during and III trimester of pregnancy. Shortly after birth, insulin requirements quickly returns to a level that was before pregnancy.
During breastfeeding NovoMiks® 30 Penfill® can be used without restrictions. The introduction of the nursing mother of insulin is not a threat to the child. However, it may be necessary to correct the dose NovoMiks® 30 Penfill®.
Dosage and administration:
NovoMiks® 30 Penfill® is intended for subcutaneous administration. You can not enter NovoMiks® 30 Penfill® intravenously, as it may result in severe hypoglycaemia. You should also avoid intramuscular NovoMiks® 30 Penfill®. Do not use NovoMiks® 30 Penfill® for subcutaneous insulin infusion (CSII) in insulin pumps.
Dose NovoMiks® Penfill® 30 determined by the physician individually in each case in accordance with the needs of the patient. In order to achieve optimal glycemic control is recommended in the blood glucose concentrations and dose adjustment.
Patients with type 2 diabetes NovoMiks® 30 Penfill® can be administered as a monotherapy, or in combination with oral hypoglycemic drugs in cases where blood glucose insufficiently regulated only oral hypoglycemic drugs.
Initiation of therapy
for patients with type 2 diabetes who are insulin first appointed, the recommended initial dose NovoMiks® 30 Penfill® is 6 units before breakfast and before dinner 6 units. Also allowed the introduction of 12 units NovoMiks® 30 Penfill® once daily in the evening (before dinner).
Translated patient with other insulin products
When transferring a patient from biphasic human insulin to NovoMiks® 30 Penfill® should start with the same dose and schedule of administration. Then the dose is adjusted according to the individual patient’s needs (see. The following recommendations for dose titration). As always when transferring a patient to a new type of insulin requires strict medical supervision in the translation between the patient and in the first week of use of the new drug.
Strengthen therapy NovoMiks® 30 Penfill® can use the transition with a single daily dose to a double. It recommended after the dose of 30 IU of the drug to pass on the use of NovoMiks® 30 Penfill® twice daily, divided dose into two equal parts – morning and evening (before breakfast and dinner).
Daylight NovoMiks® 30 Penfill® application three times a day is possible by splitting the morning dose into two equal parts and the introduction of these two parts morning and at lunch (three-times daily dose).
for dose adjustments NovoMiks® 30 Penfill® is used the least value in fasting blood glucose concentration obtained in the last three days.
To assess the adequacy of the previous dose value are used in the blood glucose concentration prior to the next meal.
Dose adjustment can be carried out once a week to reach the target value in HbA 1c .
Do not increase the dose, if hypoglycaemia was observed in this period.
Dosage adjustment may be needed in the amplification of patient physical activity, changing its usual diet or the presence of comorbidities. cernos gel