NovoRapid FlexPen, 100 me/ml syringe pens 3 ml, 5 pcs.

Composition

Active ingredient:

insulin aspart 100 units (3.5 mg);

Auxiliary substances:

glycerol — 16 mg;

phenol — 1.5 mg;

metacresol — 1,72 mg;

zinc chloride — 19.6 µg;

sodium chloride 0,58 mg;

sodium hydrogen phosphate dihydrate — 1.25 mg;

sodium hydroxide 2 M of about 2.2 mg;

hydrochloric acid 2 M — about 1.7 mg;

water for injection — up to 1 ml

Pharmacological action

NovoRapid FlexPen – hypoglycemic.

Pharmacodynamics

Insulin aspart is a short-acting human insulin analog produced by recombinant DNA biotechnology using the Saccharomyces cerevisiae strain, in which the amino acid proline at position B28 is substituted for aspartic acid.

It interacts with a specific receptor of the outer cytoplasmic membrane of cells and forms an insulin-receptor complex that stimulates intracellular processes, including the synthesis of a number of key enzymes (including hexokinase, pyruvate kinase, and glycogen synthetase). The decrease in blood glucose is caused by an increase in its intracellular transport, increased absorption by tissues, stimulation of lipogenesis, glycogenogenesis, and a decrease in the rate of glucose production by the liver.

Substitution of the amino acid proline at position B28 for aspartic acid in insulin aspart reduces the tendency of molecules to form hexamers, which is observed in a solution of ordinary insulin. In this regard, insulin aspart is absorbed much faster from subcutaneous fat and begins to act much faster than soluble human insulin. Insulin aspart reduces blood glucose levels more strongly in the first 4 hours after a meal than soluble human insulin.

The duration of action of insulin aspart after subcutaneous administration is shorter than that of soluble human insulin.

After subcutaneous administration, the effect of the drug begins within 10-20 minutes after administration. The maximum effect is observed 1-3 hours after the injection. The duration of action of the drug is 3-5 hours.

Clinical studies involving patients with type 1 diabetes mellitus have demonstrated a reduced risk of nocturnal hypoglycemia when using insulin aspart compared to soluble human insulin. The risk of daytime hypoglycemia was not significantly increased.

Insulin aspart is equipotential to soluble human insulin based on molarity indicators.

Adults. Clinical studies involving patients with type 1 diabetes mellitus demonstrate a lower postprandial blood glucose concentration when administered with insulin aspart compared to soluble human insulin.

Elderly people. A randomized, double-blind, cross-sectional study of the pharmacokinetics and pharmacodynamics (FC/PD) of insulin aspart and soluble human insulin was conducted in elderly patients with type 2 diabetes mellitus (19 patients aged 65-83 years, mean age 70 years). The relative differences in pharmacodynamic properties between insulin aspart and soluble human insulin in elderly patients were similar to those in healthy volunteers and in younger diabetic patients.

Children and teenagers. The use of insulin aspart in children showed similar results of long-term glycemic control when compared with soluble human insulin.

A clinical trial using pre-meal soluble human insulin and post-meal insulin aspart was conducted in young children (26 patients aged 2 to 6 years); and a single-dose pharmacokinetic/pharmacodynamic (FC/PD) study was conducted in children (6-12 years) and adolescents (13-17 years). The pharmacodynamic profile of insulin aspart in children was similar to that in adult patients.

Pregnancy. Clinical studies comparing the safety and efficacy of insulin aspart and human insulin in the treatment of pregnant women with type 1 diabetes mellitus (322 examined pregnant women,157 of them received insulin aspart,165-human insulin) did not reveal any negative effects of insulin aspart on the course of pregnancy or the health of the fetus/newborn.

Additional clinical studies of 27 women with gestational diabetes receiving insulin aspart and human insulin (14 women received insulin aspart and 13 received human insulin) indicate comparability of safety profiles, along with significant improvements in postprandial glucose control when treated with insulin aspart.

Preclinical safety data.

In the course of preclinical studies, no danger to humans was identified, based on data from generally accepted studies of pharmacological safety, repeated use toxicity, genotoxicity and reproductive toxicity.

In vitro tests, including binding to insulin receptors and insulin-like growth factor-1, as well as the effect on cell growth, the behavior of insulin aspart is very similar to that of human insulin. The results also showed that the dissociation of the binding of insulin aspart to the insulin receptor is equivalent to that of human insulin.

Pharmacokinetics

After subcutaneous administration of insulin aspart, Tmax in blood plasma is on average 2 times less than after administration of soluble human insulin. Cmax in blood plasma is on average (492±256) pmol / l and is reached 40 minutes after subcutaneous administration of a dose of 0.15 U / kg in patients with type 1 diabetes mellitus. The concentration of insulin returns to the initial level 4-6 hours after administration of the drug. The rate of absorption is slightly lower in patients with type 2 diabetes, resulting in a lower Cmax — (352±240) pmol / L-and a later Tmax (60 min). Intra-individual Tmax variability is significantly lower when using insulin aspart compared to soluble human insulin, while the indicated Cmax variability for insulin aspart is greater.

Pharmacokinetics in children (6-12 years) and adolescents (13-17 years) with type 1 diabetes mellitus. Insulin aspart absorption occurs rapidly in both age groups with a Tmax similar to that in adults. However, there are differences in Cmax in the two age groups, which emphasizes the importance of individual dosage of the drug.

Elderly patients. Relative differences in pharmacokinetics between insulin aspart and soluble human insulin in elderly patients (65-83 years, mean age-70 years) Patients with type 2 diabetes were similar to those in healthy volunteers and younger diabetics. In elderly patients, a decrease in the rate of absorption was observed, which led to a slowdown in Tmax-82 (variability 60-120) min, while Cmax was the same as that observed in younger patients with type 2 diabetes mellitus and slightly less than in patients with type 1 diabetes mellitus.

Insufficient liver function. The pharmacokinetics of a single dose of insulin aspart were studied in 24 patients with liver function ranging from normal to severe impairment. In individuals with impaired liver function, the rate of absorption of insulin aspart was reduced and more variable, resulting in a slowing of Tmax from about 50 minutes in individuals with normal liver function to about 85 minutes in individuals with moderate to severe hepatic impairment. AUC, Cmax in plasma and total clearance (CL/F) were similar in individuals with reduced and normal liver function.

Insufficient renal function. A study of the pharmacokinetics of insulin aspart was conducted in 18 patients whose renal function ranged from normal to severe impairment. There was no obvious effect of creatinine clearance on the AUC, Cmax, and Tmax of insulin aspart. Data were limited to those with moderate to severe renal impairment. Individuals with renal insufficiency requiring dialysis were not included in the study.

Indications

Diabetes mellitus in adults, adolescents, and children over 2 years of age.

Contraindications

Increased individual sensitivity to insulin aspart or any of the components of the drug.

It is not recommended to use the drug NovoRapid ® FlexPen® in children under 2 years of age, because clinical studies in children under 2 years of age have not been conducted.

Interaction

There are a number of drugs that affect the need for insulin. The hypoglycemic effect of insulin is enhanced by oral hypoglycemic drugs, MAO inhibitors, ACE inhibitors, carbonic anhydrase inhibitors, non-selective beta-blockers, bromocriptine, sulfonamides, anabolic steroids, tetracyclines, clofibrate, ketoconazole, mebendazole, pyridoxine, theophylline, cyclophosphamide, fenfluramine, lithium preparations, salicylates.

The hypoglycemic effect of insulin is weakened by oral contraceptives, corticosteroids, thyroid hormones, thiazide diuretics, heparin, tricyclic antidepressants, sympathomimetics, somatropin, danazol, clonidine, BCC, diazoxide, morphine, phenytoin, nicotine.

Beta-blockers can mask the symptoms of hypoglycemia.

Octreotide / lanreotide can both increase or decrease the need for insulin.

Alcohol can both increase or decrease the hypoglycemic effect of insulin.

Incompatibility. Some drugs, such as those containing thiol or sulfite groups, may cause destruction of insulin aspart when added to NovoRapid FlexPen.The drug NovoRapid ® FlexPen® should not be mixed with other drugs.

How to take, course of administration and dosage

N/ A, v/V.

NovoRapid ® FlexPen® is a fast-acting insulin analog. Dose of NovoRapid® FlexPen® it is determined by the doctor individually, in accordance with the patient’s needs.

Usually, the drug is used in combination with insulin preparations of medium duration or long-acting, which are administered at least once a day. To achieve optimal glycemic control, it is recommended to regularly measure the concentration of glucose in the blood and adjust the dose of insulin.

Usually, the individual daily need for insulin in adults and children is from 0.5 to 1 U/kg. When the drug is administered before meals, the need for insulin can be provided by the drug NovoRapid ® FlexPen® by 50-70%, the remaining need for insulin is provided by extended-acting insulin.

Increased physical activity of the patient, changes in the usual diet or concomitant diseases may lead to the need for dose adjustment.

NovoRapid ® FlexPen® has a faster onset and shorter duration of action than soluble human insulin. Due to the faster onset of action, NovoRapid® FlexPen® should usually be administered immediately before a meal, if necessary, it can be administered shortly after a meal.

Due to the shorter duration of action compared to human insulin, the risk of developing nocturnal hypoglycemia in patients receiving NovoRapid® FlexPen® is lower.

Special patient groups. As with other insulin preparations, elderly patients and patients with renal or hepatic insufficiency should be more carefully monitored for blood glucose concentrations and adjust the dose of insulin aspart individually.

Children and teenagers. It is preferable to use NovoRapid® FlexPen® instead of soluble human insulin in children when a rapid onset of action of the drug is necessary, for example, when it is difficult for the child to observe the required time interval between injection and meal.

Transfer from other insulin preparations. When transferring a patient from other insulin preparations to NovoRapid® FlexPen®, it may be necessary to adjust the dose of NovoRapid® FlexPen®and basal insulin.

NovoRapid ® FlexPen® is administered subcutaneously in the anterior abdominal wall, hip, shoulder, deltoid or gluteal region. Injection sites within the same area of the body should be changed regularly to reduce the risk of developing lipodystrophy. As with all insulin preparations, subcutaneous administration to the anterior abdominal wall provides faster absorption compared to administration to other sites. The duration of action depends on the dose, the site of administration, the intensity of blood flow, temperature and level of physical activity. However, the faster onset of action compared to soluble human insulin persists regardless of the location of the injection site.

NovoRapid® It can be used for continuous subcutaneous insulin infusions (PPIs) in insulin pumps designed for insulin infusions. PPII should be performed in the anterior abdominal wall. Infusion sites should be changed periodically.

When using an insulin pump for NovoRapid®infusions do not mix with other types of insulins.

Patients using PPII should be fully trained in the use of the pump, the appropriate reservoir, and the pump tubing system. The infusion set (tube and catheter) should be replaced in accordance with the user’s manual provided with the infusion set.

Patients receiving NovoRapid® with PPII should have additional insulin available in case of failure of the infusion system.

In / in introduction. If necessary, use NovoRapid® it can be administered intravenously, but only by qualified medical personnel.

For intravenous administration, infusion systems are used with the drug NovoRapid ® 100 U / ml with a concentration of 0.05 to 1 U/ml of insulin aspart in 0.9% sodium chloride solution,5% dextrose solution or 10% dextrose solution containing 40 mmol / l of potassium chloride, using polypropylene infusion containers. These solutions are stable at room temperature for 24 hours. Although stable for some time, a certain amount of insulin is initially absorbed by the infusion system material. During insulin infusions, it is necessary to constantly monitor the concentration of blood glucose.

Overdose

Symptoms. The exact dose required for an insulin overdose has not been established, but hypoglycemia may develop gradually if too high doses are administered in relation to the patient’s needs.

Treatment. The patient can eliminate mild hypoglycemia by taking glucose or sugar-containing foods inside. Therefore, patients with diabetes are advised to carry sugar-containing products at all times.

In the case of severe hypoglycemia, when the patient is unconscious,0.5 mg to 1 mg of glucagon should be administered intravenously or subcutaneously (can be administered by a trained person) or intravenously glucose (dextrose) solution (can only be administered by a medical professional).

It is also necessary to inject dextrose intravenously if the patient does not regain consciousness 10-15 minutes after glucagon administration. After regaining consciousness, the patient is recommended to take a carbohydrate-rich diet to prevent the recurrence of hypoglycemia.

Special instructions

Before a long trip involving jet lag, the patient should consult with their healthcare provider, as jet lag means that the patient must eat and administer insulin at a different time.

Hyperglycemia. Insufficient dosage of the drug or discontinuation of treatment, especially in patients with type 1 diabetes, can lead to the development of hyperglycemia and diabetic ketoacidosis. As a rule, the symptoms of hyperglycemia appear gradually, over several hours or days. Symptoms of hyperglycemia include nausea, vomiting, drowsiness, red and dry skin, dry mouth, increased urine output, thirst and loss of appetite, and the smell of acetone in the exhaled air. Without appropriate treatment, hyperglycemia can lead to death.

Hypoglycemia. Skipping meals, having an unplanned high level of exercise, or taking too much insulin in relation to the patient’s needs can lead to hypoglycemia. After compensation of carbohydrate metabolism, for example, with intensive insulin therapy, patients may change their typical symptoms-harbingers of hypoglycemia, which patients should be informed about. The usual harbinger symptoms may disappear with a prolonged course of diabetes mellitus.

A consequence of the pharmacodynamic characteristics of short-acting insulin analogues is that the development of hypoglycemia with their use may begin earlier than with the use of soluble human insulin.

Since NovoRapid ® FlexPen® should be used in direct connection with food intake, it is necessary to take into account the high rate of onset of the drug’s effect in the treatment of patients with concomitant diseases or taking drugs that slow down the absorption of food. Concomitant diseases, especially those that are infectious and accompanied by fever, usually increase the body’s need for insulin. Dose adjustment of the drug may also be required if the patient has concomitant diseases of the kidneys, liver, adrenal gland, pituitary gland or thyroid gland.

When a patient is switched to other types of insulin, the early warning symptoms of hypoglycemia may become less pronounced compared to those with the previous type of insulin.

Transfer of the patient from other insulin preparations. The transfer of a patient to a new type of insulin or an insulin preparation from another manufacturer must be carried out under strict medical supervision. If you change the concentration, type, manufacturer and type (human insulin, animal-derived insulin, human insulin analog) of insulin preparations and/or the manufacturing method, you may need to change the dose or increase the frequency of injections compared to previously used insulin preparations. If a dose adjustment is necessary, it can be made already at the first administration of the drug or during the first weeks or months of treatment.

Reactions at the injection site. As with other insulin preparations, reactions at the injection site may develop, which is manifested by pain, redness, urticaria, inflammation, hematoma, swelling and itching. Regularly changing the injection site in the same anatomical area can reduce symptoms or prevent the development of reactions. In very rare cases, discontinuation of NovoRapid® FlexPen®may be necessary.

Simultaneous use of drugs of the thiazolidinedione group and insulin preparations. Cases of chronic heart failure have been reported when patients are treated with thiazolidinediones in combination with insulin preparations, especially when these patients have risk factors for developing chronic heart failure. This fact should be taken into account when prescribing combination therapy with thiazolidinediones and insulin preparations to patients.When prescribing such combination therapy, it is necessary to conduct medical examinations of patients for signs and symptoms of chronic heart failure, weight gain and the presence of edema. If the symptoms of heart failure worsen in patients, treatment with thiazolidinediones should be discontinued.

Influence on the ability to drive vehicles and work with mechanisms. Patients ‘ ability to concentrate and react quickly may be impaired during hypoglycemia, which can be dangerous in situations where these abilities are particularly necessary (for example, when driving a vehicle or working with machines and mechanisms). Patients should be advised to take measures to prevent the development of hypoglycemia when driving vehicles and working with mechanisms. This is especially important for patients with the absence or reduction of symptoms-harbingers of developing hypoglycemia or suffering from frequent episodes of hypoglycemia.

Form of production

Solution for intravenous and subcutaneous administration

Storage conditions

Store in a dark place, at a temperature of 2-8 °C (do not freeze)

Shelf life

30 months

Active ingredient

Insulin aspart

Conditions of release from pharmacies

By prescription

Dosage form

solution for injection

Purpose

For pregnant women as prescribed by a doctor, For children as prescribed by a doctor, For nursing mothers as prescribed by a doctor, For adults as prescribed by a doctor

Indications

Type 2 Diabetes, Type 1 Diabetes

Weight

Weight: 149 g.