Reisodeg FlexTouch solution for subcutaneous injection 100edlml cartridge 3ml 5pcs in syringe pen

Composition

>1 ml contains: Active ingredient: a mixture of insulin degludec and insulin aspart in the ratio of 70/30 (equivalent to 2.56 mg of insulin degludec and 1.05 mg of insulin aspart) 100 UNITS*Auxiliary substances: glycerol – 19 mg, phenol – 1.5 mg, metacresol – 1.72 mg, zinc 27.4 mcg (in the form of zinc acetate 92 mcg), sodium chloride 0.58 mg, hydrochloric acid or sodium hydroxide (for pH correction), water d/i – up to 1 ml. * 1 UNIT contains 0.0256 mg of anhydrous salt-free insulin degludec and 0.0105 mg of anhydrous salt-free insulin aspart, which corresponds to 1 IU of human insulin,1 UNIT insulin detemir, insulin glargine, or biphasic insulin aspart.

Pharmacological action

Risodeg Flext Ach is a combined preparation consisting of a soluble analog of ultra-long-acting human insulin (insulin degludec) and a fast-acting soluble analog of human insulin (insulin aspart), produced by recombinant DNA biotechnology using the Saccharomyces cerevisiae strain.

Mechanism of action

Insulin degludec and insulin aspart specifically bind to the human endogenous insulin receptor and interact with it, realizing their pharmacological effect similar to that of human insulin. The hypoglycemic effect of insulin is due to an increase in glucose utilization by tissues after binding insulin to muscle and fat cell receptors, and a simultaneous decrease in the rate of glucose production by the liver.

Pharmacodynamics

The pharmacodynamic effects of the components of Risodeg Flext Ach are clearly different and the overall profile of the drug reflects the profiles of the individual components: fast-acting insulin aspart and ultra-long-acting insulin degludec.

The basal component of the drug Raizodeg Flext Ach, which has an ultra-long action (insulin degludec), after subcutaneous injection forms soluble multihexamers in the subcutaneous depot, from which a continuous slow flow of insulin degludec into the circulation occurs, providing a flat action profile and a stable hypoglycemic effect of the drug. This effect persists in combination with insulin aspart and does not affect the rate of absorption of monomers of fast-acting insulin aspart.

The drug Risodeg Flext Ach begins to act quickly, providing a prandial need for insulin shortly after injection, and while the basal component has a flat, stable and ultra-long action profile that provides a basal need for insulin. The duration of action of a single dose of Risodeg Flext Ach is more than 24 hours.

A linear relationship between increasing the dose of Risodeg Flext Ach and its overall and maximum hypoglycemic effect was proved. The equilibrium concentration of Risodeg Flext Ach is reached after 2-3 days of drug use.

There were no differences in the Pharmacodynamics of Risodeg Flext Ach in elderly and senile patients and younger patients.

Clinical efficacy and safety

Five international randomized controlled open-label clinical trials of Raizodeg in the “Treatment to the Goal” mode were conducted for 26 or 52 pedels with the participation of 1,360 patients with diabetes mellitus (362 patients with type 1 diabetes mellitus and 998 patients with type 2 diabetes mellitus). Two comparative studies were conducted on a single dose of Risodeg in combination with oral hypoglycemic drugs (PGGP) and a single dose of insulin glargine in combination with PGGP in patients with type 2 diabetes mellitus. Raizodeg twice daily in combination with PPHP was compared with biphasic insulin aspart 30 twice daily in combination with PPHP in two studies in patients with type 2 diabetes mellitus. use of Risodeg once daily in combination with insulin aspart was also compared with use of insulin detemir once or twice daily in combination with insulin aspartate in patients with type 1 diabetes mellitus.

The absence of superiority of pal comparison drugs over Risodeg in terms of reducing the HbA1c index was proved in all studies when treating patients up to the target.

In patients with type 2 diabetes mellitus who have never received insulin therapy and patients who have previously received insulipotherapy, Risodeg in combination with PHPP provides similar glycemic control compared to insulin glargine. Risodeg provides better prandial glycemic control compared to insulin glargine, with a lower incidence of nocturnal hypoglycemia (defined as episodes of hypoglycemia that occurred between 0 and 6 am, confirmed by plasma glucose measurements of less than 3.1 mmol/l, or evidence that the patient required third-party assistance).

use of Risodeg twice daily provides similar glycemic control (_HbA1c) compared to biphasic insulin aspart 30, which was also administered twice daily. The drug Risodeg provides the best positive dynamics of reducing the concentration of glucose in the blood plasma on an empty stomach. When using Raizodeg, the target plasma glucose values of 5 mmol / l were achieved faster in patients compared to patients treated with biphasic insulin aspart 30. The drug Risodeg is less likely to cause hypoglycemia (including nighttime). In patients with type 1 diabetes mellitus, treatment with Risodeg once daily in combination with insulin aspart before other meals showed similar glycemic control (HbA1c and fasting plasma glucose) with rarer cases of nocturnal hypoglycemia compared to the basic bolus regimen of insulin dstemir and insulin aspart with each meal.

Based on a meta-analysis of two 26-week open-label treat-to-target studies in patients with type 2 diabetes mellitus, twice-daily Risodeg demonstrated a lower incidence of confirmed hypoglycemia episodes in general and confirmed nocturnal hypoglycemia episodes compared to biphasic insulin aspart 30. The results showed that the drug Risodeg reduces the concentration of glucose in fasting blood plasma with a lower risk of hypoglycemia both during the study and during dose maintenance from week 16 (Table 1)

Table 1. Results of a meta-analysis of data on episodes of confirmed hypoglycemia when administered twice daily during the study and during the dose maintenance period from week 16

There was no clinically significant formation of insulin antibodies after prolonged treatment with Risodeg.

Pharmacokineticabsorption

After subcutaneous injection, soluble stable multi-heamers of insulin degludec are formed. which create an insulin depot in the subcutaneous adipose tissue, and at the same time does not prevent the rapid release of insulin monomers aspart into the bloodstream. The multihexamers gradually dissociate, releasing the monomers of insulin degludec, resulting in a slow continuous flow of the drug into the blood. The equilibrium concentration of the ultra-long-acting component (insulin degludec) in blood plasma is reached 2-3 days after use of Raizodeg.

Well-known indicators of rapid absorption of insulin aspart are preserved in Risodeg. The pharmacokinetic profile of insulin aspart appears 14 minutes after injection, the maximum concentration is observed after 72 minutes.

Distribution

The affinity of insulin degludec for serum albumin corresponds to the binding capacity of plasma protein > 99% in human blood plasma. Insulin aspart has a lower plasma protein binding capacity (

Metabolism

The breakdown of insulin degludec and insulin aspart is similar to that of human insulin; all the resulting metabolites are inactive.

Deduction

The half-life of Risodeg after subcutaneous injection is determined by the rate of its absorption from subcutaneous tissue. The half-life of insulin degludec is approximately 25 hours and does not depend on the dose.

Linearity

The total effect of Risodeg is proportional to the administered dose of the basal component (insulin degludec) and prandial component (insulin aspart) in type 1 and type 2 diabetes mellitus.

Special patient groups

There were no differences in the pharmacokinetic properties of Risodeg depending on the gender of patients.

Elderly patients, patients of different ethnic groups, patients with impaired renal or hepatic function

There were no clinically significant differences in the pharmacokinetics of Risodeg between elderly and young patients, between patients of different ethnic groups, between patients with impaired renal and hepatic function and healthy patients.

Children and teenagers

The pharmacokinetic properties of Risodeg in children (6-11 years) and adolescents (12-18 years) with type 1 diabetes mellitus are comparable to those in adult patients with a single dose.

The total concentration and maximum concentration of insulin aspart are higher in children than in adults and are the same in adolescents and adults.

The pharmacokinetic properties of insulin degludec in children and adolescents with type 1 diabetes mellitus are comparable to those in adult patients. When a single dose of insulin degludec was administered to patients with type 1 diabetes mellitus, it was demonstrated that the total effect of the drug dose in children and adolescents is higher compared to that in adult patients.

Data from preclinical safety studies

Preclinical data based on studies of pharmacological safety, repeated dose toxicity, carcinogenic potential, toxic effects on reproductive function, did not reveal any danger to humans. The ratio of metabolic and mitogenic activity of insulin degludec is similar to that of human insulin.

Indications

Diabetes mellitus in adults.

Contraindications

• increased individual sensitivity to active substances or any of the auxiliary components of the drug;
• children under 18 years of age;
• pregnancy and lactation (there is no clinical experience of using the drug in children, women during pregnancy and lactation).

Side effects

The most common side effect reported during treatment is hypoglycemia.

All of the following side effects, based on data from clinical trials, are grouped according to MedDRA and organ systems. The frequency of side effects is defined as: very common (≥1/10): common (≥ 1/100 to <1/10); infrequent (≥1/1,000 to <1/100); rare (≥1/10,000 to < 1/1,000), very rare (

Description of individual adverse reactions

Immune system disorders

When using insulin preparations, allergic reactions may develop. Immediate allergic reactions to insulin or excipients. the components of the drug can potentially endanger the patient’s life. Hypersensitivity reactions (including swelling of the tongue or lips, diarrhea, nausea, fatigue, and pruritus) and urticaria have rarely been reported with Risodeg Flext Ach.

Hypoglycemia

Hypoglycemia can develop if the dose of insulin is too high in relation to the patient’s need for it. Severe hypoglycemia can lead to loss of consciousness and / or seizures, temporary or permanent impairment of brain function up to death. Symptoms of hypoglycemia usually develop suddenly. These include “cold sweats”, pale skin, increased fatigue, nervousness or tremors, feelings of anxiety, unusual tiredness or weakness, disorientation, decreased concentration, drowsiness, severe hunger, visual disturbances, headache, nausea, rapid heartbeat.

Lipodystrophy

Lipodystrophy (including lipohypertrophy, lipoatrophy) can develop at the injection site. Following the rules for changing the injection site within one anatomical area helps to reduce the risk of developing this adverse reaction.

Injection site reactions

Reactions at the injection site (hematoma, pain, local hemorrhage, erythema, connective tissue nodules, swelling, discoloration of the skin, itching, irritation and compaction at the injection site) were observed in patients treated with Risodeg Flext Ach. Most of the reactions at the injection site are minor and temporary and usually disappear with continued treatment.

The pharmacokinetic properties of Risodeg Flext Ach were studied in children and adolescents under 18 years of age (see section Pharmacokinetics). Efficacy and safety studies in children and adolescents have not been conducted.

In clinical trials, no differences in the frequency, type, or severity of adverse reactions were found between elderly patients, patients with impaired renal or hepatic function, and the general patient population.

Interaction

There are a number of medications that affect the need for insulin.

The need for insulin can be reduced: oral hypoglycemic drugs, glucagon-like peptide-1 (GLP-1) receptor agonists, MAO inhibitors, non-selective beta-blockers, ACE inhibitors, salicylates, anabolic steroids and sulfonamides.

The need for insulin may increase: oral hormonal contraceptives, thiazide diuretics, glucocorticosteroids, thyroid hormones, sympathomimetics, somatropin and danazol.

Beta-blockers can mask the symptoms of hypoglycemia.

Octreotide / lanreotide can both increase and decrease the body’s need for insulin.

Ethanol can both enhance and decrease the hypoglycemic effect of insulin.

Incompatibility

Certain medicinal substances may cause degradation of insulin degludec and/or insulin aspart when added to Risodeg Flext Ach. Risodeg Flext Ach should not be added to infusion solutions. Do not mix this medicine with other medications.

How to take, course of use and dosage

Risodeg Flext Ach is a combination of soluble insulin analogs-basal super-long-acting insulin (insulin degludec) and fast-acting prandial insulin (insulin aspart).

The drug is administered subcutaneously 1 or 2 times a day before the main meals. If necessary, patients can independently change the time of drug use, but it should be tied to the main meal.

In patients with type 2 diabetes mellitus, Risodeg Flext Ach can be used either as monotherapy or in combination with PHGP or bolus insulin.

Patients with type 1 diabetes are prescribed Risodeg Flext Ach in combination with short-acting/ultra-short-acting insulin before other meals.

The dose of Risodeg Flext Ach is determined individually according to the patient’s needs. To optimize glycemic control, it is recommended to adjust the dose of the drug based on fasting plasma glucose.

As with all insulin preparations, dose adjustment may be necessary if the patient becomes more physically active, changes in their usual diet, or has a concomitant medical condition.

Initial dose of Risodeg Flext Ach

Patients with type 2 diabetes mellitus

The recommended initial daily dose of Risodeg Flext Ach is 10 units, followed by the selection of an individual dose of the drug.

Patients with type 1 diabetes mellitus

The recommended starting dose of Risodeg Flext Ach is 60-70% of the total daily insulin requirement.

The drug Risodeg Flext Ach is prescribed once a day during the main meal in combination with fast/short-acting insulin administered before other meals, followed by the selection of an individual dose of the drug.

Transfer from other insulin preparations

Careful monitoring of blood glucose concentration is recommended during transfer and in the first weeks of prescribing a new drug. It may be necessary to adjust the concomitant gnpoglnkemic therapy (dose and time of use of short-and ultra-short-acting insulin preparations or the dose of PHGP).

Patients with type 2 diabetes mellitus:

When transferring patients receiving basal insulin therapy or biphasic insulin therapy once a day, the dose of Risodeg Flext Ach should be calculated on a one-to-one basis from the total daily dose of insulin that the patient received before switching to a new type of insulin.

When transferring patients who are on more than a single basal or biphasic insulin regimen, the dose of Risodeg Flext Ach should be calculated according to the “unit per unit” principle, with the transfer to a two-time use of Risodeg Flext Ach in the same total daily dose of insulin that the patient received before transferring to a new type of insulin.

When transferring patients who are on the basic bolus mode of ipsulipotherapy. The dose of Risodeg Flext Ach should be calculated based on the individual needs of the patient. As a rule, patients start with the same dose of basal insulin.

Patients with type 1 diabetes mellitus:

The recommended starting dose of Risodeg Flext Ach is 60-70% of the total daily requirement for insulin in combination with short-acting/ultra-short-acting insulin with other meals and subsequent selection of an individual dose of the drug.

Flexible dosage regimen

The time of use of Risodeg Flext Ach may change if the time of the main meal changes.

If a dose of Risodeg Flext Ach is missed, the patient can enter the next dose on the same day with the next main meal, and then return to their usual time of use of the drug. No additional dose should be administered to compensate for the missed dose.

Special patient groups

Elderly patients (over 65 years of age):

Risodeg Flext Ach can be used in elderly patients. Blood glucose concentration should be carefully monitored and the insulin dose adjusted individually (see section Pharmacokinetics).

Patients with renal and hepatic insufficiency:

Risodeg Flext Ach can be used in patients with renal and hepatic insufficiency. Blood glucose concentration should be carefully monitored and the insulin dose adjusted individually (see section Pharmacokinetics).

Children and teenagers:

Existing pharmacokinetic data are presented in the Pharmacokinetics section, but the efficacy and safety of Risodeg Flext Ach in children and adolescents under 18 years of age have not been studied, and recommendations for the dose of the drug in children have not been developed.

Method of application

Risodeg Flext Ach is intended for subcutaneous use only. Risodeg Flext Ach should not be administered intravenously, as this can lead to the development of severe hypoglycemia. Risodeg Flext Ach should not be administered intramuscularly, as the absorption of the drug changes in this case.

Risodeg Flext Ach should not be used in insulin pumps.

Risodeg Flextach is administered subcutaneously in the thigh, anterior abdominal wall, or shoulder area. You should constantly change the injection sites within the same anatomical area to reduce the risk of developing lipodystrophy.

The Flext Ach pen is designed for use with NovoFaynili NovoTvist disposable needles. Flextouch allows you to enter doses from 1 to 80 units in increments of 1 UNIT.

Overdose

A specific dose required for an insulin overdose has not been established, but hypoglycemia may develop gradually if the dose of the drug is too high compared to the patient’s need (see section Special Instructions).

The patient can eliminate mild hypoglycemia by taking glucose or sugar-containing products 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, he should be administered glucagon (0.5 to 1 mg) intramuscularly or subcutaneously (can be administered by a trained person), or intravenously dextrose (glucose) 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 the introduction of glucagon. After regaining consciousness, the patient is recommended to take a diet rich in carbohydrates to prevent the recurrence of hypoglycemia.

Special instructions

Hypoglycemia

If you skip a meal or have an unplanned intense physical activity, the patient may develop hypoglycemia. Hypoglycemia can also develop if the dose of insulin is too high relative to the patient’s needs (see the sections Side effects and Overdose).

After compensation of carbohydrate metabolism (for example, during intensive chemotherapy). patients may experience changes in their typical symptoms, which are harbingers of hypoglycemia, and patients should be informed about this. The usual harbinger symptoms may disappear with a prolonged course of diabetes mellitus.

Concomitant diseases, especially those that are infectious and accompanied by fever, usually increase the body’s need for insulin. Dose adjustment may also be necessary if the patient has concomitant kidney, liver, or adrenal, pituitary, or thyroid disorders.

As with other basal insulin preparations or preparations with a basal component, recovery from hypoglycemia may be delayed when using Risodeg Flext Ach.

Hyperglycemia

Insufficient dosage of the drug or discontinuation of treatment may lead to the development of hyperglycemia or diabetic ketoacidosis. In addition, concomitant diseases. especially infectious ones, they can contribute to the development of hyperglycemic conditions. accordingly, they increase the body’s need for insulin.

As a rule, the first symptoms of hyperglycemia appear gradually, over several hours or days. These symptoms include thirst, rapid urination, nausea, vomiting, drowsiness, red and dry skin, dry mouth, loss of appetite, and the smell of acetone in the exhaled air. In type 1 diabetes, if left untreated, hyperglycemia leads to diabetic ketoacidosis and can lead to death.

For the treatment of severe hyperglycemia, fast-acting insulin is recommended.

Transferring a patient from other insulin medications

The transfer of a patient to a new type or preparation of insulin of a new brand or another manufacturer should be carried out under strict medical supervision. When transferring, a dose adjustment may be required.

Simultaneous use of drugs of the thiazolidinedione group and insulin preparations

Cases of chronic heart failure have been reported when patients are treated with hyazolidinediones 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 Risodeg Flext Ach 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 peripheral edema. If heart failure symptoms worsen in patients, treatment with thiazolidinediones should be discontinued.

Visual disturbances

The intensification of ipsulotherapy with a dramatic improvement in carbohydrate metabolism control may lead to a temporary worsening of diabetic retinopathy, while long-term improvement in glycemic control reduces the risk of diabetic retinopathy progression.

Prevent accidental mixing up of insulin preparations

The patient should be instructed to check the label markings before each injection to avoid accidentally confusing Risodeg Penfill with other insulin preparations.

Patients should check the dialed dose on the injector’s dose counter. Blind or visually impaired patients should be informed that they always need the help of people who do not have vision problems and are trained to work with the injector.

Insulin Antibodies

When using insulin, the formation of antibodies is possible. In rare cases, when antibodies are formed, it may be necessary to adjust the dose of insulin to prevent cases of hyperglycemia or hypoglycemia.

Influence on the ability to drive vehicles and mechanisms

The ability of patients to reach the ends of the walkie-talkie may be impaired during hypoglycemia, which can be dangerous in situations where this ability is particularly necessary (for example, when driving vehicles or working with mechanisms).

Patients should be advised to take measures to prevent the development of hypoglycemia when driving vehicles. This is especially important for patients with the absence or reduction of symptoms that are harbingers of developing hypoglycemia or with frequent episodes of hypoglycemia. In these cases, the feasibility of driving a vehicle should be considered.

Storage conditions

Store at a temperature of 2 to 8°C (in the refrigerator), but not near the freezer. Do not freeze it.

For a syringe pen with the drug that is used or carried as a spare pen: do not store in the refrigerator. Store at a temperature not exceeding 30°C for 4 weeks. When using, cover the pen with a cap to protect it from light.

Shelf life

30 months

Active ingredient

Insulin degludec, Insulin aspart

Conditions of release from pharmacies

By prescription

Dosage form

solution for injection