Description
Latin name
RAYZODEG FlexTouch
Packaging
5 cartridges of 3 ml.
Pharmacological action of
The drug Ryzodeg FlexTouch is a combined preparation consisting of a soluble analogue of human insulin of superlong action (insulin degludec) and a fast-acting soluble analogue of human insulin (insulin aspart) produced using recombinant molecular biochemistry recombinant DNA
Mechanism of action
Insulin degludec and insulin aspart specifically bind to the receptor of human endogenous insulin and interact with it, realize their pharmacological effect similar to the effect of human insulin. The hypoglycemic effect of insulin is due to increased glucose utilization by tissues after binding of 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 the drug Ryzodeg FlexTouch are clearly different and the general profile of the drug reflects the profiles of the action of the individual components: fast-acting insulin aspart and insulin degludec superlong.
The basal component of the drug Ryzodeg FlexTouch, which has an ultra-long action (insulin degludec), after subcutaneous injection forms soluble multihexamers in the subcutaneous depot, from which there is a continuous slow entry of insulin degludec into the circulation, providing a flat profile of action and stable hypoglycemic effect of the drug. This effect is preserved in combination with insulin aspart and does not affect the rate of absorption of monomers of fast-acting insulin aspart. arising between 0 hours and 6 hours of the morning, confirmed by the results of measuring plasma glucose concentrations of less than 3.1 mmol / l or evidence that the patient needed the help of third parties).
Twice daily administration of Ryzodeg provides similar glycemic control (HbA1c) compared with biphasic aspart 30 insulin, which was also administered twice a day. The drug Ryzodeg provides the best positive dynamics in reducing the concentration of glucose in plasma on an empty stomach. With the use of the Ryzodeg preparation, the target plasma glucose values of 5 mmol / L were achieved faster in patients compared with patients treated with biphasic aspart 30 insulin. The Ryzodeg preparation causes hypoglycemia less often (including nighttime). In patients with type 1 diabetes mellitus, treatment with Ryzodeg once a day in combination with insulin aspart before other meals showed similar glycemic control (HbA1c and fasting plasma glucose) with rarer cases of nocturnal hypoglycemia compared with the baseline-bolus regimen of insulin administration Dstemir and insulin aspart with each meal.
According to a meta-analysis of two 26-week open trials designed according to the heal for the goal principle involving patients with type 2 diabetes, the Ryzodeg drug, administered twice a day, showed a lower incidence of confirmed hypoglycemia episodes in general and episodes of confirmed nocturnal hypoglycemia compared with biphasic insulin aspart 30. The results showed that Ryzodeg reduces fasting plasma glucose concentration with a lower risk of hypoglycemia both during the study and during the maintenance of the dose from 16 weeks (Table 1)
Table 1. Results of a meta-analysis of data on episodes of confirmed hypoglycemia when administered twice a day during the study and in the period of maintaining the dose from 16 weeks
Analyzes Established relative frequency [95% CI] study period Established relative frequency [95% CI] period of maintaining the dose
Total number of confirmed hypo lycemia drug Ryzodeg ® (2 times a day) / biphasic insulin aspart 30 (2 times a day) 0.81 [0.67: 0.9S] 0.43 [0.31: 0.59]
Nightly confirmed hypoglycemia drug Ryzodeg ® (2 times a day) / two-phase insulin aspart 30 (2 times a day) 0.69 [0.55: 0.87] 0.38 [0.25 0.patients, between patients of different ethnic groups, between patients with impaired renal and hepatic function and healthy patients.
Children and adolescents
The pharmacokinetic properties of Ryzodeg in a study in children (6 11 years old) and adolescents (12 18 years old) with type 1 diabetes mellitus are comparable to those in adult patients with a single dose.
The total concentration and maximum concentration of aspart insulin is higher in children than in adults and the same in adolescents and adults.
The pharmacokinetic properties of degludec insulin in children and adolescents with type 1 diabetes are comparable to those in adult patients. Against the background of a single administration to patients with type 1 diabetes mellitus, a dose of insulin degludec has been demonstrated that the total dose exposure in children and adolescents is higher compared to that in adult patients.
Preclinical Safety Studies
Preclinical data based on pharmacological safety studies, 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 degludec insulin is similar to that of human insulin.
Indications
Diabetes mellitus in adults.
Contraindications
hypersensitivity to active substances or any of the auxiliary components of the
drug children under 18 years of age
pregnancy and breastfeeding (there is no clinical experience with the drug in children, women during pregnancy and breastfeeding).
Use during pregnancy and lactation
Pregnancy
The use of the drug Ryzodeg FlexTouch during pregnancy is contraindicated, since there is no clinical experience with its use during pregnancy. Studies of animal reproductive function have not revealed differences between degludec insulin and human insulin in terms of embryotoxicity and teratogenicity.
The period of breastfeeding
The use of the drug Ryzodeg FlexTouch during the period of breastfeeding is contraindicated, since there is no clinical experience with its use in lactating women.
Animal studies have shown that in rats, insulin degludec is excreted in breast milk, the concentration of the drug in breast milk is lower than in blood plasma. It is not known whether insulin degludec is excreted in breast milk of women.
Fertility
Animal studies have not found adverse effects of degludec insulin on fertility.
Composition
1 ml contains: Active substance: a mixture of insulin degludec and insulin aspart in a ratio of 70/30 (equivalent to 2.56 mg insulin degludec and 1.05 mg insulin aspart) 100 IU *
Excipients: glycerol – 19 mg, phenol – 1.5 mg , metacresol – 1.72 mg, zinc 27.4 μg (in the form of zinc acetate 92 μg), sodium chloride 0.58 mg, hydrochloric acid or sodium hydroxide (for pH adjustment), water d / i – up to 1 ml.
* 1 PIECE contains 0.0256 mg of anhydrous saltless insulin degludec and 0.0105 mg of anhydrous saltless insulin aspart, which corresponds to 1 IU of human insulin, 1 unit of insulin detemir, insulin glargine or biphasic insulin aspart.
Dosing and dose preparation
Rayzodeg FleksTach is a combination of soluble insulin analogues – sverhdlitelyyugo basal insulin action (insulin degludek) and fast prandial insulin (insulin aspart).
The drug is administered subcutaneously 1 or 2 times a day before main meals. If necessary, patients are able to independently change the time of administration of the drug, but it should be tied to the main meal.
In patients with type 2 diabetes mellitus, Ryzodeg FlexTouch can be used either as monotherapy, or in combination with PHGP or with bolus insulin.
Patients with type 1 diabetes mellitus are prescribed Rysodeg FlexTouch in combination with short / ultra-short-acting insulin before other meals.
The dose of Ryzodeg FlexTouch is determined individually according to the needs of the patient. To optimize glycemic control, it is recommended to correct the drug vines on the basis of fasting plasma glucose values.
As with any insulin preparation, dose adjustment may be required if the patient’s physical activity is increased, his diet is changed, or his illness is associated with it.
Initial dose of Ryzodeg FlexTouch
Patients with type 2 diabetes mellitus
The recommended initial daily dose of Ryzodeg FlexTouch 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 Ryzodeg FlexTouch is 60-70% of the total daily insulin requirement.
The drug Ryzodeg FlexTouch 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 concentrations during transfer and on the first pedals of a new drug is recommended. Maybe, Correction of concomitant gnogoglnkemicheskoy therapy (dose and time of administration of insulin preparations of short and ultrashort action or dose of PHGP) will be required.
Patients with type 2 diabetes mellitus:
When transferring patients receiving basal insulin therapy or biphasic insulin therapy once to laziness, the dose of Ryzodeg FlexTouch should be calculated on a unit-by-unit basis from the total daily dose of insulin that the patient received before transferring to a new type of insulin.
When transferring patients who are on more than a single regimen of basal or biphasic insulin administration, the dose of Ryzodeg FlexTouch should be calculated on a unit-by-unit basis, with the transfer to twice the administration of Ryzodeg FlexTouch in the same total daily dose of insulin, which the patient received before transferring to a new type of insulin.
When transferring patients on the basis of the bolus-regimen of ipsulipotherapy. the dose of Ryzodeg FlexTouch should be calculated based on the individual needs of the patient. As a rule, patients begin with the same dose of basal insulin.
Type 1 diabetes mellitus patients:
The recommended starting dose of Ryzodeg FlexTouch is 60-70% of the total daily insulin requirement in combination with short / ultra-short-acting insulin with other meals and the subsequent selection of an individual dose of the drug.
Flexible dosing regimen
The time of administration of the drug Ryzodeg FlexTouch may change if the time of the main meal changes.
If a dose of Ryzodeg FlexTouch is missed, the patient can enter the next dose on the same day with the next main meal, and then return to his usual time of administration of the drug. An additional dose should not be administered to compensate for the missed dose.
Special patient groups
Elderly patients (over 65):
Ryzodeg FlexTouch may be used in elderly patients. The concentration of blood glucose should be carefully monitored and the dose of insulin individually adjusted (see Pharmacokietics section).
Patients with impaired renal and hepatic function:
The drug Ryzodeg FlexTouch can be used in patients with impaired renal and hepatic function. Blood glucose concentration should be carefully monitored and the insulin dose adjusted individually (see Pharmacokinetics subsection).
Kids and teens:
The existing pharmacokinetic data are presented in the Pharmacokinetics subsection, however, the efficacy and safety of Raizodeg FlexTouch in children and adolescents under 18 have not been studied, and recommendations on the dose of the drug in children have not been developed.
Method of use
The preparation Ryzodeg FlexTouch is intended only for subcutaneous administration. The drug Ryzodeg FlexTouch can not be administered intravenously, as this can lead to the development of severe hypoglycemia. The drug Ryzodeg FlexTouch can not be administered intramuscularly, since in this case the absorption of the drug changes.
Ryzodeg FlexTouch cannot be used in insulin pumps.
Ryzodeg ® Flex ® is administered subcutaneously to the thigh, anterior abdominal wall, or to the shoulder. The injection sites should be constantly changed within the same anatomical region to reduce the risk of lipodystrophy.
FlexTouch Syringe Pen is designed for use with NovoFailili NovoTvist disposable needles. FlexTouch allows you to enter doses from 1 to 80 units in increments of 1 unit.
Side effects
The most common side effect reported during treatment is hypoglycemia.
All of the side effects listed below, based on data from clinical trials, are grouped according to MedDRA and organ systems. The incidence of side effects is defined as: very often ( 1/10): often ( 1/100 to <1/10) infrequently ( 1/1000 to <1/100) rarely ( 1/10 000 to < 1 / 1,000), very rarely (<1/10 000) and unknown (impossible to estimate based on available data). Immune system disorders Rarely – Hypersensitivity reactions Rarely – Urticaria Metabolism and nutrition disorders Very often – Hypoglycemia Disorders of the skin and subcutaneous tissue Unknown – Lpodystrophy General disorders and disorders at the injection site Frequently – administration Infrequently – Peripheral edema Description of individual adverse reactions Immune system disorders When using insulin preparations, allergic reactions may develop. Allergic reactions of an immediate type to insulin or auxiliary components. included in the preparation may potentially endanger the patient s life. When using the Ryzodeg FlexTouch drug, hypersensitivity reactions (including swelling of the tongue or lips, diarrhea, nausea, tiredness and skin itching) and urticaria were rare. 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 convulsions, temporary or irreversible impairment of brain function up to a fatal outcome. Symptoms of hypoglycemia, as a rule, develop suddenly. These include cold sweat , pallor of the skin, increased fatigue, nervousness or tremor, anxiety, unusual tiredness or weakness, disorientation, decreased concentration of attention, drowsiness, severe hunger, blurred vision, headache, nausea, heart palpitations. Lipodystrophy Lipodystrophy (including lipohypertrophy, lipoatrophy) may develop at the injection site. Compliance with the rules for changing the injection site within the same anatomical area helps to reduce the risk of developing this adverse reaction. Reactions at the injection site Patients treated with Ryzodeg FlexTouch showed reactions at the injection site (hematoma, pain, local hemorrhage, erythema, connective tissue nodules, swelling, discoloration of the skin, itching, irritation, and tightening at the injection site). Most reactions at the injection site are minor and temporary and usually disappear with continued treatment. The pharmacokinetic properties of Ryzodeg FlexTouch have been studied in children and adolescents under 18 years of age (see Pharmacokietics subsection). Studies of efficacy and safety in children and adolescents have not been conducted. In clinical trials, there is no difference in frequency, the type or severity of adverse reactions between elderly patients, patients with impaired renal or hepatic function and the general patient population was not detected. Drug Interaction There are a number of medicines that affect your insulin requirement. The need for insulin can be reduced by: oral hypoglycemic drugs, glucagon-like peptide-1 (GPP-1) receptor agonists, MAO inhibitors, non-selective beta-blockers, ACE inhibitors, salicylate, and anodolybic anabolic. Insulin requirements 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 potentiate and reduce the hypoglycemic effect of insulin. Incompatibility Some medicines when added to the drug Rizodeg FlexTach may cause the destruction of insulin degludek and / or insulin aspart. The drug Risodeg FlexTach cannot be added to infusion solutions. It is impossible to mix this preparation with other medicines. Overdose No specific dose required for insulin overdose has been established, however, hypoglycaemia may develop gradually, if the dose is too high compared to the patient’s need (see Special Instructions). The patient may eliminate mild hypoglycemia by taking glucose or sugary products by himself. Therefore, patients with diabetes mellitus are advised to carry sugar products with them constantly. In case of severe hypoglycemia, when the patient is unconscious, he or she should be administered glucagon (0.5 to 1 mg) intramuscularly or subcutaneously (may be administered by a trained person), or intravenously dextrose (glucose) solution (may be administered only by a healthcare professional). It is also necessary to administer intravenously dextrose in the event of seating 10-15 minutes after administration of glucagon, the patient does not regain consciousness. After regaining consciousness, the patient is advised to take a carbohydrate-rich diet, for prophylaxis of recurrence of hypoglycemia. Storage conditions Store at a temperature of 2 to 8 ° C (in the refrigerator), but not near the freezer. Do not freeze. For used or carried as a spare syringe pen with the drug: do not store in the refrigerator. Store at a temperature not exceeding 30 ° C for 4 weeks. When using, close the syringe pen with a cap to protect it from light. Expiration of 30 months D the active substance Inosine, Nicotinamide, Riboflavin, Insulin aspart pharmacy terms with prescription Dosage form dosage form injection Novo Nordisk, Denmark
