Vildagliptin - instructions for use, dose, side effects, contraindications

Clinical and pharmacological group: & nbsp

Hypoglycemic synthetic and other agents

Included in the formulation

Galvus

pills inwards

Novartis Pharma AG Switzerland

Included in the list (Order of the Government of the Russian Federation No. 2782-r of 30.12.2014):

VED

АТХ:

A.10.B Oral hypoglycemic drugs

Pharmacodynamics:

Hypoglycemic agent. Vildagliptin - Representative of the class of stimulants of the islet apparatus of the pancreas, selectively inhibits the enzyme dipeptidyl peptidase-4. Fast and complete inhibition of activity dipeptidyl peptidase-4 (> 90%) causes an increase in both basal and food-stimulated secretion of glucagon-like peptide type 1 and a glucose-dependent insulinotropic polypeptide from the intestine to the systemic circulation throughout the day.

Increasing levels glucagon-like peptide of type 1 and glucose-dependent insulinotropic polypeptide, vildagliptin causes an increase in the sensitivity of beta cells of the pancreas to glucose, which leads to an improvement in the glucose-dependent secretion of insulin. When using vildagliptin in a dose of 50-100 mg per day in patients with type 2 diabetes mellitus, there is an improvement in the function of beta cells of the pancreas. The degree of improvement in beta-cell function depends on the degree of their initial damage; so in individuals who are not suffering from diabetes (with a normal level of glucose in the blood plasma) vildagliptin does not stimulate the secretion of insulin and does not reduce the level of glucose.

Raising the levels of endogenous glucagon-like peptide of type 1, vildagliptin increases the sensitivity of alpha cells to glucose, which leads to an improvement in glucose-dependent regulation of glucagon secretion. Reducing the level of excess glucagon during meals, in turn, causes a decrease in insulin resistance.

An increase in the ratio of insulin / glucagon to a background of hyperglycemia, caused by an increase in levels glucagon-like peptide of type 1 and glucose-dependent insulinotropic polypeptide, causes a decrease in the production of glucose by the liver both in the prandial period and after eating, which leads to a decrease in the level of glucose in the blood plasma.

In addition, against the background of the use of vildagliptin, there is a decrease in the level of lipids in the blood plasma, however this effect is not related to its effect on glucagon-like peptide of the 1st type or a glucose-dependent insulinotropic polypeptide and improving the function of beta cells of the pancreas.

It is known that an increase in the level of glucagon-like peptide of type 1 can lead to a slowdown of gastric emptying, however, against the background of the use of vildagliptin, this effect is not observed.

With the use of vildagliptin in 5795 patients with type 2 diabetes mellitus for a period of 12 to 52 weeks, a significant long-term decrease in the concentration of glycated hemoglobin (HbA) was observed as monotherapy or in combination with metformin, sulfonylurea derivatives, thiazolidinedione, or with insulin_1c) and fasting blood glucose.

Pharmacokinetics:

Vildagliptin is rapidly absorbed when ingested with an absolute bioavailability of 85%. In the therapeutic range of doses, an increase in the maximum concentration in the plasma of vildagliptin and area under the curve "area-time" almost directly in proportion to the increase in dose.

After ingestion on an empty stomach, the time to reach maximum concentration Vildagliptin in blood plasma is 1 hour 45 minutes. With simultaneous intake with food, the absorption rate decreases insignificantly: a decrease maximum concentration in blood plasma by 19% and an increase in the time it takes to reach 2 hours and 30 minutes.However, eating does not affect the degree of absorption and area under the curve "concentration - time".

The binding of vildagliptin to plasma proteins is low (9.3%). Equivalently distributed between plasma and erythrocytes. The distribution of vildagliptin is presumed to be extravascular, the volume of distributionin the equilibrium state after intravenous administration is 71 liters.

Biotransformation is the main way of removing vildagliptin. In humans, 69% of people undergo transformation. The main metabolite - LAY151 (57% of the dose) is pharmacologically inactive and is a product of hydrolysis of the cyano component. About 4% undergoes amide hydrolysis. In experimental studies, there is a positive effect dipeptidyl peptidase-4 on the hydrolysis of the active substance. Vildagliptin It is not metabolized with the participation of cytochrome P450 isoenzymes, it is not a substrate, does not inhibit and does not induce these isoenzymes.

After oral administration, about 85% is excreted by the kidneys and 15% by the intestine, while renal excretion of unchanged vildagliptin is 23%. Half-lifeafter oral administration is about 3 hours regardless of the dose.

Indications:

Diabetes mellitus type 2: as a monotherapy in combination with diet and exercise; as part of a two-component combination therapy with metformin, sulfonylurea derivatives, thiazolidinedione or with insulin in the case of ineffectiveness of diet therapy, exercise and monotherapy of these drugs.

ICD-10

IV.E10-E14.E11 Non-insulin-dependent diabetes mellitus

Contraindications:

Hypersensitivity to vildagliptin and any other components of the drug;

Hereditary intolerance to galactose, insufficiency of lactase, glucosogalactose malabsorption.

The use of vildagliptin in patients with chronic heart failure of NYHA functional class IV is not recommended due to the lack of clinical research data on the use of vildagliptin in this group of patients.

The effectiveness and safety of the drug in children under 18 years of age is not established.

Carefully: severe violations of liver function, including increased activity of hepatic enzymes (alanine aminotransferase or aspartate aminotransferase>2.5 times higher than VGN - 2.5 × VGN); terminal stage of chronic renal failure in hemodialysis patients (since experience is limited); chronic heart failure of class III according to functional classification NYHA (because the application data are limited and do not allow a final conclusion).

Carefully:

It is not recommended to use in patients with severe impairment of liver function, incl. with an increase in the activity of alanine aminotransferase or aspartate aminotransferase> 2.5 times higher than ULN.

Before the start of treatment, and also regularly (1 every 3 months) during the first year of treatment, it is recommended to determine the biochemical parameters of liver function. In the case of detection of increased activity of aminotransferases, this result should be confirmed by a second study, and then the biochemical parameters of liver function should be regularly determined until they are normalized. If the excess of activity of aspartate aminotransferase or alanine aminotransferase by 3 times or more is confirmed by repeated investigation, vildagliptin is recommended to be canceled.

With the development of jaundice or other signs of impaired liver function, therapy with vildagliptin should be stopped immediately. After the normalization of the liver function, treatment can not be resumed.

It is not recommended for patients with moderate or severe renal dysfunction (including terminal stage of renal failure and the need for hemodialysis), data on the safety of use in this category of patients are limited.

The efficacy and safety of vildagliptin in children and adolescents under the age of 18 years have not been established.

Pregnancy and lactation:

In experimental studies, when administered at doses 200 times higher than recommended, the drug did not cause impairment of fertility and early development of the embryo and did not have a teratogenic effect on the fetus. Sufficient data on the use of the drug in pregnant women do not exist, and therefore the drug should not be used during pregnancy. In cases of impaired glucose metabolism, the risk of developing congenital anomalies, as well as the incidence of neonatal morbidity and mortality, is increasing in pregnant women.To normalize the concentration of blood glucose in pregnancy, therapy with insulin preparations is recommended.

Since it is not known whether vildagliptin with breast milk in humans, the drug should not be used during lactation.

Dosing and Administration:

Inside, regardless of food intake.

Dosage regimen should be selected individually, depending on the effectiveness and tolerability.

The recommended dose of the drug in monotherapy or as part of a two-component combination therapy with metformin, thiazolidinedione or insulin (in combination with or without metformin) is 50 or 100 mg once a day. In patients with a more severe course of type 2 diabetes mellitus receiving insulin treatment, the drug is recommended to be applied at a dose of 100 mg per day.

The recommended dose of the drug in the triple combination therapy (vildagliptin + derivatives of sulfonylurea + metformin) is 100 mg per day.

A dose of 50 mg per day should be given in 1 morning, a dose of 100 mg per day - 50 mg 2 times a day, morning and evening.

When used as part of a two-component combination therapy with sulfonylurea derivatives, the recommended dose of the drug is 50 mg once a day in the morning.When administered in combination with sulfonylurea derivatives, the efficacy of therapy with a drug at a dose of 100 mg per day was similar to that of a dose of 50 mg per day.

If the clinical effect is insufficient, against the background of application of the maximum recommended daily dose of 100 mg for the better control of glycemia, it is possible to additionally prescribe other hypoglycemic drugs - metformin, sulfonylureas, thiazolidinedione or insulin.

Special patient groups

Impaired liver or kidney function. Patients with mild impairment of renal and hepatic function do not require correction of the dosing regimen of the drug. In patients with moderate or severe renal dysfunction (including the terminal stage of chronic renal failure on hemodialysis), the drug should be administered at a dose of 50 mg 1 time per day.

Patients ≥65 years of age. Older patients do not need to adjust the dosage regimen of the drug.

Side effects:

From the digestive system: sometimes - constipation; rarely - violations of the liver (including hepatitis) of the asymptomatic course; when combined with insulin, often - nausea, flatulence, gastroesophageal reflux disease.

From the central nervous system: often - tremor, dizziness, headache.

From the side of metabolism: often - hypoglycemia, weight gain.

Allergic reactions: rarely angioedema (more often when combined with angiotensin converting enzyme inhibitors).

Other: often - asthenia, peripheral edema.

Overdose:

Symptoms: when using the drug at a dose of 400 mg in day can be observed pain in the muscles, rarely - light and transient paresthesia, fever, swelling and transient increase in the concentration of lipase (higher VGN in 2 times). With an increase in the dose of the drug to 600 mg in day it is possible to develop limb edema with paresthesia and increased concentration creatine phosphokinase, alanine aminotransferase, C-reactive protein and myoglobin. All symptoms of overdose and changes in laboratory parameters disappear after discontinuation of the drug.

Treatment: the removal of the drug from the body by dialysis is unlikely. However, the main hydrolysis metabolite of vildagliptin (LAY151) can be removed from the body by hemodialysis.

Interaction:

The drug has a low potential for drug interaction.

Since the preparation is not a substrate for cytochrome P450 enzymes, nor does it inhibit or induce these enzymes, drug interaction with drugs that are substrates, inhibitors or inducers of cytochrome P450 is unlikely. With simultaneous application vildagliptin also does not affect the metabolic rate of drugs that are substrates of the enzymes: CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and CYP3A4 / 5.

Clinically significant interaction of the drug with the drugs most often used in the treatment of type 2 diabetes mellitus (glibenclamide, pioglitazone, metformin) or having a narrow therapeutic range (amlodipine, digoxin, ramipril, simvastatin, valsartan, warfarin), not installed.

Special instructions:

Not recommended for use in patients with severe impairment of liver function, incl. with an increase in the activity of alanine aminotransferase or aspartate aminotransferase> 2.5 times higher than ULN.

It is not recommended for patients with moderate or severe renal dysfunction (including terminal stage of renal failure and the need for hemodialysis),data on the safety of use in this category of patients are limited.

Before the start of treatment, and also regularly (1 every 3 months) during the first year of treatment, it is recommended to determine the biochemical parameters of liver function. In the case of detection of increased activity of aminotransferases, this result should be confirmed by a second study, and then the biochemical parameters of liver function should be regularly determined until they are normalized. If the activity is exceeded alanine aminotransferase or aspartate aminotransferase 3 times or more VGN is confirmed by repeated examination, then vildagliptin it is recommended to cancel.

With the development of jaundice or other signs of impaired liver function, therapy with vildagliptin should be discontinued immediately. After the normalization of the liver function, treatment can not be resumed.

If necessary, insulin therapy vildagliptin apply only in combination with insulin.

Vildagliptin should not be used for the treatment of type 1 diabetes or for the treatment of diabetic ketoacidosis.

Use in Pediatrics

The efficacy and safety of vildagliptin in children and adolescents under the age of 18 years have not been established.

Impact on the ability to drive vehicles and manage mechanisms

When developing dizziness against the background of drug treatment, patients should not engage in potentially hazardous activities (including driving).

Instructions

Vildagliptin (Vildagliptinum)