Expiration date: 02/2025

The composition and form of issue: 

Tablets. 1 tablet contains:

vildagliptin 50 mg

other ingredients: microcrystalline cellulose lactose anhydrous carboximetilkrahmal sodium magnesium stearate 

in blister packs of 7 or 14 PCs the paper cartons 2, 4, 8 or 12 blisters.

Description pharmaceutical form:

From white to light yellow, round, smooth tablets with bevelled edges on one side marked with "NVR" on the other side — "FB".

Pharmacokinetics:

Absorption

Vildagliptin rapidly absorbed when taken orally with an absolute bioavailability of 85%. In the therapeutic dose range increase vildagliptin Cmax in plasma and AUC is almost directly proportional to the increase in dosage.

After ingestion on an empty stomach the time to reach Cmax vildagliptin in plasma is 1H 45 min. When administered simultaneously with food, the absorption rate of the drug decreases insignificantly, the reduction in Cmax of 19% and a decrease in the time to achieve up to 2 h 30 min. However, eating does not affect the extent of absorption and AUC.

Distribution

Vildagliptin binding to plasma proteins is low (9.3 per cent). Equivalent drug is distributed between plasma and erythrocytes. Distribution vildagliptin occurs presumably extravascular, VSS at steady state after the on/in the introduction is 71 HP

Metabolism

Biotransformation is the major route of excretion of vildagliptin. The human body is subjected to a conversion of 69% of the dose. The main metabolite — LAY151 (57% dose) of the pharmacologically inactive and is the hydrolysis product of the cyano-component. About 4% of the dose undergoes amide hydrolysis. In experimental studies indicated a positive influence of dipeptidylpeptidase-4 (DPP-4) hydrolysis products. Vildagliptin not metabolized with participation of cytochrome P450 isoenzymes. Vildagliptin is not a substrate of CYP450 isoenzymes, it is not inhibited and does not induce isoenzymes of cytochrome P450.

Excretion and elimination

After ingestion of the drug is about 85% of the dose is excreted by the kidneys and 15% through the intestine, renal excretion of unchanged vildagliptin is 23%. T1/2 after oral administration is about 3 hours regardless of the dose. Gender, body mass index, and ethnicity have no effect on the pharmacokinetics of vildagliptin.

The liver dysfunction. In patients with mild and moderate human liver (6-10 points according to the classification of Child-Pugh) after a single application of the drug there is a decrease in bioavailability vildagliptin 20 and 8%, respectively. In patients with severe hepatic insufficiency (12 points according to the classification of Child-Pugh) the bioavailability of vildagliptin increased by 22%. Increase or decrease the maximum bioavailability vildagliptin not exceeding 30%, is not clinically significant. The correlation between the severity of impaired liver function and bioavailability of the drug is not revealed.

The impairment of renal function. In patients with mild, moderate and severe renal impairment, in patients with end-stage chronic renal failure (CRF) on hemodialysis, a marked increase in Cmax 8-66%, and for AUC 32-134%, not correlated with the severity of the violation, as well as increase in AUC of active metabolite LAY151 1.6–6.7 times, depending on the severity of the violation. T1/2 vildagliptin not changed.

Use in patients aged &ge65 years. The maximum increase in bioavailability of the drug by 32% (increase of Cmax by 18%) in people over 70 years of age is not clinically significant and does not affect the inhibition of DPP-4.

Use in patients aged &le18 years. Pharmacokinetic features vildagliptin in children and adolescents under 18 years not installed.

Description pharmacological action:

Vildagliptin — representative of the class of stimulants of islet apparatus of the pancreas, selectively inhibits the enzyme dipeptidylpeptidase-4. Rapid and complete inhibition of the activity of DPP-4 (>90%) causes an increase in both basal and meal-stimulated secretion glucagonoma peptide type 1 (GLP-1) and glukagonovykh insulinotropic polypeptide (GIP) from the intestine into the systemic circulation throughout the day.

By increasing the levels of GLP-1 and GIP, vildagliptin causes an increase in sensitivity &beta-cells of the pancreas to glucose, resulting in improved glucosidation insulin secretion. When using vildagliptin at a dose of 50 — 100 mg per day in patients with diabetes type 2 diabetes showing improved function &beta-cells of the pancreas. The degree of improvement of function &beta-cells depends on their source of damage as in persons not suffering from diabetes (with a normal level of glucose in blood plasma) vildagliptin does not stimulate insulin secretion or reduce glucose levels.

Elevating levels of endogenous GLP-1, vildagliptin increases sensitivity &alpha-cells to glucose, which leads to improved glucosidation the regulation of secretion of glucagon. The decrease in the level of excess glucagon during meals in turn, causes a decrease in insulin resistance.

The increase in the ratio of insulin/glucagon with hyperglycemia due to increased levels of GLP-1 and GIP, causes a decrease in hepatic glucose production in the prandial period and after a meal that leads to a decrease in the level of glucose in the blood plasma.

In addition, application of vildagliptin marked reduction of lipids in blood plasma, but this effect is not associated with its effect on GLP-1 or GIP and improving the function of the &beta-cells of the pancreas.

It is known that increasing the level of GLP-1 may lead to slower emptying of the stomach, however, against the backdrop of vildagliptin a similar effect is not observed.

When using vildagliptin from 5795 patients with diabetes mellitus type 2 for 12 to 52 weeks as monotherapy or in combination with Metformin, sulfonylureas, thiazolidinediones, or insulin noted significant prolonged decline in the concentration of glycated hemoglobin (HbA1c) and fasting blood glucose.

Indications:

Diabetes type 2:

• as monotherapy in combination with diet and exercise
  
• in the two-component combination therapy with Metformin, sulfonylureas, or insulin thiazolidinediones in case of ineffective diet therapy, exercise, and monotherapy with these drugs.
  

Contraindications:

• hypersensitivity to vildagliptin and any other components of the drug
  
• children under 18 years (effectiveness and safety have not been established).
  

With caution:

• severe violations of liver function, including patients with increased activity of liver enzymes (ALT or AST >2.5 times the upper limit of normal is 2.5×ULN)
  
• moderate or severe renal dysfunction (including end-stage chronic renal failure on hemodialysis) — experience is limited, the preparation is not recommended in these patients
  
• rare inherited disorders — galactose intolerance, lactase deficiency or malabsorption of glucose-galactose.
  

Application of pregnancy and breast-feeding:

In experimental studies when administered in doses 200 times greater than recommended, the drug did not cause violations of fertility and early embryonic development and did not exert teratogenic effects on the fetus. Sufficient data on the drug Galvus in pregnant women is not, therefore the drug should not be used during pregnancy. When glucose metabolism disorders in pregnant women increase the risk of congenital anomalies and the frequency of neonatal morbidity and mortality.

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

Side effects:

In applying the drug Galvus as monotherapy or in combination with other drugs most adverse reactions were mild, were temporary and did not require discontinuation of therapy. The correlation between the frequency of adverse events (AES) and age, sex, ethnicity, duration of use, or the dosing mode is not revealed. The incidence of angioneurotic edema during therapy with the drug Galvus was &ge1/10000, <1 / 1000th (gradation rare) and was similar to that in the control group. The most frequently angioedema was observed when prescribing the drug in combination with ACE inhibitors. In most cases, angioneurotic edema was moderate severity and disappeared in the course of therapy vildagliptin.

On the background of drug therapy Galvus rarely, violations of liver function (including hepatitis), asymptomatic course. In most cases, data breaches and deviations of liver function tests from normal it fixed itself without complications after the discontinuation of drug therapy. In applying the drug Galvus dose 50 mg 1 or 2 times a day, frequency of increase of liver enzymes (ALT or AST &ge3×ULN) was 0.2 or 0.3 percent, respectively (compared with 0.2% in the control group). Increased activity of liver enzymes in most cases it is asymptomatic, not progressive and was not accompanied by cholestatic changes or jaundice.

To assess the frequency of occurrence of adverse events the following criteria were used: very common (&ge1/10) frequently (&GE. 1/100, <1/10), sometimes (&ge1/1 000, <1/100), rare (&ge1/10000, <1/1000), very rare (<1/10000), including individual messages.

In applying the drug Galvus as monotherapy

In applying the drug Galvus dose 50 mg 1 or 2 times per day, the frequency of discontinuation of therapy in connection with the development of adverse reactions (0.2 or 0.1%, respectively) were not higher than in the placebo group (0.6%) or the comparison drug (0.5 percent).

Monotherapy at a dose of 50 mg 1 or 2 times a day, frequency of hypoglycemia without increasing the severity of the condition was 0.5% (2 people out of 409) or 0.3% (4 out of 1 082), which is comparable with the comparison drug and placebo (0.2 percent). In applying the drug Galvus as monotherapy were not observed increase of body weight of the patients.

CNS: frequently — dizziness and sometimes headache.

From the digestive system: sometimes — constipation.

From the body as a whole: sometimes — peripheral edema.

Long-term clinical studies of up to 2 years did not reveal any additional abnormalities of the security profile or unforeseen risks when using vildagliptin as monotherapy.

In applying the drug Galvus dose 50 mg 1 or 2 times a day in combination with Metformin

In applying the drug Galvus dose 50 mg 1 times / day in combination with Metformin frequency of discontinuation of therapy in connection with the development of adverse reactions was 0.4% (in groups vildagliptin (50 mg 2 times a day) + Metformin and placebo + Metformin cases of discontinuation of therapy in connection with the development of adverse reactions were not observed).

In applying the drug Galvus dose 50 mg 1 or 2 times a day in combination with Metformin hypoglycemia was noted at 0.9 and 0.5%, respectively (placebo + Metformin — 0,4%). In the group of drug Galvus was not observed the development of severe hypoglycemia. Combination therapy vildagliptin + Metformin did not affect body weight of patients.

In the Central and peripheral nervous system: often — tremor, dizziness, headache.

Long-term clinical studies of up to 2 years did not reveal any additional abnormalities of the security profile or unforeseen risks when using vildagliptin in combination with Metformin.

In applying the drug Galvus dose 50 mg 1 times / day in combination with sulfonylureas

In applying the drug Galvus dose 50 mg 1 times / day in combination with glimepiride, the frequency of discontinuation of therapy in connection with the development of adverse reactions was 0.6% (compared with 0% in the glimepiride + placebo).

The frequency of hypoglycemia in patients receiving the drug Galvus in the dose of 50 mg 1 time a day along with glimepiride amounted to 1.2 percent (compared with 0.6% for placebo + glimepiride). In the group of drug Galvus was not observed the development of severe hypoglycemia.

In applying the drug Galvus in the recommended dose (50 mg 1 time a day) in combination with glimepiride there was an increase body weight of patients.

CNS: often — tremor, dizziness, headache.

From the body as a whole: often — asthenia.

In applying the drug Galvus dose 50 mg 1 or 2 times a day in combination with derivatives of thiazolidinedione

In applying the drug Galvus dose 50 mg 1 times / day in combination with pioglitazone, the frequency of discontinuation of therapy in connection with the development of adverse reactions was 0.7% (in groups vildagliptin (50 mg 2 times a day) + pioglitazone and placebo + pioglitazone cases of discontinuation of therapy in connection with the development of adverse reactions were not observed).

In applying the drug Galvus dose 50 mg 1 times / day in combination with pioglitazone at a dose of 45 mg, hypoglycemia was not observed in the group vildagliptin (dose 50 mg 2 times a day) + pioglitazone (at a dose of 45 mg) hypoglycemia was noted in 0.6% of cases, and in patients receiving placebo + pioglitazone at a dose of 45 mg, 1.9% of cases. In the group of drug Galvus was not observed the development of severe hypoglycemia. The average increase in body weight compared with the placebo patients receiving the drug Galvus dose 50 mg 1 or 2 times a day along with pioglitazone was + 0.1 kg and + 1.3 kg, respectively. When you add drug Galvus dose 50 mg 1 or 2 times a day to the dose of pioglitazone to 45 mg daily the incidence of peripheral edema was 8.2% and 7% respectively (compared to 2.5% for monotherapy with pioglitazone). However, when assigning initial combination therapy vildagliptin at a dose of 50 mg 1 or 2 times a day along with a pioglitazone dose of 45 mg per day peripheral edema was observed in 3.5 or 6.1% of the patients respectively (compared to 9.3% in the monotherapy with pioglitazone in a dose 30 mg / day).

From the side of cardiovascular system: often — peripheral edema.

From the body as a whole: often — the increase in body weight.

In applying the drug Galvus in the dose of 50 mg 2 times a day in combination with insulin

In appointing the drug in combination with insulin was observed of increased risk of hypoglycemia compared with the combination of placebo + insulin. The average increase in body weight compared with the placebo patients receiving the drug Galvus in the dose of 50 mg 2 times a day with insulin, was 0.9 kg.

CNS: frequently — headache

From the digestive system: often — nausea, flatulence, gastroesophageal reflux disease.

Disorders of metabolism and nutrition: often — hypoglycemia.

Post-marketing studies: during post-marketing studies were valeny following adverse reactions — urticaria (frequency unknown).

Drug interactions:

The drug Galvus has a low potential for drug interactions. Because the drug is not a substrate of cytochrome P450 enzymes and does not inhibit and does not induce these enzymes, interaction of drug Galvus with drugs that are substrates, inhibitors or inducers of P450 are unlikely. While the use of vildagliptin does not affect the metabolism of drugs which are substrates of enzymes: CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and CYP3A4/5.

Clinically significant drug interactions Galvus drugs most commonly used to treat diabetes type 2 diabetes (glibenclamide, pioglitazone, Metformin) or with a narrow therapeutic range (amlodipine, digoxin, ramipril, simvastatin, valsartan, warfarin) is not installed.

Method of application and dose:

Inside, regardless of meals.

Mode drug dosing should be individualized depending on efficacy and tolerability.

The recommended dose during the monotherapy or as part of a two-component combination therapy with Metformin, or insulin thiazolidinediones — 50 or 100 mg 1 time per day. In patients with more severe diabetes type 2 diabetes receiving treatment with insulin, the drug Galvus is recommended in a dose of 100 mg/day.

A dose of 50 mg/day should be administered in 1 reception in the morning, a dose of 100 mg/day — 50 mg 2 times a day morning and evening.

When used in the composition of the two-component combination therapy with sulfonylureas, the recommended dose of Galvus is 50 mg 1 time per day in the morning. When administered in combination with sulfonylureas effectiveness of drug therapy in a dose of 100 mg/day was similar to that in the dose of 50 mg/day. If insufficient clinical effect of the application of the maximum recommended daily dose of 100 mg for a better glycemic control may require the appointment of other hypoglycemic drugs Metformin, sulfonylurea derivatives, thiazolidinediones or insulin.

Patients with liver or kidney. Patients with less impaired renal function and liver does not require correction dosing regimen of the drug.

Patients aged &ge65 years. The elderly patients do not require correction dosing regimen of the drug Galvus.

Use in patients aged &le18 years. Because of experience with the drug Galvus in children and adolescents under 18 years no, it is not recommended to use the drug in this category of patients.

Overdose:

The drug Galvus is well tolerated when administered at dose up to 200 mg/day.

Symptoms: in applying the drug in a dose of 400 mg/day may experience muscle pain, rarely light and transient paraesthesia, fever, oedema and transient increase in the concentration of lipase (above ULN in 2 times). With increasing doses of the drug Galvus to 600 mg/day may develop swelling extremities with paresthesias and increasing concentrations of ck, ALT, C-reactive protein and myoglobin. All overdose symptoms and changes in laboratory parameters disappear after drug discontinuation.

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

Special instructions:

Violations liver function. Because in rare cases, when using vildagliptin was marked elevation of transaminases (usually without clinical manifestations), the appointment of a drug Galvus, and regularly during the first year of treatment (1 every 3 months), it is recommended to determine the biochemical indicators of liver function. If a patient has increased activity of aminotransferases, this result should be confirmed by repeated study, and then periodic determination of biochemical indicators of liver function as long as they are not normalized. If the increase in activity of AST or ALT above 3×ULN confirmed by repeated study, and the drug is recommended to cancel.

With the development of jaundice or other signs of impaired liver function on the background of the drug Galvus therapy with the drug should be discontinued immediately. After normalization of liver function the drug treatment can not resume. If necessary, insulin therapy the drug is Galvus used only in combination with insulin. The drug should not be used in patients with diabetes type 1 diabetes or to treat diabetic ketoacidosis.

Effects on ability to drive vehicles and/or operate machinery. The influence of the drug Galvus on the ability to drive vehicles or operate machinery is not established. With the development of vertigo on the background of drug therapy, patients should not drive vehicles or operate machinery.