Vilmitrix^® (Tablets) Instructions for Use

Marketing Authorization Holder

R-Pharm JSC (Russia)

Manufactured By

R-Pharm Novoselki LLC (Russia)

ATC Code

A10BH02 (Vildagliptin)

Active Substance

Vildagliptin (Rec.INN registered by WHO)

Dosage Form

Vilmitrix®

Tablets 50 mg: 28 or 56 pcs.

Dosage Form, Packaging, and Composition

Tablets from white to light yellow in color, round, biconvex; marbling is allowed.

Excipients: microcrystalline cellulose type 102, anhydrous lactose, sodium carboxymethyl starch type A, magnesium stearate.

14 pcs. – blister packs (2) – cardboard packs.
14 pcs. – blister packs (4) – cardboard packs.

Clinical-Pharmacological Group

Oral hypoglycemic drug

Pharmacotherapeutic Group

Hypoglycemic agent for oral administration. Dipeptidyl peptidase-4 inhibitor

Pharmacological Action

Hypoglycemic agent. Vildagliptin is a representative of the class of pancreatic islet stimulators; it selectively inhibits the enzyme dipeptidyl peptidase-4 (DPP-4).

Rapid and complete inhibition of DPP-4 activity (> 90%) causes an increase in both basal and postprandial secretion of glucagon-like peptide-1 (GLP-1) and glucose-dependent 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 the sensitivity of pancreatic β-cells to glucose, leading to improved glucose-dependent insulin secretion.

When vildagliptin is used at a dose of 50-100 mg/day in patients with type 2 diabetes mellitus, an improvement in pancreatic β-cell function is observed. The degree of improvement in β-cell function depends on the degree of their initial damage; thus, in individuals without diabetes mellitus (with normal blood glucose levels), Vildagliptin does not stimulate insulin secretion and does not reduce glucose levels.

By increasing the levels of endogenous GLP-1, Vildagliptin increases the sensitivity of α-cells to glucose, leading to improved glucose-dependent regulation of glucagon secretion.

The reduction in excessive glucagon levels during meals, in turn, causes a decrease in insulin resistance.

The increase in the insulin/glucagon ratio against the background of hyperglycemia, due to increased levels of GLP-1 and GIP, causes a decrease in hepatic glucose production both during the prandial period and after meals, leading to a decrease in plasma glucose levels.

Furthermore, during the use of vildagliptin, a decrease in plasma lipid levels is observed; however, this effect is not associated with its action on GLP-1 or GIP and the improvement of pancreatic β-cell function.

It is known that an increase in GLP-1 levels can lead to delayed gastric emptying; however, such an effect is not observed during the use of vildagliptin.

When vildagliptin was used in 5795 patients with type 2 diabetes mellitus for 12 to 52 weeks as monotherapy or in combination with metformin, sulfonylurea derivatives, thiazolidinedione, or insulin, a significant long-term reduction in glycated hemoglobin (HbA_1c) and fasting blood glucose concentrations was observed.

Pharmacokinetics

Vildagliptin is rapidly absorbed after oral administration with an absolute bioavailability of 85%. In the therapeutic dose range, the increase in C_max of vildagliptin in plasma and AUC is almost directly proportional to the increase in dose.

After oral administration on an empty stomach, the time to reach C_max of vildagliptin in blood plasma is 1 hour 45 minutes. When taken simultaneously with food, the absorption rate decreases slightly: a 19% decrease in C_max and an increase in the time to reach it to 2 hours 30 minutes are observed. However, food intake does not affect the extent of absorption and AUC.

The binding of vildagliptin to plasma proteins is low (9.3%). It is distributed equally between plasma and red blood cells. The distribution of vildagliptin is presumed to be extravascular; V_d at steady state after IV administration is 71 L.

Biotransformation is the main route of elimination for vildagliptin. In the human body, 69% undergoes 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. Experimental studies have shown a positive effect of DPP-4 on the hydrolysis of the active substance. Vildagliptin is not metabolized by cytochrome P450 isoenzymes, is not a substrate, and does not inhibit or induce these isoenzymes.

After oral administration, about 85% is excreted by the kidneys and 15% through the intestines; renal excretion of unchanged vildagliptin is 23%. T_1/2 after oral administration is about 3 hours, regardless of the dose.

Indications

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

ICD codes

Dosage Regimen

Administer the dosage individually, based on glycemic control, tolerability, and the chosen treatment regimen.

The recommended daily dose is 100 mg, taken as 50 mg twice daily.

Take one 50 mg tablet in the morning and one in the evening.

Dosing can be done with or without food; food intake does not significantly affect absorption.

For monotherapy, initiate treatment with the standard 100 mg daily dose in combination with diet and exercise.

When used in combination therapy with metformin, a sulfonylurea, a thiazolidinedione, or insulin, also use the 100 mg daily dose.

Do not use in patients with moderate or severe renal impairment; safety data in these populations are limited.

Avoid use in patients with severe hepatic impairment or if ALT/AST levels are elevated more than 2.5 times the upper limit of normal.

Monitor liver function tests before treatment initiation, every 3 months for the first year, and periodically thereafter.

Discontinue therapy immediately if a patient develops jaundice or other signs of liver dysfunction; do not restart treatment.

This drug is not indicated for the treatment of type 1 diabetes mellitus or diabetic ketoacidosis.

Adverse Reactions

From the digestive system sometimes – constipation; rarely – asymptomatic liver function disorders (including hepatitis); when combined with insulin, frequently – nausea, flatulence, GERD.

From the CNS frequently – tremor, dizziness, headache.

From metabolism frequently – hypoglycemia, weight gain.

Allergic reactions rarely – angioedema (more often when combined with ACE inhibitors).

Other frequently – asthenia, peripheral edema.

Contraindications

Hypersensitivity to vildagliptin.

Use in Pregnancy and Lactation

Adequate and strictly controlled clinical studies on the safety of vildagliptin use during pregnancy and lactation have not been conducted, therefore Vildagliptin should not be used during pregnancy and breastfeeding.

In pregnant women with glucose metabolism disorders, there is an increased risk of congenital anomalies, as well as the frequency of neonatal morbidity and mortality.

It is not known whether Vildagliptin is excreted in human breast milk.

Use in Hepatic Impairment

Not recommended for use in patients with severe liver dysfunction, including when ALT or AST activity is elevated > 2.5 times the upper limit of normal (ULN).

Before starting treatment, as well as regularly (every 3 months) during the first year of treatment, it is recommended to determine biochemical parameters of liver function.

If elevated aminotransferase activity is detected, this result should be confirmed by a repeat test, and then liver function biochemical parameters should be regularly determined until they normalize.

If an increase in AST or ALT activity of 3 times or more ULN is confirmed by a repeat test, then Vildagliptin should be discontinued.

If jaundice or other signs of liver dysfunction develop, therapy with vildagliptin should be stopped immediately. After normalization of liver function parameters, treatment should not be resumed.

Use in Renal Impairment

Not recommended for use in patients with moderate or severe renal impairment (including end-stage renal disease and the need for hemodialysis), because data on the safety of use in this category of patients are limited.

Pediatric Use

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

Special Precautions

Not recommended for use in patients with severe liver dysfunction, including when ALT or AST activity is elevated > 2.5 times the upper limit of normal (ULN).

Not recommended for use in patients with moderate or severe renal impairment (including end-stage renal disease and the need for hemodialysis), because data on the safety of use in this category of patients are limited.

Before starting treatment, as well as regularly (every 3 months) during the first year of treatment, it is recommended to determine biochemical parameters of liver function.

If elevated aminotransferase activity is detected, this result should be confirmed by a repeat test, and then liver function biochemical parameters should be regularly determined until they normalize.

If an increase in AST or ALT activity of 3 times or more ULN is confirmed by a repeat test, then Vildagliptin should be discontinued.

If jaundice or other signs of liver dysfunction develop, therapy with vildagliptin should be stopped immediately. After normalization of liver function parameters, treatment should not be resumed.

If insulin therapy is necessary, Vildagliptin is used only in combination with insulin.

Vildagliptin should not be used to treat type 1 diabetes mellitus or to treat diabetic ketoacidosis.

Use in pediatrics

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

Effect on ability to drive vehicles and operate machinery

If dizziness develops during treatment with the drug, patients should not engage in potentially hazardous activities (including driving vehicles).

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.