Vildagvus (Tablets) Instructions for Use

Marketing Authorization Holder

Grotex, LLC (Russia)

ATC Code

A10BH02 (Vildagliptin)

Active Substance

Vildagliptin (Rec.INN registered by WHO)

Dosage Form

Vildagvus

Tablets 50 mg: 7, 10, 14, 20, 21, 28, 30, 35, 40, 42, 49, 50, 56, 60, 63, 70, 80, 84, 90, 98, 100, 112, 120, 126, 130, 140 or 150 pcs.

Dosage Form, Packaging, and Composition

Tablets are round, flat-cylindrical, white or almost white in color, with a bevel; minor darker or lighter inclusions are allowed.

Excipients: microcrystalline cellulose, lactose monohydrate, sodium carboxymethyl starch, magnesium stearate.

7 pcs. – contour cell packaging (from 1 to 10) – cardboard packs.
10 pcs. – contour cell packaging (from 1 to 10) – cardboard packs.
14 pcs. – contour cell packaging (from 1 to 10) – cardboard packs.
28 pcs. – bottle (1) – cardboard packs.
30 pcs. – bottle (1) – cardboard packs.
56 pcs. – bottle (1) – cardboard packs.
60 pcs. – bottle (1) – cardboard packs.
84 pcs. – bottle (1) – cardboard packs.
90 pcs. – bottle (1) – cardboard packs.
112 pcs. – bottle (1) – cardboard packs.
120 pcs. – bottle (1) – cardboard packs.
130 pcs. – bottle (1) – cardboard packs.
140 pcs. – bottle (1) – cardboard packs.
150 pcs. – bottle (1) – cardboard packs.

Clinical-Pharmacological Group

Oral hypoglycemic drug

Pharmacotherapeutic Group

Drugs for the treatment of diabetes mellitus; hypoglycemic drugs, other than insulins; dipeptidyl peptidase-4 (DPP-4) inhibitors

Pharmacological Action

Hypoglycemic agent. Vildagliptin is a representative of the class of pancreatic islet stimulators, 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 meal-stimulated secretion of glucagon-like peptide type 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, which leads to an improvement in 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 the function of pancreatic β-cells is noted. The degree of improvement in β-cell function depends on the degree of their initial damage; thus, in individuals without diabetes (with normal blood plasma glucose levels), Vildagliptin does not stimulate insulin secretion and does not lower glucose levels.

By increasing the levels of endogenous GLP-1, Vildagliptin increases the sensitivity of α-cells to glucose, which leads to an improvement in glucose-dependent regulation of glucagon secretion. The decrease in the level of excess glucagon during meals, in turn, causes a decrease in insulin resistance.

An increase in the insulin/glucagon ratio against the background of hyperglycemia, due to increased levels of GLP-1 and GIP, causes a decrease in glucose production by the liver both during the prandial period and after meals, which leads to a decrease in blood plasma glucose levels.

In addition, against the background of vildagliptin use, a decrease in blood plasma lipid levels is noted; however, this effect is not associated with its action on GLP-1 or GIP and improvement of pancreatic β-cell function.

It is known that an increase in GLP-1 levels can lead to a slowdown in gastric emptying, but such an effect is not observed with 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 decrease in the concentration of glycated hemoglobin (HbA_1c) and fasting blood glucose was noted.

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 decrease in C_max by 19% and an increase in the time to reach it to 2 hours 30 minutes are noted. 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 erythrocytes. The distribution of vildagliptin is presumably extravascular, V_d at steady state after IV administration is 71 L.

Biotransformation is the main route of elimination of 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 dose.

Indications

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

ICD codes

Dosage Regimen

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

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

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

Administer tablets orally with a glass of water, with or without food.

For combination therapy with metformin, use the standard dosage of 50 mg twice daily.

When adding to a sulfonylurea, consider a dose reduction of the sulfonylurea to lower the risk of hypoglycemia.

For combination with insulin, the standard 50 mg twice daily regimen applies; monitor blood glucose levels closely.

Do not use in patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis.

Avoid use in patients with moderate or severe renal impairment due to limited safety data.

Do not use in patients with severe hepatic impairment or if ALT/AST is >2.5 times the upper limit of normal.

Prior to initiation and every 3 months during the first year of therapy, monitor liver function tests.

Discontinue treatment immediately if a patient develops jaundice or other signs of liver dysfunction.

If confirmed ALT or AST elevation is >3 times the upper limit of normal, discontinue Vildagvus.

Do not restart therapy after discontinuation due to liver enzyme elevations.

Adverse Reactions

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

From the CNS often – tremor, dizziness, headache.

From the metabolism often – hypoglycemia, weight gain.

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

Other often – asthenia, peripheral edema.

Contraindications

Hypersensitivity to vildagliptin.

Use in Pregnancy and Lactation

Adequate and strictly controlled clinical studies of 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 increased > 2.5 times the ULN.

Before starting treatment, as well as regularly (once every 3 months) during the first year of treatment, it is recommended to determine biochemical parameters of liver function. If increased aminotransferase activity is detected, this result should be confirmed by a repeat test, and then biochemical parameters of liver function should be regularly determined until they normalize. If an increase in AST or ALT activity by 3 times or more the 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 failure 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 increased > 2.5 times the ULN.

Not recommended for use in patients with moderate or severe renal impairment (including end-stage renal failure 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 (once every 3 months) during the first year of treatment, it is recommended to determine biochemical parameters of liver function. If increased aminotransferase activity is detected, this result should be confirmed by a repeat test, and then biochemical parameters of liver function should be regularly determined until they normalize. If an increase in AST or ALT activity by 3 times or more the 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 mechanisms

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 30°C (86°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.