Galvus®

Galvus

Active substance:

Vildagliptin*

Pharmgroup:

Hypoglycemic synthetic and other drugs

Average price in pharmacies

Instructions:

Clinical and pharmacological group

15.014 (Oral hypoglycemic drug)

Release form, composition and packaging

Tablets are white to light yellow, round, smooth, with beveled edges; on one side there is an overprint “NVR”, on the other - “FB”.

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

7 pcs. - blisters (2) - cardboard packs. 7 pcs. - blisters (4) - cardboard packs. 7 pcs. - blisters (8) - cardboard packs. 7 pcs. - blisters (12) - cardboard packs. 14 pcs. - blisters (2) - cardboard packs. 14 pcs. - blisters (4) - cardboard packs. 14 pcs. - blisters (8) - cardboard packs. 14 pcs. - blisters (12) - cardboard packs.

pharmachologic effect

Vildagliptin is a representative of the class of stimulants of the islet apparatus of the pancreas, 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 using vildagliptin 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 observed. The degree of improvement in β-cell function depends on the degree of initial damage; Thus, in individuals who do not have diabetes mellitus (with normal plasma 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, which leads to improved 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 insulin/glucagon ratio against the background of hyperglycemia, caused by an increase in the levels of GLP-1 and GIP, causes a decrease in glucose production by the liver both during the prandial period and after a meal, which leads to a decrease in plasma glucose levels.

In addition, with the use of vildagliptin, a decrease in plasma lipid levels is observed, but this effect is not associated with its effect 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 delay in gastric emptying, but no such effect is 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, sulfonylureas, thiazolidinedione, or insulin, a significant long-term decrease in the concentration of glycated hemoglobin (HbA1c) and fasting blood glucose was observed.

Pharmacokinetics

Suction

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

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

Distribution

The binding of vildagliptin to plasma proteins is low (9.3%). The drug is distributed equally between plasma and red blood cells. The distribution of vildagliptin presumably occurs extravascularly; Vd at steady state after intravenous administration is 71 l.

Metabolism

Biotransformation is the main route of elimination of vildagliptin. In the human body, 69% of the drug dose is converted. The main metabolite, LAY151 (57% of the dose), is pharmacologically inactive and is a product of hydrolysis of the cyano component. About 4% of the drug dose undergoes amide hydrolysis.

Experimental studies indicate a positive effect of DPP-4 on the hydrolysis of the drug. Vildagliptin is not metabolized with the participation of cytochrome P450 isoenzymes. Vildagliptin is not a substrate of CYP450 isoenzymes and does not inhibit or induce cytochrome P450 isoenzymes.

Removal

After oral administration of the drug, about 85% of the dose is excreted by the kidneys and 15% through the intestines; renal excretion of unchanged vildagliptin is 23%. T1/2 after oral administration is about 3 hours, regardless of dose.

Gender, body mass index and ethnicity do not affect the pharmacokinetics of vildagliptin.

Pharmacokinetics in special clinical situations

In patients with mild to moderate liver dysfunction (6-10 points according to the Child-Pugh classification), after a single dose of the drug, a decrease in the bioavailability of vildagliptin is observed by 20% and 8%, respectively. In patients with severe liver failure (Child-Pugh score 12), the bioavailability of vildagliptin increases by 22%. An increase or decrease in the maximum bioavailability of vildagliptin not exceeding 30% is not clinically significant. There was no correlation between the severity of liver dysfunction and the bioavailability of the drug.

In patients with mild, moderate and severe renal impairment, in patients with end-stage chronic renal failure on hemodialysis, there is an increase in Cmax by 8-66% and AUC by 32-134%, which does not correlate with the severity of the disorder, as well as an increase in AUC of the inactive metabolite LAY151 by 1.6-6.7 times, depending on the severity of the disorder. T1/2 of vildagliptin does not change.

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

The pharmacokinetic properties of vildagliptin in children and adolescents under 18 years of age have not been established.

Dosage

Galvus is taken orally regardless of food intake.

The dosage regimen of the drug should be selected individually depending on the effectiveness and tolerability.

The recommended dose of the drug when used as monotherapy or as part of two-component combination therapy with metformin, thiazolidinedione or insulin is 50 mg or 100 mg per day. In patients with more severe type 2 diabetes mellitus receiving insulin treatment, Galvus is recommended to be used at a dose of 100 mg/day.

A dose of 50 mg/day should be administered as one dose in the morning. A dose of 100 mg/day should be administered at 50 mg 2 times/day in the morning and evening.

When used as part of a two-component combination therapy with sulfonylurea derivatives, the recommended dose of Galvus is 50 mg 1 time per day in the morning. When prescribed in combination with sulfonylurea derivatives, the effectiveness of drug therapy at a dose of 100 mg/day was similar to that at a dose of 50 mg/day. If the clinical effect is insufficient when using the maximum recommended daily dose of 100 mg, additional administration of other hypoglycemic drugs: metformin, sulfonylurea derivatives, thiazolidinedione or insulin is possible for better glycemic control.

In patients with mild renal and liver dysfunction, no adjustment of the drug dosage regimen is required.

In elderly patients (≥ 65 years), no adjustment of the Galvus dosage regimen is required.

Since there is no experience with the use of Galvus in children and adolescents under 18 years of age, it is not recommended to use the drug in this category of patients.

Overdose

Galvus is well tolerated when administered at a dose of up to 200 mg/day.

Symptoms: when using the drug at a dose of 400 mg/day, muscle pain may be observed; rarely - mild and transient paresthesia, fever, edema and transient increase in lipase concentration (2 times higher than ULN). When the dose of Galvus is increased to 600 mg/day, edema of the extremities with paresthesia and an increase in the concentration of CPK, ALT, C-reactive protein and myoglobin are possible. All symptoms of overdose and changes in laboratory parameters disappear after stopping the use of the drug.

Treatment: 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.

Drug interactions

Galvus has a low potential for drug interactions.

Since Galvus is not a substrate of cytochrome P450 enzymes and does not inhibit or induce these enzymes, interaction of Galvus with drugs that are substrates, inhibitors or inducers of P450 is unlikely. With simultaneous use, vildagliptin also does not affect the rate of metabolism of drugs that are substrates of enzymes: CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and CYP3A4/5.

No clinically significant interaction of Galvus with drugs most commonly used in the treatment of type 2 diabetes mellitus (glibenclamide, pioglitazone, metformin) or those with a narrow therapeutic index (amlodipine, digoxin, ramipril, simvastatin, valsartan, warfarin) has been established.

Use during pregnancy and lactation

There is no sufficient data on the use of Galvus in pregnant women, and therefore the drug should not be used during pregnancy. If there are disorders of glucose metabolism in pregnant women, there is an increased risk of developing congenital anomalies, as well as the incidence of neonatal morbidity and mortality.

In experimental studies, when administered in doses 200 times higher than recommended, the drug did not cause disturbances in fertility and early development of the embryo and did not have a teratogenic effect on the fetus.

Since it is unknown whether vildagliptin is excreted in human breast milk, Galvus should not be used during lactation.

Side effects

When using Galvus as monotherapy or in combination with other drugs, most adverse reactions were mild, temporary and did not require discontinuation of therapy. There was no correlation between the incidence of adverse events and age, gender, ethnicity, duration of use, or dosage regimen.

The incidence of angioedema during treatment with Galvus was >1/10,000, <1/1,000 (graded “rare”) and was similar to that in the control group. Most often, angioedema was observed when the drug was prescribed in combination with ACE inhibitors. In most cases, angioedema was of moderate severity and disappeared with continued vildagliptin therapy.

During treatment with Galvus, asymptomatic liver dysfunction (including hepatitis) was rarely observed. In most cases, these disorders and deviations of liver function tests from normal resolved independently without complications after discontinuation of drug therapy. When using Galvus at a dose of 50 mg 1 time/day or 2 times/day, the incidence of increased liver enzyme activity (ALT or AST ≥ 3xULN) was 0.2% or 0.3%, respectively (compared to 0.2% in the control group). Increases in liver enzyme activity were in most cases asymptomatic, did not progress, and were not accompanied by cholestatic changes or jaundice.

To assess the incidence of adverse events, the following criteria were used: very often (≥1/10); often (≥1/100, <1/10), sometimes (≥1/1,000, <1/100), rarely (≥1/10,000, <1/1,000), very rarely (≤1/10,000 ), including individual messages.

When using Galvus as monotherapy

When using Galvus at a dose of 50 mg 1 time / day or 2 times / day, the frequency of discontinuation of therapy due to the development of adverse reactions (0.2% or 0.1%, respectively) was not higher than that in the placebo group (0.6%) or the reference drug (0.5% ).

During monotherapy with Galvus at a dose of 50 mg 1 time/day or 2 times/day, the incidence of hypoglycemia without increasing the severity of the condition was 0.5% (2 out of 409 people) or 0.3% (4 out of 1,082), which is comparable with the reference drug and placebo (0.2%). When Galvus was used as monotherapy, there was no increase in patient weight.

From the side of the central nervous system: often - dizziness; sometimes a 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 safety profile deviations or unexpected risks when using vildagliptin as monotherapy.

When using Galvus at a dose of 50 mg 1 time / day or 2 times / day in combination with metformin

When using Galvus at a dose of 50 mg/day in combination with metformin, the rate of discontinuation of therapy due to the development of adverse reactions was 0.4% (in the groups vildagliptin (50 mg 2 times/day) + metformin and placebo + metformin cases of discontinuation of therapy due to the development no adverse reactions were noted).

When using Galvus at a dose of 50 mg 1 time / day or 2 times / day in combination with metformin, hypoglycemia was observed in 0.9% and 0.5% of cases, respectively (in the placebo + metformin group - 0.4%). There was no development of severe hypoglycemia in the Galvus group. Combination therapy with vildagliptin + metformin did not affect the body weight of patients.

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

Long-term clinical studies of up to 2 years did not reveal any additional safety profile deviations or unexpected risks when using vildagliptin in combination with metformin.

When using Galvus at a dose of 50 mg/day in combination with sulfonylurea derivatives

When using Galvus at a dose of 50 mg/day in combination with glimepiride, the rate of discontinuation of therapy due to the development of adverse reactions was 0.6% (compared to 0% in the glimepiride + placebo group).

The incidence of hypoglycemia in patients receiving Galvus at a dose of 50 mg/day along with glimepiride was 1.2% (compared to 0.6% in the placebo + glimepiride group). There was no development of severe hypoglycemia in the Galvus group.

When using Galvus at the recommended dose (50 mg/day) in combination with glimepiride, no increase in patient weight was observed.

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

From the body as a whole: often - asthenia.

When using Galvus at a dose of 50 mg 1 time / day or 2 times / day in combination with thiazolidinedione derivatives

When using Galvus at a dose of 50 mg/day in combination with pioglitazone, the frequency of discontinuation of therapy due to the development of adverse reactions was 0.7% (in the groups vildagliptin (50 mg 2 times/day) + pioglitazone and placebo + pioglitazone cases of discontinuation of therapy due to the development no adverse reactions were noted).

When using Galvus at a dose of 50 mg/day in combination with pioglitazone at a dose of 45 mg, hypoglycemia was not observed; in the group of vildagliptin (at a dose of 50 mg 2 times a day) + pioglitazone (at a dose of 45 mg), hypoglycemia was observed in 0.6% of cases, and in patients receiving placebo + pioglitazone at a dose of 45 mg, in 1.9% of cases. There was no development of severe hypoglycemia in the Galvus group. The mean increase in body weight compared to placebo in patients receiving Galvus 50 mg once a day or twice a day with pioglitazone was +0.1 kg or +1.3 kg, respectively.

When Galvus was added at a dose of 50 mg once a day or twice a day to pioglitazone at a dose of 45 mg/day, the incidence of peripheral edema was 8.2% and 7%, respectively (compared to 2.5% with pioglitazone monotherapy). However, when prescribing initial combination therapy with vildagliptin at a dose of 50 mg 1 time / day or 2 times / day together with pioglitazone at a dose of 45 mg / day, peripheral edema was observed in 3.5% or 6.1% of patients, respectively (compared to 9.3% with pioglitazone monotherapy at a dose of 30 mg/day).

From the cardiovascular system: often - peripheral edema.

From the body as a whole: often - weight gain.

When using Galvus at a dose of 50 mg 2 times a day in combination with insulin

When prescribing the drug in combination with insulin, there was no increase in the risk of hypoglycemia compared with the combination of placebo + insulin.

The average increase in body weight compared to placebo in patients receiving Galvus at a dose of 50 mg 2 times a day with insulin was +0.9 kg.

From the side of the central nervous system: often - headache.

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

Metabolism: often - hypoglycemia.

Post-marketing studies

During post-marketing studies, the following adverse reactions were identified: urticaria (frequency unknown).

Storage conditions and periods

The drug should be stored in a dry place, out of reach of children, at a temperature not exceeding 30°C. Shelf life: 2 years. Do not use after expiration date.

Indications

Diabetes mellitus type 2:

- as monotherapy in combination with diet therapy and exercise;

- as part of a two-component combination therapy with metformin, sulfonylurea derivatives, thiazolidinedione or insulin in case of ineffectiveness of diet therapy, exercise and monotherapy with these drugs.

Contraindications

- hypersensitivity to vildagliptin and any other components of the drug.

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

Galvus is not recommended for use in patients with severely impaired liver function, including patients with elevated liver enzymes (ALT or AST > 2.5 times ULN). Since experience with Galvus in patients with moderate or severe renal impairment (including end-stage renal failure on hemodialysis) is limited, the drug is not recommended for use in this category of patients.

Because Galvus tablets contain lactose; the drug is not recommended for use in patients with rare hereditary disorders:

- galactose intolerance;

- lactase deficiency;

- impaired absorption of glucose-galactose.

special instructions

Since in rare cases, when using vildagliptin, an increase in aminotransferase activity was observed (usually without clinical manifestations), before prescribing Galvus, as well as regularly during the first year of treatment with the drug (once every 3 months), it is recommended to determine biochemical indicators of liver function. If a patient has elevated aminotransferase activity, this result should be confirmed by repeat testing, and then biochemical parameters of liver function should be regularly determined until they return to normal. If the activity of AST or ALT is 3 times higher than the ULN (as confirmed by repeated studies), it is recommended to discontinue the drug.

If jaundice or other signs of liver dysfunction develop while using Galvus, drug therapy should be stopped immediately. After normalization of liver function indicators, treatment with the drug cannot be resumed.

If insulin therapy is necessary, Galvus is used only in combination with insulin. The drug should not be used in patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis.

Impact on the ability to drive vehicles and operate machinery

The effect of Galvus on the ability to drive vehicles and operate machinery has not been established. If dizziness develops during treatment with the drug, patients should not drive vehicles or operate machinery.

Use for renal impairment

Since experience with Galvus in patients with moderate or severe renal impairment (including end-stage renal failure on hemodialysis) is limited, the drug is not recommended for use in this category of patients.

Use for liver dysfunction

Galvus is not recommended for use in patients with severely impaired liver function, including patients with elevated liver enzymes (ALT or AST > 2.5 times ULN).

Conditions for dispensing from pharmacies

The drug is available with a prescription.

Galvus

When using the drug Galvus in monotherapy or in combination with other drugs, most adverse reactions were mild, temporary and did not require discontinuation of therapy. There was no correlation between the incidence of adverse events (AEs) and age, gender, ethnicity, duration of use, or dosage regimen.

The incidence of angioedema during therapy with Galvus was ≥1/10000, <1/1000 (graded “rare”) and was similar to that in the control group. The most common cases of angioedema were observed when using the drug in combination with angiotensin-converting enzyme inhibitors. In most cases, angioedema was of moderate severity and resolved spontaneously with continued therapy with vildagliptin.

During therapy with Galvus, asymptomatic liver dysfunction (including hepatitis) was rarely observed. In most cases, these disorders and deviations of liver function tests from normal resolved independently without complications after discontinuation of drug therapy. When using the drug Galvus at a dose of 50 mg 1 or 2 times a day, the frequency of increases in liver enzyme activity (ALT or AST ≥3 x ULN) was 0.2% or 0.3%, respectively (compared to 0.2% in control group). The increase in the activity of “liver” enzymes in most cases was asymptomatic, did not progress and was not accompanied by cholestasis or jaundice.

AEs are grouped according to the MedDRA classification of organs and organ systems. Within each group of organs and organ systems, AEs are listed in order of decreasing frequency of occurrence. Within each group, the frequencies of AEs are listed in order of decreasing severity.

To assess the frequency of adverse events, the following criteria were used: very often (≥1/10), often (≥1/100, <1/10), infrequently (≥1/1,000, <1/100), rarely (≥1 /10,000, <1/1,000), very rare (<1/10,000), isolated reports (frequency unknown).

When using the drug Galvus in monotherapy

When using the drug Galvus at a dose of 50 mg 1 or 2 times a day, the frequency of discontinuation of therapy due to the development of adverse reactions (0.2% or 0.1%, respectively) was not higher than that in the placebo group (0.6%) or the drug comparison (0.5%).

During monotherapy with Galvus at a dose of 50 mg 1 or 2 times a day, the incidence of hypoglycemia without increasing the severity of the condition was 0.5% (2 out of 409 patients) and 0.3% (4 out of 1082), respectively, which is comparable with the drug comparison and placebo (0.2%).

Infectious and parasitic diseases:

very rarely - upper respiratory tract infections, nasopharyngitis.

Nervous system disorders:

often - dizziness; infrequently - headache.

Gastrointestinal disorders:

infrequently - constipation.

Vascular disorders:

infrequently - peripheral edema.

Long-term clinical studies of up to 2 years did not reveal any additional deviations in the safety profile or unexpected risks when using vildagliptin in monotherapy.

When using the drug Galvus at a dose of 50 mg 1 or 2 times a day in combination with metformin

When using the drug Galvus at a dose of 50 mg / day in combination with metformin, the frequency of discontinuation of therapy due to the development of adverse reactions was 0.4% (in the groups vildagliptin (50 mg 2 times a day) + metformin and placebo + metformin cases of discontinuation of therapy in no connection with the development of adverse reactions was noted).

When using the drug Galvus at a dose of 50 mg 1 or 2 times a day in combination with metformin, hypoglycemia was observed in 0.9% and 0.5% of cases, respectively (in the placebo + metformin group - 0.4%). There was no development of severe hypoglycemia in the Galvus group.

Combination therapy with vildagliptin + metformin did not affect the body weight of patients.

Nervous system disorders:

often - tremor, dizziness, headache.

Gastrointestinal disorders

: often - nausea.

Long-term clinical studies of up to 2 years did not reveal any additional safety profile deviations or unexpected risks when using vildagliptin in combination with metformin.

A study of the combination of vildagliptin and metformin as initial therapy for type 2 diabetes mellitus revealed no abnormal safety profile or unexpected risks.

When using the drug Galvus at a dose of 50 mg/day in combination with sulfonylurea derivatives

When using the drug Galvus at a dose of 50 mg/day in combination with glimepiride, the frequency of discontinuation of therapy due to the development of adverse reactions was 0.6% (compared to 0% in the glimepiride + placebo group).

The incidence of hypoglycemia in patients receiving Galvus at a dose of 50 mg/day with glimepiride was 1.2% (compared to 0.6% in the placebo + glimepiride group). There was no development of severe hypoglycemia in the Galvus group.

When using the drug Galvus at the recommended dose (50 mg/day) in combination with glimepiride, no increase in body weight was observed.

Infectious and parasitic diseases:

very rarely - nasopharyngitis.

Gastrointestinal disorders:

infrequently - constipation.

Nervous system disorders:

often - tremor, dizziness, headache, asthenia.

When using the drug Galvus at a dose of 50 mg 1 or 2 times a day in combination with thiazolidinedione derivatives

When using the drug Galvus at a dose of 50 mg/day in combination with pioglitazone, the frequency of discontinuation of therapy due to the development of adverse reactions was 0.7% (in the groups vildagliptin 100 mg/day + pioglitazone and placebo + pioglitazone cases of discontinuation of therapy due to the development of adverse reactions no reactions were noted).

When using the drug Galvus at a dose of 50 mg/day in combination with pioglitazone at a dose of 45 mg, no hypoglycemia was observed; in the group vildagliptin (at a dose of 50 mg 2 times a day) + pioglitazone (at a dose of 45 mg), hypoglycemia was observed in 0.6% of cases, and in patients receiving placebo + pioglitazone at a dose of 45 mg, in 1.9% of cases cases.

There was no development of severe hypoglycemia in the Galvus group. The mean increase in body weight compared to placebo in patients receiving Galvus 50 mg once or twice daily with pioglitazone was +0.1 kg or +1.3 kg, respectively.

When Galvus 50 mg once or twice daily was added to pioglitazone 45 mg/day, the incidence of peripheral edema was 8.2% and 7%, respectively (compared to 2.5% with pioglitazone monotherapy). However, with initial combination therapy of vildagliptin 50 mg once or twice daily with pioglitazone 45 mg/day, the development of peripheral edema was observed in 3.5% or 6.1% of patients, respectively (compared to 9.3% at against monotherapy with pioglitazone at a dose of 30 mg/day).

Vascular disorders:

often - peripheral edema.

Metabolic and nutritional disorders

: often - weight gain.

When using the drug Galvus at a dose of 50 mg 2 times a day in combination with insulin (with or without metformin)

When using the drug in combination with insulin (in combination with metformin or without metformin), the frequency of therapy discontinuation due to the development of side effects was equal to 0.3%; in the vildagliptin therapy group, there were no cases of therapy discontinuation in the placebo group.

When using the drug in combination with insulin (in combination with metformin or without metformin), there was no increase in the risk of hypoglycemia compared with the combination of placebo + insulin (14% in the vildagliptin group and 16.4% in the placebo group). Two patients in the vildagliptin group and 6 patients in the placebo group developed severe hypoglycemia.

At the time of completion of the study, the drug had no effect on average body weight (body weight increased by +0.6 kg compared to baseline in the vildagliptin group, and remained unchanged in the placebo group).

Nervous system disorders:

often - headache, unknown - asthenia.

Gastrointestinal disorders

: often - nausea, gastroesophageal reflux; infrequently - diarrhea, flatulence.

General and administration site disorders:

often - chills.

Metabolic and nutritional disorders:

often - hypoglycemia.

When using the drug Galvus at a dose of 50 mg twice a day in combination with sulfonylureas and metformin

There were no cases of drug withdrawal associated with AEs in the combination therapy group with vildagliptin, metformin and glimepiride. In the combination therapy group with placebo, metformin and glimepiride, the incidence of AEs was 0.6%.

Hypoglycemia was common in both groups (5.1% in the vildagliptin, metformin and glimepiride combination group and 1.9% in the placebo, metformin and glimepiride combination group). There was one episode of severe hypoglycemia in the vildagliptin group.

At the end of the study, there was no significant effect on body weight (+0.6 kg in the vildagliptin group and -0.1 kg in the placebo group).

Nervous system disorders:

often - dizziness, tremor, asthenia.

Metabolic and nutritional disorders:

often - hypoglycemia.

Skin and subcutaneous tissue disorders

: often - hyperhidrosis.

Post-registration studies

During post-registration studies, the following adverse reactions were identified (since the reports were received voluntarily from a population of unknown size, it is not possible to reliably determine the frequency of development of these AEs, and therefore they are classified as frequency unknown): hepatitis (reversible upon cessation of therapy) , urticaria, pancreatitis, bullous and exfoliative skin lesions, arthralgia, in rare cases severe, myalgia, increased activity of liver enzymes.

If any of the side effects indicated in the instructions get worse, or you notice any other side effects not listed in the instructions, tell your doctor.