Galvus^® (Tablets) Instructions for Use

ATC Code

A10BH02 (Vildagliptin)

Active Substance

Vildagliptin (Rec.INN registered by WHO)

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

Mechanism of action

Vildagliptin, a representative of the class of pancreatic islet stimulators, is a potent and selective dipeptidyl peptidase-4 (DPP-4) inhibitor that improves glycemic control. Inhibition of DPP-4 by vildagliptin leads to an increase in basal and postprandial endogenous levels of the incretin hormones GLP-1 (glucagon-like peptide 1) and GIP (glucose-dependent insulinotropic polypeptide).

Pharmacodynamic effects

When vildagliptin is used at a dose of 50-100 mg/day in patients with type 2 diabetes mellitus (T2DM), 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 (with normal plasma glucose concentration), Vildagliptin does not stimulate insulin secretion and does not reduce glucose concentration.

By increasing the concentration of endogenous GLP-1, Vildagliptin increases the sensitivity of α-cells to glucose, leading to improved glucose-dependent regulation of glucagon secretion. The reduction of elevated glucagon concentration 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 concentrations of GLP-1 and GIP, causes a decrease in hepatic glucose production both during and after meals, leading to a decrease in plasma glucose concentration.

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

It is known that an increase in GLP-1 concentration 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 T2DM for 52 weeks in monotherapy or in combination with metformin, sulfonylurea derivatives, thiazolidinedione, or insulin, a significant long-term reduction in glycated hemoglobin (HbA1c) and fasting blood glucose concentration was observed.

When using the combination of vildagliptin and metformin as initial therapy in patients with type 2 diabetes mellitus for 24 weeks, a dose-dependent reduction in HbA1c concentration was observed compared to monotherapy with these drugs. Cases of hypoglycemia were minimal in both therapy groups.

When vildagliptin was used at a dose of 50 mg once daily for 6 months in patients with T2DM with moderate (glomerular filtration rate (GFR) ≥30, <50 ml/min/1.73 m²) or severe (GFR <30 ml/min/1.73 m²) renal impairment, a clinically significant reduction in HbA1c concentration was observed compared to placebo.

When vildagliptin was used at a dose of 50 mg twice daily in combination with/without metformin and insulin (average dose 41 U/day), a reduction in HbA1c of 0.77% from the baseline mean value of 8.8% was demonstrated, with a statistically significant difference from placebo of 0.72%. The frequency of hypoglycemia in the vildagliptin group was comparable to that in the placebo group. When vildagliptin was used at a dose of 50 mg twice daily in combination with metformin (≥1500 mg/day) and glimepiride (≥4 mg/day), a statistically significant reduction in HbA1c level of 0.76% from the baseline mean value of 8.8% was shown.

Pharmacokinetics

Absorption

When taken orally on an empty stomach, Vildagliptin is rapidly absorbed, and its maximum plasma concentration (C_max) is reached 1.75 hours after administration. When taken simultaneously with food, the rate of absorption of vildagliptin decreases slightly: a 19% decrease in C_max and an increase in the time to reach it to 2.5 hours are observed. However, food intake does not affect the extent of absorption and AUC.

Vildagliptin is rapidly absorbed, and its absolute bioavailability after oral administration is 85%. C_max and AUC in the therapeutic dose range increase approximately proportionally to the dose.

Distribution

The degree of binding of vildagliptin to plasma proteins is low (9.3%). Vildagliptin is evenly distributed between plasma and red blood cells. The distribution of vildagliptin is presumed to be extravascular; the volume of distribution at steady state after intravenous administration (Vss) is 71 L.

Metabolism

The main route of elimination of vildagliptin is biotransformation. In the human body, 69% of the drug dose undergoes biotransformation. 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.

Preclinical studies indicate a positive effect of DPP-4 on the hydrolysis of vildagliptin. Vildagliptin is metabolized without the involvement of cytochrome P450 isoenzymes. Vildagliptin is not a substrate for P450 (CYP) isoenzymes, does not inhibit or induce cytochrome P450 isoenzymes.

Excretion

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%. With intravenous administration, the mean T_1/2 reaches 2 hours, the total plasma clearance and renal clearance of vildagliptin are 41 L/h and 13 L/h, respectively. T_1/2 after oral administration is about 3 hours, regardless of the dose.

Pharmacokinetics in special cases

Elderly patients (65 years and older). In healthy elderly people (≥70 years), the overall exposure to vildagliptin (100 mg once/day) increased by 32%, while C_max in plasma increased by 18% compared to young healthy people (18-40 years). Nevertheless, these changes are not considered clinically significant. Inhibition of DPP-4 by vildagliptin does not depend on the patient’s age within the studied age groups.

Hepatic impairment. In patients with mild and moderate hepatic impairment (6-9 points on the Child-Pugh scale) after a single dose of the drug, the bioavailability of vildagliptin decreases by 20% and 8%, respectively. In patients with severe hepatic impairment (10-12 points on the Child-Pugh scale), the bioavailability of vildagliptin increases by 22%. An increase or decrease in the maximum bioavailability of vildagliptin not exceeding 30% is not clinically significant. No correlation was found between the severity of hepatic impairment and the bioavailability of the drug.

Patients with renal impairment. In patients with mild, moderate, or severe renal impairment, the AUC of vildagliptin increased compared to healthy volunteers by 1.4, 1.7, and 2 times, respectively. The AUC of the metabolite LAY151 increased by 1.6, 3.2, and 7.3 times, and the metabolite BQS867 by 1.4, 2.7, and 7.3 times in patients with mild, moderate, and severe renal impairment, respectively. Limited data in patients with end-stage chronic kidney disease (CKD) indicate that the parameters in this group are similar to those in patients with severe renal impairment. The concentration of the metabolite LAY151 in patients with end-stage CKD increased 2-3 times compared to the concentration in patients with severe renal impairment.

When using the drug in patients with renal impairment, dose adjustment may be required.

Elimination of vildagliptin during hemodialysis is limited (3% after a single dose with a procedure duration of more than 3-4 hours).

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

Indications

Type 2 diabetes mellitus (in combination with diet therapy and physical exercise)

• As monotherapy in case of ineffectiveness of diet therapy and physical exercise in patients with contraindication to/intolerance of metformin or in case of ineffectiveness of metformin;
• In combination with metformin as initial drug therapy for insufficient effectiveness of diet therapy and physical exercise;
• As part of two-component combination therapy: with metformin or thiazolidinedione, or with insulin in case of ineffectiveness of diet therapy, physical exercise and monotherapy with these drugs;
• As part of two-component combination therapy with sulfonylurea derivatives in patients with insufficient glycemic control on the background of the maximum tolerated dose of sulfonylurea derivative or in the presence of contraindications to/intolerance of metformin;
• As part of triple combination therapy: in combination with sulfonylurea derivatives and metformin, in patients previously treated with sulfonylurea derivatives and metformin on the background of diet therapy and physical exercise who did not achieve adequate glycemic control;
• As part of triple combination therapy: in combination with insulin and metformin, in patients previously treated with insulin at a stable dose and metformin on the background of diet therapy and physical exercise who did not achieve adequate glycemic control.

ICD codes

Dosage Regimen

Tablets

The dose of Galvus^® should be selected individually based on efficacy and tolerability.

The recommended dose of Galvus^® is 50 mg once or twice daily. The maximum daily dose of the drug is 100 mg.

The dose of 50 mg/day should be taken once a day in the morning, the dose of 100 mg/day should be divided into 2 doses – 50 mg in the morning and in the evening. If a dose is missed, the missed dose should be taken as soon as possible. A double dose should not be taken on the same day.

Galvus^® is taken orally regardless of meals.

The recommended dose of the drug in monotherapy or as part of combination therapy with metformin, thiazolidinedione or insulin (in combination with metformin or without metformin) is 50 mg or 100 mg per day.

The recommended dose of Galvus^® as part of dual combination therapy with sulfonylurea drugs is 50 mg once/day in the morning. In this patient population, the efficacy of Galvus^® at a dose of 100 mg/day was similar to that at a dose of 50 mg/day.

The recommended dose of Galvus^® as part of triple combination therapy (Vildagliptin + sulfonylurea derivatives + metformin ) is 100 mg/day.

If glycemic control targets are not achieved with the maximum daily dose of 100 mg, the possibility of adding other hypoglycemic drugs, such as metformin, sulfonylurea derivatives, thiazolidinedione or insulin, to therapy with Galvus^® should be considered.

Patients with renal impairment

In patients with mild renal impairment (GFR ≥ 60 ml/min/1.73 m²) and moderate impairment with GFR 50-60 ml/min/1.73 m², no adjustment of the drug dosage regimen is required. In patients with moderate renal impairment with GFR 30-50 ml/min/1.73 m² and severe impairment (GFR <30 ml/min/1.73 m²), including end-stage CKD in patients on hemodialysis or undergoing hemodialysis, the drug should be used at a dose of 50 mg once/day.

Elderly patients

In elderly patients, no adjustment of the Galvus^® dosage regimen is required.

Children

The efficacy and safety of Galvus^® in children under 18 years of age have not been established. Data are not available.

Adverse Reactions

When using Galvus^® in monotherapy or in combination with other drugs, most adverse reactions were mild, temporary and did not require discontinuation of therapy. No correlation was found between the frequency of adverse events (AEs) and age, gender, ethnicity, duration of use or dosing regimen.

The frequency of angioedema during therapy with Galvus^® was >1/10000, <1/1000 (grading "rare") and was similar to that in the control group. Cases of angioedema were most often noted when the drug was used in combination with ACE inhibitors. In most cases, angioedema was of moderate severity and resolved on its own during continued therapy with vildagliptin.

During therapy with Galvus^®, liver function disorders (including hepatitis) of asymptomatic course were rarely noted. In most cases, these disorders and deviations of liver function tests from the norm resolved on their own without complications after discontinuation of therapy with the drug. When using Galvus^® at a dose of 50 mg once or twice daily, the frequency of increased liver enzyme activity (ALT or AST >3x ULN) was 0.2% or 0.3%, respectively (compared to 0.2% in the control group). The increase in liver enzyme activity was in most cases asymptomatic, non-progressive and not accompanied by cholestasis or jaundice.

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

The following criteria were used to assess the frequency of adverse events: very common (≥1/10), common (≥1/100, <1/10), uncommon (≥1/1000, <1/100), rare (≥1/10000, <1/1 000), very rare (≤1/10000), frequency not known (since reports are received voluntarily from a population of uncertain size, it is not possible to reliably determine the frequency of these ADRs, therefore they are classified as frequency unknown).

When using Galvus^® in monotherapy

When using Galvus^® at a dose of 100 mg/day, the frequency of therapy discontinuation due to the development of adverse reactions (0.2% or 0.1% respectively) was no higher than that in the placebo group (0.6%) or the comparator drug group (0.5%).

During monotherapy with Galvus^® at a dose of 100 mg/day, the frequency of hypoglycemia without an increase in severity was 0.4%, which is comparable to the comparator drug and placebo (0.2%).

Body weight did not change from baseline in clinical studies when Vildagliptin 100 mg/day was used as monotherapy (-0.3 kg and -1.3 kg in the Galvus^® and placebo groups, respectively)

Infections and infestations very rarely – upper respiratory tract infections, nasopharyngitis.

Metabolism and nutrition disorders uncommon – hypoglycemia.

Nervous system disorders common – dizziness; uncommon – headache.

Gastrointestinal disorders : uncommon – constipation.

Vascular disorders uncommon – peripheral edema.

Musculoskeletal and connective tissue disorders uncommon – arthralgia.

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

When using Galvus^® at a dose of 100 mg/day in combination with metformin

When using Galvus^® at a dose of 100 mg/day in combination with metformin or placebo in combination with metformin, no cases of therapy discontinuation due to the development of adverse reactions were noted.

When using Galvus^® at a dose of 100 mg/day in combination with metformin, hypoglycemia was noted in 1% of cases (in the placebo + metformin group – uncommon (0.4%)). No severe hypoglycemia was observed in the Galvus^® group.

Body weight did not change from baseline in clinical studies when using the combination of Galvus^® 100 mg/day and metformin (+0.2 kg and -1.0 kg in the Galvus^® and placebo groups, respectively).

Metabolism and nutrition disorders common – hypoglycemia.

Nervous system disorders common – tremor, dizziness, headache; uncommon – increased fatigue.

Gastrointestinal disorders common – nausea.

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

Study of the use of the combination of vildagliptin and metformin as starting therapy for type 2 diabetes mellitus did not reveal any deviations in the safety profile or unforeseen risks.

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 frequency of therapy discontinuation due to the development of adverse reactions was 0.6% (compared to 0% in the glimepiride + placebo group).

The frequency of hypoglycemia in patients receiving Galvus^® at a dose of 50 mg/day together with glimepiride was 1.2% (compared to 0.6% in the placebo + glimepiride group). No severe hypoglycemia was observed in the Galvus^® group.

Body weight did not change from baseline in clinical studies when Galvus^® at a dose of 50 mg once/day was added to glimepiride (-0.1 kg and -0.4 kg in the Galvus^® and placebo groups, respectively.

Infections and infestations very rarely – nasopharyngitis.

Metabolism and nutrition disorders common – hypoglycemia.

Gastrointestinal disorders : uncommon – constipation.

Nervous system disorders common – tremor, dizziness, headache, asthenia.

When using Galvus^® at a dose of 100 mg/day in combination with thiazolidinedione

When using Galvus^® at a dose of 100 mg/day + thiazolidinedione and placebo + thiazolidinedione, no cases of therapy discontinuation due to the development of adverse reactions were noted.

When using Galvus^® at a dose of 100 mg/day + pioglitazone, hypoglycemia developed in 0.6% of cases, and in patients receiving placebo + pioglitazone – in 1.9% of cases. No severe hypoglycemia was observed in the Galvus^® group.

In the study of Galvus^® as add-on therapy to pioglitazone, the absolute increase in body weight in the placebo and Galvus^® 100 mg/day groups was 1.4 and 2.7 kg, respectively.

When adding Galvus^® at a dose of 100 mg/day to pioglitazone at a dose of 45 mg/day, the frequency of peripheral edema was 7% (compared to 2.5% on the background of pioglitazone monotherapy).

Vascular disorders Common – peripheral edema.

Metabolism and nutrition disorders Common – increased body weight; Uncommon – hypoglycemia.

Nervous system disorders Uncommon – headache, asthenia.

When using Galvus^® at a dose of 50 mg twice daily 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 adverse reactions was 0.3% in the vildagliptin therapy group; in the placebo group, there were no cases of therapy discontinuation.

When using the drug in combination with insulin (in combination with metformin or without metformin), no increased risk of hypoglycemia was observed compared to the placebo + insulin combination (14% in the vildagliptin group and 16.4% in the placebo group).

Severe hypoglycemia developed in 2 patients in the vildagliptin group and in 6 patients in the placebo group.

At the study completion, the drug had no effect on mean body weight (body weight increased by +0.6 kg from baseline in the vildagliptin group, while it remained unchanged in the placebo group).

Nervous system disorders Common – headache, Unknown – asthenia.

Gastrointestinal disorders Common – nausea, gastroesophageal reflux; Uncommon – diarrhea, flatulence.

General disorders and administration site conditions : Common – chills.

Metabolism and nutrition disorders Common – hypoglycemia.

When using Galvus^® at a dose of 50 mg twice daily in combination with sulfonylurea drugs and metformin

There were no cases of drug discontinuation related to adverse reactions in the combination therapy group with vildagliptin, metformin, and glimepiride. In the combination therapy group with placebo, metformin, and glimepiride, the frequency of drug discontinuation related to adverse reactions was 0.6%.

Hypoglycemia was reported commonly in both groups (5.1% in the combination therapy group with vildagliptin, metformin, and glimepiride and 1.9% in the combination therapy group with placebo, metformin, and glimepiride). One episode of severe hypoglycemia was reported in the vildagliptin group.

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

Metabolism and nutrition disorders Common – hypoglycemia.

Nervous system disorders: Common – dizziness, tremor.

Skin and subcutaneous tissue disorders Common – hyperhidrosis.

General disorders Common – asthenia.

Post-marketing experience

The following adverse reactions have been identified during post-marketing use (since reports are received voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency, and they are therefore classified as frequency unknown).

Gastrointestinal disorders Frequency unknown – pancreatitis.

Hepatobiliary disorders Frequency unknown – hepatitis (resolved after drug discontinuation), increased liver enzyme levels (resolved after drug discontinuation), cholecystitis.

Musculoskeletal and connective tissue disorders Frequency unknown – myalgia.

Skin and subcutaneous tissue disorders Frequency unknown – urticaria, exfoliative and bullous skin lesions, including bullous pemphigoid, cutaneous vasculitis.

Reporting of adverse reactions

It is important to report suspected adverse reactions after drug registration to ensure continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are recommended to report any suspected adverse drug reactions via the national adverse reaction reporting systems of the member states of the Eurasian Economic Union.

Contraindications

• Hypersensitivity to vildagliptin and any other components of the drug;
• Hereditary galactose intolerance, lactase deficiency, glucose-galactose malabsorption;
• Type 1 diabetes mellitus;
• Acute or chronic metabolic acidosis (including diabetic ketoacidosis with or without coma). Diabetic ketoacidosis should be corrected with insulin therapy. Lactic acidosis (including history);
• Impaired liver function, including patients with elevated ‘liver’ enzyme activity (ALT or AST 3 times or more above the ULN /3×ULN/);
• Chronic heart failure (CHF) NYHA functional class IV (due to lack of clinical study data on the use of vildagliptin in this patient group);
• Children under 18 years of age (efficacy and safety of the drug use have not been established).

Use in Pregnancy and Lactation

Pregnancy

There are insufficient data on the use of Galvus^® in pregnant women, therefore the drug is contraindicated during pregnancy.

Preclinical studies have revealed reproductive toxicity at high doses; the potential risk to humans is unknown.

Breastfeeding period

Galvus^® is contraindicated during breastfeeding, as it is unknown whether Vildagliptin passes into human breast milk.

Use in Hepatic Impairment

Galvus^® is not recommended for use in patients with severe hepatic impairment, including patients with elevated liver enzyme activity (ALT or AST > 2.5 times the ULN).

Use in Renal Impairment

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

Pediatric Use

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

Geriatric Use

In elderly patients (≥ 65 years), no dose adjustment of Galvus^® is required.

Special Precautions

In preclinical studies at doses 200 times the recommended human dose, the drug did not cause impairment of fertility.

If insulin therapy is necessary, Galvus^® is used only in combination with insulin. The drug is contraindicated in patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis.

Heart failure

Since data on the use of vildagliptin in patients with CHF NYHA class III are limited and do not allow a definitive conclusion, it is recommended to use Galvus^® with caution in patients of this category.

The use of vildagliptin is not recommended in patients with CHF NYHA class IV, due to the lack of clinical study data on the use of vildagliptin in this patient group.

Renal impairment

Since experience with Galvus^® in patients with end-stage chronic kidney disease on hemodialysis or undergoing hemodialysis is limited, the drug should be used with caution in this category of patients.

Hepatic impairment

Since rare cases of elevated aminotransferase levels (usually without clinical manifestations) have been reported with the use of vildagliptin, it is recommended to determine liver function biochemical parameters before using Galvus^®, and regularly during the first year of use (every 3 months). If elevated aminotransferase levels are detected, a repeat test should be performed to confirm the result, and then liver function biochemical parameters should be determined regularly until they normalize. If an increase in AST or ALT activity to 3 or more times the ULN is confirmed by a repeat test, it is recommended to discontinue the drug.

If jaundice or other signs of liver dysfunction develop during treatment with Galvus^®, therapy should be discontinued immediately. After normalization of liver function parameters, treatment with the drug should not be resumed.

Hypoglycemia

Sulfonylurea drugs are known to potentially cause hypoglycemia. There is a risk of hypoglycemia when vildagliptin is used concomitantly with sulfonylurea drugs. If necessary, the possibility of reducing the dose of sulfonylurea drugs should be considered to minimize the risk of hypoglycemia.

Acute pancreatitis

The use of Galvus^® is associated with a risk of acute pancreatitis. Patients should be informed about symptoms characteristic of acute pancreatitis. If acute pancreatitis is suspected, Vildagliptin should be discontinued. Therapy with vildagliptin should not be resumed if acute pancreatitis was confirmed. Vildagliptin should be used with caution in patients with a history of acute pancreatitis.

Excipients

Patients with rare hereditary galactose intolerance, lactase deficiency, or glucose-galactose malabsorption should not take this drug.

Effect on ability to drive and operate machinery

Studies on the effect of Galvus^® on the ability to drive vehicles or operate machinery have not been conducted. If dizziness develops during drug use, patients should not drive vehicles or operate machinery.

Overdose

Vildagliptin is well tolerated at doses 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 activity (above 2 times the ULN). When the vildagliptin dose is increased to 600 mg/day, limb edema accompanied by paresthesia and increased CPK, C-reactive protein and myoglobin levels, and AST activity may develop. All overdose symptoms and changes in laboratory parameters are reversible after discontinuation of the drug.

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

Drug Interactions

Vildagliptin has a low potential for drug interactions.

Since Vildagliptin is not a substrate of cytochrome P450 (CYP) enzymes, and does not inhibit or induce these enzymes, interaction of vildagliptin with drugs that are substrates, inhibitors, or inducers of P450 (CYP) is unlikely. When used concomitantly, Vildagliptin also does not affect the metabolism rate of drugs that are substrates of the following enzymes: CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4/5.

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

Thiazides, corticosteroids, thyroid hormone preparations, sympathomimetics may reduce the hypoglycemic effect of vildagliptin, as well as other oral antidiabetic drugs.

The frequency of angioedema was higher with concomitant use of vildagliptin and ACE inhibitors, while it was similar to that in the control group. In most cases, angioedema was of moderate severity and resolved spontaneously during continued vildagliptin therapy.

Storage Conditions

The drug should be stored out of the reach of children, in the original packaging, at a temperature not exceeding 30°C (86°F).

Shelf Life

The shelf life is 3 years. Do not use after the expiration date.

Dispensing Status

The drug is dispensed by prescription.

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.