Vigliptic-50

Vildagliptin (LAF237) is an orally active antihyperglycemic agent that selectively inhibits the dipeptidyl peptidase-4 (DPP-4) enzyme. It is used to manage type II diabetes mellitus, where GLP-1 secretion and insulinotropic effects are impaired. By inhibiting DPP-4, vildagliptin prevents the degradation of glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which are incretin hormones that promote insulin secretion and regulate blood glucose levels. Elevated levels of GLP-1 and GIP consequently results in improved glycemic control.
White colour, scored on one side, round flat tablets.
Each Tablet Contains: Vildagliptin 50 mg, Excipients q.s.

Pharmacotherapeutic group: Drugs used in diabetes, dipeptidyl peptidase 4 (DPP-4) inhibitors. ATC code: A10BH02.
Pharmacology: Pharmacodynamics: Vildagliptin, a member of the islet enhancer class, is a potent and selective DPP-4 inhibitor.
Mechanism of action: The administration of vildagliptin results in a rapid and complete inhibition of DPP-4 activity, resulting in increased fasting and postprandial endogenous levels of the incretin hormones GLP-1 (glucagon-like peptide 1) and GIP (glucose-dependent insulinotropic polypeptide).
Pharmacodynamic effects: By increasing the endogenous levels of these incretin hormones, vildagliptin enhances the sensitivity of beta cells to glucose, resulting in improved glucose-dependent insulin secretion. Treatment with vildagliptin 50-100 mg daily in patients with type 2 diabetes significantly improved markers of beta cell function including HOMA-β (Homeostasis Model Assessment-β), proinsulin to insulin ratio and measures of beta cell responsiveness from the frequently-sampled meal tolerance test. In non-diabetic (normal glycaemic) individuals, vildagliptin does not stimulate insulin secretion or reduce glucose levels.
By increasing endogenous GLP-1 levels, vildagliptin also enhances the sensitivity of alpha cells to glucose, resulting in more glucose-appropriate glucagon secretion.
The enhanced increase in the insulin/glucagon ratio during hyperglycaemia due to increased incretin hormone levels results in a decrease in fasting and postprandial hepatic glucose production, leading to reduced glycaemia.
The known effect of increased GLP-1 levels delaying gastric emptying is not observed with vildagliptin treatment.
Pharmacokinetics: Absorption: In a fasting state, vildagliptin is rapidly absorbed following oral administration. Peak plasma concentrations are observed at 1.7 hours following administration. Plasma concentrations of vildagliptin increase in an approximately dose-proportional manner.
Distribution: The plasma protein binding of vildagliptin is low (9.3%) and vildagliptin distributes equally between plasma and red blood cells. The mean volume of distribution of vildagliptin at steady-state after intravenous administration (Vss) is 71 litres, suggesting extravascular distribution.
Metabolism: About 69% of orally administered vildagliptin is eliminated via metabolism not mediated by cytochrome P450 enzymes. Based on the findings of a rat study, DPP-4 contributes partially to the hydrolysis of vildagliptin. Vildagliptin is metabolized to pharmacologically inactive cyano (57%) and amide (4%) hydrolysis products in the kidney.
Elimination: Vildagliptin is eliminated via metabolism. Following oral administration, approximately 85% of the radiolabelled vildagliptin dose was excreted in urine and about 15% of the dose was recovered in feces.

Vildagliptin is indicated as an adjunct to diet and exercise to improve glycaemic control in adults with type 2 diabetes mellitus: as monotherapy in patients in whom metformin is inappropriate due to contraindications or intolerance; in combination with other medicinal products for the treatment of diabetes, including insulin, when these do not provide adequate glycaemic control.

Posology: Adults: When used as monotherapy, in combination with metformin, in combination with thiazolidinedione, in combination with metformin and a sulphonylurea, or in combination with insulin (with or without metformin), the recommended daily dose of vildagliptin is 100 mg, administered as one dose of 50 mg in the morning and one dose of 50 mg in the evening.
When used in dual combination with a sulphonylurea, the recommended dose of vildagliptin is 50 mg once daily administered in the morning. In this patient population, vildagliptin 100 mg daily was no more effective than vildagliptin 50 mg once daily.
When used in combination with a sulphonylurea, a lower dose of the sulphonylurea may be considered to reduce the risk of hypoglycaemia.
Doses higher than 100 mg are not recommended.
Elderly (≥65 years): No dose adjustments are necessary in elderly patients.
Renal impairment: No dose adjustment is required in patients with mild renal impairment (creatinine clearance ≥50 mL/min). In patients with moderate or severe renal impairment or with end-stage renal disease (ESRD), the recommended dose of Vildagliptin is 50 mg once daily.
Hepatic impairment: Vildagliptin should not be used in patients with hepatic impairment, including patients with pre-treatment alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3x the upper limit of normal (ULN) (see Precautions).
Paediatric population: Vildagliptin is not recommended for use in children and adolescents (<18 years). The safety and efficacy of Vildagliptin in children and adolescents (<18 years) have not been established. No data are available.
Method of administration: Oral use.
Vildagliptin can be administered with or without a meal.

Information regarding overdose with vildagliptin is limited.
Symptoms: Information on the likely symptoms of overdose was taken from a rising dose tolerability study in healthy subjects given Vildagliptin for 10 days. At 400 mg, there were three cases of muscle pain, and individual cases of mild and transient paraesthesia, fever, oedema and a transient increase in lipase levels. At 600 mg, one subject experienced oedema of the feet and hands, and increases in creatine phosphokinase (CPK), aspartate aminotransferase (AST), C-reactive protein (CRP) and myoglobin levels. Three other subjects experienced oedema of the feet, with paraesthesia in two cases. All symptoms and laboratory abnormalities resolved without treatment after discontinuation of the study medicinal product.
Management: In the event of an overdose, supportive management is recommended. Vildagliptin cannot be removed by haemodialysis. However, the major hydrolysis metabolite (LAY 151) can be removed by haemodialysis.

Hypersensitivity to the active substance or to any of the excipients of product component.

General: Vildagliptin is not a substitute for insulin in insulin-requiring patients. Vildagliptin should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis.
Liver enzyme monitoring: Rare cases of hepatic dysfunction (including hepatitis) have been reported. In these cases, the patients were generally asymptomatic without clinical sequelae and liver function test results returned to normal after discontinuation of treatment. Liver function tests should be performed prior to the initiation of treatment with Vildagliptin in order to know the patient's baseline value. Liver function should be monitored during treatment with Vildagliptin at three-month intervals during the first year and periodically thereafter. Patients who develop increased transaminase levels should be monitored with a second liver function evaluation to confirm the finding and be followed thereafter with frequent liver function tests until the abnormality(ies) return(s) to normal. Should an increase in AST or ALT of 3x ULN or greater persist, withdrawal of Vildagliptin therapy is recommended.
Patients who develop jaundice or other signs suggestive of liver dysfunction should discontinue Vildagliptin.
Following withdrawal of treatment with Vildagliptin and LFT normalisation, treatment with Vildagliptin should not be reinitiated.
Cardiac failure: A clinical trial of vildagliptin in patients with New York Heart Association (NYHA) functional class I-III showed that treatment with vildagliptin was not associated with a change in left-ventricular function or worsening of pre-existing congestive heart failure (CHF) versus placebo. Clinical experience in patients with NYHA functional class III treated with vildagliptin is still limited and results are inconclusive.
There is no experience of vildagliptin use in clinical trials in patients with NYHA functional class IV and therefore use is not recommended in these patients.
Skin disorders: Skin lesions, including blistering and ulceration have been reported in extremities of monkeys in nonclinical toxicology studies. Although skin lesions were not observed at an increased incidence in clinical trials, there was limited experience in patients with diabetic skin complications.
Furthermore, there have been post-marketing reports of bullous and exfoliative skin lesions.
Therefore, in keeping with routine care of the diabetic patient, monitoring for skin disorders, such as blistering or ulceration, is recommended.
Acute pancreatitis: Use of vildagliptin has been associated with a risk of developing acute pancreatitis. Patients should be informed of the characteristic symptom of acute pancreatitis.
If pancreatitis is suspected, vildagliptin should be discontinued; if acute pancreatitis is confirmed, vildagliptin should not be restarted. Caution should be exercised in patients with a history of acute pancreatitis.
Hypoglycaemia: Sulphonylureas are known to cause hypoglycaemia. Patients receiving vildagliptin in combination with a sulphonylurea may be at risk for hypoglycaemia. Therefore, a lower dose of sulphonylurea may be considered to reduce the risk of hypoglycaemia.
Renal impairment: There is limited experience in patients with ESRD on haemodialysis. Therefore, Vildagliptin should be used with caution in these patients (see Dosage & Administration).
Hepatic impairment: Vildagliptin should not be used in patients with hepatic impairment, including patients with pre-treatment ALT or AST >3x ULN.

Pregnancy: There are no adequate data from the use of vildagliptin in pregnant women. Studies in animals have shown reproductive toxicity at high doses. The potential risk for humans is unknown.
Due to lack of human data, Vildagliptin should not be used during pregnancy.
Breast-feeding: It is unknown whether vildagliptin is excreted in human milk. Animal studies have shown excretion of vildagliptin in milk. Vildagliptin should not be used during breast-feeding.
Fertility: No studies on the effect on human fertility have been conducted for Vildagliptin.

Safety data were obtained from a total of 3,784 patients exposed to vildagliptin at a daily dose of 50 mg (once daily) or 100 mg (50 mg twice daily or 100 mg once daily) in controlled trials of at least 12 weeks duration. Of these patients, 2,264 patients received vildagliptin as monotherapy and 1,520 patients received vildagliptin in combination with another medicinal product. 2,682 patients were treated with vildagliptin 100 mg daily (either 50 mg twice daily or 100 mg once daily) and 1,102 patients were treated with vildagliptin 50 mg once daily.
The majority of adverse reactions in these trials were mild and transient, not requiring treatment discontinuations. No association was found between adverse reactions and age, ethnicity, duration of exposure or daily dose.
Rare cases of hepatic dysfunction (including hepatitis) have been reported. In these cases, the patients were generally asymptomatic without clinical sequelae and liver function returned to normal after discontinuation of treatment. In data from controlled monotherapy and add-on therapy trials of up to 24 weeks in duration, the incidence of ALT or AST elevations ≥3x ULN (classified as present on at least 2 consecutive measurements or at the final on-treatment visit) was 0.2%, 0.3% and 0.2% for vildagliptin 50 mg once daily, vildagliptin 50 mg twice daily and all comparators, respectively. These elevations in transaminases were generally asymptomatic, non-progressive in nature and not associated with cholestasis or jaundice.
Rare cases of angioedema have been reported on vildagliptin at a similar rate to controls. A greater proportion of cases were reported when vildagliptin was administered in combination with an angiotensin converting enzyme inhibitor (ACE-Inhibitor). The majority of events were mild in severity and resolved with ongoing vildagliptin treatment.

Vildagliptin has a low potential for interactions with co-administered medicinal products. Since vildagliptin is not a cytochrome P (CYP) 450 enzyme substrate and does not inhibit or induce CYP 450 enzymes, it is not likely to interact with active substances that are substrates, inhibitors or inducers of these enzymes.
Combination with pioglitazone, metformin and glyburide: Results from studies conducted with these oral antidiabetics have shown no clinically relevant pharmacokinetic interactions.
Digoxin (P-gp substrate), warfarin (CYP2C9 substrate): Clinical studies performed with healthy subjects have shown no clinically relevant pharmacokinetic interactions. However, this has not been established in the target population.
Combination with amlodipine, ramipril, valsartan or simvastatin: Drug-drug interaction studies in healthy subjects were conducted with amlodipine, ramipril, valsartan and simvastatin. In these studies, no clinically relevant pharmacokinetic interactions were observed after co-administration with vildagliptin.
Combination with ACE-inhibitors: There may be an increased risk of angioedema in patients concomitantly taking ACE-inhibitors. (See Adverse Reactions.)
As with other oral antidiabetic medicinal products the hypoglycaemic effect of vildagliptin may be reduced by certain active substances, including thiazides, corticosteroids, thyroid products and sympathomimetics.

Store at temperatures not exceeding 30°C.

Antidiabetic Agents

A10BH02 - vildagliptin ; Belongs to the class of dipeptidyl peptidase 4 (DPP-4) inhibitors. Used in the treatment of diabetes.

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