Vilatin SR

Dosage Form & Strength

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. 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. If a dose of Vildagliptin is missed, it should be taken as soon as the patient remembers. A double dose should not be taken on the same day. The safety and efficacy of vildagliptin as triple oral therapy in combination with metformin and a thiazolidinedione have not been established.

Dosage in Special Population

Renal impairment: Should be used with caution Hepatic impairment: Should not be used in patients with hepatic impairment Pregnancy: should not be used during pregnancy Breast-feeding: Should not be used during breast-feeding

Indications

Vilatin SR is indicated for the treatment of type 2 diabetes

Adverse Effects

Common side effects noted during trials were headache, dizziness, constipation, cough, nasopharyngitis and sweating. Some of the studies also reported a feeling of hypertension amongst the patients. Vildagliptin can also lead to weight gain.

Drug Interactions

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. 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; There may be an increased risk of angioedema in patients concomitantly taking ACE-inhibitors; 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

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 (glucosedependent insulinotropic polypeptide). 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

The half life of Vildagliptin in Vilatin SR is 2 hours

Absorption, Distribution, Metabolism & Excretion

Absorption Following oral administration in the fasting state, vildagliptin is rapidly absorbed, with peak plasma concentrations observed at 1.7 hours. Food slightly delays the time to peak plasma concentration to 2.5 hours, but does not alter the overall exposure (AUC). Administration of vildagliptin with food resulted in a decreased Cmax (19%). However, the magnitude of change is not clinically significant, so that vildagliptin can be given with or without food. The absolute bioavailability is 85%. 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. Biotransformation Metabolism is the major elimination pathway for vildagliptin in humans, accounting for 69% of the dose. The major metabolite (LAY 151) is pharmacologically inactive. DPP-4 contributes partially to the hydrolysis of vildagliptin based on an in vivo study using DPP-4 deficient rats. Vildagliptin is not metabolised by CYP 450 enzymes to any quantifiable extent. Elimination Following oral administration of vildagliptin, approximately 85% of the dose was excreted into the urine and 15% of the dose is recovered in the faeces. Renal excretion of the unchanged vildagliptin accounted for 23% of the dose after oral administration. After intravenous administration to healthy subjects, the total plasma and renal clearances of vildagliptin are 41 and 13 l/h, respectively. The mean elimination half-life after intravenous administration is approximately 2 hours. The elimination half-life after oral administration is approximately 3 hours.

Drug Use in Pregnancy

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

Drug Use in Renal Impairment

Renal Impairement: 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

Drug Use in Hepatic Impairment

Hepatic impairment Vilatin (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)

Drug Use in Pediatric Population

Vildagliptin: 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

Drug Use in Geriatric Population

Elderly (≥ 65 years) No dose adjustments are necessary in elderly patients