Viglaz

A white to light yellowish, round, flat-faced tablet with beveled edges, engraved with "
Click on icon to see table/diagram/image
" logo on one side and "V" over "50" on the other side.
Each tablet contains Vildagliptin 50 mg.
Excipients/Inactive Ingredients: Anhydrous lactose, microcrystalline cellulose, sodium starch glycolate, magnesium stearate.

Pharmacology: Pharmacodynamics: Mechanism of action: Vildagliptin is a potent and selective dipeptidyl peptidase-4 (DPP-4) inhibitor of the islet enhancer class.
Such inhibition results in increased postprandial and fasting endogenous levels of the glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) hormone levels.
Vildagliptin is a rapid and complete inhibitor of DPP-4 and is used in the treatment of type 2 diabetes for a 24-hour period.
Vildagliptin improves glucose-dependent insulin secretion by raising the endogenous levels of these incretin hormones and improving beta cell sensitivity to glucose.
Patients with type 2 diabetes who received treatment with 50 to 100 mg per day had seen a significant enhancement in the markers of beta cell function. Vildagliptin does not increase insulin secretion or decrease blood glucose levels in non-diabetic persons, so the degree of beta cell function improvement depends on the initial level of dysfunction.
Vildagliptin raises endogenous GLP-1 levels, which improves the sensitivity of alpha cells to glucose and increases the amount of glucose-appropriate glucagon secretion. Increased levels of incretin hormones cause the insulin/glucagon ratio to rise more rapidly during hyperglycaemia, which lowers blood glucose levels by reducing the production of fasting and postprandial hepatic glucose.
Vildagliptin treatment does not produce the expected delay in gastric emptying caused by elevated GLP-1 levels.
Pharmacokinetics: Absorption: Following oral administration in the fasting state, Vildagliptin is rapidly absorbed with peak plasma concentration observed at 1.75 hours. The absolute bioavailability is 85%. Co-administration with food slightly decreases the rate of absorption of Vildagliptin, as characterized by a 19% decrease in peak concentrations, and a delay in the time to peak plasma concentration to 2.5 hours. There is no change in the extent of absorption, and food does not alter the overall exposure (AUC).
Distribution: The plasma protein binding of Vildagliptin is low (9.3%), and Vildagliptin is distributed equally between plasma and red blood cells. The mean volume of distribution of Vildagliptin at steady-state after intravenous administration (V_ss) is 71 litres, suggesting extravascular distribution.
Metabolism: Approximately 69% of a dose is metabolized, mainly by hydrolysis in the kidney. The major metabolite (LAY151) is pharmacologically inactive and is the hydrolysis product of cyano moiety, accounting for 57% of the dose, followed by the amide hydrolysis product (4% of the dose). DPP-4 contribute partially to the hydrolysis of Vildagliptin as shown in an in vivo study using DPP-4 deficient rats. Vildagliptin is not metabolized by CYP450 enzymes to any quantifiable extent. In vitro studies demonstrated that Vildagliptin does not inhibit or induce cytochrome P450 enzymes.
Excretion: Approximately 85% of the dose is excreted into the urine and 15% of the dose is recovered in the feces. Renal excretion of unchanged Vildagliptin accounts for 23% of the dose after oral administration. After intravenous administration to healthy subjects, the total plasma and renal clearances of Vildagliptin are 41 liter/hour and 13 liter/hour, respectively. The mean elimination half-life after intravenous administration is approximately 2 hours. The elimination half-life after oral administration is approximately 3 hours and is independent of the dose.
Linearity/non-linearity: Vildagliptin is rapidly absorbed with an absolute oral bioavailability of 85%. Peak plasma concentrations for Vildagliptin and the area under the plasma concentration versus time curve (AUC) increased in an approximately dose-proportional manner over the therapeutic dose range.
Special populations: Gender: No differences in the pharmacokinetics of Vildagliptin were observed between male and female subjects with a diverse range of age and body mass index (BMI). DPP-4 inhibition by Vildagliptin was unaffected by gender.
Obesity: Body Mass Index (BMI) does not show any impact on the pharmacokinetic parameters of Vildagliptin. DPP-4 inhibition by Vildagliptin was unaffected by BMI.
Hepatic impairment: The exposure to Vildagliptin (100 mg) after a single dose in subjects with mild and moderate hepatic impairment (Child-Pugh score 5 to 6 and 7 to 9, respectively) was decreased (20% and 8%, respectively), while exposure to Vildagliptin subjects with severe impairment (Child-Pugh score 10 to 12) was increased by 22%. The maximum change (increase or decrease) in the exposure to Vildagliptin is about 30%, which is not considered to be clinically relevant. There was no correlation between the severity of hepatic function impairment and changes in exposure to Vildagliptin.
The use of Vildagliptin is not recommended in patients with hepatic impairment including patients with a pre-treatment ALT or AST >2.5 x ULN.
Renal impairment: The AUC of Vildagliptin increased 1.4, 1.7, and 2-fold in patients with mild (CrCl 50 to less than 80 mL/min), moderate (CrCl 30 to less than 50 mL/min) and severe renal impairment (CrCl less than 30 mL/min), respectively, compared to normal healthy subjects. The AUC of the metabolites LAY151 increased 1.6, 3.2 and 7.3-fold and that of BQS867 increased 1.4, 2.7, and 7.3-fold in patients with mild, moderate and severe renal impairment, respectively, compared to healthy volunteers. Limited data from patients with end stage renal disease (ESRD) indicate that Vildagliptin exposure is similar to that in patients with severe renal impairment. LAY151 concentrations in ESRD patients were approximately 2 to 3-fold higher than in patients with severe renal impairment. Dosage adjustment may be required in patients with renal impairment. Vildagliptin was removed by hemodialysis to a limited data (3% over a 3 to 4-hour hemodialysis session starting 4 hours post dose).
Geriatric patients (65 years or above): In otherwise healthy elderly subjects (≥70 years), the overall exposure to Vildagliptin (100 mg daily) was increased by 32%, with an 18% increase in peak plasma concentration compared to young healthy subjects (18-40 years). These changes are not considered to be clinically relevant. DPP-4 inhibition by Vildagliptin is not affected by age in the age groups studied.
Pediatric patients (below 18 years): No pharmacokinetic data available.
Ethnicity: There was no evidence that ethnicity affects the pharmacokinetics of Vildagliptin.

Vildagliptin is indicated as an adjunct to diet and exercise to improve glycaemic control in adults with type 2 diabetes mellitus.
As monotherapy.
In combination therapy: Initial combination with metformin when diabetes is not adequately controlled by diet and exercise alone; in combination with other medicinal products for the treatment of diabetes, including insulin, when these do not provide adequate glycaemic control.

Recommended dose: The management of antidiabetic therapy should be individualized.
The recommended dose of Vildagliptin is 50 mg once or twice daily. The maximum daily dose of Vildagliptin is 100 mg.
For monotherapy, and for combination with metformin, with a thiazolidinedione (TZD) or with insulin (with or without metformin), the recommended dose of Vildagliptin is 50 mg or 100 mg daily.
When used in dual combination with a sulfonylurea, the recommended dose of Vildagliptin is 50 mg once daily. In this patient population, Vildagliptin 100 mg daily was no more effective than Vildagliptin 50 mg once daily.
For triple combination with metformin and a sulfonylurea (SU), the recommended dose of Vildagliptin is 100 mg daily.
If tighter glycaemic control is required on the top of the maximum recommended daily dose of Vildagliptin, the addition of other antidiabetic drugs such as metformin, an SU, a TZD or insulin may be considered.
General target population: Adults 18 years of age and above.
Special populations: Renal impairment: No dosage adjustment of Vildagliptin is required in patients with mild renal impairment. In patients with moderate or severe renal impairment or End Stage Renal Disease (ESRD), the recommended dose of Vildagliptin is 50 mg once daily.
Hepatic impairment: Vildagliptin is not recommended in patients with hepatic impairment including patients with a pre-treatment ALT or AST >2.5x the upper limit of normal (ULN).
Pediatric patient (below 18 years): Vildagliptin has not been studied in patients under 18 years of age; therefore, the use of Vildagliptin in pediatric patients is not recommended.
Geriatric patients (65 years or above): In patients treated with Vildagliptin ≥65 years of age and ≥75 years of age, no differences were observed in the overall safety, tolerability, or efficacy between this elderly population and younger patient. No dosage adjustments are therefore necessary in the elderly patients.
Mode of administration: For oral use.
Vildagliptin can be administered with or without meals.
The 50 mg dose should be administered once daily in the morning. The 100 mg dose should be administered as two divided doses of 50 mg given in the morning and evening.
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.

Information regarding overdose with Vildagliptin is limited. In the event of an overdose, supportive management is recommended. Vildagliptin is not dialyzable, however the major hydrolysis metabolite (LAY151) can be removed by hemodialysis.

Vildagliptin is contraindicated in patients with known serious hypersensitivity to Vildagliptin or to any ingredient in the formulation.

Based on the Ministry of Public Health's Announcement: Do not use in patients with known hypersensitivity to this medicine
Do not use in type I diabetes treatment, patient with ketoacidosis, severe infection or serious accident.
Avoid using in pregnancy and lactation.
Should not use concomitantly with alcohol.
This drug may increase risk of severe joint pain.

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.
Renal impairment: Patients with End Stage Renal Disease (ESRD) receiving hemodialysis have little experience. Vildagliptin should be used cautiously in these patients as a result.
Hepatic impairment: Vildagliptin is not recommended in patients with hepatic impairment, including patients with pre-treatment ALT or AST >2.5x ULN.
Liver enzyme monitoring: Hepatic dysfunction, including hepatitis, has only rarely been reported. When treatment was stopped, the patients' liver function test (LFT) results returned to normal and they were typically asymptomatic without any clinical sequelae. Before starting Vildagliptin therapy, LFTs should be carried out to determine the patient's baseline value. LFTs should be checked while taking Vildagliptin at three-month intervals for the first year and then at an event after that. Patients who develop increased transaminase levels should be followed up with a second liver functional evaluation to confirm the findings and be followed thereafter with frequent liver function tests until the abnormalities return to normal. Vildagliptin therapy should be stopped if an increase in AST or ALT of 3x ULN or more continues. Vildagliptin should be stopped by patients who develop jaundice or other symptoms of liver dysfunction and contact their physician immediately. Vildagliptin treatment shouldn't be started up again after stopping it and LFT normalization.
Cardiac failure: A clinical trial of Vildagliptin in patients with New York Heart Association (NYHA) functional classes I-III revealed that therapy with Vildagliptin was not related to changes in left ventricular function or worsening of pre-existing congestive heart failure (CHF) compared with 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.
Other: Vildagliptin should not be taken by those who have a rare hereditary condition called galactose intolerance, total lactase deficiency or glucose-galactose malabsorption because VIGLAZ (50 MG TABLET) contains lactose.

Pregnancy: There is insufficient experience with Vildagliptin in pregnant women. Vildagliptin was not teratogenic in either rats or rabbits. The fetal risk for humans is unknown. Vildagliptin should not be used during pregnancy unless the benefit to the mother outweighs the potential risk to the fetus.
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 administered to breast-feeding woman.

Monotherapy: Metabolism and nutrition disorders: Uncommon: hypoglycaemia.
Nervous system disorders: Common: dizziness.
Uncommon: headache.
Respiratory disorders: Uncommon: upper respiratory tract infection, nasopharyngitis.
Gastrointestinal disorders: Uncommon: constipation.
Frequency not known: acute pancreatitis.
Skin and subcutaneous tissue disorders: Frequency not known: angioedema, urticaria, bullous and exfoliative skin lesions, including bullous pemphigoid.
Musculoskeletal and connective tissue disorders: Uncommon: arthralgia.
Hepatic disorders: Rare: hepatic dysfunction including hepatitis (reversible upon drug discontinuation).
General disorders: Uncommon: peripheral oedema.
Combination with other drugs: Combination with metformin: Common: tremor, dizziness, headache.
Uncommon: hypoglycaemia.
Combination with sulfonylureas: Common: tremor, headache, dizziness, asthenia.
Combination with thiazolidinediones: Common: weight increase, peripheral oedema.
Uncommon: hypoglycaemia.
Combination with insulin: Common: headache, nausea, gastrooesophageal reflux disease, chills, blood glucose decreased.
Uncommon: diarrhea, flatulence.
Combination with metformin and sulfonylureas: Common: dizziness, tremor, asthenia, hypoglycaemia, hyperhidrosis.

Vildagliptin has low potential for drug interactions. Since Vidagliptin is not a cytochrome P (CYP) 450 enzyme substrate nor does it inhibit or induce CYP450 enzymes, it is not likely to interact with co-medications that are substrates, inhibitors or inducers of these enzymes.
Vildagliptin does not affect metabolic clearance of co-medications metabolized by CYP 1A2, CYP 2C8, CYP 2C9, CYP 2C19, CYP 2D6, CYP 2E1 and CYP 3A4/5. No clinically relevant interactions with other oral antidiabetics (glibenclamide, pioglitazone, metformin), amlodipine, digoxin, ramipril, simvastatin, valsartan or warfarin were observed after co-administration with Vildagliptin.
There may be an increased risk of angioedema in patients concomitantly taking ACE-inhibitors. 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.
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 below 30°C.
Protect from moisture.

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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