Vidamace 50 mg Tablets

VIDAMACE 50 mg is indicated for the treatment of type 2 diabetes mellitus in adults: VIDAMACE 50 mg is indicated as an adjunct to diet and exercise to improve glycaemic control in adult patients with type 2 diabetes mellitus, as add-on therapy, in combination with metformin, a sulphonylurea (SU), or insulin (with or without metformin) when diet, exercise and a single antidiabetic medicine do not result in adequate glycaemic control. VIDAMACE 50 mg is also indicated in triple combination with a sulphonylurea and metformin when diet and exercise plus dual therapy with these medicines do not provide adequate glycaemic control. Management of diabetes should always include diet control. Caloric restriction, weight loss, and exercise are essential for the proper treatment of the diabetic patient. This is important not only for the primary treatment of diabetes, but also as an adjunct to medicinal therapy.

Posology The management of antidiabetic therapy should be individualised. The recommended daily dose is either one VIDAMACE 50 mg a day, or one VIDAMACE 50 mg taken twice daily, in combination with metformin or with insulin (with or without metformin). When taken as triple combination with metformin and a sulphonylurea, the recommended dose is one VIDAMACE 50 mg twice a day. When used in combination with a sulphonylurea, the recommended dose of VIDAMACE is 50 mg once daily, taken in the morning. In this patient population, VIDAMACE 100 mg daily (2 x 50 mg) was no more effective than 50 mg once daily.

Special populations Renal impairment: In patients with moderate or severe renal impairment or with end-stage renal disease (ESRD) on haemodialysis, the recommended dose of VIDAMACE 50 mg is 50 mg tablet once daily (see sections 4.4 and 5.2). The maximum dose should be 50 mg in patients with mild renal impairment. Elderly: In patients treated with vildagliptin, as in VIDAMACE 50 mg, u2265 65 years of age and u2265 75 years of age no differences were observed in the overall safety, tolerability, or efficacy between this elderly population and younger patients. No dose adjustments are necessary in elderly patients (u2265 65 years old) (see section 5.2). Paediatric population VIDAMACE 50 mg is not recommended for use in children and adolescents (< 18 years) as the safety and efficacy in this population group have not been established.

Method of administration For oral use. VIDAMACE 50 mg can be taken with or without food. Missed dose: Doctors should advise patients who forget to take VIDAMACE 50 mg to take a dose as soon as possible and then continue with the normal dose. Patients should not take a double dose to compensate for the missed dose.

• hypersensitivity to vildagliptin or to any of the ingredients of VIDAMACE 50 mg (see section 6.1)
• in patients with hepatic impairment, including patients with a pre-treatment ALT or AST > 2,5 x the upper limit of normal.

Hepatic impairment: VIDAMACE 50 mg is contraindicated in patients with hepatic impairment, including patients with a pre-treatment elevated ALT or AST (see section 4.3). Liver enzyme monitoring: Cases of hepatic dysfunction (including hepatitis) have been reported. In these cases, the patientu2019s were generally asymptomatic and liver function tests (LFTs) returned to normal after discontinuation of treatment. Liver function tests should be performed prior to the initiation of treatment with VIDAMACE 50 mg to determine the patients baseline value. Liver function test-monitoring is imperative and should be monitored during treatment 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 3 x upper limit of normal or greater persist, VIDAMACE 50 mg should be discontinued. Patients who develop jaundice or other signs suggestive of liver dysfunction should discontinue VIDAMACE 50 mg and contact their medical practitioner immediately. Following withdrawal of treatment with VIDAMACE 50 mg and LFT normalisation, VIDAMACE 50 mg treatment should not be reinitiated.

Cardiac failure: Vildagliptin, as in VIDAMACE 50 mg, is not recommended in patients with New York Heart Association (NYHA) Class III. Rates of reported cardiac adverse events were higher in patients with NYHA functional class III treated with vildagliptin than with placebo. There is no experience of vildagliptin, as in VIDAMACE 50 mg, 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, as in VIDAMACE 50 mg 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, VIDAMACE 50 mg 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 VIDAMACE 50 mg 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.

Arthralgia: VIDAMACE 50 mg may cause arthralgia that can be severe.

General: VIDAMACE 50 mg is not a substitute for insulin in insulin-requiring patients. VIDAMACE 50 mg should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis.

Renal impairment: There is limited experience in patients with ESRD on haemodialysis. Therefore, VIDAMACE 50 mg should be used with caution in these patients (see sections 4.2 and 5.2).

Excipients: VIDAMACE 50 mg contains lactose. Patients with the rare hereditary conditions of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take VIDAMACE 50 mg.

VIDAMACE 50 mg has a low potential for interactions. Since VIDAMACE 50 mg is not a cytochrome P (CYP) 450 enzyme substrate nor does it inhibit nor induce CYP 450 enzymes, it is not likely to interact with co-medications that are substrates, inhibitors or inducers of these enzymes. Furthermore, VIDAMACE 50 mg does not affect metabolic clearance of co-medications metabolised by CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4/5. Interaction studies were conducted with commonly co-prescribed medicines for patients with type 2 diabetes or medications with a narrow therapeutic window. As a result of these studies 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, as in VIDAMACE 50 mg.

Combination with ACE-inhibitors: There may be an increased risk of angioedema in patients concomitantly taking ACE-inhibitors (see section 4.8). The hypoglycaemic effect of vildagliptin, as in VIDAMACE 50 mg, may be reduced by certain active substances, including thiazides, corticosteroids, thyroid products and sympathomimetics.

Pregnancy VIDAMACE 50 mg should not be used in pregnant and breastfeeding women, as safety in pregnancy and lactation has not been established.

Breastfeeding It is unknown whether vildagliptin, as in VIDAMACE 50 mg, is excreted in human milk. Mothers on VIDAMACE 50 mg should not breastfeed their infants.

Fertility No studies on the effect on human fertility have been conducted for VIDAMACE 50 mg.

Dizziness has been reported in patients taking vildagliptin, as in VIDAMACE 50 mg. Patients who experience dizziness should avoid driving vehicles or using machines.

a). Summary of the safety profile The majority of adverse reactions in 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. Cases of hepatic dysfunction (including hepatitis) have been reported. In these cases, the patients were generally asymptomatic without clinical sequelae and liver function tests (LFTs) returned to normal after discontinuation of treatment. Cases of angioedema have been reported during treatment with vildagliptin, as in VIDAMACE 50 mg. A greater proportion of cases were reported when vildagliptin was administered in combination with an ACE-Inhibitor. The majority of events were mild in severity and resolved with ongoing vildagliptin treatment.

b). Tabulated summary of adverse reactions

System Organ Class Frequency Side effects Metabolism and nutrition disorders Frequent *** Decreased blood glucose, ****hypoglycaemia Nervous system disorders Frequent *Tremor, *dizziness, headache, ***chills ***Gastrointestinal disorders Frequent Less frequent Frequency unknown Nausea, gastroesophageal reflux disease, constipation Diarrhoea, flatulence Pancreatitis, intestinal obstruction Hepatobiliary disorders Frequency unknown Cases of hepatitis, usually reversible upon medicine discontinuation, cholecystitis **** Skin and subcutaneous tissue disorders Frequent Frequency unknown Hyperhidrosis Urticaria, localised exfoliation or blister Musculoskeletal and connection tissue disorders Frequency unknown Arthralgia, sometimes severe **General disorders and administration site conditions Frequent Asthenia, peripheral oedema * Vildagliptin in combination with metformin and sulphonylurea only ** Vildagliptin in combination with sulphonylurea only *** Vildagliptin in combination with insulin (with or without metformin) ****Vildagliptin in combination with metformin and sulphonylurea

Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Healthcare providers are asked to report any suspected adverse reactions to SAHPRA via the Med Safety APP (Medsafety X SAHPRA) and eReporting platform (who-umc.org) found on SAHPRA website. An email can be sent directly to the company, [email protected] to ensure safety of the product.

Signs and symptoms: Muscle pain, paraesthesia, fever and oedema have been reported. Increases in lipase levels (2 x ULN), creatine phosphokinase (CPK) levels, accompanied by elevations of aspartate aminotransferase (AST), C-reactive protein, and myoglobin may develop.

Management of overdose: Treatment is symptomatic and supportive. VIDAMACE 50 mg is not dialysable; however, the major hydrolysis metabolite (LAY151) can be removed by haemodialysis.