Galvus

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. 3 If a dose of Galvus 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. 2). Renal impairment No dose adjustment is required in patients with mild renal impairment (creatinine clearance ≥ 50 ml/min).

2). 2). Paediatric population Galvus is not recommended for use in children and adolescents (< 18 years). The safety and efficacy of Galvus in children and adolescents (< 18 years) have not been established. 1). 2).

Summary of the safety profile Safety data were obtained from a total of 5 451 patients exposed to vildagliptin at a daily dose of 100 mg (50 mg twice daily) in randomised double-blind placebo-controlled trials of at least 12 weeks duration.

Of these patients, 4 622 patients received vildagliptin as monotherapy and 829 patients received placebo. 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.

Hypoglycaemia has been reported in patients receiving vildagliptin concomitantly with sulphonylurea and insulin. 4). Tabulated list of adverse reactions Adverse reactions reported in patients who received Galvus in double-blind studies as monotherapy and add-on therapies are listed below for each indication by system organ class and absolute frequency.

Frequencies are defined as very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1 000 to <1/100), rare (≥1/10 000 to <1/1 000), very rare (<1/10 000), not known (cannot be estimated from the available data). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

7 Table 1 Adverse reactions reported in patients who received vildagliptin as monotherapy or as add-on therapy in controlled clinical studies and in post-marketing experience System organ class - adverse reaction Frequency Infections and infestations Nasopharyngitis Very common Upper respiratory tract infection Common Metabolism and nutrition disorders Hypoglycaemia Uncommon Nervous system disorders Dizziness Common Headache Common Tremor Common Eye disorders Vision blurred Common Gastrointestinal disorders Constipation Common Nausea Common Gastro-oesophageal reflux disease Common Diarrhoea Common Abdominal pain, including upper Common Vomiting Common Flatulence Uncommon Pancreatitis Rare Hepatobiliary disorders Hepatitis Not known* Skin and subcutaneous tissue disorders Hyperhidrosis Common Rash Common Pruritis Common Dermatitis Common Urticaria Uncommon Exfoliative and bullous skin lesions, including bullous pemphigoid Not known* Cutaneous vasculitis Not known* Musculoskeletal and connective tissue disorders Arthralgia Common Myalgia Common Reproductive system and breast disorders Erectile dysfunction Uncommon General disorders and administration site conditions Asthenia Common Oedema peripheral Common Fatigue Uncommon Chills Uncommon Investigations Abnormal liver function tests Uncommon Weight increase Uncommon * Based on post-marketing experience.

General Galvus is not a substitute for insulin in insulin-requiring patients. Galvus 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.

2). 2). 4 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 Galvus in order to know the patient’s baseline value. Liver function should be monitored during treatment with Galvus 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 Galvus therapy is recommended. Patients who develop jaundice or other signs suggestive of liver dysfunction should discontinue Galvus. Following withdrawal of treatment with Galvus and LFT normalisation, treatment with Galvus 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.

1). 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. 3). Although skin lesions were not observed at an increased incidence in clinical trials, there was limited experience in patients with diabetic skin complications.

1.