Galvus 50mg Tablet

GALVUS 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.

GALVUS 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.

The management of antidiabetic therapy should be individualised. The recommended dose of GALVUS is 50 mg a day or 50 mg twice a day in combination with metformin or insulin (with or without metformin). The recommended dose of GALVUS is 50 mg twice a day for triple combination with metformin and a SU. When used in combination with a sulphonylurea, the recommended dose of GALVUS is 50 mg once daily administered in the morning. In this patient population, GALVUS 100 mg daily was no more effective than GALVUS 50 mg once daily.

Patients with renal impairment: In patients with moderate or severe renal impairment or with End Stage Renal Disease (ESRD) on haemodialysis the recommended dose of GALVUS is 50 mg once daily (see Pharmacokinetic properties: special populations). The maximum dose should be 50 mg in patients with mild renal impairment.

Elderly patients: In patients treated with GALVUS 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 dosage adjustments are therefore necessary in the elderly patients without renal impairment (see also Pharmacokinetic properties: Special populations).

Paediatric patients: GALVUS has not been studied in patients under 18 years of age; therefore, the use of GALVUS in paediatric patients is not recommended (see also Pharmacokinetic properties: Special populations).

GALVUS is contraindicated in patients with known hypersensitivity to vildagliptin or to any of the excipients of GALVUS. GALVUS is contraindicated in patients with hepatic impairment, including patients with a pre-treatment ALT or AST >2,5 X the upper limit of normal.

Hepatic impairment: GALVUS is contraindicated in patients with hepatic impairment, including patients with a pre-treatment elevated ALT or AST. (See Contraindications).

Liver enzyme monitoring: Cases of hepatic dysfunction (including hepatitis) have been reported. In these cases, the patients were generally asymptomatic and liver function tests (LFTs) returned to normal after discontinuation of treatment. LFTs should be performed prior to the initiation of treatment with GALVUS.

LFT-monitoring is imperative: LFTs should be monitored during GALVUS 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 to normal. Should an increase in AST or ALT of 3 X upper limit of normal or greater persist, GALVUS should be discontinued. Patients who develop jaundice or other signs suggestive of liver dysfunction should discontinue GALVUS and contact their medical practitioner immediately. Following withdrawal of treatment with GALVUS and LFT normalisation, GALVUS treatment should not be reinitiated.

Heart Failure: Vildagliptin 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 use in clinical trials in patients with NYHA functional class IV and therefore use is not recommended in these patients.

GALVUS may cause arthralgia that can be severe. GALVUS contains lactose. Patients with the rare hereditary conditions of galactose intolerance e.g. galactosaemia, Lapp lactase deficiency, glucose-galactose malabsorption or fructose intolerance should not take GALVUS.

GALVUS has a low potential for interactions. Since GALVUS is not a cytochrome P (CYP) 450 enzyme substrate nor does it inhibit nor induces CYP 450 enzymes, it is not likely to interact with co-medications that are substrates, inhibitors or inducers of these enzymes. Furthermore, GALVUS 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 GALVUS.

GALVUS should not be used in pregnant and breastfeeding women, as safety in pregnancy and lactation has not been established. Mothers on GALVUS should not breastfeed their infants.

GALVUS may cause dizziness. Patients who experience dizziness should avoid driving vehicles or using machines.

Safety data were obtained from 3 784 patients exposed to GALVUS in controlled trials of at least 12 weeks duration. Cases of angioedema have been reported during treatment with GALVUS. 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. In data from controlled monotherapy and add-on therapy trials up to 24 weeks in duration, the incidence of A LT or AST elevations u2265 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 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.

Adverse reactions reported in patients who received GALVUS in double-blind studies as add-on therapy, by system organ class and absolute frequency. Frequencies are defined as: very common (u2265 1/10); common (u2265 1/100, < 1/10); uncommon (u2265 1/1 000, 1/10 000 to u22641/1 000); very rare (u22641/10 000).

Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

Table 1: Adverse reactions reported in patients who received GALVUS 50 mg once daily (n=233) or 50 mg twice daily (n=183) in combination with metformin in double-blind studies, GALVUS 50 mg once daily in combination with a sulphonylurea in double-blind studies (n=170), GALVUS 50 mg twice daily in combination with insulin with or without metformin (n=371) and in combination with metformin and SU (n=157)

Nervous system disorders Common: *Tremor, *dizziness, headache; ***chills

**General disorders and administration site conditions Common: Asthenia, peripheral oedema

***Gastrointestinal disorders Common: Nausea, gastroesophageal reflux disease, constipation Uncommon: Diarrhoea, flatulence

Metabolism and nutritional disorders Common: *** Decreased blood glucose; **** Hypoglycaemia

**** Skin and subcutaneous tissue disorders: Common: Hyperhidrosis

* GALVUS in combination with metformin and sulphonylurea only ** GALVUS in combination with sulphonylurea only *** GALVUS in combination with insulin (with or without metformin) ****GALVUS in combination with metformin and sulphonylurea

In clinical trials with the combination of GALVUS + metformin, 0, 4 % of patients withdrew due to adverse reactions in the GALVUS 50 mg once daily + metformin, and no withdrawal due to adverse reactions was reported in either the GALVUS 50 mg twice daily + metformin or the placebo + metformin treatment groups. In clinical trials, the incidence of hypoglycaemia was uncommon in patients receiving GALVUS 50 mg once daily in combination with metformin (0,9 %), patients receiving GALVUS 50 mg twice daily in combination with metformin (0,5 %) and in patients receiving placebo + metformin (0,4 %). No severe hypoglycaemic events were reported in the GALVUS arms. In clinical trials, the incidence of hypoglycaemia when GALVUS 50 mg once daily was added to glimepiride was 1,2 % versus 0,6 % for placebo + glimepiride. No severe hypoglycaemic events were reported in the GALVUS arms.

Post Marketing Experience: During post-marketing experience the following additional side effects have been reported: u2022 Cases of hepatitis, usually reversible upon medicine discontinuation (see Warnings and Special Precautions) u2022 Urticaria, pancreatitis u2022 Localised exfoliation or blisters u2022 Arthralgia, sometimes severe

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

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