VELMETIA

Posology The dose of antihyperglycaemic therapy with Velmetia should be individualised on the basis of the patient’s current regimen, effectiveness, and tolerability while not exceeding the maximum recommended daily dose of 100 mg sitagliptin.

Adults with normal renal function (GFR ≥ 90 mL/min) For patients inadequately controlled on maximal tolerated dose of metformin monotherapy For patients not adequately controlled on metformin alone, the usual starting dose should provide sitagliptin dosed as 50 mg twice daily (100 mg total daily dose) plus the dose of metformin already being taken.

For patients switching from co-administration of sitagliptin and metformin For patients switching from co-administration of sitagliptin and metformin, Velmetia should be initiated at the dose of sitagliptin and metformin already being taken.

For patients inadequately controlled on dual combination therapy with the maximal tolerated dose of metformin and a sulphonylurea The dose should provide sitagliptin dosed as 50 mg twice daily (100 mg total daily dose) and a dose of metformin similar to the dose already being taken.

4). For patients inadequately controlled on dual combination therapy with the maximal tolerated dose of metformin and a PPARγ agonist The dose should provide sitagliptin dosed as 50 mg twice daily (100 mg total daily dose) and a dose of metformin similar to the dose already being taken.

For patients inadequately controlled on dual combination therapy with insulin and the maximal tolerated dose of metformin The dose should provide sitagliptin dosed as 50 mg twice daily (100 mg total daily dose) and a dose of metformin similar to the dose already being taken.

4). For the different doses on metformin, Velmetia is available in strengths of 50 mg sitagliptin and 850 mg metformin hydrochloride or 1,000 mg metformin hydrochloride. All patients should continue their recommended diet with an adequate distribution of carbohydrate intake during the day.

Special populations Renal impairment No dose adjustment is needed for patients with mild renal impairment (glomerular filtration rate [GFR] ≥ 60 mL/min). A GFR should be assessed before initiation of treatment with metformin-containing products and at least annually thereafter.

g. every 3-6 months. The maximum daily dose of metformin should preferably be divided into 2-3 daily doses. 4) should be reviewed before considering initiation of metformin in patients with GFR < 60 mL/min. If no adequate strength of Velmetia is available, individual monocomponents should be used instead of the fixed-dose combination.

2). Serious adverse reactions including pancreatitis and hypersensitivity reactions have been reported. 9 %). Tabulated list of adverse reactions Sitagliptin and metformin Adverse reactions are listed below as MedDRA preferred term by system organ class and absolute frequency (Table 1).

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) and not known (cannot be estimated from the available data).

Table 1:

The frequency of adverse reactions identified from placebo-controlled clinical studies of sitagliptin and metformin alone, and post-marketing experience Adverse reaction Frequency of adverse reaction Blood and lymphatic system disorders thrombocytopenia Rare Immune system disorders hypersensitivity reactions including anaphylactic responses*,† Frequency not known Metabolism and nutrition disorders hypoglycaemia† Common Vitamin B12 decrease/deficiency† Common Nervous system disorders somnolence Uncommon Respiratory, thoracic and mediastinal disorders interstitial lung disease* Frequency not known Gastrointestinal disorders diarrhoea Uncommon nausea Common flatulence Common constipation Uncommon upper abdominal pain Uncommon vomiting Common acute pancreatitis*,†,‡ Frequency not known fatal and non-fatal haemorrhagic and necrotizing pancreatitis*,† Frequency not known Skin and subcutaneous tissue disorders pruritus* Uncommon angioedema*,† Frequency not known rash*,† Frequency not known urticaria*,† Frequency not known Adverse reaction Frequency of adverse reaction cutaneous vasculitis*,† Frequency not known exfoliative skin conditions including Stevens-Johnson syndrome*,† Frequency not known bullous pemphigoid* Frequency not known Musculoskeletal and connective tissue disorders arthralgia* Frequency not known myalgia* Frequency not known pain in extremity* Frequency not known back pain* Frequency not known arthropathy* Frequency not known Renal and urinary disorders impaired renal function* Frequency not known acute renal failure* Frequency not known *Adverse reactions were identified through post-marketing surveillance.

General Velmetia should not be used in patients with type 1 diabetes and must not be used for the treatment of diabetic ketoacidosis. Acute pancreatitis Use of DPP-4 inhibitors has been associated with a risk of developing acute pancreatitis.

Patients should be informed of the characteristic symptom of acute pancreatitis: persistent, severe abdominal pain. Resolution of pancreatitis has been observed after discontinuation of sitagliptin (with or without supportive treatment), but very rare cases of necrotising or haemorrhagic pancreatitis and/or death have been reported.

If pancreatitis is suspected, Velmetia and other potentially suspect medicinal products should be discontinued; if acute pancreatitis is confirmed, Velmetia should not be restarted. Caution should be exercised in patients with a history of pancreatitis.

Lactic acidosis Lactic acidosis, a rare but serious metabolic complication, most often occurs at acute worsening of renal function or cardiorespiratory illness or sepsis. Metformin accumulation occurs at acute worsening of renal function and increases the risk of lactic acidosis.

In case of dehydration (severe vomiting, diarrhoea, fever or reduced fluid intake), metformin should be temporarily discontinued and contact with a health care professional is recommended. Medicinal products that can acutely impair renal function (such as antihypertensives, diuretics and NSAIDs) should be initiated with caution in metformin-treated patients.

5). Patients and/or care-givers should be informed of the risk of lactic acidosis. Lactic acidosis is characterised by acidotic dyspnoea, abdominal pain, muscle cramps, asthenia and hypothermia followed by coma. In case of suspected symptoms, the patient should stop taking metformin and seek immediate medical attention.

35), increased plasma lactate levels (> 5 mmol/L) and an increased anion gap and lactate/pyruvate ratio. 2). 3). Hypoglycaemia Patients receiving Velmetia in combination with a sulphonylurea or with insulin may be at risk for hypoglycaemia.

4); - acute or chronic disease which may cause tissue hypoxia such as: - cardiac or respiratory failure, - recent myocardial infarction, - shock; - hepatic impairment; - acute alcohol intoxication, alcoholism; - breast-feeding.