JANUMET

What it is

JANUMET is a combination medicine containing sitagliptin phosphate monohydrate and metformin hydrochloride in three strengths: 50 mg/500 mg, 50 mg/850 mg and 50 mg/1000 mg. JANUMET tablets consist of sitagliptin and an immediate-release formulation of metformin. JANUMET XR is also available in three strengths: 50 mg/500 mg, 50 mg/1000 mg and 100 mg/1000 mg. JANUMET XR tablets consist of sitagliptin and a modified release formulation of metformin.

Approved indications

— Type 2 diabetes mellitus in adults, as an adjunct to diet and exercise to improve glycaemic control when treatment with both sitagliptin and metformin is appropriate.

Dosing overview

JANUMET should generally be given twice daily with meals, with gradual dose escalation, to reduce the gastrointestinal side effects due to metformin. JANUMET XR should be given once daily with a meal preferably in the evening. The dosage 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 and 2000 mg metformin. For initial therapy, the recommended total daily starting dose is 100 mg sitagliptin and 1000 mg metformin hydrochloride. Patients with inadequate glycaemic control on this dose should have their metformin dose increased up to a maximum of 100 mg sitagliptin/2000 mg metformin hydrochloride daily.

Key safety warnings

Lactic acidosis is a rare but serious metabolic complication that can occur due to metformin accumulation; when it occurs, it is fatal in approximately 50 per cent of cases. Life-threatening lactic acidosis can occur due to accumulation of metformin, with risk factors including renal impairment, old age and the use of high doses of metformin above 2000 mg per day. The risk of lactic acidosis may be significantly decreased by regular monitoring of renal function in patients taking metformin and by use of the minimum effective dose of metformin. There have been reports of acute pancreatitis, including fatal and non-fatal haemorrhagic or necrotising pancreatitis in patients taking sitagliptin, and patients should be informed of the characteristic symptom of acute pancreatitis: persistent, severe abdominal pain. If pancreatitis is suspected, JANUMET or JANUMET XR and other potentially suspect medicinal products should be discontinued. There have been postmarketing reports of serious hypersensitivity reactions in patients treated with sitagliptin, including anaphylaxis, angioedema and exfoliative skin conditions including Stevens-Johnson syndrome. Onset of these reactions occurred within the first 3 months after initiation of treatment with sitagliptin, with some reports occurring after the first dose.

Contraindications

JANUMET and JANUMET XR are contraindicated in patients with severe renal impairment (eGFR < 30 mL/min/1.73 m²). They are contraindicated in patients with known hypersensitivity to sitagliptin phosphate monohydrate, metformin hydrochloride or any other component of JANUMET or JANUMET XR. They are contraindicated in acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma.

Regulatory history

JANUMET 50 mg/500 mg, 50 mg/850 mg and 50 mg/1000 mg tablets were first registered on the ARTG on 30 April 2009. JANUMET XR 50 mg/500 mg, 50 mg/1000 mg and 100 mg/1000 mg tablets were first registered on the ARTG on 1 November 2013.