NESINA

What it is

NESINA MET tablets contain two oral antihyperglycaemic drugs used in the management of type 2 diabetes: alogliptin (as benzoate), a dipeptidyl peptidase 4 (DPP-4) inhibitor, and metformin hydrochloride, a member of the biguanide class. NESINA MET is available as film-coated tablets for oral administration containing alogliptin benzoate equivalent to 12.5 mg alogliptin free base and 500 mg, 850 mg or 1000 mg metformin hydrochloride.

Approved indications

— To improve glycaemic control in adult patients (≥18 years old) with type 2 diabetes mellitus when diet and exercise do not provide adequate glycaemic control and treatment with both alogliptin and metformin is appropriate, when treatment with metformin alone does not provide adequate control. — To improve glycaemic control in adult patients (≥18 years old) with type 2 diabetes mellitus in combination with a thiazolidinedione or with insulin, when dual therapy does not provide adequate control.

Dosing overview

NESINA MET should be taken orally twice daily with food with gradual dose escalation to reduce the gastrointestinal side effects due to metformin. Dosing may be adjusted based on effectiveness and tolerability while not exceeding the maximum recommended daily dose of 25 mg alogliptin and 2000 mg metformin hydrochloride.

Key safety warnings

**Lactic acidosis.** Life-threatening lactic acidosis can occur due to accumulation of metformin. Risk factors include renal impairment, old age and the use of high doses of metformin above 2000 mg per day. Lactic acidosis is a very rare, but serious (high mortality in the absence of prompt treatment), metabolic complication that can occur due to metformin accumulation. Reported cases of lactic acidosis in patients on metformin have occurred primarily in diabetic patients with significant renal failure. **Renal function monitoring.** Renal function should be confirmed before initiation of NESINA MET therapy, and then at least once a year in patients with normal renal function and at least two to four times a year in patients with serum creatinine levels at or above the upper limit of normal and in elderly patients. **Hypersensitivity and pancreatitis.** Postmarketing events of serious hypersensitivity reactions in patients treated with alogliptin such as angioedema and severe cutaneous adverse reactions including Stevens-Johnson syndrome have been reported and have been associated with other DPP-4 inhibitors. Postmarketing events of acute pancreatitis have been reported for alogliptin and have been associated with other DPP-4 inhibitors. **Vitamin B12 levels.** In controlled, 29-week clinical trials of immediate release metformin, a decrease to subnormal levels of previously normal serum Vitamin B12 levels, without clinical manifestations, was observed in approximately 7% of patients. Such decrease is, however, very rarely associated with anaemia and appears to be rapidly reversible with discontinuation of metformin or Vitamin B12 supplementation.

Contraindications

NESINA MET is contraindicated in patients with renal disease or dysfunction (e.g. as suggested by serum creatinine levels ≥135 μmol/L for men, ≥110 μmol/L for women or creatinine clearance <60 mL/min) which may also result from conditions such as cardiovascular collapse (shock), acute myocardial infarction, and septicaemia. NESINA MET is contraindicated in acute or chronic metabolic acidosis, including diabetic ketoacidosis, diabetic coma or pre-coma. NESINA MET is contraindicated in known hypersensitivity to alogliptin benzoate, metformin hydrochloride or any of the excipients.

Regulatory history

NESINA MET 12.5 mg/500 mg, 12.5 mg/850 mg and 12.5 mg/1000 mg alogliptin / metformin hydrochloride film-coated tablets were first listed on the ARTG on 22 October 2013. The TGA approved Nesina and Vipidia tablets for registration on 10 September 2013.