TRAJENTAMET

What it is

TRAJENTAMET contains two oral antihyperglycaemic drugs used in the management of type 2 diabetes mellitus: linagliptin (a dipeptidyl peptidase-4 (DPP-4) inhibitor) and metformin hydrochloride. TRAJENTAMET is available in three strengths: 2.5 mg/500 mg, 2.5 mg/850 mg, and 2.5 mg/1000 mg film-coated tablets for oral administration.

Approved indications

— Improvement of glycaemic control in adults with type 2 diabetes mellitus as an adjunct to diet and exercise when treatment with both linagliptin and metformin is appropriate, in patients inadequately controlled on metformin alone, or those already being treated and well controlled with the free combination of linagliptin and metformin. — Triple combination therapy with a sulfonylurea as an adjunct to diet and exercise in patients inadequately controlled on their maximal tolerated dose of metformin and a sulfonylurea. — Triple combination therapy with an SGLT2 inhibitor as an adjunct to diet and exercise in patients inadequately controlled on their maximum tolerated dose of metformin and an SGLT2 inhibitor. — Add-on to insulin (triple combination therapy) as an adjunct to diet and exercise to improve glycaemic control in patients when insulin and metformin alone do not provide adequate glycaemic control.

Dosing overview

For adults with normal renal function (GFR ≥ 90 mL/min), the recommended dose is TRAJENTAMET 2.5 mg/500 mg, 2.5 mg/850 mg or 2.5 mg/1000 mg twice daily. The dosage should be individualised on the basis of the patient's current regimen, effectiveness, and tolerability. The maximum recommended daily dose of TRAJENTAMET is 5 mg of linagliptin and 2000 mg of metformin. TRAJENTAMET should be given with meals to reduce the gastrointestinal undesirable effects associated with metformin. For patients currently not treated with metformin, the recommended starting dose is TRAJENTAMET 2.5 mg linagliptin/500 mg metformin hydrochloride twice daily. For patients not adequately controlled on metformin alone, the usual starting dose of TRAJENTAMET should provide linagliptin dosed as 2.5 mg twice daily (5 mg total daily dose) plus the dose of metformin already being taken.

Key safety warnings

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. When TRAJENTAMET is used in combination with a sulfonylurea, a lower dose of the sulfonylurea may be required to reduce the risk of hypoglycaemia. When TRAJENTAMET is used in combination with insulin, a lower dose of insulin may be required to reduce the risk of hypoglycaemia.

Contraindications

TRAJENTAMET is contraindicated in patients with severe renal failure (creatinine clearance < 30 mL/min or eGFR < 30 mL/min/1.73 m²) due to the metformin component.

Regulatory history

TRAJENTAMET was first approved on 21 May 2013. In March 2016, the PBAC recommended an Authority Required (Streamlined) listing of linagliptin with metformin as a fixed-dose combination for the treatment of type 2 diabetes mellitus in combination with insulin, on a cost-minimisation basis to the individual components taken concomitantly in combination with insulin. In the same month, the PBAC recommended linagliptin with metformin fixed-dose combination for use with a sulfonylurea on a cost-minimisation basis with its individual components taken concomitantly.