KOMBIGLYZE XR

What it is

KOMBIGLYZE XR is a combination tablet containing saxagliptin immediate release and metformin hydrochloride modified release. Metformin is a biguanide with antihyperglycaemic effects, lowering both basal and postprandial plasma glucose, and does not stimulate insulin secretion and therefore does not cause hypoglycaemia.

Approved indications

— Type 2 diabetes mellitus in adults, children from 10 years of age and adolescents, particularly in overweight patients, when dietary management and exercise alone does not result in adequate glycaemic control.

Dosing overview

Tablets should be taken in divided doses with meals. Initially 500 mg should be taken once or twice a day and if necessary increased over a few weeks up to 1 g three times per day, with 500 mg three times a day often sufficient to obtain diabetic control, and the dose can be increased to 1 g three times daily, which is the maximum recommended daily dose. For children from 10 years of age and adolescents, the usual starting dose is one tablet of 500 mg or 850 mg once daily given during or after meals, with a maximum recommended dose of metformin of 2 g daily taken as two or three divided doses.

Key safety warnings

Lactic acidosis is a rare but serious metabolic complication that can occur due to metformin accumulation, with high mortality in the absence of prompt treatment. 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 2 g per day. The risk of lactic acidosis must be considered in the event of non-specific signs such as muscle cramps with digestive disorders such as abdominal pain and severe asthenia, and lactic acidosis is characterised by acidotic dyspnea, abdominal pain and hypothermia followed by coma. It is recommended that vitamin B12 serum levels are monitored annually, as the risk of low vitamin B12 levels increases with increasing metformin dose, treatment duration, and in patients with risk factors known to cause vitamin B12 deficiency. Metformin induces a reduction in thyrotropin levels in patients with treated or untreated hypothyroidism, and regular monitoring of TSH levels is recommended in patients with hypothyroidism.

Contraindications

Contraindications include juvenile diabetes mellitus that is uncomplicated and well regulated on insulin, diabetes mellitus regulated by diet alone, any type of metabolic acidosis (such as lactic acidosis or diabetic ketoacidosis), hypersensitivity to metformin hydrochloride or excipients, renal failure or renal dysfunction (creatinine clearance less than 60 mL/min), acute conditions with the potential to alter renal function such as dehydration or severe infection, acute or chronic disease which may cause tissue hypoxia such as cardiac failure or respiratory failure, elective major surgery, severe hepatic insufficiency, acute alcohol intoxication, and lactation.

PBS listing

KOMBIGLYZE XR is registered on the ARTG in three strengths: 2.5 mg saxagliptin with 1000 mg metformin hydrochloride (ARTG 202207), 5 mg saxagliptin with 1000 mg metformin hydrochloride (ARTG 202208), and 5 mg saxagliptin with 500 mg metformin hydrochloride (ARTG 202209), all first listed on 10 October 2013.

Regulatory history

KOMBIGLYZE XR was first registered on the ARTG on 10 October 2013 under licence category RE.