APX-METFORMIN

What it is

APX-METFORMIN contains metformin hydrochloride. The medicine is available in tablet strengths of 500 mg, 850 mg and 1000 mg. 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

— Treatment of 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. — In adult patients, as initial treatment or in sulfonylurea failures either alone or in combination with a sulfonylurea and other oral agents or as adjuvant therapy in insulin requiring type 2 diabetes.

Dosing overview

Initial dosing is 500 mg once or twice daily, titrated with gradual dose increments over a few weeks up to 1 g three times per day, with 500 mg three times daily often sufficient for diabetic control and a maximum recommended daily dose of 1 g three times daily. The tablets should be taken in divided doses with meals. In 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 meals or after meals, with a maximum recommended dose of 2 g daily taken as two or three divided doses. In elderly patients, initial and maintenance dosing should be conservative due to the potential for decreased renal function, with dosage adjustment based on careful assessment of renal function, and elderly patients generally should not be titrated to the maximum dose.

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 2 g per day. Lactic acidosis is a rare but serious metabolic complication with high mortality in the absence of prompt treatment, and reported cases have occurred primarily in diabetic patients with significant renal failure. 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. Gastrointestinal disorders such as diarrhoea, nausea, vomiting, abdominal pain and loss of appetite are very common, occurring most frequently during initiation of therapy and resolving spontaneously in most cases; taking metformin in 2 or 3 daily doses during or after meals and a slow increase of dose may improve gastrointestinal tolerability. 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/or in patients with risk factors known to cause vitamin B12 deficiency.

Contraindications

APX-METFORMIN is contraindicated in juvenile diabetes mellitus that is uncomplicated and well regulated on insulin, diabetes mellitus regulated by diet alone, during or immediately following surgery where insulin is essential, any type of metabolic acidosis such as lactic acidosis or diabetic ketoacidosis, hypersensitivity to metformin hydrochloride or to any of the excipients, diabetic pre-coma, renal failure or renal dysfunction with creatinine clearance less than 60 mL/min, acute conditions with the potential to alter renal function such as dehydration, severe infection and shock, intravascular administration of iodinated contrast materials, acute or chronic disease which may cause tissue hypoxia such as cardiac failure, recent myocardial infarction, respiratory failure, pulmonary embolism, shock, acute significant blood loss, sepsis, gangrene and pancreatitis, elective major surgery, severe hepatic insufficiency, acute alcohol intoxication, alcoholism and lactation.

PBS listing

APX-METFORMIN tablets containing metformin hydrochloride 850 mg are listed on the PBS as a restricted item with an ex-manufacturer price of A$3.00.

Regulatory history

APX-METFORMIN was first listed on the ARTG on 19 July 2017 in six variants: 500 mg and 850 mg tablets in blister pack and bottle formats, and 1000 mg tablets in blister pack and bottle formats.