DIAFORMIN

What it is

DIAFORMIN is metformin hydrochloride supplied as film coated tablets. The tablets are available in three strengths: 500 mg, 850 mg and 1000 mg.

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 — Type 2 diabetes mellitus 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

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. The dose should be titrated with gradual dose increments until the desired effect is obtained. 500 mg three times a day is often sufficient to obtain diabetic control. If necessary, the dose can be increased to 1 g three times daily, which is the maximum recommended daily dose. 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. After 10 to 15 days the dose should be adjusted on the basis of blood glucose measurements. A slow increase of dose may improve gastrointestinal tolerability. The maximum recommended dose is 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. Any dosage adjustment should be based on a careful assessment of renal function. Generally, elderly patients should not be titrated to the maximum dose.

Key safety warnings

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 2 g per day. Lactic acidosis is a rare but serious metabolic complication that can occur due to metformin accumulation, with reported cases occurring primarily in diabetic patients with significant renal failure. The incidence can be reduced by assessing other associated risk factors such as poorly controlled diabetes, ketosis, prolonged fasting, excessive alcohol intake, hepatic insufficiency and any condition associated with hypoxia. It is recommended that creatinine clearance and/or serum creatinine levels be determined before initiating treatment and regularly thereafter: at least annually in patients with normal renal function, at least two to four times a year in patients with serum creatinine levels at the upper limit of normal and in elderly subjects. The intravascular administration of iodinated contrast materials in radiologic studies can lead to renal failure, which may induce metformin accumulation and expose patients to lactic acidosis. Therefore, metformin must be discontinued either 48 hours before the test when renal function is known to be impaired or from the time of the test when renal function is known to be normal. Metformin may not be reinstituted until 48 hours afterwards, and only after renal function has been re-evaluated and found to be normal. Serum vitamin B12 levels should be measured prior to initiation of treatment with metformin, after 6 months treatment and thereafter annually because of reports of decreased vitamin B12 absorption associated with metformin administration.

Contraindications

DIAFORMIN is contraindicated in: juvenile diabetes mellitus that is uncomplicated and well regulated on insulin; diabetes mellitus regulated by diet alone; hypersensitivity to metformin hydrochloride or any excipients; during or immediately following surgery where insulin is essential; any type of metabolic acidosis such as lactic acidosis or diabetic ketoacidosis; diabetic pre-coma; renal failure or renal dysfunction (creatinine clearance less than 60 mL/min); acute conditions with the potential to alter renal function such as dehydration, severe infection or 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, gangrene, shock, acute significant blood loss, pulmonary embolism, pancreatitis or sepsis; elective major surgery; severe hepatic insufficiency; acute alcohol intoxication; alcoholism; and lactation.

PBS listing

The extended release tablet containing metformin hydrochloride 1 g is listed on the PBS as a restricted item with an ex-manufacturer price of A$4.00.

Regulatory history

DIAFORMIN 500 mg blister pack, 850 mg blister pack and bottle were first approved on 14 April 2000. The 1000 mg blister pack was first approved on 3 September 2002. The 500 mg bulk pack was approved on 13 April 2018 and the 1000 mg bulk pack on 1 February 2018.