DIAFORMIN Film-coated tablet Ref.[50318] Active ingredients: Metformin

Life threatening lactic acidosis can occur due to accumulation of metformin. The main risk factor is renal impairment, other risk factors include old age associated with reduced renal function and high doses of metformin above 2 g per day.

It is important that the tablets are 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. Control may be attained within a few days but occasionally requires up to two weeks. Once control has been obtained, the dosage should be reviewed and reduced to the lowest maintenance level consistent with good diabetic control. If dose titration has been achieved with one tablet strength, then the patient’s response should be assessed if a different strength or dose schedule has been used.

Metformin dosage should be frequently reviewed in patients stabilised on metformin, especially if they develop an illness, as they may tolerate the drug less well, particularly if the illness is accompanied by a decrease in renal function. If necessary, metformin should be ceased for a few days during an illness and then restarted at low dosage, as for initial therapy.

The action of metformin is progressive and no final assessment of the patient’s real response should be made before the 21st day of treatment; blood sugar estimations are recommended during the initial 15 days of stabilisation. Metformin will not produce a hypoglycaemic state when used alone; however, due to its action in increasing insulin effectiveness, care must be taken when metformin is initially administered with parenteral doses of insulin.

Elderly

The initial and maintenance dosing of metformin should be conservative in elderly patients, due to the potential for decreased renal function in this population. Any dosage adjustment should be based on a careful assessment of renal function. Generally, elderly patients should not be titrated to the maximum dose of metformin.

Use in Children and adolescents

Metformin can be used as monotherapy 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 of metformin is 2 g daily, taken as two or three divided doses.

In debilitated or malnourished patients

The dosing should be conservative and based on a careful assessment of renal function.

Symptoms

Hypoglycaemia has not been seen with ingestion of up to 85 g of metformin alone, although lactic acidosis has occurred in such circumstances. This disorder is a medical emergency and must be treated in hospital. The onset of lactic acidosis is often subtle and accompanied only by non-specific symptoms such as malaise, myalgia, respiratory distress, increasing somnolence and non-specific abdominal distress. There may be associated hypothermia, hypotension and resistant bradyarrhythmias with more marked acidosis. Lactic acidosis should be suspected in any diabetic patient with metabolic acidosis lacking evidence of ketoacidosis (ketonuria and ketonaemia).

Treatment

Lactic acidosis may develop in diabetic metformin-treated patients with overdose. Lactic acidosis is diagnosed and monitored by measurement of serum electrolytes, arterial pH and pCO₂ and arterial lactate plasma level.

The aim of treatment is to manage any underlying disorder, and in some cases, this will be sufficient to enable the body’s homeostatic mechanism to correct the acid-base imbalance. The advantages of more active treatment of the acidosis must be balanced against the risks, including over-alkalinisation with sodium bicarbonate. Because metformin hydrochloride is dialysable (with a clearance of up to 170 mL/min under good haemodynamic conditions), prompt haemodialysis is recommended to correct the acidosis and remove the accumulated metformin.

Contact the Poisons Information Centre on 131126 (Australia) for advice on the management of overdosage.

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

Store below 30°C (blisters and bottles).

Store below 25°C (pails only).

DIAFORMIN 500: Aluminium/PVC Blister packs of 10 (sample) and 100 tablets.

DIAFORMIN: PP pails packs* of 22700 tablets and 4540 tablets.

DIAFORMIN 850: Aluminium/PVC Blister packs and HDPE bottles of 60 tablets.

DIAFORMIN 1000: Aluminium/PVC Blister packs of 10, 30, 60 and 90 tablets. PP pails packs* of 11380 tablets and 2276 tablets.

^* Bulk pack for dose administration to aid Packers

Some strengths, pack sizes and/or pack types may not be marketed.

Australian Register of Therapeutic Goods (ARTG)

AUST R 73806 – DIAFORMIN 500 metformin hydrochloride 500mg tablet blister pack.
AUST R 299825 – DIAFORMIN metformin hydrochloride 500 mg tablet bulk pack.
AUST R 73808 – DIAFORMIN 850 metformin hydrochloride 850mg tablet blister pack.
AUST R 73807 – DIAFORMIN 850 metformin hydrochloride 850mg tablet bottle.
AUST R 82207 – DIAFORMIN 1000 metformin hydrochloride 1000mg tablet blister pack.
AUST R 294057 – DIAFORMIN 1000 metformin 1000mg (as hydrochloride) tablet bulk pack.

In Australia, any unused medicine or waste material should be disposed of by taking it to your local pharmacy.