GLUCOVANCE Film-coated tablet Ref.[50572] Active ingredients: Glibenclamide 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.

As with all hypoglycaemic drugs, the dosage should be individualised according to the metabolic response of each patient (glycaemia, HbA1c). It is recommended to initiate therapy with a low dosage and to gradually increase the dose as a function of laboratory results.

Glucovance may be used instead of a previously prescribed oral antidiabetic. This transfer can generally be made without any transition period, starting for preference with a low dosage and adjusting it thereafter as a function of the metabolic response of each patient. However, if the patient was previously taking a sulfonylurea with a long half-life, a treatment-free washout period of a few days may be necessary, so as to minimise the risk of hypoglycaemia due to an additive effect of the two drugs. It is recommended that, when switching the patient to a fixed-dose combination product containing metformin, any previously prescribed individual-component products should be discontinued, to minimise the risk of accidental overdosing or dose related adverse effects. Only one strength of the fixed-dose combination product should be prescribed and used at any one time.

Mistakes, e.g. forgetting to take a dose, must never be corrected by subsequently taking a larger dose. Measures for dealing with such mistakes (in particular forgetting a dose or skipping a meal), or in the event a dose cannot be taken at the prescribed time, must be discussed and agreed between the doctor and the patient beforehand.

Initiation of treatment

Monotherapy failure

In the event of monotherapy failure with metformin or a sulfonylurea, the usual initial dosage is 1 tablet of Glucovance 500 mg/2.5 mg daily.

Combination therapy substitution

In patients already on combination therapy with metformin and sulfonylurea, the initial dosage should be 1 to 2 tablets of Glucovance 500 mg/2.5 mg daily. It is recommended to start with a lower dose of the currently used agents in the fixed combination to reduce the risk of hypoglycaemia.

Dose titration

The dosage should be adjusted every 2 weeks or longer, by increments of 1 tablet, depending on glycaemia results. A gradual increase in the dosage may aid gastrointestinal tolerance and prevent the onset of hypoglycaemia.

Maximum daily recommended dose

The maximum recommended daily dose is 3 tablets of Glucovance 500 mg/5 mg. In exceptional cases, an increase up to 4 tablets of Glucovance 500 mg/5 mg per day may be recommended.

Dosing frequency

The tablets should be taken at the beginning of meals. The dosage regimen depends on the daily dosage in a given patient, such as:

• Once a day, in the morning at breakfast, for a dosage of 1 tablet/day,
• Twice a day, morning and evening, for a dosage of 2 or 4 tablets/day,
• Three times a day, morning, noon and evening, for a dosage of 3 tablets/day.

The dosing frequency should be adjusted according to the eating habits of each patient. However, any intake must be followed by a meal with a sufficiently high carbohydrate content to prevent the onset of hypoglycaemic episodes.

Elderly

In the elderly, the dosage of Glucovance should be adjusted depending on renal function parameters (see Section 4.4 SPECIAL WARNINGS AND PRECAUTIONS FOR USE – Use in the elderly). It is recommended to initiate treatment with one tablet daily of Glucovance 250 mg/1.25 mg, then adjust the doses according to laboratory test results.

Children

Glucovance is not recommended for use in children and adolescents (see Section 5.1 PHARMACODYNAMICS – Clinical Trials, Paediatric patients).

High overdose or the existence of concomitant risk factors may lead to lactic acidosis due to the presence of metformin (see Section 4.4 SPECIAL WARNINGS AND PRECAUTIONS FOR USE). Overdose may also precipitate hypoglycaemia due to the presence of the sulfonylurea (see Section 4.4 SPECIAL WARNINGS AND PRECAUTIONS FOR USE).

Since hypoglycaemia and its clinical symptoms may recur after apparent clinical recovery (even after several days), close and continued medical supervision and possibly referral to a hospital are indicated. In particular, significant overdosage and severe reactions, e.g. with unconsciousness or other neurological dysfunction, are emergency cases and require immediate care and hospitalisation.

If hypoglycaemic coma is diagnosed or suspected, administer glucagon (adults: 0.5 to 1 mg) intravenously, subcutaneously or intramuscularly; or an intravenous infusion of a 20% glucose solution (adults: 40 to 100 ml) until the patient recovers consciousness. In infants, glucose must be dosed very carefully, accompanied by close monitoring of blood glucose, taking into account the risk of potentially severe hyperglycaemia. Other symptomatic therapies (e.g. anticonvulsants) should be administered as necessary.

Lactic acidosis is a medical emergency and must be treated in hospital. The most effective treatment is to remove lactate and metformin by haemodialysis. The plasma clearance of glibenclamide may be prolonged in patients suffering from liver disease. Since glibenclamide is extensively bound to proteins, it is not eliminated by dialysis.

For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

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 25°C.

Glucovance 250/1.25: Blister pack 10s, 30s, 60s, 90s, 120s.

Glucovance 500/2.5: Blister pack 10s, 30s, 60s, 90s, 120s.

Glucovance 500/5: Blister pack 10s, 30s, 60s, 90s, 120s.

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

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