GLUCOVANCE

What it is

GLUCOVANCE is a combination tablet containing metformin hydrochloride and glibenclamide, available in three strength combinations: 250 mg metformin with 1.25 mg glibenclamide; 500 mg metformin with 2.5 mg glibenclamide; and 500 mg metformin with 5 mg glibenclamide. The tablets are film-coated.

Approved indications

— Second line treatment of diabetes mellitus type II in adult patients whose glycaemic control is inadequate after diet and exercise alone and where combined therapy with metformin and glibenclamide is appropriate.

Dosing overview

Dosage should be individualised according to the metabolic response of each patient, with therapy initiated at a low dosage and gradually increased according to laboratory results. For monotherapy failure with metformin or a sulfonylurea, the usual initial dosage is 1 tablet of GLUCOVANCE 500 mg/2.5 mg daily. 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, starting with a lower dose to reduce the risk of hypoglycaemia. The dosage should be adjusted every 2 weeks or longer by increments of 1 tablet, with gradual increases aiding gastrointestinal tolerance and preventing hypoglycaemia. The maximum recommended daily dose is 3 tablets of GLUCOVANCE 500 mg/5 mg, though in exceptional cases up to 4 tablets daily may be recommended. Tablets should be taken at the beginning of meals, with dosing frequency depending on daily dosage: once daily in the morning for 1 tablet, twice daily for 2 or 4 tablets, or three times daily for 3 tablets. In elderly patients, dosage should be adjusted depending on renal function parameters, with treatment initiated with one tablet daily of GLUCOVANCE 250 mg/1.25 mg.

Key safety warnings

Life threatening lactic acidosis can occur due to accumulation of metformin, with the main risk factor being renal impairment; other risk factors include old age associated with reduced renal function and high doses of metformin above 2 g per day. Lactic acidosis is a rare but serious metabolic complication that is fatal in approximately 50% of cases and must be treated in hospital immediately. The risk of lactic acidosis may be significantly decreased by regular monitoring of renal function in patients taking GLUCOVANCE and those on concomitant diuretics. Creatinine clearance and/or serum creatinine levels should be determined before initiating treatment and regularly thereafter: at least annually in patients with normal renal function, and at least two to four times a year in patients with serum creatinine levels at the upper limit of normal and in elderly subjects. GLUCOVANCE exposes patients to a risk of hypoglycaemic episodes due to the sulfonylurea component; severe hypoglycaemia can be prolonged and potentially lethal, and treatment should only be prescribed if the patient adheres to a regular meal schedule including breakfast. The use of glibenclamide in the elderly may be associated with a higher risk of hypoglycaemia than in younger adults, and hypoglycaemia may be more severe and prolonged in the elderly. Risk factors for hypoglycaemia include refusal or inability to cooperate, debilitated patients, age 65 years or older, malnutrition, irregular meals, severe exercise, renal failure, severe liver failure, overdose, certain endocrine disturbances, alcohol ingestion, and concomitant administration of certain other drugs. Alcohol is known to potentiate the effect of metformin on lactate metabolism, and patients should be warned against excessive alcohol intake due to increased risk of lactic acidosis, particularly in cases of fasting or malnutrition or hepatic insufficiency.

Contraindications

GLUCOVANCE must never be used in cases of hypersensitivity to metformin hydrochloride, glibenclamide or other sulfonylureas or sulfonamides or to any of the excipients, 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), or acute conditions with the potential to alter renal function such as dehydration, severe infection, shock, or intravascular administration of iodinated contrast materials. Acute or chronic disease which may cause tissue hypoxia such as cardiac or respiratory failure, recent myocardial infarction, shock, acute significant blood loss, sepsis, or gangrene are contraindications. Major surgery, hepatic insufficiency, acute alcohol intoxication, alcoholism, porphyria, congenital galactosemia, glucose and galactose malabsorption syndrome, lactase deficiency, lactation, and use in association with miconazole are also contraindications.

PBS listing

Information regarding PBS listing is not contained in the provided source documents.

Regulatory history

GLUCOVANCE was first registered on the ARTG on 5 August 2004, with three strength variants registered: GLUCOVANCE 250/1.25 mg, GLUCOVANCE 500/2.5 mg, and GLUCOVANCE 500/5 mg tablets. The product is a Schedule 4 Prescription Only Medicine. The medicine is sponsored by Alphapharm Pty Ltd trading as Viatris, with the initial approval date of 9 September 2008.