Glibenclamide and Metformin

Hypoglycaemic excluding Insulin · Biguanide/Sulphonylurea

Indications

Initial therapy for management of type 2 diabetes mellitus (NIDDM). Second line therapy for management of type 2 diabetes mellitus when hyperglycaemia cannot be managed with a sulphonylurea or metformin; combination therapy with a thiazolidinedione may be required to achieve control.

Dosage

Adults: Initial therapy, 250 mg/1.25 mg once daily. Patients with fasting glucose > 200 mg/dL: May start with 250 mg/1.25 mg twice daily. Dosage may be increased in increments of 250 mg/1.25 mg at intervals of not less than 2 wk; max daily dose 2000 mg/10 mg. Previously treated with a sulphonylurea or metformin alone: Initial 500 mg/2.5 mg or 500 mg/5 mg twice daily, increase in increments no greater than 500 mg/5 mg; max daily dose 2000 mg/20 mg. Children: Not recommended.

Adverse Effects

Transient visual disturbances occur at the start of treatment. Very common: Nausea, vomiting, diarrhoea, abdominal pain & loss of appetite. Common: Taste disturbances. Uncommon: Crises of hepatic porphyria & porphyria cutanea; average to moderate elevations of serum urea & creatinine conc. Rare: Leukopenia, thrombocytopenia, pruritus urticaria, maculopapular rash. Very rare: Agranulocytosis, haemolytic anaemia, bone marrow aplasia & pancytopenia; lactic acidosis; liver function test abnormality or hepatitis requiring withdrawals of treatment; cutaneous or visceral allergic angiitis, erythema multiforme, exfoliative dermatitis, photo-sensitization, urticaria evolving to shock & cross-sensitivity to sulphonamides.

Risk Factor (Pregnancy/Lactation)

Pregnancy: Risk cannot be ruled out. Lactation: Contraindicated or not recommended. Contraindications: Renal disease or renal dysfunction, CHF requiring pharmacologic treatment, acute or chronic metabolic acidosis, including diabetic ketoacidosis with or without coma. Diabetic ketoacidosis should be treated with insulin. Treatment should be temporarily discontinued in patients undergoing radiologic studies involving intravascular administration of iodinated contrast materials. Precautions: Lactic acidosis is rare & may occur in significant renal insufficiency. Regular renal monitoring, especially in the elderly, is needed. Increased risk of CV mortality. Hypoglycaemia. Monitor renal function regularly (CrCl levels: Males: > 1.5 mg/dL, female: > 1.4 mg/dL). Avoid use in patients with clinical or laboratory evidence of hepatic disease. Patients should be cautioned against excessive…

Interactions

Iodinated contrast media, alcohol, cationic drugs that are eliminated by renal tubular secretion. Decreases vit B12 absorption. Thiazide & other diuretics, corticosteroids, phenothiazines, thyroid products, oestrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, Ca-channel blockers & INH may produce hyperglycaemia & lead to loss of glycaemic control. The hypoglycaemic action of sulfonylureas may be potentiated by NSAIDs & other highly protein-bound drugs, salicylates, sulfonamides, chloramphenicol, probenecid, coumarins, MAOIs, beta-blockers, ciprofloxacin, oral miconazole. Furosemide, nifedipine & cationic drugs being eliminated by renal tubular secretion.

Pharmacokinetics

GLIBENCLAMIDE: Onset of action: 15-60 min. Duration: 24 hrs. Absorption: Within 1 hr. Metabolism: Hepatic. Bioavailability: Variable among oral dosage forms. Half-life elimination: Glibenclamide: 10 hrs. May be prolonged with renal or hepatic impairment. Time to peak, serum: Adults: 2-4 hrs. Excretion: Faeces, urine. METFORMIN: Onset of action: Within days, max effects up to 2 wks. Metabolism: Not metabolized by the liver. Bioavailability: Absolute: Fasting: 50%-60%. Half-life elimination: Plasma: 4-9 hrs. Blood: Approx. 17.6 hrs. Time to peak, serum: Immediate release: 2-3 hrs. Extended release: 7 hrs. (Range: 4-8 hrs). Excretion: Urine.

Compiled by Healify Pharmacy from published drug references. How we compile it →

Always consult a pharmacist or doctor.