gliclazide and fluconazole

Fluconazole inhibits the cytochrome P450 enzyme CYP2C9, which is responsible for the metabolism of gliclazide. This reduces gliclazide clearance, increasing its plasma concentrations and prolonging its hypoglycaemic effect.

Plasma gliclazide levels rise, enhancing its hypoglycaemic action. This increases the risk of severe, prolonged hypoglycaemia, particularly in elderly patients or those with renal impairment. Clinical manifestations may include sweating, tremor, confusion, palpitations and loss of consciousness.

Monitor blood glucose closely before and during therapy. Consider reducing the gliclazide dose or selecting an antifungal that does not inhibit CYP2C9, such as terbinafine. Advise the patient about the signs and symptoms of hypoglycaemia and to carry a fast-acting carbohydrate. If gliclazide dose is adjusted, reassess after stopping fluconazole.

This interaction is well established. Fluconazole is a recognised CYP2C9 inhibitor and gliclazide is a known substrate. Multiple case reports and pharmacokinetic studies support an increased hypoglycaemic risk.