Description
Fluconazole inhibits CYP3A4-mediated metabolism of methylprednisolone, increasing its plasma levels and prolonging corticosteroid effects, raising the risk of Cushingoid features.
Mécanisme
CYP3A4 is the primary enzyme metabolising methylprednisolone; fluconazole's potent inhibition reduces systemic clearance, leading to elevated and prolonged drug exposure.
Signification clinique
Case reports and pharmacokinetic studies document methylprednisolone AUC increases of 50–130% with concomitant fluconazole; clinically, this manifests as excessive immunosuppression, weight gain, and hyperglycaemia.
Prise en charge
Reduce methylprednisolone dose during fluconazole co-administration; monitor blood glucose and blood pressure; use the shortest effective course; consider alternative antifungals where feasible.