Major
Ketoconazole × ritonavir
Systemic antimycotics. Imidazole derivatives×HIV protease inhibitor / pharmacokinetic booster
Mechanism
Dual potent CYP3A4 inhibition. Ketoconazole plasma levels may rise 3-fold. Hepatotoxicity and adrenal cortex suppression intensify.
Symptoms
Nausea, rising liver enzymes (ALT, AST). Prolonged use: adrenal insufficiency risk with hypotension, hypoglycaemia, hyponatraemia. Cardiac symptoms from QT prolongation.
Management
Avoid the combination. Alternative antifungals on ritonavir: terbinafine for dermatophytosis or echinocandins for systemic mycoses.