Major
Ciclosporin × Ketoconazole
Immunosuppressants. Calcineurin inhibitors×Systemic antimycotics. Imidazole derivatives
Mechanism
Ketoconazole is a potent CYP3A4 and P-glycoprotein inhibitor – two main cyclosporine clearance routes. Cyclosporine plasma levels rise 2- to 3-fold; nephrotoxicity and neurotoxicity risk.
Symptoms
Acute nephrotoxicity: rising creatinine, hypertension, tremor, headache. In transplant patients: accelerated graft function decline.
Management
If unavoidable, reduce cyclosporine by 50–66% and check trough (C0) daily. Alternative antifungals: terbinafine for dermatophytosis or echinocandins for systemic mycoses.