Major
Ketoconazole × tacrolimus
Systemic antimycotics. Imidazole derivatives×Calcineurin inhibitor (immunosuppressant)
Mechanism
Ketoconazole is the most potent CYP3A4 inhibitor available – the main tacrolimus metabolic route. Tacrolimus plasma levels rise 3- to 5-fold. The narrow therapeutic window makes any rise clinically dangerous.
Symptoms
Acute nephrotoxicity: rising creatinine and falling glomerular filtration rate. Tremor, headache, hypertension, hyperglycaemia, hyperkalaemia. In transplant patients: accelerated graft function decline.
Management
Avoid the combination. Alternative antifungals: terbinafine for dermatophytosis or echinocandins for systemic mycoses. If unavoidable, reduce tacrolimus 2- to 3-fold and check trough (C0) levels daily.
Check the full regimen, not just this pair
Opens the checker with these two drugs prefilled. Add the rest of the regimen and recompute additive risks.