Moderate
Amitriptyline × Ketoconazole
Tricyclic antidepressants (TCA)×Systemic antimycotics. Imidazole derivatives
Mechanism
Ketoconazole blocks CYP3A4 (one of the amitriptyline metabolic routes). TCA plasma levels may rise.
Symptoms
Worsening anticholinergic symptoms, drowsiness, tachycardia. Older patients: delirium and fall risk.
Management
For short ketoconazole courses, reduce amitriptyline by 25% temporarily. Alternative antifungals without CYP3A4 effect: terbinafine for dermatophytosis or echinocandins for systemic mycoses.