Major
Ketoconazole × Sildenafil
Systemic antimycotics. Imidazole derivatives×Phosphodiesterase type 5 inhibitors (PDE5)
Mechanism
Ketoconazole strongly blocks CYP3A4 – the main sildenafil metabolic route. Sildenafil plasma levels rise 4- to 8-fold. The hypotensive effect surges; priapism and ischaemic optic neuropathy risks rise.
Symptoms
Sudden blood pressure drop: dizziness, syncope. Priapism – painful erection lasting more than 4 hours. Visual disturbances, tinnitus. Symptoms appear within hours of co-administration.
Management
Avoid the combination. Alternative antifungals: terbinafine for dermatophytosis or echinocandins for systemic mycoses. If ketoconazole is needed, cap sildenafil at 25 mg and one dose per 24 hours.