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.
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.