Clarithromycin × Sildenafil

Sildenafil is cleared mainly through CYP3A4 (sildenafil SmPC). The European Medicines Agency (EMA) places clarithromycin among the more potent inhibitors of this enzyme and assumes about a 7-fold increase in sildenafil exposure with it (sildenafil SmPC for pulmonary hypertension, EMA). The US Food and Drug Administration (FDA) warns that low blood pressure, fainting and prolonged erection may occur at higher sildenafil exposure (sildenafil FDA label).

Sudden blood pressure drop: dizziness, syncope. Priapism – painful erection lasting more than 4 hours, requiring emergency care. Worsening of visual disturbances (cyanopsia) and tinnitus.

Avoid the combination: the US Food and Drug Administration (FDA) does not recommend sildenafil together with clarithromycin (clarithromycin FDA label), and for pulmonary arterial hypertension it does not recommend sildenafil with any strong CYP3A4 inhibitor (sildenafil FDA label for pulmonary hypertension). If sildenafil for pulmonary hypertension is still needed during a clarithromycin course, the European Medicines Agency (EMA) recommends reducing the dose to 20 mg once daily (sildenafil SmPC for pulmonary hypertension, EMA). For erectile dysfunction, consider a 25 mg starting dose in patients taking CYP3A4 inhibitors (sildenafil SmPC, EMA; sildenafil FDA label), with no more than one dose per day (sildenafil SmPC, EMA). The clarithromycin SmPC also advises considering a lower sildenafil dose (clarithromycin SmPC). Tell the patient to seek urgent medical help if an erection lasts longer than 4 hours (sildenafil SmPC, EMA).