Ritonavir × Sildenafil

Sildenafil is broken down in the liver by CYP3A4, and ritonavir strongly inhibits this enzyme. With ritonavir 500 mg twice daily, sildenafil area under the curve (AUC) rose 11-fold and peak concentration 4-fold; 24 hours after the dose, sildenafil levels were still about 200 ng/mL compared with about 5 ng/mL without ritonavir. This raises the risk of sildenafil side effects.

A sharp drop in blood pressure with dizziness and fainting, prolonged erection, visual disturbances. An erection lasting more than 4 hours needs urgent medical care.

The European Medicines Agency (EMA) contraindicates the combination in pulmonary arterial hypertension (ritonavir label and pulmonary hypertension sildenafil label, EMA). During a nirmatrelvir/ritonavir course for COVID-19, sildenafil is contraindicated for any indication (nirmatrelvir/ritonavir label, EMA). For erectile dysfunction in a patient on long-term ritonavir, the combination is not recommended (sildenafil label). If sildenafil is still needed, use a single 25 mg dose and no more than 25 mg in 48 hours (ritonavir and sildenafil labels). The US Food and Drug Administration (FDA) sets the same limit and advises closer monitoring for side effects: low blood pressure, fainting, prolonged erection (ritonavir and sildenafil FDA labels).