Ritonavir × Tadalafil

Ritonavir inhibits CYP3A4, the enzyme that clears tadalafil. Ritonavir 200 mg twice daily doubled tadalafil exposure (AUC) after a single 20 mg dose, and 500–600 mg twice daily raised it by 32% (tadalafil and ritonavir SmPCs). Later ritonavir also induces the same enzyme, and after about one week tadalafil exposure is close to normal (US tadalafil label for pulmonary arterial hypertension, FDA).

Hypotension, headache, priapism.

The combination is not contraindicated, but the tadalafil dose is limited and the plan depends on the indication. For erectile dysfunction taken as needed, use no more than 10 mg of tadalafil once every 72 hours and watch more closely for adverse reactions (ritonavir SmPC). For once-daily use in erectile dysfunction or benign prostatic hyperplasia, the maximum is 2.5 mg a day (US tadalafil label, FDA). In pulmonary arterial hypertension, the European tadalafil SmPC (EMA) does not recommend use with ritonavir. If the pair cannot be avoided, the US label gives this plan: in a patient on ritonavir for at least one week, start tadalafil at 20 mg once daily and increase to 40 mg as tolerated; when ritonavir is added to tadalafil, stop tadalafil at least 24 hours before ritonavir starts and resume at 20 mg after at least one week (US tadalafil label, FDA).