Coadministration with nirmatrelvir/ritonavir has not been studied. Afatinib is mainly eliminated unchanged in the faeces and is a substrate of P-glycoprotein and BCRP. Administration of ritonavir (200 mg twice daily for 3 days) 1 hour before afatinib (20 mg single dose) increased afatinib AUC and Cmax by 48% and 39%. However, coadministration of ritonavir simultaneously or 6 hours after afatinib (40 mg) resulted in minimal increase in afatinib AUC and Cmax (19% and 4% for simultaneous administration; 11% and 5% for the staggered administration). The European product label for afatinib recommends to administer strong P-gp inhibitors (such as nirmatrelvir/ritonavir) 6 hours apart from afatinib. The US product label includes a recommendation to decrease afatinib daily dose by 10 mg if not tolerated for patients who require a therapy with a P-gp inhibitor. The previous afatinib dose should be resumed after discontinuation of the P-gp inhibitor as tolerated.