The pharmacokinetics of afatinib in the presence of a potent inhibitor of P-gp (ritonavir, 200 mg twice daily) were investigated in 22 HIV-negative subjects. Administration of afatinib (20 mg single dose) 1 h after ritonavir increased afatinib Cmax and AUC by 38.5% and 47.6 %, respectively. Coadministration of ritonavir either simultaneously or 6 h later than afatinib (40 mg single dose) increased afatinib Cmax and AUC by 4.1% and 18.6 % for simultaneous administration and by 5.1% and 10.8 % for staggered administration. Coadministration of a potent P-gp inhibitor had no clinically relevant effect on afatinib exposure with the effects being minimal at higher afatinib doses and can be readily managed by the timing of concomitant therapy. As afatinib is not a relevant modulator or substrate of cytochrome P450 enzymes, the drug-drug interaction potential is considered to be low.