No relevant pharmacokinetic drug–drug interaction between nintedanib and pirfenidone

Nintedanib and pirfenidone are approved treatments for idiopathic pulmonary fibrosis (IPF). This open-label, two-group trial investigated the pharmacokinetic drug–drug interaction between these two drugs in patients with IPF. Subjects not treated with antifibrotics at screening (group 1, n=20) received a single nintedanib dose (150 mg) followed by pirfenidone (titrated to 801 mg thrice daily) for 3 weeks, with a further single nintedanib dose (150 mg) on the last day (day 23). Subjects treated with pirfenidone at screening (group 2, n=17) continued to receive pirfenidone alone (801 mg thrice daily) for 7 days, then co-administered with nintedanib (150 mg twice daily) for a further 7 days, before single doses of both treatments on day 16. In group 1, adjusted geometric mean (gMean) ratios (with/without pirfenidone) were 88.6% and 80.6% for nintedanib area under the plasma concentration–time curve (AUC) and maximum plasma concentration (C max ), respectively. In group 2, gMean ratios (with/without nintedanib) were 97.2% and 99.5% for pirfenidone AUC and C max , respectively. For all parameters, the 90% confidence intervals included 100%, suggesting similar exposure for administration alone and when co-administered. Both treatments were well tolerated. These data indicate there is no relevant pharmacokinetic drug–drug interaction between nintedanib and pirfenidone when co-administered in IPF patients.