NINTEDANIB IS A SUBSTRATE OF P-GP AND, TO A MINOR EXTENT, CYP3A4. COADMINISTRATION WITH ORAL DOSES OF A P-GP AND CYP3A4 INHIBITOR, KETOCONAZOLE, INCREASED EXPOSURE TO NINTEDANIB BY 60%. CONCOMITANT USE OF P-GP AND CYP3A4 INHIBITORS (E.G., ERYTHROMYCIN) WITH OFEV MAY INCREASE EXPOSURE TO NINTEDANIB. IN SUCH CASES, PATIENTS SHOULD BE MONITORED CLOSELY FOR TOLERABILITY OF OFEV. MANAGEMENT OF ADVERSE REACTIONS MAY REQUIRE INTERRUPTION, DOSE REDUCTION, OR DISCONTINUATION OF THERAPY WITH OFEV.
COADMINISTRATION WITH ORAL DOSES OF A P-GP AND CYP3A4 INDUCER, RIFAMPICIN, DECREASED EXPOSURE TO NINTEDANIB BY 50%. CONCOMITANT USE OF P-GP AND CYP3A4 INDUCERS (E.G., CARBAMAZEPINE, PHENYTOIN, AND ST. JOHN'S WORT) WITH OFEV SHOULD BE AVOIDED AS THESE DRUGS MAY DECREASE EXPOSURE TO NINTEDANIB.
NINTEDANIB IS A VEGFR INHIBITOR AND MAY INCREASE THE RISK OF BLEEDING. MONITOR PATIENTS ON FULL ANTICOAGULATION THERAPY CLOSELY FOR BLEEDING AND ADJUST ANTICOAGULATION TREATMENT AS NECESSARY.