<p><strong>P-glycoprotein (P-gp)</strong>: Nintedanib is a substrate of P-gp. Co-administration with the potent P-gp inhibitor ketoconazole increased exposure to Nintedanib 1.61-fold based on AUC and 1.83-fold based on Cmax in a dedicated drug-drug interaction study. In a drug-drug interaction study with the potent P-gp inducer rifampicin, exposure to Nintedanib decreased to 50.3% based on AUC and to 60.3% based on Cmax upon co-administration with rifampicin compared to administration of Nintedanib alone. If co-administered with Nintedanib, potent P-gp inhibitors (e.g. ketoconazole, erythromycin or cyclosporine) may increase exposure to Nintedanib. In such cases, patients should be monitored closely for tolerability of Nintedanib. Management of side effects may require interruption, dose reduction, or discontinuation of therapy with Nintedanib. Potent P-gp inducers (e.g. rifampicin, carbamazepine, phenytoin, and St. John&rsquo;s Wort) may decrease exposure to Nintedanib. Selection of an alternate concomitant medicinal product with no or minimal P-gp induction potential should be considered.<br />
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<strong>Cytochrome (CYP)-enzymes</strong>: Only a minor extent of the biotransformation of Nintedanib consisted of CYP pathways. Nintedanib and its metabolites, the free acid moiety BIBF 1202 and its glucuronide BIBF 1202 glucuronide, did not inhibit or induce CYP enzymes in preclinical studies. The likelihood of drug-drug interactions with Nintedanib based on CYP metabolism is therefore considered to be low.<br />
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<strong>Co-administration with other medicinal products</strong>: The potential for interactions of Nintedanib with hormonal contraceptives was not explored.</p>