Drug interactions of Nintedanib

P-glycoprotein (P-gp) and CYP3A4 Inhibitors and Inducers

Nintedanib is a substrate of P-gp and, to a lesser extent, a substrate of
CYP3A4.

Concomitant use with ketoconazole, an oral P-gp and CYP3A4 inhibitor,
increases the exposure of nintedanib by 60%. Co-administration of nintedanib
with P-gp and CYP3A4 inhibitors (e.g., erythromycin) may increase nintedanib
exposure. In such cases, patients' tolerance to nintedanib should be closely
monitored. Management of adverse reactions may require interruption, dose
reduction, or discontinuation of nintedanib treatment.

Concomitant use with rifampicin, an oral P-gp and CYP3A4 inducer, reduces the
exposure of nintedanib by 50%. Co-administration of nintedanib with P-gp and
CYP3A4 inducers (e.g., carbamazepine, phenytoin, and St. John’s wort) should be
avoided, as these drugs may decrease nintedanib exposure.

Anticoagulants

Nintedanib is a VEGFR inhibitor and may increase the risk of bleeding.
Closely monitor patients receiving full-dose anticoagulant therapy for signs of
bleeding and adjust anticoagulant treatment as needed.

Pirfenidone

In a multiple-dose study evaluating the pharmacokinetic effects of the
combination therapy of nintedanib and pirfenidone, co-administration of
nintedanib with pirfenidone did not alter the exposure of either drug. No dose
adjustment is required during concurrent administration of nintedanib and
pirfenidone.