Drug interactions of Erlotinib

CYP3A4 Inhibitors

Coadministration of erlotinib with strong CYP3A4 inhibitors or dual CYP3A4/CYP1A2 inhibitors increases erlotinib exposure. Erlotinib is primarily metabolized by CYP3A4 and to a lesser extent by CYP1A2. Increased erlotinib exposure may elevate the risk of exposure-related toxicities.

Avoid concurrent use of erlotinib with strong CYP3A4 inhibitors (e.g., boceprevir, clarithromycin, conivaptan, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telithromycin, voriconazole, grapefruit, or grapefruit juice) or dual CYP3A4/CYP1A2 inhibitors (e.g., ciprofloxacin). If concurrent use of a strong CYP3A4 inhibitor or dual CYP3A4/CYP1A2 inhibitor is unavoidable, reduce the erlotinib dose.

CYP3A4 Inducers

Pretreatment with CYP3A4 inducers decreases erlotinib exposure [see Clinical Pharmacology (12.3)]. If concurrent use with CYP3A4 inducers (e.g., carbamazepine, phenytoin, rifampin, rifabutin, rifapentine, phenobarbital, and St. John's Wort) is unavoidable, increase the erlotinib dose.

CYP1A2 Inducers and Smoking

Smoking decreases erlotinib exposure. Avoid smoking (a CYP1A2 inducer) and concurrent use of erlotinib with moderate CYP1A2 inducers (e.g., teriflunomide, rifampin, or phenytoin). For patients who smoke or when concurrent use with moderate CYP1A2 inducers is unavoidable, increase the erlotinib dose.

Drugs that Increase Gastric pH

Coadministration of erlotinib with proton pump inhibitors (e.g., omeprazole) and H2 receptor antagonists (e.g., ranitidine) decreases erlotinib exposure. For proton pump inhibitors, avoid concurrent use if possible. For H2 receptor antagonists and antacids, modify the dosing schedule. Increasing the erlotinib dose is unlikely to compensate for the loss of exposure when coadministered with drugs that raise gastric pH.

Anticoagulants

Interactions between erlotinib and coumarin-derived anticoagulants (including warfarin) have been reported, resulting in elevated INR and bleeding adverse reactions, some of which are fatal. For patients taking coumarin-derived anticoagulants, periodically monitor prothrombin time or INR. No erlotinib dosage adjustment is recommended.

FDA，2016.10