Xalkori Drug Interactions

Crizotinib is a substrate of CYP3A4/5 and also a moderate inhibitor of CYP3A. In vitro studies in human liver microsomes demonstrated that crizotinib is a time-dependent inhibitor of CYP3A.
Agents that may increase crizotinib plasma concentrations: Co-administration of crizotinib with strong CYP3A inhibitors may increase crizotinib plasma concentrations (see Pharmacology: Pharmacokinetics under Actions). The concomitant use of strong CYP3A inhibitors, including but not limited to atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, troleandomycin, and voriconazole, should be avoided. Grapefruit or grapefruit juice may also increase plasma concentrations of crizotinib and should be avoided.
Agents that may decrease crizotinib plasma concentrations: Co-administration of crizotinib with strong CYP3A inducers may decrease crizotinib plasma concentrations (see Pharmacology: Pharmacokinetics under Actions). The concurrent use of strong CYP3A inducers, including but not limited to carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, and St. John's wort, should be avoided.
Agents whose plasma concentrations may be altered by crizotinib: Crizotinib has been identified as an inhibitor of CYP3A both in vitro and in vivo (see Pharmacology: Pharmacokinetics under Actions). Caution should be exercised in administering crizotinib in combination with drugs that are predominantly metabolized by CYP3A, particularly those, CYP3A substrates that have narrow therapeutic indices, including but not limited to alfentanil, cyclosporine, fentanyl, quinidine, sirolimus, and tacrolimus.
Co-administration of crizotinib should be avoided with CYP3A substrates that have narrow therapeutic indices and are associated with life-threatening arrhythmias, including but not limited to dihydroergotamine, ergotamine, astemizole, cisapride, terfenadine, and pimozide.