What drugs may increase crizotinib plasma concentrations?

Drugs that may increase crizotinib plasma concentrations?

Coadministration of crizotinib with strong inhibitors may result in increased crizotinib plasma concentrations [see Clinical Pharmacology]? . The concomitant use of the following strong inhibitors (including but not limited to) should be avoided: atazanavir clarithromycin indinavir itraconazole conazole nefazodone nelfinavir ritonavir saquinavir Clarithromycin, telithromycin, troleandomycin, and voriconazole. Grapefruit or grapefruit juice may also increase the blood concentration of crizotinib, so consumption at the same time should be avoided. Caution should be used when coadministering with moderate inhibitors. ?

Crizotinib inhibits ?[?See Clinical Pharmacology] both in vivo and in vitro. When crizotinib is used concomitantly with drugs that are primarily metabolized by ?, the latter may require a dose reduction. In particular, combination of crizotinib with substrates with a narrow therapeutic index (including but not limited to alfentanil, cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and others) should be avoided. Crolimus) combined.

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Overdose:?
????There are no known cases of overdose with crizotinib capsules. General supportive measures should be implemented for overdose of crizotinib capsules. There is currently no antidote for crizotinib capsules.

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Pharmacological effects:?
????Crizotinib is an inhibitor of tyrosine kinase receptors, including hepatocyte growth factor receptor ( R,) and R. Translocation can promote the expression of oncogenic fusion proteins caused by ? genes. The formation of fusion proteins can cause activation and dysregulation of gene expression and signaling, thereby promoting the proliferation and survival of tumor cells expressing these proteins. Crizotinib has a concentration-dependent inhibitory effect on phosphorylation of ? and ? detected at the cellular level in tumor cell lines, and has anti-tumor activity in xenograft tumor-bearing mice expressing ? or ? fusion proteins or ?

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