Generic Name and Formulations:
Crizotinib 200mg, 250mg; hard gel caps.
Indications for XALKORI:
Treatment of metastatic non-small cell lung cancer (NSCLC) that is anaplastic lymphoma kinase (ALK) or ROS1-positive as detected by an FDA-approved test.
Confirm ALK or ROS1-positive NSCLC with an FDA-approved test before treating. Swallow whole. 250mg twice daily until disease progression or intolerance. Concomitant strong CYP3A inhibitors: if unavoidable, reduce to 250mg once daily. Moderate hepatic impairment (AST and total bilirubin >1.5–≤3xULN): 200mg twice daily; severe (AST and total bilirubin >3xULN): 250mg once daily. Severe renal impairment (CrCl <30mL/min) not requiring dialysis: 250mg once daily. Dose modifications for hematologic and non-hematologic toxicities: see full labeling.
Monitor ALT, AST and total bilirubin every 2 weeks during first 2 months, then monthly, and more frequently for elevated transaminases; temporarily suspend, reduce dose, or permanently discontinue as clinically indicated. Monitor CBCs with differential monthly and more frequently if Grade 3 or 4 abnormalities, fever or infection occurs. Risk of severe pneumonitis: monitor for pulmonary symptoms; permanently discontinue if occurs. Congenital long QT syndrome; avoid. History of or predisposition for QTc prolongation (eg, CHF, bradyarrhythmias, electrolyte abnormalities, or those who are taking drugs known to prolong the QT interval): consider monitoring ECG, electrolytes periodically. Torsade de pointes, ventricular tachycardia, serious arrhythmia: permanently discontinue if QTc >500ms or ≥60ms change from baseline. Monitor HR and BP regularly; discontinue if life-threatening bradycardia occurs. Discontinue if onset of severe visual loss; perform eye evaluation. Hepatic impairment. Severe renal impairment. Embryo-fetal toxicity. Pregnancy; avoid. Use effective contraception during and for at least 45 days (females) or 90 days (males w. female partners) after final dose. Nursing mothers: not recommended (during and for 45 days after final dose).
Tyrosine kinase inhibitor.
Avoid concomitant strong CYP3A inhibitors (eg, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, troleandomycin, voriconazole, grapefruit, or grapefruit juice); see Adults. Avoid concomitant strong CYP3A inducers (eg, carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, St. John’s Wort). Avoid concomitant CYP3A substrates with narrow therapeutic indices (eg, alfentanil, cyclosporine, ergots, fentanyl, pimozide, quinidine, sirolimus, tacrolimus); if needed, reduce doses. Avoid concomitant agents known to cause bradycardia (eg, beta-blockers, non-dihydropyridine calcium channel blockers, clonidine, digoxin); adjust dose or discontinue. Caution with moderate CYP3A inhibitors.
Vision disorders, nausea, diarrhea, vomiting, edema, constipation, elevated transaminases, fatigue, decreased appetite, upper RTI, dizziness, neuropathy, neutropenia; hepatotoxicity (may be fatal), pneumonitis (may be fatal), QT prolongation, bradycardia.