Xalkori

Crizotinib

Advanced NSCLC that is anaplastic lymphoma kinase (ALK) +ve or ROS1 +ve as detected by accurate & validated assay.

250 mg bid. Dose reduction: 1st dose reduction: 200 mg bid. 2nd dose reduction: 250 mg once daily. Moderate hepatic impairment (any AST & total bilirubin >1.5x ULN & ≤3x ULN) Initially 200 mg bid. Severe hepatic impairment (any AST & total bilirubin >3x ULN) Initially 250 mg once daily. Severe renal impairment (CrCl <30 mL/min) not requiring peritoneal dialysis or hemodialysis 250 mg once daily. May be increased to 200 mg bid after at least 4 wk.

May be taken with or without food: Swallow whole, do not open.

Hypersensitivity.

Permanently discontinue treatment in patients w/ treatment-related ILD/pneumonitis. Discontinue treatment in patients w/ new onset of severe visual loss (best corrected visual acuity <6/60 in 1 or both eyes). Hold treatment in cases of symptomatic bradycardia. Consider discontinuation, interruption or reduction of dose if symptoms of heart failure (dyspnea, edema, rapid wt gain from fluid retention) are observed. Severe, life-threatening or fatal ILD/pneumonitis. Drug-induced hepatotoxicity; QTc prolongation w/o accompanying arrhythmia; asymptomatic bradycardia; severe, life-threatening, or fatal adverse reactions of cardiac failure; grade 3 or 4 neutropenia or leukopenia; grade 4 visual field defect w/ vision loss. Patients w/ history of, or pre-disposition for QTc prolongation or who are taking QT interval prolonging medications. Monitor LFTs including ALT, AST & total bilirubin every 2 wk during 1st 2 mth of treatment then once a mth, w/ more frequent repeat testing for grades 2, 3 or 4 transaminase elevations; pulmonary symptoms indicative of ILD/pneumonitis; pulse rate & BP mthly; signs & symptoms of heart failure in patients w/ or w/o pre-existing cardiac disorders; CBC including differential WBC counts, w/ more frequent repeat testing if grade 3 or 4 neutropenia or leukopenia, or if fever or infection occurs. Consider periodic monitoring w/ ECG & electrolytes when used in patients w/ history of, or pre-disposition for QTc prolongation, or taking medications known to prolong QT interval. Perform ophth evaluation consisting of best corrected visual acuity, retinal photographs, visual fields, optical coherence tomography & other evaluations as appropriate for new onset of severe visual loss & if vision disorder persists or worsens in severity. Avoid use w/ other bradycardic agents eg, β-blockers, non-dihydropyridine Ca channel blockers (verapamil & diltiazem), clonidine, digoxin. May affect ability to drive & use machines. Hepatic impairment. Severe renal impairment not requiring peritoneal dialysis or hemodialysis. May compromise male & female fertility. Women, or partners of women of childbearing potential should use adequate contraceptive methods during therapy & for at least 90 days after completing therapy. Pregnancy & lactation. Ped patients.

Neutropenia, leukopenia; decreased appetite; neuropathy, dizziness, dysgeusia; vision disorder; bradycardia; vomiting, nausea, diarrhea, constipation; elevated transaminases; rash; edema, fatigue. Cardiac failure, prolonged ECG QT, syncope; ILD; esophagitis, dyspepsia; increased blood alkaline phosphatase; renal cyst, increased blood creatinine; decreased blood testosterone.

Increased plasma conc w/ strong CYP3A inhibitors eg, atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, troleandomycin & voriconazole; grapefruit or grapefruit juice. Decreased plasma conc w/ strong CYP3A inducers eg, carbamazepine, phenobarb, phenytoin, rifabutin, rifampin & St. John's wort. May alter plasma conc of CYP3A substrates w/ narrow therapeutic indices eg, alfentanil, cyclosporine, fentanyl, quinidine, sirolimus, tacrolimus. Avoid co-administration w/ CYP3A substrates that have narrow therapeutic indices & associated w/ life-threatening arrhythmias eg, dihydroergotamine, ergotamine, astemizole, cisapride, terfenadine & pimozide.

Targeted Cancer Therapy

L01ED01 - crizotinib ; Belongs to the class of anaplastic lymphoma kinase (ALK) inhibitors. Used in the treatment of cancer.

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