Crizotinib is a kinase inhibitor indicated for the treatment of patients with–

• Metastatic non-small cell lung cancer (NSCLC) with anaplastic lymphoma kinase (ALK)-positive tumors
• Metastatic NSCLC with ROS1-positive tumors

Crizotinib is a kinase inhibitor used in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) that is ALK-positive or ROS1-positive. It was the first FDA-approved biomarker-driven therapy for both ALK-positive and ROS1-positive metastatic NSCLC. It is also the only FDA-approved therapy specifically indicated for ROS1-positive NSCLC.

Recommended Dose: 250 mg orally, twice daily

Geriatric Use: No differences in safety or efficacy were observed between older and younger patients. Clinical studies of Crizotinib in patients with ROS1-positive metastatic NSCLC did not include sufficient numbers of patients age 65 years and older to determine whether they respond differently from younger patients

Pediatric Dose: The safety and effectiveness of Crizotinib in pediatric patients have not been established.

Renal impairment: 250 mg orally, once daily in patients with severe renal impairment (creatinine clearance <30 mL/min) not requiring dialysis. No starting dose adjustment is needed for patients with mild (ClCr 60-89 mL/min) or moderate (ClCr 30-59 mL/min) renal impairment based on a population pharmacokinetic analysis.

Hepatic Impairment: Caution should be used in patients with hepatic impairment

CYP3A Inhibitors: Concurrent use of Crizotinib with strong CYP3A inhibitors should be avoided. These include drugs such as atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, troleandomycin, and voriconazole.

CYP3A Inducers: Crizotinib should not be used together with strong CYP3A inducers including carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, and St. John’s Wort.

CYP3A Substrates: Concurrent use with CYP3A substrates having a narrow therapeutic index should also be avoided. These include alfentanil, cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus.

The most commonly reported adverse effects (≥25%) include visual disturbances, nausea, diarrhea, vomiting, edema, constipation, elevated liver transaminases, fatigue, decreased appetite, upper respiratory tract infection, dizziness, and neuropathy.

Based on its mechanism of action, Crizotinib may cause fetal harm if administered during pregnancy. There is limited information regarding its use in pregnant women. Women of reproductive potential should be informed about the possible risk to the fetus and advised to use effective contraception. It is not known whether Crizotinib passes into human breast milk or affects milk production. Due to the possibility of serious adverse reactions in breastfed infants, breastfeeding should be avoided during treatment and for 45 days after the final dose.

Hepatotoxicity: Regular liver function monitoring is recommended. Depending on severity, Crizotinib may need to be temporarily withheld, dose-adjusted, or permanently discontinued.

Interstitial Lung Disease (ILD) / Pneumonitis: Treatment should be permanently stopped in patients who develop ILD or pneumonitis.

QT Interval Prolongation: ECG and electrolyte monitoring are advised in patients with a history of QT prolongation or those receiving QT-prolonging medications. Dose interruption, reduction, or discontinuation may be necessary.

Bradycardia: Crizotinib may cause bradycardia; therefore, heart rate and blood pressure should be monitored regularly. Treatment modification may be required if clinically indicated.

Severe Visual Loss: Ophthalmologic examination should be performed if severe vision problems occur. Crizotinib should be discontinued in cases of severe visual impairment.

Embryo-fetal Toxicity: Crizotinib may cause fetal harm. Women of reproductive age should be advised about fetal risk and the importance of effective contraception.

Targeted Cancer Therapy

Store below 30°C, protected from light and moisture. Keep out of reach of children.