Crizotinib is an inhibitor of receptor tyrosine kinases including ALK, Hepatocyte Growth Factor Receptor (HGFR, c-Met), ROS1 (c-ros), and Recepteur d’Origine Nantais (RON). Translocations can affect the ALK gene resulting in the expression of oncogenic fusion proteins. The formation of ALK fusion proteins results in activation and dysregulation of the gene’s expression and signaling which can contribute to increased cell proliferation and survival in tumors expressing these proteins.

Crizocent demonstrated concentration-dependent inhibition of ALK, ROS1, and c-Met phosphorylation in cell-based assays using tumor cell lines and demonstrated antitumor activity in mice bearing tumor xenografts that expressed echinoderm microtubule-associated protein-like 4 (EML4)- or nucleophosmin (NPM)-ALK fusion proteins or c-Met.

Product Features

Indications

Crizocent is a kinase inhibitor indicate for the treatment of patients with-

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

Dosage & Administration

Recommended Dose: 250 mg orally, twice daily
Renal Impairment: 250 mg orally, once daily in patients with severe renal impairment (creatinine clearance <30 mL/min) not requiring dialysis.

Geriatric Use: No differences in safety or efficacy were observed between older and younger patients. Clinical studies of Crizocent 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

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

Renal Impairment: 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. Increased exposure to crizotinib occurred in patients with severe renal impairment (CLcr <30 mL/min) not requiring dialysis. Crizotinib should administered at a dose of 250 mg taken orally once daily in patients with severe renal impairment not requiring dialysis.

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

Side effects

This is not the full list of all side effects that may occur with Crizocent 250 mg.  Please seek medical advice from your doctor about if you experience serious or unusual side effects. You must seek immediate medical help if you find symptoms of easy bleeding tendencies, Jaundice, breathing problems, heart problems or infections developing in your body.

Drug allergies are quite common and might occur as a result of reaction to active ingredients as well as inactive ingredients. The most common side effects of allergies are: itching, rashes, hives, shortness of breath, low blood pressure, dizziness and loose motions.

Precautions

Hepatotoxicity: Patients should undergo periodic liver testing. Crizotinib should temporarily suspend, dose reduced or permanently suspend.
Interstitial lung disease (ILD)/

Pneumonitis: Drug should permanently discontinue in patients with ILD/ Pneumonitis QT interval prolongation: Electrocardiograms and electrolytes in patients who have a history of or predisposition for QTc prolongation, or who are taking medications that prolong QT should monitor. Crizotinib should be temporarily suspend, dose reduce or permanently suspend.

Bradycardia: Crizotinib can cause bradycardia. Heart rate and blood pressure should regularly monitored. Crizotinib should temporarily suspend, dose reduce or permanently suspend.
Severe visual loss: Ophthalmological evaluation should be performed. Crizocent should discontinue in severe visual loss.

Embryo-fetal toxicity: Crizocent can cause fetal harm. Females of reproductive potential should advise of the potential risk to a fetus and use of effective contraception

Use in Pregnancy & Lactation

Based on its mechanism of action, Crizocent can cause fetal harm when administered to a pregnant woman. There are no available data on the use of Crizotinib during pregnancy. Females of reproductive potential should advise of the potential risk to a fetus and use of effective contraception.
There is no information regarding the presence of Crizotinib in human milk, the effects on the breastfed infant, or the effects on milk production. Because of the potential for adverse reactions in breastfed infants patients should not breastfeed during treatment with Crizotinib and for 45 days after the final dose.

Drug Interaction

Inhibitors CYP3A : Concurrent use of Crizotinib avoid with strong CYP3A inhibitors including but not limited to atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, troleandomycin, and voriconazole

Inducers CYP3A: Use of Crizotinib should avoid with strong CYP3A inducers including but not limited to carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, and St. John’s Wort

Substrates CYP3A: using of Crizotinib should avoid with CYP3A substrates with narrow therapeutic indices including but not limited to alfentanil, cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus.