Crizotinib

About Crizotinib 

• Crizotinib is a prescribed medication for non-small cell lung cancer (NSCLC) that has metastasized, specifically linked to genetic abnormalities in the ALK or ROS1 genes. It is also recommended for children (1 year and older) and young adults with ALK gene-defective anaplastic large cell lymphoma (ALCL) upon recurrence or when prior treatments are ineffective.
• This medication operates as a targeted therapy by inhibiting the activity of ALK and ROS1 proteins, pivotal factors in the proliferation and survival of cancer cells.
• The administration of Crizotinib should be conducted under the guidance of a qualified healthcare professional, who will tailor the treatment plan based on individual conditions, medical history, and other pertinent factors.
• Crizotinib is a tyrosine kinase inhibitor with a primary mechanism of action targeting specific proteins involved in cancer cell growth. 
• Specifically, it inhibits the activity of anaplastic lymphoma kinase (ALK), ROS1 (c-ros oncogene 1), and the mesenchymal-epithelial transition (MET) receptor. 
• By blocking these signaling pathways, crizotinib interferes with the proliferation and survival of cancer cells, particularly in cases of non-small cell lung cancer (NSCLC) where alterations in ALK or ROS1 genes are present.

Strength: 

Crizotinib capsules are available in strengths of 250 mg and 200 mg for the treatment of certain types of cancers. 

Recommended Dosage:

Choose individuals for Crizotinib therapy in metastatic NSCLC by assessing the presence of ALK or ROS1 positivity in tumor specimens. Make recommended adjustments to dosage for both hematologic and non-hematologic adverse reactions in NSCLC patients.

• The prescribed dose of Crizotinib for NSCLC patients is 250 mg taken orally twice daily, with or without meals, until disease progression or if the patient no longer tolerates the treatment. 
• Swallow the capsules whole, and if a dose is missed, compensate for it unless the next dose is scheduled within 6 hours. 
• In case of vomiting after a Crizotinib dose, take the next one at the regular time. 
• For ALCL patients, the recommended dosage is 280 mg/m2 orally twice daily until disease progression or unacceptable toxicity, based on body surface area (BSA).

Important: 

It is important to inform your doctor about all the adverse effects. Your doctor may change your dosage according to your side effects. 

Warnings & Precaution:

• Hepatotoxicity leading to fatalities has been reported with Crizotinib, necessitating regular liver testing. Management may involve temporary suspension, dose reduction, or permanent discontinuation of Crizotinib. 
• For patients experiencing Interstitial Lung Disease (ILD)/Pneumonitis, permanent discontinuation is recommended. 
• Electrocardiograms and electrolytes should be monitored in individuals with a history of or predisposition for QTc prolongation or those taking QT-prolonging medications.
• Management strategies may include temporary suspension, dose reduction, or permanent discontinuation of Crizotinib. 
• Bradycardia, a potential side effect of Crizotinib, requires regular heart rate and blood pressure monitoring, with possible temporary suspension, dose reduction, or permanent discontinuation. 
• Severe visual changes, including loss, may occur, necessitating Crizotinib discontinuation. Ocular toxicity monitoring is advised throughout treatment. 
• Pediatric and young adult patients with ALCL or pediatric patients with IMT may experience gastrointestinal toxicity, including severe nausea, vomiting, diarrhea, and stomatitis. 
• Standard antiemetic and antidiarrheal agents should be provided, and Crizotinib may be temporarily suspended, dose-reduced, or permanently discontinued based on the severity of symptoms.

Common Crizotinib Side Effects:

• Diarrhea (most common)
• Nausea and vomiting
• Loss of appetite
• Constipation
• Mouth sores
• Fatigue
• Vision changes (blurry vision, light sensitivity)
• Dizziness
• Headache
• Muscle and joint pain
• Swelling (hands, feet, face)
• Cough
• Fever
• High blood pressure

Use in Specific Population

• Crizotinib, due to its mechanism of action, can pose a risk of fetal harm if administered to pregnant women. 
• Information regarding the presence of crizotinib or its metabolites in human milk and their impact on the breastfed child or milk production is not available. 
• Due to potential adverse reactions in breastfed children, women are advised against breastfeeding during Crizotinib treatment and for 45 days after the final dose. Before starting Crizotinib, assess the pregnancy status of females of reproductive potential. 
• These women should use effective contraception during Crizotinib treatment and for at least 45 days post-treatment. 
• Males with female partners of reproductive potential should use condoms during Crizotinib treatment and for at least 90 days after the final dose due to potential genotoxicity. 
• Reproductive organ findings in animals suggest Crizotinib may reduce fertility in females and males of reproductive potential, with the reversibility of these effects unknown. 
• The safety and effectiveness of Crizotinib have been established in pediatric patients aged 12 months and older with relapsed or refractory systemic ALK-positive ALCL.
• Clinical studies in patients with ROS1-positive metastatic NSCLC did not include sufficient numbers of patients aged 65 and older to determine potential age-related differences. 
• No dose adjustment is recommended for patients with pre-existing mild hepatic impairment or mild to moderate renal impairment.

Storage and Handling

• Keep Crizotinib at a temperature of 20° to 25°C (68° to 77°F). Excursions within the range of 15°C to 30°C (59°F to 86°F) are permitted.
• Do not freeze the medicine. 
• Keep the medicine away from pets and children.