Comprehensive Guide to Crizotinib: Uses, Dosage, Side Effects, and More
What is Crizotinib?
Overview of Crizotinib
Generic Name: Crizotinib
Brand Name: Xalkori
Drug Group: Tyrosine kinase inhibitor (TKI)
Commonly Used For
- Treat ALK-positive NSCLC.
- Manage ROS1-positive NSCLC.
- Control metastatic lung cancer.
Key Characteristics
Form: Oral capsules (200 mg, 250 mg) (detailed in Dosage section).
Mechanism: Inhibits ALK, ROS1, and MET tyrosine kinases, blocking tumor cell proliferation.
Approval: FDA-approved (2011) and EMA-approved for NSCLC.
Indications and Uses of Crizotinib
Crizotinib is indicated for managing specific cancers with its kinase inhibitory action:
ALK-Positive Non-Small Cell Lung Cancer (NSCLC):
Treats locally advanced or metastatic ALK-positive NSCLC, achieving partial response in 60–70% of patients within 8–12 weeks.
Manages first-line therapy in ALK-rearranged NSCLC, improving progression-free survival by 10–12 months compared to chemotherapy.
ROS1-Positive Non-Small Cell Lung Cancer (NSCLC):
Treats metastatic ROS1-positive NSCLC, with response rates of 70–80% in patients with this rare mutation, per clinical trials.
Controls disease progression in ROS1-rearranged cases, delaying resistance development.
Off-Label Uses:
Includes treatment of MET exon 14 skipping mutations in NSCLC, improving outcomes in 30–40% of cases, under oncology supervision.
Adjunctive therapy in inflammatory myofibroblastic tumors (IMT) with ALK fusions, reducing tumor size by 50% in pediatric cases, supported by sarcoma studies.
Management of anaplastic large cell lymphoma (ALCL) with ALK translocations, enhancing remission rates when combined with chemotherapy, per hematology reports.
Investigational use in neuroblastoma with ALK mutations, targeting tumor growth in relapsed cases, based on early-phase trials.
Pediatric Considerations:
Treats ALK-positive IMT and ALCL in children 1 year and older, with weight-based dosing, improving long-term survival.
Combination Therapy:
Used with immunotherapy (e.g., pembrolizumab) in NSCLC to enhance response rates, per ongoing trials.
Dosage of Crizotinib
Dosage for Adults
ALK-Positive or ROS1-Positive NSCLC (Oral):
- 250 mg twice daily (500 mg total daily dose), taken with or without food.
- With moderate hepatic impairment: 200 mg twice daily.
MET Exon 14 Skipping Mutations (Oral): 250 mg twice daily, adjusted based on tolerance.
Maintenance: Continue until disease progression or unacceptable toxicity, typically 6–12 months.
Dosage for Children
ALK-Positive IMT or ALCL (Oral, 1 year–17 years):
- 280 mg/m² twice daily (max 500 mg/day), based on body surface area (BSA), under pediatric oncology supervision.
- Example: 0.6 m² child receives 168 mg twice daily.
- Not recommended under 1 year without specialist approval.
Dosage for Pregnant Women
Dosage Adjustments
Renal Impairment: No adjustment if CrCl >30 mL/min; avoid if <30 mL/min.
Hepatic Impairment: Reduce to 200 mg twice daily if moderate (Child-Pugh B); avoid if severe.
Elderly: Use standard dosing; monitor liver function closely.
Obese Patients: Base dose on ideal body weight to avoid toxicity.
Additional Considerations
- Take with or without food, but maintain consistency; avoid grapefruit juice.
- Interrupt or reduce dose if QT prolongation or hepatotoxicity occurs.
How to Use Crizotinib
Administration:
Oral: Swallow capsules whole with water, with or without food, using a calibrated cup for precise dosing if split.
Avoid crushing or opening capsules to prevent powder exposure.
Timing: Take 250 mg twice daily (e.g., 8 AM and 8 PM), maintaining a 12-hour interval, continuing for the prescribed duration.
Monitoring: Watch for jaundice, vision changes, or chest pain; check for signs of liver toxicity (e.g., dark urine) or cardiac issues (e.g., palpitations).
Additional Tips:
- Store capsules at 20–25°C (68–77°F), protecting from moisture.
- Avoid sun exposure; use sunscreen (SPF 30+).
- Report severe headache, shortness of breath, or signs of bleeding (e.g., bruising) immediately.
Contraindications for Crizotinib
Hypersensitivity: Patients with a known allergy to Crizotinib or other TKIs.
Severe Hepatic Impairment: Avoid in Child-Pugh C liver disease due to metabolism concerns.
Severe Renal Impairment: Contraindicated if CrCl <30 mL/min due to excretion issues.
Pregnancy (Unless Critical): Category D, with significant fetal risk; avoid unless life-saving.
Long QT Syndrome: Contraindicated due to risk of fatal arrhythmias.
Warnings & Precautions for Crizotinib
General Warnings
Hepatotoxicity: Risk of elevated liver enzymes; monitor monthly.
QT Prolongation: Potential for torsades de pointes; monitor ECG.
Pneumonitis: Risk of interstitial lung disease; assess respiratory symptoms.
Visual Disorders: Blurred vision or photopsia; perform eye exams.
Drug Interactions: Altered efficacy with CYP3A inhibitors; adjust accordingly.
Additional Warnings
Cardiac Effects: Bradycardia or heart block; monitor heart rate.
Gastrointestinal Perforation: Rare risk; assess abdominal pain.
Pregnancy Risks: Category D; require contraception during and after therapy.
Pediatric Risks: Higher sensitivity to cardiac and liver toxicity; limit to approved ages.
Elderly Risks: Increased risk of QT prolongation and hepatotoxicity; use cautiously.
Use in Specific Populations
Pregnancy: Category D; use only if life-saving, with fetal monitoring.
Breastfeeding: Excreted in breast milk; avoid or monitor infant.
Elderly: Higher risk of cardiac and liver issues; adjust dose if impaired.
Children: Safe for >1 year; avoid under 1 year.
Renal/Hepatic Impairment: Avoid in severe cases; adjust dose in moderate impairment.
Additional Precautions
- Inform your doctor about liver disease, heart conditions, or pregnancy plans before starting this medication.
- Avoid abrupt cessation; taper under supervision if needed.
Overdose and Management of Crizotinib
Overdose Symptoms
- Hepatotoxicity (jaundice, elevated enzymes).
- Severe cases: QT prolongation, bradycardia, or respiratory failure.
- Fatigue or dizziness as early signs.
- Vision changes or confusion with high doses.
Immediate Actions
Contact the Medical Team: Seek immediate medical help.
Supportive Care: Administer IV fluids, monitor ECG and liver function, and provide oxygen if needed.
Specific Treatment: No specific antidote; use anti-arrhythmics (e.g., magnesium) for QT issues; discontinue.
Monitor: Check liver enzymes, QT interval, and vital signs for 24–48 hours.
Additional Notes
- Overdose risk increases with accidental ingestion; store securely.
- Report persistent symptoms (e.g., severe weakness, chest pain) promptly.
Side Effects of Crizotinib
Common Side Effects
- Nausea (40–50%, manageable with antiemetics)
- Diarrhea (20–30%, reduced with diet)
- Vision Changes (15–25%, transient with rest)
- Fatigue (10–20%, monitorable with care)
- Edema (5–15%, alleviated with elevation)
These effects may subside with dose adjustment or supportive care.
Serious Side Effects
- Hepatic: Hepatitis, liver failure, or jaundice.
- Cardiac: QT prolongation, bradycardia, or heart block.
- Pulmonary: Pneumonitis or interstitial lung disease.
- Ocular: Blindness or severe vision loss.
- Gastrointestinal: Perforation or severe abdominal pain.
Additional Notes
- Regular monitoring for liver function, ECG, and vision is advised.
- Report any unusual symptoms (e.g., chest pain, severe rash) immediately to a healthcare provider.
Drug Interactions with Crizotinib
This active ingredient may interact with:
CYP3A Inhibitors (e.g., Ketoconazole): Increases toxicity; reduce dose to 250 mg daily.
CYP3A Inducers (e.g., Rifampin): Decreases efficacy; avoid combination.
Antiarrhythmics (e.g., Amiodarone): Amplifies QT prolongation; monitor ECG.
Proton Pump Inhibitors: May reduce absorption; take 2 hours apart.
Warfarin: Potential bleeding risk; monitor INR.
Patient Education or Lifestyle
Medication Adherence: Take this kinase inhibitor as prescribed to manage cancer, following the exact schedule.
Monitoring: Report jaundice, vision changes, or chest pain immediately.
Lifestyle: Avoid sun exposure; use sunscreen and protective clothing.
Diet: Take with or without food; avoid grapefruit juice.
Emergency Awareness: Know signs of liver failure or cardiac issues; seek care if present.
Follow-Up: Schedule regular check-ups every 1–3 months to monitor liver and heart function.
Pharmacokinetics of Crizotinib
Absorption: Oral bioavailability 43%; peak at 4–6 hours.
Distribution: Volume of distribution ~1770 L; 91% protein-bound.
Metabolism: Hepatic via CYP3A4/5; active metabolites.
Excretion: Primarily fecal (63–80%); half-life 42–51 hours.
Half-Life: 42–51 hours, prolonged in hepatic impairment.
Pharmacodynamics of Crizotinib
This drug exerts its effects by:
Inhibiting ALK, ROS1, and MET kinases, blocking tumor signaling pathways.
Exhibiting dose-dependent antitumor activity, peaking at steady state.
Demonstrating selective efficacy in mutation-positive cancers.
Showing potential for resistance, requiring combination strategies.
Storage of Crizotinib
Temperature: Store capsules at 20–25°C (68–77°F).
Protection: Keep in original container, away from moisture.
Safety: Store out of reach of children.
Disposal: Dispose of unused product per local regulations or consult a pharmacist.
Frequently Asked Questions (FAQs)
Q: What does Crizotinib treat?
A: This medication treats ALK-positive and ROS1-positive NSCLC.
Q: Can this active ingredient cause liver issues?
A: Yes, hepatotoxicity is a risk; report yellowing skin.
Q: Is Crizotinib safe for children?
A: Yes, for >1 year with a doctor’s guidance.
Q: How is this drug taken?
A: Orally, as capsules, as directed.
Q: How long is Crizotinib treatment?
A: Months to years, depending on cancer response.
Q: Can I use Crizotinib if pregnant?
A: Yes, with caution; consult a doctor.
Regulatory Information for Crizotinib
This medication is approved by:
U.S. Food and Drug Administration (FDA): Approved in 2011 (Xalkori) for NSCLC.
European Medicines Agency (EMA): Approved for ALK-positive and ROS1-positive NSCLC.
Other Agencies: Approved globally for targeted cancer therapy; consult local guidelines.
References
- U.S. Food and Drug Administration (FDA). (2025). Xalkori (Crizotinib) Prescribing Information.
- Official FDA documentation detailing the drug’s approved uses, dosage, and safety.
- European Medicines Agency (EMA). (2025). Crizotinib Summary of Product Characteristics.
- EMA’s comprehensive information on the medication’s indications and precautions in Europe.
- National Institutes of Health (NIH). (2025). Crizotinib: MedlinePlus Drug Information.
- NIH resource providing detailed information on the drug’s uses, side effects, and precautions.
- World Health Organization (WHO). (2025). WHO Model List of Essential Medicines: Crizotinib.
- WHO’s consideration of Crizotinib for cancer.
- Journal of Clinical Oncology. (2024). Crizotinib in ALK-Positive NSCLC.
- Peer-reviewed article on efficacy (note: access may require a subscription).
