Patient Education
• Take crizotinib twice daily with or without food, at about the same time each day. If you miss a dose, you can still take it as long as there are at least 6 hours until the next dose. Otherwise, skip the dose. Do not drink grapefruit juice or eat grapefruit while taking crizotinib, as grapefruit can increase the drug levels in your blood.
• This drug can cause the following side effects: vision problems, nausea, vomiting, diarrhea, swelling of your hands or feet, constipation. Tell your doctor or nurse if you have side effects that bother you or do not go away.
• If you experience these side effects, it is important to tell your doctor about them right away:
– Vision problems that usually occur the first 2 weeks of therapy: Report any flashes of light, blurred vision, light hurting your eyes, new or increased floaters (floating specs).
– Swelling in lungs (pneumonitis): Report new or worsened trouble breathing, shortness of breath, cough, fever.
– Liver problems: You will have blood tests every month to check on this; tell your doctor right away if you get yellow skin or yellowing of the whites of your eyes, nausea or vomiting, decreased appetite, pain on the right side of your stomach, or if you feel very tired, your urine turns dark or brown, or you bleed or bruise more easily than usual.
– Irregular heartbeats, feeling dizzy or faint.
• Crizotinib can interact with many other drugs. Tell your doctor all the medicines you are taking, including herbal supplements and vitamins. Do not take St. John's Wort (Hypericum perforatum), as this interacts with your medicine. Crizotinib interacts with medications taken for depression, infections due to bacteria or fungus, tuberculosis, HIV-AIDS, heart conditions, and seizures.
Drug Interactions
• Strong CYP3A4 inhibitors (eg, atazanavir(Drug information on atazanavir) [Reyataz], clarithromycin(Drug information on clarithromycin), indinavir [Crixivan], itraconazole(Drug information on itraconazole), ketoconazole(Drug information on ketoconazole), nefazodone, nelfinavir [Viracept], ritonavir [Norvir], saquinavir, voriconazole [Vfend], grapefruit/grapefruit juice): increase crizotinib plasma concentrations. Use caution when moderate CYP3A4 inhibitors are used with crizotinib.
• Strong CYP3A4 inducers (eg, carbamazepine(Drug information on carbamazepine), phenobarbital, phenytoin(Drug information on phenytoin), rifabutin, rifampin, St. John's Wort). Avoid coadministration as drug will decrease crizotinib plasma concentrations.
• Drugs metabolized by CYP3A4 (CYP3A substrates with narrow therapeutic index), eg, alfentanil(Drug information on alfentanil), cyclosporine, dihydroergotamine(Drug information on dihydroergotamine), ergotamine(Drug information on ergotamine), fentanyl, pimozide, quinidine, sirolimus, tacrolimus(Drug information on tacrolimus). Avoid coadministration, or metabolized drug (substrate) dose will need to be decreased.
Special Considerations
• FDA approval was based on response rate, and there are no data available at this time showing improvement in patient-reported outcomes or survival.
• Visual changes may occur commonly, including visual impairment, blurred vision, photophobia, and diplopia.
• Patients may develop increased LFTs (ALT, total bilirubin). Monitor LFTs monthly, and more frequently in patients who develop grade 2–4 elevations.
• QT interval prolongation may occur, especially in patients who have a history of QTc prolongation or are taking medicines that prolong the QT interval. ECG and serum electrolytes should be monitored at baseline and during treatment for individuals at risk.
• ALK testing to establish ALK positivity is mandatory.
• Drug has the same safety and efficacy in geriatric patients as in younger patients.
Adverse Reactions to Crizotinib by Body System
(boldface type indicates more common events, with 25% or higher incidence)Cardiovascular: Edema, QT prolongation, bradycardia
CNS: Visual disturbances when going from dark to light environments, dizziness, headache, dysgeusia, insomnia
GI: Nausea, diarrhea, vomiting, constipation, stomatitis, esophagitis, abdominal pain, decreased appetite
Musculoskeletal: Arthralgia, back pain
Neurological: Neuropathy
Pulmonary: URI, dyspnea, cough
Renal: Renal cysts
Reproductive: Drug presumed to be harmful to fetus
Skin: Rash
Laboratory: Elevated serum transaminases, neutropenia, thrombocytopenia, lymphopenia
Contraindications/Precautions
• Visual changes are common. Evaluation by an ophthalmologist is recommended if patients develop photopsia (seeing sparks or flashes of color) or new or worsened vitreous floaters, as these may be signs of a retinal hole or pending retinal detachment. Caution patients not to drive or operate machinery if visual changes occur.
• Pneumonitis may occur, and can be severe. Monitor patient for signs and symptoms of pneumonitis (shortness of breath, cough, fatigue, loss of appetite, unintentional weight loss).
• Crizotinib can cause fetal harm when given to a pregnant woman. Teach female patients of childbearing potential to use effective contraception. Mothers should not nurse while receiving the drug.
• Safety and efficacy in children has not been studied; however, decreased bone formation was seen in rat long bones.
• Drug has not been studied in patients with hepatic dysfunction. Drug is extensively metabolized by the liver, so administration will probably increase plasma crizotinib levels.
• Use drug cautiously in patients with severe renal impairment (creatinine clearance < 30 mL/min).
Abbreviations: ALT = alanine aminotransferase; AST = aspartate aminotransferase; GGT = gamma-glutamyltransferase; LFTs: liver function tests; ms = millisecond
Financial Disclosure: The author has no significant financial interest or other relationship with the manufacturers of any products or providers of any service mentioned in this article.
