Crizotinib

Crizotinib is a prescription medication used for the treatment of non-small cell lung cancer, inflammatory myofibroblastic tumors, and anaplastic large cell lymphoma.

• Crizotinib is available under various brand names: Xalkori

Common side effects of Crizotinib include:

• nausea,
• vomiting,
• decreased appetite,
• diarrhea,
• constipation,
• abnormal liver function tests,
• swelling in the hands, feet, and eyes,
• numbness or tingling in the hands and feet,
• muscle weakness,
• trouble walking,
• stuffy nose,
• sneezing,
• sore throat,
• dizziness,
• tiredness, and
• vision problems.

Serious side effects of Crizotinib include:

• hives,
• difficulty breathing,
• swelling of the face, lips, tongue, or throat,
• increased sensitivity to light,
• seeing flashes of light or “floaters”,
• blurred vision,
• double vision,
• vision loss,
• fast or pounding heartbeats,
• fluttering in the chest,
• shortness of breath,
• sudden dizziness,
• very slow heartbeats,
• lightheadedness,
• sudden chest pain or discomfort,
• wheezing,
• dry cough,
• cough with mucus,
• fever,
• swollen gums,
• painful mouth sores,
• pain when swallowing,
• cold or flu symptoms,
• easy bruising,
• unusual bleeding (nosebleeds, bleeding gums),
• nausea,
• upper stomach pain,
• itching,
• tiredness,
• loss of appetite,
• dark urine,
• clay-colored stools, and
• yellowing of the skin or eyes (jaundice)

Rare side effects of Crizotinib include:

• none

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, loss of coordination, feeling unsteady, very stiff muscles, high fever, profuse sweating, or tremors;
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult and pediatric dosage

Capsules

• 200 mg
• 250 mg

Non-Small Cell Lung Cancer

Adult dosage

• 250 mg orally twice daily

Inflammatory Myofibroblastic tumors

Adult dosage

• 250 mg orally twice daily

Pediatric dosage

• Aged below 1 year: Safety and efficacy not established
• Aged above 1 year
• 280 mg/m2 orally twice daily
• Recommended dosage based on body surface area (BSA)
• less than 0.60 m2: Safety and efficacy not established
• 0.6-0.8 m2: 200 mg orally twice daily
• 0.81-1.16 m2: 250 mg orally twice daily
• 1.17-1.51 m2: 400 mg orally twice daily
• 1.52-1.69 m2: 450 mg orally twice daily
• Above 1.70 m2: 500 mg orally twice daily
• Continue until disease progression or unacceptable toxicity

Anaplastic Large Cell Lymphoma

Pediatric dosage

• 280 mg/m2 orally twice daily
• Continue until disease progression or unacceptable toxicity
• Recommended dosage based on BSA
• Less than 0.6 m2: Dose not established
• 0.6-0.8 m2: 200 mg orally twice daily
• 0.81-1.16 m2: 250 mg orally twice daily
• 1.17-1.51 m2: 400 mg orally twice daily
• 1.52-1.69 m2: 450 mg orally twice daily
• More than 1.70 m2: 500 mg orally twice daily

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Crizotinib has severe interactions with the following drugs:
  • dronedarone
  • flibanserin
  • lefamulin
  • lomitapide
  • lonafarnib
  • pimozide
  • posaconazole
  • saquinavir
  • thioridazine
• Crizotinib has serious interactions with at least 122 other drugs.
• Crizotinib has moderate interactions with at least 306 other drugs.
• Crizotinib has no noted minor interactions with the following drugs:
  • entecavir
  • estradiol vaginal
  • lapatinib
  • rilpivirine

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all your products. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your health care professional or doctor for additional medical advice, or if you have health questions or concerns.

Contraindications

• None

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Crizotinib?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Crizotinib?”

Cautions

• Severe, including fatal, treatment-related ILD/pneumonitis reported; monitor for pulmonary symptoms indicative of pneumonitis; generally occurred within 3 months after initiation
• Drug-induced hepatoxicity reported; monitor liver function tests every 2 weeks during the first 2 months of treatment, then monthly, and as clinically needed; more frequently in patients who develop increased transaminases; withhold, reduce dose, or permanently discontinue for hepatotoxicity as recommended
• Symptomatic bradycardia reported, including syncope; monitor HR and blood pressure regularly
• Caution when driving or operating machinery because of vision disorder, dizziness, or fatigue associated with treatment
• May cause fetal harm when administered to pregnant females
• Interstitial lung disease (ILD)/Pneumonitis reported; permanently discontinue in patients with ILD/pneumonitis
• Visual loss
• Visual field defect with vision loss reported; optic atrophy and optic nerve disorder have been reported as potential causes of vision loss; most common visual symptoms were blurred vision and visual impairment in ALCL patients
• There is insufficient information to characterize risks of resumption of drug in patients who develop visual symptoms or visual loss; a decision to resume therapy should consider potential benefits versus risks to patient
• Perform an ophthalmological evaluation consisting of best corrected visual acuity, retinal photographs, visual fields, optical coherence tomography (OCT), and other evaluations as appropriate for new onset of visual loss and for other visual symptoms as clinically warranted
• Permanently discontinue therapy for Grade 3 or 4 ocular disorders or severe visual loss (best-corrected vision less than 20/200 in one or both eyes) unless another cause is identified
• Gastrointestinal toxicity
  • Severe gastrointestinal toxicities (eg, diarrhea, nausea, vomiting, stomatitis) can occur in ALCL patients; provide standard antiemetic and antidiarrheal agents for gastrointestinal toxicities in patients with ALCL; antiemetics are recommended prior to and during treatment with drug to prevent nausea and vomiting; if patients develop Grade 3 nausea lasting 3 days or Grade 3 or 4 diarrhea or vomiting despite maximum medical therapy, withhold therapy until resolved, and then resume at next lower dose level; consider supportive care such as hydration, electrolyte supplementation, and nutritional support as clinically indicated
• QT interval prolongation
  • QTc prolongation reported
  • Avoid use with congenital long QT syndrome
  • Consider periodic ECG and electrolyte monitoring in patients with congestive heart failure, bradyarrhythmias, electrolyte abnormalities, or taking medications known to prolong QT interval
• Drug interaction overview
• CYP3A4/5 and P-gp substrate; CYP3A4 inhibitor
  • Strong or moderate CYP3A inhibitors
  • Avoid coadministration
  • Strong CYP3A inhibitors increases crizotinib plasma concentration and risk of adverse reactions of crizotinib
  • If unavoidable, reduce crizotinib dosage
  • Avoid grapefruit or grapefruit
  • Use caution with concomitant use of moderate CYP3A4 inhibitors
• Strong CYP3A inducers
  • Avoid coadministration
  • Strong CYP3A inducers decreases crizotinib plasma concentrations and efficacy of crizotinib
• CYP3A substrates
  • Avoid coadministration
  • Crizotinib may increases plasma concentrations and rise of adverse effects of CYP3A substrates
  • If unavoidable, decrease CYP3A substrate dosage according to prescribing information
• Drugs that prolong the QT interval
  • Avoid coadministration
• Drugs that cause bradycardia
  • Avoid coadministration
  • Drugs include beta-blockers, nondihydropyridine calcium channel blockers, clonidine, and digoxin

Pregnancy & Lactation

• Based on its mechanism of action, can cause fetal harm when administered to a pregnant woman
• Verify pregnancy status of females of reproductive potential before initiation
• Contraception
  • Females of reproductive potential: Use effective contraception during treatment and for at least 45 days following the final dose
  • Males with female partners of reproductive potential: Use condoms during treatment and for at least 90 days after final dose
• Infertility
  • Based on reproductive organ findings in animals, reduced fertility in females and males of reproductive potential may occur
  • Unknown whether these effects on fertility are reversible
• Lactation
  • No information available on drug presence in human milk, effects on the breastfed infants, or effects on milk production
  • Do not breastfeed during treatment and for 45 days after final dose