Drug Action
Crizotinib is a tyrosine kinase inhibitor.
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Drug reference
Crizotinib is a tyrosine kinase inhibitor.
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Anaplastic lymphoma kinase (ALK)-positive advanced non-small cell lung cancer (specialist use only) | ROS1-positive advanced non-small cell lung cancer (specialist use only) ▶BY MOUTH ▶Adult: 250 mg twice daily, consult product literature for information on dose adjustments based on individual patient safety and tolerability
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History of diverticulitis (risk of gastro- intestinal perforation—discontinue treatment if gastrointestinal perforation occurs). metastases of gastrointestinal tract (risk of gastro-intestinal perforation—discontinue treatment if gastrointestinal perforation occurs). patients with susceptibility to QT- prolongation (including bradycardia, history of cardiac disease, concomitant use of drugs that prolong QT interval, and electrolyte disturbances)—periodic renal monitoring required. risk of gastro-intestinal perforation—discontinue treatment if gastrointestinal perforation occurs. vision disorders reported—consider full ophthalmological evaluation if vision disorder worsens or persists CAUTIONS, FURTHER INFORMATION ▶Fatal interstitial lung disease and pneumonitis Fatal interstitial lung disease and pneumonitis reported (monitor patients with pulmonary symptoms, withdraw treatment if suspected, and permanently discontinue treatment if diagnosed).
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NICE decisions ▶Crizotinib for untreated anaplastic lymphoma kinase-positive advanced non-small-cell lung cancer (September 2016) NICE TA406 Crizotinib is recommended, within its marketing authorisation, as an option for untreated anaplastic lymphoma kinase-positive advanced non-small-cell lung cancer in adults, only if the manufacturer provides it with the discount agreed in the patient access scheme. www.nice.org.uk/guidance/ta406 ▶Crizotinib for previously treated anaplastic lymphoma kinase- positive advanced non-small-cell lung cancer (December 2016) NICE TA422 Crizotinib is recommended, within its marketing authorisation, as an option for previously treated anaplastic lymphoma kinase-positive advanced non- small-cell lung cancer in adults, only if the manufacturer provides it with the discount agreed in the patient access scheme. www.nice.org.uk/guidance/ta422 ▶Crizotinib for treating ROS1-positive advanced non-small-cell lung cancer (July 2018) NICE TA529 Crizotinib is recommended for use within the Cancer Drugs Fund as an option for treating ROS1-positive advanced non-small-cell lung cancer (NSCLC) in adults, only if the conditions in the managed access agreement are followed. Patients whose treatment was started within the NHS before this guidance was published should have the option to continue treatment, without change to their funding arrangements, until they and their NHS clinician consider it appropriate to stop. www.nice.org.uk/guidance/ta529 Scottish Medicines Consortium (SMC) decisions SMC No. 1329/18 The Scottish Medicines Consortium has advised (June 2018) that crizotinib (Xalkori ®) is accepted for use within NHS Scotland for the treatment of adults with ROS1-positive advanced non-small cell lung cancer. This advice is contingent upon the continuing availability of the Patient Access Scheme in NHS Scotland or a list price that is equivalent or lower.
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RISKS OF INCORRECT DOSING OF ORAL ANTI-CANCER MEDICINES See Cytotoxic drugs p. 938. MHRA/CHM ADVICE (NOVEMBER 2015): RISK OF CARDIAC FAILURE Severe, sometimes fatal cases of cardiac failure have been reported in patients treated with crizotinib. The MHRA has issued the following advice: . Monitor all patients for signs and symptoms of heart failure (including dyspnoea, oedema, or rapid weight gain from fluid retention) . Consider reducing the dose, or interrupting or stopping treatment if symptoms of heart failure occur
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→Appendix 1: crizotinib
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▶Common or very common Anaemia. appetite decreased. arrhythmias. constipation. diarrhoea. dizziness. fatigue. gait abnormal. gastrointestinal discomfort. gastrointestinal disorders. heart failure. hepatic function abnormal. hypogonadism. hypophosphataemia. leucopenia. local swelling. movement disorders. muscle atrophy. muscle tone decreased. muscle weakness. nausea. nerve disorders. neuralgia. neurotoxicity. neutropenia. oedema. periorbital oedema. peroneal nerve palsy. pulmonary oedema. QT interval prolongation. renal abscess. renal cyst. respiratory disorders. sensation abnormal. skin reactions. syncope. taste altered. vision disorders. vitreous floater. vomiting ▶Uncommon Gastrointestinal perforation (including fatal cases). hepatic failure (including fatal cases). renal impairment SIDE-EFFECTS, FURTHER INFORMATION Consider reducing the dose, or interrupting or stopping treatment if symptoms of cardiac failure occur.
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Ensure effective contraception during and for at least 90 days after treatment.
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Avoid (toxicity in animal studies). See also Pregnancy and reproductive function in Cytotoxic drugs p. 938.
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Avoid—no information available.
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Manufacturer advises use with caution. Dose adjustments Manufacturer advises reduce dose in moderate to severe impairment—consult product literature.
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Dose adjustments Reduce dose to 250 mg once daily in severe impairment not requiring peritoneal dialysis or hemodialysis, may be increased to 200 mg twice daily after at least 4 weeks, based on individual assessment of safety and tolerability.
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Monitor liver function once a week during the first 2 months of treatment, then at least monthly thereafter and as clinically indicated. Monitor ECG and electrolytes (correct if abnormal) in all patients before starting treatment, then periodically and as clinically indicated thereafter. Monitor for signs and symptoms of treatment emergent bradycardia (including syncope, dizziness and hypotension)—monitor blood pressure and heart rate regularly.
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There can be variation in the licensing of different medicines containing the same drug. Capsule CAUTIONARY AND ADVISORY LABELS 25 ▶Xalkori (Pfizer Ltd) Crizotinib 200 mg Xalkori 200mg capsules | 60 capsule P £4,689.00 (Hospital only) Crizotinib 250 mg Xalkori 250mg capsules | 60 capsule P £4,689.00 (Hospital only)
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Counsel all patients on the early signs and symptoms of gastrointestinal perforation— advice to seek immediate medical attention. Driving and skilled tasks Symptomatic bradycardia (including syncope, dizziness and hypotension), vision disorder and fatigue may affect performance of skilled tasks (e.g. driving or operating machinery).
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250 mg twice daily, consult product literature for
First-line fragment. Read the complete Indications and Dose section above.
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