crizotinib: prescribing and clinical use
Focused clinical detail for use alongside current product information, local policy and patient-specific assessment.
crizotinib: clinical details
Prescribing considerations
- Confirm ALK-positive or ROS1-positive status using an accurate, validated assay before initiation.
- Treatment requires specialist anticancer supervision.
- Review hepatic and renal function, cardiac history, QT-risk factors, electrolytes, pulmonary disease, gastrointestinal-perforation risk and interacting medicines.
- Moderate or severe hepatic impairment and severe renal impairment require product-specific adjustment and specialist review.
- Advise sun protection because photosensitivity can occur.
- Discuss fertility preservation where relevant.
Contraindications and cautions
- Hypersensitivity to crizotinib or any excipient.
- Use particular caution with pre-existing QT prolongation, bradycardia, relevant cardiac disease, electrolyte disturbance, pulmonary disease or gastrointestinal-perforation risk.
Monitoring
- Check ALT, AST and total bilirubin before and during treatment.
- Monitor full blood count with differential, particularly if abnormalities, fever or infection occur.
- Obtain ECGs and electrolytes in patients at risk of QT prolongation; monitor heart rate and blood pressure.
- Assess renal function before and during treatment.
- Investigate new pulmonary symptoms promptly and withhold treatment while suspected treatment-related pneumonitis is evaluated.
- Assess persistent or worsening visual disturbance; paediatric patients require ophthalmological examinations.
- Monitor for breathlessness, oedema and rapid weight gain indicating possible heart failure.
Clinical pharmacology
Crizotinib inhibits ALK, ROS1, c-Met and RON receptor tyrosine kinases. It is extensively metabolised in the liver, mainly through CYP3A4/5, and can inhibit CYP3A and several transporters.
Formulation and product differences
- The selected product is a hard capsule that must be swallowed whole and must not be crushed, dissolved or opened.
- The hard capsule is distinct from Xalkori granules supplied in capsules specifically designed to be opened; their instructions are not interchangeable.
- The selected hard capsule is essentially sodium-free.
crizotinib preparations and strengths
Capsule
Route: Oral
Strengths: 200 mg, 250 mg
crizotinib interactions
A full review of prescription, over-the-counter and herbal products is required before and during treatment.
Clarithromycin, azole antifungals and strong antiviral CYP3A inhibitors
These can increase crizotinib exposure and adverse effects; concurrent use should generally be avoided or closely managed by specialists.
Rifampicin, carbamazepine, phenytoin, phenobarbital and St John’s wort
These can substantially reduce crizotinib exposure and effectiveness, so concurrent use should be avoided.
Grapefruit and grapefruit juice
These may increase crizotinib concentrations and should be avoided.
Sources
These sources were used to prepare and review this medicine page.
Prepared and reviewed by the iatroX editorial team.