Crizotinib with Phenytoin Interaction Details
Brand Names Associated with Crizotinib
- Crizotinib
- Xalkori®
Brand Names Associated with Phenytoin
- Dilantin®
- Phenytek®
- Phenytoin
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Dec 20, 2023
Interaction Effect
Decreased crizotinib plasma concentrations
Interaction Summary
The concomitant administration of crizotinib (a CYP3A4/5 substrate) with a strong CYP3A inducer (such as phenytoin) may result in decreased crizotinib plasma concentrations and should be avoided. Although the interaction between crizotinib and phenytoin has not been evaluated, the coadministration of crizotinib with rifampin (another strong CYP3A inducer) decreased crizotinib AUC and Cmax by 82% and 69%, respectively, compared with crizotinib alone. If coadministration of crizotinib with phenytoin is required, monitoring and dose adjustment may be warranted.
Severity
Major
Onset
Unspecified
Evidence
Theoretical
How To Manage Interaction
The concomitant use of crizotinib with phenytoin may result in reduced crizotinib exposure and should be avoided. If coadministration of crizotinib with phenytoin is required, monitoring and dose adjustment may be warranted.
Mechanism Of Interaction
Induction of CYP3A4-mediated crizotinib metabolism by phenytoin
Literature Reports
A) The coadministration of a single 250-mg oral dose of crizotinib with rifampin (a strong CYP3A inducer) 600 mg once daily decreased crizotinib AUC and Cmax by 82% and 69%, respectively, compared with crizotinib alone. The effect of CYP3A inducers on steady-state crizotinib exposure has not been studied .
Crizotinib Overview
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Crizotinib is used to treat certain types of non-small cell lung cancer (NSCLC) that has spread to nearby tissues or to other parts of the body. It is also used to treat a certain type of anaplastic large cell lymphoma (ALCL) that has returned or is unresponsive to other treatment(s) in certain adults and children 1 year of age and older. Crizotinib is also used to treat a certain type of inflammatory myofibroblastic tumor (IMT; type of cancer that occurs in mucosal tissues usually in the abdominal area, involving the lungs, bladder, stomach, uterus, liver, or intestines) that cannot be treated with surgery or that has not improved or has come back after previous treatment(s) in adults and children 1 year of age and older. Crizotinib is in a class of medications called kinase inhibitors. It works by blocking the action of a certain naturally occurring substance that may be needed to help cancer cells multiply.
Phenytoin Overview
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Phenytoin is used to control certain type of seizures, and to treat and prevent seizures that may begin during or after surgery to the brain or nervous system. Phenytoin is in a class of medications called anticonvulsants. It works by decreasing abnormal electrical activity in the brain.
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Definitions
Severity Categories
Contraindicated
These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.
Major
This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.
Moderate
This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.
Minor
While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.
Onset
Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.
Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.
Evidence
Level of documentation of the interaction.
Established: The interaction is documented and substantiated in peer-reviewed medical literature.
Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.
How To Manage The Interaction
Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.
It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.
Mechanism Of Interaction
The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.
Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.
Where Does Our Information Come From?
Information for our drug interactions is compiled from several drug compendia, including:
The prescribing information for each drug, as published on DailyMED, is also used.
Individual drug-drug interaction detail pages contain references specific to that interaction. You can click on the reference number within brackets '[]' to see what reference was utilized.
The information posted is fact-checked by HelloPharmacist clinicians and reviewed quarterly.