Drug interactions
Crizotinib + Fosphenytoin
Severity: Major
Crizotinib and Fosphenytoin: major interaction.
Last updated Sources: UK SmPC
For healthcare professionals — reference only. This page is a brief summary, not medical advice and not a substitute for official labeling or clinical judgement. Always verify before prescribing or dispensing.
Summary
Phenytoin, the active form of fosphenytoin, is a strong CYP3A4 inducer that may markedly lower crizotinib levels and reduce its efficacy. Crizotinib may in turn raise phenytoin levels, which have a narrow therapeutic range.
What this interaction means in plain words
Crizotinib and Fosphenytoin can interact in a way that may be serious. Using them together is sometimes necessary, but it needs a deliberate decision by the prescriber, a plan for monitoring, and clear advice on the warning signs to watch for.
Crizotinib belongs to Oncology; Fosphenytoin belongs to Central Nervous System.
Why it happens
Phenytoin induces CYP3A4, increasing crizotinib metabolism, while crizotinib inhibits CYP3A4 and may reduce phenytoin clearance.
What to do
Avoid strong CYP3A inducers and use a non-inducing anticonvulsant if possible. If combined, monitor phenytoin levels and tumor response.
What to ask your pharmacist
- Does the benefit of taking both outweigh the risk in my case?
- Do I need any blood test, ECG or other check while on both?
- What early warning signs should I watch for, and what should I do if they appear?
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References
- Xalkori 200 mg hard capsules - SmPC sections 4.3/4.5 (class statement: strong CYP3A inducers; "The concurrent use of strong CYP3A inducers, including but not limited to carbamazepine, phenobarbital, phenytoin, rifampicin and St. John's wort, should be avo") — electronic medicines compendium (UK SmPC)
Other interactions of Crizotinib
- Crizotinib + Flibanserin Contraindicated
- Crizotinib + Lomitapide Contraindicated
- Crizotinib + Lonafarnib Contraindicated
- Crizotinib + Pimozide Contraindicated
- Crizotinib + Saquinavir Contraindicated
- Crizotinib + Thioridazine Contraindicated
Other interactions of Fosphenytoin
- Dronedarone + Fosphenytoin Contraindicated
- Fosphenytoin + Ledipasvir-sofosbuvir Contraindicated
- Fosphenytoin + Lorlatinib Contraindicated
- Fosphenytoin + Lurasidone Contraindicated
- Fosphenytoin + Ranolazine Contraindicated
- Fosphenytoin + Sofosbuvir-velpatasvir-voxilaprevir Contraindicated
Frequently asked questions
Can I take Crizotinib with Fosphenytoin?
MediHelp rates the interaction as major. Crizotinib and Fosphenytoin can interact in a way that may be serious. Using them together is sometimes necessary, but it needs a deliberate decision by the prescriber, a plan for monitoring, and clear advice on the warning signs to watch for. Phenytoin, the active form of fosphenytoin, is a strong CYP3A4 inducer that may markedly lower crizotinib levels and reduce its efficacy. Crizotinib may in turn raise phenytoin levels, which have a narrow therapeutic range.
How serious is the interaction between Crizotinib and Fosphenytoin?
MediHelp rates it major, on a four-level scale (minor, moderate, major, contraindicated) based on published labels and references. What to do, in brief: Avoid strong CYP3A inducers and use a non-inducing anticonvulsant if possible. If combined, monitor phenytoin levels and tumor response.
What other medicines interact with Crizotinib?
MediHelp also lists interactions of Crizotinib with, for example, Flibanserin, Lomitapide, Lonafarnib. The full list is on the Crizotinib page.
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