Fedratinib with Fosphenytoin Interaction Details
Brand Names Associated with Fosphenytoin
- Cerebyx®
- Fosphenytoin Injection
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Dec 27, 2023
Interaction Effect
Increased phenytoin exposure, increased risk of phenytoin-related adverse events, reduced fedratinib exposure and reduced efficacy of fedratinib
Interaction Summary
Concomitant use of fedratinib with phenytoin may increase the concentrations of phenytoin and the risk of adverse reactions of phenytoin and may also decrease the concentrations of fedratinib resulting in reduced efficacy of fedratinib. In pharmacokinetic studies, separate coadministration with a strong or moderate CYP3A4 inducer reduced fedratinib exposure by 81% and 47%, respectively. In single-dose pharmacokinetic studies, fedratinib increased omeprazole (CYP2C19 substrate) AUC by 3-fold. Avoid coadministration of fedratinib with a strong or moderate inducer of CYP3A4. If coadministration is necessary, monitor for adverse reactions and adjust the dose of phenytoin.
Severity
Major
Onset
Unspecified
Evidence
Probable
How To Manage Interaction
Avoid coadministration of fedratinib with phenytoin (a strong CYP3A4 inducer and a CYP2C19 substrate). Concomitant use may increase the concentrations of phenytoin and the risk of adverse reactions of phenytoin and may also decrease the concentrations of fedratinib resulting in reduced efficacy of fedratinib. If coadministration is necessary, monitor for adverse reactions and adjust the dose of phenytoin.
Mechanism Of Interaction
Induction of CYP3A4-mediated metabolism of fedratinib; inhibition of CYP2C19-mediated metabolism of phenytoin
Literature Reports
A) Coadministration of rifampin 600 mg once daily (strong CYP3A4 inducer) with a single dose of fedratinib 500 mg decreased fedratinib AUC by about 81% .
B) Coadministration of a single dose of omeprazole 20 mg (CYP2C19 substrate) with fedratinib increased omeprazole AUC by 3-fold .
Fosphenytoin Overview
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Fosphenytoin injection is used to treat primary generalized tonic-clonic seizures (formerly known as a grand mal seizure; seizure that involves the entire body) and to treat and prevent seizures that may begin during or after surgery to the brain or nervous system. Fosphenytoin injection may also be used to control certain type of seizures in people who cannot take oral phenytoin. Fosphenytoin 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.