Afatinib with Fosphenytoin Interaction Details
Brand Names Associated with Afatinib
- Afatinib
- Gilotrif®
Brand Names Associated with Fosphenytoin
- Cerebyx®
- Fosphenytoin Injection
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Feb 26, 2024
Interaction Effect
Decreased afatinib exposure
Interaction Summary
Concurrent use of afatinib (a P-glycoprotein (P-gp) substrate) and a P-gp inducer may decrease the exposure of afatinib. When coadministration of afatinib with rifampicin (a P-gp inducer) was studied, pretreatment with rifampicin 600 mg daily for 7 days decreased afatinib AUC and Cmax by 34% and 22%, respectively, compared with oral administration of afatinib alone. Therefore, if chronic coadministration of afatinib and a P-gp inducer is necessary, increase the afatinib daily dose by 10 mg. If chronic concurrent P-gp inducer therapy is discontinued, resume the previous afatinib dose 2 to 3 days after discontinuation of the P-gp inducer[1].
Severity
Major
Onset
Unspecified
Evidence
Theoretical
How To Manage Interaction
Concurrent administration of afatinib (a P-glycoprotein (P-gp) substrate) and a P-gp inducer may decrease the exposure of afatinib. If chronic coadministration of a P-gp inducer is necessary with afatinib, increase the afatinib daily dose by 10 mg, as tolerated. Resume the previous afatinib dose 2 to 3 days after discontinuation of concurrent P-gp inducer[1].
Mechanism Of Interaction
Induction of P-glycoprotein-mediated efflux transport of afatinib
Literature Reports
A) In a pharmacokinetic evaluation, pretreatment with rifampicin 600 mg once daily for 7 days decreased the afatinib AUC(0 to infinity) and Cmax by 34% and 22%, respectively [1].
References
1 ) Product Information: GILOTRIF(TM) oral tablets, afatinib oral tablets. Boehringer Ingelheim Pharmaceuticals, Inc. (per FDA), Ridgefield, CT, 2013.
Afatinib Overview
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Afatinib is used to treat certain types of non-small cell lung cancer that has spread to nearby tissues or to other parts of the body. Afatinib 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.
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.