Tamoxifen with Phenytoin Interaction Details
Brand Names Associated with Tamoxifen
- Nolvadex®
- Soltamox®
- Tamoxifen
Brand Names Associated with Phenytoin
- Dilantin®
- Phenytek®
- Phenytoin
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Dec 18, 2023
Interaction Effect
Decreased exposure of tamoxifen and its active metabolite
Interaction Summary
Concomitant use of phenytoin and tamoxifen may decrease exposure of tamoxifen and its active metabolite, endoxifen. In a case report, 2 months following tamoxifen initiation, a 49-year-old woman, classified as a CYP2D6 extensive metabolizer with breast cancer, receiving stable doses of phenytoin experienced markedly low tamoxifen levels and 7-fold lower endoxifen levels compared with 195 extensive CYP2D6 metabolizer patients and 8 matched cohorts. Use of both agents is not recommended for extended periods unless therapeutic drug monitoring is done.
Severity
Major
Onset
Unspecified
Evidence
Probable
How To Manage Interaction
Concomitant use of phenytoin and tamoxifen may decrease exposure of tamoxifen and its active metabolite. Use of both agents is not recommended for extended periods unless therapeutic drug monitoring is done.
Mechanism Of Interaction
Unknown
Literature Reports
A) In a case report, a 49-year-old woman, classified as a CYP2D6 extensive metabolizer with breast cancer, receiving stable doses of phenytoin experienced markedly low tamoxifen and endoxifen (active tamoxifen metabolite) levels 2 months following tamoxifen initiation. The patient's endoxifen level of 4.72 nanomoles (nmol)/L was approximately 7-fold lower than mean endoxifen levels of 195 extensive CYP2D6 metabolizer patients (33 nmol/L) and 8 matched cohorts (27.6 nmol/L). The patient's tamoxifen level was 131.9 nmol/L compared with 286.9 nmol/L in the extensive metabolizers and 364.1 nmol/L in matched cohorts. Intermediate metabolites of tamoxifen, N-desmethyltamoxifen and 4-hydroxytamoxifen were also reduced, but to a lower extent. Phenytoin was not discontinued due to the instability of her seizure disorder, so rechallenge was not performed .
Tamoxifen Overview
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Tamoxifen is used to treat breast cancer that has spread to other parts of the body in men and women. It is used to treat early breast cancer in women who have already been treated with surgery, radiation, and/or chemotherapy. It is used to reduce the risk of developing a more serious type of breast cancer in women who have had ductal carcinoma in situ (DCIS; a type of breast cancer that does not spread outside of the milk duct where it forms) and who have been treated with surgery and radiation. It is used to reduce the risk of breast cancer in women who are at high risk for the disease due to their age, personal medical history, and family medical history.
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Tamoxifen is in a class of medications known as antiestrogens. It blocks the activity of estrogen (a female hormone) in the breast. This may stop the growth of some breast tumors that need estrogen to grow.
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.