Capecitabine with Brivudine Interaction Details
Brand Names Associated with Capecitabine
- Capecitabine
- Xeloda®
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Dec 22, 2023
Interaction Effect
Increased exposure of 5-fluorouracil (active moiety of capecitabine)
Interaction Summary
Concomitant use of capecitabine (prodrug of 5-fluorouracil, which is a DPD substrate) with brivudine, an irreversible DPD inhibitor, may result in increased exposure of 5-fluorouracil and enhanced toxicity. It has been reported that coadministration may result in a 5- to 15-fold increase in exposure of 5-fluorouracil . Two case reports, including 1 fatality have been reported . To avoid significant toxicity with potentially fatal outcomes, 4 weeks should elapse after the last dose of brivudine before initiating a fluoropyrimidine , such as capecitabine.
Severity
Major
Onset
Unspecified
Evidence
Probable
How To Manage Interaction
To avoid significant fluoropyrimidine-related toxicity with potentially fatal outcomes, 4 weeks should elapse after the last dose of brivudine before initiating a fluoropyrimidine, such as capecitabine. Concomitant use of capecitabine (prodrug of 5-fluorouracil, which is a dihydropyrimidine dehydrogenase (DPD) substrate) with brivudine, an irreversible DPD inhibitor, may result in increased exposure of 5-fluorouracil and enhanced toxicity .
Mechanism Of Interaction
Inhibition of dihydropyrimidine dehydrogenase (DPD)-mediated 5-fluorouracil metabolism (active moiety of capecitabine) by brivudine
Literature Reports
A) Concomitant use of capecitabine with brivudine resulted in a fatal reaction in an 80-year-old female with colorectal cancer. The patient was receiving capecitabine 3 g daily for 14 days followed by 1 drug-free week. Three months later, administration of 2 brivudine 125-mg doses resulted in rash, edema of lips, and inflammation of oral mucosa. Brivudine was discontinued, however she continued to deteriorate with exanthema, mucositis, vomiting, and diarrhea. Despite discontinuation of capecitabine and medical management, the patient died 3 weeks following onset of symptoms .
B) A 66-year-old woman with metastatic breast cancer, treated with 7 cycles of capecitabine experienced vesicular cutaneous lesions that were typical of herpes zoster infection. Brivudine was initiated at 125 mg/day for 7 days. Four days later, the patient complained of oral and pharyngeal grade 2 mucositis, and grade 2 hand-foot syndrome. Mucositis worsened and caused serious ulcerations, and medulla aplasia developed requiring hospitalization and administration of platelets, filgrastim, and parenteral nutrition .
Capecitabine Overview
-
Capecitabine is used in combination with other medications to treat breast cancer that has come back after treatment with other medications. It is also used alone to treat breast cancer that has not improved after treatment with other medications. Capecitabine is also used to treat colon or rectal cancer (cancer that begins in the large intestine) that has gotten worse or spread to other parts of the body. It is also used to prevent colon cancer from spreading in people who have had surgery to remove the tumor. Capecitabine is in a class of medications called antimetabolites. It works by stopping or slowing the growth of cancer cells.
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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.