Capecitabine with Levoleucovorin Interaction Details
Brand Names Associated with Capecitabine
- Capecitabine
- Xeloda®
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Dec 22, 2023
Interaction Effect
Increased concentrations of 5-fluorouracil and fluorouracil toxicity (granulocytopenia, anemia, thrombocytopenia, stomatitis, vomiting)
Interaction Summary
Leucovorin products increase the toxicity of fluorouracil. Do not initiate or continue therapy with Fusilev(R) and fluorouracil in patients with symptoms of gastrointestinal toxicity until those symptoms have resolved. Monitor patients with diarrhea until the diarrhea has resolved, as rapid deterioration leading to death may occur. Death from severe enterocolitis, diarrhea, and dehydration have been reported in elderly patients receiving levoleucovorin and fluorouracil . Capecitabine is a prodrug of 5'-deoxy-5-fluorouridine (5'-DFUR), which is converted to the active drug fluorouracil (5-FU) ; doxifluridine and tegafur are also prodrugs of fluorouracil. If coadministration is necessary, monitor for increased 5-fluorouracil cytotoxicity and consider dose adjustments if necessary.
Severity
Major
Onset
Unspecified
Evidence
Probable
How To Manage Interaction
Leucovorin products increase the toxicity of fluorouracil. Do not initiate or continue therapy with Fusilev and fluorouracil in patients with symptoms of gastrointestinal toxicity until those symptoms have resolved. Monitor patients with diarrhea until the diarrhea has resolved, as rapid deterioration leading to death may occur. Capecitabine is a prodrug of 5'-deoxy-5-fluorouridine (5'-DFUR), which is converted to the active drug fluorouracil (5-FU) ; doxifluridine and tegafur are also prodrugs of fluorouracil. If coadministration is necessary, monitor for increased 5-fluorouracil cytotoxicity and consider dose adjustments if necessary.
Mechanism Of Interaction
Formation of ternary structure with thymidylate synthase and fluorodeoxyuridine monophosphate (FdUMP) by levoleucovorin
Literature Reports
A) Thirty patients with advanced colorectal and gastric adenocarcinomas were treated with fluorouracil combined with high-dose folinic acid. The treatment used was based on biochemical and cell culture studies which have demonstrated that an excess of intracellular reduced folates is necessary to provide optimal inhibition of thymidylate synthetase and to increase the cytotoxic effect of fluorouracil. It was concluded that folinic acid at high doses (200 mg/m(2)) increases the effectiveness of fluorouracil given simultaneously .
Capecitabine Overview
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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.