Metronidazole with Doxifluridine Interaction Details
Brand Names Associated with Metronidazole
- Flagyl®
- Flagyl® 375
- Flagyl® ER
- Metronidazole
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Jan 04, 2024
Interaction Effect
Increased exposure of 5-fluorouracil
Interaction Summary
Use caution with concomitant use of 5-fluorouracil prodrugs (capecitabine, doxifluridine, fluorouracil, tegafur) with nitroimidazoles, including metronidazole and misonidazole. Nitroimidazoles may decrease the clearance of 5-fluorouracil, thereby increasing 5-fluorouracil exposure. Co-administered metronidazole significantly reduced fluorouracil clearance resulting in more severe fluorouracil side effects, without enhanced therapeutic results . If coadministration is required of a nitroimidazole with fluorouracil or one of its inactive prodrugs, monitor for fluorouracil toxicity (granulocytopenia, anemia, thrombocytopenia, stomatitis, vomiting) .
Severity
Major
Onset
Unspecified
Evidence
Theoretical
How To Manage Interaction
Use caution with concomitant use of 5-fluorouracil prodrugs (capecitabine, doxifluridine, fluorouracil, tegafur) with nitroimidazoles, including metronidazole and misonidazole, as coadministration may result in increased exposure of 5-fluorouracil. If coadministration of a nitroimidazole with fluorouracil or one of its inactive prodrugs is required, monitor for fluorouracil toxicity (granulocytopenia, anemia, thrombocytopenia, stomatitis, vomiting) .
Mechanism Of Interaction
Decreased clearance of 5-fluorouracil
Literature Reports
A) A total of 27 patients with metastatic colorectal cancer received daily metronidazole 750 mg/m(2) followed in an hour by fluorouracil 600 mg/m(2), both drugs given intravenously, for five consecutive days. This treatment was repeated every four weeks until prohibitive toxicity or disease progression occurred. The pharmacokinetics of fluorouracil, measured in 10 patients, showed a reduction in fluorouracil clearance of 26.9%, and increases of 34% and 38%, respectively, in the area under the concentration-time curve (AUC) and half-life of fluorouracil during combined therapy. The incidence of toxic effects of the metronidazole-fluorouracil regimen included granulocytopenia (74%), anemia (41%), thrombocytopenia (19%), severe stomatitis and oral ulceration (34%), intractable nausea and vomiting (22%), and peripheral neuropathy with paresthesia and weakness (7%). In vitro, metronidazole combined with fluorouracil did not enhance antitumor activity over 5-FU alone .
Metronidazole Overview
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Metronidazole capsules and tablets are used to treat infections of the reproductive system, gastrointestinal (GI) tract, skin, heart, bone, joint, lung, blood, nervous system, and other areas of the body. Metronidazole capsules and tablets are also used to treat sexually transmitted diseases (STDs). Metronidazole extended-release (long-acting) tablets are used to treat bacterial vaginosis (an infection caused by too much of certain types of harmful bacteria in the vagina) in women. Metronidazole is in a class of medications called nitroimidazole antimicrobials. It works by stopping the growth of bacteria.
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Antibiotics will not work for colds, flu, or other viral infections. Using antibiotics when they are not needed increases your risk of getting an infection later that resists antibiotic treatment.
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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.