Metronidazole with Phenytoin Interaction Details
Brand Names Associated with Metronidazole
- Flagyl®
- Flagyl® 375
- Flagyl® ER
- Metronidazole
Brand Names Associated with Phenytoin
- Dilantin®
- Phenytek®
- Phenytoin
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Jan 04, 2024
Interaction Effect
An increased risk of phenytoin toxicity or reduced metroNIDAZOLE exposure
Interaction Summary
A pharmacokinetic study of concurrent use of metroNIDAZOLE and phenytoin resulted in a small decrease in phenytoin clearance and an increase in half-life. However, drugs which induce microsomal liver enzymes, such as phenytoin, may increase the elimination of metroNIDAZOLE, resulting in reduced plasma levels of metroNIDAZOLE .
Severity
Major
Onset
Delayed
Evidence
Theoretical
How To Manage Interaction
A pharmacokinetic study of concurrent use of metroNIDAZOLE and phenytoin resulted in a small decrease in phenytoin clearance and an increase in half-life. However, drugs which induce microsomal liver enzymes, such as phenytoin, may increase the elimination of metroNIDAZOLE, resulting in reduced plasma levels of metroNIDAZOLE .
Mechanism Of Interaction
Inhibition of phenytoin metabolism ; induction of CYP450 liver enzymes-mediated metabolism of metroNIDAZOLE
Literature Reports
A) Concomitant administration of oral metroNIDAZOLE and IV phenytoin was reported to result in prolongation of the half-life and reduction in the clearance of phenytoin. In this study, phenytoin 300 mg IV was given to volunteers who had been receiving oral metroNIDAZOLE 250 mg 3 times daily for 4 days. The total clearance of phenytoin was reduced from 24 to 20 mL/min with combined therapy, whereas the half-life was increased from 16 to 23 hours. It is speculated that effects on clearance are related to impairment of aromatic hydroxylation of phenytoin by metroNIDAZOLE. The kinetics of oral ALPRAZolam (metabolized by aliphatic hydroxylation) and intravenous LORazepam (metabolized by glucuronide conjugation) were unimpaired with concurrent metroNIDAZOLE in this study. As previous reports have indicated that metroNIDAZOLE can impair the clearance of warfarin (metabolized by aliphatic hydroxylation), it is speculated that there is no apparent way to predict which drugs will be influenced by metroNIDAZOLE administration, despite its capacity to impair the clearance of certain oxidatively metabolized drugs .
B) In a pharmacokinetic study in healthy subjects, a single oral dose of phenytoin 300 mg was administered before and after 5 days of metroNIDAZOLE 400 mg twice daily. There were no changes in phenytoin half-life, volume of distribution, or elimination .
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.
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.