Metronidazole with Milk Thistle 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
Reduced metronidazole and active metabolite exposure
Interaction Summary
The concomitant administration of silymarin (a flavonoid extract of milk thistle) and metronidazole significantly accelerated the total body clearance of metronidazole and significantly reduced metronidazole exposure, in a pharmacokinetic study of healthy volunteers.
Severity
Moderate
Onset
Rapid
Evidence
Probable
How To Manage Interaction
The concurrent use of silymarin (an active flavonoid of milk thistle) and metronidazole is not recommended. If concomitant use is necessary, the dose of metronidazole may need to be increased.
Mechanism Of Interaction
Silymarin-mediated induction of intestinal p-glycoprotein clearance of metronidazole
Literature Reports
A) The concomitant administration of silymarin (a flavonoid extract of milk thistle) and metronidazole significantly accelerated the total body clearance of metronidazole and significantly reduced metronidazole exposure. In a pharmacokinetic, 2-phase study, healthy volunteers (n=12) first received a 3-day oral regimen of metronidazole 400 milligrams (mg) 3 times daily, followed by a single dose of metronidazole 400 mg on day four, after which blood and urine samples were analyzed over the next 48 hours. After a 4-day washout period, each subject received a 9-day regimen of oral silymarin 140 mg daily, with metronidazole 400 mg given 3 times daily concurrently for days 7 through 9. On day 10, metronidazole 400 mg was given, after which blood and urine samples were again analyzed over 48 hours. Compared with metronidazole alone, concomitant administration of silymarin with metronidazole significantly accelerated the mean total body clearance of metronidazole (by 42%, p less than 0.05) and its active metabolite hydroxyl-metronidazole (by 47%, p less than 0.001). Metronidazole mean area under the concentration-time curve (AUC; 0-48 hours) and mean maximum plasma concentration (Cmax) were both significantly reduced with concurrent silymarin treatment (from 230.58 to 166.22 mg x hour/milliliter (mg x hr/mL) and from 16.91 to 12.00 mg/mL respectively; p less than 0.0001, both measures); similar reductions occurred in AUC (0-48 hours; from 125.86 to 89.37 mg x hr/mL) and Cmax (from 4.56 to 3.65 mg/mL) (p less than 0.0001 and 0.01, respectively) for the active metabolite hydroxyl-metronidazole. The half-life of hydroxyl-metronidazole also declined significantly in the presence of silymarin (by 33%, p less than 0.01). The study authors suggest that silymarin induction of intestinal p-glycoprotein serves as the probable mechanism of action .
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.