Metronidazole Vaginal and Primidone: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Primidone
Metronidazole Vaginal
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
What happens
An increased risk of QT interval prolongation, reduced metroNIDAZOLE exposure and reduced metroNIDAZOLE efficacy
Interaction Deep Dive
Concomitant PHENobarbital and metroNIDAZOLE therapy may result in enhanced metroNIDAZOLE hydroxylation and metabolism producing a shorter metroNIDAZOLE half-life3 resulting in reduced metroNIDAZOLE plasma levels 21. Also, avoid the concomitant use of PHENobarbital with other products with a known potential to prolong the QTc interval or products that may increase concentrations of PHENobarbital. PHENobarbital causes QTc interval prolongation. Concomitant use of PHENobarbital with other products that prolong the QTc interval like metroNIDAZOLE may result in a greater increase in the QTc interval and adverse reactions associated with QTc interval prolongation. If concomitant use of metroNIDAZOLE and PHENobarbital is unavoidable, monitor patients for increased risk of QTc interval prolongation 4.
Why it happens (mechanism)
Additive QT interval prolongation; increased hepatic metabolism
Literature reports
3 reports — tap to read
a) In a case study with six Crohn's disease patients, the concurrent use of metroNIDAZOLE and PHENobarbital resulted in decreased half-life (9.7 hr vs 7.5 hr) and AUC (79 vs 56 mg/L/hr) 53.
b) This is also demonstrated in a young female with recurrent episodes of vaginal trichomoniasis. Although the patient responded to metroNIDAZOLE therapy, symptomatic and microbiologic relapses occurred almost immediately following therapy withdrawal. The patient was also taking PHENobarbital (100 mg daily), a known stimulator of microsomal enzymes. The pharmacokinetics of metroNIDAZOLE were studied in this patient. The half-life (3.5 hours) was significantly reduced from normal (8 to 9 hours), and the hydroxy metabolite was present in higher than normal amounts. It was therefore concluded that PHENobarbital was inducing metroNIDAZOLE hydroxylation and the patient required twice the standard oral dose of metroNIDAZOLE (500 mg three times daily for seven days) to eradicate the organism 3.
c) A study provides further evidence that PHENobarbital can significantly increase the metabolism of metroNIDAZOLE, thus reducing the drug's half-life. It is reported that complete cure in children with epilepsy treated with PHENobarbital and giardiasis occurred only when three times the recommended dosage of metroNIDAZOLE was administered. Upward dosage adjustments are indicated in children receiving PHENobarbital who are treated with metroNIDAZOLE for giardiasis 6.
Common questions
Can I take Metronidazole Vaginal and Primidone together?
An increased risk of QT interval prolongation, reduced metroNIDAZOLE exposure and reduced metroNIDAZOLE efficacy Always confirm with your pharmacist or prescriber before making any change.
How serious is the Metronidazole Vaginal and Primidone interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "delayed". Effects tend to build up gradually over days to weeks.
How strong is the evidence for this interaction?
The evidence is graded "probable". Good supporting evidence, though not definitively proven.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Metronidazole Vaginal or Primidone need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there a safer alternative to one of these medications for me?
References (6)
- Product Information: LIKMEZ(TM) oral suspension, metronidazole oral suspension. Saptalis Pharmaceuticals LLC (per FDA), Hauppauge, NY, 2023. DailyMed
- Product Information: FLAGYL ER(R) oral extended-release tablets, metronidazole oral extended-release tablets. Pfizer (per FDA), New York, NY, 2023. DailyMed
- Mead PB, Gibson M, Schentag JJ, et al: Possible alteration of metronidazole metabolism by phenobarbital (letter). N Engl J Med 1982; 306:1490. DOI
- Product Information: SEZABY(TM) intravenous injection, phenobarbital sodium intravenous injection. Sun Pharmaceutical Industries Inc (per manufacturer), Cranbury, NJ, 2022. DailyMed
- Eradiri O, Jamali F, & Thomson AB: Interaction of metronidazole with phenobarbital, cimetidine, prednisone, and sulfasalazine in Crohn's disease. Biopharm Drug Dispos 1988; 9:219-227. PubMed
- Gupte S: Phenobarbital and metabolism of metronidazole. N Engl J Med 1983; 308:529. DOI
Keep reading about Primidone
Keep reading about Metronidazole Vaginal
These medications also interact with supplements
Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:
major · moderate · minor — check everything you take with our drug–supplement interaction checker.
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