Drug & supplement interaction

Folic Acid + Primidone

Primidone brand name: Mysoline.

Moderate Interaction
Medically reviewed by · Updated September 2026
The bottom line Moderate

Folic Acid has a moderate interaction with Primidone. Folic acid might have antagonistic effects on primidone and increase the risk for seizures.

Read the full interaction report
SeverityModerate
LikelihoodProbable
EvidenceB
What do Severity, Likelihood & Evidence mean?
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Interaction report

Folic Acid and Primidone

Here is the interaction we found between these two, with the evidence behind it.

Moderate

PRIMIDONE (Mysoline)

Folic acid might have antagonistic effects on primidone and increase the risk for seizures.
Folic acid can have direct convulsant activity in some people, reversing the effects of primidone and worsening seizure control. Monitor closely for increased seizure activity. Note that primidone also reduces serum folate levels.
Severity Moderate Likelihood Probable Evidence B

Interaction has not been documented in well-controlled studies, however, the interaction has been demonstrated in some small human studies or in controlled animal studies in conjunction with multiple case reports..

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the interesting back-and-forth between these two. Folic acid in higher supplement doses may work against primidone and make seizures harder to control. In some people, extra folate seems to have its own ability to lower the seizure threshold, which can chip away at the protection primidone gives you. So the worry isn't more side effects, it's the opposite, that your seizures could break through.

There's a second piece worth knowing: primidone itself tends to lower your folate levels over time, so some people genuinely do run low. That's exactly why you don't want to guess on your own. Don't start or stop folic acid without checking first. Loop in your doctor or pharmacist so they can pick a safe dose, watch your seizure activity, and check your folate if needed.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Froscher W, Maier V, Laage M, et al. Folate deficiency, anticonvulsant drugs, and psychiatric morbidity. Clin Neuropharmacol 1995;18:165-82. PubMed
  2. Reynolds EH. Neurological aspects of folate and vitamin B12 metabolism. Clin Haematol 1976;5:661-96. DOI
  3. Reynolds EH. Folate metabolism and anticonvulsant therapy. Proc R Soc Med 1974;67:68.

What These Ratings Mean

Every interaction above is graded three ways — here’s the key to each label.

Severity how clinically significant the interaction is
Major

Clinically significant. Avoid the combination, or use only under close professional supervision.

Moderate

Usually worth avoiding or managing — may need monitoring, a dose change, or timing apart.

Minor

Generally not serious. Be aware of it and mention it to your pharmacist.

Likelihood how strong the evidence is that the interaction actually happens in people
  • LikelyWell-controlled human studies have demonstrated the likely existence of this interaction.
  • ProbableInteraction has not been documented in well-controlled studies, however, the interaction has been demonstrated in some small human studies or in controlled animal studies in conjunction with multiple case reports.
  • PossibleInteraction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.
  • UnlikelyInteraction has been demonstrated in animal or in lab research but has been shown not to occur in humans.
Evidence the quality of the studies behind the rating (graded A–D)
  • AHigh-quality meta-analysis (quantitative systematic review).
  • BCase-control study.
  • CConsensus.
  • DAnecdotal evidence.

These ratings are for information only. Never start, stop, or otherwise change your therapy before speaking with your provider.

Keep it in perspective

Folic Acid Also Interacts With Other Medications

Folic Acid has 39 moderate known drug interactions in our database — the Primidone one above is one of them. If you take anything else, check it against the full list below.

Moderate 39 No known interaction 2,791 (incl. Primidone)
Taking anything else?

Check Another of Your Medications Against Folic Acid

Covers the 2,830 medications we’ve checked against Folic Acid. Pick one to open its full report.

From our Q&A

Questions About Folic Acid or Primidone

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Folic Acid or Primidone, not necessarily both, but if one is close to what you were about to ask it will usually go further than a database entry can:

Not quite your question? Ask our pharmacists directly — it is free, there is no account required, and answers usually come back within 24 hours.

Everything else you take

See Every Supplement That Interacts With Primidone

This page covers Folic Acid only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Primidone page lists 124 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: 1,4-butanediol (major), Activated Charcoal (major), Beer (major), Gamma-hydroxybutyrate (ghb) (major) and Kava (major).

By severity: 7 major · 101 moderate · 16 minor.

Open the Primidone interaction page

One more smart check

Taking Folic Acid as Part of a Dietary Supplement Product? Check It for Interactions

We hold 92 real supplement products containing Folic Acid, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Folic Acid. Your product may carry other ingredients that interact with Primidone too, on top of Folic Acid — and those would not show on this page. Find your product and we’ll check every ingredient on its label:

How much people look this up

Where Folic Acid and Primidone Sit Against Everything Else

Out of every supplement and medication people look up on HelloPharmacist, here is where these two land this week — and which way each has been moving.

Supplement Folic Acid
Top 25%

#198 of 1,452 supplements looked up here in the last 7 days

29 days ago today
Medication Primidone
Steady interest

#2,137 of 2,830 medications looked up here in the last 7 days

29 days ago today

Position among everything looked up on this site, not a measure of how commonly either one is used or how important it is. A supplement can climb this list because of a news story. It counts every request to the page, automated ones included, and nothing here identifies anyone.

Supplement

About Folic Acid

What is Folic Acid?

  • Preventing neural tube birth defects
  • Treating or preventing folate deficiency
  • Supporting pregnancy health
  • Certain types of anemia
  • Heart and blood vessel health

Folic acid is the man-made form of vitamin B9 and is one of the most well-studied supplements, especially for preventing serious birth defects when taken before and during early pregnancy. It is widely available, inexpensive, and generally safe at recommended doses, but you should still check with your pharmacist or doctor about the right amount for you.

Read the full Folic Acid monograph & all interactions
Medication

About Primidone

What Is Primidone Used For?

Brand name: Mysoline

Primidone tablets — sold as Mysoline or under the generic name primidone — are used to control seizures in people with epilepsy. Both Mysoline and primidone tablets are approved for grand mal (generalized tonic-clonic), psychomotor, and focal (partial) epileptic seizures.

Primidone can be used alone or alongside other anti-seizure medicines. It may also help control grand mal seizures that haven't responded well to other anticonvulsant treatments.

See full Primidone drug information
Keep checking

Other Drugs & Folic Acid

Browse every other medication we’ve checked against Folic Acid — both the ones with a known interaction and the ones without. Select any drug for the full detail.

0Major
39Moderate
0Minor
2,790No known interaction
39 Moderate 2,790 No interaction
Moderate

39 interactions

No interaction 2,790 drugs checked — show the list

We also checked Folic Acid against these medications and found no known interaction in our sources. Open any page to confirm.

Showing the 60 most looked-up of 2,790 medications checked with no known interaction — see the full Folic Acid list.

See the full Folic Acid interactions page
See every supplement checked against Primidone, ranked by severity
Sources

Sources & How We Checked

Interaction details are evidence-graded and sourced from the Natural Medicines database. The medication overview comes from MedlinePlus.

Content is written and reviewed by licensed HelloPharmacist pharmacists. See our data sources and editorial standards for how this information is built and checked.

Parts of this content are provided by the Therapeutic Research Center, LLC.

DISCLAIMER: Currently this does not check for drug-drug interactions. This is not an all-inclusive comprehensive list of potential interactions and is for informational purposes only. Not all interactions are known or well-reported in the scientific literature, and new interactions are continually being reported. Input is needed from a qualified healthcare provider including a pharmacist before starting any therapy. Application of clinical judgment is necessary.

© 2021 Therapeutic Research Center, LLC

Keep exploring
Folic Acid monograph › Uses, safety, and every drug interaction in one place Primidone supplement interactions › Every supplement checked against Primidone, ranked by severity Primidone drug information › The full plain-English guide to this medication Supplement interaction checker › Check any supplement or product against your medications Browse medications A–Z › Every drug we've checked against herbs & supplements Ask a pharmacist › Free, personal answer from our licensed team
Pharmacist Counseling Corner

Taking Folic Acid and Primidone Together: Common Questions

Can you take Folic Acid with Primidone?
There is a moderate interaction, so it may be acceptable with monitoring or timing changes — but check with your pharmacist first. Read the full details on this page and confirm with your pharmacist before combining them.
How serious is the Folic Acid and Primidone interaction?
We rate it Moderate. This combination may require monitoring, a dose adjustment, or separating the times you take each one. Consult your pharmacist before using them together.

Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy

Still Have a Question About Primidone and Folic Acid?

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This information is for education only and is not a substitute for professional medical advice. Always check with your pharmacist or doctor before starting, stopping, or combining supplements and medications.