Drug & supplement interaction

Folic Acid + Phenobarbital, Phenytoin

Phenobarbital, Phenytoin brand name: Dilantin with PB.

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

Phenobarbital, Phenytoin falls into 2 drug categories that Folic Acid can interact with; the most serious is rated moderate. Folic acid might have antagonistic effects on phenobarbital and increase the risk for seizures.

Read the full interaction report
SeverityModerate
LikelihoodProbable
Interactions2
EvidenceB
What do Severity, Likelihood & Evidence mean?
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Interaction report

Folic Acid and Phenobarbital, Phenytoin

These two interact in 2 distinct ways. Each one is explained separately below.

Why Are There 2 Interactions?

Folic Acid interacts with whole categories of medication. Phenobarbital, Phenytoin falls into 2 of those categories, so it can interact with Folic Acid in 2 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

PHENOBARBITAL (Luminal)

1 of 2
Folic acid might have antagonistic effects on phenobarbital and increase the risk for seizures.
Folic acid can have direct convulsant activity in some people, reversing the effects of phenobarbital and worsening seizure control. Monitor closely for increased seizure activity.
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 gist with folic acid and your seizure medicines, phenobarbital and phenytoin. Folic acid isn't a prodrug situation here. The concern is that folic acid can sometimes work against these drugs and may even nudge the brain toward seizure activity in some people. In plain terms, your medicine could become a little less effective at holding seizures back, so the worry is more breakthrough seizures, not extra side effects.

This is a moderate, fairly likely interaction, but the evidence is modest. Small amounts of folate from food and a regular prenatal or daily multivitamin usually aren't the issue. Higher-dose folic acid supplements are where I'd be more careful. Please don't start, stop, or change anything on your own. Loop in your doctor or pharmacist first so they can check your dose and watch your seizure control.

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.
Moderate

PHENYTOIN (Dilantin)

2 of 2
Folic acid might reduce serum levels of phenytoin in some patients.
Folic acid may be a cofactor in phenytoin metabolism. Folic acid, in doses of 1 mg daily or more, can reduce serum levels of phenytoin in some patients. Increases in seizure frequency have been reported. If folic acid supplements are added to established phenytoin therapy, monitor serum phenytoin levels closely. If phenytoin and folic acid are started at the same time and continued together, adverse changes in phenytoin pharmacokinetics are avoided. Note that phenytoin 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 thing to know if you take phenytoin (Dilantin) and want to add folic acid: folic acid appears to act as a helper in how your body processes phenytoin. When you take 1 mg or more of folic acid daily, it can actually nudge your phenytoin levels down in some people. Lower phenytoin means less seizure protection, and a few patients have had more breakthrough seizures because of this.

Phenytoin is a narrow-therapeutic-index drug, so even modest changes in its level matter. Interestingly, phenytoin also lowers your folate over time, so some folks genuinely need a little folic acid. The safest move is to talk with your pharmacist or doctor before starting it. If they do add it, they'll usually want to check your phenytoin blood level to keep you in the safe zone.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Lewis DP, Van Dyke DC, Willhite LA, et al. Phenytoin-folic acid interaction. Ann Pharmacother 1995;29:726-35. PubMed
  2. Berg MJ, Stumbo PJ, Chenard CA, et al. Folic acid improves phenytoin pharmacokinetics. J Am Diet Assoc 1995;95:352-6. PubMed
  3. Berg MJ, Fincham RW, Ebert BE, et al. Phenytoin pharmacokinetics: Before and after folic acid administration. Epilepsia 1992;33:712-20. PubMed
  4. Shafer RB, Nuttall FQ. Calcium and folic acid absorption in patients taking anticonvulsant drugs. J Clin Endocrinol Metab 1975;41:1125-9. PubMed
  5. Segal S, Kaminski S. Drug-nutrient interactions. American Druggist 1996 Jul;42-8.
  6. Lambie DG, Johnson RH. Drugs and folate metabolism. Drugs 1985;30:145-55. PubMed

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 Phenobarbital, Phenytoin one above is among them. If you take anything else, check it against the full list below.

Moderate 39 No known interaction 2,791 (incl. Phenobarbital, Phenytoin)
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 Phenobarbital, Phenytoin

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 Phenobarbital, Phenytoin, 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 Phenobarbital, Phenytoin

This page covers Folic Acid only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Phenobarbital, Phenytoin page lists 229 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: 9 major · 192 moderate · 28 minor.

From our pharmacist’s overview on the Phenobarbital, Phenytoin page

“If your seizure medicine is the phenobarbital and phenytoin combination (Dilantin with PB), read this list carefully before you add any supplement. Nine of the 229 entries rate major, and most of the risk runs through two channels.”

Reviewed by 2 · Jul 18, 2026

Open the Phenobarbital, Phenytoin 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 Phenobarbital, Phenytoin 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 Phenobarbital, Phenytoin 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%

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

29 days ago today
Medication Phenobarbital, Phenytoin
Top half

#1,270 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
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 Phenobarbital, Phenytoin, 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 Phenobarbital, Phenytoin supplement interactions › Every supplement checked against Phenobarbital, Phenytoin, ranked by severity 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 Phenobarbital, Phenytoin Together: Common Questions

Can you take Folic Acid with Phenobarbital, Phenytoin?
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.
Why are there 2 interactions listed for Folic Acid and Phenobarbital, Phenytoin?
Phenobarbital, Phenytoin belongs to more than one drug category, and Folic Acid interacts with each of those categories a little differently. We list every one so nothing is missed — your overall risk is driven by the most serious of them.
How serious is the Folic Acid and Phenobarbital, Phenytoin 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 Phenobarbital, Phenytoin 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.