Drug & supplement interaction

Folic Acid + Phenytoin

Phenytoin brand names: Dilantin Kapseals, Dilantin, Di-Phen, Dilantin Infatabs, Phenytek, and others.

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

Folic Acid has a moderate interaction with Phenytoin. Folic acid might reduce serum levels of phenytoin in some patients.

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

Folic Acid and Phenytoin

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

Moderate

PHENYTOIN (Dilantin)

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 something a lot of folks don't realize about phenytoin and folic acid: they can pull on each other. Folic acid seems to act as a helper in breaking phenytoin down, so adding a supplement of 1 mg or more daily can lower your phenytoin blood levels in some people. Since phenytoin is a narrow therapeutic index drug, even a modest drop can matter, and there have been reports of more frequent seizures when folic acid was added to steady phenytoin therapy.

The flip side is that phenytoin can also lower your folate levels over time. So this isn't a reason to avoid folic acid, it's a reason to coordinate. If you and your doctor start both together and stay on them, the swings tend to even out. Please don't start, stop, or change either one on your own. Talk with your pharmacist or doctor so they can check a phenytoin level and pick the right folic acid dose for you.

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 Phenytoin 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. 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 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 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 Phenytoin

This page covers Folic Acid only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Phenytoin page lists 224 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 · 187 moderate · 28 minor.

From our pharmacist’s overview on the Phenytoin page

“Phenytoin (Dilantin) is a seizure medicine with a narrow therapeutic index, meaning small changes in its blood level can bring seizures back or tip over into toxicity, so I treat its supplement list with real seriousness. The biggest group, 78 ingredients, piles on sedation, and alcohol, kava, and GHB all rate major for exactly that re…”

Reviewed by 2 · Jul 18, 2026

Open the 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 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 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%

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

29 days ago today
Medication Phenytoin
Steady interest

#1,739 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 Phenytoin

What Is Phenytoin Used For?

Brand names: Dilantin Kapseals, Dilantin, Di-Phen, Dilantin Infatabs, Phenytek, Dilantin injection

Phenytoin is used to treat and prevent seizures. The specific types covered depend on the formulation. Oral extended-release capsules (including Phenytek), chewable tablets (including Dilantin Infatabs and Phenytoin Infatabs), and oral suspension (including Dilantin-125) are used for tonic-clonic (grand mal) and psychomotor (temporal lobe) seizures; most oral forms also cover prevention and treatment of seizures occurring during or after neurosurgery. Chewable tablets and some capsule formulations also cover complex partial seizures.

Parenteral (injectable) phenytoin sodium is used for generalized tonic-clonic status epilepticus (a prolonged, life-threatening seizure emergency) and for prevention and treatment of seizures during neurosurgery. The IV form can also substitute short-term for oral phenytoin when a patient cannot take it by mouth.

See full Phenytoin 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 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 Phenytoin supplement interactions › Every supplement checked against Phenytoin, ranked by severity Phenytoin 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 Phenytoin Together: Common Questions

Can you take Folic Acid with 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.
How serious is the Folic Acid and 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 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.