Drug & supplement interaction

Vitamin B6 + 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 Vitamin B6 can interact with; the most serious is rated moderate. High doses of vitamin B6 may reduce the levels and clinical effects of phenobarbital.

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

Vitamin B6 and Phenobarbital, Phenytoin

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

Why Are There 2 Interactions?

Vitamin B6 interacts with whole categories of medication. Phenobarbital, Phenytoin falls into 2 of those categories, so it can interact with Vitamin B6 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
High doses of vitamin B6 may reduce the levels and clinical effects of phenobarbital.
Preliminary clinical evidence suggests that vitamin B6 200 mg daily can reduce plasma levels of phenobarbital, possibly by increasing metabolism. It is not known whether lower doses have any effect. Advise people taking phenobarbital to avoid high doses of vitamin B6.
Severity Moderate Likelihood Possible Evidence D

Interaction 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.

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

Here's the gist for your seizure medicine. Some early reports suggest that high-dose vitamin B6 (around 200 mg a day) may speed up how fast your body clears phenobarbital, which can pull its blood levels down. Lower seizure control is the worry, since these drugs (phenobarbital and phenytoin) need to stay in a fairly steady range to keep seizures from breaking through.

The evidence here is thin and mostly anecdotal, so I don't want to alarm you. The B6 you get from food and a normal multivitamin is very unlikely to cause trouble. It's the big standalone B6 supplements that raise the question. Since both of these medicines have a narrow safe window, please check with your pharmacist or doctor before starting any high-dose B6, and never adjust your seizure meds on your own.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Hansten PD, Horn JR. Drug Interactions Analysis and Management. Vancouver, WA: Applied Therapeutics Inc., 1997 and updates.
  2. Hansson O, Sillanpaa M. Pyridoxine and serum concentration of phenytoin and phenobarbitone. Lancet 1976;1:256. DOI
Moderate

PHENYTOIN (Dilantin)

2 of 2
High doses of vitamin B6 may reduce the levels and clinical effects of phenytoin.
Preliminary clinical evidence suggests that vitamin B6 200 mg daily can reduce plasma levels of phenytoin, possibly by increasing metabolism. It is not known whether lower doses have any effect. Advise people taking phenytoin to avoid high doses of vitamin B6.
Severity Moderate Likelihood Possible Evidence D

Interaction 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.

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

Here's the gist for your seizure medicine: taking large doses of vitamin B6 (around 200 mg a day in the limited reports we have) may speed up how fast your body clears phenytoin. That can pull your blood levels down, and lower levels can mean your medicine isn't doing its job, which raises the risk of breakthrough seizures.

Phenytoin is a narrow therapeutic index drug, meaning small shifts in its level can matter a lot, so this is worth taking seriously. The good news is the evidence here is thin (mostly anecdotal) and the everyday B6 you get from food or a regular multivitamin is very unlikely to cause trouble. It's the concentrated high-dose B6 supplements to be cautious with. Please check with your pharmacist or doctor before starting one.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Hansten PD, Horn JR. Drug Interactions Analysis and Management. Vancouver, WA: Applied Therapeutics Inc., 1997 and updates.
  2. Hansson O, Sillanpaa M. Pyridoxine and serum concentration of phenytoin and phenobarbitone. Lancet 1976;1:256. DOI

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

Vitamin B6 Also Interacts With Other Medications

Vitamin B6 has 204 moderate, 5 minor 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 204 Minor 5 No known interaction 2,621 (incl. Phenobarbital, Phenytoin)
Taking anything else?

Check Another of Your Medications Against Vitamin B6

Covers the 2,830 medications we’ve checked against Vitamin B6. Pick one to open its full report.

Everything else you take

See Every Supplement That Interacts With Phenobarbital, Phenytoin

This page covers Vitamin B6 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 Vitamin B6 as Part of a Dietary Supplement Product? Check It for Interactions

We hold 24,838 real supplement products containing Vitamin B6, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Vitamin B6. Your product may carry other ingredients that interact with Phenobarbital, Phenytoin too, on top of Vitamin B6 — 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 Vitamin B6 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 Vitamin B6
Top 10

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

29 days ago today
Medication Phenobarbital, Phenytoin
Top half

#1,272 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 Vitamin B6

What is Vitamin B6?

  • Morning sickness in pregnancy
  • Premenstrual syndrome (PMS)
  • Preventing or treating B6 deficiency
  • Nerve health and metabolism support
  • Nausea

Vitamin B6 (pyridoxine) is an essential water-soluble vitamin that your body needs for metabolism, brain function, and making red blood cells. It is best known for helping with pregnancy-related nausea and may help some people with PMS, but taking very high doses for long periods can cause nerve damage. Get most of your B6 from food, and check with a pharmacist or doctor before taking high-dose supplements.

Read the full Vitamin B6 monograph & all interactions
Keep checking

Other Drugs & Vitamin B6

Browse every other medication we’ve checked against Vitamin B6 — both the ones with a known interaction and the ones without. Select any drug for the full detail.

0Major
204Moderate
5Minor
2,620No known interaction
204 Moderate 5 Minor 2,620 No interaction
Moderate

204 interactions

Showing 60 of 204 moderate interactions — see all 204 on the Vitamin B6 page.

Minor

5 interactions

No interaction 2,620 drugs checked — show the list

We also checked Vitamin B6 against these medications and found no known interaction in our sources. Open any page to confirm.

Showing the 60 most looked-up of 2,620 medications checked with no known interaction — see the full Vitamin B6 list.

See the full Vitamin B6 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
Vitamin B6 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 Vitamin B6 and Phenobarbital, Phenytoin Together: Common Questions

Can you take Vitamin B6 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 Vitamin B6 and Phenobarbital, Phenytoin?
Phenobarbital, Phenytoin belongs to more than one drug category, and Vitamin B6 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 Vitamin B6 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 Vitamin B6?

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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.