Drug & supplement interaction

Boneset + 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

Boneset has a moderate interaction with Phenytoin. Boneset belongs to the genus Eupatorium, and many species of this genus contain hepatotoxic pyrrolizidine alkaloids (PAs).

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

Boneset and Phenytoin

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

Moderate

CYTOCHROME P450 3A4 (CYP3A4) INDUCERS

Why this applies to Phenytoin

Phenytoin falls under CYTOCHROME P450 3A4 (CYP3A4) INDUCERS — the group Boneset interacts with.

Boneset belongs to the genus Eupatorium, and many species of this genus contain hepatotoxic pyrrolizidine alkaloids (PAs). Hepatotoxic PAs are substrates of cytochrome P450 3A4 (CYP3A4). Theoretically, drugs that induce CYP3A4 might increase the conversion of PAs to toxic metabolites. Some drugs that induce CYP3A4 include carbamazepine (Tegretol), phenobarbital, phenytoin (Dilantin), rifampin, rifabutin (Mycobutin), and others.
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 twist with this pairing: it's not that boneset changes how your phenytoin (Dilantin) works. It's the other way around. Phenytoin revs up a liver enzyme called CYP3A4, and that same enzyme can turn boneset's natural compounds (pyrrolizidine alkaloids) into byproducts that may be hard on the liver. So taking them together could, in theory, raise the risk of liver irritation.

I want to be honest that this concern is theoretical, based on how these substances behave in the lab, not on real patient studies. Still, boneset already carries its own liver cautions, and phenytoin is a sensitive medication where I don't like adding wild cards. Please run this by your pharmacist or neurologist before mixing them, and never adjust your phenytoin on your own.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Chojkier M. Hepatic sinusoidal-obstruction syndrome: toxicity of pyrrolizidine alkaloids. J Hepatol 2003;39:437-46. PubMed
  2. Wang YP, Yan J, Fu PP, Chou MW. Human liver microsomal reduction of pyrrolizidine alkaloid N-oxides to form the corresponding carcinogenic parent alkaloid. Toxicol Lett 2005;155:411-20. 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

Boneset Also Interacts With Other Medications

Boneset has 86 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 86 No known interaction 2,744 (incl. Phenytoin)
Taking anything else?

Check Another of Your Medications Against Boneset

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

From our Q&A

Questions About Boneset 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 Boneset 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 Boneset 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 Boneset as Part of a Dietary Supplement Product? Check It for Interactions

We hold 118 real supplement products containing Boneset, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Boneset. Your product may carry other ingredients that interact with Phenytoin too, on top of Boneset — 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 Boneset 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 Boneset
Top half

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

29 days ago today
Medication Phenytoin
Steady interest

#1,761 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 Boneset

What is Boneset?

  • Colds and flu
  • Fever
  • Body aches
  • Congestion
  • Immune support

Boneset is a traditional North American herb long used in teas for fevers, colds, and flu, but modern human studies are very limited. It contains compounds (pyrrolizidine alkaloids) that may harm the liver, so it should be used cautiously and avoided during pregnancy and breastfeeding.

Read the full Boneset 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 & Boneset

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

0Major
86Moderate
0Minor
2,743No known interaction
86 Moderate 2,743 No interaction
Moderate

86 interactions

Showing 60 of 86 moderate interactions — see all 86 on the Boneset page.

No interaction 2,743 drugs checked — show the list

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

Showing the 60 most looked-up of 2,743 medications checked with no known interaction — see the full Boneset list.

See the full Boneset 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
Boneset 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 Boneset and Phenytoin Together: Common Questions

Can you take Boneset 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 Boneset 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 Boneset?

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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.