Drug & supplement interaction

Butterbur + Modafinil

Modafinil brand names: Provigil, Sparlon, Alertec.

Moderate Interaction
The bottom line Moderate

Butterbur has a moderate interaction with Modafinil. Theoretically, CYP3A4 inducers might increase the toxicity of butterbur.

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

Butterbur and Modafinil

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

Moderate

CYTOCHROME P450 3A4 (CYP3A4) INDUCERS

Why this applies to Modafinil

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

Theoretically, CYP3A4 inducers might increase the toxicity of butterbur.
The pyrrolizidine alkaloid (PA) constituents found in some butterbur products are substrates of CYP3A4. Theoretically, drugs that induce CYP3A4 might increase the conversion of PAs to toxic metabolites.
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: the concern isn't really about your modafinil changing. It's the other way around. Modafinil gently speeds up a liver enzyme called CYP3A4. Certain butterbur products still contain natural compounds called pyrrolizidine alkaloids (PAs), and that same enzyme can turn those PAs into byproducts that are harder on the liver. So in theory, modafinil could nudge butterbur toward being a bit more toxic.

I want to be honest though: this is a theoretical concern based on how these things work in the lab, not real-world reports. The practical fix is easy. Choose a PA-free butterbur product, which removes the risky compounds entirely. Either way, check with your pharmacist or doctor before combining them.

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

Butterbur Also Interacts With Other Medications

Butterbur has 86 moderate known drug interactions in our database — the Modafinil one above is one of them. If you take anything else, check it against the full list below.

Taking anything else?

Check Another of Your Medications Against Butterbur

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

Everything else you take

See Every Supplement That Interacts With Modafinil

This page covers Butterbur only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Modafinil page lists 197 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Adrafinil (major), Ephedra (major), Grapefruit (major) and Peyote (major).

By severity: 8 major · 150 moderate · 39 minor.

From our pharmacist’s overview on the Modafinil page

“Of the 197 supplements and herbs flagged for modafinil (Provigil, Alertec), eight carry a major rating, and those deserve real caution. Most of the rest fall into two themes.”

Reviewed by 2 · Jul 18, 2026

Open the Modafinil interaction page

One more smart check

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

We hold 136 real supplement products containing Butterbur, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Butterbur. Your product may carry other ingredients that interact with Modafinil too, on top of Butterbur — 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 Butterbur and Modafinil 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 Butterbur
Steady interest

#1,038 of 1,452 supplements looked up here in the last 7 days

29 days ago today
Medication Modafinil
Top half

#1,312 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 Butterbur

What is Butterbur?

  • Migraine prevention
  • Hay fever (allergic rhinitis)
  • Asthma symptoms
  • Stomach and digestive upset
  • Tension headaches

Butterbur is a plant extract most studied for preventing migraines and easing hay fever symptoms, and some standardized products show promise. However, raw or unprocessed butterbur contains compounds that can seriously harm the liver, so only use PA-free (pyrrolizidine alkaloid-free) products, and avoid it during pregnancy and breastfeeding. Talk to your pharmacist or doctor before trying it.

Read the full Butterbur monograph & all interactions
Medication

About Modafinil

What Is Modafinil Used For?

Brand names: Provigil, Sparlon, Alertec

Modafinil (also sold as Provigil) is used to improve wakefulness in adults who experience excessive sleepiness due to narcolepsy, obstructive sleep apnea (OSA), or shift work disorder (SWD).

In OSA, modafinil treats the sleepiness — not the underlying airway obstruction itself. It is used alongside standard treatments such as CPAP (a breathing device worn during sleep), not as a replacement for them. If CPAP is appropriate for you, your doctor will want you to use it consistently even while taking modafinil.

See full Modafinil drug information
Keep checking

Other Drugs & Butterbur

Browse every other medication we’ve checked against Butterbur — 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
Moderate

86 interactions

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

No interaction 2,743 drugs checked — show the list
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

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Pharmacist Counseling Corner

Taking Butterbur and Modafinil Together: Common Questions

Can you take Butterbur with Modafinil?
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 Butterbur and Modafinil 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 Modafinil and Butterbur?

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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.