Drug & supplement interaction

Feverfew + Caffeine (OTC drug)

Caffeine (OTC drug) brand names: Vivarin, Overtime, Molie.

Moderate Interaction
The bottom line Moderate

Caffeine (OTC drug) falls into 2 drug categories that Feverfew can interact with; the most serious is rated moderate. Theoretically, feverfew might increase levels of drugs metabolized by CYP1A2.

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

Feverfew and Caffeine (OTC drug)

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

Why Are There 2 Interactions?

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

Moderate

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES

1 of 2

Why this applies to Caffeine (OTC drug)

Caffeine (OTC drug) falls under CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES — the group Feverfew interacts with.

Theoretically, feverfew might increase levels of drugs metabolized by CYP1A2.
Laboratory research shows that feverfew might inhibit CYP1A2. So far, this interaction has not been reported in humans.
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: your body clears caffeine mainly through a liver enzyme called CYP1A2. Lab studies hint that feverfew might slow that enzyme down a bit. If it does, caffeine could hang around a little longer than usual, meaning the jittery, wired feeling from a Vivarin or No-Doz tablet might be stronger or last longer. Think a faster heartbeat, restlessness, trouble sleeping, or feeling shaky.

That said, I want to be honest with you. This has only been seen in test-tube and animal research, never reported in real people, so it's more of a theoretical concern than a proven problem. Everyday tea or coffee likely won't cause trouble. If you notice extra jitters after starting feverfew, just check in with your pharmacist or doctor.

References
  1. Unger M, Frank A. Simultaneous determination of the inhibitory potency of herbal extracts on the activity of six major cytochrome P450 enzymes using liquid chromatography/mass spectrometry and automated online extraction. Rapid Commun Mass Spectrom 2004;1 PubMed
Moderate

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

2 of 2

Caffeine (OTC drug) also falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES.

Theoretically, feverfew might increase levels of drugs metabolized by CYP3A4.
Laboratory research shows that feverfew might inhibit CYP3A4. So far, this interaction has not been reported in humans.
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 situation with feverfew and caffeine pills like Vivarin. In a lab setting, feverfew appeared to slow down a liver enzyme called CYP3A4, which helps clear certain drugs. If that happened with caffeine, the caffeine could linger a bit longer and hit a little harder, meaning more jitteriness, a racing heart, trouble sleeping, or an upset stomach.

The important thing to know is that this is only a theoretical concern from test-tube research. It has not actually been reported in people, and most of caffeine's breakdown is handled by a different enzyme (CYP1A2), not CYP3A4. So in real life this combo is unlikely to cause trouble. Still, if you feel extra wired, mention it to your pharmacist or doctor.

References
  1. Unger M, Frank A. Simultaneous determination of the inhibitory potency of herbal extracts on the activity of six major cytochrome P450 enzymes using liquid chromatography/mass spectrometry and automated online extraction. Rapid Commun Mass Spectrom 2004;1 PubMed
  2. Sil'vestrov VP, Kinitin AV, and Chesnokova, IV. [Immunological and metabolic disorders and the means for their correction in patients with chronic bronchitis]. Ter.Arkh. 1991;63:7-11.

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

Feverfew Also Interacts With Other Medications

Feverfew has 928 moderate known drug interactions in our database — the Caffeine (OTC drug) one above is among them. If you take anything else, check it against the full list below.

Taking anything else?

Check Another of Your Medications Against Feverfew

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

Everything else you take

See Every Supplement That Interacts With Caffeine (OTC drug)

This page covers Feverfew only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Caffeine (OTC drug) page lists 208 supplements it has a documented interaction with, worst first, each one explained.

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

By severity: 7 major · 155 moderate · 46 minor.

From our pharmacist’s overview on the Caffeine (OTC drug) page

“The person swallowing a caffeine pill like Vivarin to power through a shift is often the same person drinking coffee, taking an herbal energy blend, or scooping pre-workout powder, and that overlap is exactly where the danger sits. Seven of the 208 supplement ingredients on file carry a major rating, and those seven are worth understan…”

Reviewed by 2 · Jul 18, 2026

Open the Caffeine (OTC drug) interaction page

One more smart check

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

We hold 520 real supplement products containing Feverfew, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Feverfew. Your product may carry other ingredients that interact with Caffeine (OTC drug) too, on top of Feverfew — 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 Feverfew and Caffeine (OTC drug) 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 Feverfew
Top 25%

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

29 days ago today
Medication Caffeine (OTC drug)
Top 10%

#153 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 Feverfew

What is Feverfew?

Feverfew
  • Migraine prevention
  • Headache
  • Fever (traditional)
  • Arthritis and joint pain
  • Menstrual discomfort

Feverfew is a daisy-family herb best known for migraine prevention, where some studies suggest it may modestly lower how often migraines occur, though the evidence is mixed. It is generally well tolerated for short-term use in most adults but should be avoided during pregnancy and breastfeeding and by people allergic to ragweed and related plants. Talk to your pharmacist or doctor before starting it.

Read the full Feverfew monograph & all interactions
Keep checking

Other Drugs & Feverfew

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

0Major
928Moderate
0Minor
1,901No known interaction
Moderate

928 interactions

Showing 60 of 928 moderate interactions — see all 928 on the Feverfew page.

No interaction 1,901 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 Feverfew and Caffeine (OTC drug) Together: Common Questions

Can you take Feverfew with Caffeine (OTC drug)?
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 Feverfew and Caffeine (OTC drug)?
Caffeine (OTC drug) belongs to more than one drug category, and Feverfew 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 Feverfew and Caffeine (OTC drug) 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

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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.