Drug & supplement interaction

Feverfew + Acetaminophen, Butalbital, Codeine Phosphate

Acetaminophen, Butalbital, Codeine Phosphate brand name: Phrenilin #3.

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

Acetaminophen, Butalbital, Codeine Phosphate 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 CYP2D6.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions2
EvidenceD
What do Severity, Likelihood & Evidence mean?
Know someone taking this? Share
Facebook Post Reddit Email
On this page
Interaction report

Feverfew and Acetaminophen, Butalbital, Codeine Phosphate

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. Acetaminophen, Butalbital, Codeine Phosphate 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 2D6 (CYP2D6) SUBSTRATES

1 of 2

Why this applies to Acetaminophen, Butalbital, Codeine Phosphate

Acetaminophen, Butalbital, Codeine Phosphate falls under CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES — the group Feverfew interacts with.

Theoretically, feverfew might increase levels of drugs metabolized by CYP2D6.
Laboratory research shows that feverfew might inhibit CYP2D6. 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 wrinkle with this combo. The codeine part of Phrenilin needs an enzyme called CYP2D6 to turn into morphine, which is what actually relieves pain. In lab studies, feverfew appears to slow down that same enzyme. If that held true in people, your body would make less morphine from the codeine, so you might get weaker pain relief than expected.

The good news: this has only been seen in test-tube research, never in real patients, so it's mostly theoretical. Many people use feverfew for migraine without trouble. Still, if your headache medicine seems to stop working as well after starting feverfew, mention it to your pharmacist or doctor before changing anything.

Contact Dr. Brian directly if you have additional questions on this interaction
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 1A2 (CYP1A2) SUBSTRATES

2 of 2

Acetaminophen, Butalbital, Codeine Phosphate also falls under CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES.

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 with this combo pill (acetaminophen, butalbital, and codeine). The concern on file is that feverfew might block a liver enzyme called CYP1A2. When that enzyme is slowed down, certain drugs it processes can build up a bit more than usual. In theory, that could nudge up the sedating effects of the butalbital portion, things like extra drowsiness, dizziness, or feeling foggy.

That said, I want to keep this in perspective. This interaction has only shown up in lab and animal research, never in actual people. The codeine piece is mostly a separate pathway, so the main caution is just stacking sleepiness. Don't change anything on your own, but do mention the feverfew to your pharmacist or doctor so they can keep an eye out.

Contact Dr. Brian directly if you have additional questions on this interaction
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

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 Acetaminophen, Butalbital, Codeine Phosphate one above is among them. If you take anything else, check it against the full list below.

Moderate 928 No known interaction 1,902 (incl. Acetaminophen, Butalbital, Codeine Phosphate)
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 Acetaminophen, Butalbital, Codeine Phosphate

This page covers Feverfew only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Butalbital, Codeine Phosphate page lists 240 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), Asarabacca (major), Beer (major) and Gamma-hydroxybutyrate (ghb) (major).

Open the Acetaminophen, Butalbital, Codeine Phosphate 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 Acetaminophen, Butalbital, Codeine Phosphate 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 Acetaminophen, Butalbital, Codeine Phosphate 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%

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

29 days ago today
Medication Acetaminophen, Butalbital, Codeine Phosphate
Steady interest

#1,516 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
928 Moderate 1,901 No 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

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

Showing the 60 most looked-up of 1,901 medications checked with no known interaction — see the full Feverfew list.

See the full Feverfew interactions page
See every supplement checked against Acetaminophen, Butalbital, Codeine Phosphate, 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
Feverfew monograph › Uses, safety, and every drug interaction in one place Acetaminophen, Butalbital, Codeine Phosphate supplement interactions › Every supplement checked against Acetaminophen, Butalbital, Codeine Phosphate, 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 Feverfew and Acetaminophen, Butalbital, Codeine Phosphate Together: Common Questions

Can you take Feverfew with Acetaminophen, Butalbital, Codeine Phosphate?
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 Acetaminophen, Butalbital, Codeine Phosphate?
Acetaminophen, Butalbital, Codeine Phosphate 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 Acetaminophen, Butalbital, Codeine Phosphate 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 Acetaminophen, Butalbital, Codeine Phosphate and Feverfew?

Our pharmacists answer your medication & supplement questions — free.

Ask a pharmacist

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.