Drug & supplement interaction

Feverfew + Acetaminophen, Dextromethorphan, Pseudoephedrine

Acetaminophen, Dextromethorphan, Pseudoephedrine brand names: Alka-Seltzer PLUS Flu Liquid Gels, Tylenol Flu Daytime Ex Strength, Non Aspirin Cold Caps, Tylenol Cold, Tylenol Flu Ex Strength.

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

Acetaminophen, Dextromethorphan, Pseudoephedrine falls into 3 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
Interactions3
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Feverfew and Acetaminophen, Dextromethorphan, Pseudoephedrine

These two interact in 3 distinct ways. Each one is explained separately below.

Why Are There 3 Interactions?

Feverfew interacts with whole categories of medication. Acetaminophen, Dextromethorphan, Pseudoephedrine falls into 3 of those categories, so it can interact with Feverfew in 3 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 3

Why this applies to Acetaminophen, Dextromethorphan, Pseudoephedrine

Acetaminophen, Dextromethorphan, Pseudoephedrine 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

This combo cold-and-flu product has three active ingredients, and the one that matters here is dextromethorphan, the cough suppressant. Your body clears it using a liver enzyme called CYP2D6. In test-tube studies, feverfew appeared to slow that enzyme down a bit. If that held true in people, dextromethorphan could build up and you might notice more drowsiness, dizziness, or a foggy, lightheaded feeling.

The important thing is that this is only lab-bench evidence. It has never actually been reported in real patients, so I don't want you to be alarmed. Still, if you regularly take feverfew for migraines and you reach for a product like Tylenol Cold or Flu, it's worth a quick chat with your pharmacist to be safe.

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 3

Acetaminophen, Dextromethorphan, Pseudoephedrine 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 honest version: this is a theoretical concern that has never actually been seen in real people. In lab dishes, feverfew appears to slow down a liver enzyme called CYP1A2. If that happened in your body, drugs cleared by that enzyme could build up a bit. Of the three ingredients in this cold and flu combo, none of them lean heavily on CYP1A2, so the practical impact is expected to be small.

If levels did creep up, you might notice more of the usual effects, like drowsiness or stomach upset from the dextromethorphan, or jitteriness, a racing heart, or trouble sleeping from the pseudoephedrine. Since this is only animal and test-tube data, I wouldn't lose sleep over it, but check with your pharmacist if you take feverfew regularly.

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 3A4 (CYP3A4) SUBSTRATES

3 of 3

Acetaminophen, Dextromethorphan, Pseudoephedrine 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

This combo cold-and-flu product contains three ingredients, and one of them, dextromethorphan (the cough suppressant), is partly broken down by an enzyme called CYP3A4. In a test-tube setting, feverfew appeared to slow that enzyme down. If that held true in people, dextromethorphan could build up a bit and you might feel more drowsy, dizzy, or lightheaded than usual.

Here is the reassuring part: this is only laboratory data, and it has not actually been seen in humans. So I'd call this a theoretical, low-level concern, not something dramatic. Still, since this product already has pseudoephedrine and acetaminophen on board, it's worth a quick chat with your pharmacist before pairing it with feverfew, just to be safe.

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
  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 Acetaminophen, Dextromethorphan, Pseudoephedrine 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, Dextromethorphan, Pseudoephedrine)
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, Dextromethorphan, Pseudoephedrine

This page covers Feverfew only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Dextromethorphan, Pseudoephedrine page lists 262 supplements it has a documented interaction with, worst first, each one explained.

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

By severity: 12 major · 207 moderate · 43 minor.

From our pharmacist’s overview on the Acetaminophen, Dextromethorphan, Pseudoephedrine page

“Ephedra is the ingredient to notice first here. Pseudoephedrine, the decongestant in Tylenol Flu, Alka-Seltzer PLUS Flu, and other acetaminophen, dextromethorphan, and pseudoephedrine combinations, is itself a stimulant, and 44 entries push the same direction, raising the odds of high blood pressure and a racing heart.”

Reviewed by 2 · Jul 18, 2026

Open the Acetaminophen, Dextromethorphan, Pseudoephedrine 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, Dextromethorphan, Pseudoephedrine 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, Dextromethorphan, Pseudoephedrine 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%

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

29 days ago today
Medication Acetaminophen, Dextromethorphan, Pseudoephedrine
Top 25%

#364 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, Dextromethorphan, Pseudoephedrine, 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, Dextromethorphan, Pseudoephedrine supplement interactions › Every supplement checked against Acetaminophen, Dextromethorphan, Pseudoephedrine, 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, Dextromethorphan, Pseudoephedrine Together: Common Questions

Can you take Feverfew with Acetaminophen, Dextromethorphan, Pseudoephedrine?
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 3 interactions listed for Feverfew and Acetaminophen, Dextromethorphan, Pseudoephedrine?
Acetaminophen, Dextromethorphan, Pseudoephedrine 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, Dextromethorphan, Pseudoephedrine 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, Dextromethorphan, Pseudoephedrine and Feverfew?

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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.