Drug & supplement interaction

Feverfew + Acetaminophen, Chlorpheniramine, Dextromethorphan, Pseudoephedrine

Acetaminophen, Chlorpheniramine, Dextromethorphan, Pseudoephedrine brand names: Tylenol Cold Ex Strength, Children's Tylenol Cold Plus Cough.

Moderate Interaction
The bottom line Moderate

Acetaminophen, Chlorpheniramine, 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, Chlorpheniramine, 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, Chlorpheniramine, 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, Chlorpheniramine, Dextromethorphan, Pseudoephedrine

Acetaminophen, Chlorpheniramine, 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 medicine has a few ingredients, but the one that matters here is dextromethorphan (the cough suppressant). It's cleared by an enzyme called CYP2D6, and lab studies hint that feverfew might slow that enzyme down. If that happened, dextromethorphan could build up a bit, which might mean more drowsiness, dizziness, or feeling foggy.

The honest part: this is purely a test-tube idea. It has never actually been reported in real people, so for most folks taking a normal dose of cold medicine for a few days, it's very unlikely to cause trouble. Still, if you take feverfew daily for migraines, it's worth a quick word with your pharmacist or doctor, especially if you already feel extra sleepy on it.

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, Chlorpheniramine, 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

This combination cold product packs four ingredients, and the concern here is mostly theoretical. In lab tests, feverfew appears to slow down an enzyme called CYP1A2. Of the ingredients in this medicine, that mainly matters for the cough suppressant and to a lesser extent the antihistamine. If that enzyme is dialed back, levels of those drugs could drift a little higher than usual, which in theory might mean more drowsiness, dizziness, dry mouth, or feeling foggy.

That said, this has never actually been reported in people. It comes only from test-tube research, so for most healthy adults taking either product short-term, it is unlikely to cause real trouble. Still, if you take feverfew daily for migraines, mention it to your pharmacist so they can double-check it is a good fit for you.

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, Chlorpheniramine, 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 cold-and-cough combo contains a few ingredients, and one of them, dextromethorphan, is partly handled by a liver enzyme called CYP3A4. In lab dishes, feverfew has shown it might slow that enzyme down. If that happened in people, dextromethorphan could build up a little, which in theory might mean more drowsiness, dizziness, or that floating, foggy feeling.

Here is the reassuring part: this is only test-tube research, and nothing like it has actually been reported in people. So the real-world risk looks low. Still, if you already feel extra sleepy or off on this product, mention it to your pharmacist or doctor. And remember, the acetaminophen in here is the ingredient to watch most for not doubling up across other cold or pain medicines.

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, Chlorpheniramine, Dextromethorphan, Pseudoephedrine 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 Acetaminophen, Chlorpheniramine, Dextromethorphan, Pseudoephedrine

This page covers Feverfew only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Chlorpheniramine, Dextromethorphan, Pseudoephedrine page lists 301 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: 14 major · 242 moderate · 45 minor.

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

“Because Tylenol Cold Extra Strength packs four drugs into one dose (acetaminophen, chlorpheniramine, dextromethorphan, and pseudoephedrine), its supplement list runs to 301 ingredients, and 14 carry a major rating, so I'd approach this one with real care. The biggest hazards mirror the drugs themselves.”

Reviewed by 2 · Jul 18, 2026

Open the Acetaminophen, Chlorpheniramine, 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, Chlorpheniramine, 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, Chlorpheniramine, 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%

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

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

#620 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 Acetaminophen, Chlorpheniramine, Dextromethorphan, Pseudoephedrine Together: Common Questions

Can you take Feverfew with Acetaminophen, Chlorpheniramine, 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, Chlorpheniramine, Dextromethorphan, Pseudoephedrine?
Acetaminophen, Chlorpheniramine, 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, Chlorpheniramine, 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

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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.