Drug & supplement interaction

Feverfew + Guaifenesin, Hydrocodone Bitartrate, Pseudoephedrine Hydrochloride

Guaifenesin, Hydrocodone Bitartrate, Pseudoephedrine Hydrochloride brand name: Hycofenix.

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

Guaifenesin, Hydrocodone Bitartrate, Pseudoephedrine Hydrochloride 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 Guaifenesin, Hydrocodone Bitartrate, Pseudoephedrine Hydrochloride

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. Guaifenesin, Hydrocodone Bitartrate, Pseudoephedrine Hydrochloride 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 Guaifenesin, Hydrocodone Bitartrate, Pseudoephedrine Hydrochloride

Guaifenesin, Hydrocodone Bitartrate, Pseudoephedrine Hydrochloride 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 product, which I want to flag for you. Hydrocodone is a prodrug for part of its pain relief. Your body uses an enzyme called CYP2D6 to turn some of it into hydromorphone, a stronger painkiller. Feverfew may slow that enzyme down a bit, so in theory you could get slightly less of that converted pain relief, while the rest of the hydrocodone still works.

Honestly, though, this is only seen in lab dishes, not in real people, so I wouldn't lose sleep over it. The guaifenesin (mucus thinner) and pseudoephedrine (decongestant) aren't really affected here. If you take feverfew regularly, just mention it to your pharmacist so they can keep an eye on how well your cough medicine is working for you.

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

2 of 2

Guaifenesin, Hydrocodone Bitartrate, Pseudoephedrine Hydrochloride 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 short version on combining feverfew with Hycofenix. One of its ingredients, the hydrocodone, is partly broken down by a liver enzyme called CYP3A4. In a test tube, feverfew appears to slow that enzyme down a bit. In theory, that could let hydrocodone build up slightly, which might mean a stronger opioid effect: more drowsiness, dizziness, constipation, or slowed breathing.

That said, this is purely lab-based. It has not been seen in real people, so I wouldn't lose sleep over it. The guaifenesin and pseudoephedrine pieces aren't really affected. Still, since Hycofenix already makes many folks sleepy, it's worth a quick chat with your pharmacist or doctor 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 930 moderate known drug interactions in our database — the Guaifenesin, Hydrocodone Bitartrate, Pseudoephedrine Hydrochloride one above is among them. If you take anything else, check it against the full list below.

Moderate 930 No known interaction 1,900 (incl. Guaifenesin, Hydrocodone Bitartrate, Pseudoephedrine Hydrochloride)
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 Guaifenesin, Hydrocodone Bitartrate, Pseudoephedrine Hydrochloride

This page covers Feverfew only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Guaifenesin, Hydrocodone Bitartrate, Pseudoephedrine Hydrochloride page lists 241 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), Beer (major), Ephedra (major) and Gamma-hydroxybutyrate (ghb) (major).

By severity: 13 major · 190 moderate · 38 minor.

From our pharmacist’s overview on the Guaifenesin, Hydrocodone Bitartrate, Pseudoephedrine Hydrochloride page

“Hycofenix combines guaifenesin with hydrocodone, an opioid, and pseudoephedrine, a decongestant, so supplements can collide with it from two directions at once. That is why this list of 241 ingredients deserves real caution, starting with the 13 rated major.”

Reviewed by 2 · Jul 18, 2026

Open the Guaifenesin, Hydrocodone Bitartrate, Pseudoephedrine Hydrochloride 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 Guaifenesin, Hydrocodone Bitartrate, Pseudoephedrine Hydrochloride 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 Guaifenesin, Hydrocodone Bitartrate, Pseudoephedrine Hydrochloride 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%

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

29 days ago today
Medication Guaifenesin, Hydrocodone Bitartrate, Pseudoephedrine Hydrochloride
Top 25%

#343 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
930Moderate
0Minor
1,899No known interaction
930 Moderate 1,899 No interaction
Moderate

930 interactions

Showing 60 of 930 moderate interactions — see all 930 on the Feverfew page.

No interaction 1,899 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 1,899 medications checked with no known interaction — see the full Feverfew list.

See the full Feverfew interactions page
See every supplement checked against Guaifenesin, Hydrocodone Bitartrate, Pseudoephedrine Hydrochloride, 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 Guaifenesin, Hydrocodone Bitartrate, Pseudoephedrine Hydrochloride supplement interactions › Every supplement checked against Guaifenesin, Hydrocodone Bitartrate, Pseudoephedrine Hydrochloride, 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 Guaifenesin, Hydrocodone Bitartrate, Pseudoephedrine Hydrochloride Together: Common Questions

Can you take Feverfew with Guaifenesin, Hydrocodone Bitartrate, Pseudoephedrine Hydrochloride?
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 Guaifenesin, Hydrocodone Bitartrate, Pseudoephedrine Hydrochloride?
Guaifenesin, Hydrocodone Bitartrate, Pseudoephedrine Hydrochloride 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 Guaifenesin, Hydrocodone Bitartrate, Pseudoephedrine Hydrochloride 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 Guaifenesin, Hydrocodone Bitartrate, Pseudoephedrine Hydrochloride 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.