Drug & supplement interaction

Mace + 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

Mace has a moderate interaction with Guaifenesin, Hydrocodone Bitartrate, Pseudoephedrine Hydrochloride. Several volatile oils in mace, such as methyleugenol, isoeugenol, safrole, myristicin, 1,8-cineole, and geranyl acetate, seem to have sedative effects.

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

Mace and Guaifenesin, Hydrocodone Bitartrate, Pseudoephedrine Hydrochloride

Here is the interaction we found between these two, with the evidence behind it.

Moderate

CNS DEPRESSANTS

Why this applies to Guaifenesin, Hydrocodone Bitartrate, Pseudoephedrine Hydrochloride

Guaifenesin, Hydrocodone Bitartrate, Pseudoephedrine Hydrochloride falls under CNS DEPRESSANTS — the group Mace interacts with.

Several volatile oils in mace, such as methyleugenol, isoeugenol, safrole, myristicin, 1,8-cineole, and geranyl acetate, seem to have sedative effects. Evidence from animal research suggests that methyleugenol can induce anesthesia for a similar duration as pentobarbital. Due to the sedative effects of certain mace constituents, taking medicinal amounts of mace in combination with other CNS depressants may have additive effects. However, evidence from other animal research suggests that myristicin can reduce sleeping time in rats pretreated with phenobarbital. Until more is known, use medicinal amounts of mace cautiously in combination with CNS depressants. Some CNS depressants include clonazepam (Klonopin), lorazepam (Ativan), phenobarbital (Donnatal), zolpidem (Ambien), and others.
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

The piece of this combo product that matters here is the hydrocodone, an opioid cough and pain ingredient that already slows down the brain and breathing. Mace contains aromatic oils (like myristicin and methyleugenol) that, in animal studies, have shown their own sedative effects. So the theory is simple: if you take concentrated, medicinal amounts of mace alongside this medicine, the drowsy effects could stack up. You might feel extra sleepy, foggy, dizzy, or notice slower, shallower breathing.

The good news is this concern is theoretical and based on animal data, not strong human studies. Using mace as a normal cooking spice is very unlikely to cause a problem. If you are considering mace pills or extracts, please run it by your pharmacist or doctor first.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Sangalli BC, Chiang W. Toxicology of nutmeg abuse. Clin Toxicol 2000;38:671-8. PubMed
  2. Hallstrom H, Thuvander A. Toxicological evaluation of myristicin. Nat Toxins 1997;5:186-92. DOI
  3. Jeong HG, Yun CH. Induction of rat hepatic cytochrome P450 enzymes by myristicin. Biochem Biophys Res Commun 1995;217:966-71. PubMed
  4. Sell AB, Carlini EA. Anesthetic action of methyleugenol and other eugenol derivatives. Pharmacology. 1976;14(4):367-77. PubMed
  5. Fundarò A, Cassone MC. [Action of essential oils of chamomile, cinnamon, absinthium, mace and origanum on operant conditioning behavior of the rat]. Boll Soc Ital Biol Sper. 1980;56(22):2375-80.

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

Mace Also Interacts With Other Medications

Mace has 499 moderate known drug interactions in our database — the Guaifenesin, Hydrocodone Bitartrate, Pseudoephedrine Hydrochloride one above is one of them. If you take anything else, check it against the full list below.

Moderate 499 No known interaction 2,331 (incl. Guaifenesin, Hydrocodone Bitartrate, Pseudoephedrine Hydrochloride)
Taking anything else?

Check Another of Your Medications Against Mace

Covers the 2,830 medications we’ve checked against Mace. 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 Mace 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 Mace as Part of a Dietary Supplement Product? Check It for Interactions

We hold 38 real supplement products containing Mace, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Mace. Your product may carry other ingredients that interact with Guaifenesin, Hydrocodone Bitartrate, Pseudoephedrine Hydrochloride too, on top of Mace — 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 Mace 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 Mace
Top half

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

29 days ago today
Medication Guaifenesin, Hydrocodone Bitartrate, Pseudoephedrine Hydrochloride
Top 10%

#231 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 Mace

What is Mace?

  • Digestive upset and gas
  • Flavoring and culinary spice
  • Nausea
  • Appetite stimulation
  • Traditional pain or muscle relief

Mace is the lacy red covering of the nutmeg seed and comes from the same tree as nutmeg. It is mostly used as a cooking spice and in traditional medicine for digestion, but there is little solid human research to support its health uses. In normal food amounts it is generally safe, but large doses can be toxic, so use it as a spice and check with your pharmacist before taking concentrated supplements.

Read the full Mace monograph & all interactions
Keep checking

Other Drugs & Mace

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

0Major
499Moderate
0Minor
2,330No known interaction
499 Moderate 2,330 No interaction
Moderate

499 interactions

Showing 60 of 499 moderate interactions — see all 499 on the Mace page.

No interaction 2,330 drugs checked — show the list

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

Showing the 60 most looked-up of 2,330 medications checked with no known interaction — see the full Mace list.

See the full Mace 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
Mace 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 Mace and Guaifenesin, Hydrocodone Bitartrate, Pseudoephedrine Hydrochloride Together: Common Questions

Can you take Mace 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.
How serious is the Mace 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 Mace?

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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.