Drug & supplement interaction

Mace + Propoxyphene

Propoxyphene brand names: Darvon, Prophene-65, Margesic, Davon.

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

Mace has a moderate interaction with Propoxyphene. 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 Propoxyphene

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

Moderate

CNS DEPRESSANTS

Why this applies to Propoxyphene

Propoxyphene 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

Here's the simple version: propoxyphene is an opioid pain reliever that already slows down your brain and body. Some of the aromatic oils in mace appear to have a mild calming, sedative quality of their own. Put the two together in larger, concentrated amounts and those effects could stack up, leaving you more drowsy, foggy, or lightheaded than you'd expect, with slower breathing in extreme cases.

I'll be honest with you though, this concern is theoretical and based mostly on animal studies, not real people. A pinch of mace in your cooking is very unlikely to cause any trouble. The caution really applies to medicinal or concentrated mace supplements. Before adding any of those, 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 Propoxyphene 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. Propoxyphene)
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 Propoxyphene

This page covers Mace only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Propoxyphene page lists 172 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), Gamma-hydroxybutyrate (ghb) (major) and Kava (major).

By severity: 8 major · 141 moderate · 23 minor.

From our pharmacist’s overview on the Propoxyphene page

“Propoxyphene (Darvon) is an opioid painkiller, and the biggest hazard among the 172 supplement interactions on file is anything else that slows the brain and breathing. Seventy-eight of these ingredients pile on that sedation, alcohol and kava among the worst rated, and with an opioid the combination can push breathing dangerously low.”

Reviewed by 2 · Jul 18, 2026

Open the Propoxyphene 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 Propoxyphene 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 Propoxyphene 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

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

29 days ago today
Medication Propoxyphene
Top 5%

#85 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
Medication

About Acetaminophen, Butalbital, and Caffeine

What Is Acetaminophen, Butalbital, and Caffeine Used For?

Brand names: Darvon, Prophene-65, Margesic, Davon

This three-ingredient combination — butalbital, acetaminophen, and caffeine — is used to relieve the symptoms of tension headache (also called muscle contraction headache). All supported products, including tablets, capsules, and oral solution, share this same approved use.

It is worth knowing that evidence for using this combination to treat repeated, frequent tension headaches over time is limited. Because butalbital can be habit-forming, extended or repeated use is not recommended.

See full Acetaminophen, Butalbital, and Caffeine drug information
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 Propoxyphene, 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 Propoxyphene supplement interactions › Every supplement checked against Propoxyphene, ranked by severity Acetaminophen, Butalbital, and Caffeine drug information › The full plain-English guide to this medication 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 Propoxyphene Together: Common Questions

Can you take Mace with Propoxyphene?
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 Propoxyphene 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 Propoxyphene 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.