Drug & supplement interaction

Nutmeg + Benzhydrocodone, Acetaminophen

Benzhydrocodone, Acetaminophen brand name: Apadaz.

Moderate Interaction
The bottom line Moderate

Benzhydrocodone, Acetaminophen falls into 3 drug categories that Nutmeg can interact with; the most serious is rated moderate. Theoretically, nutmeg might increase the risk of additive sedation when taken with CNS depressants.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions3
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Nutmeg and Benzhydrocodone, Acetaminophen

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

Why Are There 3 Interactions?

Nutmeg interacts with whole categories of medication. Benzhydrocodone, Acetaminophen falls into 3 of those categories, so it can interact with Nutmeg in 3 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

CNS DEPRESSANTS

1 of 3

Why this applies to Benzhydrocodone, Acetaminophen

Benzhydrocodone, Acetaminophen falls under CNS DEPRESSANTS — the group Nutmeg interacts with.

Theoretically, nutmeg might increase the risk of additive sedation when taken with CNS depressants.
Animal studies suggest that nutmeg extracts and several volatile oils in nutmeg, such as methyleugenol, isoeugenol, safrole, myristicin, trimyristin, 1,8-cineole, and geranyl acetate, have sedative effects. One animal study shows that petroleum ether extracts of nutmeg can potentiate the effects of pentobarbital or phenobarbital. However, evidence from other animal research suggests that the nutmeg constituent myristicin can actually reduce sleeping time in rats pretreated with phenobarbital.
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: Apadaz contains an opioid (benzhydrocodone, which your body turns into hydrocodone) plus acetaminophen, and opioids already slow down the brain and nervous system. In lab and animal studies, some of the natural oils in nutmeg also showed a mild calming or sedating effect. So the worry is that the two together might add up to extra drowsiness, dizziness, slowed breathing, or feeling foggy.

I'll be honest with you though, this is a theoretical concern based only on animal research, and the findings were even mixed. A sprinkle of nutmeg in your food is very unlikely to cause a problem. Large "medicinal" doses of nutmeg are a different story and aren't safe anyway. If you're taking Apadaz, check with your pharmacist or doctor before using concentrated nutmeg supplements.

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.
  6. Grover JK, Khandkar S, Vats V, Dhunnoo Y, Das D. Pharmacological studies on Myristica fragrans--antidiarrheal, hypnotic, analgesic and hemodynamic (blood pressure) parameters. Methods Find Exp Clin Pharmacol. 2002;24(10):675-80. PubMed
  7. Sherry CJ, Ray LE, Herron RE. The pharmacological effects of the ligroin extract of nutmeg (Myristica fragrans). J Ethnopharmacol. 1982;6(1):61-6.
Moderate

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES

2 of 3

Benzhydrocodone, Acetaminophen also falls under CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES.

Theoretically, nutmeg might decrease levels of drugs metabolized by CYP1A2.
Animal research suggests that intraperitoneal injections of myristicin, a constituent of nutmeg, can induce CYP1A2.
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 picture with Apadaz (benzhydrocodone with acetaminophen) and nutmeg. Benzhydrocodone is actually a prodrug, meaning your body converts it into hydrocodone, the part that relieves pain. The interaction on file is about nutmeg possibly speeding up an enzyme called CYP1A2, which could in theory clear certain drugs a bit faster. For this medicine, that might mean slightly less pain relief, though this is far from certain.

The important thing: this is based only on animal studies using injected nutmeg compounds, not real-world human use. Everyday cooking amounts of nutmeg are very unlikely to matter here. Large "medicinal" doses of nutmeg are dangerous on their own and should be avoided. If you have questions, please check with your pharmacist or doctor.

References
  1. Jeong HG, Yun CH. Induction of rat hepatic cytochrome P450 enzymes by myristicin. Biochem Biophys Res Commun 1995;217:966-71. PubMed
Moderate

ANTICHOLINERGIC DRUGS

3 of 3

Benzhydrocodone, Acetaminophen also falls under ANTICHOLINERGIC DRUGS.

Theoretically, concomitant use of nutmeg and anticholinergic drugs might decrease the effectiveness of either agent.
Animal research suggests that nutmeg extract can inhibit acetylcholinesterase and might increase acetylcholine levels.
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 picture for Apadaz (benzhydrocodone with acetaminophen). The interaction on file comes from animal and lab work only, where nutmeg seemed to nudge up a brain chemical called acetylcholine. The thought is that this could slightly oppose medications with anticholinergic-type activity. For a pain combo like this one, that's a very theoretical, low-strength concern, not something proven in people.

In normal cooking amounts, the nutmeg in your food is not going to change how well this medicine controls your pain. The bigger thing to remember is that large "medicinal" doses of nutmeg can be genuinely toxic on their own, so please don't take it that way. If you have questions about your pain relief, check in with your pharmacist or doctor.

References
  1. Mukherjee PK, Kumar V, Houghton PJ. Screening of Indian medicinal plants for acetylcholinesterase inhibitory activity. Phytother Res. 2007;21(12):1142-5. PubMed

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

Nutmeg Also Interacts With Other Medications

Nutmeg has 527 moderate known drug interactions in our database — the Benzhydrocodone, Acetaminophen 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 Nutmeg

Covers the 2,830 medications we’ve checked against Nutmeg. Pick one to open its full report.

Everything else you take

See Every Supplement That Interacts With Benzhydrocodone, Acetaminophen

This page covers Nutmeg only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Benzhydrocodone, Acetaminophen page lists 299 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), Asarabacca (major), Beer (major) and Gamma-hydroxybutyrate (ghb) (major).

By severity: 14 major · 239 moderate · 46 minor.

Open the Benzhydrocodone, Acetaminophen interaction page

One more smart check

Taking Nutmeg as Part of a Dietary Supplement Product? Check It for Interactions

We hold 182 real supplement products containing Nutmeg, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Nutmeg. Your product may carry other ingredients that interact with Benzhydrocodone, Acetaminophen too, on top of Nutmeg — 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 Nutmeg and Benzhydrocodone, Acetaminophen 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 Nutmeg
Top half

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

29 days ago today
Medication Benzhydrocodone, Acetaminophen
Steady interest

#2,186 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 Nutmeg

What is Nutmeg?

Nutmeg
  • Digestive upset
  • Diarrhea
  • Sleep and relaxation
  • Pain and inflammation
  • Flavoring spice

Nutmeg is a popular cooking spice that has long been used in traditional medicine for digestion and other complaints, but there is little solid human research to support its medicinal use. In normal cooking amounts it is generally safe, but larger "medicinal" doses can cause serious poisoning, so it should never be taken in high amounts.

Read the full Nutmeg monograph & all interactions
Medication

About Benzhydrocodone and Acetaminophen

What Is Benzhydrocodone and Acetaminophen Used For?

Brand name: Apadaz

Apadaz is indicated for the short-term management of acute pain — up to 14 days — that is severe enough to require an opioid and for which non-opioid treatments have not worked or are not expected to work. It combines benzhydrocodone (a prodrug that converts to the opioid hydrocodone) with acetaminophen.

Because of serious risks including addiction, abuse, and misuse, Apadaz is reserved for patients who have not tolerated or have not gotten adequate relief from alternative pain treatments. It should not be used for an extended period of time unless the pain remains severe enough to require an opioid and alternatives remain inadequate.

See full Benzhydrocodone and Acetaminophen drug information
Keep checking

Other Drugs & Nutmeg

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

0Major
527Moderate
0Minor
2,302No known interaction
Moderate

527 interactions

Showing 60 of 527 moderate interactions — see all 527 on the Nutmeg page.

No interaction 2,302 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 Nutmeg and Benzhydrocodone, Acetaminophen Together: Common Questions

Can you take Nutmeg with Benzhydrocodone, Acetaminophen?
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 Nutmeg and Benzhydrocodone, Acetaminophen?
Benzhydrocodone, Acetaminophen belongs to more than one drug category, and Nutmeg 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 Nutmeg and Benzhydrocodone, Acetaminophen 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.