Drug & supplement interaction

Ephedra + Acetaminophen, Orphenadrine

Acetaminophen, Orphenadrine brand name: Orfenagesic.

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

Acetaminophen, Orphenadrine falls into 2 drug categories that Ephedra can interact with; the most serious is rated moderate. Theoretically, ephedra might decrease levels of drugs metabolized by CYP1A2.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions2
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Ephedra and Acetaminophen, Orphenadrine

These two interact in 2 distinct ways. Each one is explained separately below.

Why Are There 2 Interactions?

Ephedra interacts with whole categories of medication. Acetaminophen, Orphenadrine falls into 2 of those categories, so it can interact with Ephedra 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 1A2 (CYP1A2) SUBSTRATES

1 of 2

Why this applies to Acetaminophen, Orphenadrine

Acetaminophen, Orphenadrine falls under CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES — the group Ephedra interacts with.

Theoretically, ephedra might decrease levels of drugs metabolized by CYP1A2.
Some animal research suggests that ephedra induces CYP1A2 and increases the clearance of CYP1A2 substrates such as caffeine.
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 gist for your acetaminophen and orphenadrine combo pill. Some early animal studies hint that ephedra may speed up a liver enzyme called CYP1A2, which helps clear certain medications. If that enzyme runs faster, your body might break down and remove these ingredients a little quicker, so you could get less pain and muscle-relaxing relief than you'd expect.

Honestly though, this is theoretical and based only on lab and animal work, so I wouldn't lose sleep over it. The bigger concern is ephedra itself, which is banned in supplements because it can dangerously raise blood pressure and heart rate. Please skip ephedra and ask your pharmacist about safer choices.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Tang J, Zhou X, Ji H, Zhu D, Wu L. Effects of ephedra water decoction and cough tablets containing ephedra and liquorice on CYP1A2 and the pharmacokinetics of theophylline in rats. Phytother Res. 2012;26(3):470-4. PubMed
Moderate

HEPATOTOXIC DRUGS

2 of 2

Acetaminophen, Orphenadrine also falls under HEPATOTOXIC DRUGS.

Theoretically, concomitant use might have additive adverse hepatotoxic effects.
There are numerous cases of liver toxicity from ephedra-containing supplements.
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 concern with combining ephedra and a product like Orfenagesic (which pairs acetaminophen with the muscle relaxer orphenadrine). Both ephedra and acetaminophen can be hard on the liver. The worry is that taken together, their effects on liver cells could stack up. This is a theoretical idea based on how these substances behave, not something proven in studies, so I don't want to overstate it.

That said, ephedra has caused real cases of liver damage and is banned in U.S. supplements for good reason. Acetaminophen itself is a leading cause of liver injury when taken in excess. I'd steer clear of ephedra entirely and watch your daily acetaminophen total. Please check with your pharmacist or doctor about safer options before mixing anything.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Nadir A, Agrawal S, King PD, Marshall JB. Acute hepatitis associated with the use of a Chinese herbal product, ma-huang. Am J Gastroenterol 1996;91:1436-8.
  2. Borum, M. L. Fulminant exacerbation of autoimmune hepatitis after the use of ma huang. Am J Gastroenterol. 2001;96(5):1654-1655. PubMed
  3. Vigano, M., Lampertico, P., and Colombo, M. Acute hepatitis following assumption of a herbal remedy. Eur.J.Gastroenterol.Hepatol. 2008;20(4):364-365. PubMed
  4. Neff, G. W., Reddy, K. R., Durazo, F. A., Meyer, D., Marrero, R., and Kaplowitz, N. Severe hepatotoxicity associated with the use of weight loss diet supplements containing ma huang or usnic acid. J Hepatol. 2004;41(6):1062-1064. PubMed
  5. Bajaj J, Knox JF, Komorowski R, Saeian K. The irony of herbal hepatitis: Ma-Huang-induced hepatotoxicity associated with compound heterozygosity for hereditary hemochromatosis. Dig Dis Sci. 2003;48(10):1925-8.
  6. Charalampopoulos A, Karatsourakis T, Tsiodra P. Acute hepatitis associated with the use of Ma-huang in a young adult. Eur J Intern Med. 2007;18(1):81. PubMed
  7. Skoulidis F, Alexander GJ, Davies SE. Ma huang associated acute liver failure requiring liver transplantation. Eur J Gastroenterol Hepatol. 2005;17(5):581-4. PubMed
  8. Drug record: Ma huang. U.S. National Library of Medicine: Livertox Database. https://livertox.nlm.nih.gov/Ephedra.htm. Updated October 16, 2017. Accessed November 1, 2017.

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

Ephedra Also Interacts With Other Medications

Ephedra has 337 major, 495 moderate known drug interactions in our database — the Acetaminophen, Orphenadrine one above is among them. If you take anything else, check it against the full list below.

Major 337 Moderate 495 No known interaction 1,998 (incl. Acetaminophen, Orphenadrine)
Taking anything else?

Check Another of Your Medications Against Ephedra

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

Everything else you take

See Every Supplement That Interacts With Acetaminophen, Orphenadrine

This page covers Ephedra only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Orphenadrine page lists 160 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), Procaine (major) and Siberian Cocklebur (major).

By severity: 6 major · 119 moderate · 35 minor.

From our pharmacist’s overview on the Acetaminophen, Orphenadrine page

“Orfenagesic combines acetaminophen with orphenadrine, a muscle relaxant, and the acetaminophen half is what makes its interaction list worth real vigilance. Six of the 160 supplement ingredients on file carry a major rating, and the largest risky cluster, 38 ingredients including beer and wine, adds to the strain acetaminophen already…”

Reviewed by 2 · Jul 18, 2026

Open the Acetaminophen, Orphenadrine interaction page

One more smart check

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

We hold 37 real supplement products containing Ephedra, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Ephedra. Your product may carry other ingredients that interact with Acetaminophen, Orphenadrine too, on top of Ephedra — 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 Ephedra and Acetaminophen, Orphenadrine 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 Ephedra
Top half

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

29 days ago today
Medication Acetaminophen, Orphenadrine
Top half

#896 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 Ephedra

What is Ephedra?

Ephedra
  • Weight loss
  • Nasal and sinus congestion
  • Asthma and breathing problems
  • Boosting energy and athletic performance
  • Allergies

Ephedra (ma huang) contains powerful stimulants like ephedrine that affect the heart and nervous system. Because it has been linked to serious harms including high blood pressure, stroke, and death, it is banned for use in dietary supplements in the U.S. and many other countries. We do not recommend using ephedra-containing supplements; talk to your pharmacist or doctor about safer, approved options.

Read the full Ephedra monograph & all interactions
Keep checking

Other Drugs & Ephedra

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

337Major
495Moderate
0Minor
1,997No known interaction
337 Major 495 Moderate 1,997 No interaction
Major

337 interactions

Showing 60 of 337 major interactions — see all 337 on the Ephedra page.

Moderate

495 interactions

Showing 60 of 495 moderate interactions — see all 495 on the Ephedra page.

No interaction 1,997 drugs checked — show the list

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

Showing the 60 most looked-up of 1,997 medications checked with no known interaction — see the full Ephedra list.

See the full Ephedra interactions page
See every supplement checked against Acetaminophen, Orphenadrine, 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
Ephedra monograph › Uses, safety, and every drug interaction in one place Acetaminophen, Orphenadrine supplement interactions › Every supplement checked against Acetaminophen, Orphenadrine, 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 Ephedra and Acetaminophen, Orphenadrine Together: Common Questions

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