Drug & supplement interaction

Ephedra + Acetaminophen, Caffeine, Isometheptene

Acetaminophen, Caffeine, Isometheptene brand name: Migralam.

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

Acetaminophen, Caffeine, Isometheptene falls into 4 drug categories that Ephedra can interact with; the most serious is rated major. Theoretically, concomitant use might increase the risk for serious adverse effects.

Read the full interaction report
SeverityMajor
LikelihoodProbable
Interactions4
EvidenceD
What do Severity, Likelihood & Evidence mean?
Know someone taking this? Share
Facebook Post Reddit Email
On this page
Interaction report

Ephedra and Acetaminophen, Caffeine, Isometheptene

These two interact in 4 distinct ways. Each one is explained separately below.

Why Are There 4 Interactions?

Ephedra interacts with whole categories of medication. Acetaminophen, Caffeine, Isometheptene falls into 4 of those categories, so it can interact with Ephedra in 4 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Major).

Major

STIMULANT DRUGS

1 of 4

Why this applies to Acetaminophen, Caffeine, Isometheptene

Acetaminophen, Caffeine, Isometheptene falls under STIMULANT DRUGS — the group Ephedra interacts with.

Theoretically, concomitant use might increase the risk for serious adverse effects.
Drugs with CNS stimulant properties might increase the risk of hypertension and the adverse cardiovascular effects of ephedra.
Severity Major Likelihood Probable Evidence D

Interaction 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..

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the concern with combining ephedra and Migralam (which contains acetaminophen, caffeine, and isometheptene). Both ephedra and two ingredients in this product, caffeine and isometheptene, are stimulants. Isometheptene tightens blood vessels, and caffeine is a mild stimulant on its own. Stacking these on top of ephedra's strong stimulant punch can push your heart and blood pressure too hard at the same time.

What could that look like? A racing or pounding heart, jitteriness, headache, a spike in blood pressure, and in rare cases more serious heart problems. The evidence here is mostly anecdotal and theoretical, but the potential harm is real. On top of that, ephedra isn't recommended at all. Please check with your pharmacist or doctor before mixing these, and ask about safer migraine options.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. White LM, Gardner SF, Gurley BJ, et al. Pharmacokinetics and Cardiovascular Effects of Ma-Huang (Ephedra sinica) in Normotensive Adults. J Clin Pharmacol 1997;37:116-22.
  2. Haller CA, Benowitz NL. Adverse cardiovascular and central nervous system events associated with dietary supplements containing ephedra alkaloids. N Engl J Med 2000;343:1833-8. PubMed
  3. Kernan, W. N., Viscoli, C. M., Brass, L. M., Broderick, J. P., Brott, T., Feldmann, E., Morgenstern, L. B., Wilterdink, J. L., and Horwitz, R. I. Phenylpropanolamine and the risk of hemorrhagic stroke. N.Engl.J Med 12-21-2000;343(25):1826-1832. PubMed
Major

METHYLXANTHINES

2 of 4

Acetaminophen, Caffeine, Isometheptene also falls under METHYLXANTHINES.

Concomitant use might increase the risk of serious adverse effects.
Use of ephedra with caffeine or other methylxanthines such as theophylline might increase the risk of stimulatory adverse effects. There is also some evidence that using ephedra with caffeine might increase the risk of serious life-threatening or debilitating adverse effects such as hypertension, myocardial infarction (MI), stroke, seizures, and death.
Severity Major Likelihood Probable Evidence D

Interaction 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..

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here is the key thing about Migralam: it already contains caffeine, which is a stimulant. Ephedra brings its own powerful stimulants (ephedrine and pseudoephedrine) to the table. When you stack two stimulants together, their effects pile up. That can mean a racing or pounding heart, jitteriness, trouble sleeping, anxiety, and rising blood pressure. In serious cases the concern is much bigger problems like dangerous blood pressure spikes, heart rhythm trouble, heart attack, stroke, or seizures.

The evidence here is mostly anecdotal, but ephedra is risky enough that it is banned in U.S. supplements. I would not combine these. Please talk with your pharmacist or doctor about safer migraine options before using anything with ephedra in it.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Vahedi K, Domingo V, Amarenco P, Bousser MG. Ischemic stroke in a sportsman who consumed MaHuang extract and creatine monohydrate for bodybuilding. J Neurol Neurosurg Psychiatr 2000;68:112-3.
  2. Haller CA, Benowitz NL. Adverse cardiovascular and central nervous system events associated with dietary supplements containing ephedra alkaloids. N Engl J Med 2000;343:1833-8. PubMed
  3. Dulloo AG. Herbal simulation of ephedrine and caffeine in treatment of obesity. Int J Obes Relat Metab Disord 2002;26:590-2. PubMed
  4. Kockler DR, McCarthy MW, Lawson CL. Seizure activity and unresponsiveness after hydroxycut ingestion. Pharmacotherapy 2001;21:647-51.. PubMed
  5. Weinberger M and Bronsky E. Interaction of ephedrine and theophylline. Clin Pharmacol Ther 1974;15(2):223. PubMed
  6. Tormey, W. P. and Bruzzi, A. Acute psychosis due to the interaction of legal compounds--ephedra alkaloids in 'vigueur fit' tablets, caffeine in 'red bull' and alcohol. Med Sci Law 2001;41(4):331-336. PubMed
  7. Ryall JE. Caffeine and ephedrine fatality. Bull Int Assoc Forensic Toxicol 1984;17:13.
  8. Rejent T, Michalek R, and Krajewski M. Caffeine fatality with coincident ephedrine. Bull Int Assoc Forensic Toxicol 1981;16:18-19.
Moderate

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES

3 of 4

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

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

Let's focus on the caffeine part of your Migralam (acetaminophen, caffeine, and isometheptene) here. In some animal studies, ephedra appears to speed up an enzyme called CYP1A2, which is the same enzyme your body uses to clear caffeine. If that happened in people, your body might break down the caffeine in this product a little faster, so you could get less of its effect. Caffeine is added to help these headache pills work better, so in theory you might notice a weaker boost.

Honestly, the bigger concern is the combo itself. Ephedra and caffeine are both stimulants, and stacking them can really push up your heart rate and blood pressure. Ephedra is banned in U.S. supplements for good reason. Please talk with your pharmacist or doctor before mixing these.

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

4 of 4

Acetaminophen, Caffeine, Isometheptene 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

This combination product (Migralam) contains acetaminophen, which your liver has to process, along with caffeine and isometheptene to help with migraine pain. The concern here is mostly about the liver. Ephedra supplements have been tied to a number of real cases of liver injury, and acetaminophen on its own can stress the liver too, especially at higher doses or with regular alcohol use. Stacking the two could, in theory, add up and make liver irritation more likely.

To be honest, this worry is based on how these substances behave, not on solid studies pairing them. Even so, ephedra is banned in U.S. supplements for good reason. I'd skip it and check with your pharmacist or doctor about safer migraine options.

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 336 major, 496 moderate known drug interactions in our database — the Acetaminophen, Caffeine, Isometheptene one above is among them. If you take anything else, check it against the full list below.

Major 336 Moderate 496 No known interaction 1,998 (incl. Acetaminophen, Caffeine, Isometheptene)
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, Caffeine, Isometheptene

This page covers Ephedra only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Caffeine, Isometheptene page lists 248 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), Grapefruit (major) and Peyote (major).

By severity: 11 major · 194 moderate · 43 minor.

Open the Acetaminophen, Caffeine, Isometheptene 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, Caffeine, Isometheptene 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, Caffeine, Isometheptene 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

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

29 days ago today
Medication Acetaminophen, Caffeine, Isometheptene
Top half

#1,039 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.

336Major
496Moderate
0Minor
1,997No known interaction
336 Major 496 Moderate 1,997 No interaction
Major

336 interactions

Showing 60 of 336 major interactions — see all 336 on the Ephedra page.

Moderate

496 interactions

Showing 60 of 496 moderate interactions — see all 496 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, Caffeine, Isometheptene, 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, Caffeine, Isometheptene supplement interactions › Every supplement checked against Acetaminophen, Caffeine, Isometheptene, 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, Caffeine, Isometheptene Together: Common Questions

Can you take Ephedra with Acetaminophen, Caffeine, Isometheptene?
This is rated a major interaction, so the combination is best avoided unless your doctor or pharmacist has specifically told you otherwise. Read the full details on this page and confirm with your pharmacist before combining them.
Why are there 4 interactions listed for Ephedra and Acetaminophen, Caffeine, Isometheptene?
Acetaminophen, Caffeine, Isometheptene 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, Caffeine, Isometheptene interaction?
We rate it Major. This is a clinically significant combination that is generally best avoided, or used only under the direct supervision of your physician or pharmacist.

Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy

Still Have a Question About Acetaminophen, Caffeine, Isometheptene and Ephedra?

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.