Drug & supplement interaction

Acacia Rigidula + Acetaminophen, Aspirin, Caffeine

Acetaminophen, Aspirin, Caffeine brand names: Excedrin Migraine, Excedrin, Excedrin Extra Strength.

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

Acetaminophen, Aspirin, Caffeine falls into 2 drug categories that Acacia Rigidula can interact with; the most serious is rated moderate. Theoretically, Acacia rigidula products that are adulterated with beta-methylphenylethylamine (BMPEA) might increase the levels of CYP3A4 substrates.

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

Acacia Rigidula and Acetaminophen, Aspirin, Caffeine

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

Why Are There 2 Interactions?

Acacia Rigidula interacts with whole categories of medication. Acetaminophen, Aspirin, Caffeine falls into 2 of those categories, so it can interact with Acacia Rigidula 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 3A4 (CYP3A4) SUBSTRATES

1 of 2

Why this applies to Acetaminophen, Aspirin, Caffeine

Acetaminophen, Aspirin, Caffeine falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES — the group Acacia Rigidula interacts with.

Theoretically, Acacia rigidula products that are adulterated with beta-methylphenylethylamine (BMPEA) might increase the levels of CYP3A4 substrates.
In vitro research shows that BMPEA, an adulterant found in many Acacia rigidula products, inhibits CYP3A4 enzyme by 37%.
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 thing to keep in mind with Excedrin (acetaminophen, aspirin, and caffeine). Some Acacia rigidula products have been found spiked with a hidden stimulant called BMPEA. In lab testing, BMPEA slowed down a liver enzyme called CYP3A4 by about a third. If that happens in real life, drugs cleared by that enzyme could build up a bit more than usual. None of the three ingredients in Excedrin are prodrugs, so they wouldn't be weakened by this.

I'll be honest, this is only theoretical and based on test-tube work, not people. The bigger worry is simply stacking two stimulants: the caffeine in Excedrin plus a stimulant-laced supplement can leave you jittery, with a racing heart, or trouble sleeping. I'd skip the Acacia product and check with your pharmacist first.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Liu Y, Santillo MF. Cytochrome P450 2D6 and 3A4 enzyme inhibition by amine stimulants in dietary supplements. Drug Test Anal. 2016;8(3-4):307-10. PubMed
Moderate

STIMULANT DRUGS

2 of 2

Acetaminophen, Aspirin, Caffeine also falls under STIMULANT DRUGS.

Theoretically, taking Acacia rigidula with stimulant drugs might increase the risk of adverse cardiovascular effects.
Constituents and adulterants found in Acacia rigidula can have stimulant effects.
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 to focus on here is the caffeine in Excedrin Migraine. Caffeine is already a stimulant, and Acacia rigidula products may contain natural stimulant-like amines (and some have even been found spiked with an unapproved stimulant called BMPEA). Stacking two stimulants together can add up, so the worry is mostly about your heart and nerves: a racing or pounding heartbeat, higher blood pressure, jitteriness, anxiety, and trouble sleeping.

To be fair, this is a theoretical concern based on how these ingredients behave, not on solid human studies, so I don't want to alarm you. Still, given the quality and safety questions around Acacia rigidula, I'd avoid combining them and check with your pharmacist or doctor first, especially if you have any heart or blood pressure issues.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Pawar RS, Grundel E, Fardin-Kia AR, Rader JI. Determination of selected biogenic amines in Acacia rigidula plant materials and dietary supplements using LC-MS/MS methods. J Pharm Biomed Anal. 2014 Jan;88:457-66. doi: 10.1016/j.jpba.2013.09.012. Epub 2013 PubMed
  2. Cohen PA, Bloszies C, Yee C, Gerona R. An amphetamine isomer whose efficacy and safety in humans has never been studied, ß-methylphenylethylamine (BMPEA), is found in multiple dietary supplements. Drug Test Anal. 2015 Apr 7. 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

Acacia Rigidula Also Interacts With Other Medications

Acacia Rigidula has 812 moderate known drug interactions in our database — the Acetaminophen, Aspirin, Caffeine one above is among them. If you take anything else, check it against the full list below.

Moderate 812 No known interaction 2,018 (incl. Acetaminophen, Aspirin, Caffeine)
Taking anything else?

Check Another of Your Medications Against Acacia Rigidula

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

Everything else you take

See Every Supplement That Interacts With Acetaminophen, Aspirin, Caffeine

This page covers Acacia Rigidula only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Aspirin, Caffeine page lists 371 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), Danshen (major) and Ephedra (major).

By severity: 13 major · 312 moderate · 46 minor.

From our pharmacist’s overview on the Acetaminophen, Aspirin, Caffeine page

“Excedrin (acetaminophen, aspirin, and caffeine) packs three drugs into one tablet, which multiplies the ways supplements can collide with it, so treat this list with real care. Most entries involve the aspirin: hundreds of herbs add to its blood-thinning effect and raise bleeding risk, and even beer or wine earns a major rating for sto…”

Reviewed by 2 · Jul 18, 2026

Open the Acetaminophen, Aspirin, Caffeine interaction page

How much people look this up

Where Acacia Rigidula and Acetaminophen, Aspirin, Caffeine 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 Acacia Rigidula
Top half

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

29 days ago today
Medication Acetaminophen, Aspirin, Caffeine
Top 5%

#64 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 Acacia Rigidula

What is Acacia Rigidula?

Acacia Rigidula
  • Weight loss
  • Energy and stimulation
  • Boosting metabolism
  • Appetite control
  • Pre-workout/athletic performance

Acacia rigidula is a shrub from Texas and Mexico that is marketed in weight-loss and energy supplements. There is very little reliable human evidence that it works, and some products have been found to contain an unapproved stimulant drug (BMPEA), which raises real safety concerns. Most people should avoid it and talk to a pharmacist or doctor before trying any product containing it.

Read the full Acacia Rigidula monograph & all interactions
Keep checking

Other Drugs & Acacia Rigidula

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

0Major
812Moderate
0Minor
2,017No known interaction
812 Moderate 2,017 No interaction
Moderate

812 interactions

Showing 60 of 812 moderate interactions — see all 812 on the Acacia Rigidula page.

No interaction 2,017 drugs checked — show the list

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

Showing the 60 most looked-up of 2,017 medications checked with no known interaction — see the full Acacia Rigidula list.

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

Can you take Acacia Rigidula with Acetaminophen, Aspirin, Caffeine?
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 Acacia Rigidula and Acetaminophen, Aspirin, Caffeine?
Acetaminophen, Aspirin, Caffeine belongs to more than one drug category, and Acacia Rigidula 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 Acacia Rigidula and Acetaminophen, Aspirin, Caffeine 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.