Drug & supplement interaction

Acacia Rigidula + Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine

Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine brand name: Colrex.

Moderate Interaction
The bottom line Moderate

Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine falls into 3 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 CYP2D6 substrates.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions3
EvidenceD
What do Severity, Likelihood & Evidence mean?
Know someone taking this? Share
Interaction report

Acacia Rigidula and Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine

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

Why Are There 3 Interactions?

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

Moderate

CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES

1 of 3

Why this applies to Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine

Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine falls under CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES — the group Acacia Rigidula interacts with.

Theoretically, Acacia rigidula products that are adulterated with beta-methylphenylethylamine (BMPEA) might increase the levels of CYP2D6 substrates.
In vitro research shows that BMPEA, an adulterant found in many Acacia rigidula products, strongly inhibits CYP2D6 enzyme.
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 wrinkle with this combo cold-and-cough product: the codeine part is a prodrug. Your body has to use an enzyme called CYP2D6 to turn codeine into morphine, which is what actually relieves pain and quiets a cough. Some Acacia rigidula products have been found spiked with a stimulant called BMPEA, and in lab studies BMPEA blocks that very enzyme.

If that enzyme is blocked, codeine may not convert well, so you could get less cough and pain relief than expected. On top of that, the supplement's stimulant effects could clash with the drowsiness from chlorpheniramine, and stack onto phenylephrine to raise blood pressure or heart rate. This is only theoretical (lab data, not people), but given the safety questions around these products, I'd check with your pharmacist before mixing them.

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

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

2 of 3

Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine also falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES.

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

This Colrex product is a combination cold medicine, and the piece I want to focus on is the codeine. Some Acacia rigidula products have been found spiked with a hidden stimulant called BMPEA, and in lab dishes that compound slowed down the CYP3A4 enzyme a bit. Your liver uses CYP3A4 to help clear codeine, so in theory codeine could hang around a little longer and feel stronger. That could mean more drowsiness, dizziness, constipation, or slowed breathing.

Honestly though, this is only test-tube data, so it is more theoretical than proven. The bigger concern for me is the unapproved stimulant itself stacking with phenylephrine, which can raise blood pressure and heart rate. I would skip the Acacia product and run it by your pharmacist first.

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

3 of 3

Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine 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

Here's the piece I want you to focus on with Colrex: it already contains phenylephrine, a decongestant that gently revs up your heart and can nudge your blood pressure upward. Acacia rigidula is sold as a stimulant, and some of these products have even tested positive for a hidden stimulant drug called BMPEA. Stacking two stimulant-type ingredients together is the worry here.

So the concern isn't about your liver or how the codeine gets activated. It's that the stimulant effects could add up, possibly leaving you with a racing heart, jitteriness, higher blood pressure, or trouble sleeping. This is a theoretical, pharmacology-based caution rather than something proven, but given the shaky safety record of these products, I'd skip the acacia and check with your pharmacist first.

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, Chlorpheniramine, Codeine, Phenylephrine 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 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, Chlorpheniramine, Codeine, Phenylephrine

This page covers Acacia Rigidula only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine page lists 338 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 Ephedra (major).

By severity: 18 major · 275 moderate · 45 minor.

From our pharmacist’s overview on the Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine page

“Someone taking Colrex is usually fighting a miserable cold, and cold season is also when people reach for herbal sleep aids and energy boosters, which is exactly where this list bites hardest. Colrex combines acetaminophen, chlorpheniramine, codeine, and phenylephrine, and 18 of its 338 supplement interactions rate major, enough to war…”

Reviewed by 2 · Jul 18, 2026

Open the Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine interaction page

How much people look this up

Where Acacia Rigidula and Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine 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
Steady interest

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

29 days ago today
Medication Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine
Top 10%

#268 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
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
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
Pharmacist Counseling Corner

Taking Acacia Rigidula and Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine Together: Common Questions

Can you take Acacia Rigidula with Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine?
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 Acacia Rigidula and Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine?
Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine 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, Chlorpheniramine, Codeine, Phenylephrine 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 Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine and Acacia Rigidula?

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.