Drug & supplement interaction

Acacia Rigidula + Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine

Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine brand name: Hycomine Compound.

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

Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, 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?
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Interaction report

Acacia Rigidula and Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, 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, Caffeine, Chlorpheniramine, Hydrocodone, 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, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine

Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, 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

This combination cold and pain product contains hydrocodone, which is worth a closer look here. Hydrocodone is actually a prodrug for part of its effect, meaning your body uses the CYP2D6 enzyme to convert some of it into hydromorphone, a stronger painkiller. Some Acacia rigidula products are tainted with a stimulant called BMPEA, and lab studies suggest BMPEA can block CYP2D6.

If that enzyme is slowed, you may get less of that converted pain relief. On top of that, the stimulant amines in this supplement could clash with the caffeine and decongestant (phenylephrine) here, possibly raising heart rate or blood pressure. This is theoretical and based only on lab data, so don't panic, but please run it past 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

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

2 of 3

Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, 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 combination product (Hycomine Compound) packs in several ingredients, and the one that matters most here is hydrocodone, the opioid pain reliever. Hydrocodone is partly cleared by a liver enzyme called CYP3A4. Some Acacia rigidula products have been found to contain a hidden stimulant (BMPEA), and lab studies suggest it can mildly slow that same enzyme. In theory, that could let a bit more hydrocodone build up, leading to more drowsiness, dizziness, slowed breathing, or constipation.

I want to be honest though: this is only based on test-tube research, not real people, so the actual risk is uncertain. There's also a separate worry, since both that stimulant and the caffeine here can speed up your heart and raise blood pressure. Honestly, I'd skip the Acacia supplement 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

3 of 3

Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, 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 thing to keep in mind: this combination product (Hycomine Compound) already has two things that rev up your body, caffeine (a stimulant) and phenylephrine (a decongestant that can raise blood pressure and heart rate). Acacia rigidula products may contain natural amines, and some have even been found spiked with an unapproved stimulant called BMPEA. Stacking another stimulant on top can add up.

So in theory, taking them together could push your heart rate and blood pressure higher, leaving you jittery, anxious, with a racing or pounding heartbeat, or trouble sleeping. This is a theoretical concern based on how these ingredients work, not strong human proof. Still, with an unpredictable supplement like this, I'd hold off and check with your pharmacist or doctor first.

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, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine 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, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine)
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, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine

This page covers Acacia Rigidula only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine page lists 339 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: 17 major · 276 moderate · 46 minor.

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

“If you've been prescribed Hycomine Compound (acetaminophen, caffeine, chlorpheniramine, hydrocodone, and phenylephrine) for a hard cough or cold, this list deserves real attention, since 17 of the 339 flagged supplements are rated major and most of those magnify what the medicine already does. Anything sedating, alcohol included, stack…”

Reviewed by 2 · Jul 18, 2026

Open the Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine interaction page

How much people look this up

Where Acacia Rigidula and Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, 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
Top half

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

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

#144 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, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine, 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, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine supplement interactions › Every supplement checked against Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine, 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, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine Together: Common Questions

Can you take Acacia Rigidula with Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, 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, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine?
Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, 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, Caffeine, Chlorpheniramine, Hydrocodone, 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

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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.