Drug & supplement interaction

Higenamine + Guaifenesin, Hydrocodone

Guaifenesin, Hydrocodone brand names: Pneumotussin, Entuss.

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

Guaifenesin, Hydrocodone falls into 2 drug categories that Higenamine can interact with; the most serious is rated moderate. Theoretically, higenamine might increase the levels and clinical effects of drugs metabolized by CYP2D6.

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

Higenamine and Guaifenesin, Hydrocodone

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

Why Are There 2 Interactions?

Higenamine interacts with whole categories of medication. Guaifenesin, Hydrocodone falls into 2 of those categories, so it can interact with Higenamine 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 2D6 (CYP2D6) SUBSTRATES

1 of 2

Why this applies to Guaifenesin, Hydrocodone

Guaifenesin, Hydrocodone falls under CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES — the group Higenamine interacts with.

Theoretically, higenamine might increase the levels and clinical effects of drugs metabolized by CYP2D6.
In vitro research shows that higenamine inhibits CYP2D6 enzymes. However, this effect has not been reported in humans.
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 combo product pairs an expectorant (guaifenesin, which thins mucus) with hydrocodone, an opioid cough suppressant and pain reliever. Here's the wrinkle worth knowing: hydrocodone is partly a prodrug. Your body uses the CYP2D6 enzyme to convert it into hydromorphone, a stronger active form. Higenamine has been shown in lab dish studies to block CYP2D6, but this has never been confirmed in actual people.

If that blocking did happen, you'd expect less conversion to the potent form, so the pain or cough relief might feel weaker, while levels of hydrocodone itself could shift unpredictably. Since this is theoretical only, I wouldn't panic. Still, given higenamine's effects on heart rate and blood pressure, please run this pairing by your pharmacist or doctor 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 2

Guaifenesin, Hydrocodone also falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES.

Theoretically, higenamine might increase the levels and clinical effects drugs metabolized by CYP3A4.
In vitro research shows that higenamine inhibits CYP3A4 enzymes by 21%. However, this effect has not been reported in humans.
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 with this combo. Your cough medicine contains hydrocodone, an opioid that the liver partly processes using an enzyme called CYP3A4. Lab studies (not real people) hint that higenamine can slightly slow that enzyme. In theory, that could let a bit more hydrocodone linger in your system, nudging up its usual effects like drowsiness, dizziness, constipation, or slower, shallower breathing.

I want to be honest though: this is based only on test-tube data, and the blocking effect was small (around 21%). It hasn't been shown in humans. On top of that, higenamine is a heart stimulant with iffy labeling, so I'd skip it and check with your pharmacist or doctor before mixing the two.

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

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

Higenamine Also Interacts With Other Medications

Higenamine has 890 moderate known drug interactions in our database — the Guaifenesin, Hydrocodone one above is among them. If you take anything else, check it against the full list below.

Moderate 890 No known interaction 1,940 (incl. Guaifenesin, Hydrocodone)
Taking anything else?

Check Another of Your Medications Against Higenamine

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

Everything else you take

See Every Supplement That Interacts With Guaifenesin, Hydrocodone

This page covers Higenamine only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Guaifenesin, Hydrocodone page lists 212 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), Beer (major), Gamma-hydroxybutyrate (ghb) (major) and Grapefruit (major).

By severity: 9 major · 164 moderate · 39 minor.

Open the Guaifenesin, Hydrocodone interaction page

One more smart check

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

We hold 154 real supplement products containing Higenamine, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Higenamine. Your product may carry other ingredients that interact with Guaifenesin, Hydrocodone too, on top of Higenamine — 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 Higenamine and Guaifenesin, Hydrocodone 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 Higenamine
Top half

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

29 days ago today
Medication Guaifenesin, Hydrocodone
Steady interest

#2,057 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 Higenamine

What is Higenamine?

  • Weight loss and fat burning
  • Pre-workout energy and performance
  • Appetite suppression
  • Athletic stimulant
  • Traditional medicine remedies

Higenamine is a plant-based stimulant compound added to many weight-loss and pre-workout supplements, but there is very little human evidence that it works and real concerns about heart and blood pressure effects. It is banned in sports by the World Anti-Doping Agency (WADA), and product labels often list inaccurate amounts, so most people should approach it with caution and talk to a pharmacist or doctor first.

Read the full Higenamine monograph & all interactions
Keep checking

Other Drugs & Higenamine

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

0Major
890Moderate
0Minor
1,939No known interaction
890 Moderate 1,939 No interaction
Moderate

890 interactions

Showing 60 of 890 moderate interactions — see all 890 on the Higenamine page.

No interaction 1,939 drugs checked — show the list

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

Showing the 60 most looked-up of 1,939 medications checked with no known interaction — see the full Higenamine list.

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

Can you take Higenamine with Guaifenesin, Hydrocodone?
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 Higenamine and Guaifenesin, Hydrocodone?
Guaifenesin, Hydrocodone belongs to more than one drug category, and Higenamine 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 Higenamine and Guaifenesin, Hydrocodone 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 Guaifenesin, Hydrocodone and Higenamine?

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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.