Drug & supplement interaction

Guggul + 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

Guggul has a moderate interaction with Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine. Theoretically, guggul might reduce the effects of CYP3A4 substrates.

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

Guggul and Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine

Here is the interaction we found between these two, with the evidence behind it.

Moderate

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

Why this applies to Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine

Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES — the group Guggul interacts with.

Theoretically, guggul might reduce the effects of CYP3A4 substrates.
In vitro research shows that guggul constituents known as guggulsterones can induce CYP3A4.
Severity Moderate 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

This combination product (sold as Hycomine Compound) includes hydrocodone, a narcotic cough and pain reliever that your liver activates and clears using the CYP3A4 enzyme. The concern here is that guggul, in lab studies, seems to speed up (induce) that same enzyme. In theory, that could push your body to process hydrocodone faster, so you might notice less pain relief or less cough control than expected.

I want to be honest about how thin this evidence is. It comes only from test-tube and animal studies, not real patients, so we genuinely do not know how much it matters in everyday life. Culinary amounts are not the issue, concentrated guggul supplements are. If you take this medicine and want to try guggul, please run it by your pharmacist or doctor first.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Brobst DE, Ding X, Creech KL, et al. Guggulsterone activates multiple nuclear receptors and induces CYP3A gene expression through the pregnane X receptor. J Pharmacol Exp Ther 2004;310:528-35. 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

Guggul Also Interacts With Other Medications

Guggul has 756 moderate known drug interactions in our database — the Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine one above is one of them. If you take anything else, check it against the full list below.

Moderate 756 No known interaction 2,074 (incl. Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine)
Taking anything else?

Check Another of Your Medications Against Guggul

Covers the 2,830 medications we’ve checked against Guggul. 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 Guggul 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

One more smart check

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

We hold 955 real supplement products containing Guggul, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Guggul. Your product may carry other ingredients that interact with Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine too, on top of Guggul — 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 Guggul 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 Guggul
Top 25%

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

29 days ago today
Medication Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine
Top 25%

#445 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 Guggul

What is Guggul?

Guggul
  • High cholesterol
  • Joint pain and arthritis
  • Weight management
  • Acne
  • Skin conditions

Guggul is a gum resin from the Commiphora wightii tree, long used in Ayurvedic medicine for cholesterol, joint, and skin problems. Modern studies are mixed and often low-quality, and it can cause stomach upset and skin rashes. Talk to your pharmacist or doctor before using it, and avoid it during pregnancy and breastfeeding.

Read the full Guggul monograph & all interactions
Keep checking

Other Drugs & Guggul

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

0Major
756Moderate
0Minor
2,073No known interaction
756 Moderate 2,073 No interaction
Moderate

756 interactions

Showing 60 of 756 moderate interactions — see all 756 on the Guggul page.

No interaction 2,073 drugs checked — show the list

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

Showing the 60 most looked-up of 2,073 medications checked with no known interaction — see the full Guggul list.

See the full Guggul 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
Guggul 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 Guggul and Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine Together: Common Questions

Can you take Guggul 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.
How serious is the Guggul 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

Still Have a Question About Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine and Guggul?

Our pharmacists answer your medication & supplement questions — free.

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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.