Drug & supplement interaction

Eleuthero + 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 Eleuthero can interact with; the most serious is rated moderate. Theoretically, eleuthero might increase levels of drugs metabolized by CYP1A2.

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

Eleuthero and Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine

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

Why Are There 3 Interactions?

Eleuthero interacts with whole categories of medication. Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine falls into 3 of those categories, so it can interact with Eleuthero 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 1A2 (CYP1A2) SUBSTRATES

1 of 3

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

Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine falls under CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES — the group Eleuthero interacts with.

Theoretically, eleuthero might increase levels of drugs metabolized by CYP1A2.
In vitro and animal research suggest that standardized extracts of eleuthero inhibit CYP1A2. 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 thing to know about this combo product (Hycomine Compound): it contains caffeine, and caffeine is cleared from your body mainly by a liver enzyme called CYP1A2. Lab and animal studies hint that eleuthero may slow that enzyme down. If that happens in people, caffeine could hang around longer than usual, which might mean more jitteriness, a racing heart, trouble sleeping, or feeling wired.

I want to be honest about the evidence here, though. This effect has only shown up in test-tube and animal research, not in actual humans, so it's theoretical at this point. For most folks it's likely a minor concern. Still, if you notice extra restlessness or a pounding heart, mention it to your pharmacist or doctor before changing anything.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Harkey MR, Henderson GL, Zhou L, et al. Effects of Siberian ginseng (Eleutherococcus senticosus) on c-DNA-expressed P450 drug metabolizing enzymes. Alt Ther 2001;7:S14.
Minor

CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES

2 of 3

Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine also falls under CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES.

Theoretically, eleuthero might increase levels of drugs metabolized by CYP2D6.
In vitro and animal research suggest that standardized extracts of eleuthero might inhibit CYP2D6. However, research in healthy human volunteers has found that taking eleuthero 485 mg twice daily for 14 days does not inhibit CYP2D6 drug metabolism.
Severity Minor Likelihood Unlikely Evidence B

Interaction has been demonstrated in animal or in lab research but has been shown not to occur in humans..

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

This combination product (Hycomine Compound) contains hydrocodone, which is the piece that matters here. Hydrocodone is a prodrug partly turned into its stronger painkilling form by an enzyme called CYP2D6. Lab and animal studies hinted that eleuthero might slow that enzyme down, which could, in theory, mean less of hydrocodone's active form and slightly weaker pain relief.

Here's the reassuring part: a study in healthy people taking eleuthero twice daily for two weeks found no real effect on CYP2D6. So this is mostly a theoretical concern, rated minor and unlikely. I wouldn't lose sleep over it. Still, if your pain relief feels off or you have questions, check with your pharmacist or doctor before changing anything.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Harkey MR, Henderson GL, Zhou L, et al. Effects of Siberian ginseng (Eleutherococcus senticosus) on c-DNA-expressed P450 drug metabolizing enzymes. Alt Ther 2001;7:S14.
  2. Donovan JL, DeVane CL, Chavin KD, et al. Siberian Ginseng (Eleutheroccus senticosus) Effects on CYP2D6 and CYP3A4 Activity in Normal Volunteers. Drug Metab Dispos 2003;31:519-22.. PubMed
Minor

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

3 of 3

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

Theoretically, eleuthero might increase levels of drugs metabolized by CYP3A4.
In vitro and animal research suggest that standardized extracts of eleuthero might inhibit CYP3A4. However, research in healthy human volunteers has found that taking eleuthero 485 mg twice daily for 14 days does not inhibit CYP3A4 drug metabolism.
Severity Minor Likelihood Unlikely Evidence B

Interaction has been demonstrated in animal or in lab research but has been shown not to occur in humans..

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

This combo pill is a mix of pain reliever, cough/cold ingredients, and the opioid hydrocodone. On paper, eleuthero was once thought to slow down a liver enzyme called CYP3A4, which helps break down hydrocodone. If that happened, you might in theory feel more opioid effects like extra drowsiness, dizziness, slowed breathing, or constipation.

The reassuring part: when researchers actually tested eleuthero in healthy people for two weeks, it did not meaningfully block this enzyme. So this interaction is mostly theoretical and unlikely to cause trouble. Still, since hydrocodone is an opioid, it never hurts to mention any supplement to your pharmacist or doctor, especially if you notice unusual sleepiness.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Harkey MR, Henderson GL, Zhou L, et al. Effects of Siberian ginseng (Eleutherococcus senticosus) on c-DNA-expressed P450 drug metabolizing enzymes. Alt Ther 2001;7:S14.
  2. Donovan JL, DeVane CL, Chavin KD, et al. Siberian Ginseng (Eleutheroccus senticosus) Effects on CYP2D6 and CYP3A4 Activity in Normal Volunteers. Drug Metab Dispos 2003;31:519-22.. 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

Eleuthero Also Interacts With Other Medications

Eleuthero has 678 moderate, 461 minor 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 678 Minor 461 No known interaction 1,691 (incl. Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine)
Taking anything else?

Check Another of Your Medications Against Eleuthero

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

From our Q&A

Questions About Eleuthero or Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Eleuthero or Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine, not necessarily both, but if one is close to what you were about to ask it will usually go further than a database entry can:

Not quite your question? Ask our pharmacists directly — it is free, there is no account required, and answers usually come back within 24 hours.

Everything else you take

See Every Supplement That Interacts With Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine

This page covers Eleuthero 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 Eleuthero as Part of a Dietary Supplement Product? Check It for Interactions

We hold 3,795 real supplement products containing Eleuthero, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Eleuthero. Your product may carry other ingredients that interact with Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine too, on top of Eleuthero — 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 Eleuthero 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 Eleuthero
Top 5%

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

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

#716 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 Eleuthero

What is Eleuthero?

Eleuthero
  • Fatigue and low energy
  • Physical and athletic performance
  • Stress resistance (adaptogen)
  • Immune support
  • Mental focus and alertness

Eleuthero is an herb traditionally used as an 'adaptogen' to fight fatigue, boost energy, and help the body handle stress. The scientific evidence behind these uses is limited and mixed, so it should not replace proven treatments. It is generally well tolerated short-term, but pregnant and breastfeeding people and those with certain conditions should avoid it or check with a healthcare provider first.

Read the full Eleuthero monograph & all interactions
Keep checking

Other Drugs & Eleuthero

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

0Major
678Moderate
461Minor
1,690No known interaction
678 Moderate 461 Minor 1,690 No interaction
Moderate

678 interactions

Showing 60 of 678 moderate interactions — see all 678 on the Eleuthero page.

Minor

461 interactions

Showing 60 of 461 minor interactions — see all 461 on the Eleuthero page.

No interaction 1,690 drugs checked — show the list

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

Showing the 60 most looked-up of 1,690 medications checked with no known interaction — see the full Eleuthero list.

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

Can you take Eleuthero 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 Eleuthero and Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine?
Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine belongs to more than one drug category, and Eleuthero 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 Eleuthero 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 Eleuthero?

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.