Drug & supplement interaction

Indian Snakeroot + 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 Indian Snakeroot can interact with; the most serious is rated moderate. Theoretically, taking Indian snakeroot might cause additive sedative effects.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions3
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Indian Snakeroot and Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine

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

Why Are There 3 Interactions?

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

Moderate

CNS DEPRESSANTS

1 of 3

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

Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine falls under CNS DEPRESSANTS — the group Indian Snakeroot interacts with.

Theoretically, taking Indian snakeroot might cause additive sedative effects.
Sedation and drowsiness have been reported in clinical trials using Indian snakeroot.
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 watch with this combo product (sold as Hycomine Compound). It already contains two ingredients that can make you sleepy: hydrocodone, an opioid cough and pain reliever, and chlorpheniramine, a sedating antihistamine. Indian snakeroot, thanks to its reserpine content, has its own calming, drowsy effect. Stack them together and the sleepiness can add up.

What that might look like in real life: feeling extra groggy, foggy-headed, dizzy, or slowed down, especially when driving or moving around. This is a theoretical concern based on how these things work, not strong study data, so don't panic. Still, since you're mixing sedating ingredients, it's worth a quick chat with your pharmacist or doctor before combining them.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Sheldon MB, Kotte JH. Effect of Rauwolfia serpentina and reserpine on the blood pressure in essential hypertension; a long-term double-blind study. Circulation. 1957 Aug;16(2):200-6.
  2. Vakil RJ. A clinical trial of Rauwolfia serpentina in essential hypertension. Br Heart J. 1949 Oct;11(4):350-5. PubMed
  3. Achor RW, Hanson NO, Gifford RW Jr. Hypertension treated with Rauwolfia serpentina (whole root) and with reserpine; controlled study disclosing occasional severe depression. J Am Med Assoc. 1955 Oct 29;159(9):841-5. PubMed
  4. Wilkins RW, Judson WE. The use of Rauwolfia serpentina in hypertensive patients. N Engl J Med. 1953 Jan 8;248(2):48-53.
Moderate

CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES

2 of 3

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

Theoretically, Indian snakeroot might inhibit CYP2D6 enzymes and reduce the metabolism of CYP2D6 substrates.
Indian snakeroot contains small amounts of the drug yohimbine. In vitro research shows that yohimbine inhibits CYP2D6 enzyme activity.
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 pill (Hycomine Compound) contains hydrocodone, and that's the ingredient worth thinking about here. Hydrocodone is a bit of a prodrug: your liver's CYP2D6 enzyme converts part of it into a stronger painkiller. The concern on file is that Indian snakeroot may contain a trace of yohimbine that could block CYP2D6.

If that blocking actually happened, your body might make less of hydrocodone's active form, so you could get less pain relief than expected. The flip side is that more unchanged drug could linger, which may add to drowsiness. Honestly, this is theoretical, based only on lab data, so I wouldn't lose sleep over it. Still, because snakeroot itself can drop your blood pressure and add sedation, please check with your pharmacist or doctor before pairing them.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. VandenBrink, B. M., Foti, R. S., Rock, D. A., Wienkers, L. C., and Wahlstrom, J. L. Prediction of CYP2D6 drug interactions from in vitro data: evidence for substrate-dependent inhibition. Drug Metab Dispos. 2012;40(1):47-53. PubMed
Moderate

STIMULANT DRUGS

3 of 3

Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine also falls under STIMULANT DRUGS.

Theoretically, concomitant use might cause additive effects.
Yohimbine, a constituent of Indian snakeroot, has sympathomimetic effects and increases blood pressure in a dose-dependent manner. Theoretically, taking Indian snakeroot with stimulant drugs can have additive stimulant and hypertensive 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 that matters for this combo: your Hycomine Compound includes two stimulant-type ingredients, caffeine and phenylephrine (a decongestant that raises blood pressure). Indian snakeroot can carry compounds with their own sympathomimetic, blood-pressure-raising activity. The concern on file is theoretical, meaning it's based on how these things work in the body rather than strong studies, but the worry is an additive effect.

In plain terms, stacking them could nudge your blood pressure up and leave you feeling jittery, racing-hearted, or restless from the caffeine and phenylephrine side. That said, Indian snakeroot's reserpine actually lowers blood pressure, so the overall picture is genuinely unpredictable. Please don't combine these without checking with your pharmacist or doctor first.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Leung AY, Foster S. Encyclopedia of Common Natural Ingredients Used in Food, Drugs and Cosmetics. 2nd ed. New York, NY: John Wiley & Sons, 1996.
  2. McGuffin M, Hobbs C, Upton R, Goldberg A, eds. American Herbal Products Association's Botanical Safety Handbook. Boca Raton, FL: CRC Press, LLC 1997.
  3. Bharucha AE, Skaar T, Andrews CN, et al Relationship of cytochrome P450 pharmacogenetics to the effects of yohimbine on gastrointestinal transit and catecholamines in healthy subjects. Neurogastroenterol Motil. 2008;20(8):891-9. 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

Indian Snakeroot Also Interacts With Other Medications

Indian Snakeroot has 83 major, 759 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.

Major 83 Moderate 759 No known interaction 1,988 (incl. Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine)
Taking anything else?

Check Another of Your Medications Against Indian Snakeroot

Covers the 2,830 medications we’ve checked against Indian Snakeroot. 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 Indian Snakeroot 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 Indian Snakeroot as Part of a Dietary Supplement Product? Check It for Interactions

We hold 70 real supplement products containing Indian Snakeroot, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Indian Snakeroot. Your product may carry other ingredients that interact with Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine too, on top of Indian Snakeroot — 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 Indian Snakeroot 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 Indian Snakeroot
Top half

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

29 days ago today
Medication Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine
Top 5%

#103 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 Indian Snakeroot

What is Indian Snakeroot?

Indian Snakeroot
  • High blood pressure
  • Anxiety and stress
  • Insomnia
  • Agitation
  • Fever (traditional use)

Indian snakeroot is a traditional Ayurvedic plant that contains reserpine, a compound with real blood-pressure-lowering and sedative effects. Because its potent alkaloids can cause serious side effects like depression and very low blood pressure, it should never be used without medical supervision. It is not a safe or simple home remedy, and many countries restrict its use.

Read the full Indian Snakeroot monograph & all interactions
Keep checking

Other Drugs & Indian Snakeroot

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

83Major
759Moderate
0Minor
1,987No known interaction
83 Major 759 Moderate 1,987 No interaction
Major

83 interactions

Showing 60 of 83 major interactions — see all 83 on the Indian Snakeroot page.

Moderate

759 interactions

Showing 60 of 759 moderate interactions — see all 759 on the Indian Snakeroot page.

No interaction 1,987 drugs checked — show the list

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

Showing the 60 most looked-up of 1,987 medications checked with no known interaction — see the full Indian Snakeroot list.

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

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