Drug & supplement interaction

Indian Snakeroot + Acetaminophen, Butalbital, Codeine Phosphate

Acetaminophen, Butalbital, Codeine Phosphate brand name: Phrenilin #3.

Moderate Interaction
The bottom line Moderate

Acetaminophen, Butalbital, Codeine Phosphate falls into 2 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
Interactions2
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Indian Snakeroot and Acetaminophen, Butalbital, Codeine Phosphate

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

Why Are There 2 Interactions?

Indian Snakeroot interacts with whole categories of medication. Acetaminophen, Butalbital, Codeine Phosphate falls into 2 of those categories, so it can interact with Indian Snakeroot in 2 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 2

Why this applies to Acetaminophen, Butalbital, Codeine Phosphate

Acetaminophen, Butalbital, Codeine Phosphate 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 simple version: this combination product already brings two sleepy ingredients to the table. Butalbital is a barbiturate that calms the nervous system, and codeine is an opioid that can also make you drowsy and slow your breathing. Indian snakeroot contains reserpine, which has its own sedating, calming effect. Stack them together and the drowsiness can add up.

So the worry here isn't about your body breaking the drug down differently. It's simply additive sedation, more grogginess, dizziness, slow reactions, and possibly lower blood pressure. This is a theoretical concern based on how these things work, not from strong studies, but it's reasonable to take seriously since both can knock you out. Please check with your pharmacist or doctor before combining them, and avoid driving until you know how you feel.

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 2

Acetaminophen, Butalbital, Codeine Phosphate 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

Here's the wrinkle with this combo pill: the codeine part is actually a prodrug. Your body has to use an enzyme called CYP2D6 to turn codeine into morphine, which is what gives the pain relief. Indian snakeroot is thought to slow that same enzyme down (this is only lab-dish research, so it's theoretical, not proven in people).

If that slowdown does happen, you'd likely get less pain relief from the codeine, not more, since less of it gets activated. On top of that, snakeroot's reserpine strongly lowers blood pressure and can cause sedation and low mood, which can pile onto the drowsiness from the butalbital and codeine. Please don't change anything on your own. Run this pairing by your pharmacist or doctor first.

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

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, Butalbital, Codeine Phosphate one above is among them. If you take anything else, check it against the full list below.

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, Butalbital, Codeine Phosphate

This page covers Indian Snakeroot only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Butalbital, Codeine Phosphate page lists 240 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 Gamma-hydroxybutyrate (ghb) (major).

Open the Acetaminophen, Butalbital, Codeine Phosphate 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, Butalbital, Codeine Phosphate 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, Butalbital, Codeine Phosphate 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

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

29 days ago today
Medication Acetaminophen, Butalbital, Codeine Phosphate
Steady interest

#1,700 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
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
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

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Pharmacist Counseling Corner

Taking Indian Snakeroot and Acetaminophen, Butalbital, Codeine Phosphate Together: Common Questions

Can you take Indian Snakeroot with Acetaminophen, Butalbital, Codeine Phosphate?
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 Indian Snakeroot and Acetaminophen, Butalbital, Codeine Phosphate?
Acetaminophen, Butalbital, Codeine Phosphate 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, Butalbital, Codeine Phosphate 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.