Drug & supplement interaction

Eleuthero + Aspirin, Butalbital, Caffeine, Codeine Phosphate

Aspirin, Butalbital, Caffeine, Codeine Phosphate brand name: Fiorinal w/ Codeine.

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

Aspirin, Butalbital, Caffeine, Codeine Phosphate falls into 4 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
Interactions4
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Eleuthero and Aspirin, Butalbital, Caffeine, Codeine Phosphate

These two interact in 4 distinct ways. Each one is explained separately below.

Why Are There 4 Interactions?

Eleuthero interacts with whole categories of medication. Aspirin, Butalbital, Caffeine, Codeine Phosphate falls into 4 of those categories, so it can interact with Eleuthero in 4 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 4

Why this applies to Aspirin, Butalbital, Caffeine, Codeine Phosphate

Aspirin, Butalbital, Caffeine, Codeine Phosphate 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

The piece of this combo pill that matters here is the caffeine. Your liver clears caffeine using an enzyme called CYP1A2, and lab and animal studies hint that eleuthero might slow that enzyme down a bit. If that happened in people, caffeine could hang around longer, which might leave you feeling jittery, restless, or wired, with a racing heartbeat or trouble sleeping.

Here's the honest part: this is only a theoretical concern. It has been seen in test tubes and animals, not in actual humans, so the real-world risk is likely small. The aspirin, butalbital, and codeine portions are cleared by different pathways and shouldn't be affected. Still, if you notice extra caffeine jitters, mention it to your pharmacist or doctor.

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.
Moderate

ANTICOAGULANT/ANTIPLATELET DRUGS

2 of 4

Aspirin, Butalbital, Caffeine, Codeine Phosphate also falls under ANTICOAGULANT/ANTIPLATELET DRUGS.

Theoretically, eleuthero may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
In vitro and animal research shows that a constituent of eleuthero, dihydroxybenzoic acid, appears to inhibit platelet aggregation. Concomitant use with anticoagulant or antiplatelet drugs might increase the risk of bleeding. 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 piece that matters with this combination: your Fiorinal with Codeine contains aspirin, and aspirin already thins the blood by keeping platelets from clumping together. Eleuthero may do a little of the same thing. In lab and animal studies, one of its compounds (dihydroxybenzoic acid) slowed platelet clumping. Stacked on top of aspirin, that could in theory nudge your bleeding risk up a notch, showing up as easier bruising, nosebleeds, or a cut that's slow to stop.

I want to be honest with you though: this has never actually been reported in people, and the evidence is only test-tube and animal level. So it's worth a quick mention to your pharmacist or doctor, especially before surgery or dental work, but it's not a reason to panic.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Yun-Choi HS, Kim JH, Lee JR. Potential inhibitors of platelet aggregation from plant sources, III. J Nat Prod 1987;50:1059-64. PubMed
  2. Bazaz'ian, G. G., Liapina, L. A., Pastorova, V. E., and Zvereva, E. G. [Effect of Eleutherococcus on the functional status of the anticoagulation system in older animals]. Fiziol.Zh.SSSR Im I.M.Sechenova 1987;73(10):1390-1395.
Minor

CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES

3 of 4

Aspirin, Butalbital, Caffeine, Codeine Phosphate 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

Here's the part of Fiorinal with Codeine that matters most: the codeine piece needs an enzyme called CYP2D6 to turn into morphine, which is what actually relieves pain. So codeine is a prodrug. In a test tube and in animals, eleuthero looked like it might block that enzyme. If that happened in people, you could get less pain relief from the codeine, since less of it would be converted to its active form.

The good news is that careful human studies showed eleuthero did not actually slow down CYP2D6 at typical doses. So this concern stays mostly theoretical and ranks as minor and unlikely. Still, if your pain isn't well controlled or you have questions, just check with your pharmacist or doctor.

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

4 of 4

Aspirin, Butalbital, Caffeine, Codeine Phosphate 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

Let me put your mind at ease here. This combination product (Fiorinal with Codeine) has several ingredients, and the one that touches the CYP3A4 enzyme is mainly butalbital, the barbiturate that gives it that relaxing, sedating quality. The theory on file is that eleuthero might slow down CYP3A4, which could in theory let a little more drug build up. With butalbital, that might mean feeling extra drowsy, foggy, or dizzy.

Here's the reassuring part: this concern comes from lab and animal studies only. When researchers actually gave healthy people eleuthero (485 mg twice daily for two weeks), it did not change CYP3A4 activity. So a real-world problem is unlikely. Still, since this medicine also contains codeine and a barbiturate, please run it by your pharmacist before combining.

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 Aspirin, Butalbital, Caffeine, Codeine Phosphate 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. Aspirin, Butalbital, Caffeine, Codeine Phosphate)
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 Aspirin, Butalbital, Caffeine, Codeine Phosphate

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 Aspirin, Butalbital, Caffeine, Codeine Phosphate, 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 Aspirin, Butalbital, Caffeine, Codeine Phosphate

This page covers Eleuthero only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Aspirin, Butalbital, Caffeine, Codeine Phosphate page lists 398 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 Danshen (major).

By severity: 17 major · 334 moderate · 47 minor.

From our pharmacist’s overview on the Aspirin, Butalbital, Caffeine, Codeine Phosphate page

“Fiorinal with Codeine packs four active drugs into one capsule, and I would treat its supplement list with genuine wariness rather than a quick skim. The aspirin component is why roughly half of the 398 ingredients on file raise bleeding risk, while the codeine and butalbital explain a second large cluster that deepens sedation, someti…”

Reviewed by 2 · Jul 18, 2026

Open the Aspirin, Butalbital, Caffeine, Codeine Phosphate 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 Aspirin, Butalbital, Caffeine, Codeine Phosphate 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 Aspirin, Butalbital, Caffeine, 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 Eleuthero
Top 5%

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

29 days ago today
Medication Aspirin, Butalbital, Caffeine, Codeine Phosphate
Steady interest

#1,786 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 Aspirin, Butalbital, Caffeine, Codeine Phosphate, 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 Aspirin, Butalbital, Caffeine, Codeine Phosphate supplement interactions › Every supplement checked against Aspirin, Butalbital, Caffeine, Codeine Phosphate, 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 Aspirin, Butalbital, Caffeine, Codeine Phosphate Together: Common Questions

Can you take Eleuthero with Aspirin, Butalbital, Caffeine, 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 4 interactions listed for Eleuthero and Aspirin, Butalbital, Caffeine, Codeine Phosphate?
Aspirin, Butalbital, Caffeine, Codeine Phosphate 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 Aspirin, Butalbital, Caffeine, 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

Still Have a Question About Aspirin, Butalbital, Caffeine, Codeine Phosphate and Eleuthero?

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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.