Drug & supplement interaction

Gymnema + Acetaminophen, Butalbital, Caffeine, Codeine

Acetaminophen, Butalbital, Caffeine, Codeine brand names: Esgic with Codeine, Fioricet w/ Codeine.

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

Acetaminophen, Butalbital, Caffeine, Codeine falls into 2 drug categories that Gymnema can interact with; the most serious is rated moderate. Theoretically, gymnema might increase levels of drugs metabolized by CYP1A2.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions2
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Gymnema and Acetaminophen, Butalbital, Caffeine, Codeine

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

Why Are There 2 Interactions?

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

Why this applies to Acetaminophen, Butalbital, Caffeine, Codeine

Acetaminophen, Butalbital, Caffeine, Codeine falls under CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES — the group Gymnema interacts with.

Theoretically, gymnema might increase levels of drugs metabolized by CYP1A2.
Animal and in vitro research shows that gymnema can inhibit the CYP1A2 enzyme. In one animal study, oral administration of gymnema for 7 days increased the plasma concentrations of phenacetin, a CYP1A2 substrate, by about 1.4-fold and reduced the clearance of phenacetin by about 29%.
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 part of this combo pill that matters most with Gymnema: the caffeine. Caffeine is cleared by a liver enzyme called CYP1A2, and lab and animal studies hint that Gymnema may slow that enzyme down a bit. If it does, caffeine could hang around longer than usual, so you might notice more jitteriness, a faster heartbeat, trouble sleeping, or feeling wired.

I want to be honest about the evidence though: this is only theoretical, based on test-tube and animal work, not real people. The effect, if any, looks small. The other ingredients (acetaminophen, butalbital, and codeine) aren't really driven by this enzyme. Still, if you plan to use Gymnema regularly, run it by your pharmacist or doctor first.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Rammohan B, Samit K, Chinmoy D, et al. Human cytochrome P450 enzyme modulation by gymnema sylvestre: a predictive safety evaluation by LC-MS/MS. Pharmacogn Mag. 2016 Jul;12(Suppl 4):S389-S394.
  2. Vaghela M, Sahu N, Kharkar P, Pandita N. In vivo pharmacokinetic interaction by ethanolic extract of gymnema sylvestre with CYP2C9 (tolbutamide), CYP3A4 (amlodipine) and CYP1A2 (phenacetin) in rats. Chem Biol Interact. 2017 Dec 25;278:141-151. PubMed
  3. Vaghela M, Iyer K, Pandita N. In vitro inhibitory effect of gymnema sylvestre extracts and total gymnemic acids fraction on select cytochrome P450 activities in rat liver microsomes. Eur J Drug Metab Pharmacokinet. 2017 Oct 10. PubMed
Minor

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

2 of 2

Acetaminophen, Butalbital, Caffeine, Codeine also falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES.

Theoretically, gymnema might increase levels of drugs metabolized by CYP3A4.
One in vitro study using rat liver microsomes shows that gymnema can modestly inhibit the CYP3A4 enzyme. However, other in vitro research using human liver microsomes shows that gymnema does not affect CYP3A4 activity. Animal research also shows that gymnema does not alter the function of CYP3A4. In one study in rats, oral administration of gymnema for 7 days did not alter the clearance of amlodipine, a CYP3A4 substrate.
Severity Minor Likelihood Unlikely Evidence D

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 pill bundles acetaminophen, butalbital, caffeine, and codeine. The interaction on file is about CYP3A4, an enzyme your liver uses to help process some of these ingredients. The idea is that gymnema might slightly slow that enzyme, which could let certain components linger a bit longer. In theory, that might mean a touch more drowsiness, dizziness, or grogginess from the butalbital and codeine pieces.

Honestly though, this is very weak. The concern comes from a single rat-tissue lab study, while human-tissue and live animal studies showed no real effect. So a meaningful problem is unlikely. Still, since codeine and butalbital already cause sedation, it's worth a quick chat with your pharmacist or doctor before adding gymnema, especially if you have diabetes.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Rammohan B, Samit K, Chinmoy D, et al. Human cytochrome P450 enzyme modulation by gymnema sylvestre: a predictive safety evaluation by LC-MS/MS. Pharmacogn Mag. 2016 Jul;12(Suppl 4):S389-S394.
  2. Vaghela M, Sahu N, Kharkar P, Pandita N. In vivo pharmacokinetic interaction by ethanolic extract of gymnema sylvestre with CYP2C9 (tolbutamide), CYP3A4 (amlodipine) and CYP1A2 (phenacetin) in rats. Chem Biol Interact. 2017 Dec 25;278:141-151. PubMed
  3. Vaghela M, Iyer K, Pandita N. In vitro inhibitory effect of gymnema sylvestre extracts and total gymnemic acids fraction on select cytochrome P450 activities in rat liver microsomes. Eur J Drug Metab Pharmacokinet. 2017 Oct 10. 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

Gymnema Also Interacts With Other Medications

Gymnema has 346 moderate, 504 minor known drug interactions in our database — the Acetaminophen, Butalbital, Caffeine, Codeine one above is among them. If you take anything else, check it against the full list below.

Moderate 346 Minor 504 No known interaction 1,980 (incl. Acetaminophen, Butalbital, Caffeine, Codeine)
Taking anything else?

Check Another of Your Medications Against Gymnema

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

Everything else you take

See Every Supplement That Interacts With Acetaminophen, Butalbital, Caffeine, Codeine

This page covers Gymnema only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Butalbital, Caffeine, Codeine page lists 305 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: 15 major · 245 moderate · 45 minor.

Open the Acetaminophen, Butalbital, Caffeine, Codeine interaction page

One more smart check

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

We hold 1,084 real supplement products containing Gymnema, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Gymnema. Your product may carry other ingredients that interact with Acetaminophen, Butalbital, Caffeine, Codeine too, on top of Gymnema — 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 Gymnema and Acetaminophen, Butalbital, Caffeine, Codeine 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 Gymnema
Top 25%

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

29 days ago today
Medication Acetaminophen, Butalbital, Caffeine, Codeine
Top half

#923 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 Gymnema

What is Gymnema?

Gymnema
  • Blood sugar support
  • Type 2 diabetes
  • Sugar cravings
  • Weight management
  • Cholesterol support

Gymnema is an Ayurvedic herb best known for possibly helping lower blood sugar and reducing the taste of sweetness on the tongue. Some early human studies are encouraging for blood sugar support, but the evidence is still limited and not strong enough to replace standard treatment. If you have diabetes or take other medicines, talk with your pharmacist or doctor before using it.

Read the full Gymnema monograph & all interactions
Keep checking

Other Drugs & Gymnema

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

0Major
346Moderate
504Minor
1,979No known interaction
346 Moderate 504 Minor 1,979 No interaction
Moderate

346 interactions

Showing 60 of 346 moderate interactions — see all 346 on the Gymnema page.

Minor

504 interactions

Showing 60 of 504 minor interactions — see all 504 on the Gymnema page.

No interaction 1,979 drugs checked — show the list

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

Showing the 60 most looked-up of 1,979 medications checked with no known interaction — see the full Gymnema list.

See the full Gymnema interactions page
See every supplement checked against Acetaminophen, Butalbital, Caffeine, Codeine, 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
Gymnema monograph › Uses, safety, and every drug interaction in one place Acetaminophen, Butalbital, Caffeine, Codeine supplement interactions › Every supplement checked against Acetaminophen, Butalbital, Caffeine, Codeine, 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 Gymnema and Acetaminophen, Butalbital, Caffeine, Codeine Together: Common Questions

Can you take Gymnema with Acetaminophen, Butalbital, Caffeine, Codeine?
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 Gymnema and Acetaminophen, Butalbital, Caffeine, Codeine?
Acetaminophen, Butalbital, Caffeine, Codeine belongs to more than one drug category, and Gymnema 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 Gymnema and Acetaminophen, Butalbital, Caffeine, Codeine 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.