Drug & supplement interaction

Panax Ginseng + Acetaminophen, Butalbital, Caffeine, Codeine

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

Moderate Interaction
The bottom line Moderate

Acetaminophen, Butalbital, Caffeine, Codeine falls into 4 drug categories that Panax Ginseng can interact with; the most serious is rated moderate. Theoretically, Panax ginseng might increase levels of drugs metabolized by CYP2D6.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions4
EvidenceB
What do Severity, Likelihood & Evidence mean?
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Interaction report

Panax Ginseng and Acetaminophen, Butalbital, Caffeine, Codeine

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

Why Are There 4 Interactions?

Panax Ginseng interacts with whole categories of medication. Acetaminophen, Butalbital, Caffeine, Codeine falls into 4 of those categories, so it can interact with Panax Ginseng 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 2D6 (CYP2D6) SUBSTRATES

1 of 4

Why this applies to Acetaminophen, Butalbital, Caffeine, Codeine

Acetaminophen, Butalbital, Caffeine, Codeine falls under CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES — the group Panax Ginseng interacts with.

Theoretically, Panax ginseng might increase levels of drugs metabolized by CYP2D6. However, research is conflicting.
There is some evidence that Panax ginseng can inhibit the CYP2D6 enzyme by approximately 6%. In addition, in animal research, Panax ginseng inhibits the metabolism of dextromethorphan, a drug metabolized by CYP2D6, by a small amount. However, contradictory research suggests Panax ginseng might not inhibit CYP2D6. Until more is known, use Panax ginseng cautiously in patients taking drugs metabolized by these enzymes.
Severity Moderate Likelihood Possible Evidence B

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 product: the codeine part is what we call a prodrug. Your body uses an enzyme called CYP2D6 to convert codeine into morphine, which is what actually relieves pain. Panax ginseng may very slightly block that same enzyme. In theory, that could mean a little less codeine gets turned into morphine, so you might get weaker pain relief rather than stronger.

I want to be honest, though: the evidence here is thin and conflicting. One study suggested ginseng dampens CYP2D6 by only about 6 percent, which is tiny, and other research found no real effect. So for most people this likely won't be noticeable. The acetaminophen, butalbital, and caffeine pieces aren't really part of this. Still, it's worth a quick word with your pharmacist or doctor before adding ginseng.

References
  1. Gurley BJ, Gardner SF, Hubbard MA. Clinical assessment of potential cytochrome P450-mediated herb-drug interactions. AAPS Ann Mtg & Expo Indianapolis, IN: 2000; Oct 29 - Nov 2:presentation #3460.
  2. Gurley BJ, Gardner SF, Hubbard MA, et al. Cytochrome P450 phenotypic ratios for predicting herb-drug interactions in humans. Clin Pharmacol Ther 2002;72:276-87.. PubMed
  3. Gurley, B. J., Gardner, S. F., Hubbard, M. A., Williams, D. K., Gentry, W. B., Cui, Y., and Ang, C. Y. Clinical assessment of effects of botanical supplementation on cytochrome P450 phenotypes in the elderly: St John's wort, garlic oil, Panax ginseng and DOI
  4. Kim Y, Jo JJ, Cho P, et al. Characterization of red ginseng-drug interaction by CYP3A activity increased in high dose administration in mice. Biopharm Drug Dispos. 2020;41(7):295-306. PubMed
Moderate

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

2 of 4

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

Theoretically, Panax ginseng might increase or decrease levels of drugs metabolized by CYP3A4.
Panax ginseng may affect the clearance of drugs metabolized by CYP3A4. One such drug is imatinib. Inhibition of CYP3A4 was believed to be responsible for a case of imatinib-induced hepatotoxicity. In contrast, Panax ginseng has been shown to increase the clearance of midazolam, another drug metabolized by CYP3A4. Clinical research shows that Panax ginseng can reduce midazolam area under the curve by 44%, maximum plasma concentration by 26%, and time to reach maximum plasma concentration by 29%. Midazolam metabolism was also increased in animals given Panax ginseng. Until more is known, use Panax ginseng cautiously in combination with CYP3A4 substrates.
Severity Moderate Likelihood Possible Evidence B

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 is a mix, and the piece most affected here is butalbital, the barbiturate that handles your tension headache. It's partly broken down by a liver enzyme called CYP3A4, and Panax ginseng can nudge that enzyme in either direction. The research is mostly theoretical, with mixed results in studies, so I wouldn't lose sleep over it.

If ginseng speeds that enzyme up, butalbital may clear faster and feel less effective. If it slows it down, you could feel groggier or more drowsy than usual. Keep in mind codeine here is a prodrug, but it relies on a different enzyme (CYP2D6), so this particular interaction shouldn't change its pain relief much. Just mention the ginseng to your pharmacist so they can keep an eye on things.

References
  1. Malati CY, Robertson SM, Hunt JD, Chairez C, Alfaro RM, Kovacs JA, Penzak SR. Influence of Panax ginseng on cytochrome P450 (CYP)3A and P-glycoprotein (P-gp) activity in healthy participants. J Clin Pharmacol 2012;52(6):932-9.
  2. Bilgi N, Bell K, Ananthakrishnan AN, Atallah E. Imatinib and Panax ginseng: a potential interaction resulting in liver toxicity. Ann Pharmacother 2010;44(5):926-8.
  3. Kim Y, Jo JJ, Cho P, et al. Characterization of red ginseng-drug interaction by CYP3A activity increased in high dose administration in mice. Biopharm Drug Dispos. 2020;41(7):295-306. PubMed
Moderate

STIMULANT DRUGS

3 of 4

Acetaminophen, Butalbital, Caffeine, Codeine also falls under STIMULANT DRUGS.

Theoretically, taking Panax ginseng with stimulant drugs might increase the risk of adverse stimulant effects.
Panax ginseng has been shown to have stimulant 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 simple version. The product you're asking about is a combo: acetaminophen, butalbital, caffeine, and codeine. The piece that matters for ginseng is the caffeine, which is a stimulant. Panax ginseng can have mild stimulant-like effects of its own, so pairing the two could stack up and possibly leave you feeling jittery, anxious, restless, with a racing heartbeat or trouble sleeping.

I want to be honest about how strong this concern is. It's a theoretical interaction based on how these things work in the body, not solid studies, so for most people it's a minor issue rather than a danger. Still, if you notice extra jitteriness or poor sleep, mention it to your pharmacist or doctor before changing anything.

References
  1. Scaglione F, Cattaneo G, Alessandria M, Cogo R. Efficacy and safety of the standardized Ginseng extract G115 for potentiating vaccination against the influenza syndrome and protection against the common cold. Drugs Exp Clin Res 1996;22:65-72.
  2. Gonzalez-Seijo JC, Ramos YM, Lastra I. Manic episode and ginseng: Report of a possible case. J Clin Psychopharmacol 1995;15:447-8.
Moderate

CAFFEINE

4 of 4

Acetaminophen, Butalbital, Caffeine, Codeine also falls under CAFFEINE.

Theoretically, taking Panax ginseng with caffeine might increase the risk of adverse stimulant effects.
Panax ginseng has been shown to have stimulant effects. Theoretically, caffeine might have an additive effect on the stimulant effects of Panax ginseng.
Severity Moderate Likelihood Probable Evidence B

Interaction 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..

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

This combination product contains caffeine, and that is the piece that matters here. Panax ginseng can have its own mild stimulant effect, so pairing it with the caffeine in your Fioricet or Esgic with Codeine could add up. You might notice more jitteriness, a racing or pounding heart, trouble falling asleep, or feeling on edge. To be clear, this is mostly a theoretical concern based on lower quality evidence, not a dangerous reaction.

The codeine, butalbital, and acetaminophen parts are not really involved in this particular interaction. If you take ginseng regularly, just give your pharmacist or doctor a heads up so they can keep an eye on how you are tolerating it.

References
  1. Scaglione F, Cattaneo G, Alessandria M, Cogo R. Efficacy and safety of the standardized Ginseng extract G115 for potentiating vaccination against the influenza syndrome and protection against the common cold. Drugs Exp Clin Res 1996;22:65-72.
  2. Gonzalez-Seijo JC, Ramos YM, Lastra I. Manic episode and ginseng: Report of a possible case. J Clin Psychopharmacol 1995;15:447-8.

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

Panax Ginseng Also Interacts With Other Medications

Panax Ginseng has 1,129 moderate 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.

Taking anything else?

Check Another of Your Medications Against Panax Ginseng

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

Everything else you take

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

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

We hold 517 real supplement products containing Panax Ginseng, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Panax Ginseng. Your product may carry other ingredients that interact with Acetaminophen, Butalbital, Caffeine, Codeine too, on top of Panax Ginseng — 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 Panax Ginseng 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 Panax Ginseng
Top 25%

#244 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 Panax Ginseng

What is Panax Ginseng?

Panax Ginseng
  • Boosting energy and fighting fatigue
  • Improving mental focus and memory
  • Coping with stress (adaptogen)
  • Erectile dysfunction
  • Supporting immune health
  • Blood sugar support

Panax ginseng is a popular traditional herb used to boost energy, ease stress, and support overall wellness, though scientific evidence is mixed and mostly preliminary. It is generally well tolerated for short-term use in healthy adults, but it can cause side effects like trouble sleeping and may not be safe during pregnancy or breastfeeding. Always check with your pharmacist or doctor before starting it, especially if you have a medical condition or take other medicines.

Read the full Panax Ginseng monograph & all interactions
Keep checking

Other Drugs & Panax Ginseng

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

0Major
1,129Moderate
0Minor
1,700No known interaction
Moderate

1,129 interactions

Showing 60 of 1,129 moderate interactions — see all 1,129 on the Panax Ginseng page.

No interaction 1,700 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 Panax Ginseng and Acetaminophen, Butalbital, Caffeine, Codeine Together: Common Questions

Can you take Panax Ginseng 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 4 interactions listed for Panax Ginseng and Acetaminophen, Butalbital, Caffeine, Codeine?
Acetaminophen, Butalbital, Caffeine, Codeine belongs to more than one drug category, and Panax Ginseng 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 Panax Ginseng 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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