Drug & supplement interaction

Danshen + 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 4 drug categories that Danshen can interact with; the most serious is rated moderate. Theoretically, danshen may increase the levels and clinical effects 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

Danshen and Acetaminophen, Butalbital, Caffeine, Codeine

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

Why Are There 4 Interactions?

Danshen interacts with whole categories of medication. Acetaminophen, Butalbital, Caffeine, Codeine falls into 4 of those categories, so it can interact with Danshen 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 Acetaminophen, Butalbital, Caffeine, Codeine

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

Theoretically, danshen may increase the levels and clinical effects of drugs metabolized by CYP1A2.
In vitro research shows that danshen tincture and various constituents of danshen inhibit the activity of CYP1A2. However, this activity has not been shown in humans when theophylline, a CYP1A2 substrate, was used as a target drug.
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 of your combo pill that this interaction touches: the caffeine. Caffeine is cleared by a liver enzyme called CYP1A2, and lab studies suggest Danshen may slow that enzyme down a little. In theory, that could let caffeine hang around longer, so you might feel jittery, have a racing heart, or trouble sleeping. The codeine, acetaminophen, and butalbital pieces are handled by different pathways, so they aren't really the concern here.

The honest part: this comes only from test-tube and animal work. When researchers actually tested it in people using another CYP1A2 drug, they didn't see a real effect. So I wouldn't lose sleep over it, but do mention the Danshen to your pharmacist or doctor before combining, just to be safe.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Wang X, Cheung CM, Lee WY, Or PM, Yeung JH. Major tanshinones of Danshen (Salvia miltiorrhiza) exhibit different modes of inhibition on human CYP1A2, CYP2C9, CYP2E1 and CYP3A4 activities in vitro. Phytomedicine. 2010 Sep;17(11):868-75. PubMed
  2. Wang X, Yeung JH. Investigation of cytochrome P450 1A2 and 3A inhibitory properties of Danshen tincture. Phytomedicine. 2012 Feb 15;19(3-4):348-54. PubMed
  3. Zhou X, Chan K, Yeung JH. Herb-drug interactions with Danshen (Salvia miltiorrhiza): a review on the role of cytochrome P450 enzymes. Drug Metabol Drug Interact. 2012 Mar 2;27(1):9-18.
Moderate

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

2 of 4

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

Danshen might alter the levels and clinical effects of drugs metabolized by CYP3A4.
Preliminary clinical research in healthy males shows that the administration of danshen for 10-14 days induces intestinal CYP3A4 and increases the clearance of midazolam, a CYP3A4 substrate. The maximum concentration of midazolam was decreased by 31% to 67%, and drug levels were decreased by 27% to 80%. However, a single dose of danshen has the opposite effect, increasing maximum concentrations of midazolam by 87%.
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 combination pill is a mixed bag when it comes to Danshen. The piece that matters most here is the butalbital, which is partly handled by the CYP3A4 enzyme. Research suggests that taking Danshen daily for a week or two may speed that enzyme up, which could lower butalbital levels and make it less effective at easing your headache. Oddly, a single dose of Danshen seems to do the reverse and bump levels up, so the timing and amount really matter.

Keep in mind the codeine part is mainly activated by a different enzyme (CYP2D6), so this particular interaction is less about pain relief from codeine. Since the evidence is early and modest, I would not panic, but please check with your pharmacist or doctor before adding Danshen.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Qiu F, Wang G, Zhang R, Sun J, et al. Effect of danshen extract on the activity of CYP3A4 in healthy volunteers. Br J Clin Pharmacol 2010;69:656-62. PubMed
  2. Qiu F, Jiang J, Ma Y, Wang G, Gao C, Zhang X, Zhang L, Liu S, He M, Zhu L, Ye Y, Li Q, Miao P. Opposite Effects of Single-Dose and Multidose Administration of the Ethanol Extract of Danshen on CYP3A in Healthy Volunteers. Evid Based Complement Alternat Me PubMed
Moderate

CYTOCHROME P450 2E1 (CYP2E1) SUBSTRATES

3 of 4

Acetaminophen, Butalbital, Caffeine, Codeine also falls under CYTOCHROME P450 2E1 (CYP2E1) SUBSTRATES.

Theoretically, danshen may increase the levels and clinical effects of drugs metabolized by CYP2E1.
In vitro research shows that various constituents of danshen inhibit the activity of CYP2E1. So far, this interaction 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 short version on combining Danshen with this combo pill (Fioricet with Codeine). The piece that touches the liver enzyme CYP2E1 mostly involves acetaminophen, the Tylenol part. Danshen, in lab studies, seems to slow that enzyme down a bit. CYP2E1 is one route that turns a small amount of acetaminophen into a harmful byproduct, so in theory, blocking it could actually be neutral or even mildly protective for the liver. Honestly, the real-world meaning here is unclear.

This is based only on test-tube and animal data, and it has never been reported in actual people, so I wouldn't lose sleep over it. Still, because Danshen can thin the blood, and this medicine already carries codeine and a barbiturate, it's worth a quick chat with your pharmacist before mixing them.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Wang X, Cheung CM, Lee WY, Or PM, Yeung JH. Major tanshinones of Danshen (Salvia miltiorrhiza) exhibit different modes of inhibition on human CYP1A2, CYP2C9, CYP2E1 and CYP3A4 activities in vitro. Phytomedicine. 2010 Sep;17(11):868-75. PubMed
Moderate

GLUCURONIDATED DRUGS

4 of 4

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

Theoretically, danshen might affect the levels and clinical effects of drugs requiring glucuronidation.
In vitro research shows that danshen induces the expression of glucuronosyltransferases. However, it also inhibits the activity of glucuronosyltransferases, including various members of the 1A and 2B families. The extent of inhibition of a specific glucuronosyltransferase seems to be dependent on whether or not the danshen is processed via 'sweating'. This type of processing may affect the levels of constituents in danshen that alter glucuronosyltransferase activity. So far, this interaction 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 gist with this combo pill (Fioricet with Codeine). Several pieces of it, including the acetaminophen and the codeine, get cleared partly through a process called glucuronidation. Danshen, in test tube studies only, seems to nudge that pathway in both directions, sometimes speeding it up and sometimes slowing it down. Honestly, the lab signals are mixed and this has never actually been reported in real people.

Because the science is so theoretical, I wouldn't lose sleep over it. If levels did shift, you could in theory see a bit more grogginess, dizziness, or constipation, or on the flip side less pain relief. The bigger point with Danshen is its known effect on blood clotting, so please run it by your pharmacist or doctor first.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Liu J, Shi Y, Wu C, et al. Comparison of sweated and non-sweated ethanol extracts of Salvia miltiorrhiza Bge. (Danshen) effects on human and rat hepatic UDP-glucuronosyltransferase and preclinic herb-drug interaction potential evaluation. Curr Drug Metab

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

Danshen Also Interacts With Other Medications

Danshen has 123 major, 935 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.

Major 123 Moderate 935 No known interaction 1,772 (incl. Acetaminophen, Butalbital, Caffeine, Codeine)
Taking anything else?

Check Another of Your Medications Against Danshen

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

Everything else you take

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

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

We hold 18 real supplement products containing Danshen, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Danshen. Your product may carry other ingredients that interact with Acetaminophen, Butalbital, Caffeine, Codeine too, on top of Danshen — 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 Danshen 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 Danshen
Top half

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

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

#1,019 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 Danshen

What is Danshen?

Danshen
  • Heart and circulation support
  • Angina (chest pain)
  • High blood pressure
  • Anxiety and stress
  • Liver health

Danshen is a root used in traditional Chinese medicine, mainly for heart and circulation problems. Some early research is promising, but the evidence is not strong enough to confirm it works for any condition, and it may affect blood clotting. Talk to a pharmacist or doctor before using it, especially if you take other medicines or have a health condition.

Read the full Danshen monograph & all interactions
Keep checking

Other Drugs & Danshen

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

123Major
935Moderate
0Minor
1,771No known interaction
123 Major 935 Moderate 1,771 No interaction
Major

123 interactions

Showing 60 of 123 major interactions — see all 123 on the Danshen page.

Moderate

935 interactions

Showing 60 of 935 moderate interactions — see all 935 on the Danshen page.

No interaction 1,771 drugs checked — show the list

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

Showing the 60 most looked-up of 1,771 medications checked with no known interaction — see the full Danshen list.

See the full Danshen 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
Danshen 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 Danshen and Acetaminophen, Butalbital, Caffeine, Codeine Together: Common Questions

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