Drug & supplement interaction

Danshen + Benzhydrocodone, Acetaminophen

Benzhydrocodone, Acetaminophen brand name: Apadaz.

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

Benzhydrocodone, Acetaminophen 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 Benzhydrocodone, Acetaminophen

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. Benzhydrocodone, Acetaminophen 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 Benzhydrocodone, Acetaminophen

Benzhydrocodone, Acetaminophen 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 gist: laboratory studies hint that Danshen may slow down a liver enzyme called CYP1A2. The theory is that medicines cleared by that enzyme could build up a bit. With Apadaz (benzhydrocodone and acetaminophen), this connection is pretty loose. Benzhydrocodone is a prodrug that turns into hydrocodone, but that activation leans on other enzymes (like CYP3A4 and CYP2D6), not mainly CYP1A2, so the practical effect here is uncertain.

This warning comes only from test-tube and animal data, and in actual people Danshen didn't change levels of another CYP1A2 drug. So I wouldn't lose sleep over it. Still, since Danshen can also thin the blood and opioids carry real risks like drowsiness, slowed breathing, and constipation, please run this combo past your pharmacist or doctor first.

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

Benzhydrocodone, Acetaminophen 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

Here's the wrinkle with Apadaz: the benzhydrocodone part is actually a prodrug. Your body has to convert it into hydrocodone before it can ease your pain, and CYP3A4 plays a role in how hydrocodone is then processed. Danshen can nudge this enzyme system, but the direction depends on how you take it. Taken regularly for a week or two, Danshen seems to speed up CYP3A4, which could lower the amount of active medicine around and leave your pain less controlled. A single dose appeared to do the opposite.

This research is early and was done with a different drug, so it's not a sure thing. Still, since pain relief matters, I'd run this combo by your pharmacist or doctor before mixing them.

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

Benzhydrocodone, Acetaminophen 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 situation with Apadaz (benzhydrocodone and acetaminophen) and Danshen. One of your liver's enzymes, called CYP2E1, helps process the acetaminophen part of this combo. Lab and animal studies suggest Danshen may slow that enzyme down a bit. In theory, that could let acetaminophen hang around longer. The bigger concern with acetaminophen is the liver, since how it's broken down affects how the liver handles it.

Here's the important part: this interaction has only been seen in test tubes and animals, never reported in real people, so it's quite theoretical. Still, since acetaminophen is already hard on the liver, I'd play it safe. Please check with your pharmacist or doctor before pairing concentrated Danshen supplements with Apadaz, especially if you drink alcohol or have any liver concerns.

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

Benzhydrocodone, Acetaminophen 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 Apadaz (benzhydrocodone with acetaminophen) and Danshen. Part of how your body clears acetaminophen is a process called glucuronidation, basically tagging the drug so it can be flushed out. Lab and animal studies hint that Danshen can tug on those clearing enzymes in both directions, either speeding them up or slowing them down. In theory, slowing them down could let levels linger a bit longer, which for an opioid combo might mean more drowsiness, constipation, or slowed breathing.

The honest truth is this has never actually been reported in real people. It's a theoretical concern from test-tube work, not a proven problem. Still, Danshen may also thin the blood, so please run it by your pharmacist or doctor before combining the two.

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 Benzhydrocodone, Acetaminophen 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. Benzhydrocodone, Acetaminophen)
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 Benzhydrocodone, Acetaminophen

This page covers Danshen only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Benzhydrocodone, Acetaminophen page lists 299 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).

By severity: 14 major · 239 moderate · 46 minor.

Open the Benzhydrocodone, Acetaminophen 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 Benzhydrocodone, Acetaminophen 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 Benzhydrocodone, Acetaminophen 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

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

29 days ago today
Medication Benzhydrocodone, Acetaminophen
Steady interest

#2,150 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
Medication

About Benzhydrocodone and Acetaminophen

What Is Benzhydrocodone and Acetaminophen Used For?

Brand name: Apadaz

Apadaz is indicated for the short-term management of acute pain — up to 14 days — that is severe enough to require an opioid and for which non-opioid treatments have not worked or are not expected to work. It combines benzhydrocodone (a prodrug that converts to the opioid hydrocodone) with acetaminophen.

Because of serious risks including addiction, abuse, and misuse, Apadaz is reserved for patients who have not tolerated or have not gotten adequate relief from alternative pain treatments. It should not be used for an extended period of time unless the pain remains severe enough to require an opioid and alternatives remain inadequate.

See full Benzhydrocodone and Acetaminophen drug information
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 Benzhydrocodone, Acetaminophen, 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 Benzhydrocodone, Acetaminophen supplement interactions › Every supplement checked against Benzhydrocodone, Acetaminophen, ranked by severity Benzhydrocodone and Acetaminophen drug information › The full plain-English guide to this medication 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 Benzhydrocodone, Acetaminophen Together: Common Questions

Can you take Danshen with Benzhydrocodone, Acetaminophen?
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 Benzhydrocodone, Acetaminophen?
Benzhydrocodone, Acetaminophen 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 Benzhydrocodone, Acetaminophen 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 Benzhydrocodone, Acetaminophen and Danshen?

Our pharmacists answer your medication & supplement questions — free.

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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.