Drug & supplement interaction

Danshen + Acetaminophen, Butalbital, Codeine Phosphate

Acetaminophen, Butalbital, Codeine Phosphate brand name: Phrenilin #3.

Moderate Interaction
The bottom line Moderate

Acetaminophen, Butalbital, Codeine Phosphate falls into 3 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
Interactions3
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Danshen and Acetaminophen, Butalbital, Codeine Phosphate

These two interact in 3 distinct ways. Each one is explained separately below.

Why Are There 3 Interactions?

Danshen interacts with whole categories of medication. Acetaminophen, Butalbital, Codeine Phosphate falls into 3 of those categories, so it can interact with Danshen in 3 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 3

Why this applies to Acetaminophen, Butalbital, Codeine Phosphate

Acetaminophen, Butalbital, Codeine Phosphate 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 short version: this combination pill (acetaminophen, butalbital, and codeine) is mostly handled by liver enzymes, and Danshen has been shown in test tubes to slow down one of them called CYP1A2. In theory, slowing that enzyme could let some of the drug build up a bit, which might mean more drowsiness, dizziness, foggy thinking, or constipation from the codeine and butalbital parts.

The honest truth, though, is that this concern comes only from lab studies. When Danshen was tested in actual people using a similar CYP1A2 drug, no real change showed up. So I wouldn't lose sleep over it, but since Danshen can also affect bleeding and this medicine already makes you sleepy, please check with your pharmacist or doctor before combining them.

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 2E1 (CYP2E1) SUBSTRATES

2 of 3

Acetaminophen, Butalbital, Codeine Phosphate 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 Danshen and your Phrenilin with Codeine. The piece that connects them is an enzyme called CYP2E1. In lab dishes, compounds in Danshen seem to slow this enzyme down. The acetaminophen part of your combo pill is partly handled by CYP2E1, so in theory, blocking it could shift how acetaminophen is processed. The good news here is that this has never actually been reported in real people, only in test-tube and animal work, so the evidence is quite thin.

I wouldn't lose sleep over this one, but since both products can touch your liver, and Danshen may also thin the blood, it's worth a quick chat with your pharmacist or doctor before combining them, especially with regular use.

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

3 of 3

Acetaminophen, Butalbital, Codeine Phosphate 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 practical picture. Your combo pill (Phrenilin with codeine) leans heavily on a clearing pathway called glucuronidation, especially for the acetaminophen and codeine parts. Danshen, in lab and animal studies, seems to tug on this pathway in both directions: it can speed it up in some cases and slow it down in others. So the theory is that your medicine's levels could drift up or down, but honestly the effect is hard to predict and has never actually been reported in real people.

If levels nudged up, you might notice more drowsiness, dizziness, constipation, or nausea. If they dropped, you might get less pain relief. Because this is only theoretical right now, I wouldn't lose sleep over it, but please run it by your pharmacist or doctor before pairing the two, especially since both can affect alertness.

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, Codeine Phosphate 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 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, Codeine Phosphate

This page covers Danshen only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Butalbital, Codeine Phosphate page lists 240 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).

Open the Acetaminophen, Butalbital, Codeine Phosphate 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, Codeine Phosphate 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, 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 Danshen
Top half

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

29 days ago today
Medication Acetaminophen, Butalbital, Codeine Phosphate
Steady interest

#1,580 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
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
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 Danshen and Acetaminophen, Butalbital, Codeine Phosphate Together: Common Questions

Can you take Danshen with Acetaminophen, Butalbital, 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 3 interactions listed for Danshen and Acetaminophen, Butalbital, Codeine Phosphate?
Acetaminophen, Butalbital, Codeine Phosphate 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, 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

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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.