Drug & supplement interaction

Danshen + Acetaminophen, Caffeine, Isometheptene

Acetaminophen, Caffeine, Isometheptene brand name: Migralam.

Moderate Interaction
The bottom line Moderate

Acetaminophen, Caffeine, Isometheptene 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, Caffeine, Isometheptene

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, Caffeine, Isometheptene 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, Caffeine, Isometheptene

Acetaminophen, Caffeine, Isometheptene 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 simple version for Migralam, which combines acetaminophen, caffeine, and isometheptene. The caffeine part is cleared by a liver enzyme called CYP1A2. In test-tube studies, Danshen seems to slow that enzyme down, which could let caffeine linger longer in your body. If that happened, you might feel more of caffeine's jittery side, things like a racing heart, restlessness, trouble sleeping, or feeling shaky.

Honestly though, this is a theoretical concern. When researchers tested Danshen against a real CYP1A2 drug in people, they didn't see a meaningful effect. There's also a separate point worth mentioning: Danshen may thin the blood, so combining it with any medicine deserves a quick chat with your pharmacist or doctor first.

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, Caffeine, Isometheptene 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

Migralam combines acetaminophen, caffeine, and isometheptene to ease migraine headaches. Here's the practical part: when Danshen is taken regularly for a couple of weeks, it can speed up a gut enzyme called CYP3A4, which may lower the levels of medicines that rely on it. In theory, that could make this combo work a little less well, so your headache relief might not be as strong. Oddly, a single dose of Danshen seems to do the opposite and briefly raise drug levels.

Honestly, the evidence here is limited and was studied with a different drug (midazolam), not Migralam itself, so I wouldn't lose sleep over it. Still, if you take Danshen, mention it to your pharmacist or doctor so they can keep an eye on how well your migraine medicine is working.

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, Caffeine, Isometheptene 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 gist for Migralam, which combines acetaminophen, caffeine, and a mild blood vessel narrower called isometheptene. The acetaminophen part is partly handled by a liver enzyme called CYP2E1. In test tube studies, compounds in danshen seem to slow that enzyme down. In theory, that could let a little more acetaminophen linger in your system.

I want to be honest about how soft this evidence is. It comes only from lab work, and nothing like it has actually been reported in people. So I'm not losing sleep over it, but acetaminophen is hard on the liver if levels run high, so it's worth a quick chat with your pharmacist before pairing the two, 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

4 of 4

Acetaminophen, Caffeine, Isometheptene 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

If you're reaching for Migralam (which combines acetaminophen, caffeine, and isometheptene) for a headache and you also take Danshen, here's the honest picture. The acetaminophen part of this product is cleared by your body partly through a process called glucuronidation. In lab and animal studies, Danshen has shown mixed effects on those clearing enzymes, both speeding them up and slowing them down depending on how the root is processed. Because the signals point in both directions, we can't say cleanly which way it would push acetaminophen levels.

Importantly, this has never actually been reported in people, so it stays theoretical for now. Still, since acetaminophen overload is hard on the liver, it's worth a quick chat with your pharmacist before pairing them.

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, Caffeine, Isometheptene 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, Caffeine, Isometheptene

This page covers Danshen only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Caffeine, Isometheptene page lists 248 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Asarabacca (major), Beer (major), Ephedra (major) and Grapefruit (major).

By severity: 11 major · 194 moderate · 43 minor.

Open the Acetaminophen, Caffeine, Isometheptene 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, Caffeine, Isometheptene 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, Caffeine, Isometheptene 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

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

29 days ago today
Medication Acetaminophen, Caffeine, Isometheptene
Top 25%

#637 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, Caffeine, Isometheptene Together: Common Questions

Can you take Danshen with Acetaminophen, Caffeine, Isometheptene?
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, Caffeine, Isometheptene?
Acetaminophen, Caffeine, Isometheptene 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, Caffeine, Isometheptene 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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