Drug & supplement interaction

Atractylodes + Aspirin, Caffeine, Orphenadrine

Aspirin, Caffeine, Orphenadrine brand names: Norgesic Forte, Invagesic, Invagesic Forte, Orphengesic, Norgesic, and others.

Moderate Interaction
The bottom line Moderate

Aspirin, Caffeine, Orphenadrine falls into 3 drug categories that Atractylodes can interact with; the most serious is rated moderate. Theoretically, atractylodes might increase the risk of bleeding when used concomitantly with anticoagulant and antiplatelet drugs.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions3
EvidenceD
What do Severity, Likelihood & Evidence mean?
Know someone taking this? Share
Interaction report

Atractylodes and Aspirin, Caffeine, Orphenadrine

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

Why Are There 3 Interactions?

Atractylodes interacts with whole categories of medication. Aspirin, Caffeine, Orphenadrine falls into 3 of those categories, so it can interact with Atractylodes in 3 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

ANTICOAGULANT/ANTIPLATELET DRUGS

1 of 3

Why this applies to Aspirin, Caffeine, Orphenadrine

Aspirin, Caffeine, Orphenadrine falls under ANTICOAGULANT/ANTIPLATELET DRUGS — the group Atractylodes interacts with.

Theoretically, atractylodes might increase the risk of bleeding when used concomitantly with anticoagulant and antiplatelet drugs.
Laboratory research suggests that atractylenolides II and III, constituents of atractylodes, reduce platelet activation. So far, this has not been shown 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 piece to pay attention to in this combination pill: the aspirin. Aspirin is an antiplatelet drug, meaning it makes your platelets less sticky so blood clots more slowly. Lab studies hint that certain compounds in atractylodes (atractylenolides II and III) may also calm down platelet activity. Stack those two together and, in theory, you could see a little more bleeding tendency, things like easier bruising, nosebleeds, or a cut that's slow to stop.

The honest truth is this is theoretical right now. It's only been seen in test-tube and animal research, not in people, so I wouldn't lose sleep over it. Still, since you're already taking aspirin, it's worth a quick chat with your pharmacist or doctor before adding atractylodes, especially if you bruise or bleed easily.

References
  1. Chen Y, Yang W, Guo L, Wu X, Zhang T, Liu J, Zhang J. Atractylodes lactone compounds inhibit platelet activation. Platelets. 2017 Mar;28(2):194-202. PubMed
Minor

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES

2 of 3

Aspirin, Caffeine, Orphenadrine also falls under CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES.

Theoretically, atractylodes might decrease the levels of CYP1A2 substrates.
In animals, atractylodes administered at high doses has been shown to induce CYP1A2 activity. This effect has not been shown in humans.
Severity Minor 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 (aspirin, caffeine, and orphenadrine): the caffeine portion is cleared by a liver enzyme called CYP1A2. In animal studies using high doses, atractylodes seemed to speed that enzyme up. If that happened in people, your body might clear caffeine a little faster, which could mean the caffeine feels slightly weaker or wears off sooner. None of these are prodrugs, so we're not flipping any direction here.

Honestly, this is a theoretical, minor concern only seen in animals, not humans, so I wouldn't lose sleep over it. The aspirin and orphenadrine parts aren't really affected. If you take this regularly and want to add atractylodes, just run it by your pharmacist or doctor first.

References
  1. Muhamad N, Plengsuriyakarn T, Na-Bangchang K. Atractylodes lancea for cholangiocarcinoma: Modulatory effects on CYP1A2 and CYP3A1 and pharmacokinetics in rats and biodistribution in mice. PLoS One 2022;17(11):e0277614. PubMed
Minor

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

3 of 3

Aspirin, Caffeine, Orphenadrine also falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES.

Theoretically, atractylodes might increase the levels of CYP3A4 substrates.
In animals, atractylodes administered at high doses has been shown to inhibit CYP3A1 activity, which is a homolog to the human CYP3A4 enzyme. This effect has not been shown in humans.
Severity Minor 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 (aspirin, caffeine, and orphenadrine). One of those ingredients, orphenadrine, is partly cleared by a liver enzyme called CYP3A4. In high-dose animal studies, atractylodes slowed a similar enzyme down. If that were to happen in people, orphenadrine could build up a bit, which might mean more of its usual effects like drowsiness, dry mouth, blurred vision, dizziness, or a faster heartbeat from the caffeine on board.

The honest takeaway: this is theoretical and based only on lab and animal work, not human studies, so the real-world risk looks small. Still, if you take a steady dose of this medicine, it's worth a quick chat with your pharmacist or doctor before adding atractylodes.

References
  1. Muhamad N, Plengsuriyakarn T, Na-Bangchang K. Atractylodes lancea for cholangiocarcinoma: Modulatory effects on CYP1A2 and CYP3A1 and pharmacokinetics in rats and biodistribution in mice. PLoS One 2022;17(11):e0277614. PubMed

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

Atractylodes Also Interacts With Other Medications

Atractylodes has 126 moderate, 674 minor known drug interactions in our database — the Aspirin, Caffeine, Orphenadrine 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 Atractylodes

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

Everything else you take

See Every Supplement That Interacts With Aspirin, Caffeine, Orphenadrine

This page covers Atractylodes only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Aspirin, Caffeine, Orphenadrine page lists 350 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), Danshen (major) and Ephedra (major).

By severity: 14 major · 289 moderate · 47 minor.

From our pharmacist’s overview on the Aspirin, Caffeine, Orphenadrine page

“Aspirin, caffeine, and orphenadrine (the Norgesic and Orphengesic brands) come with a supplement list that deserves real vigilance, with 14 of its 350 entries rated major. Over 200 of those ingredients can add to aspirin's effect on platelets and raise bleeding risk, another 44 stack stimulant effects on top of the caffeine, and grapef…”

Reviewed by 2 · Jul 18, 2026

Open the Aspirin, Caffeine, Orphenadrine interaction page

One more smart check

Taking Atractylodes as Part of a Dietary Supplement Product? Check It for Interactions

We hold 691 real supplement products containing Atractylodes, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Atractylodes. Your product may carry other ingredients that interact with Aspirin, Caffeine, Orphenadrine too, on top of Atractylodes — 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 Atractylodes and Aspirin, Caffeine, Orphenadrine 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 Atractylodes
Top 25%

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

29 days ago today
Medication Aspirin, Caffeine, Orphenadrine
Top 25%

#595 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 Atractylodes

What is Atractylodes?

Atractylodes
  • Digestive upset and poor appetite
  • Bloating and fluid retention
  • General fatigue or 'weakness'
  • Diarrhea
  • Support within traditional formulas

Atractylodes is a root used for centuries in traditional Chinese, Japanese, and Thai medicine, mostly for digestive complaints and fatigue, often as part of multi-herb formulas. Modern research is still early and mostly from lab and animal studies, so its true benefits in people are not well proven. If you want to try it, talk with a pharmacist or doctor first, and avoid it during pregnancy and breastfeeding.

Read the full Atractylodes monograph & all interactions
Keep checking

Other Drugs & Atractylodes

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

0Major
126Moderate
674Minor
2,029No known interaction
Moderate

126 interactions

Showing 60 of 126 moderate interactions — see all 126 on the Atractylodes page.

Minor

674 interactions

Showing 60 of 674 minor interactions — see all 674 on the Atractylodes page.

No interaction 2,029 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

Keep exploring
Pharmacist Counseling Corner

Taking Atractylodes and Aspirin, Caffeine, Orphenadrine Together: Common Questions

Can you take Atractylodes with Aspirin, Caffeine, Orphenadrine?
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 Atractylodes and Aspirin, Caffeine, Orphenadrine?
Aspirin, Caffeine, Orphenadrine belongs to more than one drug category, and Atractylodes 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 Atractylodes and Aspirin, Caffeine, Orphenadrine 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 Aspirin, Caffeine, Orphenadrine and Atractylodes?

Our pharmacists answer your medication & supplement questions — free.

Ask a pharmacist

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.