Drug & supplement interaction

Evodia + Acetaminophen, Ibuprofen

Acetaminophen, Ibuprofen brand name: Combogesic.

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

Acetaminophen, Ibuprofen falls into 3 drug categories that Evodia can interact with; the most serious is rated moderate. Evodia might reduce the levels and clinical effects of CYP1A2 substrates through induction of CYP1A2.

Read the full interaction report
SeverityModerate
LikelihoodProbable
Interactions3
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Evodia and Acetaminophen, Ibuprofen

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

Why Are There 3 Interactions?

Evodia interacts with whole categories of medication. Acetaminophen, Ibuprofen falls into 3 of those categories, so it can interact with Evodia 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, Ibuprofen

Acetaminophen, Ibuprofen falls under CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES — the group Evodia interacts with.

Evodia might reduce the levels and clinical effects of CYP1A2 substrates through induction of CYP1A2.
Evodia extract and the evodia constituent rutaecarpine induce hepatic CYP1A2 enzyme activity. Evodia decreases levels of theophylline and caffeine, CYP1A2 substrates, by about 70% in animal models.
Severity Moderate Likelihood Probable Evidence D

Interaction 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..

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

If you're reaching for Combogesic (the acetaminophen and ibuprofen combo) alongside evodia, here's the honest picture. Evodia, and its compound rutaecarpine, appear to speed up a liver enzyme called CYP1A2. In theory, a faster enzyme could clear certain drugs out of your body a bit quicker. For these two pain relievers, that would mean a slightly weaker effect, so your aches, fever, or headache might not be controlled as well.

That said, this is based only on test tube and animal work, not real people, and acetaminophen and ibuprofen aren't strongly tied to CYP1A2 anyway. So I'd call this low-concern but worth mentioning. Before pairing them regularly, just check with your pharmacist or doctor.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Ueng YF, Tsai TH, Don MJ, et al. Alteration of the pharmacokinetics of theophylline by rutaecarpine, an alkaloid of the medicinal herb Evodia rutaecarpa, in rats. J Pharm Pharmacol 2005;57:227-32.
  2. Ueng YF, Jan WC, Lin LC, et al. The alkaloid rutaecarpine is a selective inhibitor of cytochrome P450 1A in mouse and human liver microsomes. Drug Metab Dispos 2002;30:349-53. PubMed
  3. Tsai TH, Chang CH, Lin LC. Effects of Evodia rutaecarpa and rutaecarpine on the pharmacokinetics of caffeine in rats. Planta Med 2005;71:640-5.
  4. Lee SK, Kim NH, Lee J, et al. Induction of cytochrome P450s by rutaecarpine and metabolism of rutaecarpine by cytochrome P450s. Planta Med 2004;70:753-7. PubMed
Moderate

ANTICOAGULANT/ANTIPLATELET DRUGS

2 of 3

Acetaminophen, Ibuprofen also falls under ANTICOAGULANT/ANTIPLATELET DRUGS.

Theoretically, taking evodia with antiplatelet or anticoagulant drugs might increase the risk of bruising and bleeding.
In vitro and animal studies show that rutaecarpine, a constituent of evodia, inhibits platelet aggregation.
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 Combogesic (acetaminophen plus ibuprofen): the ibuprofen part already has a mild blood-thinning effect because it slows down how your platelets stick together and form clots. Evodia contains a compound called rutaecarpine that may do something similar. Stack the two and, in theory, you could see a bit more bruising, nosebleeds, or stomach irritation than usual.

That said, this is based only on test tube and animal research, so the real-world risk in people isn't well proven. It's worth a heads-up, not a panic. If you regularly take Combogesic, especially with any other blood thinner, just run the evodia idea past your pharmacist or doctor first and watch for unusual bruising or bleeding.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Sheu JR, Kan YC, Hung WC, et al. The antiplatelet activity of rutaecarpine, an alkaloid isolated from Evodia rutaecarpa, is mediated through inhibition of phospholipase C. Thromb Res 1998;92:53-64. PubMed
  2. Sheu JR, Hung WC, Lee YM, Yen MH. Mechanism of inhibition of platelet aggregation by rutaecarpine, an alkaloid isolated from Evodia rutaecarpa. Eur J Pharmacol 1996;318:469-75. PubMed
  3. Sheu JR, Hung WC, Wu CH, et al. Antithrombotic effect of rutaecarpine, an alkaloid isolated from Evodia rutaecarpa, on platelet plug formation in in vivo experiments. Br J Haematol 2000;110:110-5.
  4. Huang CJ, Huang WC, Lin WT, et al. Rutaecarpine, an alkaloid from Evodia rutaecarpa, can prevent platelet activation in humans and reduce microvascular thrombosis in mice: crucial role of the PI3K/Akt/GSK3ß signal axis through a cyclic nucleotides/VASP-in
Moderate

CYTOCHROME P450 2E1 (CYP2E1) SUBSTRATES

3 of 3

Acetaminophen, Ibuprofen also falls under CYTOCHROME P450 2E1 (CYP2E1) SUBSTRATES.

Theoretically, evodia might reduce the levels and clinical effects of CYP2E1 substrates through induction of CYP2E1.
Animal research suggests that rutaecarpine, a constituent of evodia, induces CYP2E1 activity. In rats, rutaecarpine increases markers of CYP2E1 activity, and administration of rutaecarpine with chlorzoxazone, a known CYP2E1 substrate, reduces the area under the curve (AUC) of chlorzoxazone by 84% and increases its clearance by 646%.
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 thing to keep in mind with this combination. Evodia contains a compound called rutaecarpine that, at least in animal studies, seems to speed up a liver enzyme called CYP2E1. The acetaminophen part of Combogesic is partly handled by that enzyme, so in theory evodia could make your body process acetaminophen a little faster.

One important wrinkle: when CYP2E1 works faster, it can produce more of acetaminophen's toxic byproduct (NAPQI), which is the part that stresses the liver. So the real concern isn't weaker pain relief, it's a potential extra burden on the liver, especially with regular or higher dosing. The ibuprofen side isn't really affected here. This is only theoretical lab and animal data, so don't panic, but please check with your pharmacist or doctor before pairing them.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Bista SR, Lee SK, Thapa D, et al. Effects of oral rutaecarpine on the pharmacokinetics of intravenous chlorzoxazone in rats. Toxicol Res 2008;24(3):195-9. 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

Evodia Also Interacts With Other Medications

Evodia has 949 moderate known drug interactions in our database — the Acetaminophen, Ibuprofen one above is among them. If you take anything else, check it against the full list below.

Moderate 949 No known interaction 1,881 (incl. Acetaminophen, Ibuprofen)
Taking anything else?

Check Another of Your Medications Against Evodia

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

Everything else you take

See Every Supplement That Interacts With Acetaminophen, Ibuprofen

This page covers Evodia only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Ibuprofen page lists 342 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 Piracetam (major).

By severity: 7 major · 290 moderate · 45 minor.

From our pharmacist’s overview on the Acetaminophen, Ibuprofen page

“Combogesic pairs acetaminophen with ibuprofen, so it inherits the vulnerabilities of both drugs, and its supplement list deserves real attention before you add anything to it. Of the 342 ingredients on file, 7 carry a major rating, and those are the ones to understand first.”

Reviewed by 2 · Jul 18, 2026

Open the Acetaminophen, Ibuprofen interaction page

One more smart check

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

We hold 182 real supplement products containing Evodia, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Evodia. Your product may carry other ingredients that interact with Acetaminophen, Ibuprofen too, on top of Evodia — 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 Evodia and Acetaminophen, Ibuprofen 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 Evodia
Top half

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

29 days ago today
Medication Acetaminophen, Ibuprofen
Top 25%

#405 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 Evodia

What is Evodia?

  • Digestive upset and nausea
  • Headaches
  • Menstrual cramps
  • Abdominal pain
  • Diarrhea

Evodia is a fruit used in traditional Chinese medicine, most often for digestive complaints, headaches, and menstrual pain. Human evidence for these uses is very limited, and it is mostly studied in laboratory and animal research. Talk with a pharmacist or doctor before using it, and avoid it during pregnancy and breastfeeding.

Read the full Evodia monograph & all interactions
Keep checking

Other Drugs & Evodia

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

0Major
949Moderate
0Minor
1,880No known interaction
949 Moderate 1,880 No interaction
Moderate

949 interactions

Showing 60 of 949 moderate interactions — see all 949 on the Evodia page.

No interaction 1,880 drugs checked — show the list

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

Showing the 60 most looked-up of 1,880 medications checked with no known interaction — see the full Evodia list.

See the full Evodia interactions page
See every supplement checked against Acetaminophen, Ibuprofen, 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
Evodia monograph › Uses, safety, and every drug interaction in one place Acetaminophen, Ibuprofen supplement interactions › Every supplement checked against Acetaminophen, Ibuprofen, 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 Evodia and Acetaminophen, Ibuprofen Together: Common Questions

Can you take Evodia with Acetaminophen, Ibuprofen?
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 Evodia and Acetaminophen, Ibuprofen?
Acetaminophen, Ibuprofen belongs to more than one drug category, and Evodia 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 Evodia and Acetaminophen, Ibuprofen 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.