Drug & supplement interaction

Evodia + Aspirin, Caffeine, Codeine Phosphate

Aspirin, Caffeine, Codeine Phosphate brand name: Anacin w/ Codeine.

Moderate Interaction
The bottom line Moderate

Aspirin, Caffeine, Codeine Phosphate falls into 4 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
Interactions4
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Evodia and Aspirin, Caffeine, Codeine Phosphate

These two interact in 4 distinct ways. Each one is explained separately below.

Why Are There 4 Interactions?

Evodia interacts with whole categories of medication. Aspirin, Caffeine, Codeine Phosphate falls into 4 of those categories, so it can interact with Evodia 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 Aspirin, Caffeine, Codeine Phosphate

Aspirin, Caffeine, Codeine Phosphate 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

This combination pill has three pieces, and the one that matters here is the caffeine. Your liver clears caffeine using an enzyme called CYP1A2, and lab and animal studies suggest Evodia speeds that enzyme up. In practice that means caffeine could get cleared faster, so the little energizing boost it normally adds (it's there to help the pain relief work) may feel weaker than usual.

The good news: this is based on test tube and animal research, not solid human studies, and the aspirin and codeine portions aren't affected this way. The pain relief itself should stay intact. Still, if you take Evodia regularly, it's worth a quick chat with your pharmacist or doctor before combining them, and please don't change anything on your own.

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

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

2 of 4

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

Theoretically, evodia might increase the levels and clinical effects of CYP3A4 substrates.
In vitro research shows that evodia extract inhibits hepatic CYP3A4. This effect 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

This combination pill carries three ingredients, but the one worth thinking about here is the caffeine portion. Caffeine is partly cleared by a liver enzyme called CYP3A4. In lab studies (test tubes only, not people yet), evodia seems to slow that enzyme down. If that held true in real life, caffeine might hang around a little longer, so you could feel more jittery, restless, sleepless, or notice a racing heartbeat.

I want to be honest about the strength of this: it is theoretical, based only on lab work, and has not been seen in actual patients. The codeine and aspirin parts are not the main concern with this enzyme. Still, since evodia itself is not well studied, please run it by your pharmacist or doctor before pairing the two.

References
  1. Iwata H, Tezuka Y, Kadota S, et al. Mechanism-based inactivation of human liver microsomal CYP3A4 by rutaecarpine and limonin from Evodia fruit extract. Drug Metab Pharmacokinet 2005;20:34-45. PubMed
Moderate

ANTICOAGULANT/ANTIPLATELET DRUGS

3 of 4

Aspirin, Caffeine, Codeine Phosphate 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 thing to keep an eye on with this combo product. The part that matters for evodia is the aspirin piece, since aspirin already thins the blood by keeping platelets from clumping together. A compound in evodia called rutaecarpine seems to do something similar in lab and animal studies, so stacking the two could, in theory, nudge your bleeding risk up a bit. That might look like easier bruising, nosebleeds, or bleeding gums.

I want to be honest about how soft this evidence is. We're talking test tube and animal data, not real human studies, so this is more of a caution than a proven problem. Casual food use is unlikely to matter much, but concentrated supplements are a different story. Before adding evodia, just run it by your pharmacist or doctor first.

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

CAFFEINE

4 of 4

Aspirin, Caffeine, Codeine Phosphate also falls under CAFFEINE.

Theoretically, evodia might decrease the levels and clinical effects of caffeine.
In animal models, evodia extract decreases caffeine levels by up to 71%. Evodia extract induces hepatic cytochrome P450 1A2 (CYP1A2) enzyme, of which caffeine is a substrate.
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

Here's what's going on with this combo pill. The interaction we have on file is specifically about the caffeine part of your medicine. Evodia appears to speed up a liver enzyme called CYP1A2, which is the same enzyme your body uses to break caffeine down. So in theory, taking Evodia could clear caffeine out faster and make that piece of the pill feel weaker (less of that mild alertness or headache-relief boost from the caffeine).

I want to be honest about the evidence, though. This comes only from lab and animal studies, where Evodia dropped caffeine levels quite a bit. We don't have solid human data, so it stays theoretical. The good news is this doesn't touch the aspirin or codeine. Still, before adding Evodia, check with your pharmacist or doctor.

References
  1. 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.

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 Aspirin, Caffeine, 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 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 Aspirin, Caffeine, Codeine Phosphate

This page covers Evodia only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Aspirin, Caffeine, Codeine Phosphate page lists 398 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 Danshen (major).

By severity: 17 major · 334 moderate · 47 minor.

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

“Anacin with Codeine combines aspirin, caffeine, and codeine, and each of the three picks up its own supplement problems, so this is a list worth real caution. Just over half of the 398 ingredients here, 202 of them, can add to aspirin's blood-thinning action and raise bleeding risk.”

Reviewed by 2 · Jul 18, 2026

Open the Aspirin, Caffeine, Codeine Phosphate 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 Aspirin, Caffeine, Codeine Phosphate 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 Aspirin, Caffeine, 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 Evodia
Top half

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

29 days ago today
Medication Aspirin, Caffeine, Codeine Phosphate
Top half

#1,390 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
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
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 Evodia and Aspirin, Caffeine, Codeine Phosphate Together: Common Questions

Can you take Evodia with Aspirin, Caffeine, 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 4 interactions listed for Evodia and Aspirin, Caffeine, Codeine Phosphate?
Aspirin, Caffeine, Codeine Phosphate 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 Aspirin, Caffeine, 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.