Drug & supplement interaction

Evodia + Aspirin, Caffeine, Dihydrocodeine Bitartrate

Aspirin, Caffeine, Dihydrocodeine Bitartrate brand name: Synalgos DC.

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

Aspirin, Caffeine, Dihydrocodeine Bitartrate 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, Dihydrocodeine Bitartrate

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, Dihydrocodeine Bitartrate 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, Dihydrocodeine Bitartrate

Aspirin, Caffeine, Dihydrocodeine Bitartrate 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

Out of the three ingredients in Synalgos DC, the one that really interacts with Evodia is the caffeine. Your liver uses an enzyme called CYP1A2 to break caffeine down, and lab and animal studies suggest Evodia (specifically a compound called rutaecarpine) speeds that enzyme up. In animals, that dropped caffeine levels by roughly 70 percent. So in theory, Evodia could clear the caffeine faster and you might notice less of its perk, like a little less alertness or a caffeine-withdrawal headache.

Keep in mind this is based only on test-tube and animal research, not human studies, so the real-world effect is uncertain. The aspirin and dihydrocodeine parts are not expected to change much here. Before combining them, it is worth a quick chat 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

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

2 of 4

Aspirin, Caffeine, Dihydrocodeine Bitartrate 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

Here's the gist with Synalgos DC, which mixes aspirin, caffeine, and dihydrocodeine. In test-tube studies, evodia appears to slow down a liver enzyme called CYP3A4. That enzyme helps process several medicines, including the dihydrocodeine and caffeine in this combo. In theory, if evodia blocks it, more of the drug could linger in your body, which might mean stronger opioid effects like extra drowsiness, dizziness, constipation, or slowed breathing, plus more caffeine jitters or a racing heart.

That said, this has only been seen in lab research, not in real people, so the actual risk is uncertain. Still, since this product contains an opioid, it's worth a quick chat with your pharmacist or doctor before pairing it with evodia.

Contact Dr. Brian directly if you have additional questions on this interaction
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, Dihydrocodeine Bitartrate 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 piece to focus on with Synalgos DC: the aspirin in this combination is already a blood thinner that keeps your platelets from clumping together. Evodia contains a compound called rutaecarpine, which in test tube and animal studies seemed to do something similar (it slowed platelet activity too). Stack the two and, in theory, you could see a bit more bruising, nosebleeds, bleeding gums, or stomach upset that's slow to stop.

I want to be honest, though: this is based only on lab and animal research, not on people, so it's more of a caution than a proven problem. The caffeine and dihydrocodeine parts aren't really the concern here. Before adding evodia, run it by your pharmacist or doctor so they can look at your full picture.

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

CAFFEINE

4 of 4

Aspirin, Caffeine, Dihydrocodeine Bitartrate 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 the gist for Synalgos DC, which pairs aspirin and dihydrocodeine with a dose of caffeine. The caffeine part is the piece Evodia can touch. Your liver uses an enzyme called CYP1A2 to clear caffeine, and Evodia appears to speed that enzyme up. In animal studies it dropped caffeine levels by as much as 71 percent, so in theory the caffeine in your tablet might not stick around as long or work as well.

In practice this is a mild concern. Caffeine is included mainly to give a small lift to the pain relief, so a faster clearance might make that boost a bit weaker. Importantly, this is only lab and animal evidence, not human studies, and it shouldn't change the aspirin or dihydrocodeine. Still, check with your pharmacist or doctor before combining them.

Contact Dr. Brian directly if you have additional questions on this interaction
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, Dihydrocodeine Bitartrate 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. Aspirin, Caffeine, Dihydrocodeine Bitartrate)
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, Dihydrocodeine Bitartrate

This page covers Evodia only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Aspirin, Caffeine, Dihydrocodeine Bitartrate 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.

Open the Aspirin, Caffeine, Dihydrocodeine Bitartrate 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, Dihydrocodeine Bitartrate 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, Dihydrocodeine Bitartrate 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, Dihydrocodeine Bitartrate
Steady interest

#1,526 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 Aspirin, Caffeine, Dihydrocodeine Bitartrate, 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 Aspirin, Caffeine, Dihydrocodeine Bitartrate supplement interactions › Every supplement checked against Aspirin, Caffeine, Dihydrocodeine Bitartrate, 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 Aspirin, Caffeine, Dihydrocodeine Bitartrate Together: Common Questions

Can you take Evodia with Aspirin, Caffeine, Dihydrocodeine Bitartrate?
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, Dihydrocodeine Bitartrate?
Aspirin, Caffeine, Dihydrocodeine Bitartrate 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, Dihydrocodeine Bitartrate 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.