Drug & supplement interaction

Evodia + Ramelteon

Ramelteon brand name: Rozerem.

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

Ramelteon falls into 2 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
Interactions2
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Evodia and Ramelteon

These two interact in 2 distinct ways. Each one is explained separately below.

Why Are There 2 Interactions?

Evodia interacts with whole categories of medication. Ramelteon falls into 2 of those categories, so it can interact with Evodia in 2 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 2

Why this applies to Ramelteon

Ramelteon 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

Here's the simple version: your body relies heavily on a liver enzyme called CYP1A2 to break down ramelteon (Rozerem). Evodia appears to rev up that enzyme, so it may clear ramelteon out of your system faster than usual. Since ramelteon is an active sleep aid (not a prodrug that needs switching on), speeding up its breakdown could leave you with less drug working. In real terms, that might mean ramelteon doesn't help you fall asleep as well, and you're back to tossing and turning.

Keep in mind this is based on animal and lab studies, not people, so it's more of a heads-up than a sure thing. Before combining the two, just check with your pharmacist or doctor so they can keep an eye on how well your sleep medicine is working.

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 2

Ramelteon 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 for these two together. Your body relies on a liver enzyme called CYP3A4 to break down ramelteon (Rozerem). Lab studies suggest evodia may slow that enzyme down. If that happens in people, ramelteon could clear out more slowly and build up a bit, which might make it feel stronger than usual. With a sleep medicine, that could mean extra drowsiness, grogginess the next morning, or feeling dizzy when you get up.

I want to be honest, though: this is only seen in test-tube research, not in actual patients, so it's more of a theoretical caution than a proven problem. Ramelteon is generally gentle, so the risk is likely small. Still, run it past your pharmacist or doctor before pairing them.

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

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 Ramelteon 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. Ramelteon)
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.

From our Q&A

Questions About Evodia or Ramelteon

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Evodia or Ramelteon, not necessarily both, but if one is close to what you were about to ask it will usually go further than a database entry can:

Not quite your question? Ask our pharmacists directly — it is free, there is no account required, and answers usually come back within 24 hours.

Everything else you take

See Every Supplement That Interacts With Ramelteon

This page covers Evodia only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Ramelteon page lists 228 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), Beer (major), Gamma-hydroxybutyrate (ghb) (major) and Grapefruit (major).

By severity: 9 major · 173 moderate · 46 minor.

From our pharmacist’s overview on the Ramelteon page

“Ramelteon (Rozerem) is a prescription sleep aid, and its 228 interacting supplements call for real care, starting with the nine rated major. The frustrating part is that the things sleepless people typically reach for, kava, CBD, a glass of wine before bed, sit at the heart of the problem.”

Reviewed by 2 · Jul 18, 2026

Open the Ramelteon 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 Ramelteon 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 Ramelteon 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

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

29 days ago today
Medication Ramelteon
Top half

#1,182 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
Medication

About Ramelteon

What Is Ramelteon Used For?

Brand name: Rozerem

Ramelteon tablets — sold as the brand Rozerem and as generic ramelteon — are used to treat insomnia when the main problem is trouble falling asleep at the start of the night. It is not indicated for difficulty staying asleep.

Clinical studies supporting its effectiveness ran up to six months in both adults and elderly patients.

See full Ramelteon drug information
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 Ramelteon, 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 Ramelteon supplement interactions › Every supplement checked against Ramelteon, ranked by severity Ramelteon drug information › The full plain-English guide to this medication 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 Ramelteon Together: Common Questions

Can you take Evodia with Ramelteon?
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 2 interactions listed for Evodia and Ramelteon?
Ramelteon 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 Ramelteon 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 Ramelteon and Evodia?

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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.