Drug & supplement interaction

Evodia + Leuprolide Acetate, Norethindrone Acetate

Leuprolide Acetate, Norethindrone Acetate brand name: Lupaneta Pack.

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

Leuprolide Acetate, Norethindrone Acetate falls into 3 drug categories that Evodia can interact with; the most serious is rated moderate. Theoretically, CYP3A4 inhibitors might increase the levels and clinical effects of evodia.

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

Evodia and Leuprolide Acetate, Norethindrone Acetate

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. Leuprolide Acetate, Norethindrone Acetate 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 3A4 (CYP3A4) INHIBITORS

1 of 3

Why this applies to Leuprolide Acetate, Norethindrone Acetate

Leuprolide Acetate, Norethindrone Acetate falls under CYTOCHROME P450 3A4 (CYP3A4) INHIBITORS — the group Evodia interacts with.

Theoretically, CYP3A4 inhibitors might increase the levels and clinical effects of evodia.
Animal research shows that concomitant administration of ketoconazole, a known CYP3A4 inhibitor, with the alkaloid constituents of evodia significantly increases the area under the curve (AUC), maximum concentration (Cmax), and half-life of these constituents.
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 the direction is the reverse of what folks usually expect. The Lupaneta Pack (leuprolide plus norethindrone) isn't being changed by Evodia. Instead, the norethindrone part can act as a mild CYP3A4 inhibitor, which is the liver enzyme that helps break down Evodia's active compounds (like evodiamine and rutaecarpine). So in theory, your medication could slow Evodia's clearance and let those plant compounds build up a bit higher than expected.

To be clear, this is very weak evidence, drawn only from lab and animal studies, so I wouldn't lose sleep over it. There's no good human data showing real-world harm. Still, because Evodia itself is poorly studied, I'd run it past your pharmacist or doctor before combining the two rather than guessing.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Zhang W, Guo J, Wang D, et al. Effect of CYP3A inducer/inhibitor on pharmacokinetics of five alkaloids in Evodiae Fructus. Chem Biol Interact 2020;327:109146. PubMed
Moderate

CYTOCHROME P450 1A2 (CYP1A2) INHIBITORS

2 of 3

Leuprolide Acetate, Norethindrone Acetate also falls under CYTOCHROME P450 1A2 (CYP1A2) INHIBITORS.

Theoretically, drugs that inhibit CYP1A2 might increase the levels and clinical effects of evodia.
The evodia constituent rutaecarpine is metabolized by CYP1A2.
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 key thing to understand about this particular pairing: the interaction runs in the opposite direction from what you might expect. It's not your Lupaneta Pack (leuprolide plus norethindrone) that gets affected. Instead, this medication may block a liver enzyme called CYP1A2, which happens to be the enzyme that helps clear one of evodia's active compounds, rutaecarpine. So the concern is that evodia levels could climb in your system, not your hormone therapy levels.

To be fair, this is purely theoretical and based only on test tube and animal work, so I wouldn't lose sleep over it. Still, since evodia has so little human safety data, it's worth a quick chat with your pharmacist or doctor before combining the two.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. 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

3 of 3

Leuprolide Acetate, Norethindrone Acetate 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

Lupaneta Pack combines leuprolide (an injectable hormone medicine) with norethindrone, an oral progestin that your liver processes using an enzyme called CYP3A4. The concern here is with the norethindrone part. In test-tube studies, evodia appears to slow down CYP3A4, which could in theory let norethindrone build up a bit and lead to more progestin-type side effects like breakthrough bleeding or spotting, breast tenderness, headaches, mood changes, or bloating.

Here's the important context: this is only seen in lab studies, not in real people, so we honestly don't know if it matters in everyday use. Leuprolide itself isn't affected. To be safe, run your evodia use past your pharmacist or doctor before combining the two.

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 Leuprolide Acetate, Norethindrone Acetate 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. Leuprolide Acetate, Norethindrone Acetate)
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 Leuprolide Acetate, Norethindrone Acetate

This page covers Evodia only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Leuprolide Acetate, Norethindrone Acetate page lists 152 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Grapefruit (major), St. John's Wort (major), Acacia Rigidula (moderate) and Adrafinil (moderate).

By severity: 3 major · 108 moderate · 41 minor.

From our pharmacist’s overview on the Leuprolide Acetate, Norethindrone Acetate page

“Lupaneta Pack (leuprolide acetate with norethindrone acetate) treats endometriosis pain, and the norethindrone tablet is where nearly all of these interactions land. Most ingredients on this page change how the liver handles that hormone through the CYP3A4 enzyme, some raising its level and side effects, others lowering it enough to we…”

Reviewed by 2 · Jul 18, 2026

Open the Leuprolide Acetate, Norethindrone Acetate 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 Leuprolide Acetate, Norethindrone Acetate 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 Leuprolide Acetate, Norethindrone Acetate 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

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

29 days ago today
Medication Leuprolide Acetate, Norethindrone Acetate
Top half

#1,368 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 Leuprolide Acetate, Norethindrone Acetate, 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 Leuprolide Acetate, Norethindrone Acetate supplement interactions › Every supplement checked against Leuprolide Acetate, Norethindrone Acetate, 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 Leuprolide Acetate, Norethindrone Acetate Together: Common Questions

Can you take Evodia with Leuprolide Acetate, Norethindrone Acetate?
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 Leuprolide Acetate, Norethindrone Acetate?
Leuprolide Acetate, Norethindrone Acetate 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 Leuprolide Acetate, Norethindrone Acetate 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.