Drug & supplement interaction

Neem + Ethinyl Estradiol, Norethindrone

Ethinyl Estradiol, Norethindrone brand names: Femhrt, Loestrin 21, Ovcon 35 21, Ovcon 50 28, Necon 0.5 35 21, and others.

Moderate Interaction
The bottom line Moderate

Ethinyl Estradiol, Norethindrone falls into 3 drug categories that Neem can interact with; the most serious is rated moderate. Theoretically, neem leaf extract might increase the levels and clinical effects of CYP1A2 substrates.

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

Neem and Ethinyl Estradiol, Norethindrone

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

Why Are There 3 Interactions?

Neem interacts with whole categories of medication. Ethinyl Estradiol, Norethindrone falls into 3 of those categories, so it can interact with Neem 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 Ethinyl Estradiol, Norethindrone

Ethinyl Estradiol, Norethindrone falls under CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES — the group Neem interacts with.

Theoretically, neem leaf extract might increase the levels and clinical effects of CYP1A2 substrates.
In vitro research shows that neem leaf extract inhibits CYP1A2 enzymes. So far, this reaction 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 situation with your birth control pill (or hormone therapy), which contains ethinyl estradiol and norethindrone. In lab dishes, neem leaf extract appears to slow down an enzyme called CYP1A2, one of the pathways your body uses to break down these hormones. If that enzyme is blocked, the hormones could theoretically build up a bit higher than usual. That might mean more of the common estrogen-type side effects, such as nausea, breast tenderness, bloating, headaches, or mood changes.

I want to be honest with you though: this is only a test-tube finding, and it has never actually been seen in real people. So I wouldn't lose sleep over it. Still, if you plan to take concentrated neem supplements regularly, give your pharmacist or doctor a quick heads-up first.

References
  1. Amaeze O, Marques ES, Wei W, et al. Evaluation of Nigerian Medicinal Plants Extract on Human P-glycoprotein and Cytochrome P450 Enzyme Induction: Implications for Herb-drug Interaction. Curr Drug Metab. 2021;22(14):1103-1113. PubMed
Moderate

P-GLYCOPROTEIN SUBSTRATES

2 of 3

Ethinyl Estradiol, Norethindrone also falls under P-GLYCOPROTEIN SUBSTRATES.

Theoretically, neem leaf extract might increase the levels and clinical effects of P-glycoprotein substrates.
In vitro research shows that neem leaf methanol extract inhibits renal P-glycoprotein transport activity. So far, this reaction 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 your birth control pill (the combo of ethinyl estradiol and norethindrone). Neem leaf extract has been shown, in test-tube studies, to slow down a transporter called P-glycoprotein. This hormone pill is partly handled by that transporter, so in theory neem could let a bit more of the medication hang around in your body. That might mean slightly stronger hormone effects, like nausea, breast tenderness, bloating, headaches, or spotting.

The honest truth: this is purely lab and animal data. It has never been reported in real people, so I wouldn't lose sleep over it. Still, since neem can be risky if swallowed, please run any neem supplement past your pharmacist or doctor before combining the two.

References
  1. Amaeze O, Marques ES, Wei W, et al. Evaluation of Nigerian Medicinal Plants Extract on Human P-glycoprotein and Cytochrome P450 Enzyme Induction: Implications for Herb-drug Interaction. Curr Drug Metab. 2021;22(14):1103-1113. PubMed
Moderate

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

3 of 3

Ethinyl Estradiol, Norethindrone also falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES.

Theoretically, neem leaf extract might increase the levels and clinical effects of CYP3A4 substrates.
In vitro research shows that neem leaf methanol extract inhibits CYP3A4 enzymes. So far, this reaction 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

Your birth control combo, ethinyl estradiol with norethindrone, is processed by a liver enzyme called CYP3A4. In test-tube studies, neem leaf extract appeared to slow that enzyme down. If that happened in the body, it could let more of the hormones build up, which might bump up typical estrogen-related side effects like nausea, breast tenderness, headaches, bloating, or mood changes.

Here's the reassuring part: this is only lab data, and nothing like it has actually been seen in people. So it's a theoretical concern, not a proven one. The hormones still do their job here, so this isn't about losing pregnancy protection. If you're using neem regularly and not just in skin or dental products, mention it to your pharmacist or doctor so they can keep an eye on things.

References
  1. Amaeze O, Eng H, Horlbogen L, Varma MVS, Slitt A. Cytochrome P450 Enzyme Inhibition and Herb-Drug Interaction Potential of Medicinal Plant Extracts Used for Management of Diabetes in Nigeria. Eur J Drug Metab Pharmacokinet. 2021;46(3):437-450. 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

Neem Also Interacts With Other Medications

Neem has 1,012 moderate known drug interactions in our database — the Ethinyl Estradiol, Norethindrone 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 Neem

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

Everything else you take

See Every Supplement That Interacts With Ethinyl Estradiol, Norethindrone

This page covers Neem only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Ethinyl Estradiol, Norethindrone page lists 240 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Beer (major), Grapefruit (major), Siberian Cocklebur (major) and St. John's Wort (major).

By severity: 6 major · 196 moderate · 38 minor.

From our pharmacist’s overview on the Ethinyl Estradiol, Norethindrone page

“If you take a birth control pill or hormone therapy containing ethinyl estradiol and norethindrone (Loestrin, Femhrt, and others), a few supplements can genuinely undermine it, so read this page with care. Six of the 240 ingredients on file are rated major, and those six come first.”

Reviewed by 2 · Jul 18, 2026

Open the Ethinyl Estradiol, Norethindrone interaction page

One more smart check

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

We hold 288 real supplement products containing Neem, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Neem. Your product may carry other ingredients that interact with Ethinyl Estradiol, Norethindrone too, on top of Neem — 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 Neem and Ethinyl Estradiol, Norethindrone 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 Neem
Top 25%

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

29 days ago today
Medication Ethinyl Estradiol, Norethindrone
Top 25%

#316 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 Neem

What is Neem?

Neem
  • Skin conditions
  • Dental and gum health
  • Antimicrobial and antiparasitic
  • Digestive upset
  • Blood sugar support
  • Insect repellent/pesticide

Neem is a tree from India used for centuries in traditional medicine, especially for skin, dental, and antimicrobial purposes. Some small studies are promising for oral health and skin, but high-quality human evidence is limited for most uses. Neem oil and seed extracts can be toxic if swallowed, especially in children, so use with caution and talk to your pharmacist or doctor first.

Read the full Neem monograph & all interactions
Keep checking

Other Drugs & Neem

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

0Major
1,012Moderate
0Minor
1,817No known interaction
Moderate

1,012 interactions

Showing 60 of 1,012 moderate interactions — see all 1,012 on the Neem page.

No interaction 1,817 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 Neem and Ethinyl Estradiol, Norethindrone Together: Common Questions

Can you take Neem with Ethinyl Estradiol, Norethindrone?
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 Neem and Ethinyl Estradiol, Norethindrone?
Ethinyl Estradiol, Norethindrone belongs to more than one drug category, and Neem 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 Neem and Ethinyl Estradiol, Norethindrone 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.