Drug & supplement interaction

Ergot + Estradiol, Norethindrone Acetate

Estradiol, Norethindrone Acetate brand name: Activella.

Moderate Interaction
The bottom line Moderate

Ergot has a moderate interaction with Estradiol, Norethindrone Acetate. Ergotamine, a constituent of ergot, is a substrate of cytochrome P450 3A4 (CYP3A4).

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

Ergot and Estradiol, Norethindrone Acetate

Here is the interaction we found between these two, with the evidence behind it.

Moderate

CYTOCHROME P450 3A4 (CYP3A4) INHIBITORS

Why this applies to Estradiol, Norethindrone Acetate

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

Ergotamine, a constituent of ergot, is a substrate of cytochrome P450 3A4 (CYP3A4). Theoretically, drugs that inhibit CYP3A4 might increase the risk of ergot toxicity. Some of these drugs include amiodarone (Cordarone), clarithromycin (Biaxin), diltiazem (Cardizem), erythromycin (E-mycin, Erythrocin), indinavir (Crixivan), ritonavir (Norvir), saquinavir (Fortovase, Invirase), and many others.
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 about this pairing: it works in the opposite direction from what you might expect. Ergot itself is the ingredient that gets cleared by the CYP3A4 enzyme, and the estrogen in Activella (estradiol) is one of the things that can mildly slow that enzyme down. So in theory, your hormone therapy could let ergot build up a little, raising the odds of ergot toxicity, things like cold, numb hands and feet, leg cramps, nausea, headache, or a dangerous narrowing of blood vessels.

Honestly, the bigger point is that ergot itself isn't safe to take as a supplement at all, no matter what else you're on. This concern rests on weak, anecdotal evidence, but please don't experiment. Run it by your pharmacist or doctor first.

References
  1. Eadie MJ. Convulsive ergotism: epidemics of the serotonin syndrome? Lancet Neurol 2003;2:429-34. 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

Ergot Also Interacts With Other Medications

Ergot has 461 moderate known drug interactions in our database — the Estradiol, Norethindrone Acetate one above is one of them. If you take anything else, check it against the full list below.

Taking anything else?

Check Another of Your Medications Against Ergot

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

Everything else you take

See Every Supplement That Interacts With Estradiol, Norethindrone Acetate

This page covers Ergot only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Estradiol, Norethindrone Acetate page lists 212 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 · 171 moderate · 38 minor.

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

“Activella pairs estradiol with norethindrone as hormone therapy, and because the treatment depends on steady hormone levels in the blood, supplements that raise or lower those levels warrant real scrutiny. Three of the 212 interacting ingredients rate major, and all three hit that weak point: St.”

Reviewed by 2 · Jul 18, 2026

Open the Estradiol, Norethindrone Acetate interaction page

How much people look this up

Where Ergot and Estradiol, 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 Ergot
Steady interest

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

29 days ago today
Medication Estradiol, Norethindrone Acetate
Top half

#1,371 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 Ergot

What is Ergot?

Ergot
  • Heavy menstrual or uterine bleeding
  • Bleeding after childbirth
  • Migraine headaches
  • Stimulating uterine contractions

Ergot is a toxic fungus that grows on rye and contains powerful chemicals (ergot alkaloids) that strongly narrow blood vessels and squeeze the uterus. Because raw ergot is poisonous and the dose is impossible to control safely, it should never be used as a home remedy or supplement. Some purified ergot chemicals are used as prescription drugs under strict medical supervision, but the crude herb is not safe to take.

Read the full Ergot monograph & all interactions
Keep checking

Other Drugs & Ergot

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

0Major
461Moderate
0Minor
2,368No known interaction
Moderate

461 interactions

Showing 60 of 461 moderate interactions — see all 461 on the Ergot page.

No interaction 2,368 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 Ergot and Estradiol, Norethindrone Acetate Together: Common Questions

Can you take Ergot with Estradiol, 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.
How serious is the Ergot and Estradiol, 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.