Drug & supplement interaction

Devil's Claw + Estradiol, Norethindrone Acetate

Estradiol, Norethindrone Acetate brand name: Activella.

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

Estradiol, Norethindrone Acetate falls into 2 drug categories that Devil's Claw can interact with; the most serious is rated moderate. Theoretically, devil's claw might increase levels of drugs metabolized by CYP3A4.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions2
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Devil's Claw and Estradiol, Norethindrone Acetate

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

Why Are There 2 Interactions?

Devil's Claw interacts with whole categories of medication. Estradiol, Norethindrone Acetate falls into 2 of those categories, so it can interact with Devil's Claw 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 3A4 (CYP3A4) SUBSTRATES

1 of 2

Why this applies to Estradiol, Norethindrone Acetate

Estradiol, Norethindrone Acetate falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES — the group Devil's Claw interacts with.

Theoretically, devil's claw might increase levels of drugs metabolized by CYP3A4.
In vitro research shows that devil's claw might inhibit CYP3A4, although this 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 Activella combines estradiol with norethindrone, and your liver uses an enzyme called CYP3A4 to help break down these hormones and clear them out. Devil's claw has shown, in test-tube studies only, that it might slow this same enzyme down. If that happened in real life, your hormone levels could creep up a bit, which might mean more of the usual estrogen-related effects like breast tenderness, bloating, nausea, headaches, or spotting.

Here's the reassuring part: this is purely theoretical. It's been seen in lab dishes, not in actual people, so we really don't know if it matters at all. I wouldn't lose sleep over it, but since both affect your body, it's worth a quick chat with your pharmacist or doctor before adding devil's claw.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Unger M, Frank A. Simultaneous determination of the inhibitory potency of herbal extracts on the activity of six major cytochrome P450 enzymes using liquid chromatography/mass spectrometry and automated online extraction. Rapid Commun Mass Spectrom 2004;1 PubMed
Minor

P-GLYCOPROTEIN SUBSTRATES

2 of 2

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

Theoretically, devil's claw might increase levels of P-glycoprotein substrates.
In vitro research shows that devil's claw inhibits P-glycoprotein, which transports many drugs out of cells. This might increase intracellular levels of P-glycoprotein substrates, although it is unclear if this effect would be clinically important.
Severity Minor 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

Activella combines two hormones, estradiol (an estrogen) and norethindrone (a progestin), and it's used to ease menopausal symptoms like hot flashes. The concern here is that devil's claw, in lab studies, appears to block a cellular pump called P-glycoprotein that helps move certain drugs out of cells. In theory, that could let a bit more of these hormones build up in your body, which might mean slightly more of the usual estrogen-related effects like breast tenderness, bloating, nausea, or spotting.

I want to be honest with you though: this is based only on test-tube research, the rating is minor, and we don't know if it actually matters in real people. It's worth mentioning to your pharmacist or doctor, but no need to panic.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Romiti N, Tramonti G, Corti A, Chieli E. Effects of Devil's Claw (Harpagophytum procumbens) on the multidrug transporter ABCB1/P-glycoprotein. Phytomedicine 2009;16:1095-100. 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

Devil's Claw Also Interacts With Other Medications

Devil's Claw has 730 moderate, 73 minor known drug interactions in our database — the Estradiol, Norethindrone Acetate one above is among them. If you take anything else, check it against the full list below.

Moderate 730 Minor 73 No known interaction 2,027 (incl. Estradiol, Norethindrone Acetate)
Taking anything else?

Check Another of Your Medications Against Devil's Claw

Covers the 2,830 medications we’ve checked against Devil's Claw. Pick one to open its full report.

Everything else you take

See Every Supplement That Interacts With Estradiol, Norethindrone Acetate

This page covers Devil's Claw 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

One more smart check

Taking Devil's Claw as Part of a Dietary Supplement Product? Check It for Interactions

We hold 585 real supplement products containing Devil's Claw, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Devil's Claw. Your product may carry other ingredients that interact with Estradiol, Norethindrone Acetate too, on top of Devil's Claw — 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 Devil's Claw 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 Devil's Claw
Top 25%

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

29 days ago today
Medication Estradiol, Norethindrone Acetate
Steady interest

#2,243 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 Devil's Claw

What is Devil's Claw?

Devil's Claw
  • Osteoarthritis pain
  • Lower back pain
  • Joint pain and stiffness
  • General inflammation
  • Digestive upset and loss of appetite

Devil's claw is a southern African plant used mainly for arthritis and back pain, and some studies suggest it may help ease these types of discomfort. The evidence is moderate at best, and product strength varies, so talk with your pharmacist or doctor before trying it, especially if you have a health condition or take medications.

Read the full Devil's Claw monograph & all interactions
Keep checking

Other Drugs & Devil's Claw

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

0Major
730Moderate
73Minor
2,026No known interaction
730 Moderate 73 Minor 2,026 No interaction
Moderate

730 interactions

Showing 60 of 730 moderate interactions — see all 730 on the Devil's Claw page.

Minor

73 interactions

Showing 60 of 73 minor interactions — see all 73 on the Devil's Claw page.

No interaction 2,026 drugs checked — show the list

We also checked Devil's Claw against these medications and found no known interaction in our sources. Open any page to confirm.

Showing the 60 most looked-up of 2,026 medications checked with no known interaction — see the full Devil's Claw list.

See the full Devil's Claw interactions page
See every supplement checked against Estradiol, 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
Devil's Claw monograph › Uses, safety, and every drug interaction in one place Estradiol, Norethindrone Acetate supplement interactions › Every supplement checked against Estradiol, 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 Devil's Claw and Estradiol, Norethindrone Acetate Together: Common Questions

Can you take Devil's Claw 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.
Why are there 2 interactions listed for Devil's Claw and Estradiol, Norethindrone Acetate?
Estradiol, Norethindrone Acetate belongs to more than one drug category, and Devil's Claw 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 Devil's Claw 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

Still Have a Question About Estradiol, Norethindrone Acetate and Devil's Claw?

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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.