Drug & supplement interaction

Ceylon Leadwort + 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 3 drug categories that Ceylon Leadwort can interact with; the most serious is rated moderate. Plumbagin, a constituent of Ceylon leadwort, has been shown to inhibit cytochrome P450 1A2 (CYP1A2) in vitro.

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

Ceylon Leadwort and Estradiol, Norethindrone Acetate

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

Why Are There 3 Interactions?

Ceylon Leadwort interacts with whole categories of medication. Estradiol, Norethindrone Acetate falls into 3 of those categories, so it can interact with Ceylon Leadwort 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 Estradiol, Norethindrone Acetate

Estradiol, Norethindrone Acetate falls under CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES — the group Ceylon Leadwort interacts with.

Plumbagin, a constituent of Ceylon leadwort, has been shown to inhibit cytochrome P450 1A2 (CYP1A2) in vitro. So far, this interaction has not been reported in humans. Theoretically, Ceylon leadwort might increase the levels of drugs metabolized by CYP1A2. Some substrates of CYP1A2 include clozapine (Clozaril), cyclobenzaprine (Flexeril), fluvoxamine (Luvox), haloperidol (Haldol), imipramine (Tofranil), mexiletine (Mexitil), olanzapine (Zyprexa), pentazocine (Talwin), propranolol (Inderal), tacrine (Cognex), zileuton (Zyflo), zolmitriptan (Zomig), and 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 gist for your Activella (estradiol plus norethindrone). A compound in Ceylon Leadwort called plumbagin has slowed down a liver enzyme named CYP1A2 in test-tube studies. Your estrogen is partly broken down by this enzyme, so in theory, blocking it could let a bit more estrogen build up in your system. That might mean stronger estrogen-type effects, like breast tenderness, bloating, nausea, headaches, or breakthrough spotting.

I want to be honest about the strength of this, though. It's only been seen in lab dishes, never in actual people, so it's quite theoretical. Still, since hormone therapy can be sensitive, I'd run any Ceylon Leadwort supplement past your pharmacist or doctor first before adding it.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Chen A, Zhou X, Tang S, Liu M, Wang X. Evaluation of the inhibition potential of plumbagin against cytochrome P450 using LC-MS/MS and cocktail approach. Sci Rep. 2016 Jun 22;6:28482. PubMed
Moderate

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

2 of 3

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

Plumbagin, a constituent of Ceylon leadwort, has been shown to inhibit cytochrome P450 3A4 (CYP3A4) in vitro. So far, this interaction has not been reported in humans. Theoretically, Ceylon leadwort might increase the levels of drugs metabolized by CYP3A4. Some drugs metabolized by CYP3A4 include lovastatin (Mevacor), clarithromycin (Biaxin), indinavir (Crixivan), sildenafil (Viagra), triazolam (Halcion), and numerous 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

Your Activella combines estradiol (an estrogen) with norethindrone, and both hormones get cleared by a liver enzyme called CYP3A4. Ceylon Leadwort contains plumbagin, which in test-tube studies appears to slow that enzyme down. In plain terms, if it slows the breakdown of these hormones, slightly more could linger in your body. That might mean more of the typical estrogen-related effects, like breast tenderness, bloating, nausea, headaches, or spotting.

Here's the reassuring part: this has only been seen in lab dishes, never confirmed in real people, so it stays theoretical for now. Still, since hormones are sensitive to small shifts, it's worth a quick chat with your pharmacist or doctor before pairing them, especially with concentrated supplement doses.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Chen A, Zhou X, Tang S, Liu M, Wang X. Evaluation of the inhibition potential of plumbagin against cytochrome P450 using LC-MS/MS and cocktail approach. Sci Rep. 2016 Jun 22;6:28482. PubMed
Moderate

ESTROGENS

3 of 3

Estradiol, Norethindrone Acetate also falls under ESTROGENS.

Laboratory research suggests that Ceylon leadwort root extract has anti-estrogenic activity. Theoretically, Ceylon leadwort may interfere with hormone therapy.
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

Activella combines estradiol with a progestin (norethindrone), and it's usually prescribed to ease menopause symptoms like hot flashes, night sweats, and vaginal dryness. The concern here is that Ceylon Leadwort root has shown anti-estrogenic activity in lab studies, meaning it may work against estrogen. In theory, that could blunt how well your hormone therapy controls those symptoms, so you might notice your hot flashes or other complaints creeping back.

I'll be honest with you though: this warning comes only from test-tube and animal research, not from real people, so we can't say how much it actually matters in everyday use. It's not a dangerous combination, just a possible one. Before adding this supplement, please check with your pharmacist or doctor.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Sandeep G, Dheeraj A, Sharma NK, Jhade D, Bharti A. Effect of plumbagin free alcohol extract of Plumbago zeylanica Linn. root on reproductive system of female Wistar rats. Asian Pac J Trop Med. 2011 Dec;4(12):978-84. 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

Ceylon Leadwort Also Interacts With Other Medications

Ceylon Leadwort has 1,096 moderate 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 1,096 No known interaction 1,734 (incl. Estradiol, Norethindrone Acetate)
Taking anything else?

Check Another of Your Medications Against Ceylon Leadwort

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

Everything else you take

See Every Supplement That Interacts With Estradiol, Norethindrone Acetate

This page covers Ceylon Leadwort 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 Ceylon Leadwort as Part of a Dietary Supplement Product? Check It for Interactions

We hold 96 real supplement products containing Ceylon Leadwort, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Ceylon Leadwort. Your product may carry other ingredients that interact with Estradiol, Norethindrone Acetate too, on top of Ceylon Leadwort — 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 Ceylon Leadwort 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 Ceylon Leadwort
Top half

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

29 days ago today
Medication Estradiol, Norethindrone Acetate
Steady interest

#2,398 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 Ceylon Leadwort

What is Ceylon Leadwort?

  • Digestive complaints and poor appetite
  • Skin conditions and wounds (applied to the skin)
  • Joint pain and swelling
  • Traditional 'metabolism-boosting' tonics
  • Antimicrobial folk remedy

Ceylon Leadwort (Plumbago zeylanica) is a plant long used in Ayurvedic and other traditional medicine systems, mainly for digestion, skin problems, and pain. Solid human studies are lacking, and the plant contains plumbagin, a compound that can irritate skin and tissues and may be unsafe in larger amounts. Talk to a pharmacist or doctor before using it, and avoid it in pregnancy.

Read the full Ceylon Leadwort monograph & all interactions
Keep checking

Other Drugs & Ceylon Leadwort

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

0Major
1,096Moderate
0Minor
1,733No known interaction
1,096 Moderate 1,733 No interaction
Moderate

1,096 interactions

Showing 60 of 1,096 moderate interactions — see all 1,096 on the Ceylon Leadwort page.

No interaction 1,733 drugs checked — show the list

We also checked Ceylon Leadwort against these medications and found no known interaction in our sources. Open any page to confirm.

Showing the 60 most looked-up of 1,733 medications checked with no known interaction — see the full Ceylon Leadwort list.

See the full Ceylon Leadwort 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
Ceylon Leadwort 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 Ceylon Leadwort and Estradiol, Norethindrone Acetate Together: Common Questions

Can you take Ceylon Leadwort 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 3 interactions listed for Ceylon Leadwort and Estradiol, Norethindrone Acetate?
Estradiol, Norethindrone Acetate belongs to more than one drug category, and Ceylon Leadwort 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 Ceylon Leadwort 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 Ceylon Leadwort?

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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.