Drug & supplement interaction

Kava + Estradiol, Norgestimate

Estradiol, Norgestimate brand name: Ortho-Prefest.

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

Estradiol, Norgestimate falls into 2 drug categories that Kava can interact with; the most serious is rated moderate. It is unclear if kava inhibits P-glycoprotein (P-gp); research is conflicting.

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

Kava and Estradiol, Norgestimate

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

Why Are There 2 Interactions?

Kava interacts with whole categories of medication. Estradiol, Norgestimate falls into 2 of those categories, so it can interact with Kava in 2 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

P-GLYCOPROTEIN SUBSTRATES

1 of 2

Why this applies to Estradiol, Norgestimate

Estradiol, Norgestimate falls under P-GLYCOPROTEIN SUBSTRATES — the group Kava interacts with.

It is unclear if kava inhibits P-glycoprotein (P-gp); research is conflicting.
In vitro research shows that kava can inhibit P-gp efflux. However, a clinical study in healthy volunteers shows that taking kava standardized to provide 225 mg kavalactones daily for 14 days does not affect the pharmacokinetics of digoxin, a P-gp substrate. It is possible that the use of other P-gp substrates or higher doses of kava might still inhibit P-gp.
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 short version on combining kava with Ortho-Prefest (estradiol and norgestimate). On paper, this hormone combo can be moved around the body by a transporter called P-glycoprotein, and lab studies hint that kava might slow that transporter down. If it did, slightly more hormone could linger, which in theory might mean more of the usual estrogen-type effects like breast tenderness, nausea, bloating, or headaches.

But I want to keep this in perspective. The evidence here is weak, mostly test-tube data, and a human study using kava didn't actually change levels of another P-gp drug. So a real-world problem is unlikely. The bigger concern with kava is its rare link to liver damage, so please check with your pharmacist or doctor before using it.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Weiss J, Sauer A, Frank A, Unger M. Extracts and kavalactones of Piper methysticum G. Forst (kava-kava) inhibit P-glycoprotein in vitro. Drug Metab Dispos 2005;33:1580-3. PubMed
  2. Gurley BJ, Swain A, Barone GW, et al. Effect of goldenseal (Hydrastis canadensis) and kava kava (Piper methysticum) supplementation on digoxin pharmacokinetics in humans. Drug Metab Dispos 2007;35:240-5. PubMed
  3. Asher GN, Corbett AH, Hawke RL. Common Herbal Dietary Supplement-Drug Interactions. Am Fam Physician. 2017;96(2):101-107.
Minor

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES

2 of 2

Estradiol, Norgestimate also falls under CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES.

It is unclear if kava inhibits CYP1A2; research is conflicting.
Although in vitro research and a case report suggest that kava inhibits CYP1A2, more robust clinical evidence shows that kava has no effect on CYP1A2. In a clinical study in healthy volunteers, taking kava 1000 mg twice daily (containing a daily dose of 138 mg kavalactones) for 28 days had no effect on CYP1A2 activity.
Severity Minor Likelihood Unlikely Evidence B

Interaction has been demonstrated in animal or in lab research but has been shown not to occur in humans..

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Good news here: the worry with kava and your Ortho-Prefest (estradiol with norgestimate) is mostly theoretical, and the better evidence doesn't back it up. The concern was that kava might block a liver enzyme called CYP1A2, which helps process estrogen. If that happened, estrogen levels could creep up and you might notice things like breast tenderness, bloating, nausea, or mood changes. But in a careful human study, kava didn't actually change this enzyme's activity. So a real-world problem is unlikely.

One thing I'd flag separately: both kava and estrogen can stress the liver. Since kava has rare links to liver harm, it's worth a quick chat with your pharmacist or doctor before combining them.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Mathews JM, Etheridge AS, Black SR. Inhibition of human cytochrome P450 activities by kava extract and kavalactones. Drug Metab Dispos 2002;30:1153-7. PubMed
  2. 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
  3. Gurley BJ, Gardner SF, Hubbard MA, et al. In vivo effects of goldenseal, kava kava, black cohosh, and valerian on human cytochrome P450 1A2, 2D6, 2E1, and 3A4/5 phenotypes. Clin Pharmacol Ther 2005;77:415-26. PubMed
  4. Toohey TP, Lu BY, Wada C. Toxic effects of psychotropics related to possible p450 enzyme inhibition by kava:report of 2 cases. Prim Care Companion CNS Disord 2013;15(5). PubMed
  5. Asher GN, Corbett AH, Hawke RL. Common Herbal Dietary Supplement-Drug Interactions. Am Fam Physician. 2017;96(2):101-107.

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

Kava Also Interacts With Other Medications

Kava has 248 major, 576 moderate, 341 minor known drug interactions in our database — the Estradiol, Norgestimate one above is among them. If you take anything else, check it against the full list below.

Major 248 Moderate 576 Minor 341 No known interaction 1,665 (incl. Estradiol, Norgestimate)
Taking anything else?

Check Another of Your Medications Against Kava

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

Everything else you take

See Every Supplement That Interacts With Estradiol, Norgestimate

This page covers Kava only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Estradiol, Norgestimate page lists 159 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), Adrafinil (moderate) and African Wild Potato (moderate).

By severity: 3 major · 126 moderate · 30 minor.

From our pharmacist’s overview on the Estradiol, Norgestimate page

“Ortho-Prefest pairs estradiol with norgestimate, a hormone therapy most often prescribed for menopause symptoms, and its interaction list warrants genuine care rather than a quick skim. Of the 159 supplements and herbs on file, three carry a major rating, and all involve common products.”

Reviewed by 2 · Jul 18, 2026

Open the Estradiol, Norgestimate interaction page

One more smart check

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

We hold 403 real supplement products containing Kava, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Kava. Your product may carry other ingredients that interact with Estradiol, Norgestimate too, on top of Kava — 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 Kava and Estradiol, Norgestimate 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 Kava
Top 25%

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

29 days ago today
Medication Estradiol, Norgestimate
Steady interest

#1,478 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 Kava

What is Kava?

Kava
  • Anxiety and stress
  • Restlessness
  • Trouble sleeping
  • Relaxation in social or cultural settings
  • Menopausal symptoms

Kava is a Pacific Island plant traditionally used to promote relaxation and ease anxiety, and some studies suggest it may help mild anxiety. However, kava has been linked to rare but serious liver damage, so it should be used with caution, avoided by people with liver problems, and only used after talking with your pharmacist or doctor.

Read the full Kava monograph & all interactions
Keep checking

Other Drugs & Kava

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

248Major
576Moderate
341Minor
1,664No known interaction
248 Major 576 Moderate 341 Minor 1,664 No interaction
Major

248 interactions

Showing 60 of 248 major interactions — see all 248 on the Kava page.

Moderate

576 interactions

Showing 60 of 576 moderate interactions — see all 576 on the Kava page.

Minor

341 interactions

Showing 60 of 341 minor interactions — see all 341 on the Kava page.

No interaction 1,664 drugs checked — show the list

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

Showing the 60 most looked-up of 1,664 medications checked with no known interaction — see the full Kava list.

See the full Kava interactions page
See every supplement checked against Estradiol, Norgestimate, 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
Kava monograph › Uses, safety, and every drug interaction in one place Estradiol, Norgestimate supplement interactions › Every supplement checked against Estradiol, Norgestimate, 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 Kava and Estradiol, Norgestimate Together: Common Questions

Can you take Kava with Estradiol, Norgestimate?
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 Kava and Estradiol, Norgestimate?
Estradiol, Norgestimate belongs to more than one drug category, and Kava 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 Kava and Estradiol, Norgestimate 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.