Drug & supplement interaction

K2/spice + Relugolix, Estradiol, Norethindrone Acetate

Relugolix, Estradiol, Norethindrone Acetate brand name: Myfembree.

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

K2/spice has a moderate interaction with Relugolix, Estradiol, Norethindrone Acetate. Theoretically, K2/spice might have an additive effect with drugs that prolong the QT interval and increase the risk of ventricular arrhythmias.

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

K2/spice and Relugolix, Estradiol, Norethindrone Acetate

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

Moderate

QT INTERVAL-PROLONGING DRUGS

Why this applies to Relugolix, Estradiol, Norethindrone Acetate

Relugolix, Estradiol, Norethindrone Acetate falls under QT INTERVAL-PROLONGING DRUGS — the group K2/spice interacts with.

Theoretically, K2/spice might have an additive effect with drugs that prolong the QT interval and increase the risk of ventricular arrhythmias.
There have been numerous cases of increased QT and corrected QT intervals in patients using K2/spice.
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

First, an honest word about K2/Spice: this isn't a real herbal product. It's plant material sprayed with lab-made cannabinoid chemicals that change from batch to batch, and it's been tied to seizures, heart rhythm problems, psychosis, and deaths. I'd steer clear of it entirely.

Here's the specific concern with Myfembree (relugolix, estradiol, norethindrone acetate). Both this medication and K2/Spice can stretch out the heart's electrical cycle, something we call the QT interval. When two QT-stretching things stack up, the worry is a dangerous, irregular heartbeat (palpitations, fainting, or worse). This is based on scattered case reports rather than strong studies, so it's theoretical, but the stakes are high enough that I wouldn't gamble. Please talk with your doctor or pharmacist before changing anything.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Ahmed T, Khan A, See VY, Robinson S. Cardiac arrest associated with synthetic cannabinoid use and acquired prolonged QTc interval: A case report and review of literature. HeartRhythm Case Rep. 2020;6(5):283-286. PubMed
  2. Yildiz SS, Sutasir MN, Sigirci S, et al. Acute effects of synthetic cannabinoids on ventricular repolarization parameters. Turk Kardiyol Dern Ars. 2019;47(5):384-390.

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

K2/spice Also Interacts With Other Medications

K2/spice has 207 moderate known drug interactions in our database — the Relugolix, Estradiol, Norethindrone Acetate one above is one of them. If you take anything else, check it against the full list below.

Moderate 207 No known interaction 2,623 (incl. Relugolix, Estradiol, Norethindrone Acetate)
Taking anything else?

Check Another of Your Medications Against K2/spice

Covers the 2,830 medications we’ve checked against K2/spice. Pick one to open its full report.

Everything else you take

See Every Supplement That Interacts With Relugolix, Estradiol, Norethindrone Acetate

This page covers K2/spice only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Relugolix, Estradiol, Norethindrone Acetate page lists 219 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), American Hellebore (major), Arsenic (major), Cesium (major) and Ephedra (major).

By severity: 8 major · 174 moderate · 37 minor.

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

“Grapefruit is where I would start on this page. Myfembree (relugolix, estradiol, and norethindrone acetate) depends on the CYP3A4 enzyme to be cleared, and grapefruit juice blocks that enzyme, raising drug levels and side effect risk.”

Reviewed by 2 · Jul 18, 2026

Open the Relugolix, Estradiol, Norethindrone Acetate interaction page

How much people look this up

Where K2/spice and Relugolix, 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 K2/spice
Steady interest

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

29 days ago today
Medication Relugolix, Estradiol, Norethindrone Acetate
Top 5%

#131 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 K2/spice

What is K2/spice?

  • Recreational drug ('legal high')
  • Marijuana substitute
  • Mood or perception changes
  • Sometimes used to avoid drug testing

K2/Spice is NOT a herbal supplement — it is plant material sprayed with man-made synthetic cannabinoid chemicals. It is dangerous, unpredictable, and has caused seizures, heart problems, psychosis, and deaths, so it should not be used.

Read the full K2/spice monograph & all interactions
Medication

About Relugolix, Estradiol, and Norethindrone

What Is Relugolix, Estradiol, and Norethindrone Used For?

Brand name: Myfembree

Myfembree is approved for two conditions in premenopausal women: managing heavy menstrual bleeding caused by uterine fibroids (non-cancerous growths in the uterus), and managing moderate to severe pain caused by endometriosis (a condition where tissue similar to the uterine lining grows outside the uterus).

Treatment with Myfembree should not exceed 24 months because of the risk of ongoing bone loss that may not fully reverse after stopping the medication.

See full Relugolix, Estradiol, and Norethindrone drug information
Keep checking

Other Drugs & K2/spice

Browse every other medication we’ve checked against K2/spice — both the ones with a known interaction and the ones without. Select any drug for the full detail.

0Major
207Moderate
0Minor
2,622No known interaction
207 Moderate 2,622 No interaction
Moderate

207 interactions

Showing 60 of 207 moderate interactions — see all 207 on the K2/spice page.

No interaction 2,622 drugs checked — show the list

We also checked K2/spice against these medications and found no known interaction in our sources. Open any page to confirm.

Showing the 60 most looked-up of 2,622 medications checked with no known interaction — see the full K2/spice list.

See the full K2/spice interactions page
See every supplement checked against Relugolix, 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
K2/spice monograph › Uses, safety, and every drug interaction in one place Relugolix, Estradiol, Norethindrone Acetate supplement interactions › Every supplement checked against Relugolix, Estradiol, Norethindrone Acetate, ranked by severity Relugolix, Estradiol, and Norethindrone drug information › The full plain-English guide to this medication 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 K2/spice and Relugolix, Estradiol, Norethindrone Acetate Together: Common Questions

Can you take K2/spice with Relugolix, 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 K2/spice and Relugolix, 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 Relugolix, Estradiol, Norethindrone Acetate and K2/spice?

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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.