Drug & supplement interaction

Melatonin + Mifepristone

Mifepristone brand names: Mifeprex, Korlym.

Minor Interaction
The bottom line Minor

Melatonin has a minor interaction with Mifepristone. Theoretically, melatonin might increase levels of drugs metabolized by CYP3A4.

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

Melatonin and Mifepristone

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

Minor

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

Why this applies to Mifepristone

Mifepristone falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES — the group Melatonin interacts with.

Theoretically, melatonin might increase levels of drugs metabolized by CYP3A4.
Laboratory research shows that certain lots of melatonin inhibit CYP3A4. Theoretically, combined administration of melatonin with certain drugs metabolized by CYP3A4 may reduce the metabolism of these drugs, resulting in increased serum levels. Until more is known, use melatonin cautiously in patients taking drugs metabolized by these enzymes.
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

Here's the gist for your Korlym (mifepristone): your liver uses an enzyme called CYP3A4 to help break it down. Some lab studies suggest melatonin might slow that enzyme a little. If that happened, mifepristone could clear out a bit more slowly and build up, which in theory could nudge up side effects like nausea, fatigue, low potassium, dizziness, or headache.

I want to be honest about the strength of this, though. It's only seen in test-tube and animal research, the concern is rated minor, and we don't have real-world cases showing it matters in people. So this isn't something to lose sleep over. Since mifepristone is a serious medication, just give your pharmacist or doctor a heads-up before adding melatonin so they can keep an eye on things.

References
  1. Foster BC, Cvijovic K, Boon HS, et al. Melatonin Interaction Resulting in Severe Sedation. J Pharm Pharm Sci 2015;18(2):124-31. 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

Melatonin Also Interacts With Other Medications

Melatonin has 1,116 moderate, 344 minor known drug interactions in our database — the Mifepristone 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 Melatonin

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

From our Q&A

Questions About Melatonin or Mifepristone

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Melatonin or Mifepristone, not necessarily both, but if one is close to what you were about to ask it will usually go further than a database entry can:

Not quite your question? Ask our pharmacists directly — it is free, there is no account required, and answers usually come back within 24 hours.

Everything else you take

See Every Supplement That Interacts With Mifepristone

This page covers Melatonin only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Mifepristone page lists 151 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 · 104 moderate · 39 minor.

From our pharmacist’s overview on the Mifepristone page

“Mifepristone is a drug where a failed dose has real consequences, whether it is Mifeprex used to end an early pregnancy or Korlym taken daily for Cushing's syndrome, so its interaction list deserves genuine respect. Most of the 151 ingredients on file act on the CYP3A4 enzyme that clears the drug, pushing its blood level up or dragging…”

Reviewed by 2 · Jul 18, 2026

Open the Mifepristone interaction page

One more smart check

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

We hold 2,885 real supplement products containing Melatonin, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Melatonin. Your product may carry other ingredients that interact with Mifepristone too, on top of Melatonin — 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 Melatonin and Mifepristone 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 Melatonin
Top 5%

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

29 days ago today
Medication Mifepristone
Steady interest

#2,041 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 Melatonin

What is Melatonin?

Melatonin
  • Trouble falling asleep (insomnia)
  • Jet lag
  • Delayed sleep phase syndrome
  • Non-24-hour sleep-wake disorder
  • Shift-work sleep problems
  • Sleep problems in some children with conditions like autism or ADHD

Melatonin is a hormone your body makes naturally to help control your sleep-wake cycle, and the supplement form is widely used to help with sleep timing problems and jet lag. The evidence is strongest for certain circadian (body-clock) disorders and is more mixed for everyday insomnia. It is generally well tolerated for short-term use, but talk with your pharmacist or doctor before starting, especially for children or during pregnancy.

Read the full Melatonin monograph & all interactions
Medication

About Mifepristone (Korlym)

What Is Mifepristone (Korlym) Used For?

Brand names: Mifeprex, Korlym

Korlym is prescribed for adults with endogenous Cushing's syndrome — a condition where the body produces too much cortisol — who also have type 2 diabetes or trouble controlling blood sugar. It works to bring those blood sugar levels under control.

It is only for blood sugar problems that are directly caused by Cushing's syndrome. It should not be used to treat ordinary type 2 diabetes unrelated to this condition.

See full Mifepristone (Korlym) drug information
Keep checking

Other Drugs & Melatonin

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

0Major
1,116Moderate
344Minor
1,369No known interaction
Moderate

1,116 interactions

Showing 60 of 1,116 moderate interactions — see all 1,116 on the Melatonin page.

Minor

344 interactions

Showing 60 of 344 minor interactions — see all 344 on the Melatonin page.

No interaction 1,369 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

Keep exploring
Pharmacist Counseling Corner

Taking Melatonin and Mifepristone Together: Common Questions

Can you take Melatonin with Mifepristone?
There is only a minor interaction, which is usually not serious. Read the full details on this page and confirm with your pharmacist before combining them.
How serious is the Melatonin and Mifepristone interaction?
We rate it Minor. This interaction is generally not clinically significant, but it remains worth noting and discussing with your pharmacist.

Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy

Still Have a Question About Mifepristone and Melatonin?

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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.