Drug & supplement interaction

Melatonin + Ulipristal Acetate

Ulipristal Acetate brand name: Ella.

Moderate Interaction
The bottom line Moderate

Ulipristal Acetate falls into 2 drug categories that Melatonin can interact with; the most serious is rated moderate. Theoretically, taking contraceptive drugs with melatonin might increase the effects and adverse effects of melatonin.

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

Melatonin and Ulipristal Acetate

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

Why Are There 2 Interactions?

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

Moderate

CONTRACEPTIVE DRUGS

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Why this applies to Ulipristal Acetate

Ulipristal Acetate falls under CONTRACEPTIVE DRUGS — the group Melatonin interacts with.

Theoretically, taking contraceptive drugs with melatonin might increase the effects and adverse effects of melatonin.
Contraceptive drugs can increase the levels of endogenous melatonin. Theoretically, these drugs may increase the effects and adverse effects of oral melatonin.
Severity Moderate Likelihood Probable Evidence B

Interaction 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..

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

Here's an important point about how this pairing works: the interaction runs in one direction. It's the contraceptive that can nudge up your melatonin levels, not the other way around. So with ella (ulipristal), the concern is that you might feel melatonin's effects a little more strongly, things like extra drowsiness, grogginess, or vivid dreams.

Honestly, though, ella is a single one-time dose used for emergency contraception, not a daily pill you keep taking. That makes any real-world buildup of melatonin unlikely to add up to much. This is also a theoretical, lower-quality finding, so I wouldn't lose sleep over it. If you feel unusually sleepy or off, just check in with your pharmacist or doctor.

References
  1. Wright KP Jr, Myers BL, Plenzler SC, et al. Acute effects of bright light and caffeine on nighttime melatonin and temperature levels in women taking and not taking oral contraceptives. Brain Res 2000;873:310-7.
Minor

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

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Ulipristal Acetate also falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES.

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 short version: ulipristal (Ella) is cleared by a liver enzyme called CYP3A4. Some lab studies suggest melatonin might slow that same enzyme down. If that happened, your body could hold onto a bit more ulipristal than usual, which in theory might mean slightly more of its typical effects, like nausea, headache, belly cramps, or a shift in when your next period shows up.

I want to be honest about how weak this is. The signal comes only from test-tube research, not from real people, and it's rated a minor, possible interaction. Ulipristal is also a one-time emergency dose, so there isn't much window for buildup. I wouldn't lose sleep over it, but it never hurts to run it by your pharmacist if you're unsure.

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 1,115 moderate, 345 minor known drug interactions in our database — the Ulipristal Acetate one above is among 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 Ulipristal Acetate

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 Ulipristal Acetate, 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 Ulipristal Acetate

This page covers Melatonin only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Ulipristal Acetate page lists 158 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 · 107 moderate · 48 minor.

From our pharmacist’s overview on the Ulipristal Acetate page

“St. John's wort worries me most with ulipristal acetate (Ella), the emergency contraceptive that gets exactly one chance to work.”

Reviewed by 2 · Jul 18, 2026

Open the Ulipristal Acetate 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 Ulipristal Acetate 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 Ulipristal 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 Melatonin
Top 5%

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

29 days ago today
Medication Ulipristal Acetate
Steady interest

#2,097 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 Ulipristal

What Is Ulipristal Used For?

Brand name: Ella

Ella (ulipristal acetate) is used to prevent pregnancy after unprotected sex or when another form of birth control has failed or was used incorrectly. It must be taken as soon as possible, within 5 days (120 hours) of that event.

Ella is intended for occasional, emergency use only — it is not a substitute for regular, ongoing contraception.

See full Ulipristal 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
1,115Moderate
345Minor
1,369No known interaction
Moderate

1,115 interactions

Showing 60 of 1,115 moderate interactions — see all 1,115 on the Melatonin page.

Minor

345 interactions

Showing 60 of 345 minor interactions — see all 345 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

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Pharmacist Counseling Corner

Taking Melatonin and Ulipristal Acetate Together: Common Questions

Can you take Melatonin with Ulipristal 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 Melatonin and Ulipristal Acetate?
Ulipristal Acetate belongs to more than one drug category, and Melatonin 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 Melatonin and Ulipristal 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

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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.