Drug & supplement interaction

Melatonin + Warfarin

Warfarin brand name: Warfarin.

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

Warfarin falls into 5 drug categories that Melatonin can interact with; the most serious is rated moderate. Theoretically, melatonin might increase levels of drugs metabolized by CYP1A2.

Read the full interaction report
SeverityModerate
LikelihoodProbable
Interactions5
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Melatonin and Warfarin

These two interact in 5 distinct ways. Each one is explained separately below.

Why Are There 5 Interactions?

Melatonin interacts with whole categories of medication. Warfarin falls into 5 of those categories, so it can interact with Melatonin in 5 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 5

Why this applies to Warfarin

Warfarin falls under CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES — the group Melatonin interacts with.

Theoretically, melatonin might increase levels of drugs metabolized by CYP1A2. Also, other CYP1A2 substrates might decrease the metabolism of melatonin, increasing melatonin levels.
Melatonin is metabolized in the liver primarily by the CYP2C19 and CYP1A2 enzymes. Theoretically, combined administration of melatonin with drugs metabolized by the CYP1A2 enzyme might reduce the metabolism of these drugs, resulting in increased serum levels. Conversely, some drugs metabolized by CYP1A2 may inhibit the metabolism of melatonin, resulting in increased serum levels of melatonin. Until more is known, use melatonin cautiously in patients taking drugs metabolized by these enzymes.
Severity Moderate Likelihood Probable Evidence D

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 the gist with melatonin and your warfarin. On paper, melatonin could slow down one of the liver enzymes (CYP1A2) that helps clear certain drugs, which might let those drug levels drift a little higher. Warfarin is a classic blood thinner that gets handled partly by this same enzyme system, and it's a medicine where even small shifts matter.

If warfarin levels nudged up, you could see more of its effect, meaning easier bruising, nosebleeds, bleeding gums, or longer bleeding from a cut, which shows up as a higher INR. I want to be honest though: this concern is theoretical, based on how the enzymes work rather than real cases. I wouldn't panic. Just loop in your pharmacist or doctor before starting melatonin, and keep up with your regular INR checks so any change gets caught early.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Yeleswaram, K., Vachharajani, N., and Santone, K. Involvement of cytochrome P-450 isozymes in melatonin metabolism and clinical implications. J Pineal Res 1999;26(3):190-191. PubMed
  2. Faber, M. S., Jetter, A., and Fuhr, U. Assessment of CYP1A2 activity in clinical practice: why, how, and when? Basic Clin Pharmacol Toxicol. 2005;97(3):125-134. PubMed
  3. Foster BC, Cvijovic K, Boon HS, et al. Melatonin Interaction Resulting in Severe Sedation. J Pharm Pharm Sci 2015;18(2):124-31. PubMed
Moderate

CYTOCHROME P450 2C19 (CYP2C19) SUBSTRATES

2 of 5

Warfarin also falls under CYTOCHROME P450 2C19 (CYP2C19) SUBSTRATES.

Theoretically, melatonin might increase levels of drugs metabolized by CYP2C19. Also, other CYP2C19 substrates might decrease the metabolism of melatonin, increasing melatonin levels.
Melatonin is metabolized in the liver primarily by the CYP2C19 and CYP1A2 enzymes. Theoretically, combined administration of melatonin with certain drugs metabolized by the CYP2C19 enzyme may reduce the metabolism of these drugs, resulting in increased serum levels. Conversely, some drugs metabolized by CYP2C19 may inhibit the metabolism of melatonin, resulting in increased serum levels of melatonin. Until more is known, use melatonin cautiously in patients taking drugs metabolized by these enzymes.
Severity Moderate Likelihood Probable Evidence D

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 the short version for warfarin and melatonin. Warfarin is partly cleared by a liver enzyme called CYP2C19, and the theory is that melatonin could slow that enzyme down a bit. If that happens, warfarin levels could nudge upward, which means a slightly stronger blood-thinning effect. With warfarin that matters, because it's a narrow-therapeutic-index drug where small shifts can change your INR and raise the risk of bruising or bleeding.

I want to be honest though: this is a theoretical concern based on how the enzyme works, not solid proof in people. It's not a reason to panic or stop anything. If you'd like to try melatonin, just check with your pharmacist or doctor first, and watch your INR a little more closely when you start.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Yeleswaram, K., Vachharajani, N., and Santone, K. Involvement of cytochrome P-450 isozymes in melatonin metabolism and clinical implications. J Pineal Res 1999;26(3):190-191. PubMed
  2. Faber, M. S., Jetter, A., and Fuhr, U. Assessment of CYP1A2 activity in clinical practice: why, how, and when? Basic Clin Pharmacol Toxicol. 2005;97(3):125-134. PubMed
Moderate

ANTICOAGULANT/ANTIPLATELET DRUGS

3 of 5

Warfarin also falls under ANTICOAGULANT/ANTIPLATELET DRUGS.

Theoretically, melatonin may have anticoagulant effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
There are isolated case reports of minor bleeding and decreased prothrombin activity in people taking melatonin with warfarin (Coumadin). The mechanism, if any, of this interaction is unknown. Taking melatonin orally seems to decrease coagulation activity within one hour of dosing in healthy men.
Severity Moderate Likelihood Possible Evidence B

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 deal with pairing melatonin and your warfarin. Warfarin is a finicky blood thinner with a narrow safety window, meaning even small shifts in how thin your blood gets can matter. There are a few scattered case reports where people taking both noticed minor bleeding or a bump in their INR (the blood test that tracks warfarin). Melatonin may have a mild blood-thinning effect of its own, so stacking it on top of warfarin could, in theory, nudge your bleeding risk up a bit.

I want to be honest, though: this is mostly theoretical and based on a handful of reports, not strong proof. Watch for easy bruising, bleeding gums, nosebleeds, or dark stools. Don't start or stop anything on your own. Just give your pharmacist or doctor a heads-up so they can keep a closer eye on your INR.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Herxheimer A, Petrie KJ. Melatonin for the prevention and treatment of jet lag. Cochrane Database Syst Rev 2002;2:CD001520. PubMed
  2. Wirtz, P. H., Spillmann, M., Bartschi, C., Ehlert, U., and von Kanel, R. Oral melatonin reduces blood coagulation activity: a placebo-controlled study in healthy young men. J Pineal Res 2008;44(2):127-133. PubMed
  3. U.S.Food and Drug Administration. Special Nutritionals Adverse Events Monitoring System: registered case reports.
Moderate

WARFARIN (Coumadin)

4 of 5
Theoretically, melatonin may have antiplatelet effects and may increase the risk of bleeding with warfarin.
Three cases of increased prothrombin time have been reported for patients aged 48-72 years who took melatonin orally in combination with warfarin. However, three cases of decreased prothrombin time have also been reported for patients aged 51-84 years who took melatonin orally in combination with warfarin. Until more is known, use melatonin cautiously in patients taking warfarin.
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 honest picture with melatonin and your warfarin. Warfarin is a blood thinner with a very narrow safety window, so even small shifts in how it works can matter. The concern is mostly theoretical plus a handful of scattered case reports. In some people melatonin seemed to thin the blood a bit more (higher INR, more bleeding or bruising risk), while in others it actually had the opposite effect (lower INR, which could let a clot form). So the direction isn't even consistent.

Because the evidence is weak and goes both ways, I wouldn't panic, but I would loop in whoever manages your warfarin before adding melatonin. They may simply check your INR a little more closely for a few weeks. Watch for unusual bruising, nosebleeds, or pink urine, and call your doctor if you see them.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Herxheimer A, Petrie KJ. Melatonin for the prevention and treatment of jet lag. Cochrane Database Syst Rev 2002;2:CD001520. PubMed
Minor

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

5 of 5

Warfarin 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 on pairing melatonin with warfarin. Warfarin is a blood thinner with a very narrow safety window, so even small shifts in its levels can matter. The theory here is that some batches of melatonin may slow down a liver enzyme (CYP3A4) that helps clear warfarin. If that happens, warfarin could build up a bit and thin your blood more than intended, raising the risk of bruising or bleeding (think nosebleeds, bleeding gums, or blood in urine or stool).

I want to be honest though: this is based only on lab research, not real patients, and it's rated as a minor, theoretical concern. Still, because warfarin is so sensitive, please check with your pharmacist or doctor before adding melatonin, and watch your INR closely.

Contact Dr. Brian directly if you have additional questions on this interaction
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 Warfarin one above is among them. If you take anything else, check it against the full list below.

Moderate 1,115 Minor 345 No known interaction 1,370 (incl. Warfarin)
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 Warfarin

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 Warfarin, 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 Warfarin

This page covers Melatonin only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Warfarin page lists 361 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Alfalfa (major), American Ginseng (major), Beer (major) and Cannabis (major).

By severity: 16 major · 301 moderate · 44 minor.

From our pharmacist’s overview on the Warfarin page

“People take warfarin to prevent dangerous clots, and many are the same people reaching for glucosamine for sore joints or a multivitamin containing vitamin K, which makes this a list that deserves genuine respect. Of the 361 supplements on file for warfarin, 16 carry a major rating, and the danger runs in both directions: some add to w…”

Reviewed by 2 · Jul 18, 2026

Open the Warfarin 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 Warfarin 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 Warfarin 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 Warfarin
Top 10

#4 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 Warfarin

What Is Warfarin Used For?

Brand name: Warfarin

Warfarin sodium tablets and Jantoven tablets are both used to prevent and treat venous thrombosis (blood clots in the veins) and pulmonary embolism (a clot in the lungs). They are also used to prevent clot-related complications in people with atrial fibrillation (an irregular heart rhythm) or who have had a heart valve replaced.

In people who have had a heart attack, warfarin is used to reduce the risk of death, another heart attack, stroke, or other clotting events. It does not dissolve an existing clot, but it helps prevent the clot from growing and stops new dangerous clots from forming.

See full Warfarin 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
1,115 Moderate 345 Minor 1,369 No 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

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

Showing the 60 most looked-up of 1,369 medications checked with no known interaction — see the full Melatonin list.

See the full Melatonin interactions page
See every supplement checked against Warfarin, 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
Melatonin monograph › Uses, safety, and every drug interaction in one place Warfarin supplement interactions › Every supplement checked against Warfarin, ranked by severity Warfarin 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 Melatonin and Warfarin Together: Common Questions

Can you take Melatonin with Warfarin?
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 5 interactions listed for Melatonin and Warfarin?
Warfarin 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 Warfarin 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 Warfarin 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.