Drug & supplement interaction

Melatonin + Sirolimus

Sirolimus brand name: Rapamune.

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

Sirolimus falls into 2 drug categories that Melatonin can interact with; the most serious is rated moderate. Theoretically, melatonin might interfere with immunosuppressive therapy.

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

Melatonin and Sirolimus

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. Sirolimus 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

IMMUNOSUPPRESSANTS

1 of 2

Why this applies to Sirolimus

Sirolimus falls under IMMUNOSUPPRESSANTS — the group Melatonin interacts with.

Theoretically, melatonin might interfere with immunosuppressive therapy.
Melatonin can stimulate immune function. Theoretically, melatonin might interfere with immunosuppressive therapy.
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 concern with pairing melatonin and sirolimus. Sirolimus is a transplant medicine whose whole job is to calm down your immune system so your body doesn't reject the new kidney. Melatonin, on the other hand, can give your immune system a little nudge to be more active. So in theory these two work against each other, and a more active immune response could chip away at the protection sirolimus is providing.

I want to be honest about the evidence here: this is mostly theoretical, and we don't have strong studies showing real rejection happening because of melatonin. Still, with a transplant on the line, this isn't something to gamble on alone. Please loop in your transplant team or pharmacist before starting melatonin so they can weigh in for your situation.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Lissoni P, Barni S, Mandala M, et al. Decreased toxicity and increased efficacy of cancer chemotherapy using the pineal hormone melatonin in metastatic solic tumor patients with poor clinical status. Eur J Cancer 1999;35:1688-92.
Minor

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

2 of 2

Sirolimus 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 gist for Sirolimus (Rapamune): your body clears it using a liver enzyme called CYP3A4. Some lab research hints that certain batches of melatonin might slow that enzyme down a bit. In theory, that could let sirolimus build up a little higher in your blood, which might mean more side effects like mouth sores, swelling, higher cholesterol or triglycerides, or changes in your blood counts.

I want to be honest about how weak this is. It's only a theoretical concern from test-tube studies, not from real patients, and it's rated minor. Still, sirolimus is a drug where your team checks blood levels closely, so even small shifts matter. Please run melatonin by your transplant pharmacist or doctor before starting it.

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 Sirolimus 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. Sirolimus)
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 Sirolimus

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 Sirolimus, 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 Sirolimus

This page covers Melatonin only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Sirolimus page lists 188 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 Active Hexose Correlated Compound (ahcc) (moderate).

By severity: 3 major · 149 moderate · 36 minor.

From our pharmacist’s overview on the Sirolimus page

“Sirolimus (Rapamune) is the anti-rejection medicine transplant patients depend on, and it is a narrow-therapeutic-index drug, meaning small shifts in its blood level can invite rejection on one side or toxicity on the other. That is why the 188 supplements on this page deserve genuine wariness, starting with the three rated major.”

Reviewed by 2 · Jul 18, 2026

Open the Sirolimus 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 Sirolimus 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 Sirolimus 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 Sirolimus
Steady interest

#2,241 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 Sirolimus

What Is Sirolimus Used For?

Brand name: Rapamune

Sirolimus oral solution and tablets are used to help prevent organ rejection in kidney (renal) transplant patients aged 13 and older. They are also used to treat lymphangioleiomyomatosis (LAM) — a rare lung disease in which abnormal muscle-like cells invade lung tissue.

Fyarro (sirolimus, intravenous injection) is used to treat adults with locally advanced, unresectable, or metastatic malignant PEComa — a rare tumor that grows in soft tissue or organs. Hyftor (sirolimus topical gel) is used to treat facial angiofibroma (small benign skin growths on the face) associated with tuberous sclerosis in adults and children aged 6 and older.

See full Sirolimus 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 Sirolimus, 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 Sirolimus supplement interactions › Every supplement checked against Sirolimus, ranked by severity Sirolimus 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 Sirolimus Together: Common Questions

Can you take Melatonin with Sirolimus?
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 Sirolimus?
Sirolimus 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 Sirolimus 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.