Drug & supplement interaction

Melatonin + Cyclosporine

Cyclosporine brand names: Neoral, Gengraf, Sandimmune, Ciclosporine, Cequa, and others.

Moderate Interaction
The bottom line Moderate

Cyclosporine falls into 3 drug categories that Melatonin can interact with; the most serious is rated moderate. Theoretically, taking melatonin with drugs that lower the seizure threshold might increase the risk of seizure activity.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions3
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Melatonin and Cyclosporine

These two interact in 3 distinct ways. Each one is explained separately below.

Why Are There 3 Interactions?

Melatonin interacts with whole categories of medication. Cyclosporine falls into 3 of those categories, so it can interact with Melatonin in 3 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

SEIZURE THRESHOLD LOWERING DRUGS

1 of 3

Why this applies to Cyclosporine

Cyclosporine falls under SEIZURE THRESHOLD LOWERING DRUGS — the group Melatonin interacts with.

Theoretically, taking melatonin with drugs that lower the seizure threshold might increase the risk of seizure activity.
Some clinical evidence suggests that melatonin may increase the frequency of seizures in certain patients, particularly children with neurological disabilities.
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 gist with cyclosporine and melatonin. Cyclosporine isn't a prodrug, and this particular concern isn't about melatonin changing your cyclosporine levels. Instead, it's grouped here because cyclosporine can slightly lower the seizure threshold (make seizures a bit easier to trigger), and melatonin has been linked, in theory, to more seizure activity in some people.

I want to be honest about the evidence: this is mostly theoretical, and the real-world signal comes mainly from children with existing neurological problems. For most adults taking cyclosporine for a transplant, arthritis, or psoriasis, this is a low-level worry. Still, if you or your child has a seizure history, it's worth a quick chat with your doctor or pharmacist before adding melatonin. Don't stop your cyclosporine on your own.

References
  1. Sheldon SH. Pro-convulsant effects of oral melatonin in neurologically disabled children. Lancet 1998;351:1254. PubMed
  2. Stewart LS. Endogenous melatonin and epileptogenesis: facts and hypothesis. Int J Neurosci 2001;107:77-85.. PubMed
Moderate

IMMUNOSUPPRESSANTS

2 of 3

Cyclosporine also falls under IMMUNOSUPPRESSANTS.

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 cyclosporine. Cyclosporine works by calming down your immune system, which is exactly what you need after a transplant or to control rheumatoid arthritis or psoriasis. Melatonin, on the other hand, can give the immune system a little nudge to be more active. So in theory, melatonin could push against what cyclosporine is trying to do, making it slightly less effective at keeping your immune system in check.

I want to be honest about the evidence here: this is mostly theoretical and based on lower-quality studies, so it may never cause a real problem for you. But because cyclosporine is doing such an important job (like protecting a transplanted organ), I wouldn't want to take chances. Please check with your pharmacist or transplant team before adding melatonin.

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

3 of 3

Cyclosporine 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 situation with these two. Your body clears cyclosporine mainly through a liver enzyme called CYP3A4. Some lab studies suggest melatonin can slow that enzyme down a bit. In theory, if cyclosporine is broken down more slowly, its levels in your blood could creep up, which might mean more side effects like higher blood pressure, kidney strain, tremor, or swollen gums.

Now the honest part: this concern comes only from test-tube and animal research, not from real patients, so it's rated as a minor, theoretical interaction. Still, cyclosporine is a drug where even small level changes matter, so I wouldn't add melatonin on your own. Please run it by your transplant team or pharmacist first.

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 Cyclosporine 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 Cyclosporine

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 Cyclosporine, 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 Cyclosporine

This page covers Melatonin only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Cyclosporine page lists 229 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Asarabacca (major), Beer (major), Berberine (major) and Grapefruit (major).

By severity: 9 major · 182 moderate · 38 minor.

From our pharmacist’s overview on the Cyclosporine page

“Cyclosporine (Neoral, Sandimmune, Gengraf) keeps a transplanted organ from being rejected, and small shifts in its blood level can tip you toward rejection on one side or toxicity on the other. So approach these 229 interacting supplements with real care.”

Reviewed by 2 · Jul 18, 2026

Open the Cyclosporine 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 Cyclosporine 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 Cyclosporine 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 Cyclosporine
Top 25%

#633 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 Cyclosporine

What Is Cyclosporine Used For?

Brand names: Neoral, Gengraf, Sandimmune, Ciclosporine, Cequa, Verkazia, Vevye

Cyclosporine is prescribed to help prevent the body from rejecting a transplanted kidney, liver, or heart. It is often used alongside other immunosuppressive medicines as part of a full transplant care plan.

It is also used for adults with severe, active rheumatoid arthritis that hasn't responded well enough to methotrexate, and for adults with severe plaque psoriasis who haven't had success with other standard treatments.

See full Cyclosporine 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 Cyclosporine Together: Common Questions

Can you take Melatonin with Cyclosporine?
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 3 interactions listed for Melatonin and Cyclosporine?
Cyclosporine 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 Cyclosporine 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.