Drug & supplement interaction

Melatonin + Fosnetupitant, Palonosetron (IV)

Fosnetupitant, Palonosetron (IV) brand name: Akynzeo.

Minor Interaction
Medically reviewed by · Updated October 2026
The bottom line Minor

Melatonin has a minor interaction with Fosnetupitant, Palonosetron (IV). 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 Fosnetupitant, Palonosetron (IV)

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

Minor

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

Why this applies to Fosnetupitant, Palonosetron (IV)

Fosnetupitant, Palonosetron (IV) 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 short version on combining melatonin with Akynzeo (the netupitant/fosnetupitant plus palonosetron combo you get for chemo nausea). The netupitant piece is partly cleared by a liver enzyme called CYP3A4. Some lab tests suggest melatonin might slow that enzyme a little, which in theory could let levels of the drug edge up. If that happened, you might notice more of its usual effects, like headache, tiredness, or constipation.

That said, this is a theoretical, lab-only concern rated as minor, and it came from certain melatonin batches, not from real patient cases. For most people taking a single dose of Akynzeo before chemo, it isn't likely to cause trouble. Still, it never hurts to mention your melatonin to your oncology team or pharmacist so they can keep an eye on you.

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 1,117 moderate, 345 minor known drug interactions in our database — the Fosnetupitant, Palonosetron (IV) one above is one of them. If you take anything else, check it against the full list below.

Moderate 1,117 Minor 345 No known interaction 1,368 (incl. Fosnetupitant, Palonosetron (IV))
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 Fosnetupitant, Palonosetron (IV)

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 Fosnetupitant, Palonosetron (IV), 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 Fosnetupitant, Palonosetron (IV)

This page covers Melatonin only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Fosnetupitant, Palonosetron (IV) 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), Lithium (major), St. John's Wort (major) and 5-htp (moderate).

By severity: 4 major · 113 moderate · 41 minor.

Open the Fosnetupitant, Palonosetron (IV) 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 Fosnetupitant, Palonosetron (IV) 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 Fosnetupitant, Palonosetron (IV) 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%

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

29 days ago today
Medication Fosnetupitant, Palonosetron (IV)
Top 25%

#468 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 Netupitant and Palonosetron

What Is Netupitant and Palonosetron Used For?

Brand name: Akynzeo

Netupitant and palonosetron helps prevent nausea and vomiting from cancer chemotherapy in adults. It is used together with dexamethasone, a steroid medicine. It covers both the first day (acute phase) and the days after (delayed phase).

Akynzeo capsules are used for initial and repeat courses of chemotherapy, including highly emetogenic (strongly nausea-causing) chemotherapy. Akynzeo for injection and Akynzeo injection are used for highly emetogenic chemotherapy only. They have not been studied with anthracycline plus cyclophosphamide chemotherapy.

See full Netupitant and Palonosetron 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
1,117Moderate
345Minor
1,367No known interaction
1,117 Moderate 345 Minor 1,367 No interaction
Moderate

1,117 interactions

Showing 60 of 1,117 moderate interactions — see all 1,117 on the Melatonin page.

Minor

345 interactions

Showing 60 of 345 minor interactions — see all 345 on the Melatonin page.

No interaction 1,367 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 1,367 medications checked with no known interaction — see the full Melatonin list.

See the full Melatonin interactions page
See every supplement checked against Fosnetupitant, Palonosetron (IV), 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 Fosnetupitant, Palonosetron (IV) supplement interactions › Every supplement checked against Fosnetupitant, Palonosetron (IV), ranked by severity Netupitant and Palonosetron 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 Fosnetupitant, Palonosetron (IV) Together: Common Questions

Can you take Melatonin with Fosnetupitant, Palonosetron (IV)?
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 Fosnetupitant, Palonosetron (IV) 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 Fosnetupitant, Palonosetron (IV) 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.