Drug & supplement interaction

Kratom + Fosnetupitant, Palonosetron (IV)

Fosnetupitant, Palonosetron (IV) brand name: Akynzeo.

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

Fosnetupitant, Palonosetron (IV) falls into 3 drug categories that Kratom can interact with; the most serious is rated moderate. Kratom might increase the levels and clinical effects of drugs metabolized by CYP3A4.

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

Kratom and Fosnetupitant, Palonosetron (IV)

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

Why Are There 3 Interactions?

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

Moderate

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

1 of 3

Why this applies to Fosnetupitant, Palonosetron (IV)

Fosnetupitant, Palonosetron (IV) falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES — the group Kratom interacts with.

Kratom might increase the levels and clinical effects of drugs metabolized by CYP3A4.
In vitro research shows that kratom extract inhibits CYP3A4 enzyme activity. A pharmacokinetic study in adults shows that taking kratom tea 2 grams modestly increases the plasma concentration time-curve (AUC) and maximum concentration (Cmax) of CYP3A4 probe midazolam by 40-50% and its CYP3A4-mediated metabolites 18-27%. However, a lack of change in the half-life of midazolam and a simulation of the kratom-midazolam interaction suggest that kratom inhibits CYP3A4 enzymes in the small intestine but not the liver. Additionally, there is one case report of a 27-year-old male who died from neuroleptic malignant-like symptoms after concomitant use of kratom and quetiapine, a CYP3A4 substrate. Although it did not appear that the patient had consumed large quantities of quetiapine, postmortem plasma levels were in the lethal range, indicating possible inhibition of CYP3A4 by kratom. In another case report, a 63-year-old male presented with possible serotonin syndrome after taking an unknown dose of kratom for up to 3 months along with serotonergic prescription medications bupropion, buspirone, desvenlafaxine, trazodone, and ziprasidone. It is hypothesized that CYP3A4 inhibition by kratom reduced metabolism of desvenlafaxine, trazodone, and ziprasidone and consequently increased systemic exposure to serotonin.
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 simple version. The netupitant part of Akynzeo is cleared from your body by a liver enzyme called CYP3A4. Kratom appears to slow that enzyme down, mostly in the gut. In theory, that could let netupitant build up a bit higher than usual, which might mean more of its typical side effects like headache, tiredness, or constipation.

I want to be honest about how solid this is. It's really a theoretical concern based on lab work and a few case reports, not strong human studies with this exact drug. Akynzeo is usually given just once before chemo, so the window is short. Still, kratom carries serious risks on its own. Please loop in your oncology team or pharmacist before mixing the two.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Kong WM, Chik Z, Ramachandra M, et al. Evaluation of the effects of Mitragyna speciosa alkaloid extract on cytochrome P450 enzymes using a high throughput assay. Molecules. 2011;16(9):7344-7356. PubMed
  2. Hughes RL. Fatal combination of mitragynine and quetiapine - a case report with discussion of a potential herb-drug interaction. Forensic Sci Med Pathol. 2019 Mar;15(1):110-113. PubMed
  3. Eudaley ST, Brooks SP, Hamilton LA. Case Report: Possible Serotonin Syndrome in a Patient Taking Kratom and Multiple Serotonergic Agents. J Pharm Pract 2022. PubMed
  4. Tanna RS, Nguyen JT, Hadi DL, et al. Clinical Assessment of the Drug Interaction Potential of the Psychotropic Natural Product Kratom. Clin Pharmacol Ther 2023;113(6):1315-1325. PubMed
Moderate

SEROTONERGIC DRUGS

2 of 3

Fosnetupitant, Palonosetron (IV) also falls under SEROTONERGIC DRUGS.

Theoretically, taking kratom in combination with serotonergic drugs may increase levels of serotonin, increasing the risk of serotonin syndrome.
A 63-year-old male presented with possible serotonin syndrome after taking an unknown dose of kratom for up to 3 months along with serotonergic prescription medications bupropion, buspirone, desvenlafaxine, trazodone, and ziprasidone. It was hypothesized that kratom inhibited the cytochrome P450 3A4-, 2C9-, 2D6-, and 1A2-mediated metabolism of several of these serotonergic medications, consequently increasing systemic exposure to serotonin.
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 thing to know about combining kratom with Akynzeo (which contains palonosetron). Palonosetron works by blocking serotonin signals that trigger nausea, so it nudges your serotonin system. Kratom also touches the serotonin system. In theory, stacking the two could push serotonin a little too high and raise the small risk of something called serotonin syndrome.

What would that look like? Agitation, a racing heart, sweating, shivering, muscle twitching, or feeling confused. I want to be honest, though: this concern is theoretical and comes mainly from one case report involving several other drugs, so it's far from proven. Still, since you're already going through chemo, please loop in your oncology pharmacist or doctor before using kratom.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Eudaley ST, Brooks SP, Hamilton LA. Case Report: Possible Serotonin Syndrome in a Patient Taking Kratom and Multiple Serotonergic Agents. J Pharm Pract 2022. PubMed
Moderate

CYTOCHROME P450 3A4 (CYP3A4) INHIBITORS

3 of 3

Fosnetupitant, Palonosetron (IV) also falls under CYTOCHROME P450 3A4 (CYP3A4) INHIBITORS.

CYP3A4 inhibitors might increase the concentrations and clinical effects of kratom's primary active alkaloid mitragynine.
A pharmacokinetic study in healthy adults suggests that CYP3A4 inhibition with itraconazole increases the peak plasma concentration (Cmax) of mitragynine by about 1.5-fold. However, CYP3A4 inhibition reduces the Cmax and area under the plasma concentration time curve (AUC) over 72 hours of 7-hydroxymitragynine, one of kratom's active constituents, by about 3-fold, possibly by decreasing the metabolism of mitragynine to 7-hydroxymitragynin.
Animal research suggests that CYP3A4 inhibition with ketoconazole reduces the metabolism and clearance of kratom, increasing the Cmax of the active metabolite mitragynine by 130%, time to reach maximum plasma concentration (Tmax) from 1 to 2.6 hours, and AUC by 120%. Additionally, CYP3A4-mediated conversion of mitragynine into 7-hydroxymitragynine increases systematic exposure by 130%. However, other CYP isoforms are likely involved in this conversion. CYP3A4 inhibition could lead to increased adverse effects and mu-opioid-receptor-mediated behavioral effects associated with kratom and its metabolites.
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 situation with Akynzeo (the netupitant and palonosetron combo). The netupitant part can mildly slow down an enzyme in your body called CYP3A4. That same enzyme helps break down kratom's main active compound, mitragynine. So if you took kratom while this drug is in your system, mitragynine could build up a bit higher than usual, which may strengthen kratom's opioid-like effects.

In plain terms, that could mean more drowsiness, slowed breathing, constipation, dizziness, or nausea, which is ironic since Akynzeo is given to stop nausea. The evidence here is limited and mostly from lab and small studies, so this isn't a sure thing. Still, kratom carries real risks on its own. Please talk with your oncology pharmacist or doctor before mixing the two.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Kamble SH, Obeng S, León F, et al. Pharmacokinetic and Pharmacodynamic Consequences of Cytochrome P450 3A Inhibition on Mitragynine Metabolism in Rats. J Pharmacol Exp Ther 2023;385(3):180-192. PubMed
  2. Mongar P, Jaisi A, Inkviya T, Wungsintaweekul J, Wiwattanawongsa K. Effects of Itraconazole on Pharmacokinetics of Mitragynine and 7-Hydroxymitragynine in Healthy Volunteers. ACS Pharmacol Transl Sci 2024;7(3):823-833. 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

Kratom Also Interacts With Other Medications

Kratom has 983 moderate, 12 minor known drug interactions in our database — the Fosnetupitant, Palonosetron (IV) one above is among them. If you take anything else, check it against the full list below.

Moderate 983 Minor 12 No known interaction 1,835 (incl. Fosnetupitant, Palonosetron (IV))
Taking anything else?

Check Another of Your Medications Against Kratom

Covers the 2,830 medications we’ve checked against Kratom. Pick one to open its full report.

From our Q&A

Questions About Kratom 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 Kratom 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 Kratom 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 Kratom as Part of a Dietary Supplement Product? Check It for Interactions

We hold 8 real supplement products containing Kratom, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Kratom. Your product may carry other ingredients that interact with Fosnetupitant, Palonosetron (IV) too, on top of Kratom — 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 Kratom 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 Kratom
Top 25%

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

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

#560 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 Kratom

What is Kratom?

Kratom
  • Pain relief
  • Opioid withdrawal symptoms
  • Anxiety and stress
  • Low energy or fatigue
  • Mood enhancement

Kratom is a Southeast Asian plant whose leaves act on the brain's opioid receptors and can produce both stimulant-like and opioid-like effects. It is not approved or proven safe by health regulators, carries real risks of dependence and serious harm, and its legal status varies widely. Talk to a pharmacist or doctor before considering it.

Read the full Kratom 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 & Kratom

Browse every other medication we’ve checked against Kratom — both the ones with a known interaction and the ones without. Select any drug for the full detail.

0Major
983Moderate
12Minor
1,834No known interaction
983 Moderate 12 Minor 1,834 No interaction
Moderate

983 interactions

Showing 60 of 983 moderate interactions — see all 983 on the Kratom page.

Minor

12 interactions

No interaction 1,834 drugs checked — show the list

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

Showing the 60 most looked-up of 1,834 medications checked with no known interaction — see the full Kratom list.

See the full Kratom 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
Kratom 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 Kratom and Fosnetupitant, Palonosetron (IV) Together: Common Questions

Can you take Kratom with Fosnetupitant, Palonosetron (IV)?
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 Kratom and Fosnetupitant, Palonosetron (IV)?
Fosnetupitant, Palonosetron (IV) belongs to more than one drug category, and Kratom 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 Kratom and Fosnetupitant, Palonosetron (IV) 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 Fosnetupitant, Palonosetron (IV) and Kratom?

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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.