Drug & supplement interaction

Kratom + Tapentadol

Tapentadol brand names: Nucynta, Nucynta ER.

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

Tapentadol falls into 2 drug categories that Kratom can interact with; the most serious is rated moderate. Theoretically, taking kratom in combination with serotonergic drugs may increase levels of serotonin, increasing the risk of serotonin syndrome.

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

Kratom and Tapentadol

These two interact in 2 distinct ways. Each one is explained separately below.

Why Are There 2 Interactions?

Kratom interacts with whole categories of medication. Tapentadol falls into 2 of those categories, so it can interact with Kratom in 2 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

SEROTONERGIC DRUGS

1 of 2

Why this applies to Tapentadol

Tapentadol falls under SEROTONERGIC DRUGS — the group Kratom interacts with.

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 pairing kratom with tapentadol: both can raise serotonin in your body. Tapentadol doesn't just dull pain like a classic opioid, it also boosts a brain chemical called norepinephrine and has mild serotonin activity. Kratom acts on opioid receptors too. Stack them together and you may nudge serotonin too high, which can lead to serotonin syndrome, things like agitation, a racing heart, sweating, shivering, muscle twitching, or confusion.

On top of that, both calm the nervous system, so you could see extra drowsiness or slowed breathing. This warning rests on a single case report and theory, so it's far from proven, but tapentadol is potent enough that I'd play it safe. Please run this by your pharmacist or doctor before combining them.

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
Minor

CYTOCHROME P450 2C19 (CYP2C19) SUBSTRATES

2 of 2

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

Theoretically, kratom might increase the levels of drugs metabolized by CYP2C19.
In vitro research shows that kratom extract weakly inhibits CYP2C19 enzyme activity.
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 bigger picture with these two together. On paper, kratom may slightly slow down a liver enzyme called CYP2C19, which is one of the pathways that helps clear tapentadol. If that pathway slows, a little more tapentadol could linger in your system, possibly nudging up its effects and side effects like drowsiness, dizziness, constipation, or feeling foggy. The honest truth is this enzyme effect is weak and only seen in lab dishes, so it's mostly theoretical.

My real worry isn't the enzyme at all. Both kratom and tapentadol act on opioid receptors and can depress your breathing. Stacking them raises the risk of dangerous sedation. Please don't combine these without talking to your doctor or pharmacist first.

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

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 982 moderate, 12 minor known drug interactions in our database — the Tapentadol one above is among them. If you take anything else, check it against the full list below.

Moderate 982 Minor 12 No known interaction 1,836 (incl. Tapentadol)
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 Tapentadol

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 Tapentadol, 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 Tapentadol

This page covers Kratom only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Tapentadol page lists 113 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Lithium (major), 5-htp (moderate), Acetyl-l-carnitine (moderate) and Adrafinil (moderate).

By severity: 2 major · 84 moderate · 27 minor.

From our pharmacist’s overview on the Tapentadol page

“Tapentadol (Nucynta, Nucynta ER) is an opioid painkiller that also boosts serotonin signaling on its own, and that is exactly where its supplement list bites hardest. The two major-rated entries among the 113 on file deserve a hard look first: lithium, which alongside a serotonergic drug like tapentadol can raise the risk of serotonin…”

Reviewed by 2 · Jul 18, 2026

Open the Tapentadol 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 Tapentadol 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 Tapentadol 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 half

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

29 days ago today
Medication Tapentadol
Top 25%

#695 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 Tapentadol

What Is Tapentadol Used For?

Brand names: Nucynta, Nucynta ER

Tapentadol tablets (including Nucynta and Tapentadol Hydrochloride tablets) are used for severe acute pain in adults when other treatments are not adequate. Nucynta tablets are also approved for acute pain in children aged 6 and older who weigh at least 40 kg.

Nucynta ER and tapentadol extended-release tablets are used for severe, ongoing pain that requires around-the-clock opioid treatment and cannot be managed with other options, including severe neuropathic pain (nerve pain) caused by diabetic peripheral neuropathy in adults. Extended-release formulations are not intended for as-needed use.

See full Tapentadol 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
982Moderate
12Minor
1,835No known interaction
982 Moderate 12 Minor 1,835 No interaction
Moderate

982 interactions

Showing 60 of 982 moderate interactions — see all 982 on the Kratom page.

Minor

12 interactions

No interaction 1,835 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 1,835 medications checked with no known interaction — see the full Kratom list.

See the full Kratom interactions page
See every supplement checked against Tapentadol, 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 Tapentadol supplement interactions › Every supplement checked against Tapentadol, ranked by severity Tapentadol 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 Tapentadol Together: Common Questions

Can you take Kratom with Tapentadol?
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 Kratom and Tapentadol?
Tapentadol 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 Tapentadol 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 Tapentadol 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.