Drug & supplement interaction

Kratom + Itraconazole

Itraconazole brand names: Sporanox, Sporanox Injection, Tolsura.

Moderate Interaction
The bottom line Moderate

Itraconazole falls into 2 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
Interactions2
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Kratom and Itraconazole

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. Itraconazole 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

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

1 of 2

Why this applies to Itraconazole

Itraconazole 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 wrinkle with itraconazole: it's a bit of a two-way street. Kratom can mildly block an enzyme called CYP3A4, mostly in your gut, and itraconazole is partly handled by that same enzyme. So in theory, kratom could nudge your itraconazole levels up a little, which might mean more of its usual side effects like nausea, stomach upset, headache, or in rarer cases effects on the heart or liver.

What makes me cautious is that itraconazole is itself a strong CYP3A4 blocker, so the bigger real-world worry is itraconazole raising the levels of other things you take, including kratom's own active compounds. Honestly, this combo is mostly theoretical and based on lab work, but kratom carries its own serious risks. Please loop in your pharmacist or doctor before mixing the two.

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

CYTOCHROME P450 3A4 (CYP3A4) INHIBITORS

2 of 2

Itraconazole 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 key thing to know: itraconazole is a strong blocker of an enzyme called CYP3A4, and that same enzyme helps your body process kratom's main active compound, mitragynine. When itraconazole slows that breakdown, more mitragynine can build up in your blood (a study in healthy adults saw the peak level rise about 1.5-fold). In plain terms, the kratom may hit harder and last longer.

That can mean stronger opioid-like effects from the kratom, such as deeper drowsiness, slowed breathing, constipation, nausea, or dizziness. I'd also gently remind you that kratom itself isn't proven safe, so combining it with this antifungal adds uncertainty. Please don't start, stop, or change anything on your own. Talk with your pharmacist or doctor first so they can guide you safely.

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 982 moderate, 12 minor known drug interactions in our database — the Itraconazole 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 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 Itraconazole

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 Itraconazole, 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 Itraconazole

This page covers Kratom only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Itraconazole page lists 182 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Beer (major), Grapefruit (major), Siberian Cocklebur (major) and St. John's Wort (major).

By severity: 6 major · 136 moderate · 40 minor.

From our pharmacist’s overview on the Itraconazole page

“Serious fungal infections are what itraconazole (Sporanox, Tolsura) is for, and the drug travels through CYP3A4, the liver enzyme that also handles a large share of supplements. That overlap is why this list reaches 182 ingredients, and it earns genuine care; start with the six rated major.”

Reviewed by 2 · Jul 18, 2026

Open the Itraconazole 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 Itraconazole 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 Itraconazole 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

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

29 days ago today
Medication Itraconazole
Top half

#732 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 Itraconazole

What Is Itraconazole Used For?

Brand names: Sporanox, Sporanox Injection, Tolsura

Itraconazole capsules (including Sporanox capsules and generic itraconazole capsules) treat serious fungal infections — blastomycosis, histoplasmosis, and aspergillosis — in both people with normal immune systems and those who are immunocompromised. Capsule forms are also approved for nail fungus (onychomycosis) caused by dermatophytes in non-immunocompromised patients. Tolsura (a gelatin-coated capsule formulation) treats blastomycosis, histoplasmosis, and aspergillosis in adults, but is not approved for nail fungus and is not interchangeable with other itraconazole products.

Itraconazole oral solution is specifically approved for oropharyngeal candidiasis (thrush — a fungal infection of the mouth) and esophageal candidiasis (a fungal infection of the food pipe). Only the oral solution has been shown to work for these mouth and throat infections; capsules cannot be substituted for this use.

See full Itraconazole 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
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
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 Kratom and Itraconazole Together: Common Questions

Can you take Kratom with Itraconazole?
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 Itraconazole?
Itraconazole 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 Itraconazole 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 Itraconazole 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.