Drug & supplement interaction

Kratom + Hydrocodone, Pseudoephedrine, Chlorpheniramine

Hydrocodone, Pseudoephedrine, Chlorpheniramine brand name: Zutripro.

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

Hydrocodone, Pseudoephedrine, Chlorpheniramine falls into 4 drug categories that Kratom can interact with; the most serious is rated moderate. Theoretically, concomitant use might increase the risk for adverse CNS depressant effects.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions4
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Kratom and Hydrocodone, Pseudoephedrine, Chlorpheniramine

These two interact in 4 distinct ways. Each one is explained separately below.

Why Are There 4 Interactions?

Kratom interacts with whole categories of medication. Hydrocodone, Pseudoephedrine, Chlorpheniramine falls into 4 of those categories, so it can interact with Kratom in 4 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

CNS DEPRESSANTS

1 of 4

Why this applies to Hydrocodone, Pseudoephedrine, Chlorpheniramine

Hydrocodone, Pseudoephedrine, Chlorpheniramine falls under CNS DEPRESSANTS — the group Kratom interacts with.

Theoretically, concomitant use might increase the risk for adverse CNS depressant effects.
Kratom contains mitragynine, a mu-receptor agonist that may cause respiratory depression. Although results from animal research suggest that mitragynine causes less respiratory depression than the CNS depressant codeine, fatalities have been reported for patients who ingested a combination of kratom and O-desmethyltramadol, another mu-receptor agonist. Additionally, observational research suggests that adverse effects such as drowsiness and coma are more likely to occur in individuals taking kratom in combination with agents such as opioids and sedatives. Theoretically, ingesting kratom along with other CNS depressants can increase the risk of adverse effects, including drowsiness, coma, and/or severe or fatal respiratory depression.
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 watch with Zutripro: it already carries two ingredients that can slow you down. Hydrocodone is an opioid that calms the brain and breathing, and chlorpheniramine is a sedating antihistamine that adds drowsiness. Kratom acts on those same opioid receptors in your brain, so stacking it on top can pile on the same effects.

The concern is mostly theoretical and based on how these compounds behave, not on strong studies. Still, taking both together could mean more drowsiness, foggy thinking, very slow or shallow breathing, and in the worst cases, dangerous over-sedation. That's a real risk worth respecting. Please don't combine them without checking first, and have a chat with your pharmacist or doctor before mixing kratom with anything in Zutripro.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Backstrom BG, Classon G, Lowenhielm P, Thelander G. [Krypton--new, deadly Internet drug. Since October 2009 have nine young persons died in Sweden]. Lakartidningen 2010;107(50):3196-3197.
  2. Kronstrand R, Roman M, Thelander G, Eriksson A. Unintentional fatal intoxications with mitragynine and O-desmethyltramadol from the herbal blend Krypton. J Anal Toxicol 2011;35(4):242-247. PubMed
  3. Jansen KL, Prast CJ. Ethnopharmacology of kratom and the Mitragyna alkaloids. J Ethnopharmacol 1988;23(1):115-119. PubMed
  4. Davidson C, Cao D, King T, et al. A comparative analysis of kratom exposure cases in Thailand and the United States from 2010-2017. Am J Drug Alcohol Abuse. 2020:1-10. PubMed
Moderate

CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES

2 of 4

Hydrocodone, Pseudoephedrine, Chlorpheniramine also falls under CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES.

Theoretically, kratom might increase the levels and clinical effects of drugs metabolized by CYP2D6.
In vitro research suggests that kratom extract inhibits CYP2D6 enzyme activity. However, human research shows that a single low dose of kratom tea 2 grams does not inhibit CYP2D6 activity. However, this kratom dose is lower than what is normally taken for psychoactive effects. In one 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 was hypothesized that kratom inhibited CYP2D6-mediated metabolism of buspirone and consequently increased systemic exposure to serotonin. In another case, a 37-year-old male stable for 15 years on amitriptyline presented with anticholinergic symptoms including xerostomia, dry eyes, and constipation, along with mildly elevated bilirubin and liver enzymes after taking progressively higher doses of up to 14 grams of kratom daily for 12 weeks. It was hypothesized that the adverse effects of amitriptyline were precipitated by CYP2D6 inhibition by kratom.
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 Zutripro: the hydrocodone part is actually a prodrug. Your body uses an enzyme called CYP2D6 to turn some of it into hydromorphone, the more powerful pain-relieving piece. Lab studies hint that kratom may slow that same enzyme down. If that happens, less hydrocodone gets converted, so you could feel less pain relief than expected. On the flip side, kratom itself hits opioid receptors, so stacking it on top of an opioid still raises the real risk of heavy sedation and dangerously slow breathing.

Honestly, this enzyme effect is theoretical and based mostly on test-tube work, not solid human data. The bigger, more certain concern is combining two opioid-acting substances. Please run this by your pharmacist or doctor before mixing them.

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. 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
  3. 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
  4. Vanani NB, Stevanovic SG, Stevanovic N. Adverse Drug Interaction Between Kratom and Amitriptyline With Gastrointestinal and Mild Hepatic Effects. Cureus 2023;15(1):e33809. PubMed
Moderate

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

3 of 4

Hydrocodone, Pseudoephedrine, Chlorpheniramine also falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES.

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

The hydrocodone part of Zutripro is the piece I'd watch most here. Kratom appears to slow down a liver and gut enzyme called CYP3A4, which is one of the main pathways that breaks hydrocodone down. If that breakdown is blocked, more of the opioid can hang around, leading to stronger effects like heavy drowsiness, slowed breathing, confusion, or constipation. On top of that, kratom itself acts on opioid receptors, so the two can pile on each other even apart from the enzyme issue.

To be fair, this is mostly a theoretical concern based on lab studies, and the gut effect seems modest. Still, opioids plus kratom is a combination I wouldn't take lightly. Please check with your pharmacist or doctor before pairing them.

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

4 of 4

Hydrocodone, Pseudoephedrine, Chlorpheniramine 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

Zutripro is a combo product, and the piece that overlaps with kratom here is the chlorpheniramine, an antihistamine that nudges serotonin activity. On paper, pairing kratom with serotonin-raising medicines could push serotonin levels too high, which sometimes leads to so-called serotonin syndrome (agitation, shivering, sweating, fast heartbeat, or confusion). I'll be honest with you though: this concern rests on a single case report and theory, not solid proof, so it's a possible, not a likely, problem.

There's a second worry worth naming. Both kratom and the hydrocodone in Zutripro can slow breathing and bring on heavy drowsiness, and combining sedating things stacks that risk. Please don't start, stop, or change anything on your own. Run this combination by your pharmacist or doctor first.

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

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 Hydrocodone, Pseudoephedrine, Chlorpheniramine 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. Hydrocodone, Pseudoephedrine, Chlorpheniramine)
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 Hydrocodone, Pseudoephedrine, Chlorpheniramine

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 Hydrocodone, Pseudoephedrine, Chlorpheniramine, 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 Hydrocodone, Pseudoephedrine, Chlorpheniramine

This page covers Kratom only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Hydrocodone, Pseudoephedrine, Chlorpheniramine page lists 285 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: 1,4-butanediol (major), Activated Charcoal (major), Beer (major), Ephedra (major) and Gamma-hydroxybutyrate (ghb) (major).

By severity: 16 major · 228 moderate · 41 minor.

From our pharmacist’s overview on the Hydrocodone, Pseudoephedrine, Chlorpheniramine page

“Zutripro pairs an opioid (hydrocodone) with a decongestant and a sedating antihistamine, which means supplements can interfere from three directions at once, and with 16 major-rated interactions among the 285 on file, this is a list to treat with genuine respect. The biggest cluster, 78 sedating ingredients including alcohol in any for…”

Reviewed by 2 · Jul 18, 2026

Open the Hydrocodone, Pseudoephedrine, Chlorpheniramine 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 Hydrocodone, Pseudoephedrine, Chlorpheniramine 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 Hydrocodone, Pseudoephedrine, Chlorpheniramine 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%

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

29 days ago today
Medication Hydrocodone, Pseudoephedrine, Chlorpheniramine
Steady interest

#2,829 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
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 Hydrocodone, Pseudoephedrine, Chlorpheniramine, 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 Hydrocodone, Pseudoephedrine, Chlorpheniramine supplement interactions › Every supplement checked against Hydrocodone, Pseudoephedrine, Chlorpheniramine, ranked by severity 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 Hydrocodone, Pseudoephedrine, Chlorpheniramine Together: Common Questions

Can you take Kratom with Hydrocodone, Pseudoephedrine, Chlorpheniramine?
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 4 interactions listed for Kratom and Hydrocodone, Pseudoephedrine, Chlorpheniramine?
Hydrocodone, Pseudoephedrine, Chlorpheniramine 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 Hydrocodone, Pseudoephedrine, Chlorpheniramine 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 Hydrocodone, Pseudoephedrine, Chlorpheniramine 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.