Drug & supplement interaction

Kratom + Acetaminophen, Pseudoephedrine, Triprolidine

Acetaminophen, Pseudoephedrine, Triprolidine brand name: Actifed Plus ES.

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

Kratom has a moderate interaction with Acetaminophen, Pseudoephedrine, Triprolidine. Theoretically, kratom might increase the levels and clinical effects of drugs metabolized by CYP1A2.

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

Kratom and Acetaminophen, Pseudoephedrine, Triprolidine

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

Moderate

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES

Why this applies to Acetaminophen, Pseudoephedrine, Triprolidine

Acetaminophen, Pseudoephedrine, Triprolidine falls under CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES — the group Kratom interacts with.

Theoretically, kratom might increase the levels and clinical effects of drugs metabolized by CYP1A2.
In vitro research suggests that kratom extract inhibits the activity of CYP1A2. 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 CYP1A2-mediaed metabolism of ziprasidone which 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 thing about combining kratom with a cold and allergy combo like Actifed Plus ES (acetaminophen, pseudoephedrine, and triprolidine): lab studies hint that kratom may slow down a liver enzyme called CYP1A2. In theory, that could let certain drugs build up a bit higher than usual. But for these three ingredients specifically, CYP1A2 isn't a major pathway, so any real-world effect is likely small.

What I'd actually keep an eye on is the overlap in side effects. Triprolidine (an antihistamine) and kratom can both make you drowsy or foggy, while kratom's opioid-like activity stacked with that sedation isn't something to take lightly. Pseudoephedrine can leave you jittery or raise your heart rate too. Please check with your pharmacist or doctor before pairing these, and don't start, stop, or change anything on your own.

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

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 Acetaminophen, Pseudoephedrine, Triprolidine one above is one of them. If you take anything else, check it against the full list below.

Moderate 982 Minor 12 No known interaction 1,836 (incl. Acetaminophen, Pseudoephedrine, Triprolidine)
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 Acetaminophen, Pseudoephedrine, Triprolidine

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 Acetaminophen, Pseudoephedrine, Triprolidine, 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 Acetaminophen, Pseudoephedrine, Triprolidine

This page covers Kratom only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Pseudoephedrine, Triprolidine page lists 197 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Asarabacca (major), Beer (major), Ephedra (major) and Peyote (major).

By severity: 9 major · 149 moderate · 39 minor.

From our pharmacist’s overview on the Acetaminophen, Pseudoephedrine, Triprolidine page

“Actifed Plus ES combines acetaminophen, pseudoephedrine, and triprolidine, and the pseudoephedrine is why I would check this page carefully before adding any supplement. Stimulation dominates the list: 44 ingredients, from ephedra to the everyday caffeine in coffee, tea, and cocoa, can stack on the decongestant and push blood pressure…”

Reviewed by 2 · Jul 18, 2026

Open the Acetaminophen, Pseudoephedrine, Triprolidine 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 Acetaminophen, Pseudoephedrine, Triprolidine 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 Acetaminophen, Pseudoephedrine, Triprolidine 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 Acetaminophen, Pseudoephedrine, Triprolidine
Steady interest

#1,433 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 Acetaminophen, Pseudoephedrine, Triprolidine, 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 Acetaminophen, Pseudoephedrine, Triprolidine supplement interactions › Every supplement checked against Acetaminophen, Pseudoephedrine, Triprolidine, 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 Acetaminophen, Pseudoephedrine, Triprolidine Together: Common Questions

Can you take Kratom with Acetaminophen, Pseudoephedrine, Triprolidine?
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.
How serious is the Kratom and Acetaminophen, Pseudoephedrine, Triprolidine 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 Acetaminophen, Pseudoephedrine, Triprolidine 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.