Drug & supplement interaction

Black Pepper + Acetaminophen, Pseudoephedrine, Triprolidine

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

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

Black Pepper has a minor interaction with Acetaminophen, Pseudoephedrine, Triprolidine. Theoretically, black pepper might decrease levels and clinical effects of drugs metabolized by CYP1A2.

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

Black Pepper and Acetaminophen, Pseudoephedrine, Triprolidine

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

Minor

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES

Why this applies to Acetaminophen, Pseudoephedrine, Triprolidine

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

Theoretically, black pepper might decrease levels and clinical effects of drugs metabolized by CYP1A2.
In vitro research suggests that black pepper induces CYP1A2. This has not been reported in humans.
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 bottom line for your Actifed Plus ES (the combo of acetaminophen, pseudoephedrine, and triprolidine). The concern on file is purely theoretical and comes from lab and animal studies, not from real people. In those test-tube studies, piperine (the active part of black pepper) seemed to speed up a liver enzyme called CYP1A2. If that happened in the body, it could in theory clear these medicines a little faster and make them slightly less effective, so your cold and allergy relief might feel a touch weaker.

Honestly, I wouldn't lose sleep over this one. None of these three ingredients leans heavily on CYP1A2, the evidence is weak, and food amounts of pepper are a non-issue. If you take a concentrated piperine supplement regularly, just mention it to your pharmacist so they can keep an eye on things.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Haron MH, Dale O, Martin K, et al. Evaluation of the Herb-Drug Interaction Potential of Commonly Used Botanicals on the US Market with Regard to PXR- and AhR-Mediated Influences on CYP3A4 and CYP1A2. J Diet Suppl 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

Black Pepper Also Interacts With Other Medications

Black Pepper has 976 moderate, 42 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 976 Minor 42 No known interaction 1,812 (incl. Acetaminophen, Pseudoephedrine, Triprolidine)
Taking anything else?

Check Another of Your Medications Against Black Pepper

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

From our Q&A

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

We hold 5,528 real supplement products containing Black Pepper, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Black Pepper. Your product may carry other ingredients that interact with Acetaminophen, Pseudoephedrine, Triprolidine too, on top of Black Pepper — 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 Black Pepper 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 Black Pepper
Top 5%

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

29 days ago today
Medication Acetaminophen, Pseudoephedrine, Triprolidine
Top half

#1,380 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 Black Pepper

What is Black Pepper?

Black Pepper
  • Flavoring and culinary use
  • Digestive complaints like bloating and indigestion
  • Boosting absorption of other supplements
  • Antioxidant and anti-inflammatory support
  • Cold and congestion remedies

Black pepper is a common kitchen spice that is generally safe in the amounts used in food. Its extract, piperine, is mostly added to supplements to help the body absorb other ingredients (like curcumin from turmeric). Strong human evidence for black pepper treating specific health conditions is limited, so use supplement-strength products with care and check with your pharmacist.

Read the full Black Pepper monograph & all interactions
Keep checking

Other Drugs & Black Pepper

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

0Major
976Moderate
42Minor
1,811No known interaction
976 Moderate 42 Minor 1,811 No interaction
Moderate

976 interactions

Showing 60 of 976 moderate interactions — see all 976 on the Black Pepper page.

Minor

42 interactions

No interaction 1,811 drugs checked — show the list

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

Showing the 60 most looked-up of 1,811 medications checked with no known interaction — see the full Black Pepper list.

See the full Black Pepper 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
Black Pepper 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 Black Pepper and Acetaminophen, Pseudoephedrine, Triprolidine Together: Common Questions

Can you take Black Pepper with Acetaminophen, Pseudoephedrine, Triprolidine?
There is only a minor interaction, which is usually not serious. Read the full details on this page and confirm with your pharmacist before combining them.
How serious is the Black Pepper and Acetaminophen, Pseudoephedrine, Triprolidine interaction?
We rate it Minor. This interaction is generally not clinically significant, but it remains worth noting and discussing with your pharmacist.

Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy

Still Have a Question About Acetaminophen, Pseudoephedrine, Triprolidine and Black Pepper?

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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.