Drug & supplement interaction

Grapefruit + Acetaminophen, Pseudoephedrine, Triprolidine

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

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

Grapefruit has a moderate interaction with Acetaminophen, Pseudoephedrine, Triprolidine. Theoretically, grapefruit juice might increase levels 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

Grapefruit 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 Grapefruit interacts with.

Theoretically, grapefruit juice might increase levels of drugs metabolized by CYP1A2.
In vitro research suggests that grapefruit juice might inhibit CYP1A2 enzymes. So far, this interaction has not been reported in humans.
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

This combination product (Actifed Plus ES) pairs acetaminophen for pain and fever with pseudoephedrine, a decongestant, and triprolidine, an antihistamine. The concern on file is that grapefruit may block a liver enzyme called CYP1A2, which could in theory let certain medicines build up a bit higher in your system. None of these ingredients is a prodrug, so if levels did rise, you'd simply expect their normal effects to feel a touch stronger.

Here's the reassuring part: this is based only on lab studies, not real people, so it is mostly theoretical. If anything happened, you might notice more drowsiness or dry mouth from the triprolidine, or a bit more jitteriness from the pseudoephedrine. An occasional grapefruit is unlikely to cause trouble, but check with your pharmacist if you eat it often.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Unger M, Frank A. Simultaneous determination of the inhibitory potency of herbal extracts on the activity of six major cytochrome P450 enzymes using liquid chromatography/mass spectrometry and automated online extraction. Rapid Commun Mass Spectrom 2004;1 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

Grapefruit Also Interacts With Other Medications

Grapefruit has 776 major, 150 moderate, 63 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.

Major 776 Moderate 150 Minor 63 No known interaction 1,841 (incl. Acetaminophen, Pseudoephedrine, Triprolidine)
Taking anything else?

Check Another of Your Medications Against Grapefruit

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

From our Q&A

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

We hold 1,144 real supplement products containing Grapefruit, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Grapefruit. Your product may carry other ingredients that interact with Acetaminophen, Pseudoephedrine, Triprolidine too, on top of Grapefruit — 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 Grapefruit 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 Grapefruit
Top 10%

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

29 days ago today
Medication Acetaminophen, Pseudoephedrine, Triprolidine
Steady interest

#1,494 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 Grapefruit

What is Grapefruit?

Grapefruit
  • Source of vitamin C
  • Digestive complaints
  • Antimicrobial (seed extract)
  • Weight management
  • Skin and cosmetic uses

Grapefruit is a nutritious citrus fruit rich in vitamin C and other nutrients, and it is generally safe to eat. However, grapefruit is famous for serious interactions with many prescription medicines, so anyone taking medication should check with a pharmacist or doctor before consuming it regularly.

Read the full Grapefruit monograph & all interactions
Keep checking

Other Drugs & Grapefruit

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

776Major
150Moderate
63Minor
1,840No known interaction
776 Major 150 Moderate 63 Minor 1,840 No interaction
Major

776 interactions

Showing 60 of 776 major interactions — see all 776 on the Grapefruit page.

Moderate

150 interactions

Showing 60 of 150 moderate interactions — see all 150 on the Grapefruit page.

Minor

63 interactions

Showing 60 of 63 minor interactions — see all 63 on the Grapefruit page.

No interaction 1,840 drugs checked — show the list

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

Showing the 60 most looked-up of 1,840 medications checked with no known interaction — see the full Grapefruit list.

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

Can you take Grapefruit 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 Grapefruit 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 Grapefruit?

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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.