Drug & supplement interaction

Devil's Claw + Acetaminophen, Chlorpheniramine, Phenylephrine

Acetaminophen, Chlorpheniramine, Phenylephrine brand names: Protid, Histex SR, Alka-Seltzer PLUS.

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

Devil's Claw has a moderate interaction with Acetaminophen, Chlorpheniramine, Phenylephrine. Theoretically, devil's claw might increase levels of drugs metabolized by CYP3A4.

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

Devil's Claw and Acetaminophen, Chlorpheniramine, Phenylephrine

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

Moderate

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

Why this applies to Acetaminophen, Chlorpheniramine, Phenylephrine

Acetaminophen, Chlorpheniramine, Phenylephrine falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES — the group Devil's Claw interacts with.

Theoretically, devil's claw might increase levels of drugs metabolized by CYP3A4.
In vitro research shows that devil's claw might inhibit CYP3A4, although this 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

Here's the deal with this combination cold and pain product (the acetaminophen, chlorpheniramine, and phenylephrine mix). Some of these ingredients are partly broken down by a liver enzyme called CYP3A4. In test-tube studies, devil's claw appeared to slow that enzyme down a bit, which could in theory let these ingredients linger a little longer in your body. None of these are prodrugs, so slower clearance would mean slightly stronger effects, not weaker ones.

If that happened, you might notice more drowsiness or dry mouth from the chlorpheniramine, or a bit more of the jittery, raised blood pressure feeling from phenylephrine. But honestly, this has only been seen in lab dishes, never in real people, so I wouldn't lose sleep over it. Just check with your pharmacist before pairing them.

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

Devil's Claw Also Interacts With Other Medications

Devil's Claw has 730 moderate, 73 minor known drug interactions in our database — the Acetaminophen, Chlorpheniramine, Phenylephrine one above is one of them. If you take anything else, check it against the full list below.

Moderate 730 Minor 73 No known interaction 2,027 (incl. Acetaminophen, Chlorpheniramine, Phenylephrine)
Taking anything else?

Check Another of Your Medications Against Devil's Claw

Covers the 2,830 medications we’ve checked against Devil's Claw. Pick one to open its full report.

Everything else you take

See Every Supplement That Interacts With Acetaminophen, Chlorpheniramine, Phenylephrine

This page covers Devil's Claw only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Chlorpheniramine, Phenylephrine page lists 292 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 Grapefruit (major).

By severity: 14 major · 232 moderate · 46 minor.

From our pharmacist’s overview on the Acetaminophen, Chlorpheniramine, Phenylephrine page

“Picture the week you are sick enough to reach for Alka-Seltzer PLUS or another acetaminophen, chlorpheniramine, and phenylephrine combination, while still taking whatever supplements you always take. That is where trouble hides, and with 14 of its 292 supplement interactions rated major, this medicine warrants real vigilance.”

Reviewed by 2 · Jul 18, 2026

Open the Acetaminophen, Chlorpheniramine, Phenylephrine interaction page

One more smart check

Taking Devil's Claw as Part of a Dietary Supplement Product? Check It for Interactions

We hold 585 real supplement products containing Devil's Claw, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Devil's Claw. Your product may carry other ingredients that interact with Acetaminophen, Chlorpheniramine, Phenylephrine too, on top of Devil's Claw — 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 Devil's Claw and Acetaminophen, Chlorpheniramine, Phenylephrine 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 Devil's Claw
Top 25%

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

29 days ago today
Medication Acetaminophen, Chlorpheniramine, Phenylephrine
Top 25%

#493 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 Devil's Claw

What is Devil's Claw?

Devil's Claw
  • Osteoarthritis pain
  • Lower back pain
  • Joint pain and stiffness
  • General inflammation
  • Digestive upset and loss of appetite

Devil's claw is a southern African plant used mainly for arthritis and back pain, and some studies suggest it may help ease these types of discomfort. The evidence is moderate at best, and product strength varies, so talk with your pharmacist or doctor before trying it, especially if you have a health condition or take medications.

Read the full Devil's Claw monograph & all interactions
Keep checking

Other Drugs & Devil's Claw

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

0Major
730Moderate
73Minor
2,026No known interaction
730 Moderate 73 Minor 2,026 No interaction
Moderate

730 interactions

Showing 60 of 730 moderate interactions — see all 730 on the Devil's Claw page.

Minor

73 interactions

Showing 60 of 73 minor interactions — see all 73 on the Devil's Claw page.

No interaction 2,026 drugs checked — show the list

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

Showing the 60 most looked-up of 2,026 medications checked with no known interaction — see the full Devil's Claw list.

See the full Devil's Claw interactions page
See every supplement checked against Acetaminophen, Chlorpheniramine, Phenylephrine, 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
Devil's Claw monograph › Uses, safety, and every drug interaction in one place Acetaminophen, Chlorpheniramine, Phenylephrine supplement interactions › Every supplement checked against Acetaminophen, Chlorpheniramine, Phenylephrine, 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 Devil's Claw and Acetaminophen, Chlorpheniramine, Phenylephrine Together: Common Questions

Can you take Devil's Claw with Acetaminophen, Chlorpheniramine, Phenylephrine?
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 Devil's Claw and Acetaminophen, Chlorpheniramine, Phenylephrine 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, Chlorpheniramine, Phenylephrine and Devil's Claw?

Our pharmacists answer your medication & supplement questions — free.

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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.