Drug & supplement interaction

Horny Goat Weed + 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

Acetaminophen, Chlorpheniramine, Phenylephrine falls into 2 drug categories that Horny Goat Weed can interact with; the most serious is rated moderate. Theoretically, horny goat weed might increase the effects and side effects of CYP1A2 substrates.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions2
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Horny Goat Weed and Acetaminophen, Chlorpheniramine, Phenylephrine

These two interact in 2 distinct ways. Each one is explained separately below.

Why Are There 2 Interactions?

Horny Goat Weed interacts with whole categories of medication. Acetaminophen, Chlorpheniramine, Phenylephrine falls into 2 of those categories, so it can interact with Horny Goat Weed in 2 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES

1 of 2

Why this applies to Acetaminophen, Chlorpheniramine, Phenylephrine

Acetaminophen, Chlorpheniramine, Phenylephrine falls under CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES — the group Horny Goat Weed interacts with.

Theoretically, horny goat weed might increase the effects and side effects of CYP1A2 substrates.
In vitro, horny goat weed leaf extract inhibits CYP1A2. This effect 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 gist for this cold and allergy combo. In the test tube, horny goat weed slows down a liver enzyme called CYP1A2. That same enzyme helps clear certain medicines, so in theory the supplement could let them linger a bit longer and feel stronger. For this particular product, the chlorpheniramine (the antihistamine) is the piece most likely to lean on that pathway, so you might notice more drowsiness, dry mouth, or dizziness. The phenylephrine and acetaminophen aren't really driven by CYP1A2.

The reassuring part: this is only lab data and has never been shown to happen in real people, so I wouldn't lose sleep over it. Still, if you plan to use both, run it past your pharmacist or doctor first.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Zhong Q, Shi Z, Zhang L, et al. The potential of Epimedium koreanum Nakai for herb-drug interaction. J Pharm Pharmacol 2017;69(10):1398-408. doi: 10.1111/jphp.12773.
Moderate

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

2 of 2

Acetaminophen, Chlorpheniramine, Phenylephrine also falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES.

Theoretically, horny goat weed might increase the effects and side effects of CYP3A4 substrates.
In vitro, horny goat weed extract inhibits CYP3A4 and suppresses CYP3A4 mRNA expression. This effect 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 combo cold product pairs acetaminophen (a pain and fever reducer) with chlorpheniramine (an antihistamine) and phenylephrine (a decongestant). The concern here is mostly theoretical: in lab dish studies, horny goat weed appears to slow down an enzyme called CYP3A4, which helps clear some of these ingredients. If that slowdown happened in people, levels could creep up a bit, possibly nudging the drowsiness and dry mouth from chlorpheniramine, or the jittery, raised blood pressure feeling from phenylephrine.

Keep this in perspective. This was only seen in test tubes, never confirmed in humans, so the real-world risk is low. Still, if you have heart issues or take other medicines, it's worth a quick chat with your pharmacist before combining them.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Li K, Yu XH, Maskey AR, et al. Cytochrome P450 3A4 suppression by epimedium and active compound kaempferol leads to synergistic anti-inflammatory effect with corticosteroid. Front Pharmacol 2023;13:1042756. 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

Horny Goat Weed Also Interacts With Other Medications

Horny Goat Weed has 962 moderate known drug interactions in our database — the Acetaminophen, Chlorpheniramine, Phenylephrine one above is among them. If you take anything else, check it against the full list below.

Moderate 962 No known interaction 1,868 (incl. Acetaminophen, Chlorpheniramine, Phenylephrine)
Taking anything else?

Check Another of Your Medications Against Horny Goat Weed

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

From our Q&A

Questions About Horny Goat Weed or Acetaminophen, Chlorpheniramine, Phenylephrine

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Horny Goat Weed or Acetaminophen, Chlorpheniramine, Phenylephrine, 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, Chlorpheniramine, Phenylephrine

This page covers Horny Goat Weed 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 Horny Goat Weed as Part of a Dietary Supplement Product? Check It for Interactions

We hold 183 real supplement products containing Horny Goat Weed, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Horny Goat Weed. Your product may carry other ingredients that interact with Acetaminophen, Chlorpheniramine, Phenylephrine too, on top of Horny Goat Weed — 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 Horny Goat Weed 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 Horny Goat Weed
Top 25%

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

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

#632 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 Horny Goat Weed

What is Horny Goat Weed?

Horny Goat Weed
  • Erectile dysfunction
  • Low libido
  • Fatigue and low energy
  • Bone health
  • Joint and menopausal symptoms
  • General 'vitality' or performance

Horny goat weed (Epimedium) is a traditional Chinese herb most often marketed for low libido and erectile problems, but solid human evidence for these uses is lacking. While short-term use seems generally tolerated by some people, quality and safety are not well studied, so talk to your pharmacist or doctor before trying it—especially if you have heart problems or take other medicines.

Read the full Horny Goat Weed monograph & all interactions
Keep checking

Other Drugs & Horny Goat Weed

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

0Major
962Moderate
0Minor
1,867No known interaction
962 Moderate 1,867 No interaction
Moderate

962 interactions

Showing 60 of 962 moderate interactions — see all 962 on the Horny Goat Weed page.

No interaction 1,867 drugs checked — show the list

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

Showing the 60 most looked-up of 1,867 medications checked with no known interaction — see the full Horny Goat Weed list.

See the full Horny Goat Weed 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
Horny Goat Weed 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 Horny Goat Weed and Acetaminophen, Chlorpheniramine, Phenylephrine Together: Common Questions

Can you take Horny Goat Weed 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.
Why are there 2 interactions listed for Horny Goat Weed and Acetaminophen, Chlorpheniramine, Phenylephrine?
Acetaminophen, Chlorpheniramine, Phenylephrine belongs to more than one drug category, and Horny Goat Weed 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 Horny Goat Weed 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 Horny Goat Weed?

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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.