Drug & supplement interaction

Hordenine + Acetaminophen, Caffeine, Codeine

Acetaminophen, Caffeine, Codeine brand names: Gesic C8, Gesic C15, Lenoltec 2, Gesic C30, Lenoltec 3, and others.

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

Acetaminophen, Caffeine, Codeine falls into 2 drug categories that Hordenine can interact with; the most serious is rated moderate. Hordenine is structurally similar to N-methyltyramine and synephrine, constituents in bitter orange known to have stimulant properties.

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

Hordenine and Acetaminophen, Caffeine, Codeine

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

Why Are There 2 Interactions?

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

Moderate

STIMULANT DRUGS

1 of 2

Why this applies to Acetaminophen, Caffeine, Codeine

Acetaminophen, Caffeine, Codeine falls under STIMULANT DRUGS — the group Hordenine interacts with.

Hordenine is structurally similar to N-methyltyramine and synephrine, constituents in bitter orange known to have stimulant properties. Theoretically, taking hordenine with drugs with stimulant properties might increase the risk of hypertension and other adverse cardiovascular effects.
Some of these drugs include amphetamine, caffeine, methylphenidate, pseudoephedrine, and many others.
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

The piece of this combo pill that matters here is the caffeine. Hordenine acts like a mild stimulant, much like the compounds in bitter orange, so stacking it on top of the caffeine in this medication could add up. In theory that might push your heart rate and blood pressure higher and leave you feeling jittery, restless, or with a racing or pounding heartbeat. The acetaminophen and codeine parts aren't really the concern with hordenine.

Keep in mind this is a theoretical caution based on how these stimulants behave, not on strong human studies, so for most people it's a minor issue. Still, if you have any heart trouble or high blood pressure, it's worth a quick chat with your pharmacist or doctor before combining them.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Nelson BC, Putzbach K, Sharpless KE, Sander LC. Mass spectrometric determination of the predominant adrenergic protoalkaloids in bitter orange (Citrus aurantium). J Agric Food Chem 2007;55(24):9769-75. PubMed
Minor

CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES

2 of 2

Acetaminophen, Caffeine, Codeine also falls under CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES.

Hordenine weakly inhibits cytochrome P450 2D6 (CYP2D6) enzymes in vitro. Theoretically, hordenine might increase the levels of CYP2D6 substrates.
Some of drugs that are CYP2D6 substrates include amitriptyline (Elavil), clozapine (Clozaril), codeine, desipramine (Norpramin), donepezil (Aricept), fentanyl (Duragesic), flecainide (Tambocor), fluoxetine (Prozac), meperidine (Demerol), methadone (Dolophine), metoprolol (Lopressor, Toprol XL), olanzapine (Zyprexa), ondansetron (Zofran), tramadol (Ultram), trazodone (Desyrel), and others.
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 wrinkle with this combo: the codeine part of your tablet is what we call a prodrug. It only relieves pain after your body converts it into morphine, and the enzyme that does that conversion is CYP2D6. Hordenine has been shown in lab dishes to weakly block that same enzyme. So in theory, if hordenine slows CYP2D6, you might make less morphine from your codeine, meaning weaker pain relief rather than more side effects.

I'll be honest, this is based only on test-tube data, the effect looked weak, and it's rated minor. So I wouldn't lose sleep over it. Still, since hordenine itself is a stimulant and poorly studied, it's worth a quick chat with your pharmacist or doctor before pairing the two.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Liu Y, Santillo MF. Cytochrome P450 2D6 and 3A4 enzyme inhibition by amine stimulants in dietary supplements. Drug Test Anal. 2016;8(3-4):307-10. 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

Hordenine Also Interacts With Other Medications

Hordenine has 179 moderate, 149 minor known drug interactions in our database — the Acetaminophen, Caffeine, Codeine one above is among them. If you take anything else, check it against the full list below.

Moderate 179 Minor 149 No known interaction 2,502 (incl. Acetaminophen, Caffeine, Codeine)
Taking anything else?

Check Another of Your Medications Against Hordenine

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

Everything else you take

See Every Supplement That Interacts With Acetaminophen, Caffeine, Codeine

This page covers Hordenine only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Caffeine, Codeine page lists 303 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: 1,4-butanediol (major), Activated Charcoal (major), Asarabacca (major), Beer (major) and Ephedra (major).

By severity: 15 major · 244 moderate · 44 minor.

Open the Acetaminophen, Caffeine, Codeine interaction page

One more smart check

Taking Hordenine as Part of a Dietary Supplement Product? Check It for Interactions

We hold 339 real supplement products containing Hordenine, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Hordenine. Your product may carry other ingredients that interact with Acetaminophen, Caffeine, Codeine too, on top of Hordenine — 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 Hordenine and Acetaminophen, Caffeine, Codeine 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 Hordenine
Top 25%

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

29 days ago today
Medication Acetaminophen, Caffeine, Codeine
Top 5%

#82 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 Hordenine

What is Hordenine?

Hordenine
  • Energy and stimulation
  • Athletic and workout performance
  • Weight loss/fat burning
  • Focus and mood
  • Appetite control

Hordenine is a natural alkaloid found in barley and some cacti that is marketed as a stimulant for energy, focus, and fat loss, but solid human evidence for these benefits is lacking. Its safety in people has not been well studied, so caution is warranted, and it should be avoided in pregnancy, breastfeeding, and by people with heart conditions.

Read the full Hordenine monograph & all interactions
Keep checking

Other Drugs & Hordenine

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

0Major
179Moderate
149Minor
2,501No known interaction
179 Moderate 149 Minor 2,501 No interaction
Moderate

179 interactions

Showing 60 of 179 moderate interactions — see all 179 on the Hordenine page.

Minor

149 interactions

Showing 60 of 149 minor interactions — see all 149 on the Hordenine page.

No interaction 2,501 drugs checked — show the list

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

Showing the 60 most looked-up of 2,501 medications checked with no known interaction — see the full Hordenine list.

See the full Hordenine interactions page
See every supplement checked against Acetaminophen, Caffeine, Codeine, 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
Hordenine monograph › Uses, safety, and every drug interaction in one place Acetaminophen, Caffeine, Codeine supplement interactions › Every supplement checked against Acetaminophen, Caffeine, Codeine, 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 Hordenine and Acetaminophen, Caffeine, Codeine Together: Common Questions

Can you take Hordenine with Acetaminophen, Caffeine, Codeine?
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 Hordenine and Acetaminophen, Caffeine, Codeine?
Acetaminophen, Caffeine, Codeine belongs to more than one drug category, and Hordenine 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 Hordenine and Acetaminophen, Caffeine, Codeine 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

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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.