Drug & supplement interaction

Clove + Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine

Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine brand name: Hycomine Compound.

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

Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine falls into 3 drug categories that Clove can interact with; the most serious is rated moderate. Theoretically, concomitant use of clove may increase levels of drugs metabolized by CYP2D6.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions3
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Clove and Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine

These two interact in 3 distinct ways. Each one is explained separately below.

Why Are There 3 Interactions?

Clove interacts with whole categories of medication. Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine falls into 3 of those categories, so it can interact with Clove in 3 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES

1 of 3

Why this applies to Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine

Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine falls under CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES — the group Clove interacts with.

Theoretically, concomitant use of clove may increase levels of drugs metabolized by CYP2D6.
In vitro research shows that eugenol, the principal constituent of clove, can inhibit CYP2D6 in a dose-dependent manner. 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 wrinkle with this combo product: the hydrocodone in it is a prodrug. Your body uses an enzyme called CYP2D6 to convert part of it into hydromorphone, which adds to the pain relief. Lab studies suggest eugenol, the main compound in clove, can slow that same enzyme down. In theory, that could mean slightly less of that converted pain relief from the hydrocodone piece.

I want to be honest about the evidence here. This effect has only shown up in test tube studies, never in real people, so it's mostly theoretical. Sprinkling clove on your food won't do anything. Concentrated clove oil or supplements are where any concern would come from. If you're using clove medicinally, just run it by your pharmacist or doctor first.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Alharbi NFM, Ahad A, Bin Jardan YA, Al-Jenoobi FI. Effect of eugenol on cytochrome P450 1A2, 2C9, 2D6, and 3A4 activity in human liver microsomes. Saudi Pharm J 2024;32(7):102118. PubMed
Moderate

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES

2 of 3

Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine also falls under CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES.

Theoretically, concomitant use of clove may increase levels of drugs metabolized by CYP1A2.
In vitro research shows that eugenol, the principal constituent of clove, can inhibit CYP1A2 in a dose-dependent manner,. 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 practical scoop on this combo product (which pairs acetaminophen, caffeine, chlorpheniramine, hydrocodone, and phenylephrine). The one ingredient most affected by clove is the caffeine, which your body clears using an enzyme called CYP1A2. Lab studies suggest eugenol, the main compound in clove, may slow that enzyme down. In theory, that could let caffeine linger a bit longer, possibly nudging up jitteriness, a racing heartbeat, or trouble sleeping.

The important thing to know: this has only been seen in test-tube studies, not in real people, so the risk looks small. Normal cooking amounts of clove almost certainly won't matter. Concentrated clove oil or supplements are where I'd be a little more cautious. If you use those regularly, just give your pharmacist or doctor a quick heads-up.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Alharbi NFM, Ahad A, Bin Jardan YA, Al-Jenoobi FI. Effect of eugenol on cytochrome P450 1A2, 2C9, 2D6, and 3A4 activity in human liver microsomes. Saudi Pharm J 2024;32(7):102118. PubMed
Moderate

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

3 of 3

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

Theoretically, concomitant use of clove may increase levels of drugs metabolized by CYP3A4.
In vitro research shows that eugenol, the principal constituent of clove, can inhibit CYP3A4 in a dose-dependent manner. 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-and-pain product contains hydrocodone, an opioid that your body partly relies on the liver enzyme CYP3A4 to process. Lab studies suggest that eugenol, the main oil in clove, can slow down CYP3A4. In theory, that could let hydrocodone build up a bit, nudging up its effects like extra drowsiness, dizziness, constipation, or slowed breathing. The same enzyme also helps clear chlorpheniramine, so sedation could feel stronger too.

Here's the honest part: this is only seen in test-tube research, not in real people, so the actual risk is likely small. Cooking with clove won't matter, but concentrated clove oil or supplements are a different story. If you use those regularly, check with your pharmacist or doctor first.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Alharbi NFM, Ahad A, Bin Jardan YA, Al-Jenoobi FI. Effect of eugenol on cytochrome P450 1A2, 2C9, 2D6, and 3A4 activity in human liver microsomes. Saudi Pharm J 2024;32(7):102118. 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

Clove Also Interacts With Other Medications

Clove has 916 moderate, 60 minor known drug interactions in our database — the Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine one above is among them. If you take anything else, check it against the full list below.

Moderate 916 Minor 60 No known interaction 1,854 (incl. Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine)
Taking anything else?

Check Another of Your Medications Against Clove

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

Everything else you take

See Every Supplement That Interacts With Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine

This page covers Clove only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine page lists 339 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: 17 major · 276 moderate · 46 minor.

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

“If you've been prescribed Hycomine Compound (acetaminophen, caffeine, chlorpheniramine, hydrocodone, and phenylephrine) for a hard cough or cold, this list deserves real attention, since 17 of the 339 flagged supplements are rated major and most of those magnify what the medicine already does. Anything sedating, alcohol included, stack…”

Reviewed by 2 · Jul 18, 2026

Open the Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine interaction page

One more smart check

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

We hold 59 real supplement products containing Clove, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Clove. Your product may carry other ingredients that interact with Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine too, on top of Clove — 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 Clove and Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, 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 Clove
Top 25%

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

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

#704 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 Clove

What is Clove?

Clove
  • Toothache and oral pain
  • Digestive upset
  • Antimicrobial and antifungal
  • Cough and respiratory complaints
  • Flavoring in food and drinks

Clove is a common cooking spice that is also used in traditional medicine, especially as a topical numbing agent for tooth pain thanks to its main compound, eugenol. Food amounts are generally safe, but concentrated clove oil and supplements can be irritating or toxic if overused, and human evidence for most health claims is limited. Talk to your pharmacist or doctor before using clove medicinally, especially in children or during pregnancy.

Read the full Clove monograph & all interactions
Keep checking

Other Drugs & Clove

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

0Major
916Moderate
60Minor
1,853No known interaction
916 Moderate 60 Minor 1,853 No interaction
Moderate

916 interactions

Showing 60 of 916 moderate interactions — see all 916 on the Clove page.

Minor

60 interactions

No interaction 1,853 drugs checked — show the list

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

Showing the 60 most looked-up of 1,853 medications checked with no known interaction — see the full Clove list.

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

Can you take Clove with Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, 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 3 interactions listed for Clove and Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine?
Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine belongs to more than one drug category, and Clove 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 Clove and Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, 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, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine and Clove?

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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.