Drug & supplement interaction

Clove + Acetaminophen, Butalbital, Caffeine, Codeine

Acetaminophen, Butalbital, Caffeine, Codeine brand names: Esgic with Codeine, Fioricet w/ Codeine.

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

Acetaminophen, Butalbital, Caffeine, Codeine 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, Butalbital, Caffeine, Codeine

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, Butalbital, Caffeine, Codeine 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, Butalbital, Caffeine, Codeine

Acetaminophen, Butalbital, Caffeine, Codeine 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 pill: the codeine part is a prodrug. Your body has to convert it into morphine using a liver enzyme called CYP2D6 before it actually relieves pain. Lab studies suggest that eugenol, the main compound in clove, can slow down that same enzyme. So in theory, heavy clove use could mean less codeine gets turned into its active form, leaving you with weaker pain relief.

I want to be honest about the evidence though. This has only been seen in test-tube studies, never in real people, so it's mostly theoretical. Cooking with clove almost certainly won't matter. Concentrated clove oil or supplements are the bigger question mark. If you use those regularly and notice your pain isn't well controlled, check in with your pharmacist or doctor.

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, Butalbital, Caffeine, Codeine 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

This combination pill has a lot going on, but the part that lines up with clove is the caffeine. Caffeine is cleared by a liver enzyme called CYP1A2, and lab studies suggest eugenol (the main compound in clove) can slow that enzyme down. If that happened in a person, caffeine could linger longer, which might mean more jitteriness, a racing heart, or trouble sleeping. Honestly, this is mostly theoretical and comes only from test-tube work, not from real patients.

The good news: the small amount of clove you get from cooking is very unlikely to matter. Concentrated clove oil or supplements are where I'd be more cautious. 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 3A4 (CYP3A4) SUBSTRATES

3 of 3

Acetaminophen, Butalbital, Caffeine, Codeine 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 pill has a few moving parts, and clove may touch the one called butalbital, a barbiturate cleared in part by a liver enzyme called CYP3A4. In lab dishes, eugenol (the main compound in clove) slows that enzyme down. If that held true in people, butalbital could build up a little, which might mean more drowsiness, dizziness, or feeling foggy and sluggish.

Here's the honest part: this is only seen in test-tube and animal studies, never confirmed in humans, so it's mostly theoretical. The caffeine piece also leans on a different enzyme, so it's less of a concern here. Sprinkling clove on food won't matter. If you're using concentrated clove oil or supplements regularly, just mention it to your pharmacist or doctor.

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, Butalbital, Caffeine, Codeine 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, Butalbital, Caffeine, Codeine)
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, Butalbital, Caffeine, Codeine

This page covers Clove only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Butalbital, Caffeine, Codeine page lists 305 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 · 245 moderate · 45 minor.

Open the Acetaminophen, Butalbital, Caffeine, Codeine 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, Butalbital, Caffeine, Codeine 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, Butalbital, 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 Clove
Top 25%

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

29 days ago today
Medication Acetaminophen, Butalbital, Caffeine, Codeine
Top half

#911 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, Butalbital, 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
Clove monograph › Uses, safety, and every drug interaction in one place Acetaminophen, Butalbital, Caffeine, Codeine supplement interactions › Every supplement checked against Acetaminophen, Butalbital, 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 Clove and Acetaminophen, Butalbital, Caffeine, Codeine Together: Common Questions

Can you take Clove with Acetaminophen, Butalbital, 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 3 interactions listed for Clove and Acetaminophen, Butalbital, Caffeine, Codeine?
Acetaminophen, Butalbital, Caffeine, Codeine 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, Butalbital, 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.