Drug & supplement interaction

Clove + Aspirin, Butalbital, Caffeine, Codeine Phosphate

Aspirin, Butalbital, Caffeine, Codeine Phosphate brand name: Fiorinal w/ Codeine.

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

Aspirin, Butalbital, Caffeine, Codeine Phosphate falls into 4 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
Interactions4
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Clove and Aspirin, Butalbital, Caffeine, Codeine Phosphate

These two interact in 4 distinct ways. Each one is explained separately below.

Why Are There 4 Interactions?

Clove interacts with whole categories of medication. Aspirin, Butalbital, Caffeine, Codeine Phosphate falls into 4 of those categories, so it can interact with Clove in 4 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 4

Why this applies to Aspirin, Butalbital, Caffeine, Codeine Phosphate

Aspirin, Butalbital, Caffeine, Codeine Phosphate 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: the codeine in Fiorinal with Codeine is a prodrug. Your body has to convert it into morphine using a liver enzyme called CYP2D6 before it can relieve much pain. Lab studies suggest eugenol, the main compound in clove, can block that very enzyme. So in theory, heavy clove use could mean less codeine gets turned into morphine, leaving you with weaker pain relief.

I want to be honest about how thin this evidence is. It comes from test-tube research only and has never been shown in actual people. Normal cooking amounts of clove almost certainly won't matter. If you're using concentrated clove oil or supplements, just mention it to your pharmacist or doctor before changing anything.

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 4

Aspirin, Butalbital, Caffeine, Codeine Phosphate 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 piece that matters with your Fiorinal with Codeine combo: the caffeine in it is cleared by a liver enzyme called CYP1A2. In lab studies, eugenol (the main compound in clove) can slow that enzyme down. If that happened in real life, caffeine could hang around longer, which might mean more jitteriness, a racing heart, restlessness, or trouble sleeping.

I want to be straight with you, though: this is only seen in test-tube research, not in actual people, so it's mostly theoretical. The aspirin, butalbital, and codeine parts aren't really affected by this pathway. Normal cooking amounts of clove are very unlikely to do anything. Concentrated clove oil or supplements are a different story, so just run those 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 4

Aspirin, Butalbital, Caffeine, Codeine Phosphate 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

Here's the gist for Fiorinal with Codeine. Lab studies (not people) suggest the eugenol in clove may slow down a liver enzyme called CYP3A4. A couple of pieces in this combo lean on that enzyme, especially the butalbital and partly the codeine. In theory, slowing it could let those levels drift up a bit, which might mean more drowsiness, dizziness, slowed breathing, or feeling overly sedated.

One twist: codeine is a prodrug that mainly needs a different enzyme (CYP2D6) to turn into its active painkiller, so the clove effect here is mostly theoretical and based only on test-tube data. Normal cooking amounts of clove are very unlikely to matter. If you're using concentrated clove oil or supplements, 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
Minor

ANTICOAGULANT/ANTIPLATELET DRUGS

4 of 4

Aspirin, Butalbital, Caffeine, Codeine Phosphate also falls under ANTICOAGULANT/ANTIPLATELET DRUGS.

Theoretically, clove oil may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Laboratory research suggests that eugenol, a constituent of clove, has antiplatelet activity. This interaction has not been reported in humans.
Severity Minor Likelihood Unlikely Evidence D

Interaction has been demonstrated in animal or in lab research but has been shown not to occur in humans..

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the connection worth knowing about. This combination pill (Fiorinal with Codeine) contains aspirin, which already thins the blood a little by making platelets less sticky. Clove's main compound, eugenol, has shown a similar blood-thinning effect in lab studies only, so stacking the two could in theory add up and slightly raise your chance of bruising, nosebleeds, or stomach irritation.

The honest take: this is a theoretical concern that has never actually been reported in people, and it's rated minor. A sprinkle of clove in cooking is a non-issue. Concentrated clove oil or supplements taken regularly are where I'd pay attention. Before adding any clove product, just run it by your pharmacist or doctor, especially if you bleed or bruise easily.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Chen SJ, Wang MH, Chen IJ. Antiplatelet and calcium inhibitory properties of eugenol and sodium eugenol acetate. Gen Pharmacol 1996;27:629-33. PubMed
  2. Srivastava, K. C. and Malhotra, N. Acetyl eugenol, a component of oil of cloves (Syzygium aromaticum L.) inhibits aggregation and alters arachidonic acid metabolism in human blood platelets. Prostaglandins Leukot.Essent.Fatty Acids 1991;42(1):73-81. PubMed
  3. Saeed, S. A. and Gilani, A. H. Antithrombotic activity of clove oil. J Pak Med Assoc 1994;44(5):112-115.
  4. Srivastava, K. C. Antiplatelet principles from a food spice clove (Syzygium aromaticum L) [corrected]. Prostaglandins Leukot.Essent.Fatty Acids 1993;48(5):363-372.

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 Aspirin, Butalbital, Caffeine, Codeine Phosphate 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. Aspirin, Butalbital, Caffeine, Codeine Phosphate)
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 Aspirin, Butalbital, Caffeine, Codeine Phosphate

This page covers Clove only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Aspirin, Butalbital, Caffeine, Codeine Phosphate page lists 398 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 Danshen (major).

By severity: 17 major · 334 moderate · 47 minor.

From our pharmacist’s overview on the Aspirin, Butalbital, Caffeine, Codeine Phosphate page

“Fiorinal with Codeine packs four active drugs into one capsule, and I would treat its supplement list with genuine wariness rather than a quick skim. The aspirin component is why roughly half of the 398 ingredients on file raise bleeding risk, while the codeine and butalbital explain a second large cluster that deepens sedation, someti…”

Reviewed by 2 · Jul 18, 2026

Open the Aspirin, Butalbital, Caffeine, Codeine Phosphate 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 Aspirin, Butalbital, Caffeine, Codeine Phosphate 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 Aspirin, Butalbital, Caffeine, Codeine Phosphate 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%

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

29 days ago today
Medication Aspirin, Butalbital, Caffeine, Codeine Phosphate
Top 25%

#379 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 Aspirin, Butalbital, Caffeine, Codeine Phosphate, 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 Aspirin, Butalbital, Caffeine, Codeine Phosphate supplement interactions › Every supplement checked against Aspirin, Butalbital, Caffeine, Codeine Phosphate, 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 Aspirin, Butalbital, Caffeine, Codeine Phosphate Together: Common Questions

Can you take Clove with Aspirin, Butalbital, Caffeine, Codeine Phosphate?
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 4 interactions listed for Clove and Aspirin, Butalbital, Caffeine, Codeine Phosphate?
Aspirin, Butalbital, Caffeine, Codeine Phosphate 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 Aspirin, Butalbital, Caffeine, Codeine Phosphate 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 Aspirin, Butalbital, Caffeine, Codeine Phosphate 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.