Drug & supplement interaction

Breadfruit + 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 2 drug categories that Breadfruit can interact with; the most serious is rated moderate. Breadfruit might increase the levels of drugs metabolized by uridine diphosphoglucuronosyl transferase (UGT).

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions2
EvidenceD
What do Severity, Likelihood & Evidence mean?
Know someone taking this? Share
Facebook Post Reddit Email
On this page
Interaction report

Breadfruit and Acetaminophen, Butalbital, Caffeine, Codeine

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

Why Are There 2 Interactions?

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

Moderate

GLUCURONIDATED DRUGS

1 of 2

Why this applies to Acetaminophen, Butalbital, Caffeine, Codeine

Acetaminophen, Butalbital, Caffeine, Codeine falls under GLUCURONIDATED DRUGS — the group Breadfruit interacts with.

Breadfruit might increase the levels of drugs metabolized by uridine diphosphoglucuronosyl transferase (UGT). So far, this interaction has not been reported in humans. However, in vitro evidence shows that the breadfruit constituent artocarpin inhibits UGT. Theoretically, this could decrease the clearance and increase levels of glucuronidated drugs. Some drugs that are metabolized through glucuronide conjugation include acetaminophen (Tylenol, others) and oxazepam (Serax), haloperidol (Haldol), lamotrigine (Lamictal), morphine (MS Contin, Roxanol), zidovudine (AZT, Retrovir), and 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

Here's the thing to know about this combo. Your medication contains acetaminophen (the Tylenol part), which your body partly clears through a process called glucuronidation, run by UGT enzymes. A compound in breadfruit called artocarpin appears to block those enzymes in lab tests. In theory, that could slow acetaminophen's breakdown and let it build up a bit higher than usual.

Now, I want to be honest about how soft this evidence is. So far this has only been seen in test tubes, never in actual people, and eating breadfruit as a food is very different from taking concentrated leaf extracts. Higher acetaminophen levels are mainly a concern for the liver, so I wouldn't lose sleep over a meal. If you're using breadfruit leaf supplements regularly, just give your pharmacist a heads-up first.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Qu W, Liu X. Identification of cytochrome P450 isoforms involved in the metabolism of artocarpin and assessment of its drug-drug interaction. Biomed Chromatogr. 2018;32(4). PubMed
Minor

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

2 of 2

Acetaminophen, Butalbital, Caffeine, Codeine also falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES.

Theoretically, breadfruit might inhibit cytochrome P450 3A4 (CYP3A4) and increase levels of drugs metabolized by these enzymes; until more is known, use with caution. In vitro, the breadfruit constituent artocarpin can inhibit CYP3A4 enzymes. Also, animal research shows that breadfruit leaf extract can weakly inhibit CYP3A4 enzymes. However, it is unclear if this inhibitory activity causes a clinically meaningful effect on the metabolism of CYP3A4 substrates.
Some drugs metabolized by CYP3A4 include amitriptyline (Elavil), amiodarone (Cordarone), citalopram (Celexa), felodipine (Plendil), lansoprazole (Prevacid), ondansetron (Zofran), prednisone (Deltasone), sertraline (Zoloft), and many 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 thing about this combo pill (Fioricet with Codeine): a few of its pieces lean on a liver enzyme called CYP3A4 to be processed. Breadfruit, in test tube and animal studies only, looks like it might gently slow that enzyme down. If that happened in a person, drugs like the butalbital could clear a little slower and pile up, which might mean more drowsiness, dizziness, or feeling foggy and oversedated.

One twist worth knowing: codeine is a prodrug. Your body has to convert it (mostly through a different enzyme, CYP2D6) into the active painkiller, so the CYP3A4 angle isn't really the main driver for pain relief here. Honestly, the evidence behind all this is very thin, and eating breadfruit as food is unlikely to matter. Concentrated leaf teas or extracts are the bigger question mark, so check with your pharmacist before using those.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Nwokocha CR, Owu DU, McLaren M, et al. Possible mechanisms of action of the aqueous extract of Artocarpus altilis (breadfruit) leaves in producing hypotension in normotensive Sprague-Dawley rats. Pharm Biol. 2012;50(9):1096-102.
  2. Qu W, Liu X. Identification of cytochrome P450 isoforms involved in the metabolism of artocarpin and assessment of its drug-drug interaction. Biomed Chromatogr. 2018;32(4). 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

Breadfruit Also Interacts With Other Medications

Breadfruit has 437 moderate, 504 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 437 Minor 504 No known interaction 1,889 (incl. Acetaminophen, Butalbital, Caffeine, Codeine)
Taking anything else?

Check Another of Your Medications Against Breadfruit

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

Everything else you take

See Every Supplement That Interacts With Acetaminophen, Butalbital, Caffeine, Codeine

This page covers Breadfruit 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

How much people look this up

Where Breadfruit 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 Breadfruit
Top half

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

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

#100 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 Breadfruit

What is Breadfruit?

  • Source of nutrition and energy
  • High blood pressure
  • Diabetes and blood sugar support
  • Inflammation and joint discomfort
  • Skin conditions

Breadfruit is a starchy tropical fruit eaten as a staple food, and its leaves are used in traditional medicine for conditions like high blood pressure and diabetes. As a food it is nutritious and generally safe, but the medicinal use of leaf teas or extracts has very little human research to back it up. Talk with your pharmacist or doctor before using breadfruit products for a health condition.

Read the full Breadfruit monograph & all interactions
Keep checking

Other Drugs & Breadfruit

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

0Major
437Moderate
504Minor
1,888No known interaction
437 Moderate 504 Minor 1,888 No interaction
Moderate

437 interactions

Showing 60 of 437 moderate interactions — see all 437 on the Breadfruit page.

Minor

504 interactions

Showing 60 of 504 minor interactions — see all 504 on the Breadfruit page.

No interaction 1,888 drugs checked — show the list

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

Showing the 60 most looked-up of 1,888 medications checked with no known interaction — see the full Breadfruit list.

See the full Breadfruit 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
Breadfruit 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 Breadfruit and Acetaminophen, Butalbital, Caffeine, Codeine Together: Common Questions

Can you take Breadfruit 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 2 interactions listed for Breadfruit and Acetaminophen, Butalbital, Caffeine, Codeine?
Acetaminophen, Butalbital, Caffeine, Codeine belongs to more than one drug category, and Breadfruit 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 Breadfruit 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

Still Have a Question About Acetaminophen, Butalbital, Caffeine, Codeine and Breadfruit?

Our pharmacists answer your medication & supplement questions — free.

Ask a pharmacist

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.