Drug & supplement interaction

Breadfruit + Acetaminophen, Caffeine, Codeine

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

Moderate Interaction
The bottom line Moderate

Acetaminophen, 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?
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Interaction report

Breadfruit and Acetaminophen, 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, 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, Caffeine, Codeine

Acetaminophen, 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 gist for this combo pill (which pairs acetaminophen, caffeine, and codeine). One of breadfruit's compounds, called artocarpin, was shown in lab dish studies only to slow down an enzyme system called UGT. Your body uses UGT to clear out acetaminophen and to process morphine, the active form codeine turns into. In theory, if that clearance slows, levels of these drugs could creep up, which might mean more drowsiness, nausea, constipation, or added strain on the liver from the acetaminophen.

That said, this has never actually been seen in people, and eating breadfruit as a food almost certainly won't cause trouble. Concentrated leaf teas or extracts are the bigger unknown. If you want to use those regularly, just run it by your pharmacist or doctor first.

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, 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 to know about this combo pill: the codeine part is actually a prodrug. Your body has to convert it into morphine before it does much for pain. That activation depends mostly on a different enzyme (CYP2D6), not the CYP3A4 enzyme that breadfruit may gently block in lab studies. CYP3A4 plays more of a side role, helping route codeine down an inactive path.

So even in theory, slowing CYP3A4 wouldn't cause a big or dangerous shift here. At most you might nudge a touch more codeine toward becoming morphine, which could mean slightly more drowsiness or constipation. But this is based only on test-tube and animal data, and eating breadfruit as food is very unlikely to matter. If you're using concentrated leaf extracts, just run it by your pharmacist first.

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, 506 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.

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, Caffeine, Codeine

This page covers Breadfruit 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

How much people look this up

Where Breadfruit 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 Breadfruit
Top half

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

29 days ago today
Medication Acetaminophen, Caffeine, Codeine
Top 10%

#224 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
506Minor
1,886No known interaction
Moderate

437 interactions

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

Minor

506 interactions

Showing 60 of 506 minor interactions — see all 506 on the Breadfruit page.

No interaction 1,886 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 1,886 medications checked with no known interaction — see the full Breadfruit list.

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

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Pharmacist Counseling Corner

Taking Breadfruit and Acetaminophen, Caffeine, Codeine Together: Common Questions

Can you take Breadfruit 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 Breadfruit and Acetaminophen, Caffeine, Codeine?
Acetaminophen, 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, 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.