Drug & supplement interaction

American Pawpaw + Fluorouracil

Fluorouracil brand names: Efudex, Tolak.

Minor Interaction
The bottom line Minor

American Pawpaw has a minor interaction with Fluorouracil. American pawpaw (Asimina triloba) contains Annonacin, a natural compound that has been investigated for its potential anticancer effects.

Read the full interaction report
SeverityMinor
LikelihoodUnlikely
EvidenceC
What do Severity, Likelihood & Evidence mean?
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Interaction report

American Pawpaw and Fluorouracil

Here is the interaction we found between these two, with the evidence behind it.

Minor

Antineoplastics

Why this applies to Fluorouracil

Fluorouracil falls under Antineoplastics — the group American Pawpaw interacts with.

American pawpaw (Asimina triloba) contains Annonacin, a natural compound that has been investigated for its potential anticancer effects. Laboratory studies suggest that Annonacin may inhibit or prevent the growth and spread of tumors or malignant cells by disrupting mitochondrial function, leading to cell death (source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6672878/; https://www.nature.com/articles/s41419-018-0772-x). It is currently unknown how American pawpaw may interact, if at all, with prescription antineoplastic drugs. However, since both Annonacin and antineoplastic drugs can affect cell processes and metabolism, there is a theoretical risk of interactions that could affect treatment efficacy or increase the risk of side effects. Therefore, caution should be exercised when combining pawpaw with prescription antineoplastic drugs, and consulting with a healthcare professional is recommended before making changes to your medication regimen.
Severity Minor Likelihood Unlikely Evidence C

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 honest picture: we don't have solid human data showing that American pawpaw and fluorouracil actually interact. The concern is purely theoretical. Pawpaw's acetogenins (like annonacin) can disrupt how cells make energy in lab dishes, and fluorouracil already works hard to interfere with cancer cell growth. Stacking two things that both poke at cell metabolism could in theory change how well treatment works or add to side effects, but nobody has actually proven this.

With a chemo drug like this, I'd play it safe. Fluorouracil can cause mouth sores, diarrhea, low blood counts, and skin reactions, and you don't want anything muddying that picture. Please don't start pawpaw without first running it by your oncologist or pharmacist.

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

American Pawpaw Also Interacts With Other Medications

American Pawpaw has 24 minor known drug interactions in our database — the Fluorouracil one above is one of them. If you take anything else, check it against the full list below.

Taking anything else?

Check Another of Your Medications Against American Pawpaw

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

Everything else you take

See Every Supplement That Interacts With Fluorouracil

This page covers American Pawpaw only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Fluorouracil page lists 26 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Alfalfa (moderate), Angelica Archangelica (moderate), Arrach (moderate), Bergamot (moderate) and Bishop's Weed (moderate).

By severity: 23 moderate · 3 minor.

From our pharmacist’s overview on the Fluorouracil page

“If you are using fluorouracil cream (Efudex, Tolak) on sun-damaged skin, your skin is already primed to react to sunlight, and that is where most of its supplement interactions sit. Of the 26 ingredients on file, 20 can make skin more sun-sensitive on their own, chlorophyll, chlorella, and bergamot oil among them, so pairing one with t…”

Reviewed by 2 · Jul 18, 2026

Open the Fluorouracil interaction page

How much people look this up

Where American Pawpaw and Fluorouracil 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 American Pawpaw
Steady interest

#1,412 of 1,452 supplements looked up here in the last 7 days

29 days ago today
Medication Fluorouracil
Steady interest

#2,063 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 American Pawpaw

What is American Pawpaw?

American Pawpaw
  • Anticancer interest
  • Lice and head lice treatment (topical)
  • Traditional digestive remedy
  • General wellness/antioxidant
  • Insecticide (historical seed use)

American pawpaw is a North American fruit tree whose leaves, twigs, and seeds contain compounds called acetogenins that have shown cancer-cell-killing activity in laboratory studies. However, strong human evidence for any health benefit is lacking, and the seeds, bark, and unripe parts can be toxic, so supplements should be used cautiously and only under professional guidance.

Read the full American Pawpaw monograph & all interactions
Medication

About Fluorouracil Injection

What Is Fluorouracil Injection Used For?

Brand names: Efudex, Tolak

Fluorouracil Injection is used to treat four types of adenocarcinoma (a common form of cancer that begins in glandular cells): cancer of the colon and rectum, breast cancer, stomach (gastric) cancer, and pancreatic cancer.

It is nearly always given as part of a combination chemotherapy regimen alongside other cancer medicines, and the specific drugs paired with it depend on which cancer is being treated.

See full Fluorouracil Injection drug information
Keep checking

Other Drugs & American Pawpaw

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

0Major
0Moderate
24Minor
2,805No known interaction
Minor

24 interactions

No interaction 2,805 drugs checked — show the 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 American Pawpaw and Fluorouracil Together: Common Questions

Can you take American Pawpaw with Fluorouracil?
There is only a minor interaction, which is usually not serious. Read the full details on this page and confirm with your pharmacist before combining them.
How serious is the American Pawpaw and Fluorouracil interaction?
We rate it Minor. This interaction is generally not clinically significant, but it remains worth noting and discussing with your pharmacist.

Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy

Still Have a Question About Fluorouracil and American Pawpaw?

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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.