Drug & supplement interaction

American Pawpaw + Hydroxyurea

Hydroxyurea brand names: Droxia, Hydrea, Siklos, Xromi.

Minor Interaction
The bottom line Minor

American Pawpaw has a minor interaction with Hydroxyurea. 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 Hydroxyurea

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

Minor

Antineoplastics

Why this applies to Hydroxyurea

Hydroxyurea 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 actually know whether American pawpaw interacts with hydroxyurea in real people. The concern is purely theoretical. Pawpaw contains acetogenins like annonacin that, in lab dishes, can damage the energy factories (mitochondria) inside cells. Hydroxyurea works in its own way, by blocking an enzyme cells need to copy their DNA. Both touch cell growth and metabolism, so on paper there's a chance of overlapping effects.

What that could mean is hard to predict. It might add to hydroxyurea's side effects (think low blood counts, fatigue, nausea, mouth sores), or it could theoretically change how well your treatment works. Since this is unproven and pawpaw's seeds and bark can be toxic, please don't start it without first checking with 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 Hydroxyurea 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.

From our Q&A

Questions About American Pawpaw or Hydroxyurea

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers American Pawpaw or Hydroxyurea, not necessarily both, but if one is close to what you were about to ask it will usually go further than a database entry can:

Not quite your question? Ask our pharmacists directly — it is free, there is no account required, and answers usually come back within 24 hours.

Everything else you take

See Every Supplement That Interacts With Hydroxyurea

This page covers American Pawpaw only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Hydroxyurea page lists 18 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Coffee Charcoal (moderate), European Mandrake (moderate), Glucomannan (moderate) and Guar Gum (moderate).

By severity: 1 major · 7 moderate · 10 minor.

From our pharmacist’s overview on the Hydroxyurea page

“People take hydroxyurea (Droxia, Hydrea, Siklos, Xromi) for serious reasons, most often sickle cell disease or certain blood cancers, and it only works if a steady dose reaches the bloodstream. That is exactly what nearly all 18 supplements listed here can undermine, so this page earns real vigilance rather than a skim.”

Reviewed by 2 · Jul 18, 2026

Open the Hydroxyurea interaction page

How much people look this up

Where American Pawpaw and Hydroxyurea 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

#1,167 of 1,452 supplements looked up here in the last 7 days

29 days ago today
Medication Hydroxyurea
Top 5%

#39 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 Hydroxyurea

What Is Hydroxyurea Used For?

Brand names: Droxia, Hydrea, Siklos, Xromi

Hydroxyurea is used for several serious conditions. Droxia, Siklos, and Xromi are each indicated to reduce the frequency of painful crises and reduce the need for blood transfusions in patients with sickle cell anemia who have recurrent moderate to severe painful crises. Siklos is approved for adults and children 2 years and older; Xromi is approved for children 6 months and older; Droxia is approved for adults.

Hydrea capsules and Hydroxyurea capsules are indicated for resistant chronic myeloid leukemia and for locally advanced squamous cell carcinomas of the head and neck (excluding the lip) when used together with chemoradiation.

See full Hydroxyurea 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 Hydroxyurea Together: Common Questions

Can you take American Pawpaw with Hydroxyurea?
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 Hydroxyurea 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 Hydroxyurea 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.