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Dietary supplement

Papaya Enzyme Ingredients & Drug Interactions

by 21st Century

Tablet Or Pill Category: Other Combinations
Most serious interaction: Moderate
The interaction bottom line Most serious interaction: Moderate

Papaya Enzyme is a dietary supplement by 21st Century with 1 active ingredient. Its ingredients are commonly taken for digestive upset and indigestion, constipation, wound and skin care (topical).Based on those ingredients, 231 medications have a known interaction with it, the most serious rated moderate. The ingredients most likely to interact are Papaya Enzyme Blend. Use the checker below to test your specific medication, or read the full HelloPharmacist Interaction Report.

HelloPharmacist Scorecard of Papaya Enzyme by 21st Century

Our pharmacy team’s full take, with four database checks built into the cards below — a summary of what is known, not a grade of the product itself.

From our pharmacy team — supplement deep dive

What’s inside

Low disclosure
Ingredient Transparency · database check
Low

Most active ingredients don't disclose an individual amount — you can't tell how much of each you're getting.

Why this rating?
  • The label discloses an exact amount for 0 of its 3 active ingredients.
  • “Papaya Enzyme Blend” is a proprietary blend — the label gives one combined amount (22 mg) without saying how much of each component you get.

This product has 3 active ingredients: bromelain (a protein-digesting enzyme from pineapple), papain (a similar enzyme from papaya), and papaya powder. Together they're meant to act as digestive enzymes.

The tablet also contains inactive ingredients—sucrose, sorbitol, natural pineapple flavor, cellulose, stearic acid, silicon dioxide, yellow dye, and magnesium stearate—which serve as sweeteners, binders, and flow agents.

Does it work?

Not established
Evidence for Intended Use · database check
By FDA rules, dietary supplements can’t claim to treat, cure, or prevent disease — so labels speak in careful marketing language. We discern each product’s intended use from its name, label claims, and label statements, then grade the clinical evidence for that use. How these ratings are computed
Not established

The graded evidence we hold for these ingredients covers different conditions than the ones this product is marketed for, so there's no established rating for its stated use.

Why this rating?
  • The label markets this product for: Digestive enzyme support.
  • We looked for evidence on: Exercise-induced muscle soreness, Postoperative pain, Postoperative swelling, Sprains, Wound healing, Protein digestion — and 1 related terms.
  • The closest evidence on file: Papain is rated "Insufficient Reliable Evidence To Rate" for Exercise-induced muscle soreness (Natural Medicines).
  • Also on file: Papain is rated "Insufficient Reliable Evidence To Rate" for Wound healing.
  • Also on file: Papaya is rated "Insufficient Reliable Evidence To Rate" for Wound healing.

The evidence we hold for all three active ingredients rates as insufficient to make a clear call. Bromelain has been studied for hay fever, burns, cancer, and a few other conditions, but the data doesn't establish that it works.

The same is true for papain and papaya powder—they're studied for things like exercise soreness, infections, and skin conditions, but we don't have reliable evidence they deliver results for any of those uses.

The evidence, ingredient by ingredient Papaya Bromelain Papain

How safe is it?

Well-documented data
Safety Information · database check
Well characterized

Adverse-effect, pregnancy, and general safety data are on file for most of these ingredients.

Why this rating?
  • We hold adverse-effect (side-effect) data for 3 of the 3 matched ingredients.
  • Pregnancy & breastfeeding safety ratings cover 3 of 3.
  • General safety write-ups exist for 3 of 3.
  • Remember: this measures how much safety information exists. Thin data is not the same as being safe.

Bromelain and papain are both generally well tolerated when used short-term, but long-term safety data is limited. The most common side effects from bromelain taken by mouth are diarrhea, flatulence, stomach upset, and headache.

Papain may trigger allergic reactions in sensitive people—itching, watery eyes, sneezing, and diarrhea—and high doses can cause serious harm like esophageal perforation or severe stomach inflammation. Both ingredients may cause respiratory allergic reactions if you inhale them as dust.

Papaya powder as a food is well tolerated, but concentrated supplements are less well studied. During pregnancy, the safety data advises against bromelain and concentrated papain or unripe papaya products.

For papaya powder during pregnancy, some sources caution against large amounts. While breastfeeding, bromelain and papain should be avoided due to insufficient safety information; data on papaya powder while breastfeeding is not on file.

Side effects, ingredient by ingredient Papaya Bromelain Papain

Meds to double-check

Moderate interaction found
Known Interaction Concern · database check
Moderate identified

The most serious documented interaction for these ingredients is Moderate. Check your medications for a personalized result.

Why this rating?
  • 3 of the 3 matched ingredients can interact with medications — Papain, Papaya, Bromelain.
  • The most serious interaction on file is rated Moderate.
  • Some involve high-stakes drug classes: anticoagulant / antiplatelet drugs; diabetes medications.
  • For scale: 231 individual medications appear in the full list. A big number alone doesn't make a product dangerous — what matters is whether YOUR medication is on it, so run yours through the interaction checker on this page.

Before taking this product, double-check with your pharmacist if you take blood thinners like warfarin or antiplatelet drugs like aspirin (Moderate risk of increased bleeding), diabetes medications (Moderate risk of low blood sugar), amiodarone for heart rhythm (Moderate risk of increased drug levels), levothyroxine for thyroid (Moderate risk of reduced effectiveness), or tetracycline antibiotics (Minor risk of increased levels).

Check your own medication Run your meds through the checker above

The bottom line

Scorecard at a glanceFormula with limited ingredient disclosure with no established evidence rating for its marketed use. Moderate medication interactions have been identified, and safety information is well characterized.

If you're looking for a digestive enzyme and have no blood thinners, diabetes meds, heart drugs, or thyroid medication in your routine, this product is generally well tolerated short-term. But if you take any of those medications—or if you're pregnant or breastfeeding—talk with your pharmacist before you start.

The effectiveness evidence isn't strong for any condition, so be clear on why you want to try it.

Educational only — not medical advice; always confirm with your pharmacist. Our editorial policy · How we use AI

Assessment coverage: 3 of 3 active ingredients matched to our full ingredient reviews (monographs). Based on the product label dated Feb 23, 2025.

This Scorecard evaluates available label information, ingredient evidence, and known medication-safety considerations. It does not independently verify product identity, purity, potency, contamination, or manufacturing quality. How these ratings are computed

At a glance

General information

Key facts about Papaya Enzyme, straight from the product label.

Brand 21st Century
Barcode (UPC) 740985226629
Net contents 100 Tablet(s)
Market status On market
Date entered into DSLD Feb 23, 2025
DSLD ID 326340
Product type Other Combinations
Supplement form Tablet Or Pill
Dietary claims / uses All Other, Structure/Function
Intended target group(s) Adult (18 - 50 Years), Gluten Free
From the label
Everything in this section is reproduced from the manufacturer’s own product label — it’s the label speaking, not HelloPharmacist. We show it so you can see exactly what the maker states; we don’t verify or endorse those statements.

Supplement Facts

The label details for Papaya Enzyme by 21st Century, sourced from the NIH Dietary Supplement Label Database.

Supplement Facts

Daily Value (DV) Target Group(s):
Adults and children 4 or more years of age
Minimum serving Sizes:
1 Tablet(s)
Maximum serving Sizes:
1 Tablet(s)
Servings per container
100
UPC/BARCODE
740985226629
IngredientAmount% DV
Bromelain0 NP--
Papain0 NP--
Papaya, Powder0 NP--
Papaya Enzyme Blend22 mg--

Other ingredients: Sucrose, Sorbitol, Pineapple Flavor, Natural, Cellulose, Stearic Acid, Silicon Dioxide, FD&C Yellow #6, Magnesium Stearate

Tap any ingredient to jump to its full detail below.

Label statements
These statements are the manufacturer’s wording, reproduced from the product label — the label is saying it, not HelloPharmacist. We don’t verify or endorse them.
Suggested/Recommended/Usage/Directions

Directions: As a dietary supplement, adults chew one (1) tablet with any meal, three (3) times daily or as directed by a healthcare provider. Do not exceed recommended dosage. Individual results may vary.

Precautions

Do not exceed recommended dosage.

Warning: Consult a healthcare provider prior to use if pregnant, nursing, on medications, have a medical procedure.

Stop use and contact a physician if adverse reactions occur. Do not use if product appears to be tampered with or seal is broken.

Keep out of reach of children.

Storage

Store at room temperature.

Formulation

No added salt, yeast, preservatives or artificial flavors.

Chewable Digestive support

Gluten free

FDA Disclaimer Statement

These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.

FDA Statement of Identity

Dietary Supplement

Seals/Symbols

Guaranteed Quality Laboratory Tested

Formula

Papaya Enzyme is a delicious chewable tablet that supports digestive function.

See for yourself

Papaya Enzyme by 21st Century label

The label scan from the NIH Dietary Supplement Label Database. Tap to enlarge.

What’s inside

The Ingredients in Papaya Enzyme by 21st Century

This is the 1 active ingredient this product is made of. Select it to open its full monograph.

Serving size1 Tablet(s) Dosage formTablet Or Pill Servings per container100 Amounts shown are per serving.

Papaya Enzyme Blend

Interacts with
92 drugs
22 mg per serving

Papaya is a tropical fruit that is nutritious and generally safe to eat as food, and it contains an enzyme called papain used as a digestive aid and m...

Papaya Enzyme Blend monograph & interactions

Other (inactive) ingredients: Sucrose, Sorbitol, Pineapple Flavor, Natural, Cellulose, Stearic Acid, Silicon Dioxide, FD&C Yellow #6, Magnesium Stearate. These complete the product’s ingredient list but are not active constituents.

Interaction report

Papaya Enzyme by 21st Century Drug Interactions

Want to check YOUR meds against Papaya Enzyme?

Ask about interactions with your drugs in plain English — “Can I take it with lisinopril?” — and we find you the answer in seconds, ingredient by ingredient.

Go to the checker
231Drugs
212 Moderate 19 Minor

Ingredients driving the most interactions

Each ingredient & the kinds of drugs it affects

For each ingredient in Papaya Enzyme with known interactions, here are the types of medications it can affect. Open any type for the detail — or search your exact drug in the checker above.

Papaya Enzyme Blend4 drug types · 92 drugs

Amiodarone (Cordarone)

Theoretically, papaya extract may increase the levels and clinical effects of amiodarone.
Animal research in rats shows that a single oral dose of papaya extract, as well as multiple doses of papaya extract daily over 14 days, prior to a single dose of amiodarone delays the time to maximum amiodarone concentration. However, only the 14-day papaya extract regimen increases systemic amiodarone exposure by 60% to 70%. This interaction has not been reported in humans.

Likelihood Probable Evidence D
Antidiabetes Drugs

Concomitant use of antidiabetic drugs with fermented papaya can produce additive effects. It is unclear if other forms of papaya have the same effect.
A small low-quality clinical study in patients with type 2 diabetes who are taking glibenclamide shows that taking a fermented papaya preparation 3 grams daily for 2 months decreases fasting and postprandial blood glucose levels when compared to baseline. Additionally, of the 25 patients in the study, 9 required a reduction in glibenclamide dose.

Likelihood Probable Evidence B
Levothyroxine (Synthroid, Others)

Theoretically, consuming large quantities of papaya fruit can reduce the clinical effects of levothyroxine.
In one case-report, a 37-year-old male with a history of thyroidectomy who was stabilized on levothyroxine for 5 years presented with hypothyroidism after consuming 5-6 papaya fruits daily for 14 days during vacation. In a controlled re-challenge test involving 5-6 papayas daily, the patient remained euthyroid for 7 days, but developed mild hypothyroidism after 14 days. Both times, thyroid levels normalized 40-45 days after discontinuing papaya.

Likelihood Possible Evidence D
Warfarin (Coumadin)

Theoretically, concomitant use of warfarin with papain-containing papaya extract might increase the effects and side effects of warfarin.
In one case report, a patient previously stable on warfarin was found to have an international normalization ratio (INR) of 7.4, which was attributed to ingestion of a supplement containing papain from papaya extract.

Likelihood Possible Evidence D
The maker

Brand information

Manufacturer and brand details for Papaya Enzyme, from the product label.

21st Century

See all 21st Century products
Name
21st Century HealthCare, Inc.
Street Address
2119 S. Wilson St.
City
Tempe
State
AZ
ZipCode
85282
Web Address
21stcenturyvitamins.com
Pharmacist Counseling Corner

Papaya Enzyme by 21st Century: Common Questions

Does Papaya Enzyme by 21st Century interact with any medications?
Yes. Based on its ingredients, Papaya Enzyme has a known interaction with 231 medications. Use the checker to see how it interacts with a specific drug.
How can one product interact with so many drugs?
Papaya Enzyme contains a single active ingredient, and that one ingredient can interact with many different medications on its own. We check it against each medication and show the mechanism responsible.
Where does this information come from?
The product label data comes from the NIH Dietary Supplement Label Database (DSLD); the interaction data is built on the Natural Medicines database and reviewed by HelloPharmacist pharmacists.
Can I take this if I'm on warfarin?
No—both papain and papaya powder in this product may increase warfarin's effects and raise your bleeding risk. A case report documented a patient's INR spiking to 7.4 after taking papain. Talk to your doctor or pharmacist before taking any papaya enzyme product if you're on warfarin.
What are the most common side effects?
From bromelain, you might experience diarrhea, gas, stomach upset, or headache. Papain may cause allergic reactions—itchy eyes, sneezing, abdominal cramps, or diarrhea—especially if you're sensitive to it. Both are usually mild and short-term.
Is this safe during pregnancy?
No. The safety data advises against bromelain, papain, and concentrated papaya products during pregnancy. Talk with your doctor or pharmacist about whether it's right for you.
What does bromelain actually do?
Bromelain is a protein-digesting enzyme from pineapple meant to aid digestion. It's been studied for conditions like hay fever, burns, and cancer, but we don't have reliable evidence it works for any of them.
Will this work for my diabetes if I'm already on metformin?
Papaya powder in this product may lower blood sugar and could add to metformin's effect, potentially causing low blood sugar. Talk with your doctor or pharmacist before starting it.
Can I take this with my thyroid medication?
Papaya powder may reduce how well levothyroxine (thyroid medication) works. A case report documented a patient whose thyroid symptoms returned after eating 5–6 papaya fruits daily for two weeks. Check with your pharmacist before taking this supplement.

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

Not sure if Papaya Enzyme is safe with your meds?

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Label information is sourced from the NIH Dietary Supplement Label Database and reflects the product version on file; always read your actual product label. This page is for education only and is not a substitute for professional medical advice. Confirm with your pharmacist or doctor before combining supplements and medications.

Papaya Enzyme label
Sources

Sources & How We Checked

Papaya Enzyme's label data comes from the NIH Dietary Supplement Label Database; the ingredient interaction data is from the Natural Medicines database, reviewed by our pharmacists.

Content is written and reviewed by licensed HelloPharmacist pharmacists. See our data sources and editorial standards for how this information is built and checked.

The 44 references behind this product’s interaction data

Every citation that drives the interaction findings for this product’s ingredients, from the evidence-graded Natural Medicines (TRC Healthcare) database. Open an ingredient to browse its citations — links open the study on PubMed or the publisher’s site.

Bromelain 19 references
  1. Nettis E, Napoli G, Ferrannini A, Tursi A. IgE-mediated allergy to bromelain. Allergy 2001;56:257-8. PubMed
  2. Taussig SJ, Batkin S. Bromelain, the enzyme complex of pineapple (Ananas comosus) and its clinical application. An update. J Ethnopharmacol 1988;22:191-203.. PubMed
  3. Bradbrook ID, Morrison PJ, Rogers HJ. The effect of bromelain on the absorption of orally administered tetracycline. Br J Clin Pharmacol 1978;6:552-4. PubMed
  4. Bush TM, Rayburn KS, Holloway SW, et al. Adverse interactions between herbal and dietary substances and prescription medications: a clinical survey. Altern Ther Health Med 2007;13:30-5.
  5. Brien S, Lewith G, Walker AF, et al. Bromelain as an adjunctive treatment for moderate-to-severe osteoarthritis of the knee: a randomized placebo-controlled pilot study. QJM 2006;99:841-50. PubMed
  6. Mori S, Ojima Y, Hirose T, et al. The clinical effect of proteolytic enzyme containing bromelain and trypsin on urinary tract infection evaluated by double blind method. Acta Obstet Gynaecol Jpn 1972;19:147-53.
  7. Glaser D, Hilberg T. The influence of bromelain on platelet count and platelet activity in vitro. Platelets 2006;17:37-41. PubMed
  8. Heinicke R M, van der Wal L, Yokoyama M. Effect of bromelain (Ananase) on human platelet aggregation. Experientia 1972;28:844-5. PubMed
  9. Gailhofer, G., Wilders-Truschnig, M., Smolle, J., and Ludvan, M. Asthma caused by bromelain: an occupational allergy. Clin Allergy 1988;18(5):445-450. PubMed
  10. Mattei, O., Fabri, G., and Farina, G. [Occupational health experience regarding four cases of asthma due to bromelain (author's transl)]. Medicina del Lavoro 1979;70(5):404-409.
  11. Galleguillos, F. and Rodriguez, J. C. Asthma caused by bromelin inhalation. Clin Allergy 1978;8(1):21-24. PubMed
  12. Perez-Camo I, Quirce S, Duran MA, and et al. Latex allergy: evidence of cross-reactivity with papain and bromelain [abstract]. Allergy 1996;51(suppl 31):48.
  13. Martin GJ, Ehrenreich J, and Asbell N. Bromelain: pineapple proteases with anti-edema activity. Exp Med Surg 1962;20:227-247.
  14. Kasemsuk T, Saengpetch N, Sibmooh N, Unchern S. Improved WOMAC score following 16-week treatment with bromelain for knee osteoarthritis. Clin Rheumatol. 2016 Oct;35(10):2531-40. PubMed
  15. Kutlu Ö, DemirbaS A, Elmas ÖF, Güvenç U, Metin A. Fixed drug eruption: a new side effect of bromelain. Contact Dermatitis 2020. Online ahead of print. PubMed
  16. Shoham Y, Shapira E, Haik J, et al. Bromelain-based enzymatic debridement of chronic wounds: Results of a multicentre randomized controlled trial. Wound Repair Regen 2021;29(6):899-907. PubMed
  17. Pfister P, Garcia Wendel PD, Kim BS, et al. Coagulation side effects of enzymatic debridement in burned patients. Burns 2022. PubMed
  18. Hasham S, Riyat H, Fletcher A, O'Boyle CP, Alexander S. To bleed or not to bleed? Case series and discussion of haemorrhage risk with enzymatic debridement in burn injuries. Scars Burn Heal 2023;9:20595131231168333. PubMed
  19. Leelakanok N, Petchsomrit A, Janurai T, Saechan C, Sunsandee N. Efficacy and safety of bromelain: A systematic review and meta-analysis. Nutr Health 2023. PubMed

See these in context on the Bromelain monograph →

Papain 11 references
  1. The Review of Natural Products by Facts and Comparisons. St. Louis, MO: Wolters Kluwer Co., 1999.
  2. Shaw D, Leon C, Kolev S, Murray V. Traditional remedies and food supplements: a 5-year toxicological study (1991-1995). Drug Saf 1997;17:342-56.
  3. Shuttleworth D, Hill S, Marks R, Connelly DM. Relief of experimentally induced pruritus with a novel eutectic mixture of local anaesthetic agents. Br J Dermatol 1988;119:535-40.
  4. Mansfield LE, Ting S, Haverly RW, Yoo TJ. The incidence and clinical implications of hypersensitivity to papain in an allergic population, confirmed by blinded oral challenge. Ann Allergy 1985;55:541-3.
  5. Martin, T., Uhder, K., Kurek, R., Roeddiger, S., Schneider, L., Vogt, H. G., Heyd, R., and Zamboglou, N. Does prophylactic treatment with proteolytic enzymes reduce acute toxicity of adjuvant pelvic irradiation? Results of a double-blind randomized trial PubMed
  6. Walker-Renard, P. Update on the medicinal management of phytobezoars. Am J Gastroenterol. 1993;88(10):1663-1666.
  7. Tymoszuk D, Wiszniewska M, Walusiak-Skorupa J. Papain-induced occupational rhinoconjunctivitis and asthma - A case report. Med Pr 2016;67(1):109-12. PubMed
  8. Soto-Mera MT, López-Rico MR, Filgueira JF, et al. Occupational allergy to papain. Allergy 2000;55(10):983-4. PubMed
  9. Tarlo SM, Shaikh W, Bell B, et al. Papain-induced allergic reactions. Clin Allergy 1978;8(3):207-15. PubMed
  10. Baur X, König G, Bencze K, Fruhmann G. Clinical symptoms and results of skin test, RAST and bronchial provocation test in thirty-three papain workers: Evidence for strong immunogenic potency and clinically relevant proteolytic e?ects of airborne papain. C
  11. Novey HS, Keenan WJ, Fairshter RD, Wells ID, Wilson AF, Culver BD. Pulmonary disease in workers exposed to papain: clinico-physiological and immunological studies. Clin Allergy 1980;10(6):721-31. PubMed

See these in context on the Papain monograph →

Papaya 14 references
  1. The Review of Natural Products by Facts and Comparisons. St. Louis, MO: Wolters Kluwer Co., 1999.
  2. Leung AY, Foster S. Encyclopedia of Common Natural Ingredients Used in Food, Drugs and Cosmetics. 2nd ed. New York, NY: John Wiley & Sons, 1996.
  3. Shaw D, Leon C, Kolev S, Murray V. Traditional remedies and food supplements: a 5-year toxicological study (1991-1995). Drug Saf 1997;17:342-56.
  4. Mansfield LE, Ting S, Haverly RW, Yoo TJ. The incidence and clinical implications of hypersensitivity to papain in an allergic population, confirmed by blinded oral challenge. Ann Allergy 1985;55:541-3.
  5. Blanco C, Diaz-Perales A, Collada C, et al. Class I chitinases as potential panallergens involved in the latex-fruit syndrome. J Allergy Clin Immunol 1999;103(3 Pt 1):507-13. PubMed
  6. Diaz-Perales A, Collada C, Blanco C, et al. Cross-reactions in the latex-fruit syndrome: A relevant role of chitinases but not of complex asparagine-linked glycans. J Allergy Clin Immunol 1999;104:681-7. PubMed
  7. Castillo, R., Delgado, J., Quiralte, J., Blanco, C., and Carrillo, T. Food hypersensitivity among adult patients: epidemiological and clinical aspects. Allergol.Immunopathol.(Madr.) 1996;24(3):93-97.
  8. Oderinde, O., Noronha, C., Oremosu, A., Kusemiju, T., and Okanlawon, O. A. Abortifacient properties of aqueous extract of Carica papaya (Linn) seeds on female Sprague-Dawley rats. Niger.Postgrad.Med J 2002;9(2):95-98. DOI
  9. Danese, C., Esposito, D., D'Alfonso, V., Cirene, M., Ambrosino, M., and Colotto, M. Plasma glucose level decreases as collateral effect of fermented papaya preparation use. Clin Ter. 2006;157(3):195-198.
  10. Iliev, D. and Elsner, P. Generalized drug reaction due to papaya juice in throat lozenges. Dermatology 1997;194(4):364-366. PubMed
  11. Andersen HA, Bernatz PE, Grindlay JH. Perforation of the esophagus after use of a digestant agent: report of case and experimental study. Ann Otol Rhinol Laryngol 1959;68:890-6. PubMed
  12. Deiana L, Marini S, Mariotti S. Ingestion of large amounts of papaya fruit and impaired effectiveness of levothyroxine therapy. Endocr Pract 2012;18(1):98-100. PubMed
  13. Rodrigues M, Alves G, Francisco J, Fortuna A, Falcão A. Herb-drug pharmacokinetic interaction between Carica papaya extract and amiodarone in rats. J Pharm Pharm Sci 2014;17(3):302-15. PubMed
  14. Rajapakse S, de Silva NL, Weeratunga P, Rodrigo C, Sigera C, Fernando SD. Carica papaya extract in dengue: a systematic review and meta-analysis. BMC Complement Altern Med. 2019;19(1):265. PubMed

See these in context on the Papaya monograph →

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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