Major interaction on record — check this product against your medications before combining. Based on 4 of 5 ingredients. Check your meds →
Dietary supplement

Papaya Enzyme Ingredients & Drug Interactions

by Puritan's Pride

Papaya Enzyme label
See full label image
Tablet Or Pill Category: Other Combinations
Most serious interaction: Major
Clinical methodology reviewed by · Updated Sep 16, 2026 · Label data from the NIH DSLD
What is this page for?

First and foremost: checking Papaya Enzyme against your medications. The heart of this page is the interaction checker and the full interaction report — how this product’s ingredients may interact with prescription and over-the-counter medicines you may be taking.

Around that, we add a pharmacist’s high-level view of the product as a whole — what’s inside, the evidence for its stated use, how transparent the label is, and what safety data exists — so you can see the full picture in one place. It’s educational information from our licensed clinical databases and the clinical staff at HelloPharmacist — not medical advice — and we don’t sell or endorse products. Our editorial policy

The interaction bottom line Most serious interaction: Major

Papaya Enzyme is a dietary supplement by Puritan's Pride with 5 active ingredients. Its ingredients are commonly taken for bone health and osteoporosis prevention, dietary calcium deficiency, heartburn relief (calcium carbonate antacids).Based on those ingredients, 257 medications have a known interaction with it, the most serious rated major. The ingredients most likely to interact are Calcium, Papaya, Papain. Use the checker below to test your specific medication, or read the full HelloPharmacist Interaction Report.

Jump to a section

Check Your Meds Against Papaya Enzyme by Puritan's Pride

Ask about any prescription or over-the-counter medication and we check it for interactions with Papaya Enzyme by Puritan's Pride — and tell you which ingredient is responsible.

Pharmacist-reviewed data Checks every ingredient Answer in seconds
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HelloPharmacist Scorecard of Papaya Enzyme by Puritan's Pride

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

Generated from HelloPharmacist’s pharmacist-curated databases and editorial rules · Last generated Sep 3, 2026

What’s inside

Full disclosure
Ingredient Transparency · database check
Full

Every active ingredient lists its own amount on the label.

Why this rating?
  • The label discloses an exact amount for 5 of its 5 active ingredients.
  • No proprietary blends here — you can verify the dose of every single component.

This product contains 5 active ingredients. Calcium is included to support bone and cellular health.

The enzyme amylase breaks down carbohydrates, and protease breaks down protein—both aid digestion. Papaya and papain are plant-derived enzymes that work similarly to protease, helping your body digest protein.

Together, these ingredients are meant to ease digestion and reduce bloating. The product also contains inactive ingredients (fillers and binders) including sucrose, calcium carbonate, natural flavors, maltodextrin, corn starch, vegetable magnesium stearate, and vegetable stearic acid.

Does it work?

Strong evidence
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

This product doesn't appear to be marketed for a specific use, so we graded its ingredients' overall clinical evidence instead.

Strong

Strong clinical evidence supports its ingredients for:

Why this rating?
  • We looked at the product name, claims, and label statements and couldn't find a stated purpose to grade.
  • Since the label doesn't commit to one use, we graded the ingredients' overall clinical evidence instead.
  • On file: Hyperkalemia — rated "Effective" (Calcium) (Natural Medicines).
  • On file: Dyspepsia — rated "Effective" (Calcium) (Natural Medicines).
  • On file: Hypocalcemia — rated "Effective" (Calcium) (Natural Medicines).
  • On file: Kidney failure — rated "Effective" (Calcium) (Natural Medicines).
  • On file: Hyperparathyroidism — rated "Likely Effective" (Calcium) (Natural Medicines).

The calcium in this product is established as effective for kidney failure, heartburn (dyspepsia), low blood calcium (hypocalcemia), high potassium (hyperkalemia), and likely effective for osteoporosis prevention. We hold no established effectiveness ratings for the papaya, papain, amylase, or protease enzymes for any condition—the evidence in our data is insufficient to rate their benefit.

The evidence, ingredient by ingredient Calcium Proteolytic Enzymes (proteases) Papaya 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 4 of the 4 matched ingredients.
  • Pregnancy & breastfeeding safety ratings cover 4 of 4.
  • General safety write-ups exist for 4 of 4.
  • Remember: this measures how much safety information exists. Thin data is not the same as being safe.

Calcium is generally well tolerated at recommended doses, though high amounts can cause problems. Common side effects from oral calcium include belching, constipation, diarrhea, bloating, and stomach upset.

Rare serious concerns include kidney stones and a condition called calciphylaxis. Some research suggests very high daily calcium intake (above 1,500–2,000 mg) might be linked to increased prostate cancer risk and possibly heart disease risk, though these findings are debated.

Protease enzymes are generally well tolerated but may cause digestive upset or allergic reactions in sensitive people. Papaya and papain are well tolerated as food, but concentrated supplements are less studied.

Both can trigger allergic reactions—including itchy eyes, runny nose, sneezing, stomach cramps, and diarrhea—especially in people sensitive to latex. Unripe papaya should be avoided.

During pregnancy, unripe papaya and concentrated papain are not recommended. For breastfeeding, reliable safety data is limited, so supplements are best avoided without medical advice.

Side effects, ingredient by ingredient Calcium Proteolytic Enzymes (proteases) Papaya Papain

Meds to double-check

Major interaction found
Known Interaction Concern · database check
Major identified

At least one ingredient has a documented Major-severity interaction. Check your medications for a personalized result.

Why this rating?
  • 3 of the 4 matched ingredients can interact with medications — Papain, Papaya, Calcium.
  • The most serious interaction on file is rated Major.
  • Some involve high-stakes drug classes: anticoagulant / antiplatelet drugs; diabetes medications; heart-rhythm medications; lithium.
  • For scale: 257 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, check whether you use HIV integrase inhibitors (dolutegravir, elvitegravir, raltegravir), the antibiotic ceftriaxone, blood thinners (warfarin), thyroid medication (levothyroxine), diabetes drugs, heart rhythm medications (sotalol, diltiazem, amiodarone), or the psoriasis drug calcipotriene. These carry Major or Moderate interactions with calcium or papaya that may reduce their effectiveness or increase risks.

Use the medication checker below to verify your specific drugs.

Check your own medication Run your meds through the checker above

The bottom line

Scorecard at a glanceFully disclosed formula with strong clinical evidence behind its ingredients' uses. Major medication interactions have been identified, and safety information is well characterized.

This product may help with general digestion thanks to its enzyme blend, but the calcium and papaya compounds can interfere with several important medications—especially HIV drugs, thyroid medication, and blood thinners. If you take any prescription medications, check them against the interaction tool on this page before starting.

Talk with your doctor or pharmacist about whether this product fits your personal health picture.

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

Assessment coverage: 4 of 5 active ingredients matched to our full ingredient reviews (monographs). Based on the product label dated Jul 21, 2022.

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 Puritan's Pride
Barcode (UPC) 074312111334
Net contents 250 Delicious Chewable Tablet(s)
Market status On market
Date entered into DSLD Jul 21, 2022
DSLD ID 271057
Product type Other Combinations
Supplement form Tablet Or Pill
Dietary claims / uses All Other, Structure/Function
Intended target group(s) Vegetarian, Adult (18 - 50 Years), Gluten Free, Dairy 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 Puritan's Pride, 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:
3 Tablet(s)
Maximum serving Sizes:
3 Tablet(s)
Servings per container
83
UPC/BARCODE
074312111334
IngredientAmount% DV
Calcium157 mg12%
Amylase6 mg--
Protease6 mg--
Calories5 Calorie(s)--
Total Carbohydrate1 Gram(s)1%
Total Sugars1 Gram(s)--
added Sugars1 Gram(s)2%
Papaya3 mg--
Papain45 mg--

Other ingredients: Sucrose, Calcium Carbonate, Natural Flavors, Maltodextrin, Corn Starch, Vegetable Magnesium Stearate, Vegetable Stearic Acid

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.
Formulation

Puritan's pride supplements are produced from the finest raw materials under stringent quality control standards. State-of-the-art manufacturing and packaging facilities ensure you the highest quality nutritional supplements money can buy. When it comes to your health...choose the best.

Digestive Aid

Vegetarian

No artificial color, flavor or sweetener, no milk, no lactose, no soy, no gluten, no wheat, no yeast, no fish. Sodium free.

Precautions

Warning: If you are pregnant, nursing, taking any medications or have any medical condition, including a known sensitivity to latex, consult your doctor before use.

Discontinue use and consult your doctor if any adverse reactions occur.

Do not use if seal under cap is broken or missing.

Keep out of reach of children.

Storage

Store at room temperature.

FDA Disclaimer Statement

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

General Statements

To reorder item #1133 www.puritan.com 1-800-645-1030

Brand IP Statement(s)

Copyright 2020 Puritan's Pride, Inc.

The "After Meal" Supplement

FDA Statement of Identity

Dietary Supplement

Suggested/Recommended/Usage/Directions

Directions: For adults, chew three (3) tablets with a meal, up to three times daily.

Seals/Symbols

QA Quality Assured

Is this label outdated? Report a formula or label change and our pharmacy team will review it.

See for yourself

Papaya Enzyme by Puritan's Pride label

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

Papaya Enzyme label

Label images are published by the NIH Dietary Supplement Label Database for the version of this product on file. Always read your actual product label.

View the full label (PDF)
What’s inside

The Ingredients in Papaya Enzyme by Puritan's Pride

These are the 5 active ingredients this product is made of. Select any to open its full monograph.

Serving size3 Tablet(s) Dosage formTablet Or Pill Servings per container83 Amounts shown are per serving.

Most supplement products combine several ingredients, and a medication can interact with the product through any one of them. Each ingredient below shows whether it has known drug interactions.

Calcium

Interacts with
168 drugs
157 mg per serving

Calcium is an essential mineral your body needs for strong bones, nerve signaling, and muscle function, and supplements can help fill gaps when diet f...

Calcium monograph & interactions

Amylase

6 mg per serving

Protease

No known
interactions
6 mg per serving

Proteolytic enzymes are proteins that help break down other proteins, and common examples include bromelain (from pineapple), papain (from papaya), tr...

Protease monograph & interactions

Papaya

Interacts with
92 drugs
3 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 monograph & interactions

Papain

Interacts with
2 drugs
45 mg per serving Form: Papaya

Papain is a protein-digesting enzyme from the papaya plant that is used in digestive supplements and some topical products. While it has clear food an...

Papain monograph & interactions

Other (inactive) ingredients: Sucrose, Calcium Carbonate, Natural Flavors, Maltodextrin, Corn Starch, Vegetable Magnesium Stearate, Vegetable Stearic Acid. These complete the product’s ingredient list but are not active constituents.

Interaction report

Papaya Enzyme by Puritan's Pride 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
257Drugs
7 Major 232 Moderate 18 Minor

Ingredients driving the most interactions

Calcium 168
Papaya 92
Papain 2

Individual Drug Interactions

The ingredients in Papaya Enzyme interact with 257 drugs. Click any drug to see the details.

3 of the 5 ingredients in Papaya Enzyme interact with drugs. Each result below shows which ingredient is responsible. Calcium Papaya Papain

Each ingredient & the kinds of drugs it affects

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

Calcium18 drug types · 168 drugs

Ceftriaxone (Rocephin)

Co-administration of intravenous calcium and ceftriaxone can result in precipitation of a ceftriaxone-calcium salt in the lungs and kidneys.
Avoid administering intravenous calcium in any form, such as parenteral nutrition or Lactated Ringers, within 48 hours of intravenous ceftriaxone. Case reports in neonates show that administering intravenous ceftriaxone and calcium can result in precipitation of a ceftriaxone-calcium salt in the lungs and kidneys. In several cases, neonates have died as a result of this interaction. So far there are no reports in adults; however, there is still concern that this interaction might occur in adults.

Likelihood Probable Evidence D
Dolutegravir (Tivicay)

Calcium seems to reduce levels of dolutegravir.
Advise patients to take dolutegravir either 2 hours before or 6 hours after taking calcium supplements. Pharmacokinetic research suggests that taking calcium carbonate 1200 mg concomitantly with dolutegravir 50 mg reduces plasma levels of dolutegravir by almost 40%. Calcium appears to decrease levels of dolutegravir through chelation.

Likelihood Probable Evidence B
Elvitegravir (Vitekta)

Calcium seems to reduce levels of elvitegravir.
Advise patients to take elvitegravir either 2 hours before or 2 hours after taking calcium supplements. Pharmacokinetic research suggests that taking calcium along with elvitegravir can reduce blood levels of elvitegravir through chelation.

Likelihood Probable Evidence B
Aluminum

Calcium citrate might increase aluminum absorption and toxicity. Other types of calcium do not increase aluminum absorption.
Calcium citrate can increase the absorption of aluminum when taken with aluminum hydroxide. The increase in aluminum levels may become toxic, particularly in individuals with kidney disease. However, the effect of calcium citrate on aluminum absorption is due to the citrate anion rather than calcium cation. Calcium acetate does not appear to increase aluminum absorption.

Likelihood Possible Evidence B
Bictegravir/Emtricitabine/Tenofovir Alafenamide (Biktarvy)

Calcium might decrease levels of bictegravir/emtricitabine/tenofovir alafenamide by reducing its absorption when taken in a fasting state.
Advise patients that bictegravir/emtricitabine/tenofovir alafenamide and calcium can be taken together if taken with food. However, if taken on an empty stomach, bictegravir/emtricitabine/tenofovir alafenamide should not be taken with, or 2 hours after, calcium containing products.

Likelihood Probable Evidence D
Bisphosphonates

Calcium reduces the absorption of bisphosphonates.
Advise patients to take bisphosphonates at least 30 minutes before calcium, but preferably at a different time of day. Calcium supplements decrease absorption of bisphosphonates.

Likelihood Probable Evidence C
Calcipotriene (Dovonex)

Taking calcipotriene with calcium might increase the risk for hypercalcemia.
Calcipotriene is a vitamin D analog used topically for psoriasis. It can be absorbed in sufficient amounts to cause systemic effects, including hypercalcemia. Theoretically, combining calcipotriene with calcium supplements might increase the risk of hypercalcemia.

Likelihood Possible Evidence B
Digoxin (Lanoxin)

Using intravenous calcium with digoxin might increase the risk of fatal cardiac arrhythmias.
Hypercalcemia increases the risk of fatal cardiac arrhythmias with digoxin. However, one retrospective analysis of clinical data suggests that intravenous calcium does not increase the risk of dysrhythmias or mortality in patients receiving digoxin.

Likelihood Possible Evidence B
Diltiazem (Cardizem, Others)

Theoretically, calcium may reduce the therapeutic effects of diltiazem.
Hypercalcemia can reduce the effectiveness of verapamil in atrial fibrillation. Theoretically, calcium might increase this risk of hypercalcemia and reduce the effectiveness of diltiazem.

Likelihood Probable Evidence D
Levothyroxine (Synthroid, Others)

Calcium seems to reduce the absorption and effectiveness of levothyroxine.
Advise patients to take levothyroxine and calcium supplements at least 4 hours apart. Calcium reduces levothyroxine absorption, probably by forming insoluble complexes. Calcium carbonate supplements reduce effectiveness of levothyroxine in patients with hypothyroidism.

Likelihood Probable Evidence B
Lithium

Theoretically, concomitant use of calcium and lithium may increase this risk of hypercalcemia.
Clinical research suggests that long-term use of lithium may cause hypercalcemia in 10% to 60% of patients. Theoretically, concomitant use of lithium and calcium supplements may further increase this risk.

Likelihood Possible Evidence B
Quinolone Antibiotics

Calcium seems to reduce the absorption of quinolone antibiotics.
Advise patients to take oral quinolones at least 2 hours before or 4-6 hours after calcium supplements or calcium-fortified foods. Taking calcium at the same time as oral quinolones can reduce quinolone absorption. Calcium binds to quinolones in the gut.

Likelihood Probable Evidence B
Raltegravir (Isentress)

Calcium may reduce levels of raltegravir.
Pharmacokinetic research shows that taking a single dose of calcium carbonate 3000 mg along with raltegravir 400 mg twice daily modestly decreases the mean area under the curve of raltegravir, but the decrease does not necessitate a dose adjustment of raltegravir. However, a case of elevated HIV-1 RNA levels and documented resistance to raltegravir has been reported for a patient taking calcium carbonate 1 gram three times daily plus vitamin D3 (cholecalciferol) 400 IU three times daily in combination with raltegravir 400 mg twice daily for 11 months. It is thought that calcium reduced raltegravir levels by chelation, leading to treatment failure.

Likelihood Possible Evidence B
Sotalol (Betapace)

Calcium seems to reduce the absorption of sotalol.
Advise patients to separate doses by at least 2 hours before or 4-6 hours after calcium. Calcium appears to reduce the absorption of sotalol, probably by forming insoluble complexes.

Likelihood Possible Evidence B
Tetracycline Antibiotics

Calcium seems to reduce the absorption of tetracycline antibiotics.
Advise patients to take oral tetracyclines at least 2 hours before, or 4-6 hours after calcium supplements. Taking calcium at the same time as oral tetracyclines can reduce tetracycline absorption. Calcium binds to tetracyclines in the gut.

Likelihood Probable Evidence C
Thiazide Diuretics

Taking calcium along with thiazides might increase the risk of hypercalcemia and renal failure.
Thiazides reduce calcium excretion by the kidneys. Using thiazides along with moderately large amounts of calcium carbonate increases the risk of milk-alkali syndrome (hypercalcemia, metabolic alkalosis, renal failure). Patients may need to have their serum calcium levels and/or parathyroid function monitored regularly.

Likelihood Probable Evidence C
Verapamil (Calan, Others)

Theoretically, calcium may reduce the therapeutic effects of verapamil.
Hypercalcemia can reduce the effectiveness of verapamil in atrial fibrillation. Theoretically, use of calcium supplements may increase this risk of hypercalcemia and reduce the effectiveness of verapamil.

Likelihood Probable Evidence D
Calcium Channel Blockers

Intravenous calcium may decrease the effects of calcium channel blockers; oral calcium is unlikely to have this effect.
Intravenous calcium is used to decrease the effects of calcium channel blockers in the management of overdose. Intravenous calcium gluconate has been used before intravenous verapamil (Isoptin) to prevent or reduce the hypotensive effects without affecting the antiarrhythmic effects. But there is no evidence that dietary or supplemental calcium when taken orally interacts with calcium channel blockers.

Likelihood Unlikely Evidence D
Calcium full monograph & interactions

Papaya4 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
Papaya full monograph & interactions

Papain1 drug type · 2 drugs

Warfarin (Coumadin)

Theoretically, papain 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
Papain full monograph & interactions
The maker

Brand information

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

Puritan's Pride

See all Puritan's Pride products
Name
Puritan's Pride, Inc.
City
Ronkonkoma
State
NY
ZipCode
11779
Phone Number
1-800-645-1030
Web Address
www.puritan.com
Pharmacist Counseling Corner

Papaya Enzyme by Puritan's Pride: Common Questions

Does Papaya Enzyme by Puritan's Pride interact with any medications?
Yes. Based on its ingredients, Papaya Enzyme has a known interaction with 257 medications, including 7 rated major. Use the checker to see how it interacts with a specific drug.
How can one product interact with so many drugs?
Papaya Enzyme contains 5 active ingredients, and an interaction can come from any of them. We check every ingredient, combine the results into one list per medication, and show which ingredient and mechanism is 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 pregnant?
The calcium in this product is considered likely safe during pregnancy at recommended amounts. However, papaya is possibly unsafe—especially unripe forms and concentrated papain. There isn't enough data on protease and amylase in pregnancy. Talk with your doctor or pharmacist before taking this supplement while pregnant to make sure it's appropriate for you.
Is this safe while breastfeeding?
Calcium is considered likely safe during breastfeeding at recommended amounts. Papaya fruit is likely safe, but there's limited safety data on papaya supplements and papain during breastfeeding, so they're best avoided without medical advice. There's also little safety information for protease supplements while nursing. Check with your doctor or pharmacist.
What side effects might I get from the calcium?
Common side effects include belching, constipation, diarrhea, bloating, and stomach upset. Rare but serious concerns include kidney stones. Very high doses have been linked in some research to increased prostate cancer and heart disease risk, though these findings remain debated.
Can papain cause allergic reactions?
Yes. Some people—especially those sensitive to latex—can have allergic reactions to papain, including itchy watery eyes, runny nose, sneezing, stomach cramps, and diarrhea. Severe allergic reactions are rare but possible. If you have a latex allergy, be cautious.
Does this product actually help with digestion?
Calcium is established as effective for heartburn (dyspepsia). The papaya, papain, protease, and amylase enzymes are intended to aid digestion, but we don't hold enough evidence in our data to say whether they work for this purpose.
Will this interfere with my levothyroxine?
Yes—both the calcium and papaya can reduce how well levothyroxine works. The calcium effect is documented and Moderate severity; the papaya effect appears strongest with large amounts of whole fruit (5–6 fruits daily). If you take levothyroxine, check with your doctor or pharmacist before adding this product.

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

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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
Go deeper

The Full Monographs Behind Papaya Enzyme’s Ingredients

Every ingredient we hold a full HelloPharmacist monograph for — uses, evidence, safety, and the complete interaction list.

Herb & supplement monograph

Calcium

Interacts with 168 drugs

Calcium is an essential mineral your body needs for strong bones, nerve signaling, and muscle function, and supplements can help fill gaps when diet falls short. Most people do best getting...

Read the full Calcium monograph → Herb & supplement monograph

Proteolytic Enzymes (proteases)

Proteolytic enzymes are proteins that help break down other proteins, and common examples include bromelain (from pineapple), papain (from papaya), trypsin, chymotrypsin, and pancreatin. Peo...

Read the full Proteolytic Enzymes (proteases) monograph → Herb & supplement monograph

Papaya

Interacts with 92 drugs

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 meat tenderizer. Papaya leaf extract is b...

Read the full Papaya monograph → Herb & supplement monograph

Papain

Interacts with 2 drugs

Papain is a protein-digesting enzyme from the papaya plant that is used in digestive supplements and some topical products. While it has clear food and laboratory uses, strong human evidence...

Read the full Papain monograph →
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 90 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.

Calcium 62 references
  1. Shils M, Olson A, Shike M. Modern Nutrition in Health and Disease. 8th ed. Philadelphia, PA: Lea and Febiger, 1994.
  2. Hernandez-Avila M, Gonzalez-Cossio T, Hernandez-Avila JE, et al. Dietary calcium supplements to lower blood lead levels in lactating women: a randomized placebo-controlled trial. Epidemiology 2003;14:206-12.. PubMed
  3. Thys-Jacobs S, Ceccarelli S, Bierman A, et al. Calcium supplementation in premenstrual syndrome: a randomized crossover trial. J Gen Intern Med 1989;4:183-9. PubMed
  4. Maton PN, Burton ME. Antacids revisited: a review of their clinical pharmacology and recommended therapeutic use. Drugs 1999;57:855-70.
  5. Clemens JD, Feinstein AR. Calcium carbonate and constipation: a historical review of medical mythopoeia. Gastroenterology 1977;72:957-61. DOI
  6. Saunders D, Sillery J, Chapman R. Effect of calcium carbonate and aluminum hydroxide on human intestinal function. Dig Dis Sci 1988;33:409-13. PubMed
  7. Friedman PA, Bushinsky DA. Diuretic effects on calcium metabolism. Semin Nephrol 1999;19:551-6.
  8. Koo WK, Walters JC, Esterlitz J, et al. Maternal calcium supplementation and fetal bone mineralization. Obstet Gynecol 1999;94:577-82. DOI
  9. Raman L, Rajalakshmi K, Krishnamachari KAVR, et al. Effect of calcium supplementation to undernourished mothers during pregnancy on the bone density of the neonates. Am J Clin Nutr 1978; 31:466-9. DOI
  10. Murry JJ, Healy MD. Drug-mineral interactions: a new responsibility for the hospital dietician. J Am Diet Assoc 1991;91:66-73.
  11. Chan JM, Giovannucci E, Andersson SO, et al. Dairy products, calcium, phosphorous, vitamin D, and risk of prostate cancer. Cancer Causes Control 1998;9:559-66.
  12. Butner LE, Fulco PP, Feldman G, et al. Calcium carbonate-induced hypothyroidism. Ann Intern Med 2000:132:595. PubMed
  13. Schneyer CR. Calcium carbonate and reduction of levothyroxine efficacy. JAMA 1998;279:750. PubMed
  14. Moser LR, Smythe MA, Tisdale JE. The use of calcium salts in the prevention and management of verapamil-induced hypotension. Ann Pharmacother 2000;34:622-9. PubMed
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Proteolytic Enzymes (proteases) 3 references
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Papain 11 references
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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.

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