Major interaction on record — check this product against your medications before combining. Based on 4 of 6 ingredients. Check your meds →
Dietary supplement

Zygest Papaya Enzyme Ingredients & Drug Interactions

by Vitamin World

Zygest 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 Zygest 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

Zygest Papaya Enzyme is a dietary supplement by Vitamin World with 6 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 Zygest Papaya Enzyme by Vitamin World

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

Pharmacist-reviewed data Checks every ingredient Answer in seconds
Prefer a human? Send your question to our licensed pharmacists — free, answered by email within 24 hours.

HelloPharmacist Scorecard of Zygest Papaya Enzyme by Vitamin World

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 Jul 11, 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.
  • “Zygest(R) Blend” is a proprietary blend — the label gives one combined amount (60 mg) without saying how much of each component you get.

Zygest Papaya Enzyme contains 5 active ingredients designed to support digestion. Calcium is included for its established role in bone and mineral health.

The product also contains papain and protease—digestive enzymes that break down proteins—along with amylase (which we cannot verify) and papaya extract, which contains natural enzymes and other compounds. The tablet also holds inactive ingredients including sucrose, calcium carbonate, stearic acid, and vegetable magnesium stearate as binders and fillers.

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
Strong

Clinical evidence supports at least one of this product's ingredients for its stated purpose.

Why this rating?
  • The label markets this product for: Natural digestive aid for after meals.
  • We looked for evidence on: Dyspepsia, Exercise-induced muscle damage, Exercise-induced muscle soreness, Intestinal parasite infection, Oral mucositis, Pressure ulcers — and 4 related terms.
  • The strongest evidence on file: Calcium is rated "Effective" for Dyspepsia (Natural Medicines).
  • Also on file: Papain is rated "Insufficient Reliable Evidence To Rate" for Exercise-induced muscle soreness, Intestinal parasite infection, Wound healing, Tonsillopharyngitis, and more.

Calcium in this product is established as effective for preventing kidney failure, relieving indigestion (dyspepsia), treating low blood calcium (hypocalcemia), managing high potassium levels (hyperkalemia), and is likely effective for osteoporosis. However, the effectiveness of papain, papaya extract, and protease in this product has not been established in our data.

Papain and papaya are rated as having insufficient reliable evidence for cancer, dental cavities, radiation skin damage, exercise-related muscle soreness, shingles, and parasitic infections. Protease has no effectiveness ratings on file.

The evidence, ingredient by ingredient Calcium Papain Proteolytic Enzymes (proteases) Papaya

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 doses can cause problems. Most people taking oral calcium experience only minor digestive effects—belching, constipation, diarrhea, flatulence, or stomach upset.

Rare serious concerns with very high intakes (over 1500–2000 mg daily) include possible increased risk of kidney stones, calciphylaxis, and cardiovascular or prostate concerns, though research is mixed. Papain is generally tolerated as a food but may irritate the digestive tract or trigger allergic reactions in sensitive people; concentrated papain should be avoided in pregnancy.

Protease is generally well tolerated but may cause digestive upset or allergic reactions. We hold no pregnancy or breastfeeding data for papain or protease beyond the cautions above.

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

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, double-check these medication types with your pharmacist: HIV integrase inhibitors (dolutegravir, elvitegravir) and HIV protease inhibitors—these require strict spacing; blood thinners like warfarin; thyroid medications like levothyroxine; heart rhythm drugs including amiodarone and sotalol; calcium channel blockers like diltiazem; and diabetes medications. If you take intravenous ceftriaxone (an antibiotic), inform your care team about any calcium in this product.

No interactions are documented for protease.

Check your own medication Run your meds through the checker above

The bottom line

Scorecard at a glanceFully disclosed formula with clinical evidence supporting its stated purpose. Major medication interactions have been identified, and safety information is well characterized.

Zygest Papaya Enzyme is a calcium and enzyme supplement best suited for people seeking digestive support or mineral supplementation, but it carries significant interactions with HIV medications, blood thinners, thyroid drugs, and several heart medications. If you take any prescription drugs—especially antiretrovirals, warfarin, levothyroxine, or cardiac medications—check your medications with the tool on this page before starting.

Talk with your pharmacist or doctor to make sure the timing and dose are safe for you.

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 Apr 25, 2013.

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 Zygest Papaya Enzyme, straight from the product label.

Brand Vitamin World
Barcode (UPC) 074312711350
Net contents 500 Delicious Chewable Tablet(s)
Market status On market
Date entered into DSLD Apr 25, 2013
DSLD ID 20773
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 Zygest Papaya Enzyme by Vitamin World, 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
166
UPC/BARCODE
074312711350
IngredientAmount% DV
Calories5 {Calories}--
Total Carbohydrates1 g1%
Sugar1 g--
Calcium157 mg16%
Amylase6 mg--
Papain45 mg--
Protease6 mg--
Papaya3 mg--
Zygest(R) Blend60 mg--

Other ingredients: Sucrose, Calcium Carbonate, Stearic Acid, Vegetable Magnesium Stearate, Contains <2% of:

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.
General Statements

Chewable

Papaya enjoys a reputation as the perfect “after meal” supplement. That is because it is a natural digestive aid* - and the ideal complement to a busy breakfast, on-the-go lunch, or formal dinner. Take these tablets everywhere and enjoy all the exotic goodness of the “melon of the tropics.”

Vitamin World products are subject to critically stringent quality assurance analysis. Our state-of-the-art laboratory, manufacturing and packaging facilities insure the highest quality nutritional supplements money can buy. Your health & safety are our first priority!

Enzymatic Digestive Care* Natural Digestive Aid**

Get healthy.

Seals/Symbols

QA QUALITY ASSURED

V VITAMIN WORLD(R) get healthy.

Formulation

No Artificial Color, No Preservatives, No Milk, No Lactose, No Soy, No Gluten, No Wheat, No Yeast, No Fish. Sodium Free.

The chewable supplements in this product are formulated without chemical additives or preservatives.

Precautions

WARNING: If you are pregnant, nursing, taking any medications or have any medical condition, consult your doctor before use.

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

Keep out of reach of children.

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

Storage

Store at room temperature.

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.

Brand IP Statement(s)

(C)2012 Vitamin World, Inc.

Formula

These delicious tablets are made from beneficial ingredients including: ripe papaya fruit, papain (a papaya enzyme), protease and amylase, plus an added touch of sucrose for that flavor-filled taste.

FDA Statement of Identity

Vegetarian Dietary Supplement

Suggested/Recommended/Usage/Directions

DIRECTIONS: For adults, chew three (3) tablets following a meal, one to three times daily.

General

PROD. #1135 B1132 07C

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

See for yourself

Zygest Papaya Enzyme by Vitamin World label

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

Zygest 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 Zygest Papaya Enzyme by Vitamin World

These are the 6 active ingredients this product is made of. Select any to open its full monograph.

Serving size3 Tablet(s) Dosage formTablet Or Pill Servings per container166 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.

Sugar

1 g per serving

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

Zygest(R) Blend

60 mg per serving

Other (inactive) ingredients: Sucrose, Calcium Carbonate, Stearic Acid, Vegetable Magnesium Stearate, Contains <2% of:. These complete the product’s ingredient list but are not active constituents.

Interaction report

Zygest Papaya Enzyme by Vitamin World Drug Interactions

Want to check YOUR meds against Zygest 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 Zygest Papaya Enzyme interact with 257 drugs. Click any drug to see the details.

3 of the 6 ingredients in Zygest 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 Zygest 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 Zygest Papaya Enzyme, from the product label.

Vitamin World

See all Vitamin World products
Name
Vitamin World, Inc.
City
Ronkonkoma
State
NY
ZipCode
11779
Pharmacist Counseling Corner

Zygest Papaya Enzyme by Vitamin World: Common Questions

Does Zygest Papaya Enzyme by Vitamin World interact with any medications?
Yes. Based on its ingredients, Zygest 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?
Zygest Papaya Enzyme contains 6 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.
Is this safe to take if I'm pregnant?
The calcium in this product is likely safe in pregnancy at recommended amounts—adequate calcium is important during pregnancy—but stay within advised doses unless your doctor says otherwise. However, we don't have enough safety data on papain, papaya extract, and protease in pregnancy. Talk with your doctor before starting any supplement during pregnancy.
What's papain, and why is it in a digestive enzyme supplement?
Papain is a natural protein-digesting enzyme from papaya. It's included because it breaks down proteins in food to aid digestion. However, its effectiveness for various health conditions hasn't been proven, and it may trigger allergic reactions or digestive irritation in some people.
Can I take this with my blood thinner?
If you take warfarin (Coumadin), this product carries a Moderate interaction risk through both its papain and papaya content—papain has been linked to dangerous increases in warfarin levels. You must talk with your pharmacist or doctor before adding this supplement; they may need to monitor your blood-thinning levels closely or adjust timing.
Will this help my digestion?
The calcium in this product is established as effective for relieving indigestion. However, we don't have enough evidence to say whether papain, protease, or papaya are effective for digestive support in supplement form, though they are digestive enzymes.
What side effects should I watch for?
Most people experience only mild digestive symptoms—belching, constipation, diarrhea, or stomach upset. Allergic reactions (itchy eyes, sneezing, rash, swelling) can occur, especially if you're sensitive to papaya or papain. Stop and contact your doctor if you have severe stomach pain, esophageal discomfort, or signs of an allergic reaction.
Is this safe to take while breastfeeding?
Calcium at recommended amounts is safe during breastfeeding and helps meet your calcium needs. We don't have reliable safety data for papain or papaya supplements while breastfeeding, so check with your doctor or pharmacist before starting.

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

Not sure if Zygest Papaya Enzyme is safe with your meds?

Our pharmacists answer your medication & supplement questions — free.

Ask a pharmacist

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.

Zygest Papaya Enzyme label
Go deeper

The Full Monographs Behind Zygest 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

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 → 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 →
Sources

Sources & How We Checked

Zygest 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
  15. Singh N, Singh PN, Hershman JM. Effect of calcium carbonate on the absorption of levothyroxine. JAMA 2000;283:2822-5. PubMed
  16. Kahela P, Anttila M, Tikkanen R, Sundquist H. Effect of food, food constituents and fluid volume on the bioavailability of sotalol. Acta Pharmacol Toxicol (Copenh) 1979;44:7-12.. PubMed
  17. Pletz MW, Petzold P, Allen A, et al. Effect of calcium carbonate on bioavailability of orally administered gemifloxacin. Antimicrob Agents Chemother 2003;47:2158-60.. PubMed
  18. Bar-Or D, Yoel G. Calcium and calciferol antagonize effect of verapamil in atrial fibrillation. Br Med J 1981;282:1585-6.
  19. Decktor DL, Robinson M, Maton PN, et al. Effects of aluminum/magnesium hydroxide and calcium carbonate on esophageal and gastric pH in subjects with heartburn. Am J Ther 1995;2:546-52. PubMed
  20. Simoneau G. Absence of rebound effect with calcium carbonate. Eur J Drug Metab Pharmacokinet 1996;21:351-7. PubMed
  21. Peters ML, Leonard M, Licata AA. Role of alendronate and risedronate in preventing and treating osteoporosis. Cleve Clin J Med 2001;68:945-51. PubMed
  22. Bourke JF, Mumford R, Whittaker P, et al. The effects of topical calcipotriol on systemic calcium homeostasis in patients with chronic plaque psoriasis. J Am Acad Dermatol 1997;37:929-34.
  23. Gueguen L, Pointillart A. The bioavailability of dietary calcium. J Am Coll Nutr 2000;19:119s-136s. PubMed
  24. Vella A, Gerber TC, Hayes DL, Reeder GS. Digoxin, hypercalcaemia, and cardiac conduction. Postgrad Med J 1999;75:554-6. PubMed
  25. Bania TC, Blaufeux B, Hughes S, et al. Calcium and digoxin vs. calcium alone for severe verapamil toxicity. Acad Emerg Med 2000;7:1089-96. PubMed
  26. Tseng M, Breslow RA, Graubard BI, Ziegler RG. Dairy, calcium, and vitamin D intakes and prostate cancer risk in the National Health and Nutrition Examination Epidemiologic Follow-up Study cohort. Am J Clin Nutr 2005;81:1147-54. PubMed
  27. Weingarten MA, Zalmanovici A, Yaphe J. Dietary calcium supplementation for preventing colorectal cancer and adenomatous polyps. Cochrane Database Syst Rev 2004;(1):CD003548. PubMed
  28. Tavani A, Bertuccio P, Bosetti C, et al. Dietary intake of calcium, vitamin D, phosphorus and the risk of prostate cancer. Eur Urol 2005;48:27-33. PubMed
  29. Giovannucci E, Liu Y, Stampfer MJ, Willett WC. A prospective study of calcium intake and incident and fatal prostate cancer. Cancer Epidemiol Biomarkers Prev 2006;15:203-10. PubMed
  30. Rocephin (ceftriaxone) and calcium interaction. Pharmacist's Letter / Prescriber's Letter 2007;23(10):231005.
  31. Bolland MJ, Barber PA, Doughty RN, et al. Vascular events in healthy older women receiving calcium supplementation: randomised control trial. BMJ 2008;336:262-6.
  32. Bolland MJ, Avenell A, Baron JA, et al. Effect of calcium supplements on risk of myocardial infarction and cardiovascular events: meta-analysis. BMJ 2010;341:c3691. PubMed
  33. Calcium supplementation and vascular events. Pharmacist's Letter / Prescriber's Letter 2008;24(3):240306.
  34. Dietary reference intakes for calcium and vitamin D. Institute of Medicine, November 30, 2010. Available at: http://www.iom.edu/~/media/Files/Report%20Files/2010/Dietary-Reference-Intakes-for-Calcium-and-Vitamin-D/Vitamin%20D%20and%20Calcium%202010%20Repo
  35. Coburn JW, Mischel MG, Goodman WG, et al. Calcium citrate markedly enhances aluminum absorption from aluminum hydroxide. Am J Kidney Dis. 1991;17(6):708-11. PubMed
  36. Bradley JS, Wassel RT, Lee L, et al. Intravenous ceftriaxone and calcium in the neonate: assessing the risk for cardiopulmonary adverse events. Pediatrics. 2009;123(4):e609-13. PubMed
  37. Kays MB, Overholser BR, Mueller BA, et al. Effects of sevelamer hydrochloride and calcium acetate on the oral bioavailability of ciprofloxacin. Am J Kidney Dis. 2003;42(6):1253-9. PubMed
  38. Neuhofel, A. L., Wilton, J. H., Victory, J. M., Hejmanowsk, L. G., and Amsden, G. W. Lack of bioequivalence of ciprofloxacin when administered with calcium-fortified orange juice: a new twist on an old interaction. J Clin Pharmacol. 2002;42(4):461-466. DOI
  39. Dickinson, H. O., Nicolson, D. J., Cook, J. V., Campbell, F., Beyer, F. R., Ford, G. A., and Mason, J. Calcium supplementation for the management of primary hypertension in adults. Cochrane.Database.Syst.Rev. 2006;(2):CD004639. PubMed
  40. Jones, B. J. and Twomey, P. J. Requesting patterns for serum calcium concentration in patients on long-term lithium therapy. Int J Clin Pract. 2009;63(1):170-172. PubMed
  41. Levine, M., Nikkanen, H., and Pallin, D. J. The effects of intravenous calcium in patients with digoxin toxicity. J Emerg.Med. 2011;40(1):41-46. PubMed
  42. Castelo-Branco, C., Ciria-Recasens, M., Cancelo-Hidalgo, M. J., Palacios, S., Haya-Palazuelos, J., Carbonell-Abello, J., Blanch-Rubio, J., Martinez-Zapata, M. J., Manasanch, J., and Perez-Edo, L. Efficacy of ossein-hydroxyapatite complex compared with ca
  43. Li K, Kaaks R, Linseisen J, Rohrmann S. Associations of dietary calcium intake and calcium supplementation with myocardial infarction and stroke risk and overall cardiovascular mortality in the Heidelberg cohort of the European Prospective Investigation i
  44. Chung M, Tang AM, Fu Z. Calcium Intake and Cardiovascular Disease Risk: An Updated Systematic Review and Meta-analysis. Ann Intern Med. 2016 Oct 25. PubMed
  45. Nolan CR, Califano JR, Butzin CA. Influence of calcium acetate or calcium citrate on intestinal aluminum absorption. Kidney Int. 1990;38(5):937-41. PubMed
  46. Lewis JR, Radavelli-Bagatini S, Rejnmark L, et al. The effects of calcium supplementation on verified coronary heart disease hospitalization and death in postmenopausal women: a collaborative meta-analysis of randomized controlled trials. J Bone Miner Res PubMed
  47. Jalloh MA, Gregory PJ, Hein D, et al. Dietary supplement interactions with antiretrovirals: a systematic review. Int J STD AIDS. 2017 Jan;28(1):4-15. PubMed
  48. Lappe J, Watson P, Travers-Gustafson D, Recker R, Garland C, Gorham E, Baggerly K, McDonnell SL. Effect of Vitamin D and Calcium Supplementation on Cancer Incidence in Older Women: A Randomized Clinical Trial. JAMA. 2017 Mar 28;317(12):1234-1243. PubMed
  49. Grove ML, Cook D. Calcium and heart attacks. Doesn't apply to most calcium prescriptions. BMJ. 2010;341:c5003. PubMed
  50. Insentress [package insert]. Whitehouse Station, NJ: Merck Sharp & Dohme Corp.; 2014.
  51. Roberts JL, Kiser JJ, Hindman JT, Meditz AL. Virologic failure with a raltegravir-containing antiretroviral regimen and concomitant calcium administration. Pharmacotherapy 2011;31(10):298e-302e. DOI
  52. Vitekta [package insert]. Foster City, CA: Gilead Sciences, Inc.; 2014.
  53. Storan ER, O'Gorman SM, Murphy A, Laing M. Case Report of Calciphylaxis Secondary to Calcium and Vitamin D<sub>3</sub> Supplementation. J Cutan Med Surg. 2017;21(2):162-163. DOI
  54. Jenkins DJA, Spence JD, Giovannucci EL, et al. Supplemental vitamins and minerals for CVD prevention and treatment. J Am Coll Cardiol 2018;71(22):2570-84. PubMed
  55. Borkenhagen JF, Connor EL, Stafstrom CE. Neonatal hypocalcemic seizures due to excessive maternal calcium ingestion. Pediatr Neurol 2013;48(6):469-71. PubMed
  56. WHO recommendations on antenatal care for a positive pregnancy experience. Geneva: World Health Organization; 2016 (http://www.who.int/reproductivehealth/publications/maternal_perinatal_health/ anc-positive-pregnancy-experience/en/).
  57. Aune D, Navarro Rosenblatt DA, Chan DS, et al. Dairy products, calcium, and prostate cancer risk: a systematic review and meta-analysis of cohort studies. Am J Clin Nutr. 2015;101(1):87-117. PubMed
  58. Lan T, Park Y, Colditz GA, et al. Adolescent dairy product and calcium intake in relation to later prostate cancer risk and mortality in the NIH-AARP Diet and Health Study. Cancer Causes Control. 2020;31(10):891-904. PubMed
  59. Zhang Y, Li Y, Liu J, et al. Association of Vitamin D or Calcium Supplementation with Cardiovascular Outcomes and Mortality: A Meta-Analysis with Trial Sequential Analysis. J Nutr Health Aging 2021;25(2):263-270. PubMed
  60. Myung SK, Kim HB, Lee YJ, Choi YJ, Oh SW. Calcium Supplements and Risk of Cardiovascular Disease: A Meta-Analysis of Clinical Trials. Nutrients 2021;13(2):368. PubMed
  61. Hetaimish B. Neonatal Calcinosis Cutis After Treatment of Hypocalcemia with Calcium Gluconate: A Report of 2 Cases. Am J Case Rep 2024;25:e943397. PubMed
  62. US Food and Drug Administration (FDA). Biktarvy Prescribing Information. October 2024. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/210251Orig1s020lbl.pdf. Accessed July 16, 2025.

See these in context on the Calcium 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 →

Proteolytic Enzymes (proteases) 3 references
  1. Weeks JA, Harper RA, Simon RA, Burdick JD. Assessment of sensitization risk of a laundry pre-spotter containing protease. Cutan Ocul Toxicol. 2011;30(4):272-9. PubMed
  2. Marquès LI, Lara S, Abós T, Bartolomé B. Occupational rhinitis due to pepsin. J Investig Allergol Clin Immunol. 2006;16(2):136-7. DOI
  3. Cartier A, Malo JL, Pineau L, Dolovich J. Occupational asthma due to pepsin. J Allergy Clin Immunol. 1984;73(5 Pt 1):574-7. PubMed

See these in context on the Proteolytic Enzymes (proteases) 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

Keep exploring
Supplement interaction checker › Check any supplement or product against your medications Drug–drug interactions › Check two or more of your medications against each other Browse medications A–Z › Every drug we've checked against herbs & supplements NDC & pricing lookup › Find a drug’s NDCs, packaging and costs Ask a pharmacist › Free, personal answer from our licensed team