Major interaction on record — check this product against your medications before combining. Based on 7 of 9 ingredients. Check your meds →
Dietary supplement

Digest-Rite Advanced Ingredients & Drug Interactions

by NewtonEverett

Digest-Rite Advanced label
See full label image
Capsule Category: Other Combinations
Most serious interaction: Major
Clinical methodology reviewed by · Updated Sep 23, 2026 · Label data from the NIH DSLD
What is this page for?

First and foremost: checking Digest-Rite Advanced 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

Digest-Rite Advanced is a dietary supplement by NewtonEverett with 9 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, 394 medications have a known interaction with it, the most serious rated major. The ingredients most likely to interact are Calcium, Bromelain, Papaya fruit powder. Use the checker below to test your specific medication, or read the full HelloPharmacist Interaction Report.

Jump to a section

Check Your Meds Against Digest-Rite Advanced by NewtonEverett

Ask about any prescription or over-the-counter medication and we check it for interactions with Digest-Rite Advanced by NewtonEverett — and tell you which ingredient is responsible.

Pharmacist-reviewed data Checks every ingredient Answer in seconds
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HelloPharmacist Scorecard of Digest-Rite Advanced by NewtonEverett

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 23, 2026

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 4 of its 11 active ingredients.
  • “Enzyme Blend” is a proprietary blend — the label gives one combined amount (225 mg) without saying how much of each component you get.
  • “Pancreatin” is listed as a grouped ingredient — the label doesn't break down how much of each component you get.

Digest-Rite Advanced contains 11 ingredients, most of them digestive enzymes. The active components include calcium (for bone health and other functions), multiple digestive enzymes—amylase, papain, bromelain, protease, lipase, cellulase, acid protease—plus betaine HCl (which increases stomach acid), papaya fruit powder, ox bile extract, and pancreatin (a blend of enzymes).

The product also contains inactive ingredients: gelatin, microcrystalline cellulose, vegetable magnesium stearate, and silicon dioxide.

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: Support digestive health and food breakdown.
  • We looked for evidence on: Dyspepsia, Pancreatic insufficiency, Intestinal parasite infection, Diarrhea, indigestion, bloating and gas — and 1 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 Intestinal parasite infection.
  • Also on file: Lipase is rated "Insufficient Reliable Evidence To Rate" for Dyspepsia.

Calcium in this product is effective for kidney failure, dyspepsia (indigestion), low blood calcium (hypocalcemia), high blood potassium (hyperkalemia), and is likely effective for osteoporosis. For the digestive enzymes—papain, bromelain, lipase, and betaine HCl—the evidence we hold shows insufficient reliable data to rate their effectiveness for conditions like allergies, burns, cancer, chronic venous insufficiency, diabetes, or digestive issues.

Papaya fruit powder likewise lacks sufficient evidence for aging skin, hair loss, cancer, or diabetes. The bottom line: calcium has established benefits, but most of the other active ingredients in this product lack strong evidence supporting their claimed digestive or health effects.

The evidence, ingredient by ingredient Calcium Papain Bromelain Pancreatic Enzyme Products Betaine Hydrochloride Papaya Proteolytic Enzymes (proteases)

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 7 of the 7 matched ingredients.
  • Pregnancy & breastfeeding safety ratings cover 7 of 7.
  • General safety write-ups exist for 7 of 7.
  • 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. Common side effects are belching, constipation, diarrhea, flatulence, and stomach upset.

Rare serious effects include kidney stones and calciphylaxis. There is also epidemiological concern that calcium intake over 1500–2000 mg daily might be linked to increased prostate cancer risk and possibly cardiovascular disease, though these findings have been debated.

Papain supplements may irritate the digestive tract and cause allergic reactions; it is possibly unsafe in pregnancy. Bromelain is generally well tolerated short-term but is best avoided in pregnancy; safety while breastfeeding is unknown.

Betaine HCl may irritate the stomach and is unsafe for people with ulcers, gastritis, or reflux; it is best avoided in pregnancy and breastfeeding. Protease and acid protease are generally well tolerated but may cause digestive upset or allergic reactions.

Papaya fruit (ripe) is safe as food, but unripe papaya, latex, and seeds should be avoided in pregnancy; large amounts may also reduce thyroid medication effectiveness.

Side effects, ingredient by ingredient Calcium Papain Bromelain Pancreatic Enzyme Products Betaine Hydrochloride Papaya Proteolytic Enzymes (proteases)

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?
  • 5 of the 7 matched ingredients can interact with medications — Papain, Betaine Hydrochloride, Papaya, Calcium, Bromelain.
  • 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: 394 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 Digest-Rite Advanced, check with your doctor or pharmacist if you take HIV integrase inhibitors (dolutegravir, elvitegravir), blood thinners or antiplatelet drugs (particularly warfarin), thyroid medication (levothyroxine), heart drugs (diltiazem, amiodarone, sotalol), diabetes medications, antibiotics (especially tetracycline or ceftriaxone), or acid-reducing medications (H2-blockers, antacids, PPIs). Calcium and papaya components can significantly affect how these drugs work.

Check your own medication Run your meds through the checker above

The bottom line

Scorecard at a glanceFormula with limited ingredient disclosure with clinical evidence supporting its stated purpose. Major medication interactions have been identified, and safety information is well characterized.

This product combines digestive enzymes with calcium, which works well for bone health and certain digestive conditions, but most of the enzyme components lack strong evidence of benefit. The bigger concern is that calcium and papain/papaya can significantly interact with common medications—especially blood thinners, thyroid drugs, HIV treatments, and heart medications.

If you take any prescription drugs, check them against this product's interaction data before starting, and talk it over with your own doctor or pharmacist to make sure it is right for you.

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

Assessment coverage: 8 of 11 active ingredients matched to our full ingredient reviews (monographs). Based on the product label dated Feb 26, 2020.

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 Digest-Rite Advanced, straight from the product label.

Brand NewtonEverett
Barcode (UPC) 818423027067
Net contents 90 Capsule(s)
Market status On market
Date entered into DSLD Feb 26, 2020
DSLD ID 213261
Product type Other Combinations
Supplement form Capsule
Dietary claims / uses All Other, Structure/Function
Intended target group(s) 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 Digest-Rite Advanced by NewtonEverett, 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 Capsule(s)
Maximum serving Sizes:
1 Capsule(s)
Servings per container
90
UPC/BARCODE
818423027067
IngredientAmount% DV
Calcium36 mg3%
Amylase0 NP--
Papain0 NP--
Bromelain0 NP--
Protease0 NP--
Lipase0 NP--
Cellulase0 NP--
Enzyme Blend225 mg--
Betaine HCl200 mg--
Papaya fruit powder45 mg--
Ox Bile extract100 mg--
Pancreatin0 NP--
Acid Protease0 NP--

Other ingredients: Gelatin, Microcrystalline Cellulose, Vegetable Magnesium Stearate, Silicon Dioxide

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

Support digestive health with Digest-Rite.

Formula

During digestion, enzymes are secreted in the gastrointestinal tract to break down foods in the body so that the nutrients can be absorbed. This comprehensive enzyme formula works to help your body break down fats, carbohydrates and proteins for optimal nutrient uptake. A healthy digestive system is important for overall health and vitality. Digest-Rite is formulated with key ingredients, including: Bromelain to support protein breakdown & digestion Betaine HCI to support overall digestive function Papain to promote protein digestion

Complete Formula Including Betaine HCl Papaya Bromelain

Suggested/Recommended/Usage/Directions

Suggested Use: As a dietary supplement, take 1 capsule with a meal.

Precautions

Not manufactured with wheat, gluten, soy, milk, egg, fish, shellfish or tree nut ingredients. Produced in a GMP facility that processes other ingredients containing these allergens.

Warning: For adults only.

Consult physician if pregnant/nursing, taking medication, or have a medical condition.

Do not eat freshness packet. Keep in bottle.

Keep out of reach of children.

Do not use if safety seal is damaged or missing.

Formulation

Not manufactured with wheat, gluten, soy, milk, egg, fish, shellfish or tree nut ingredients.

Optimizes nutrient uptake Digestion support

Storage

Store in a cool, dry place after opening.

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

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

See for yourself

Digest-Rite Advanced by NewtonEverett label

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

Digest-Rite Advanced 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 Digest-Rite Advanced by NewtonEverett

These are the 9 active ingredients this product is made of. Select any to open its full monograph.

Serving size1 Capsule(s) Dosage formCapsule Servings per container90 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
36 mg per serving Form: Calcium Carbonate

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

Papain

Interacts with
2 drugs
0 NP per serving

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

Bromelain

Interacts with
141 drugs
0 NP per serving Form: Pineapple

Bromelain is a group of protein-digesting enzymes from pineapple that people take mainly for inflammation, swelling, and sinus problems. Some early st...

Bromelain monograph & interactions

Cellulase

0 NP per serving

Enzyme Blend

225 mg per serving

Betaine HCl

Interacts with
36 drugs
200 mg per serving

Betaine hydrochloride is a supplement used to temporarily increase stomach acid in people who may have low acid levels. Evidence for its benefits is l...

Betaine HCl monograph & interactions

Papaya fruit powder

Interacts with
92 drugs
45 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 fruit powder monograph & interactions

Ox Bile extract

100 mg per serving Form: Total Cholic Acids

Acid Protease

No known
interactions
0 NP per serving Form: Aspergillopepsin

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

Acid Protease monograph & interactions

Other (inactive) ingredients: Gelatin, Microcrystalline Cellulose, Vegetable Magnesium Stearate, Silicon Dioxide. These complete the product’s ingredient list but are not active constituents.

Interaction report

Digest-Rite Advanced by NewtonEverett Drug Interactions

Want to check YOUR meds against Digest-Rite Advanced?

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
394Drugs
7 Major 347 Moderate 40 Minor

Ingredients driving the most interactions

Calcium 168
Bromelain 141
Papaya fruit powder 92
Betaine HCl 36
Papain 2

Individual Drug Interactions

The ingredients in Digest-Rite Advanced interact with 394 drugs. Click any drug to see the details.

6 of the 9 ingredients in Digest-Rite Advanced interact with drugs. Each result below shows which ingredient is responsible. Calcium Bromelain Papaya fruit powder Betaine HCl Papain Pancreatin

Each ingredient & the kinds of drugs it affects

For each ingredient in Digest-Rite Advanced 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

Bromelain2 drug types · 141 drugs

Anticoagulant/Antiplatelet Drugs

Bromelain may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
There is one case report of a patient experiencing minor bruising while taking bromelain with naproxen. Bromelain is thought to have antiplatelet activity. Whether this interaction is of concern with topical bromelain is unclear. Interference with coagulation of burn wounds has been reported in a patient receiving bromelain-based enzymatic debridement. However, observational research has found that topical bromelain debridement is not associated with increases or decreases in laboratory markers of coagulation when compared with surgical debridement.

Likelihood Possible Evidence D
Tetracycline Antibiotics

Theoretically, bromelain might increase levels of tetracycline antibiotics.
Laboratory research suggests that bromelain might increase the absorption of tetracycline antibiotics. However, a study in healthy adults reported no difference in tetracycline plasma levels when a 500 mg dose was taken with or without bromelain 80 mg.

Likelihood Possible Evidence B
Bromelain full monograph & interactions

Papaya fruit powder4 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 fruit powder full monograph & interactions

Betaine HCl3 drug types · 36 drugs

Antacids

Betaine hydrochloride increases stomach acidity and could decrease the effects of antacids.
In human research, betaine hydrochloride increases stomach acidity. Antacids are taken to decrease stomach acidity. Theoretically, taking betaine hydrochloride along with antacids might decrease the effects of the antacids.

Likelihood Possible Evidence D
H2-Blockers

Betaine hydrochloride increases stomach acidity and could decrease the effects of H2-blockers.
In human research, betaine hydrochloride increases stomach acidity. H2-blockers are used to decrease stomach acidity. Theoretically, taking betaine hydrochloride along with H2-blockers might decrease the effects of H2-blockers.

Likelihood Possible Evidence D
Proton Pump Inhibitors (Ppis)

Betaine hydrochloride increases stomach acidity and could decrease the effects of PPIs.
In human research, betaine hydrochloride increases stomach acidity. PPIs are used to decrease stomach acidity. Theoretically, taking betaine hydrochloride along with PPIs might decrease the effects of PPIs

Likelihood Possible Evidence D
Betaine HCl 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

Pancreatin1 drug type · 1 drug

Acarbose (Precose, Prandase)

Theoretically, pancreatic enzyme products may reduce the effects of acarbose.
The digestive enzymes present in pancreatic enzyme products may break down acarbose, reducing its effects.

Likelihood Possible Evidence D
Pancreatin full monograph & interactions
The maker

Brand information

Manufacturer and brand details for Digest-Rite Advanced, from the product label.

NewtonEverett

See all NewtonEverett products
Name
Newton-Everett Nutraceuticals
Street Address
PO Box 27793
City
Scottsdale
State
AZ
ZipCode
85255
Phone Number
866.593.3424
Pharmacist Counseling Corner

Digest-Rite Advanced by NewtonEverett: Common Questions

Does Digest-Rite Advanced by NewtonEverett interact with any medications?
Yes. Based on its ingredients, Digest-Rite Advanced has a known interaction with 394 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?
Digest-Rite Advanced contains 9 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 Digest-Rite Advanced if I'm on blood thinners like warfarin?
No, not without checking first. Papain and papaya fruit powder in this product can increase the effects of warfarin, raising your bleeding risk. Talk with your pharmacist or doctor before taking it.
Does this product work for digestion?
Calcium is effective for indigestion (dyspepsia), but for most of the digestive enzymes in this product—like papain, bromelain, and protease—we don't have enough reliable evidence to say they work. The effectiveness of those ingredients for digestive problems is not established in our data.
What are the most common side effects?
From calcium: belching, constipation, diarrhea, flatulence, and stomach upset. From the enzymes: diarrhea, flatulence, headache, gastric upset, and allergic reactions in sensitive people. Betaine HCl may cause heartburn or stomach irritation.
Is this safe to take in pregnancy?
Calcium at recommended amounts is safe in pregnancy and even important for bone health. However, papain and papaya are possibly unsafe in pregnancy—concentrated papain and unripe papaya especially. Bromelain and betaine HCl should be avoided. Check with your doctor or pharmacist before taking this product during pregnancy.
Will this interfere with my thyroid medication?
Possibly. Both calcium and papaya fruit powder can reduce how well levothyroxine (thyroid medication) works. If you take thyroid medication, space this product at least 4 hours away from your dose and confirm with your pharmacist first.
Is there anything in this product we don't have safety information for?
We could not check amylase, cellulase, and ox bile extract—no interaction data is held for these. For most of the enzyme ingredients, long-term safety data is limited. Use only as directed and check with your provider if you have concerns.

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.

Digest-Rite Advanced label
Go deeper

The Full Monographs Behind Digest-Rite Advanced’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

Bromelain

Interacts with 141 drugs

Bromelain is a group of protein-digesting enzymes from pineapple that people take mainly for inflammation, swelling, and sinus problems. Some early studies are promising, but the overall evi...

Read the full Bromelain monograph → Herb & supplement monograph

Pancreatic Enzyme Products

Interacts with 1 drug

Pancreatic enzyme products supply the digestive enzymes (lipase, protease, and amylase) that some people cannot make enough of, helping them break down and absorb food. Prescription versions...

Read the full Pancreatic Enzyme Products monograph → Herb & supplement monograph

Betaine Hydrochloride

Interacts with 36 drugs

Betaine hydrochloride is a supplement used to temporarily increase stomach acid in people who may have low acid levels. Evidence for its benefits is limited and mostly based on tradition rat...

Read the full Betaine Hydrochloride 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

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 →
Sources

Sources & How We Checked

Digest-Rite Advanced'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 152 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
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  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 →

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 →

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 →

Lipase 1 reference
  1. Casper C, Hascoet JM, Ertl T, et al. Recombinant bile salt-stimulated lipase in preterm infant feeding: A randomized phase 3 study. PLoS One. 2016;11(5):e0156071. PubMed

See these in context on the Lipase monograph →

Betaine Hydrochloride 2 references
  1. Yago MR, Frymoyer A, Benet LZ, Smelick GS, Frassetto LA, Ding X, Dean B, Salphati L, Budha N, Jin JY, Dresser MJ, Ware JA. The use of betaine HCl to enhance dasatinib absorption in healthy volunteers with rabeprazole-induced hypochlorhydria. AAPS J. 2014 PubMed
  2. Yago MR, Frymoyer AR, Smelick GS, Frassetto LA, Budha NR, Dresser MJ, Ware JA, Benet LZ. Gastric reacidification with betaine HCl in healthy volunteers with rabeprazole-induced hypochlorhydria. Mol Pharm. 2013 Nov 4;10(11):4032-7. PubMed

See these in context on the Betaine Hydrochloride 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 →

Pancreatic Enzyme Products 40 references
  1. Martindale W. Martindale the Extra Pharmacopoeia. Pharmaceutical Press, 1999.
  2. McEvoy GK, ed. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists, 1998.
  3. Smyth RL, van Velzen D, Smyth AR, et al. Strictures of ascending colon in cystic fibrosis and high-strength pancreatic enzymes. Lancet 1994;343:85-6. PubMed
  4. Bergner A, Bergner RK. Pulmonary hypersensitivity associated with pancreatin powder exposure. Pediatrics 1975;55:814-7. DOI
  5. Wiessmann KJ, Baur X. Occupational lung disease following long-term inhalation of pancreatic extracts. Eur J Respir Dis 1985;66:13-20.
  6. Bragelmann, R., Armbrecht, U., Rosemeyer, D., Schneider, B., Zilly, W., and Stockbrugger, R. W. The effect of pancreatic enzyme supplementation in patients with steatorrhoea after total gastrectomy. Eur.J Gastroenterol.Hepatol. 1999;11(3):231-237. PubMed
  7. Halm, U., Loser, C., Lohr, M., Katschinski, M., and Mossner, J. A double-blind, randomized, multicentre, crossover study to prove equivalence of pancreatin minimicrospheres versus microspheres in exocrine pancreatic insufficiency. Aliment.Pharmacol.Ther. PubMed
  8. O'Keefe, S. J., Cariem, A. K., and Levy, M. The exacerbation of pancreatic endocrine dysfunction by potent pancreatic exocrine supplements in patients with chronic pancreatitis. J Clin Gastroenterol. 2001;32(4):319-323. PubMed
  9. Shin, S. Y., Hur, G. Y., Ye, Y. M., and Park, H. S. A case of occupational rhinitis caused by porcine pancreatic extract developing into occupational asthma. J Korean Med Sci. 2008;23(2):347-349. PubMed
  10. Andersen, H. O., Hjelt, K., Waever, E., and Overgaard, K. The age-related incidence of meconium ileus equivalent in a cystic fibrosis population: the impact of high-energy intake. J Pediatr Gastroenterol.Nutr 1990;11(3):356-360. DOI
  11. Ramo, O. J., Puolakkainen, P. A., Seppala, K., and Schroder, T. M. Self-administration of enzyme substitution in the treatment of exocrine pancreatic insufficiency. Scand.J Gastroenterol. 1989;24(6):688-692. PubMed
  12. Aparisi, L., Rodrigo, J. M., Serra, M. A., Del Olmo, J., Bisquert, M., and Raga, F. [Efficacy of a new microencapsulated pancreatin versus a conventional preparation, in the treatment of steatorrhea of pancreatic origin]. Rev.Esp.Enferm.Apar.Dig. 1989;76
  13. Ansaldi-Balocco, N., Santini, B., and Sarchi, C. Efficacy of pancreatic enzyme supplementation in children with cystic fibrosis: comparison of two preparations by random crossover study and a retrospective study of the same patients at two different ages DOI
  14. Beverley, D. W., Kelleher, J., Macdonald, A., Littlewood, J. M., Robinson, T., and Walters, M. P. Comparison of four pancreatic extracts in cystic fibrosis. Arch Dis.Child 1987;62(6):564-568. PubMed
  15. Silber, W. Pankreoflat in benign diseases of the oesophagus: a blind therapeutic trial. S.Afr.Med J 7-7-1973;47(26):1137-1138.
  16. Sack, J., Blau, H., Goldfarb, D., Ben-Zaray, S., and Katznelson, D. Hyperuricosuria in cystic fibrosis patients treated with pancreatic enzyme supplements. A study of 16 patients in Israel. Isr.J Med Sci. 1980;16(6):417-419.
  17. Oades, P. J., Bush, A., Ong, P. S., and Brereton, R. J. High-strength pancreatic enzyme supplements and large-bowel stricture in cystic fibrosis. Lancet 1-8-1994;343(8889):109. DOI
  18. Mac Sweeney, E. J., Oades, P. J., Buchdahl, R., Rosenthal, M., and Bush, A. Relation of thickening of colon wall to pancreatic-enzyme treatment in cystic fibrosis. Lancet 3-25-1995;345(8952):752-756. PubMed
  19. Jones, R., Franklin, K., Spicer, R., and Berry, J. Colonic strictures in children with cystic fibrosis on low-strength pancreatic enzymes. Lancet 8-19-1995;346(8973):499. DOI
  20. Taylor, C. J. and Steiner, G. M. Fibrosing colonopathy in a child on low-dose pancreatin. Lancet 10-21-1995;346(8982):1106-1107. PubMed
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See these in context on the Pancreatic Enzyme Products monograph →

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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.

© 2021 Therapeutic Research Center, LLC

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