Probiotic Multi-Enzyme Digestive Formula Ingredients & Drug Interactions
What is this page for?
First and foremost: checking Probiotic Multi-Enzyme Digestive Formula 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
Probiotic Multi-Enzyme Digestive Formula is a dietary supplement by Spring Valley with 13 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, 451 medications have a known interaction with it, the most serious rated major. The ingredients most likely to interact are Lactobacillus Acidophilus, Calcium, Bromelain. Use the checker below to test your specific medication, or read the full HelloPharmacist Interaction Report.
Check Your Meds Against Probiotic Multi-Enzyme Digestive Formula by Spring Valley
Ask about any prescription or over-the-counter medication and we check it for interactions with Probiotic Multi-Enzyme Digestive Formula by Spring Valley — and tell you which ingredient is responsible.
AI summaries are generated from our interaction database for education only — always confirm with your pharmacist. How we use AI
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HelloPharmacist Scorecard of Probiotic Multi-Enzyme Digestive Formula by Spring Valley
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.
What’s inside
Full disclosure
This formula contains 13 ingredients—both active components and inactive binders. The active ingredients are calcium (a mineral for bone and metabolic health), betaine hydrochloride (a stomach acid enhancer), digestive enzymes (amylase, papain, bromelain, lipase, cellulase, pepsin, and protease), ox bile (which aids fat digestion), pancreatin (a blend of digestive enzymes from pork pancreas), and Lactobacillus acidophilus (a live probiotic bacterium).
The inactive ingredients are cellulose, dicalcium phosphate, maltodextrin, croscarmellose, silica, stearic acid, and vegetable magnesium stearate—these are fillers and binders that give the tablet its form and stability.
Does it work?
Strong evidence
Calcium in this product is effective for preventing kidney failure, treating indigestion (dyspepsia), low blood calcium (hypocalcemia), high potassium levels (hyperkalemia), and likely effective for osteoporosis. Lactobacillus acidophilus is possibly effective for irritable bowel syndrome, Helicobacter pylori infection, antibiotic-associated diarrhea, and bacterial vaginosis.
For the other enzymes—betaine hydrochloride, papain, bromelain, pepsin, protease, and lipase—there isn't enough reliable evidence to determine whether they work for their intended uses in this product.
How safe is it?
Well-documented data
Calcium is generally well tolerated at recommended doses, but high amounts can cause problems. You're safe to take it during pregnancy and breastfeeding as long as you stay within recommended amounts; talk with your doctor if you have questions.
Very high doses (over 1500 mg daily) have been weakly linked in some studies to increased prostate cancer risk and possibly cardiovascular concerns, though research on this remains debated. Common side effects are belching, constipation, diarrhea, flatulence, and stomach upset.
Betaine hydrochloride may irritate your stomach and isn't safe if you have ulcers, gastritis, or acid reflux disease; it's best avoided in pregnancy and during breastfeeding. Papain and bromelain are generally well tolerated short-term but may cause allergic reactions, diarrhea, or stomach upset in sensitive people; papain is possibly unsafe in pregnancy, and neither has enough safety data for breastfeeding.
Pepsin and protease can trigger occupational respiratory allergies in sensitive individuals. Lactobacillus acidophilus is generally well tolerated in healthy adults and children, though rare cases of infection have been reported in people with compromised immunity.
Common side effects from the probiotic include gas, bloating, and mild digestive discomfort.
Meds to double-check
Major interaction found
Before you start this product, check with your doctor or pharmacist if you take any HIV integrase inhibitors (dolutegravir, elvitegravir, raltegravir), the antibiotic ceftriaxone given by IV, levothyroxine (thyroid hormone), sotalol (heart rhythm medication), diltiazem (a heart medication), calcipotriene (for psoriasis), warfarin or other blood thinners, antiplatelet drugs, antacids, H2-blockers, proton pump inhibitors, tetracycline antibiotics, or any antibiotics. The calcium and enzymes in this formula can interfere with how these drugs work.
The bottom line
Scorecard at a glanceFully disclosed formula with strong clinical evidence behind its ingredients' uses. Major medication interactions have been identified, and safety information is well characterized.
This is a multi-ingredient digestive and probiotic formula best suited for people looking to support digestion and gut flora. It's particularly important to check your medications before starting—especially if you take HIV drugs, thyroid hormone, heart medications, blood thinners, antibiotics, stomach acid reducers, or warfarin.
If you have ulcers, acid reflux, a compromised immune system, or are pregnant or breastfeeding, talk with your doctor or pharmacist before taking it, since some ingredients carry cautions for these situations.
Educational only — not medical advice; always confirm with your pharmacist. Our editorial policy · How we use AI
Assessment coverage: 8 of 13 active ingredients matched to our full ingredient reviews (monographs). Based on the product label dated Jan 7, 2019.
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
General information
Key facts about Probiotic Multi-Enzyme Digestive Formula, straight from the product label.
| Brand | Spring Valley |
|---|---|
| Barcode (UPC) | 681131111782 |
| Net contents | 200 Tablet(s) |
| Market status | On market |
| Date entered into DSLD | Jan 7, 2019 |
| DSLD ID | 184036 |
| Product type | Other Combinations |
| Supplement form | Tablet Or Pill |
| Dietary claims / uses | All Other, Structure/Function |
| Intended target group(s) | Adult (18 - 50 Years), Dairy Free, Sugar Free |
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 Probiotic Multi-Enzyme Digestive Formula by Spring Valley, sourced from the NIH Dietary Supplement Label Database.
Supplement Facts
| Ingredient | Amount | % DV |
|---|---|---|
| Phosphorus | 111 mg | 11% |
| Calcium | 144 mg | 14% |
| Betaine Hydrochloride | 100 mg | -- |
| Amylase | 50 mg | -- |
| Papain | 25 mg | -- |
| Bromelain | 25 mg | -- |
| Lipase | 10 mg | -- |
| Cellulase | 5 mg | -- |
| Pepsin | 25 mg | -- |
| Pancreatin | 100 mg | -- |
| Ox Bile | 15 mg | -- |
| Protease | 50 mg | -- |
| Lactobacillus Acidophilus | 5 mg | -- |
Other ingredients: Cellulose, Dicalcium Phosphate, Maltodextrin, Croscarmellose, Silica, Stearic Acid, Vegetable Magnesium Stearate
Tap any ingredient to jump to its full detail below.
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.
Precautions
For your protection, do not use if seal under cap is broken or missing.
Contains: Wheat ingredients.
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.
Formula
With Active Acidophilus Cultures
Contains: Wheat ingredients.
General Statements
Digestive health
This formula provides a combination of enzymes and probiotics that support digestive health.
Quality guaranteed
FDA Statement of Identity
Dietary Supplement
Formulation
No Milk or Milk Derivatives, Lactose, Sugar, Preservatives, Soy, Artificial Color, Artificial Flavor, Sodium (less than 5 mg per serving)
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.
Suggested/Recommended/Usage/Directions
Suggested use: Adults, take three tablets before or after a meal.
Storage
Store unopened container at room temperature. Keep bottle tightly closed. Refrigerator after opening.
General
Item No. 57748 B18605W 00A 108234
Is this label outdated? Report a formula or label change and our pharmacy team will review it.
Probiotic Multi-Enzyme Digestive Formula by Spring Valley label
The label scan from the NIH Dietary Supplement Label Database. Tap to enlarge.
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)The Ingredients in Probiotic Multi-Enzyme Digestive Formula by Spring Valley
These are the 13 active ingredients this product is made of. Select any to open its full monograph.
Serving size3 Tablet(s) Dosage formTablet Or Pill Servings per container66 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.
Phosphorus
Calcium
Interacts with168 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 f...
Calcium monograph & interactionsBetaine Hydrochloride
Interacts with36 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 l...
Betaine Hydrochloride monograph & interactionsAmylase
Papain
Interacts with2 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 an...
Papain monograph & interactionsBromelain
Interacts with141 drugs
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 & interactionsLipase
No knowninteractions
Lipase is a digestive enzyme that helps your body break down dietary fats. It is well established as part of prescription pancreatic enzyme therapy fo...
Lipase monograph & interactionsCellulase
Pepsin
No knowninteractions
Proteolytic enzymes are proteins that help break down other proteins, and common examples include bromelain (from pineapple), papain (from papaya), tr...
Pepsin monograph & interactionsPancreatin
Ox Bile
Protease
No knowninteractions
Proteolytic enzymes are proteins that help break down other proteins, and common examples include bromelain (from pineapple), papain (from papaya), tr...
Protease monograph & interactionsLactobacillus Acidophilus
Interacts with182 drugs
Lactobacillus acidophilus is a 'friendly' bacterium used as a probiotic to support gut and vaginal health. It is generally well tolerated in healthy p...
Lactobacillus Acidophilus monograph & interactionsOther (inactive) ingredients: Cellulose, Dicalcium Phosphate, Maltodextrin, Croscarmellose, Silica, Stearic Acid, Vegetable Magnesium Stearate. These complete the product’s ingredient list but are not active constituents.
Probiotic Multi-Enzyme Digestive Formula by Spring Valley Drug Interactions
HelloPharmacist Interaction Report
Spring Valley's Probiotic Multi-Enzyme Digestive Formula interacts with medications through its calcium, betaine hydrochloride, papain, bromelain, and Lactobacillus acidophilus content.
The most serious interaction is calcium with HIV integrase inhibitors (dolutegravir and elvitegravir)—calcium can cut their blood levels by up to 40%, potentially reducing their ability to control HIV. This requires spacing doses by 2 to 6 hours apart.
Read the full breakdown — every affected drug type, severity by severity
Calcium also poses major risks with the antibiotic ceftriaxone when given intravenously; the two can form dangerous deposits in the lungs and kidneys and must not be used within 48 hours of each other. Additionally, calcium moderately reduces the absorption of levothyroxine (thyroid hormone), sotalol (a heart medication), and raltegravir (another HIV drug), and may lower diltiazem effectiveness or raise calcium levels if you're already taking calcipotriene for psoriasis.
Betaine hydrochloride theoretically weakens antacids, H2-blockers (stomach acid reducers), and proton pump inhibitors (PPIs) by counteracting their effect. Papain may increase warfarin's blood-thinning effect, and bromelain may boost bleeding risk if combined with blood thinners or antiplatelet drugs.
Lactobacillus acidophilus could be killed off if taken at the same time as antibiotics, reducing the probiotic's benefit.
Altogether, these interactions span 451 individual medications. We could not check phosphorus, amylase, cellulase, pancreatin, or ox bile for interactions.
Use the medication checker below to see if any of your prescriptions are on this list before you start.
Check your own medications below · Editorial policy · How we use AI
Want to check YOUR meds against Probiotic Multi-Enzyme Digestive Formula?
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 checkerIngredients driving the most interactions
Individual Drug Interactions
The ingredients in Probiotic Multi-Enzyme Digestive Formula interact with 451 drugs. Click any drug to see the details.
5 of the 13 ingredients in Probiotic Multi-Enzyme Digestive Formula interact with drugs. Each result below shows which ingredient is responsible. Lactobacillus Acidophilus Calcium Bromelain Betaine Hydrochloride Papain
Ampicillin, SulbactamUnasyn
How Ampicillin, Sulbactam interacts with Probiotic Multi-Enzyme Digestive Formula — through 1 ingredient. Tap an ingredient for the detail:
Lactobacillus AcidophilusAntibiotic Drugs Moderate
Interaction Summary
Theoretically, taking Lactobacillus acidophilus with antibiotic drugs might decrease the effectiveness of L.
Read the full Lactobacillus Acidophilus + Ampicillin, Sulbactam interactionAnacaulase-bcdbNexoBrid
How Anacaulase-bcdb interacts with Probiotic Multi-Enzyme Digestive Formula — through 1 ingredient. Tap an ingredient for the detail:
BromelainAnticoagulant/antiplatelet Drugs Moderate
Interaction Summary
Bromelain may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Read the full Bromelain + Anacaulase-bcdb interactionAnagrelideAgrylin
How Anagrelide interacts with Probiotic Multi-Enzyme Digestive Formula — through 1 ingredient. Tap an ingredient for the detail:
BromelainAnticoagulant/antiplatelet Drugs Moderate
Interaction Summary
Bromelain may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Read the full Bromelain + Anagrelide interactionAnisindioneMiradon
How Anisindione interacts with Probiotic Multi-Enzyme Digestive Formula — through 1 ingredient. Tap an ingredient for the detail:
BromelainAnticoagulant/antiplatelet Drugs Moderate
Interaction Summary
Bromelain may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Read the full Bromelain + Anisindione interactionAntithrombin IiiThrombate III
How Antithrombin Iii interacts with Probiotic Multi-Enzyme Digestive Formula — through 1 ingredient. Tap an ingredient for the detail:
BromelainAnticoagulant/antiplatelet Drugs Moderate
Interaction Summary
Bromelain may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Read the full Bromelain + Antithrombin Iii interactionApixabanEliquis
How Apixaban interacts with Probiotic Multi-Enzyme Digestive Formula — through 1 ingredient. Tap an ingredient for the detail:
BromelainAnticoagulant/antiplatelet Drugs Moderate
Interaction Summary
Bromelain may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Read the full Bromelain + Apixaban interactionArgatrobanArgatroban
How Argatroban interacts with Probiotic Multi-Enzyme Digestive Formula — through 1 ingredient. Tap an ingredient for the detail:
BromelainAnticoagulant/antiplatelet Drugs Moderate
Interaction Summary
Bromelain may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Read the full Bromelain + Argatroban interactionAspirinAngettes 75, ASA, Asaphen, Aspirin, Caprin, Cartia +8 more
How Aspirin interacts with Probiotic Multi-Enzyme Digestive Formula — through 1 ingredient. Tap an ingredient for the detail:
BromelainAnticoagulant/antiplatelet Drugs Moderate
Interaction Summary
Bromelain may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Read the full Bromelain + Aspirin interactionAspirin, Aluminum Hydroxide, Codeine Phosphate, Magnesium HydroxideAscriptin Codeine #3
How Aspirin, Aluminum Hydroxide, Codeine Phosphate, Magnesium Hydroxide interacts with Probiotic Multi-Enzyme Digestive Formula — through 3 ingredients. Tap an ingredient for the detail:
BromelainAnticoagulant/antiplatelet Drugs Moderate
Interaction Summary
Bromelain may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Read the full Bromelain + Aspirin, Aluminum Hydroxide, Codeine Phosphate, Magnesium Hydroxide interactionCalciumAluminum Moderate
Interaction Summary
Calcium citrate might increase aluminum absorption and toxicity.
Read the full Calcium + Aspirin, Aluminum Hydroxide, Codeine Phosphate, Magnesium Hydroxide interactionBetaine HydrochlorideAntacids Minor
Interaction Summary
Betaine hydrochloride increases stomach acidity and could decrease the effects of antacids.
Read the full Betaine Hydrochloride + Aspirin, Aluminum Hydroxide, Codeine Phosphate, Magnesium Hydroxide interactionAspirin, ButalbitalAxotal
How Aspirin, Butalbital interacts with Probiotic Multi-Enzyme Digestive Formula — through 1 ingredient. Tap an ingredient for the detail:
BromelainAnticoagulant/antiplatelet Drugs Moderate
Interaction Summary
Bromelain may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Read the full Bromelain + Aspirin, Butalbital interactionAspirin, Butalbital, CaffeineFiorinal
How Aspirin, Butalbital, Caffeine interacts with Probiotic Multi-Enzyme Digestive Formula — through 1 ingredient. Tap an ingredient for the detail:
BromelainAnticoagulant/antiplatelet Drugs Moderate
Interaction Summary
Bromelain may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Read the full Bromelain + Aspirin, Butalbital, Caffeine interactionAspirin, Butalbital, Caffeine, Codeine PhosphateFiorinal w/ Codeine
How Aspirin, Butalbital, Caffeine, Codeine Phosphate interacts with Probiotic Multi-Enzyme Digestive Formula — through 1 ingredient. Tap an ingredient for the detail:
BromelainAnticoagulant/antiplatelet Drugs Moderate
Interaction Summary
Bromelain may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Read the full Bromelain + Aspirin, Butalbital, Caffeine, Codeine Phosphate interactionAspirin, Butalbital, Caffeine, PhenacetinMarnal
How Aspirin, Butalbital, Caffeine, Phenacetin interacts with Probiotic Multi-Enzyme Digestive Formula — through 1 ingredient. Tap an ingredient for the detail:
BromelainAnticoagulant/antiplatelet Drugs Moderate
Interaction Summary
Bromelain may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Read the full Bromelain + Aspirin, Butalbital, Caffeine, Phenacetin interactionAspirin, CaffeineAnacin
How Aspirin, Caffeine interacts with Probiotic Multi-Enzyme Digestive Formula — through 1 ingredient. Tap an ingredient for the detail:
BromelainAnticoagulant/antiplatelet Drugs Moderate
Interaction Summary
Bromelain may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Read the full Bromelain + Aspirin, Caffeine interactionAspirin, Caffeine, Codeine PhosphateAnacin w/ Codeine
How Aspirin, Caffeine, Codeine Phosphate interacts with Probiotic Multi-Enzyme Digestive Formula — through 1 ingredient. Tap an ingredient for the detail:
BromelainAnticoagulant/antiplatelet Drugs Moderate
Interaction Summary
Bromelain may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Read the full Bromelain + Aspirin, Caffeine, Codeine Phosphate interactionAspirin, Caffeine, Dihydrocodeine BitartrateSynalgos DC
How Aspirin, Caffeine, Dihydrocodeine Bitartrate interacts with Probiotic Multi-Enzyme Digestive Formula — through 1 ingredient. Tap an ingredient for the detail:
BromelainAnticoagulant/antiplatelet Drugs Moderate
Interaction Summary
Bromelain may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Read the full Bromelain + Aspirin, Caffeine, Dihydrocodeine Bitartrate interactionAspirin, Caffeine, Dover's PwdAcedoval, Dovacet
How Aspirin, Caffeine, Dover's Pwd interacts with Probiotic Multi-Enzyme Digestive Formula — through 1 ingredient. Tap an ingredient for the detail:
BromelainAnticoagulant/antiplatelet Drugs Moderate
Interaction Summary
Bromelain may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Read the full Bromelain + Aspirin, Caffeine, Dover's Pwd interactionAspirin, Caffeine, HydrocodoneDamason-P
How Aspirin, Caffeine, Hydrocodone interacts with Probiotic Multi-Enzyme Digestive Formula — through 1 ingredient. Tap an ingredient for the detail:
BromelainAnticoagulant/antiplatelet Drugs Moderate
Interaction Summary
Bromelain may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Read the full Bromelain + Aspirin, Caffeine, Hydrocodone interactionAspirin, Caffeine, Isobutylallylbarbituric Acid, PhenacetinLanorinal
How Aspirin, Caffeine, Isobutylallylbarbituric Acid, Phenacetin interacts with Probiotic Multi-Enzyme Digestive Formula — through 1 ingredient. Tap an ingredient for the detail:
BromelainAnticoagulant/antiplatelet Drugs Moderate
Interaction Summary
Bromelain may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Read the full Bromelain + Aspirin, Caffeine, Isobutylallylbarbituric Acid, Phenacetin interactionAspirin, Caffeine, OrphenadrineInvagesic, Invagesic Forte, Norgesic, Norgesic Forte, Orphengesic, Orphengesic Forte
How Aspirin, Caffeine, Orphenadrine interacts with Probiotic Multi-Enzyme Digestive Formula — through 1 ingredient. Tap an ingredient for the detail:
BromelainAnticoagulant/antiplatelet Drugs Moderate
Interaction Summary
Bromelain may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Read the full Bromelain + Aspirin, Caffeine, Orphenadrine interactionAspirin, Caffeine, Phenacetin, PropoxypheneMargesic Comp. 65
How Aspirin, Caffeine, Phenacetin, Propoxyphene interacts with Probiotic Multi-Enzyme Digestive Formula — through 1 ingredient. Tap an ingredient for the detail:
BromelainAnticoagulant/antiplatelet Drugs Moderate
Interaction Summary
Bromelain may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Read the full Bromelain + Aspirin, Caffeine, Phenacetin, Propoxyphene interactionAspirin, Calcium Carbonate, Magnesium Carbonate, Magnesium OxideBufferin
How Aspirin, Calcium Carbonate, Magnesium Carbonate, Magnesium Oxide interacts with Probiotic Multi-Enzyme Digestive Formula — through 2 ingredients. Tap an ingredient for the detail:
BromelainAnticoagulant/antiplatelet Drugs Moderate
Interaction Summary
Bromelain may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Read the full Bromelain + Aspirin, Calcium Carbonate, Magnesium Carbonate, Magnesium Oxide interactionBetaine HydrochlorideAntacids Minor
Interaction Summary
Betaine hydrochloride increases stomach acidity and could decrease the effects of antacids.
Read the full Betaine Hydrochloride + Aspirin, Calcium Carbonate, Magnesium Carbonate, Magnesium Oxide interactionAspirin, CarisoprodolSoma Compound
How Aspirin, Carisoprodol interacts with Probiotic Multi-Enzyme Digestive Formula — through 1 ingredient. Tap an ingredient for the detail:
BromelainAnticoagulant/antiplatelet Drugs Moderate
Interaction Summary
Bromelain may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Read the full Bromelain + Aspirin, Carisoprodol interactionAspirin, Carisoprodol, Codeine PhosphateSoma Compound w/ Codeine
How Aspirin, Carisoprodol, Codeine Phosphate interacts with Probiotic Multi-Enzyme Digestive Formula — through 1 ingredient. Tap an ingredient for the detail:
BromelainAnticoagulant/antiplatelet Drugs Moderate
Interaction Summary
Bromelain may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Read the full Bromelain + Aspirin, Carisoprodol, Codeine Phosphate interactionAspirin, Chlorpheniramine, PhenylpropanolamineAlka-Seltzer Plus Cold
How Aspirin, Chlorpheniramine, Phenylpropanolamine interacts with Probiotic Multi-Enzyme Digestive Formula — through 1 ingredient. Tap an ingredient for the detail:
BromelainAnticoagulant/antiplatelet Drugs Moderate
Interaction Summary
Bromelain may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Read the full Bromelain + Aspirin, Chlorpheniramine, Phenylpropanolamine interactionAspirin, Citric Acid, Sodium BicarbonateAlka-Seltzer Pain Reliever and Antacid
How Aspirin, Citric Acid, Sodium Bicarbonate interacts with Probiotic Multi-Enzyme Digestive Formula — through 2 ingredients. Tap an ingredient for the detail:
BromelainAnticoagulant/antiplatelet Drugs Moderate
Interaction Summary
Bromelain may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Read the full Bromelain + Aspirin, Citric Acid, Sodium Bicarbonate interactionBetaine HydrochlorideAntacids Minor
Interaction Summary
Betaine hydrochloride increases stomach acidity and could decrease the effects of antacids.
Read the full Betaine Hydrochloride + Aspirin, Citric Acid, Sodium Bicarbonate interactionAspirin, Codeine PhosphateAspirin w/ Codeine
How Aspirin, Codeine Phosphate interacts with Probiotic Multi-Enzyme Digestive Formula — through 1 ingredient. Tap an ingredient for the detail:
BromelainAnticoagulant/antiplatelet Drugs Moderate
Interaction Summary
Bromelain may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Read the full Bromelain + Aspirin, Codeine Phosphate interactionAspirin, Codeine Phosphate, MethocarbamolRobaxisal C
How Aspirin, Codeine Phosphate, Methocarbamol interacts with Probiotic Multi-Enzyme Digestive Formula — through 1 ingredient. Tap an ingredient for the detail:
BromelainAnticoagulant/antiplatelet Drugs Moderate
Interaction Summary
Bromelain may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Read the full Bromelain + Aspirin, Codeine Phosphate, Methocarbamol interactionAspirin, Codeine Phosphate, PhenobarbitalPhenaphen
How Aspirin, Codeine Phosphate, Phenobarbital interacts with Probiotic Multi-Enzyme Digestive Formula — through 1 ingredient. Tap an ingredient for the detail:
BromelainAnticoagulant/antiplatelet Drugs Moderate
Interaction Summary
Bromelain may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Read the full Bromelain + Aspirin, Codeine Phosphate, Phenobarbital interactionAspirin, Diphenhydramine, PhenylpropanolamineAlka Seltzer Plus Night Time Effervescent
How Aspirin, Diphenhydramine, Phenylpropanolamine interacts with Probiotic Multi-Enzyme Digestive Formula — through 1 ingredient. Tap an ingredient for the detail:
BromelainAnticoagulant/antiplatelet Drugs Moderate
Interaction Summary
Bromelain may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Read the full Bromelain + Aspirin, Diphenhydramine, Phenylpropanolamine interactionEach ingredient & the kinds of drugs it affects
For each ingredient in Probiotic Multi-Enzyme Digestive Formula 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.
Lactobacillus Acidophilus
Antibiotic Drugs
Theoretically, taking Lactobacillus acidophilus with antibiotic drugs might decrease the effectiveness of L. acidophilus.
L. acidophilus preparations usually contain live and active organisms. Therefore, simultaneously taking antibiotics might kill a significant number of the organisms. Tell patients to separate administration of antibiotics and L. acidophilus preparations by at least two hours.
Calcium
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Bromelain
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.
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.
Betaine Hydrochloride
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.
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.
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
Papain
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.
Brand information
Manufacturer and brand details for Probiotic Multi-Enzyme Digestive Formula, from the product label.
Spring Valley
See all Spring Valley products- Name
- Wal-Mart Stores, Inc.
- City
- Bentonville
- State
- AR
- ZipCode
- 72716
- Phone Number
- 1-866-251-1662
- Web Address
- Walmart.com/springvalley
Probiotic Multi-Enzyme Digestive Formula by Spring Valley: Common Questions
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Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy
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The Full Monographs Behind Probiotic Multi-Enzyme Digestive Formula’s Ingredients
Every ingredient we hold a full HelloPharmacist monograph for — uses, evidence, safety, and the complete interaction list.
Calcium
Interacts with 168 drugsCalcium 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 monographBetaine Hydrochloride
Interacts with 36 drugsBetaine 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 monographPapain
Interacts with 2 drugsPapain 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 monographBromelain
Interacts with 141 drugsBromelain 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 monographLipase
Lipase is a digestive enzyme that helps your body break down dietary fats. It is well established as part of prescription pancreatic enzyme therapy for people who cannot make enough of their...
Read the full Lipase monograph → Herb & supplement monographProteolytic 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 monographLactobacillus Acidophilus
Interacts with 182 drugsLactobacillus acidophilus is a 'friendly' bacterium used as a probiotic to support gut and vaginal health. It is generally well tolerated in healthy people, and there is reasonable evidence...
Read the full Lactobacillus Acidophilus monograph →Sources & How We Checked
Probiotic Multi-Enzyme Digestive Formula'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.
- NIH Dietary Supplement Label Database (DSLD) — The official product label on file for this supplement.
- Natural Medicines (Therapeutic Research Center) — Evidence-graded clinical reference behind the ingredient interaction data.
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 113 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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- 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
- 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
- Maton PN, Burton ME. Antacids revisited: a review of their clinical pharmacology and recommended therapeutic use. Drugs 1999;57:855-70.
- Clemens JD, Feinstein AR. Calcium carbonate and constipation: a historical review of medical mythopoeia. Gastroenterology 1977;72:957-61. DOI
- 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
- Friedman PA, Bushinsky DA. Diuretic effects on calcium metabolism. Semin Nephrol 1999;19:551-6.
- Koo WK, Walters JC, Esterlitz J, et al. Maternal calcium supplementation and fetal bone mineralization. Obstet Gynecol 1999;94:577-82. DOI
- 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
- Murry JJ, Healy MD. Drug-mineral interactions: a new responsibility for the hospital dietician. J Am Diet Assoc 1991;91:66-73.
- 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.
- Butner LE, Fulco PP, Feldman G, et al. Calcium carbonate-induced hypothyroidism. Ann Intern Med 2000:132:595. PubMed
- Schneyer CR. Calcium carbonate and reduction of levothyroxine efficacy. JAMA 1998;279:750. PubMed
- 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
- Singh N, Singh PN, Hershman JM. Effect of calcium carbonate on the absorption of levothyroxine. JAMA 2000;283:2822-5. PubMed
- 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
- 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
- Bar-Or D, Yoel G. Calcium and calciferol antagonize effect of verapamil in atrial fibrillation. Br Med J 1981;282:1585-6.
- 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
- Simoneau G. Absence of rebound effect with calcium carbonate. Eur J Drug Metab Pharmacokinet 1996;21:351-7. PubMed
- 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
- 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.
- Gueguen L, Pointillart A. The bioavailability of dietary calcium. J Am Coll Nutr 2000;19:119s-136s. PubMed
- Vella A, Gerber TC, Hayes DL, Reeder GS. Digoxin, hypercalcaemia, and cardiac conduction. Postgrad Med J 1999;75:554-6. PubMed
- 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
- 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
- Weingarten MA, Zalmanovici A, Yaphe J. Dietary calcium supplementation for preventing colorectal cancer and adenomatous polyps. Cochrane Database Syst Rev 2004;(1):CD003548. PubMed
- 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
- 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
- Rocephin (ceftriaxone) and calcium interaction. Pharmacist's Letter / Prescriber's Letter 2007;23(10):231005.
- 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.
- 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
- Calcium supplementation and vascular events. Pharmacist's Letter / Prescriber's Letter 2008;24(3):240306.
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- Grove ML, Cook D. Calcium and heart attacks. Doesn't apply to most calcium prescriptions. BMJ. 2010;341:c5003. PubMed
- Insentress [package insert]. Whitehouse Station, NJ: Merck Sharp & Dohme Corp.; 2014.
- 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
- Vitekta [package insert]. Foster City, CA: Gilead Sciences, Inc.; 2014.
- 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
- 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
- Borkenhagen JF, Connor EL, Stafstrom CE. Neonatal hypocalcemic seizures due to excessive maternal calcium ingestion. Pediatr Neurol 2013;48(6):469-71. PubMed
- 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/).
- 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
- 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
- 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
- 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
- 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
- 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.
Betaine Hydrochloride 2 references
- 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
- 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 →
Papain 11 references
- The Review of Natural Products by Facts and Comparisons. St. Louis, MO: Wolters Kluwer Co., 1999.
- 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.
- 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.
- 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.
- 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
- Walker-Renard, P. Update on the medicinal management of phytobezoars. Am J Gastroenterol. 1993;88(10):1663-1666.
- Tymoszuk D, Wiszniewska M, Walusiak-Skorupa J. Papain-induced occupational rhinoconjunctivitis and asthma - A case report. Med Pr 2016;67(1):109-12. PubMed
- Soto-Mera MT, López-Rico MR, Filgueira JF, et al. Occupational allergy to papain. Allergy 2000;55(10):983-4. PubMed
- Tarlo SM, Shaikh W, Bell B, et al. Papain-induced allergic reactions. Clin Allergy 1978;8(3):207-15. PubMed
- 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
- 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
Bromelain 19 references
- Nettis E, Napoli G, Ferrannini A, Tursi A. IgE-mediated allergy to bromelain. Allergy 2001;56:257-8. PubMed
- 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
- 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
- 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.
- 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
- 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.
- Glaser D, Hilberg T. The influence of bromelain on platelet count and platelet activity in vitro. Platelets 2006;17:37-41. PubMed
- Heinicke R M, van der Wal L, Yokoyama M. Effect of bromelain (Ananase) on human platelet aggregation. Experientia 1972;28:844-5. PubMed
- 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
- 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.
- Galleguillos, F. and Rodriguez, J. C. Asthma caused by bromelin inhalation. Clin Allergy 1978;8(1):21-24. PubMed
- 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.
- Martin GJ, Ehrenreich J, and Asbell N. Bromelain: pineapple proteases with anti-edema activity. Exp Med Surg 1962;20:227-247.
- 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
- 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
- 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
- Pfister P, Garcia Wendel PD, Kim BS, et al. Coagulation side effects of enzymatic debridement in burned patients. Burns 2022. PubMed
- 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
- 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
Lipase 1 reference
- 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
Proteolytic Enzymes (proteases) 3 references
- 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
- Marquès LI, Lara S, Abós T, Bartolomé B. Occupational rhinitis due to pepsin. J Investig Allergol Clin Immunol. 2006;16(2):136-7. DOI
- 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 →
Lactobacillus Acidophilus 15 references
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See these in context on the Lactobacillus Acidophilus monograph →
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