Interactions on record — worth a quick check against your medications. Based on 7 of 13 ingredients. Check your meds →
Dietary supplement

Fibrenza Systemic Enzyme 500 mg Ingredients & Drug Interactions

by HCP Formulas

Fibrenza Systemic Enzyme 500 mg label
See full label image
Capsule Category: Non-nutrient/non-botanical
Most serious interaction: Moderate
Clinical methodology reviewed by · Updated Sep 16, 2026 · Label data from the NIH DSLD
What is this page for?

First and foremost: checking Fibrenza Systemic Enzyme 500 mg 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: Moderate

Fibrenza Systemic Enzyme 500 mg is a dietary supplement by HCP Formulas with 13 active ingredients. Its ingredients are commonly taken for digestive support for protein digestion, wound cleaning (debridement of dead tissue), sore throat and inflammation.Based on those ingredients, 308 medications have a known interaction with it, the most serious rated moderate. The ingredients most likely to interact are Nattokinase NSK-SD, Bromelain, Papain. Use the checker below to test your specific medication, or read the full HelloPharmacist Interaction Report.

Jump to a section

Check Your Meds Against Fibrenza Systemic Enzyme 500 mg by HCP Formulas

Ask about any prescription or over-the-counter medication and we check it for interactions with Fibrenza Systemic Enzyme 500 mg by HCP Formulas — and tell you which ingredient is responsible.

Pharmacist-reviewed data Checks every ingredient Answer in seconds
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HelloPharmacist Scorecard of Fibrenza Systemic Enzyme 500 mg by HCP Formulas

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 30, 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 0 of its 13 active ingredients.
  • “Proprietary Enzyme Blend” is a proprietary blend — the label gives one combined amount (1,000 mg) without saying how much of each component you get.

This 13-ingredient capsule is a systemic enzyme blend—meaning enzymes designed to work throughout your body rather than just in your stomach. The active ingredients include digestive enzymes (amylase, protease, lipase, peptidase, chymotrypsin, trypsin, and an acid-stable protease variant), plant enzymes (papain from papaya, bromelain from pineapple, and serratiopeptidase from bacteria), fibrinolytic (clot-breaking) enzymes (nattokinase NSK-SD), and antioxidant enzymes (superoxide dismutase and chymotrypsin again for its other roles).

Seaprose-S is included as well. The inactive ingredients are cellulose, rice bran, and rice extract.

Does it work?

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

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

Why this rating?
  • The label markets this product for: fibrin defense, joint health, and recovery support.
  • We looked for evidence on: Osteoarthritis, Knee pain, Sprains, Exercise-induced muscle soreness, Postoperative pain, Postoperative swelling — and 4 related terms.
  • The closest evidence on file: Papain is rated "Insufficient Reliable Evidence To Rate" for Exercise-induced muscle soreness (Natural Medicines).
  • Also on file: Papain is rated "Insufficient Reliable Evidence To Rate" for Wound healing.
  • Also on file: Trypsin is rated "Insufficient Reliable Evidence To Rate" for Exercise-induced muscle soreness, Osteoarthritis, Wound healing, Sprains, and more.

The evidence for most of these enzymes' uses is thin. Papain, bromelain, chymotrypsin, trypsin, lipase, and nattokinase all carry multiple conditions marked "Insufficient Reliable Evidence To Rate"—meaning research hasn't established that they work for those uses.

The one exception is chymotrypsin, which is rated Effective for cataracts; for its other listed uses (burns, fractures, chronic obstructive parotitis) the evidence is also insufficient. For the rest of the ingredients, no effectiveness ratings are on file in our data.

The evidence, ingredient by ingredient Papain Bromelain Proteolytic Enzymes (proteases) Lipase Chymotrypsin Trypsin Nattokinase

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.

Most of these enzymes are generally well tolerated at short-term doses, but some important caveats apply. Papain commonly comes from papaya; in food amounts it's tolerated, but high-dose supplements may irritate your digestive tract and can cause allergic reactions—including rare cases of severe gastritis or esophageal perforation.

Bromelain and nattokinase are also generally tolerated short-term, though both carry a bleeding risk in susceptible people. Trypsin combined with other enzymes may cause mild-to-moderate stomach upset (nausea, heartburn, stomach pain).

Chymotrypsin rarely causes anaphylaxis (a severe allergic reaction). Protease, lipase, and trypsin require medical guidance in pregnancy; papain and bromelain should be avoided.

During breastfeeding, papain, bromelain, protease, lipase, chymotrypsin, trypsin, and nattokinase all lack adequate safety data—talk with your doctor or pharmacist before using.

Side effects, ingredient by ingredient Papain Bromelain Proteolytic Enzymes (proteases) Lipase Chymotrypsin Trypsin Nattokinase

Meds to double-check

Moderate interaction found
Known Interaction Concern · database check
Moderate identified

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

Why this rating?
  • 3 of the 7 matched ingredients can interact with medications — Papain, Bromelain, Nattokinase.
  • The most serious interaction on file is rated Moderate.
  • Some involve high-stakes drug classes: anticoagulant / antiplatelet drugs.
  • For scale: 308 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 Fibrenza, check with your doctor or pharmacist if you take warfarin or other blood thinners (anticoagulants)—papain may dangerously increase warfarin's effect. If you take aspirin or other blood-clotting preventers (antiplatelet drugs), bromelain and nattokinase may raise your bleeding risk (Moderate severity).

If you're on blood-pressure-lowering drugs, nattokinase may lower your pressure further (Moderate severity). Bromelain may slightly increase tetracycline antibiotic levels, though the effect is uncertain (Minor severity).

Check your own medication Run your meds through the checker above

The bottom line

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

This is an enzyme-blend supplement marketed for systemic use, but evidence that it works for specific conditions is limited. The real concern is drug interaction: if you take warfarin, aspirin, other blood thinners, or blood-pressure medication, this product poses a documented bleeding or pressure-drop risk through its papain, bromelain, and nattokinase.

Talk with your doctor or pharmacist before starting, especially if you're on any of those medications or planning pregnancy or breastfeeding.

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 Jun 22, 2023.

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 Fibrenza Systemic Enzyme 500 mg, straight from the product label.

Brand HCP Formulas
Barcode (UPC) 765573629507
Net contents 240 Capsule(s)
Market status On market
Date entered into DSLD Jun 22, 2023
DSLD ID 287146
Product type Non-nutrient/non-botanical
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 Fibrenza Systemic Enzyme 500 mg by HCP Formulas, 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:
2 Capsule(s)
Maximum serving Sizes:
2 Capsule(s)
Servings per container
120
UPC/BARCODE
765573629507
IngredientAmount% DV
Amylase0 NP--
Papain0 NP--
Bromelain0 NP--
Protease0 NP--
Serratiopeptidase0 NP--
Lipase0 NP--
Peptidase0 NP--
Superoxide Dismutase0 NP--
Chymotrypsin0 NP--
Trypsin0 NP--
acid stable Protease0 NP--
Proprietary Enzyme Blend1000 mg--
Nattokinase NSK-SD0 NP--
Seaprose-S0 NP--

Other ingredients: Cellulose, Rice Bran, Rice extract

Tap any ingredient to jump to its full detail below.

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

Suggested Use: Adults take 2 capsules twice daily on an empty stomach (at least 45 minutes before or 60 minutes after meals) with water or as recommended by our healthcare provider.

Formulation

Healthcare professionals worldwide recommend systemic enzymes for their ability to defend against excess fibrin formation, cleanse the body of impurities, improve recovery following exertion, and to help maintain healthy joints, flexibility, and mobility. Fibrenza is a powerful advanced blend of systemic enzymes utilizing AcidDefenz capsule technology that allows the enzymes to withstand harsh stomach acids, providing maximum systemic benefit.

Fibrin Defense Maintain Healthy Joints & Mobility Detoxification Cardiovascular Support

AcidDefenz Time Release Capsule

No Phthalates, No Dairy, No Wheat, No Yeast, No Gluten, No Fish, No Magnesium Stearate, No Talc, No Artificial Colors or Flavors, Non-GMO

Encapsulated in the USA

FDA Disclaimer Statement

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

FDA Statement of Identity

Dietary Supplement

Precautions

Keep out of reach of children

Caution: As with any dietary supplement, consult your healthcare provider before using this product, especially if you are pregnant, nursing, or are taking medication.

Storage

Store in a cool, dry place with lid tightly closed

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

See for yourself

Fibrenza Systemic Enzyme 500 mg by HCP Formulas label

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

Fibrenza Systemic Enzyme 500 mg 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 Fibrenza Systemic Enzyme 500 mg by HCP Formulas

These are the 13 active ingredients this product is made of. Select any to open its full monograph.

Serving size2 Capsule(s) Dosage formCapsule Servings per container120 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.

Proprietary Enzyme Blend

1000 mg per serving

Other (inactive) ingredients: Cellulose, Rice Bran, Rice extract. These complete the product’s ingredient list but are not active constituents.

Interaction report

Fibrenza Systemic Enzyme 500 mg by HCP Formulas Drug Interactions

Want to check YOUR meds against Fibrenza Systemic Enzyme 500 mg?

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
308Drugs
289 Moderate 19 Minor

Ingredients driving the most interactions

Nattokinase NSK-SD 289
Bromelain 141
Papain 2

Individual Drug Interactions

The ingredients in Fibrenza Systemic Enzyme 500 mg interact with 308 drugs. Click any drug to see the details.

3 of the 13 ingredients in Fibrenza Systemic Enzyme 500 mg interact with drugs. Each result below shows which ingredient is responsible. Nattokinase NSK-SD Bromelain Papain

Each ingredient & the kinds of drugs it affects

For each ingredient in Fibrenza Systemic Enzyme 500 mg 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.

Nattokinase NSK-SD2 drug types · 289 drugs

Anticoagulant/Antiplatelet Drugs

Nattokinase might increase the risk of bleeding when used with anticoagulant/antiplatelet drugs.
Nattokinase has thrombolytic and anticoagulant effects. There is a case report of intracranial hemorrhage in a patient who added nattokinase to aspirin therapy.

Likelihood Possible Evidence D
Antihypertensive Drugs

Theoretically, nattokinase might increase the risk of hypotension when used with antihypertensive drugs.
Some clinical research suggests that nattokinase may reduce systolic and diastolic blood pressure.

Likelihood Possible Evidence D
Nattokinase NSK-SD 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

Papain1 drug type · 2 drugs

Warfarin (Coumadin)

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

Likelihood Possible Evidence D
Papain full monograph & interactions
The maker

Brand information

Manufacturer and brand details for Fibrenza Systemic Enzyme 500 mg, from the product label.

HCP Formulas

See all HCP Formulas products
Name
HCP Formulas
Street Address
9830 S. 51st St. A129
City
Phoenix
State
AZ
ZipCode
85044
Phone Number
800-710-2585
Web Address
www.fibrenza.com
Pharmacist Counseling Corner

Fibrenza Systemic Enzyme 500 mg by HCP Formulas: Common Questions

Does Fibrenza Systemic Enzyme 500 mg by HCP Formulas interact with any medications?
Yes. Based on its ingredients, Fibrenza Systemic Enzyme 500 mg has a known interaction with 308 medications. Use the checker to see how it interacts with a specific drug.
How can one product interact with so many drugs?
Fibrenza Systemic Enzyme 500 mg contains 13 active ingredients, and an interaction can come from any of them. We check every ingredient, combine the results into one list per medication, and show which ingredient and mechanism is responsible.
Where does this information come from?
The product label data comes from the NIH Dietary Supplement Label Database (DSLD); the interaction data is built on the Natural Medicines database and reviewed by HelloPharmacist pharmacists.
Can I take this if I'm on warfarin (Coumadin)?
Not without checking with your doctor first. Papain in this product has a documented interaction with warfarin—it may increase warfarin's blood-thinning effect and raise your bleeding risk. A case report shows a patient's warfarin level spiked dangerously after taking a papain supplement. Your doctor or pharmacist needs to evaluate your specific situation.
Can I use this while pregnant or breastfeeding?
The safety data advises against it during pregnancy—papain and bromelain are considered possibly or likely unsafe. During breastfeeding, most of the enzymes here lack adequate safety information. Talk with your doctor or pharmacist about whether it's right for you in either situation.
What are papain and bromelain, and why are they in here?
Papain is a digestive enzyme from papaya; bromelain is one from pineapple. Both are included because they're thought to help break down proteins in the body. However, the evidence that either works for the conditions listed is insufficient—research hasn't confirmed their benefit.
Could this cause stomach problems?
Possibly. Papain and bromelain can irritate the digestive tract in some people; trypsin combined with other enzymes may cause nausea, heartburn, or stomach pain. High-dose papain is rarely linked to severe gastritis. If you have a sensitive stomach or serious digestive condition, check with your doctor first.
Is nattokinase (NSK-SD) safe if I take aspirin?
Not without medical guidance. Nattokinase has blood-thinning effects similar to aspirin, and there's a case report of brain bleeding in a woman who combined them. Talk with your doctor before adding this product to aspirin or any other blood thinner.
Does this product have a lot of fillers?
The inactive ingredients are cellulose, rice bran, and rice extract—a modest list. Whether that matters to you depends on your preferences and any food sensitivities you have.

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

Not sure if Fibrenza Systemic Enzyme 500 mg is safe with your meds?

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

Fibrenza Systemic Enzyme 500 mg label
Go deeper

The Full Monographs Behind Fibrenza Systemic Enzyme 500 mg’s Ingredients

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

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

Proteolytic Enzymes (proteases)

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

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

Lipase

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 monograph

Chymotrypsin

Chymotrypsin is a protein-digesting (proteolytic) enzyme, usually taken from the pancreas of cattle or pigs, that is mainly used to help reduce swelling and support healing after injury or s...

Read the full Chymotrypsin monograph → Herb & supplement monograph

Trypsin

Trypsin is a protein-digesting enzyme usually taken from the pancreas of animals and used either by mouth (often combined with other enzymes like chymotrypsin and bromelain) for swelling and...

Read the full Trypsin monograph → Herb & supplement monograph

Nattokinase

Interacts with 289 drugs

Nattokinase is an enzyme from the fermented soybean food natto that may have mild blood-thinning and blood-flow effects. Some small studies hint at benefits for blood pressure and circulatio...

Read the full Nattokinase monograph →
Sources

Sources & How We Checked

Fibrenza Systemic Enzyme 500 mg'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 66 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.

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 →

Chymotrypsin 6 references
  1. Martindale W. Martindale the Extra Pharmacopoeia. Pharmaceutical Press, 1999.
  2. Dukes, MNG. Meyler's Side Effects of Drugs. 13th ed. Elsevier: Amsterdam, 1997.
  3. Latha B, Ramakrishnan M, Jayaraman V, Babu M. Serum enzymatic changes modulated using trypsin: chymotrypsin preparation during burn wounds in humans. Burns 1997;23:560-4. PubMed
  4. Shaw PC. The use of a trypsin-chymotrypsin formulation in fractures of the hand. Br J Clin Pract 1969;23:25-6. DOI
  5. McCue FC, Webster TM, Gieck J. Clinical effects of proteolytic enzymes after reconstructive hand surgery. Int Surg 1972;57:479-82.
  6. Sun HJ, Xiao JQ, Qiao QH, et al. Chymotrypsin with sialendoscopy-assisted surgery for the treatment of chronic obstructive parotitis. Int J Oral Maxillofac Surg 2017;46(7):877-82. doi: 10.1016/j.ijom.2017.02.1267. PubMed

See these in context on the Chymotrypsin monograph →

Trypsin 17 references
  1. Burnham TH, ed. Drug Facts and Comparisons, Updated Monthly. Facts and Comparisons, St. Louis, MO.
  2. Latha B, Ramakrishnan M, Jayaraman V, Babu M. The efficacy of trypsin: chymotrypsin preparation in the reduction of oxidative damage during burn injury. Burns 1998;24:532-8. PubMed
  3. Latha B, Ramakrishnan M, Jayaraman V, Babu M. Serum enzymatic changes modulated using trypsin: chymotrypsin preparation during burn wounds in humans. Burns 1997;23:560-4. PubMed
  4. Klein, G., Kullich, W., Schnitker, J., and Schwann, H. Efficacy and tolerance of an oral enzyme combination in painful osteoarthritis of the hip. A double-blind, randomised study comparing oral enzymes with non-steroidal anti-inflammatory drugs. Clin Exp
  5. Dale, P. S., Tamhankar, C. P., George, D., and Daftary, G. V. Co-medication with hydrolytic enzymes in radiation therapy of uterine cervix: evidence of the reduction of acute side effects. Cancer Chemother.Pharmacol 2001;47 Suppl:S29-S34. PubMed
  6. 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
  7. Miller, P. C., Bailey, S. P., Barnes, M. E., Derr, S. J., and Hall, E. E. The effects of protease supplementation on skeletal muscle function and DOMS following downhill running. J Sports Sci 2004;22(4):365-372. PubMed
  8. Bolten WW, Glade MJ, Raum S, Ritz BW. The safety and efficacy of an enzyme combination in managing knee osteoarthritis pain in adults: a randomized, double-blind, placebo-controlled trial. Arthritis 2015;2015:251521. PubMed
  9. US Department of Justice. U.S. Files Complaint Against Texas-Based Healthpoint Ltd. Under the False Claims Act. https://www.justice.gov/opa/pr/us-files-complaint-against-texas-based-healthpoint-ltd-under-false-claims-act. (Accessed June 19, 2019).
  10. Grabs V, Kersten A, Haller B, et al. Rutoside and hydrolytic enzymes do not attenuate marathon-induced inflammation. Med Sci Sports Exerc. 2017;49(3):387-395. PubMed
  11. Baumhackl U, Kappos L, Radue EW, et al. A randomized, double-blind, placebo-controlled study of oral hydrolytic enzymes in relapsing multiple sclerosis. Mult Scler. 2005;11(2):166-8. PubMed
  12. Gujral MS, Patnaik PM, Kaul R, et al. Efficacy of hydrolytic enzymes in preventing radiation therapy-induced side effects in patients with head and neck cancers. Cancer Chemother Pharmacol. 2001;47 Suppl:S23-8. PubMed
  13. Kempf K, Manzo G, Hanifi-Moghaddam P, et al. Effect of combined oral proteases and flavonoid treatment in subjects at risk of Type 1 diabetes. Diabet Med. 2009;26(12):1309-10. PubMed
  14. Kerkhoffs GM, Struijs PA, de Wit C, Rahlfs VW, Zwipp H, van Dijk CN. A double blind, randomised, parallel group study on the efficacy and safety of treating acute lateral ankle sprain with oral hydrolytic enzymes. Br J Sports Med. 2004;38(4):431-5. PubMed
  15. Popiela T, Kulig J, Klek S, Wachol D, Bock PR, Hanisch J. Double-blind pilot-study on the efficacy of enzyme therapy in advanced colorectal cancer. Przegl Lek. 2000;57 Suppl 5:142.
  16. Shetty V, Mohan A. A prospective, randomized, double-blind, placebo-controlled clinical trial comparing the efficacy of systemic enzyme therapy for edema control in orthognathic surgery using ultrasound scan to measure facial swelling. J Oral Maxillofac S PubMed
  17. Comparison of Chronic Wound Care Products. Pharmacist's Letter/Prescriber's Letter 2008;12(3):1203.

See these in context on the Trypsin monograph →

Nattokinase 9 references
  1. Suzuki Y, Kondo K, Matsumoto Y, et al. Dietary supplementation of fermented soybean, natto, suppresses intimal thickening and modulates the lysis of mural thrombi after endothelial injury in rat femoral artery. Life Sci 2003;73:1289-98.. PubMed
  2. Sumi H, Hamada H, Nakanishi K, Hiratani H. Enchancement of fibrinolytic activity in plasma by oral administration of nattokinase. Acta Haematol 1990;84:139-43.
  3. Chang, Y. Y., Liu, J. S., Lai, S. L., Wu, H. S., and Lan, M. Y. Cerebellar hemorrhage provoked by combined use of nattokinase and aspirin in a patient with cerebral microbleeds. Intern Med 2008;47(5):467-469. PubMed
  4. Kim, J. Y., Gum, S. N., Paik, J. K., Lim, H. H., Kim, K. C., Ogasawara, K., Inoue, K., Park, S., Jang, Y., and Lee, J. H. Effects of nattokinase on blood pressure: a randomized, controlled trial. Hypertens.Res 2008;31(8):1583-1588. PubMed
  5. <p>Maruyama M, Sumi H (eds): Effect of natto diet on blood pressure, in Basic and Clinical Aspects of Japanese Traditional Food Natto II. Japan Technology Transfer Association (JTTAS), 1998, pp 1–3.</p>
  6. Kurosawa Y, Nirengi S, Homma T, et al. A single-dose of oral nattokinase potentiates thrombolysis and anti-coagulation profiles. Sci Rep 2015;5:11601. PubMed
  7. Ramachandran L, Aqeel A, Jafri A, Sidhu Y, Mohamed Djirdeh T. Nattokinase-associated hemoperitoneum in an elderly woman. Cureus 2021;13(12):e20074. PubMed
  8. Awatani-Yoshidome K, Hashimoto T, Satoh T. Anaphylaxis from nattokinase in a patient with fermented soybean (natto) allergy. Allergol Int 2022;71(1):153-4. PubMed
  9. Suzuki K, Nakamura M, Sato N, Futamura K, Matsunaga K, Yagami A. Nattokinase, a subtilisin family serine protease, is a novel allergen contained in the traditional Japanese fermented food natto. Allergol Int 2022.

See these in context on the Nattokinase monograph →

Parts of this content are provided by the Therapeutic Research Center, LLC.

DISCLAIMER: Currently this does not check for drug-drug interactions. This is not an all-inclusive comprehensive list of potential interactions and is for informational purposes only. Not all interactions are known or well-reported in the scientific literature, and new interactions are continually being reported. Input is needed from a qualified healthcare provider including a pharmacist before starting any therapy. Application of clinical judgment is necessary.

© 2021 Therapeutic Research Center, LLC

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