Interactions on record — worth a quick check against your medications. Based on 8 of 10 ingredients. Check your meds →
Dietary supplement

Digestive Enzymes Ingredients & Drug Interactions

by Michael's Naturopathic Programs

Capsule Category: Other Combinations
Most serious interaction: Moderate
The interaction bottom line Most serious interaction: Moderate

Digestive Enzymes is a dietary supplement by Michael's Naturopathic Programs with 10 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, 878 medications have a known interaction with it, the most serious rated moderate. The ingredients most likely to interact are Fennel, Anise, Bromelain. Use the checker below to test your specific medication, or read the full HelloPharmacist Interaction Report.

HelloPharmacist Scorecard of Digestive Enzymes by Michael's Naturopathic Programs

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

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 10 active ingredients.
  • “Proprietary Blend” is a proprietary blend — the label gives one combined amount (401 mg) without saying how much of each component you get.

This product contains 10 active ingredients, all digestive enzymes and botanicals meant to support digestion. Papain, bromelain, trypsin, chymotrypsin, pancreatin, amylase, and lipase are all proteases, lipases, or other enzymes that break down food proteins, fats, and carbohydrates.

Rutin is a flavonoid (plant compound), and fennel and anise are seeds traditionally used to aid digestion and reduce gas. The capsules also contain gelatin, rice flour, and vegetable magnesium stearate as inactive ingredients.

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: Digestive enzyme support.
  • We looked for evidence on: Dyspepsia, Flatulence, Colic, Cough, Irritable bowel syndrome (IBS), Inflammatory bowel disease (IBD) — 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: Lipase is rated "Insufficient Reliable Evidence To Rate" for Inflammatory bowel disease (IBD), Dyspepsia.
  • Also on file: Rutin is rated "Insufficient Reliable Evidence To Rate" for Inflammatory bowel disease (IBD), Sprains, Postoperative swelling.

The evidence base for most of these ingredients is limited. Papain, bromelain, rutin, fennel, and anise all lack sufficient reliable evidence for most conditions they're used for — the facts we have list only "insufficient evidence to rate" for nearly all their proposed uses.

Fennel is the sole exception: it is rated possibly effective for dysmenorrhea (period pain). Trypsin, lipase, and chymotrypsin similarly show insufficient evidence for their listed indications, though chymotrypsin is rated effective for cataracts.

For general digestive support — the main use of enzyme blends — effectiveness data are not established in the information we hold.

The evidence, ingredient by ingredient Papain Bromelain Rutin Trypsin Lipase Fennel Anise Chymotrypsin

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 8 of the 8 matched ingredients.
  • Pregnancy & breastfeeding safety ratings cover 8 of 8.
  • General safety write-ups exist for 8 of 8.
  • Remember: this measures how much safety information exists. Thin data is not the same as being safe.

Most ingredients are generally well tolerated short-term at appropriate doses, but several come with cautions. Papain may irritate the digestive tract and cause allergic reactions, and high doses may be unsafe.

Bromelain commonly causes diarrhea, gas, and stomach upset. Rutin may cause headache, flushing, or rash in some people.

Fennel and anise can both trigger allergic reactions including asthma and, rarely, seizures or anaphylaxis. Trypsin and chymotrypsin, when taken by mouth in combination with other enzymes, may cause nausea, heartburn, and stomach pain.

Pregnant people should avoid papain, bromelain, trypsin, and chymotrypsin; fennel and anise are possibly unsafe in pregnancy. For breastfeeding, safety data are limited or lacking for papain, bromelain, rutin, trypsin, lipase, and chymotrypsin — check with your healthcare provider before taking this product if you are breastfeeding.

Side effects, ingredient by ingredient Papain Bromelain Rutin Trypsin Lipase Fennel Anise Chymotrypsin

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?
  • 5 of the 8 matched ingredients can interact with medications — Papain, Rutin, Fennel, Anise, Bromelain.
  • The most serious interaction on file is rated Moderate.
  • Some involve high-stakes drug classes: anticoagulant / antiplatelet drugs; diabetes medications.
  • For scale: 879 individual medications appear in the full list. A big number alone doesn't make a product dangerous — what matters is whether YOUR medication is on it, so run yours through the interaction checker on this page.

Before taking this product, check your medications against these types: blood thinners and antiplatelet drugs (warfarin, aspirin, clopidogrel), diabetes medications, birth control pills and hormone replacement therapy, liver-metabolized drugs (especially CYP3A4 substrates), ciprofloxacin, tetracycline antibiotics, fluoxetine, imipramine, diazepam, codeine, and caffeine. The most serious concerns are Moderate-severity interactions with anticoagulants and antiplatelet medications.

Use the medication checker on this page to confirm your specific drugs.

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 blend is aimed at people seeking digestive enzyme support, but the evidence for most ingredients is still being established. If you take blood thinners, diabetes medications, birth control, psychiatric medications, or ciprofloxacin, talk with your doctor or pharmacist before starting this product — it may affect how those drugs work.

Anyone allergic to papaya, pineapple, or fennel should avoid it. Check your specific medications using the tool on this page, then discuss the results with your own healthcare provider.

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

Assessment coverage: 8 of 10 active ingredients matched to our full ingredient reviews (monographs). Based on the product label dated Mar 23, 2018.

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 Digestive Enzymes, straight from the product label.

Brand Michael's Naturopathic Programs
Barcode (UPC) 755929011582
Net contents 20 Capsule(s)
Market status On market
Date entered into DSLD Mar 23, 2018
DSLD ID 174082
Product type Other Combinations
Supplement form Capsule
Dietary claims / uses All Other, Structure/Function
Intended target group(s) Adult (18 - 50 Years)
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 Digestive Enzymes by Michael's Naturopathic Programs, sourced from the NIH Dietary Supplement Label Database.

Supplement Facts

Daily Value (DV) Target Group(s):
Adults and children 4 or more years of age
Minimum serving Sizes:
1 Capsule(s)
Maximum serving Sizes:
1 Capsule(s)
UPC/BARCODE
755929011582
IngredientAmount% DV
Papain0 NP--
Bromelain0 NP--
Rutin0 NP--
Amylase0 NP--
Proprietary Blend401 mg--
Trypsin0 NP--
Pancreatin0 NP--
Lipase0 NP--
Fennel0 NP--
Anise0 NP--
L-Chymotrypsin0 NP--

Other ingredients: Gelatin, Rice Flour, Vegetable Magnesium Stearate

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.
FDA Statement of Identity

Dietary Supplement

General Statements

Tried & truthful

Our products contain organically grown herbs, when available.

United States Pharmacopeia units of enzyme activity

A Division of Inner Health Group, Inc.

General

Product #01158 H020617

Suggested/Recommended/Usage/Directions

Directions: As a dietary supplement, take one (1) capsule with each meal. Dosage may be increased as directed by a healthcare practitioner.

Precautions

Sealed for your protection. Do not use if seal is broken or missing.

Caution: Keep out of reach of children.

Made in a GMP facility that processes egg, fish, milk, shellfish, soy, tree nut and wheat products.

Formula

Pancreatin Enzyme Profile: Amylase................100 USP units/mg Lipase.....................20 USP units/mg Protease...............100 USP units/mg

FDA Disclaimer Statement

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

See for yourself

Digestive Enzymes by Michael's Naturopathic Programs label

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

What’s inside

The Ingredients in Digestive Enzymes by Michael's Naturopathic Programs

These are the 10 active ingredients this product is made of. Select any to open its full monograph.

Serving size1 Capsule(s) Dosage formCapsule 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 Blend

401 mg per serving

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

Interaction report

Digestive Enzymes by Michael's Naturopathic Programs Drug Interactions

Want to check YOUR meds against Digestive Enzymes?

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
878Drugs
834 Moderate 44 Minor

Ingredients driving the most interactions

Fennel 740
Anise 245
Bromelain 141
Rutin 86
Papain 2

Each ingredient & the kinds of drugs it affects

For each ingredient in Digestive Enzymes 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.

Fennel6 drug types · 740 drugs

Anticoagulant/Antiplatelet Drugs

Theoretically, fennel might increase the risk of bleeding when used with antiplatelet or anticoagulant drugs.

Animal research suggests that fennel oil has antithrombotic and antiplatelet effects.

Likelihood Possible Evidence D
Ciprofloxacin (Cipro)

Theoretically, fennel might decrease the levels and clinical effects of ciprofloxacin.

Animal research shows that fennel reduces ciprofloxacin bioavailability by nearly 50%, possibly due to the metal cations such as calcium, iron, and magnesium contained in fennel. This study also found that fennel increased tissue distribution and slowed elimination of ciprofloxacin.

Likelihood Probable Evidence D
Contraceptive Drugs

Theoretically, taking large amounts of fennel might decrease the effects of contraceptive drugs due to competition for estrogen receptors.

Some constituents of fennel have estrogenic activity.

Likelihood Possible Evidence D
Cytochrome P450 3A4 (Cyp3A4) Substrates

Theoretically, fennel might increase levels of drugs metabolized by CYP3A4.

In vitro research suggests that fennel inhibits CYP3A4 enzyme activity. This effect has not been reported in humans.

Likelihood Possible Evidence D
Estrogens

Theoretically, taking large amounts of fennel might interfere with hormone replacement therapy due to competition for estrogen receptors.

Some constituents of fennel have estrogenic activity.

Likelihood Possible Evidence D
Tamoxifen (Nolvadex)

Theoretically, taking large amounts of fennel might decrease the antiestrogenic effect of tamoxifen.

Some constituents of fennel have estrogenic activity, which may interfere with the antiestrogenic activity of tamoxifen.

Likelihood Possible Evidence D

Anise11 drug types · 245 drugs

Antidiabetes Drugs

Theoretically, anise seed might increase the risk of hypoglycemia when taken with antidiabetes drugs.
A small clinical study shows that anise seed powder decreases fasting blood glucose levels by 36% when compared to baseline.

Likelihood Possible Evidence B
Caffeine

Theoretically, anise oil might decrease the efficacy of caffeine.
Animal research shows that taking anise oil with caffeine decreases the bioavailability of caffeine. Whether this interaction will occur in humans is unclear.

Likelihood Possible Evidence D
Codeine

Theoretically, anise oil might increase the effects and adverse effects of codeine.
Animal research shows that anise oil increases the analgesic effects of codeine, possibly by inducing its phase I metabolism and increasing conversion to morphine. Whether this interaction occurs in humans is unclear.

Likelihood Possible Evidence D
Contraceptive Drugs

Theoretically, anise might interfere with contraceptive drug therapy.
Some in vitro research suggests that anise has estrogenic effects, while other in vitro research suggests that anise has antiestrogenic effects.

Likelihood Possible Evidence D
Diazepam (Valium)

Theoretically, anise oil might increase the effects and adverse effects of diazepam.
Animal research shows that taking anise oil with diazepam increases the motor impairment associated with diazepam, possibly by inhibiting its breakdown by cytochrome P450 3A4. Whether this interaction occurs in humans is unclear.

Likelihood Possible Evidence D
Estrogens

Theoretically, anise might interfere with estrogen-based hormone replacement therapy.
Some in vitro research suggests that anise has estrogenic effects, while other in vitro research suggests that anise has antiestrogenic effects.

Likelihood Possible Evidence D
Fluoxetine (Prozac)

Theoretically, anise oil might decrease the efficacy of fluoxetine.
Animal research shows that taking anise oil with fluoxetine reduces the antidepressant effects of fluoxetine, possibly by promoting its breakdown by cytochrome P450 2D6. Whether this interaction occurs in humans is unclear.

Likelihood Possible Evidence D
Imipramine (Tofranil)

Theoretically, anise oil might decrease the efficacy of imipramine.
Animal research shows that taking anise oil with imipramine reduces the antidepressant effects of imipramine, possibly by promoting its breakdown by cytochrome P450 2D6. Whether this interaction occurs in humans is unclear.

Likelihood Possible Evidence D
Midazolam (Versed)

Theoretically, anise oil might increase the effects and adverse effects of midazolam.
Animal research shows that taking anise oil with midazolam increases the motor impairment associated with midazolam, possibly by inhibiting its breakdown by cytochrome P450 3A4. Whether this interaction occurs in humans is unclear.

Likelihood Possible Evidence D
Tamoxifen (Nolvadex)

Theoretically, anise might interfere with tamoxifen therapy.
Some in vitro research suggests that anise has estrogenic effects, while other in vitro research suggests that anise has antiestrogenic effects.

Likelihood Possible Evidence D
Acetaminophen (Tylenol, Others)

Theoretically, anise oil might decrease the levels and clinical effects of acetaminophen.
Animal research shows that taking anise oil with acetaminophen decreases peak plasma levels of acetaminophen but does not reduce overall bioavailability. Whether this interaction will occur in humans is unclear.

Likelihood Possible Evidence D

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

Rutin1 drug type · 86 drugs

Antidiabetes Drugs

Theoretically, taking rutin with antidiabetes drugs might increase the risk of hypoglycemia.
Animal research suggests that rutin has hypoglycemic effects.

Likelihood Possible Evidence D

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
The maker

Brand information

Manufacturer and brand details for Digestive Enzymes, from the product label.

Michael's Naturopathic Programs

See all Michael's Naturopathic Programs products
Name
Michael's Naturopathic Programs
Street Address
6003 Randolph Blvd
City
San Antonio
State
Texas
ZipCode
78233
Phone Number
800-845-2730
Web Address
michaelshealth.com
Pharmacist Counseling Corner

Digestive Enzymes by Michael's Naturopathic Programs: Common Questions

Does Digestive Enzymes by Michael's Naturopathic Programs interact with any medications?
Yes. Based on its ingredients, Digestive Enzymes has a known interaction with 878 medications. Use the checker to see how it interacts with a specific drug.
How can one product interact with so many drugs?
Digestive Enzymes contains 10 active ingredients, and an interaction can come from any of them. We check every ingredient, combine the results into one list per medication, and show which ingredient and mechanism is responsible.
Where does this information come from?
The product label data comes from the NIH Dietary Supplement Label Database (DSLD); the interaction data is built on the Natural Medicines database and reviewed by HelloPharmacist pharmacists.
Is this safe to take if I'm pregnant?
Several ingredients in this blend are not recommended in pregnancy: papain is possibly unsafe, bromelain is best avoided, trypsin and chymotrypsin lack established safety data, and fennel and anise are possibly unsafe. Talk with your doctor before taking this product if you're pregnant.
Can I take this if I'm breastfeeding?
Safety while breastfeeding has not been well studied for most of these ingredients. Papain, bromelain, rutin, trypsin, lipase, and chymotrypsin all have insufficient data. Check with your healthcare provider to see whether this product is right for you while breastfeeding.
What is papain and why is it in here?
Papain is an enzyme from papaya fruit that breaks down proteins during digestion. It's included in this blend to help your body digest food, though the evidence for how well it works is still limited.
I'm taking warfarin — is this safe?
No. Papain in this product may increase warfarin's effects and blood-thinning action, which can raise your bleeding risk. Talk with your doctor before taking any digestive enzyme product while on warfarin.
Does this really work for digestion?
The evidence that this blend helps digestion as a whole is not established in the data we hold. Individual ingredients like bromelain and lipase show promise in some studies, but most lack sufficient reliable evidence for digestive support overall.
What are the inactive ingredients?
The capsules contain gelatin, rice flour, and vegetable magnesium stearate — all standard fillers and binding agents with no active role in digestion.

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

Not sure if Digestive Enzymes is safe with your meds?

Our pharmacists answer your medication & supplement questions — free.

Ask a pharmacist

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

Digestive Enzymes label
Go deeper

The Full Monographs Behind Digestive Enzymes’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

Rutin

Interacts with 86 drugs

Rutin is a plant flavonoid (often taken from buckwheat or citrus) that people use mainly for blood vessel and circulation problems like varicose veins and hemorrhoids. The evidence is limite...

Read the full Rutin 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

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

Fennel

Interacts with 740 drugs

Fennel is a Mediterranean herb widely used as a food and spice, and traditionally taken for digestive complaints, colic, and menstrual cramps. Some small studies suggest possible benefit for...

Read the full Fennel monograph →
Herb & supplement monograph

Anise

Interacts with 245 drugs

Anise is a fragrant, licorice-flavored seed used for centuries to ease digestion and soothe coughs. Most of its health claims are based on tradition and small or laboratory studies rather th...

Read the full Anise 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 →
Sources

Sources & How We Checked

Digestive Enzymes'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 85 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 →

Rutin 2 references
  1. Mehta DK (Ex Ed). British National Formulary, Number 37. British Medical Association and Royal Pharmaceutical Society of Great Britain: London, England, March 1999.
  2. Sun C, Wang L, Sun J, Wang Z, Tang Z. Hypoglycemic and hypolipidemic effects of rutin on hyperglycemic rats. J Tradit Chin Med. 2020;40(4):640-645.

See these in context on the Rutin 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 →

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 →

Fennel 17 references
  1. Leung AY, Foster S. Encyclopedia of Common Natural Ingredients Used in Food, Drugs and Cosmetics. 2nd ed. New York, NY: John Wiley & Sons, 1996.
  2. Brinker F. Herb Contraindications and Drug Interactions. 2nd ed. Sandy, OR: Eclectic Medical Publications, 1998.
  3. Zhu M, Wong PY, Li RC. Effect of oral administration of fennel (Foeniculum vulgare) on ciprofloxacin absorption and disposition in the rat. J Pharm Pharmacol 1999;51:1391-6.
  4. Gral N, Beani JC, Bonnot D, et al. [Plasma levels of psoralens after celery ingestion]. Ann Dermatol Venereol 1993;120:599-603.
  5. Burkhard PR, Burkhardt K, Haenggeli CA, Landis T. Plant-induced seizures: reappearance of an old problem. J Neurol 1999;246:667-70. PubMed
  6. Rosti L, Nardini A, Bettinelli ME, Rosti D. Toxic effects of a herbal tea mixture in two newborns. Acta Paediatrica 1994;83:683. PubMed
  7. Cuzzolin L, Zaffani S, and Benoni G. Safety implications regarding use of phytomedicines. Eur.J Clin Pharmacol. 2006;62:37-42. PubMed
  8. Tognolini, M., Ballabeni, V., Bertoni, S., Bruni, R., Impicciatore, M., and Barocelli, E. Protective effect of Foeniculum vulgare essential oil and anethole in an experimental model of thrombosis. Pharmacol.Res 2007;56(3):254-260. PubMed
  9. Subehan, Usia, T., Iwata, H., Kadota, S., and Tezuka, Y. Mechanism-based inhibition of CYP3A4 and CYP2D6 by Indonesian medicinal plants. J Ethnopharmacol. 5-24-2006;105(3):449-455. PubMed
  10. Tognolini, M., Barocelli, E., Ballabeni, V., Bruni, R., Bianchi, A., Chiavarini, M., and Impicciatore, M. Comparative screening of plant essential oils: phenylpropanoid moiety as basic core for antiplatelet activity. Life Sci. 2-23-2006;78(13):1419-1432. PubMed
  11. Subehan, Zaidi, S. F., Kadota, S., and Tezuka, Y. Inhibition on human liver cytochrome P450 3A4 by constituents of fennel (Foeniculum vulgare): identification and characterization of a mechanism-based inactivator. J Agric.Food Chem. 12-12-2007;55(25):101 PubMed
  12. LEVY, S. B. Bronchial asthma due to ingestion of fennel and fennel seed. Ann.Allergy 1948;6(4):415.
  13. Ottolenghi, A., De Chiara, A., Arrigoni, S., Terracciano, L., and De Amici, M. [Diagnosis of food allergy caused by fruit and vegetables in children with atopic dermatitis]. Pediatr Med Chir 1995;17(6):525-530.
  14. Trabace L, Tucci P, Ciuffreda L, et al. "Natural" relief of pregnancy-related symptoms and neonatal outcomes: above all do no harm. J Ethnopharmacol. 2015;174:396-402. PubMed
  15. Denaxa D, Arkwright PD. Fennel as a cause of immediate hypersensitivity to toothpaste. Ann Allergy Asthma Immunol. 2020;125(1):99-100. PubMed
  16. Lee HW, Ang L, Lee MS, Alimoradi Z, Kim E. Fennel for reducing pain in primary dysmenorrhea: a systematic review and meta-analysis of randomized controlled trials. Nutrients 2020;12(11):3438. PubMed
  17. Mathew T, John SK, Javali M, Vasireddy M, Nadig R, Sarma GRK. Substance use related cluster headache: A case series. Headache 2022;62(7):908-910. PubMed

See these in context on the Fennel monograph →

Anise 12 references
  1. Electronic Code of Federal Regulations. Title 21. Part 182 -- Substances Generally Recognized As Safe. Available at: https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=182
  2. Kassi E, Papoutsi Z, Fokialakis N, et al. Greek plant extracts exhibit selective estrogen receptor modulator (SERM)-like properties. J Agric Food Chem 2004;52:6956-61. PubMed
  3. Mumcuoglu KY, Miller J, Zamir C, et al. The in vivo pediculicidal efficacy of a natural remedy. Isr Med Assoc J 2002;4:790-3.
  4. Garcia-Gonzalez JJ, Bartolome-Zavala B, Fernandez-Melendez S, et al. Occupational rhinoconjunctivitis and food allergy because of aniseed sensitization. Ann Allergy Asthma Immunol 2002;88:518-22. . PubMed
  5. Tabanca N, Khan SI, Bedir E, et al. Estrogenic activity of isolated compounds and essential oils of Pimpinella species from Turkey, evaluated using a recombinant yeast screen. Planta Med 2004;70:728-35.
  6. Gonzalez-Gutierrez, M. L., Sanchez-Fernandez, C., Esteban-Lopez, M. I., Sempere-Ortells, J. M., and Diaz-Alperi, P. Allergy to anis. Allergy 2000;55(2):195-196.
  7. Anliker, M. D., Borelli, S., and Wuthrich, B. Occupational protein contact dermatitis from spices in a butcher: a new presentation of the mugwort-spice syndrome. Contact Dermatitis 2002;46(2):72-74. PubMed
  8. Poon, T. S. and Freeman, S. Cheilitis caused by contact allergy to anethole in spearmint flavoured toothpaste. Australas.J Dermatol. 2006;47(4):300-301. PubMed
  9. Andersen, K. E. Contact allergy to toothpaste flavors. Contact Dermatitis 1978;4(4):195-198. PubMed
  10. Samojlik I, Mijatovic V, Petkovic S, et al. The influence of essential oil of aniseed (Pimpinella anisum, L.) on drug effects on the central nervous system. Fitoterapia 2012;83:1466-73. PubMed
  11. Samojlik I, Petkovic S, Stilinovic N, et al. Pharmacokinetic herb-drug interaction between essential oil of aniseed (Pimpinella anisum L., Apiaceae) and acetaminophen and caffeine: A potential risk for clinical practice. Phytother Res 2016;30:253-9.
  12. Rajeshwari U, Shobha I, Andallu B. Comparison of aniseeds and coriander seeds for antidiabetic, hypolipidemic and antioxidant activities. Spatula DD-Peer Reviewed Journal on Complementary Medicine and Drug Discovery 2011;1:9-16. DOI

See these in context on the Anise 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 →

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

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