Drug & supplement interaction

Proteolytic Enzymes (proteases) + Tolbutamide

Tolbutamide brand name: Orinase.

No Known Interaction
Medically reviewed by · Updated July 2026 · Pair last verified Sep 20, 2026
The bottom line No known interaction

We found no known interaction between Proteolytic Enzymes (proteases) and Tolbutamide in our sources. Absence of a documented interaction is not the same as proven safety, and does not guarantee one does not exist. Do not start, stop, or change a medication or supplement based on this page; confirm with your pharmacist or doctor first.

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Interaction report

Proteolytic Enzymes (proteases) and Tolbutamide

We checked these two against our interaction database. Here is what we found.

No Known Interaction Found

We did not find a documented interaction between Tolbutamide and Proteolytic Enzymes (proteases) in our sources. This does not guarantee that the combination is completely free of risk — there is often limited research on supplements and herbal products, especially around drug interactions.

Worth understanding: our licensed dataset holds no drug-interaction record for Proteolytic Enzymes (proteases) at all — not against Tolbutamide, and not against any other medication we track. This verdict therefore rests on the absence of any recorded data, not on research that looked at this combination and found nothing. We cannot rule an interaction out.

If you decide to take both, the practical routine is simple: add one new thing at a time and note the date you started it. If the combination is going to disagree with you, it usually shows in the first days to a couple of weeks — and a start date turns “I’ve been feeling off” into something a pharmacist can actually work with. Do not stop a prescribed medicine on your own.

Always talk with your pharmacist or doctor before making changes to your medications or supplements, particularly if you take several medications or have an ongoing health condition.

Proteolytic Enzymes (proteases) safety at a glance

Proteolytic Enzyme... overall Use caution Generally well tolerated for most adults, but may cause digestive upset or allergic reactions.
Pregnancy Avoid Safety has not been established, so it is best avoided during pregnancy unless prescribed.
Breastfeeding Use caution There is little safety data during breastfeeding, so use is not recommended without medical advice.

Safety guidance is general; always confirm with your pharmacist or doctor for your situation.

Still wondering about combining Tolbutamide and Proteolytic Enzymes (proteases)? Ask Dr. Brian Staiger, PharmD, BCPS directly ›
What to actually watch for

What Proteolytic Enzymes (proteases) Itself Has Been Linked To

This is not an interaction — nothing below involves Tolbutamide. It is the side-effect record for Proteolytic Enzymes (proteases) on its own, from the licensed Natural Medicines monograph. If something new turns up after you add Proteolytic Enzymes (proteases), this list is the first place to look. One entry is worth acting on rather than waiting out — marked below.

  • Wheezing Worth acting on Additional detail

    “Proteolytic enzymes are commonly found in laundry detergents and pre-spotter products. Rarely, protease specific IgE positive tests possibly related to these products have occurred. Exposure may be airborne or topical. In addition, in case reports, occupational exposure to the airborne proteolytic enzyme pepsin has resulted in allergic rhinoconjunctivitis or asthma.”

    Proteolytic Enzymes (proteases) · Natural Medicines adverse-effect record, reported in asthma.

    3 sources cited
    1. 102705. 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. 102706. 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. 102707. 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

Everything above comes from the Natural Medicines adverse-effect record for Proteolytic Enzymes (proteases) — expand a row for the licensed statement it rests on. We haven’t matched Tolbutamide to its FDA label in our system yet, so we can’t compare its own side-effect list here — the leaflet that comes with your prescription is the authoritative list for Tolbutamide.

Everything else you take

See Every Supplement That Interacts With Tolbutamide

This page covers Proteolytic Enzymes (proteases) only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Tolbutamide page lists 305 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Siberian Cocklebur (major), Acai (moderate), Adrafinil (moderate) and African Wild Potato (moderate).

By severity: 2 major · 255 moderate · 48 minor.

From our pharmacist’s overview on the Tolbutamide page

“People take tolbutamide (Orinase) to lower blood sugar in type 2 diabetes, and diabetes is exactly the condition supplement shelves target, which is why this list runs to 305 ingredients and deserves real caution. Of those, 239 also push glucose around, most often downward, so combining them can drive sugar lower than intended.”

Reviewed by 2 · Jul 18, 2026

Open the Tolbutamide interaction page

One more smart check

Taking Proteolytic Enzymes (proteases) as Part of a Dietary Supplement Product? Check It for Interactions

We hold 713 real supplement products containing Proteolytic Enzymes (proteases), each one broken down to its full ingredient list — and combination products often carry several ingredients besides Proteolytic Enzymes (proteases). Even though Proteolytic Enzymes (proteases) itself has no known interaction with Tolbutamide, another ingredient on your label might. Find your product and we’ll check every ingredient on its label:

How much people look this up

Where Proteolytic Enzymes (proteases) and Tolbutamide Sit Against Everything Else

Out of every supplement and medication people look up on HelloPharmacist, here is where these two land this week — and which way each has been moving.

Supplement Proteolytic Enzymes (proteases)
Top 5%

#39 of 1,452 supplements looked up here in the last 7 days

29 days ago today
Medication Tolbutamide
Steady interest

#1,749 of 2,830 medications looked up here in the last 7 days

29 days ago today

Position among everything looked up on this site, not a measure of how commonly either one is used or how important it is. A supplement can climb this list because of a news story. It counts every request to the page, automated ones included, and nothing here identifies anyone.

Where does our data come from?
  • Source: the Natural Medicines (TRC Healthcare) clinical database — the evidence-graded professional reference for herb & supplement interactions.
  • Citation library: 103,510 references behind our interaction content, 65,311 of them resolved to verified PubMed/DOI sources. See every Proteolytic Enzymes (proteases) reference on this page ↓
  • Freshness: we automatically re-check this combination every week — this pair was last verified September 20, 2026. The Proteolytic Enzymes (proteases) and Tolbutamide records this page draws on were last updated July 10, 2026.
  • What “no known interaction” means: no documented interaction in the sources above — not a guarantee of safety. Supplements are studied far less than prescription drugs, so we say exactly what the evidence supports, and nothing more.
Data structure & sourcing designed and verified by .
Supplement

About Proteolytic Enzymes (proteases)

What is Proteolytic Enzymes (proteases)?

  • Digestion and bloating
  • Muscle soreness and exercise recovery
  • Inflammation and swelling
  • Sinus and respiratory congestion
  • Post-surgery or injury recovery

Proteolytic enzymes are proteins that help break down other proteins, and common examples include bromelain (from pineapple), papain (from papaya), trypsin, chymotrypsin, and pancreatin. People take them for digestion, inflammation, and muscle recovery, but the evidence is mixed and stronger for some uses (like aiding digestion in people who lack natural enzymes) than others. They are generally well tolerated, but talk with a pharmacist or doctor before use, especially if you have allergies, a bleeding risk, or are pregnant.

Enzymes sourced from fruit (pineapple, papaya), animal pancreas, or microbial/fungal fermentation · Capsules, tablets (often enteric-coated), powders

An interaction check asks whether these two react with each other — it does not ask whether Proteolytic Enzymes (proteases) is a good idea for someone in your situation. Here is what our Proteolytic Enzymes (proteases) record says about it on its own.

Proteolytic Enzymes (proteases): dosing

There is no single standardized dose for proteolytic enzyme supplements. Products vary widely in their source, strength, and how they measure enzyme activity (for example, units may be listed differently from one brand to another).Because of this, the best approach is to follow the directions on the product label and not exceed the recommended amount. Do not assume an over-the-counter product replaces a prescription pancreatic enzyme.

From our Proteolytic Enzymes (proteases) monograph — the full record covers uses, side effects and every documented interaction.

Read the full Proteolytic Enzymes (proteases) monograph & all interactions
Medication

About Tolbutamide

What Is Tolbutamide Used For?

Brand name: Orinase

  • Tolbutamide is used along with diet and exercise, and sometimes with other medications, to treat type 2 diabetes (condition in which the body does not use insulin normally and, therefore, cannot control the amount of sugar in the blood). Tolbutamide is in a class of medications called sulfonylureas. Tolbutamide lowers blood sugar by causing the pancreas to produce insulin (a natural substance that is needed to break down sugar in the body) and helping the body use insulin efficiently. This medication will only help lower blood sugar in people whose bodies produce insulin naturally. Tolbutamide is not used to treat type 1 diabetes (condition in which the body does not produce insulin and, therefore, cannot control the amount of sugar in the blood) or diabetic ketoacidosis (a serious condition that may occur if high blood sugar is not treated).

  • Over time, people who have diabetes and high blood sugar can develop serious or life-threatening complications, including heart disease, stroke, kidney problems, nerve damage, and eye problems. Taking medication(s), making lifestyle changes (e.g., diet, exercise, quitting smoking), and regularly checking your blood sugar may help to manage your diabetes and improve your health. This therapy may also decrease your chances of having a heart attack, stroke, or other diabetes-related complications such as kidney failure, nerve damage (numb, cold legs or feet; decreased sexual ability in men and women), eye problems, including changes or loss of vision, or gum disease. Your doctor and other healthcare providers will talk to you about the best way to manage your diabetes.

See full Tolbutamide drug information
Keep checking

Other Drugs & Proteolytic Enzymes (proteases)

Browse every other medication we’ve checked against Proteolytic Enzymes (proteases) — both the ones with a known interaction and the ones without. Select any drug for the full detail.

0Major
0Moderate
0Minor
2,829No known interaction
2,829 No interaction
No interaction 2,829 drugs checked — show the list

We also checked Proteolytic Enzymes (proteases) against these medications and found no known interaction in our sources. Open any page to confirm.

Showing the 60 most looked-up of 2,829 medications checked with no known interaction — see the full Proteolytic Enzymes (proteases) list.

See the full Proteolytic Enzymes (proteases) interactions page
See every supplement checked against Tolbutamide, ranked by severity
Evidence & sources

Proteolytic Enzymes (proteases) References

The 3 references that drive our Proteolytic Enzymes (proteases) monograph and interaction data, from the evidence-graded Natural Medicines (TRC Healthcare) database. Citations with a link open the study on PubMed or the publisher’s site.

  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

Medication overviews come from MedlinePlus (NIH); supplement label data from the NIH Dietary Supplement Label Database. Content is written and reviewed by licensed HelloPharmacist pharmacists — see our data sources and editorial standards.

Pharmacist Counseling Corner

Taking Proteolytic Enzymes (proteases) and Tolbutamide Together: Common Questions

Is it safe to take Proteolytic Enzymes (proteases) with Tolbutamide?
We do not list a known interaction between Proteolytic Enzymes (proteases) and Tolbutamide. That does not guarantee the combination is risk-free, so confirm with your pharmacist or doctor — especially if you take other medications or have a health condition.
Does Tolbutamide interact with any supplements?
Yes. Tolbutamide has documented interactions with 305 supplements in our database — Proteolytic Enzymes (proteases) is not one of them. The Tolbutamide interaction page linked on this page lists every one, ranked by severity.

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

Where next

Keep Exploring

Proteolytic Enzymes (proteases) monograph Uses, safety profile, and every drug interaction in one place Tolbutamide drug information The full plain-English guide to this medication Tolbutamide supplement interactions Every supplement checked against Tolbutamide, ranked by severity Supplement interaction checker Check any supplement or product against your medications Browse medications A–Z Every drug we’ve checked against herbs & supplements References The 3 citations behind this page Ask a pharmacist Free, personal answer from our licensed team

Still Have a Question About Tolbutamide and Proteolytic Enzymes (proteases)?

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This information is for education only and is not a substitute for professional medical advice. Always check with your pharmacist or doctor before starting, stopping, or combining supplements and medications.