Protease

Pancreatic enzyme products contain a mixture of lipases, proteases, and amylases that catalyze the hydrolysis of fats to monoglycerides, glycerol, and free fatty acids, protein into peptides and amino acids, and starch into dextrins and short chain sugars such as maltose and maltriose in the duodenum and proximal small intestine, thereby acting like digestive enzymes physiologically secreted by the pancreas.

• ZENPEP ® is indicated for the treatment of exocrine pancreatic insufficiency in adult and pediatric patients. ZENPEP ® is indicated for the treatment of exocrine pancreatic insufficiency in adult and pediatric patients.

• None.contraindicated

Important Dosing Information ( 2.1 ) ZENPEP is a mixture of enzymes including lipases, proteases, and amylases and dosing is based on lipase units. Dosing scheme based on actual body weight or fat ingestion. Individualize the dosage based on clinical symptoms, the degree of steatorrhea present, and the fat content of the diet. Do not exceed 2,500 lipase units/kg/meal, 10,000 lipase units/kg/day, or 4,000 lipase units/g fat ingested/day in adult and pediatric patients greater than 12 months of age without further investigation. ( 5.1 ) The total daily dosage in adult and pediatric patients greater than 12 months of age should reflect approximately three meals plus two or three snacks per day. With each snack, administer approximately half the prescribed dose for a meal. Do not substitute other pancreatic enzyme products for ZENPEP. When switching from another pancreatic enzyme product to ZENPEP, monitor patients for clinical symptoms of exocrine pancreatic insufficiency and titrate the dosage as needed. Recommended Dosage ( 2.2 ) Adult and Pediatric Patients Greater than 12 Months : The recommended initial starting dosage is: 500 lipase units/kg/meal for adult and pediatric patients 4 years of age and older. 1,000 lipase units/kg/meal for pediatric patients greater than 12 months of age to less than 4 years of age. Titrate to either 2,500 lipase units/kg/meal, 10,000 lipase units/kg/day, or 4,000 lipase units/g fat ingested/day. Higher dosages may be administered if documented effective by fecal fat measures or improvement in malabsorption.

Fibrosing Colonopathy : Associated with high doses, usually over prolonged use and in pediatric patients with cystic fibrosis. Colonic stricture reported in pediatric patients less than 12 years of age with dosages exceeding 6,000 lipase units/kg/meal. Monitor during treatment for progression of preexisting disease. Do not exceed the recommended dosage, unless clinically indicated. ( 2.1 , 5.1 ) Irritation of the Oral Mucosa : May occur due to loss of protective enteric coating on the capsule contents. ( 2.3 , 5.2 ) Hyperuricemia : Reported with high dosages; consider monitoring blood uric acid levels in patients with gout, renal impairment, or hyperuricemia. ( 5.3 ) Risk of Viral Transmission : The presence of porcine viruses that might infect humans cannot be definitely excluded. ( 5.4 ) Hypersensitivity Reactions : Monitor patients with known reactions to proteins of porcine origin. If symptoms occur, initiate appropriate medical management; consider the risks and benefits of continued treatment. ( 5.5 ) 5.1 Fibrosing Colonopathy Fibrosing colonopathy has been reported following treatment with pancreatic enzyme products. Fibrosing colonopathy is a rare serious adverse reaction initially described in association with use of high-dose pancreatic enzyme products, usually with use over a prolonged period of time and most commonly reported in pediatric patients with cystic fibrosis.

The following serious or otherwise important adverse reactions are described elsewhere in the labeling: Fibrosing Colonopathy [see Warnings and Precautions (5.1) ] Irritation of the Oral Mucosa [see Warnings and Precautions (5.2) ] Hyperuricemia [see Warnings and Precautions (5.3) ] Risk of Viral Transmission [see Warnings and Precautions (5.4) ] Hypersensitivity Reactions [see Warnings and Precautions (5.5) ] Most common adverse reactions (≥6%) are: headache, contusion, cough, and early satiety. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Aimmune Therapeutics, Inc at 1-833-AIM2KNO (1-833-246-2566) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to the rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. The data described below reflect exposure to ZENPEP in 53 adult and pediatric patients with exocrine pancreatic insufficiency due to cystic fibrosis in two clinical trials conducted [see Clinical Studies (14) ] . In both trials, ZENPEP was administered at dosages of approximately 5,000 lipase units/kg/day for 19 to 42 days. Study 1 was a randomized, double-blind, placebo-controlled, crossover study of 34 adult and pediatric patients, aged 7 to 23 years.

8.1 Pregnancy Risk Summary Published data from case reports with pancrelipase use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes. Pancrelipase is minimally absorbed systematically; therefore, maternal use is not expected to result in fetal exposure to the drug. Animal reproduction studies have not been conducted with pancrelipase. The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. 8.2 Lactation Risk Summary There are no data on the presence of pancrelipase in either human or animal milk, the effects on the breastfed infant or the effects on milk production. Pancrelipase is minimally absorbed systemically following oral administration, therefore maternal use is not expected to result in clinically relevant exposure of breastfed infants to the drug.

Metabolism

Following oral administration, the lipases, proteases, and amylases released from ZENPEP are not absorbed from the gastrointestinal tract in appreciable amounts. Drug Interactions The lipases, proteases, and amylases of ZENPEP are not substrates of CYP enzymes or transporters.

Chronic high dosages of pancreatic enzyme products have been associated with fibrosing colonopathy and colonic strictures [see Warnings and Precautions (5.1) ] . High dosages of pancreatic enzyme products have been associated with hyperuricosuria and hyperuricemia [see Warnings and Precautions (5.3) ] .

• Aug 27, 2009BLABLA022210Eurand Pharma Ltd
• Apr 12, 2010BLABLA022523Vivus Inc

1. 1Diarrhoea5238.2%
2. 2Infective Pulmonary Exacerbation Of Cystic Fibrosis4747.4%
3. 3Hospitalisation3275.1%
4. 4Death3124.9%
5. 5Cystic Fibrosis3064.8%
6. 6Nausea2944.6%
7. 7Headache2644.1%
8. 8Pneumonia2544.0%
9. 9Fatigue2513.9%
10. 10Weight Decreased2273.5%
11. 11Drug Ineffective2133.3%
12. 12Abdominal Pain2123.3%
13. 13Dyspnoea2093.3%
14. 14Abdominal Pain Upper2083.2%
15. 15Constipation2083.2%

Recent PubMed references pinned to Protease as a MeSH major topic. Citations link to pubmed.ncbi.nlm.nih.gov.

• Integrative Pan-Cancer Mapping of Proteasome Dependency Prioritizes PSMB5 and PSMB6 as Context-Dependent Vulnerability Biomarkers Linked to Immune Context.
  Molecules (Basel, Switzerland) · 2026 · Kim JH, Park H, Kim HJ, et al.
  PMID 42280256DOI 10.3390/molecules31111954
• The Role of Matrix Metalloproteinases in Orthodontics, Dental Trauma, Restorative Dentistry, and Endodontics: Molecular Mechanisms and Clinical Implications.
  International journal of molecular sciences · 2026 · Ławicka R, Królikowska K, Błaszczak K, et al.
  PMID 42278329DOI 10.3390/ijms27114800
• Mechanism of PCSK9-Mediated Macrophage Activation via the CAP1/NF-κB Pathway in CAWS-Induced Kawasaki Disease Vasculitis.
  IUBMB life · 2026 · Zhang H, Shuai D, Ruan M, et al.
  PMID 42276750DOI 10.1002/iub.70119
• [A study of soy protein proteolysis by digestive enzymes and description of the peptide profile of the obtained hydrolysates].
  Voprosy pitaniia · 2026 · Fomenko VV, Detinkin IA, Chernukha IM, et al.
  PMID 42272414DOI 10.33029/0042-8833-2026-95-2-70-91
• Multi-omics profiling identifies ADAM9 as a key efferocytosis driver in lung adenocarcinoma.
  Frontiers in immunology · 2026 · Lin G, Lin L, Zhao J, et al.
  PMID 42266684DOI 10.3389/fimmu.2026.1772167
• Assessing the Effectiveness of "Onabotulinumtoxin A" (Botox®) Intradetrusor Injection for Overactive Bladder (OAB) Patients After Medical Therapy Failure.
  Archivos espanoles de urologia · 2026 · Saitta G, Calabrese B, Striano V, et al.
  PMID 42265958DOI 10.56434/j.arch.esp.urol.20267904.70
• Effect of collagenase ointment versus silver sulfadiazine ointment on the healing of deep second-degree burns: a prospective randomised study.
  Journal of wound care · 2026 · Tong L, Shi X, Hu X, et al.
  PMID 42262984DOI 10.12968/jowc.2023.0130
• The risk of developing cardiovascular diseases based on the determination of VEGF, MMP-9 and visfatin concentrations in adolescent girls with polycystic ovary syndrome.
  Ginekologia polska · 2026 · Skrzynska KJ, Zachurzok A, Pietrusik A, et al.
  PMID 42261713DOI 10.5603/gpl.104729

The 10 most recently updated of 2,725 ClinicalTrials.gov registrations naming Protease as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Multi-Scale Analysis of Phenotypes in Heart Failure (MAP-HEART)
  Enrolling by invitation · Observational · 2,000 enrolled · National Heart, Lung, and Blood Institute (NHLBI)
  NCT06280820updated 2026-06-12
• BOTOX Injection Technique for LUTS Due to BPH
  Completed · Phase 1 · Interventional · 60 enrolled · Benha University
  NCT07645456updated 2026-06-12
• Alteplase Through an Indwelling Pleural Catheter for the Management of Symptomatic Septated Malignant Pleural Effusion
  Recruiting · Early phase 1 · Interventional · 30 enrolled · M.D. Anderson Cancer Center
  NCT06184321updated 2026-06-12
• Postoperative Non-Opioid Pain Management Utilizing Local Anesthetics Coupled With Modulated Coagulation
  Not yet recruiting · Phase 4 · Interventional · 40 enrolled · NYU Langone Health
  NCT07644923updated 2026-06-12
• CleaRRAflow: Isotonic Solution vs. TPA for IVH Clearance
  Not yet recruiting · Phase 4 · Interventional · 80 enrolled · David Dornbos
  NCT07643493updated 2026-06-11
• ONC206 for Treatment of Newly Diagnosed, Recurrent Diffuse Midline Gliomas, and Other Recurrent Malignant CNS Tumors
  Recruiting · Phase 1 · Interventional · 208 enrolled · Sabine Mueller, MD, PhD
  NCT04732065updated 2026-06-11
• Phase 2 Study to Assess the Safety and Efficacy of ANG003
  Recruiting · Phase 2 · Interventional · 113 enrolled · Anagram Therapeutics, Inc.
  NCT07450547updated 2026-06-10
• Botulinum Toxin-A for Bruxism Using Digital Occlusal Analysis
  Not yet recruiting · Early phase 1 · Interventional · 36 enrolled · Bilecik Seyh Edebali Universitesi
  NCT07640035updated 2026-06-10
• Endovascular Thrombectomy Alone Versus Intravenous Thrombolysis Plus Thrombectomy on Acute Basilar Artery Occlusion
  Recruiting · Phase 3 · Interventional · 338 enrolled · The First Affiliated Hospital of University of Science and Technology of China
  NCT05827042updated 2026-06-09
• Effect of Topical Bromelain Versus Topical Corticosteroids in the Management of Oral Lichen Planus
  Recruiting · Phase 2 · Interventional · 42 enrolled · Cairo University
  NCT06981767updated 2026-06-09

Frequently asked questions

How does Protease work?

Pancreatic enzyme products contain a mixture of lipases, proteases, and amylases that catalyze the hydrolysis of fats to monoglycerides, glycerol, and free fatty acids, protein into peptides and amino acids, and starch into dextrins and short chain sugars such as maltose and maltriose in the duodenum and proximal small intestine, thereby acting like digestive enzymes physiologically secreted by the pancreas.

What is Protease used for?

According to FDA labeling, Protease carries indications including: ZENPEP ® is indicated for the treatment of exocrine pancreatic insufficiency in adult and pediatric patients. ZENPEP ® is indicated for the treatment of exocrine pancreatic insufficiency in adult and pediatric patients.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What are the brand names for Protease?

Protease is marketed under brand names including Creon, PanaKare, PancrePlus, Pancreaze, Pertzye, Viokace, Zenpep.

What are the contraindications for Protease?

Protease labeling lists contraindications including: None.. Always consult the full prescribing information and a clinician.