Pancreatic Enzyme Products: Overview, Uses, Side Effects, Precautions, Interactions, Dosing and Reviews

Overview

Pancreatic enzyme products contain pancreatin or pancrelipase, which is a mixture of amylase, lipase, and protease. These enzymes are made by the pancreas.

Amylase, lipase, and protease are normally made by the pancreas to help the body digest food. In the US, pancreatic enzyme products are available as a prescription or in dietary supplements. The enzymes in these products usually come from the pancreas in pigs.

People use prescription pancreatic enzyme products to treat digestion problems that occur when the pancreas has been removed or is not working well. Prescription products are FDA-approved for pancreatic insufficiency. People use supplement products to help with digestion and for other conditions, but there is no good scientific evidence to support these uses.

Prescription pancreatic enzyme products are not the same as supplement pancreatic enzyme products. Prescription products contain a standardized amount of enzymes, while the contents of supplement products vary. Also, pancreatic enzyme products usually come from the pancreas in pigs. Pigs may carry viruses. It might be possible for someone to get sick from these viruses. But this has not been reported.

Uses & Effectiveness

Effective for

Digestion problems due to a disorder of the pancreas (pancreatic insufficiency). Taking prescription pancreatic enzyme products by mouth improves the absorption of fat, protein, and energy in people with who are unable to digest food properly due to cystic fibrosis, pancreas removal, or pancreas swelling (pancreatitis). It's not clear if non-prescription pancreatic products help.

There is interest in using pancreatic enzyme products for a number of other purposes, but there isn't enough reliable information to say whether it might be helpful.

Side Effects

When taken by mouth: Prescription pancreatic enzyme products are likely safe when used under the guidance of a healthcare provider. Side effects might include stomach pain, nausea, or vomiting. Taking prescription pancreatic enzyme products in amounts greater than prescribed is possibly unsafe. Higher doses might increase the risk of having a rare bowel disorder.

There isn't enough reliable information to know if pancreatic enzyme SUPPLEMENTS are safe.

Special Precautions and Warnings

Pregnancy and breast-feeding: There isn't enough reliable information to know if pancreatic enzyme products are safe to use when pregnant or breast-feeding. Stay on the safe side and avoid use unless prescribed to you by a healthcare professional.

Children: Prescription pancreatic enzyme products are likely safe when taken by mouth under the guidance of a healthcare provider. Be sure to follow the prescribed dosing instructions. Taking prescription pancreatic enzyme products in amounts greater than prescribed is possibly unsafe. There isn't enough reliable information to know if pancreatic enzyme SUPPLEMENTS are safe.

Diabetes: Pancreatic enzyme products might make it harder for some people with diabetes to control their blood sugar. Monitor your blood sugar carefully if you have diabetes and use pancreatic enzyme products.

Interactions

Moderate Interaction

Be cautious with this combination

Acarbose (Precose, Prandase) interacts with Pancreatic Enzyme Products
Pancreatic enzyme products might break down acarbose, removing it from the body. This might reduce the effects of acarbose.

Dosing

In the US, pancreatic enzyme products are available as prescription products (Creon, Zenpep, Pancreaze, Ultresa, Viokace, and Pertzye) and as dietary supplements. Prescription products should only be used under the guidance of a healthcare provider. Supplement products should not be used in place of prescription products because the amount of active ingredient in these products can vary from one batch to the next. Speak with your healthcare provider before use.

View References

REFERENCES:

Martindale W. Martindale the Extra Pharmacopoeia. Pharmaceutical Press, 1999.

McEvoy GK, ed. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists, 1998.

Gennaro A. Remington: The Science and Practice of Pharmacy. 19th ed. Lippincott: Williams & Wilkins, 1996.

Burnham TH, ed. Drug Facts and Comparisons, Updated Monthly. Facts and Comparisons, St. Louis, MO.

Smyth RL, van Velzen D, Smyth AR, et al. Strictures of ascending colon in cystic fibrosis and high-strength pancreatic enzymes. Lancet 1994;343:85-6.

Russell RM, Dutta SK, Oaks EV, et al. Impairment of folic acid absorption by oral pancreatic extracts. Dig Dis Sci 1980;25:369-73.

Bergner A, Bergner RK. Pulmonary hypersensitivity associated with pancreatin powder exposure. Pediatrics 1975;55:814-7.

Wiessmann KJ, Baur X. Occupational lung disease following long-term inhalation of pancreatic extracts. Eur J Respir Dis 1985;66:13-20.

Bragelmann, R., Armbrecht, U., Rosemeyer, D., Schneider, B., Zilly, W., and Stockbrugger, R. W. The effect of pancreatic enzyme supplementation in patients with steatorrhoea after total gastrectomy. Eur.J Gastroenterol.Hepatol. 1999;11(3):231-237.

Halm, U., Loser, C., Lohr, M., Katschinski, M., and Mossner, J. A double-blind, randomized, multicentre, crossover study to prove equivalence of pancreatin minimicrospheres versus microspheres in exocrine pancreatic insufficiency. Aliment.Pharmacol.Ther. 1999;13(7):951-957.

Neoptolemos, J. P., Ghaneh, P., Andren-Sandberg, A., Bramhall, S., Patankar, R., Kleibeuker, J. H., and Johnson, C. D. Treatment of pancreatic exocrine insufficiency after pancreatic resection. Results of a randomized, double-blind, placebo-controlled, crossover study of high vs standard dose pancreatin. Int.J.Pancreatol. 1999;25(3):171-180.

Farkas, G., Takacs, T., Baradnay, G., and Szasz, Z. [Effect of pancreatin replacement on pancreatic function in the postoperative period after pancreatic surgery]. Orv.Hetil. 12-5-1999;140(49):2751-2754.

Lauque, S., Nourhashemi, F., Baudouin, M., Ghisolfi-Marque, A., Beziat, F., Moreau, J., Dyard, F., Vellas, B., and Albarede, J. L. Assessment of the effectiveness of drug therapies on nutritional status in the elderly: "concerning a randomised, double-blind clinical study of the activity of pancreatic extracts and a placebo during the renutrition of elderly subjects suffering from protein caloric undernutrition". J Nutr.Health Aging 1998;2(1):18-20.

O'Keefe, S. J., Cariem, A. K., and Levy, M. The exacerbation of pancreatic endocrine dysfunction by potent pancreatic exocrine supplements in patients with chronic pancreatitis. J Clin Gastroenterol. 2001;32(4):319-323.

Farkas, G., Leindler, L., and Mihalovits, G. [Dose-dependent effect of pancreatin replacement upon the pancreatic function in the period after pancreatic surgery]. Magy.Seb. 2001;54(6):347-350.

Mossner, J., Secknus, R., Meyer, J., Niederau, C., and Adler, G. Treatment of pain with pancreatic extracts in chronic pancreatitis: results of a prospective placebo-controlled multicenter trial. Digestion 1992;53(1-2):54-66.

Patchell, C. J., Desai, M., Weller, P. H., Macdonald, A., Smyth, R. L., Bush, A., Gilbody, J. S., and Duff, S. A. Creon 10,000 Minimicrospheres vs. Creon 8,000 microspheres--an open randomised crossover preference study. J Cyst.Fibros. 2002;1(4):287-291.

Elliott, R. B., Escobar, L. C., Lees, H. R., Akroyd, R. M., and Reilly, H. C. A comparison of two pancreatin microsphere preparations in cystic fibrosis. N.Z.Med.J. 3-25-1992;105(930):107-108.

Zentler-Munro, P. L., Assoufi, B. A., Balasubramanian, K., Cornell, S., Benoliel, D., Northfield, T. C., and Hodson, M. E. Therapeutic potential and clinical efficacy of acid-resistant fungal lipase in the treatment of pancreatic steatorrhoea due to cystic fibrosis. Pancreas 1992;7(3):311-319.

DiMagno, E. P., Malagelada, J. R., Go, V. L., and Moertel, C. G. Fate of orally ingested enzymes in pancreatic insufficiency. Comparison of two dosage schedules. N.Engl.J Med 6-9-1977;296(23):1318-1322.

Ewald, N., Bretzel, R. G., Fantus, I. G., Hollenhorst, M., Kloer, H. U., and Hardt, P. D. Pancreatin therapy in patients with insulin-treated diabetes mellitus and exocrine pancreatic insufficiency according to low fecal elastase 1 concentrations. Results of a prospective multi-centre trial. Diabetes Metab Res Rev. 2007;23(5):386-391.

Delchier, J. C., Vidon, N., Saint-Marc Girardin, M. F., Soule, J. C., Moulin, C., Huchet, B., and Zylberberg, P. Fate of orally ingested enzymes in pancreatic insufficiency: comparison of two pancreatic enzyme preparations. Aliment.Pharmacol Ther. 1991;5(4):365-378.

Shin, S. Y., Hur, G. Y., Ye, Y. M., and Park, H. S. A case of occupational rhinitis caused by porcine pancreatic extract developing into occupational asthma. J Korean Med Sci. 2008;23(2):347-349.

Williams, J., Macdonald, A., Weller, P. H., Fields, J., and Pandov, H. Two enteric coated microspheres in cystic fibrosis. Arch Dis.Child 1990;65(6):594-597.

Glasbrenner, B., Malfertheiner, P., Kerner, W., Scherbaum, W. A., and Ditschuneit, H. [Effect of pancreatin on diabetes mellitus in chronic pancreatitis]. Z.Gastroenterol. 1990;28(6):275-279.

Andersen, H. O., Hjelt, K., Waever, E., and Overgaard, K. The age-related incidence of meconium ileus equivalent in a cystic fibrosis population: the impact of high-energy intake. J Pediatr Gastroenterol.Nutr 1990;11(3):356-360.

Stern, M., Plettner, C., and Gruttner, R. [Pancreatic enzyme replacement in mucoviscidosis (CF): clinical evaluation of a gastric acid-resistant pancreatin preparation in encapsulated microtablet form]. Klin.Padiatr. 1988;200(1):36-39.

Littlewood, J. M., Kelleher, J., Walters, M. P., and Johnson, A. W. In vivo and in vitro studies of microsphere pancreatic supplements. J Pediatr.Gastroenterol.Nutr. 1988;7 Suppl 1:S22-S29.

Ramo, O. J., Puolakkainen, P. A., Seppala, K., and Schroder, T. M. Self-administration of enzyme substitution in the treatment of exocrine pancreatic insufficiency. Scand.J Gastroenterol. 1989;24(6):688-692.

Herrerias, J. M., Gomez, Parra M., Garcia Montes, J. M., Petit, M. A., and Valladolid Leon, J. M. [A comparative cross-over study of pellet pancreatin and tablet pancreatin in chronic pancreatitis]. Rev.Esp.Enferm.Apar.Dig. 1989;76(6 Pt 2):651-653.

Robinson, P. J., Olinsky, A., Smith, A. L., and Chitravanshi, S. B. High compared with standard dose lipase pancreatic supplement. Arch Dis.Child 1989;64(1):143-145.

Aparisi, L., Rodrigo, J. M., Serra, M. A., Del Olmo, J., Bisquert, M., and Raga, F. [Efficacy of a new microencapsulated pancreatin versus a conventional preparation, in the treatment of steatorrhea of pancreatic origin]. Rev.Esp.Enferm.Apar.Dig. 1989;76(1):25-30.

Stead, R. J., Skypala, I., and Hodson, M. E. Treatment of steatorrhoea in cystic fibrosis: a comparison of enteric-coated microspheres of pancreatin versus non-enteric-coated pancreatin and adjuvant cimetidine. Aliment.Pharmacol.Ther. 1988;2(6):471-482.

Ansaldi-Balocco, N., Santini, B., and Sarchi, C. Efficacy of pancreatic enzyme supplementation in children with cystic fibrosis: comparison of two preparations by random crossover study and a retrospective study of the same patients at two different ages. J Pediatr Gastroenterol.Nutr 1988;7 Suppl 1:S40-S45.

Carroccio, A., Pardo, F., Montalto, G., Japichino, L., Iacono, G., Collura, M., and Notarbartolo, A. Effectiveness of enteric-coated preparations on nutritional parameters in cystic fibrosis. A long-term study. Digestion 1988;41(4):201-206.

Duhamel, J. F., Vidailhet, M., Le Luyer, B., Douchain, F., Jehanne, M., Clavel, R., and Guillot, M. [Multicenter comparative study of a new formulation of pancreatin in gastro-resistant microgranules for the treatment of exocrine pancreatic insufficiency in children with mucoviscidosis]. Ann.Pediatr.(Paris) 1988;35(1):69-74.

Beverley, D. W., Kelleher, J., Macdonald, A., Littlewood, J. M., Robinson, T., and Walters, M. P. Comparison of four pancreatic extracts in cystic fibrosis. Arch Dis.Child 1987;62(6):564-568.

Stead, R. J., Skypala, I., Hodson, M. E., and Batten, J. C. Enteric coated microspheres of pancreatin in the treatment of cystic fibrosis: comparison with a standard enteric coated preparation. Thorax 1987;42(7):533-537.

Lankisch, P. G., Lembcke, B., Goke, B., and Creutzfeldt, W. Therapy of pancreatogenic steatorrhoea: does acid protection of pancreatic enzymes offer any advantage? Z.Gastroenterol. 1986;24(12):753-757.

Petersen, W., Heilmann, C., and Garne, S. Pancreatic enzyme supplementation as acid-resistant microspheres versus enteric-coated granules in cystic fibrosis. A double placebo-controlled cross-over study. Acta Paediatr.Scand 1987;76(1):66-69.

Halgreen, H., Pedersen, N. T., and Worning, H. Symptomatic effect of pancreatic enzyme therapy in patients with chronic pancreatitis. Scand J Gastroenterol. 1986;21(1):104-108.

Zentler-Munro, P. L., Fine, D. R., Batten, J. C., and Northfield, T. C. Effect of cimetidine on enzyme inactivation, bile acid precipitation, and lipid solubilisation in pancreatic steatorrhoea due to cystic fibrosis. Gut 1985;26(9):892-901.

Braggion, C. and Mastella, G. [Clinical trial of several preparation types of the pancreatic extract Pancrex V in the treatment of cystic fibrosis]. Minerva Pediatr 11-30-1985;37(21-22):891-896.

Silber, W. Pankreoflat in benign diseases of the oesophagus: a blind therapeutic trial. S.Afr.Med J 7-7-1973;47(26):1137-1138.

Buckle, R. M. Maintenance therapy of pancreatic steatorrhoea with concentrated pancreatic extract. Br.J Clin.Pract. 1965;19(12):683-686.

Slaff, J., Jacobson, D., Tillman, C. R., Curington, C., and Toskes, P. Protease-specific suppression of pancreatic exocrine secretion. Gastroenterology 1984;87(1):44-52.

O'Keefe, S. J. and Adam, J. Assessment of adequacy of pancreatic enzyme replacement with the multiple-phase carbon-14-triolein test. S.Afr.Med J 11-17-1984;66(20):763-765.

Isaksson, G. and Ihse, I. Pain reduction by an oral pancreatic enzyme preparation in chronic pancreatitis. Dig.Dis.Sci 1983;28(2):97-102.

Sack, J., Blau, H., Goldfarb, D., Ben-Zaray, S., and Katznelson, D. Hyperuricosuria in cystic fibrosis patients treated with pancreatic enzyme supplements. A study of 16 patients in Israel. Isr.J Med Sci. 1980;16(6):417-419.

Mischler, E. H., Parrell, S., Farrell, P. M., and Odell, G. B. Comparison of effectiveness of pancreatic enzyme preparations in cystic fibrosis. Am J Dis.Child 1982;136(12):1060-1063.

Oades, P. J., Bush, A., Ong, P. S., and Brereton, R. J. High-strength pancreatic enzyme supplements and large-bowel stricture in cystic fibrosis. Lancet 1-8-1994;343(8889):109.

Mac Sweeney, E. J., Oades, P. J., Buchdahl, R., Rosenthal, M., and Bush, A. Relation of thickening of colon wall to pancreatic-enzyme treatment in cystic fibrosis. Lancet 3-25-1995;345(8952):752-756.

Jones, R., Franklin, K., Spicer, R., and Berry, J. Colonic strictures in children with cystic fibrosis on low-strength pancreatic enzymes. Lancet 8-19-1995;346(8973):499.

Taylor, C. J. and Steiner, G. M. Fibrosing colonopathy in a child on low-dose pancreatin. Lancet 10-21-1995;346(8982):1106-1107.

Ong, P. S., Oades, P. J., Bush, A., and Brereton, R. J. Colonic stricture in a boy with cystic fibrosis. Postgrad.Med J 1995;71(835):309-312.

Malesci, A., Gaia, E., Fioretta, A., Bocchia, P., Ciravegna, G., Cantor, P., and Vantini, I. No effect of long-term treatment with pancreatic extract on recurrent abdominal pain in patients with chronic pancreatitis. Scand.J Gastroenterol. 1995;30(4):392-398.

Layer, P. and Groger, G. Fate of pancreatic enzymes in the human intestinal lumen in health and pancreatic insufficiency. Digestion 1993;54 Suppl 2:10-14.

Mossner, J. Is there a place for pancreatic enzymes in the treatment of pain in chronic pancreatitis? Digestion 1993;54 Suppl 2:35-39.

Gan, K. H., Heijerman, H. G., Geus, W. P., Bakker, W., and Lamers, C. B. Comparison of a high lipase pancreatic enzyme extract with a regular pancreatin preparation in adult cystic fibrosis patients. Aliment.Pharmacol.Ther. 1994;8(6):603-607.

Nakamura, T., Takebe, K., Kudoh, K., Ishii, M., Imamura, K., Kikuchi, H., Kasai, F., Tandoh, Y., Yamada, N., Arai, Y., and . Effects of pancreatic digestive enzymes, sodium bicarbonate, and a proton pump inhibitor on steatorrhoea caused by pancreatic diseases. J Int Med Res 1995;23(1):37-47.

Milla, C. E., Wielinski, C. L., and Warwick, W. J. High-strength pancreatic enzymes. Lancet 3-5-1994;343(8897):599.

McHugh, K., Thomson, A., and Tam, P. Case report: colonic stricture and fibrosis associated with high-strength pancreatic enzymes in a child with cystic fibrosis. Br.J Radiol. 1994;67(801):900-901.

Santini, B. and Ivaldi, A. P. [Pancreatic extract therapy in exocrine pancreatic insufficiency]. Minerva Gastroenterol.Dietol. 1993;39(3):133-137.

Nouisa-Arvanitakis, S., Stapleton, F. B., Linshaw, M. A., and Kennedy, J. Therapeutic approach to pancreatic extract-induced hyperuricosuria in cystic fibrosis. J Pediatr 1977;90(2):302-305.

Guarner, L., Rodriguez, R., Guarner, F., and Malagelada, J. R. Fate of oral enzymes in pancreatic insufficiency. Gut 1993;34(5):708-712.

Lancellotti, L., Cabrini, G., Zanolla, L., and Mastella, G. High- versus low-lipase acid-resistant enzyme preparations in cystic fibrosis: a crossover randomized clinical trial. J Pediatr.Gastroenterol.Nutr. 1996;22(1):73-78.

Van Hoozen, C. M., Peeke, P. G., Taubeneck, M., Frey, C. F., and Halsted, C. H. Efficacy of enzyme supplementation after surgery for chronic pancreatitis. Pancreas 1997;14(2):174-180.

FitzSimmons, S. C., Burkhart, G. A., Borowitz, D., Grand, R. J., Hammerstrom, T., Durie, P. R., Lloyd-Still, J. D., and Lowenfels, A. B. High-dose pancreatic-enzyme supplements and fibrosing colonopathy in children with cystic fibrosis. N.Engl.J Med 5-1-1997;336(18):1283-1289.

Stapleton, F. B., Kennedy, J., Nousia-Arvanitakis, S., and Linshaw, M. A. Hyperuricosuria due to high-dose pancreatic extract therapy in cystic fibrosis. N.Engl.J Med 7-29-1976;295(5):246-248.

Brown, A., Hughes, M., Tenner, S., and Banks, P. A. Does pancreatic enzyme supplementation reduce pain in patients with chronic pancreatitis: a meta-analysis. Am J Gastroenterol. 1997;92(11):2032-2035.

Bruno, M. J., Haverkort, E. B., Tijssen, G. P., Tytgat, G. N., and van Leeuwen, D. J. Placebo controlled trial of enteric coated pancreatin microsphere treatment in patients with unresectable cancer of the pancreatic head region. Gut 1998;42(1):92-96.

Miyoshi, H. and Kanzaki, T. Drug eruption (erythema multiforme type) due to a digestive enzyme drug. J Dermatol. 1998;25(1):28-31.

Layer, P. and Keller, J. Pancreatic enzymes: secretion and luminal nutrient digestion in health and disease. J Clin Gastroenterol. 1999;28(1):3-10.

Chazalette, J. P. A Double-Blind Placebo-Controlled Trial of a Pancreatic Enzyme Formulation (Panzytrat 25 000) in the Treatment of Impaired Lipid Digestion in Patients with Cystic Fibrosis. Drug Investigation 1993;5(5):274.

Salen, G. and Prakash, A. Evaluation of enteric-coated microspheres for enzyme replacement therapy in adults with pancreatic insufficiency. Curr Ther Res 1979;25:650-656.

Larvin, M., McMahon, M. J., and Thomas, W. E. G. Creon (enteric coated pancreatin microspheres) for the treatment of pain in chronic pancreatitis: A double blind randomised placebo-controlled crossover study (abstract). Gastroenterology 1991;1000:A283.

Gardner TB, Munson JC, Morden NE. The FDA and Prescription Pancreatic Enzyme Product Cost. Am J Gastroenterol. 2014;109(5):624-5.

U.S. Food and Drug Administration. Updated Questions and Answers for Healthcare Professionals and the Public: Use an Approved Pancreatic Enzyme Product (PEP). Available at: https://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm204745.htm. Accessed April 24, 2019.

Catarci M, Berlanda M, Grassi GB, Masedu F, Guadagni S. Pancreatic enzyme supplementation after gastrectomy for gastric cancer: a randomized controlled trial. Gastric Cancer. 2018;21(3):542-551.

Seiler CM, Izbicki J, Varga-Szabó L, et al. Randomised clinical trial: a 1-week, double-blind, placebo-controlled study of pancreatin 25 000 Ph. Eur. minimicrospheres (Creon 25000 MMS) for pancreatic exocrine insufficiency after pancreatic surgery, with a 1-year open-label extension. Aliment Pharmacol Ther. 2013;37(7):691-702.

Thorat V, Reddy N, Bhatia S, et al. Randomised clinical trial: the efficacy and safety of pancreatin enteric-coated minimicrospheres (Creon 40000 MMS) in patients with pancreatic exocrine insufficiency due to chronic pancreatitis--a double-blind, placebo-controlled study. Aliment Pharmacol Ther. 2012;36(5):426-36.

Lee SK, Kim MS, Lee UH. Acute generalized exanthematous pustulosis induced by a digestive enzyme drug, Festal(®). Clin Exp Dermatol. 2018;43(3):321-323.

Whitcomb DC, Bodhani A, Beckmann K, et al. Efficacy and safety of pancrelipase/pancreatin in patients with exocrine pancreatic insufficiency and a medical history of diabetes mellitus. Pancreas. 2016;45(5):679-86.

Ramesh H, Reddy N, Bhatia S, et al. A 51-week, open-label clinical trial in India to assess the efficacy and safety of pancreatin 40000 enteric-coated minimicrospheres in patients with pancreatic exocrine insufficiency due to chronic pancreatitis. Pancreatology. 2013;13(2):133-9.

Saito T, Nakai Y, Isayama H, et al. A multicenter open-label randomized controlled trial of pancreatic enzyme replacement therapy in unresectable pancreatic cancer. Pancreas. 2018;47:800-806.

Satoi S, Sho M, Yanagimoto H, et al. Do pancrelipase delayed-release capsules have a protective role against non-alcoholic fatty liver disease after pancreatoduodenectomy in patients with pancreatic cancer? A randomized controlled trial. J Hepatobiliary Pancreat Sci. 2016;23(3):167-73.

Nagai M, Sho M, Satoi S, et al. Effects of pancrelipase on nonalcoholic fatty liver disease after pancreaticoduodenectomy. J Hepatobiliary Pancreat Sci. 2014;21(3):186-92.

Woo SM, Joo J, Kim SY, et al. Efficacy of pancreatic exocrine replacement therapy for patients with unresectable pancreatic cancer in a randomized trial. Pancreatology. 2016;16(6):1099-1105.

Toskes PP, Secci A, Thieroff-Ekerdt R; ZENPEP Study Group. Efficacy of a novel pancreatic enzyme product, EUR-1008 (Zenpep), in patients with exocrine pancreatic insufficiency due to chronic pancreatitis. Pancreas. 2011;40(3):376-82.

Whitcomb DC, Lehman GA, Vasileva G, et al. Pancrelipase delayed-release capsules (CREON) for exocrine pancreatic insufficiency due to chronic pancreatitis or pancreatic surgery: A double-blind randomized trial. Am J Gastroenterol. 2010;105(10):2276-86.

Kahl S, Schütte K, Glasbrenner B, et al. The effect of oral pancreatic enzyme supplementation on the course and outcome of acute pancreatitis: a randomized, double-blind parallel-group study. JOP. 2014;15(2):165-74.

Trapnell BC, Strausbaugh SD, Woo MS, et al. Efficacy and safety of PANCREAZE® for treatment of exocrine pancreatic insufficiency due to cystic fibrosis. J Cyst Fibros. 2011;10(5):350-6.

Graff GR, Maguiness K, McNamara J, et al. Efficacy and tolerability of a new formulation of pancrelipase delayed-release capsules in children aged 7 to 11 years with exocrine pancreatic insufficiency and cystic fibrosis: a multicenter, randomized, double-blind, placebo-controlled, two-period crossover, superiority study. Clin Ther. 2010;32(1):89-103.

Trapnell BC, Maguiness K, Graff GR, Boyd D, Beckmann K, Caras S. Efficacy and safety of Creon 24,000 in subjects with exocrine pancreatic insufficiency due to cystic fibrosis. J Cyst Fibros. 2009;8(6):370-7.

Munck A, Duhamel JF, Lamireau T, et al. Pancreatic enzyme replacement therapy for young cystic fibrosis patients. J Cyst Fibros. 2009;8(1):14-8.

Taylor CJ, Thieroff-Ekerdt R, Shiff S, Magnus L, Fleming R, Gommoll C. Comparison of two pancreatic enzyme products for exocrine insufficiency in patients with cystic fibrosis. J Cyst Fibros. 2016;15(5):675-80.

Carroccio A, Guarino A, Zuin G, et al. Efficacy of oral pancreatic enzyme therapy for the treatment of fat malabsorption in HIV-infected patients. Aliment Pharmacol Ther. 2001;15(10):1619-25.

Santini B, Antonelli M, Battistini A, et al. Comparison of two enteric coated microsphere preparations in the treatment of pancreatic exocrine insufficiency caused by cystic fibrosis. Dig Liver Dis. 2000;32(5):406-11.

Brady MS, Garson JL, Krug SK, et al. An enteric-coated high-buffered pancrelipase reduces steatorrhea in patients with cystic fibrosis: a prospective, randomized study. J Am Diet Assoc. 2006;106(8):1181-6.

Stern RC, Eisenberg JD, Wagener JS, et al. A comparison of the efficacy and tolerance of pancrelipase and placebo in the treatment of steatorrhea in cystic fibrosis patients with clinical exocrine pancreatic insufficiency. Am J Gastroenterol. 2000;95(8):1932-8.

Safdi M, Bekal PK, Martin S, Saeed ZA, Burton F, Toskes PP. The effects of oral pancreatic enzymes (Creon 10 capsule) on steatorrhea: a multicenter, placebo-controlled, parallel group trial in subjects with chronic pancreatitis. Pancreas. 2006;33(2):156-62.

Trang T, Chan J, Graham DY. Pancreatic enzyme replacement therapy for pancreatic exocrine insufficiency in the 21(st) century. World J Gastroenterol. 2014;20(33):11467-85.

Guidance for Industry Exocrine Pancreatic Insufficiency Drug Products - Submitting NDAs. Available at: https://www.fda.gov/ucm/groups/fdagov-public/@fdagov-drugs-gen/documents/document/ucm071651.pdf. Accessed March 29, 2019.

Singer S, Koenekoop J, Meddings J, Powell J, Desroches A, Seidman EG. Pancreatic Enzyme Supplementation in Patients with Atopic Dermatitis and Food Allergies: An Open-Label Pilot Study. Paediatr Drugs. 2019 Feb;21(1):41-45.

Kim H, Yoon YS, Han Y, et al. Effects of Pancreatic Enzyme Replacement Therapy on Body Weight and Nutritional Assessments After Pancreatoduodenectomy in a Randomized Trial. Clin Gastroenterol Hepatol. 2019 Sep 12. pii: S1542-3565(19)30990-5.

EFSA Panel on Food Contact Materials, Enzymes and Processing Aids (CEP), Silano V, et al. Safety evaluation of a food enzyme containing trypsin and chymotrypsin from porcine pancreas. EFSA J 2021;19(1):e06369.

EFSA Panel on Food Contact Materials, Enzymes and Processing Aids (CEP), Silano V, et al. Safety evaluation of a food enzyme containing trypsin, chymotrypsin, elastase and carboxypeptidase from porcine pancreas. EFSA J 2021;19(1):e06368.

EFSA Panel on Food Contact Materials, Enzymes and Processing Aids (CEP), Lambré C, et al. Safety evaluation of a food enzyme containing trypsin and chymotrypsin from porcine pancreas. EFSA J 2021;19(6):e06640.

Amoateng R, Hardman B, Liu C, Austin S. Rare case of pancrelipase therapy-induced neutropaenia. BMJ Case Rep 2021;14(3):e241799.

US Food and Drug Administration (FDA). Zenpep (pancrelipase liapse, pancrelipase protease, prancrelipase amylase) Prescribing Information. February 2024. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022210s000lbl.pdf. Accessed August 11, 2025.

Zhou J, Liu K, Pan Q. Porcine-derived pancreatic enzyme replacement therapy linking to chronic hepatitis E: broad implications. Gut 2024.

Kamar N, Marion O, Abravanel F, Esposito L, Del Bello A, Izopet J. Porcine-derived pancreatic enzyme replacement therapy: a cause of hepatitis E virus transmission?. Gut 2024.

Thornton CS, Waddell BJ, Congly SE, et al. Porcine-derived pancreatic enzyme replacement therapy may be linked to chronic hepatitis E virus infection in cystic fibrosis lung transplant recipients. Gut 2024;73(10):1702-1711.

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