Pancreatic enzymes (medication)

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Pancreatic enzymes
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Complex of lipase with colipase
Clinical data
Trade names Creon, Pancreaze, Pertzye, others [1]
AHFS/Drugs.com Monograph
MedlinePlus a604035
Routes of
administration 		By mouth
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only)
  • EU:Rx-only [2]
  • In general: ℞ (Prescription only)
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CAS Number
DrugBank
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  • none
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Pancreatic enzymes, also known as pancreases or pancrelipase and pancreatin, are commercial mixtures of amylase, lipase, protease and lactase. [3] [4] They are used to treat malabsorption syndrome due to certain pancreatic problems. [3] These pancreatic problems may be due to cystic fibrosis, surgical removal of the pancreas, long term pancreatitis, pancreatic cancer, or MODY 5, among others. [3] [5] The preparation is taken by mouth. [3]

Contents

Common side effects include vomiting, abdominal pain, constipation, and diarrhea. [3] Other side effects include perianal irritation and high blood uric acid. [5] The enzymes are from pigs. [5] Use is believed to be safe during pregnancy. [5] The components are digestive enzymes similar to those normally produced by the human pancreas. [6] They help the person digest fats, starches, and proteins. [5]

Pancreatic enzymes have been used as medications since at least the 1800s. [7] They are on the World Health Organization's List of Essential Medicines. [8] In 2022, it was the 253rd most commonly prescribed medication in the United States, with more than 1 million prescriptions. [9] [10]

Medical uses

Pancrelipases are generally a first line approach in treatment of exocrine pancreatic insufficiency and other digestive disorders, accompanying cystic fibrosis, complicating surgical pancreatectomy, or resulting from chronic pancreatitis. The formulations are generally hard capsules filled with gastro-resistant granules. Pancrelipases and pancreatins are similar, except pancrelipases has an increased lipase component.[ citation needed ]

Pancreatin is a mixture of several digestive enzymes produced by the exocrine cells of the pancreas. It is composed of amylase, lipase and protease. [11] This mixture is used to treat conditions in which pancreatic secretions are deficient, such as surgical pancreatectomy, pancreatitis and cystic fibrosis. [11] [12] It has been claimed to help with food allergies, celiac disease, autoimmune disease, cancer and weight loss. Pancreatin is sometimes called "pancreatic acid", although it is neither a single chemical substance nor an acid.[ citation needed ]

A similar mixture of enzymes is sold as pancrelipase, which contains more active lipase enzyme than does pancreatin. The trypsin found in pancreatin works to hydrolyze proteins into oligopeptides; amylase hydrolyzes starches into oligosaccharides and the disaccharide maltose; and lipase hydrolyzes triglycerides into fatty acids and glycerols. Pancreatin is an effective enzyme supplement for replacing missing pancreatic enzymes, and aids in the digestion of foods in cases of pancreatic insufficiency. [13]

Pancreatin reduces the absorption of iron from food in the duodenum during digestion. [14]

Some contact lens-cleaning solutions contain porcine pancreatin extractives to assist in the intended protein-removal process. [15]

Side effects

High doses over a long period of time are associated with fibrosing colonopathy. [16] Due to this association a maximum dose of 10,000 IU of lipase per kilogram per day is recommended. [17]

Though never reported there is a theoretical risk of a viral infection as they are from pigs. [18]

Society and culture

Brand names

Brand names include Creon, [19] Pancreaze, Pertzye, Sollpura [20] (Liprotamase [21] [note 1] ), Ultresa, [22] and Zenpep. [23]

In some countries, Creon is marketed by Viatris after Upjohn merged with Mylan to create Viatris. [24] [25]

United States

Longstanding pancreatic enzyme replacement products (PERPs)—some in use for a century or more—fell under a 2006 FDA requirement that pharmaceutical companies with porcine-derived PERP products submit a New Drug Application (NDA) for each; Creon (AbbVie Inc.), the first of the commercial PERP products approved after the FDA directive, reached market in 2009. [19]

The specific requirement and reasoning for the FDA directive was that manufacturers submit a Risk Evaluation and Mitigation Strategy (REMS) and Medication Guide to ensure patients are adequately informed regarding potential risks associated with administration of high doses of porcine-derived PERP products, especially with regard to "the theoretical risk of transmission of viral disease from pigs to patients", the risk of which (alongside other off-target effects) is reduced by patient adherence to label dosing instructions. [19]

Shortages and alternatives

Due to its non-constant supply, being sourced from pigs, there have been several pancreatin shortages in different markets. [26] [27] [28]

This has led for alternative sources of enzymes to be studied and commercialised, mainly being of bacterial or fungal origin. [29] [30]

Notes

  1. ↑ Did not make it past Phase 3 trials

Related Research Articles

<span class="mw-page-title-main">Pancreas</span> Organ of the digestive system and endocrine system of vertebrates

The pancreas is an organ of the digestive system and endocrine system of vertebrates. In humans, it is located in the abdomen behind the stomach and functions as a gland. The pancreas is a mixed or heterocrine gland, i.e., it has both an endocrine and a digestive exocrine function. 99% of the pancreas is exocrine and 1% is endocrine. As an endocrine gland, it functions mostly to regulate blood sugar levels, secreting the hormones insulin, glucagon, somatostatin and pancreatic polypeptide. As a part of the digestive system, it functions as an exocrine gland secreting pancreatic juice into the duodenum through the pancreatic duct. This juice contains bicarbonate, which neutralizes acid entering the duodenum from the stomach; and digestive enzymes, which break down carbohydrates, proteins and fats in food entering the duodenum from the stomach.

<span class="mw-page-title-main">Pancreatitis</span> Inflammation of the pancreas

Pancreatitis is a condition characterized by inflammation of the pancreas. The pancreas is a large organ behind the stomach that produces digestive enzymes and a number of hormones. There are two main types: acute pancreatitis, and chronic pancreatitis.

In medicine, the fecal fat test is a diagnostic test for fat malabsorption conditions, which lead to excess fat in the feces (steatorrhea).

Steatorrhea is the presence of excess fat in feces. Stools may be bulky and difficult to flush, have a pale and oily appearance, and can be especially foul-smelling. An oily anal leakage or some level of fecal incontinence may occur. There is increased fat excretion, which can be measured by determining the fecal fat level.

<span class="mw-page-title-main">Acute pancreatitis</span> Medical condition

Acute pancreatitis (AP) is a sudden inflammation of the pancreas. Causes include a gallstone impacted in the common bile duct or the pancreatic duct, heavy alcohol use, systemic disease, trauma, elevated calcium levels, hypertriglyceridemia, certain medications, hereditary causes and, in children, mumps. Acute pancreatitis may be a single event, it may be recurrent, or it may progress to chronic pancreatitis and/or pancreatic failure.

<span class="mw-page-title-main">Chronic pancreatitis</span> Medical condition

Chronic pancreatitis is a long-standing inflammation of the pancreas that alters the organ's normal structure and functions. It can present as episodes of acute inflammation in a previously injured pancreas, or as chronic damage with persistent pain or malabsorption. It is a disease process characterized by irreversible damage to the pancreas as distinct from reversible changes in acute pancreatitis. Tobacco smoke and alcohol misuse are two of the most frequently implicated causes, and the two risk factors are thought to have a synergistic effect with regards to the development of chronic pancreatitis. Chronic pancreatitis is a risk factor for the development of pancreatic cancer.

<span class="mw-page-title-main">Digestive enzyme</span> Class of enzymes

Digestive enzymes take part in the chemical process of digestion, which follows the mechanical process of digestion. Food consists of macromolecules of proteins, carbohydrates, and fats that need to be broken down chemically by digestive enzymes in the mouth, stomach, pancreas, and duodenum, before being able to be absorbed into the bloodstream. Initial breakdown is achieved by chewing (mastication) and the use of digestive enzymes of saliva. Once in the stomach further mechanical churning takes place mixing the food with secreted gastric acid. Digestive gastric enzymes take part in some of the chemical process needed for absorption. Most of the enzymatic activity, and hence absorption takes place in the duodenum.

Trypsinogen is the precursor form of trypsin, a digestive enzyme. It is produced by the pancreas and found in pancreatic juice, along with amylase, lipase, and chymotrypsinogen. It is cleaved to its active form, trypsin, by enteropeptidase, which is found in the intestinal mucosa. Once activated, the trypsin can cleave more trypsinogen into trypsin, a process called autoactivation. Trypsin cleaves the peptide bond on the carboxyl side of basic amino acids such as arginine and lysine.

<span class="mw-page-title-main">Lingual lipase</span> Mammalian protein found in Homo sapiens

Lingual lipase is a member of a family of digestive enzymes called triacylglycerol lipases, EC 3.1.1.3, that use the catalytic triad of aspartate, histidine, and serine to hydrolyze medium and long-chain triglycerides into partial glycerides and free fatty acids. The enzyme, released into the mouth along with the saliva, catalyzes the first reaction in the digestion of dietary lipid, with diglycerides being the primary reaction product. However, due to the unique characteristics of lingual lipase, including a pH optimum 4.5–5.4 and its ability to catalyze reactions without bile salts, the lipolytic activity continues through to the stomach. Enzyme release is signaled by autonomic nervous system after ingestion, at which time the serous glands under the circumvallate and foliate lingual papillae on the surface of the tongue secrete lingual lipase to the grooves of the circumvallate and foliate papillae, co-localized with fat taste receptors. The hydrolysis of the dietary fats is essential for fat absorption by the small intestine, as long chain triacylglycerides cannot be absorbed, and as much as 30% of fat is hydrolyzed within 1 to 20 minutes of ingestion by lingual lipase alone.

<span class="mw-page-title-main">Pancreatectomy</span> Surgical removal of the pancreas

In medicine, a pancreatectomy is the surgical removal of all or part of the pancreas. Several types of pancreatectomy exist, including pancreaticoduodenectomy, distal pancreatectomy, segmental pancreatectomy, and total pancreatectomy. In total pancreatectomy, the gallbladder, distal stomach, a portion of the small intestine, associated lymph nodes and in certain cases the spleen are removed in addition to the entire pancreas. In recent years, the TP-IAT has also gained respectable traction within the medical community. These procedures are used in the management of several conditions involving the pancreas, such as benign pancreatic tumors, pancreatic cancer, and pancreatitis.

<span class="mw-page-title-main">Exocrine pancreatic insufficiency</span> Inability to properly digest food due to a lack of digestive enzymes from the pancreas

Exocrine pancreatic insufficiency (EPI) is the inability to properly digest food due to a lack or reduction of digestive enzymes made by the pancreas. EPI can occur in humans and is prevalent in many conditions such as cystic fibrosis, Shwachman–Diamond syndrome, different types of pancreatitis, multiple types of diabetes mellitus, advanced renal disease, older adults, celiac disease, IBS-D, IBD, HIV, alcohol-related liver disease, Sjogren syndrome, tobacco use, and use of somatostatin analogues.

Pancreatic diseases are diseases that affect the pancreas, an organ in most vertebrates and in humans and other mammals located in the abdomen. The pancreas plays a role in the digestive and endocrine system, producing enzymes which aid the digestion process and the hormone insulin, which regulates blood sugar levels. The most common pancreatic disease is pancreatitis, an inflammation of the pancreas which could come in acute or chronic form. Other pancreatic diseases include diabetes mellitus, exocrine pancreatic insufficiency, cystic fibrosis, pseudocysts, cysts, congenital malformations, tumors including pancreatic cancer, and hemosuccus pancreaticus.

Pancreatic elastase is a form of elastase that is produced in the acinar cells of the pancreas, initially produced as an inactive zymogen and later activated in the duodenum by trypsin. Elastases form a subfamily of serine proteases, characterized by a distinctive structure consisting of two beta barrel domains converging at the active site that hydrolyze amides and esters amongst many proteins in addition to elastin, a type of connective tissue that holds organs together. Pancreatic elastase 1 is a serine endopeptidase, a specific type of protease that has the amino acid serine at its active site. Although the recommended name is pancreatic elastase, it can also be referred to as elastase-1, pancreatopeptidase, PE, or serine elastase.

The secretin-cholecystokinin test is a combination of the secretin test and the cholecystokinin test and is used to assess the function of both the pancreas and gall bladder.

Fibrosing colonopathy is a disease that arises in people with cystic fibrosis treated with high doses of pancreatic enzyme supplements. Symptoms are non-specific with abdominal pain, abdominal swelling, vomiting, and constipation.

<span class="mw-page-title-main">Pancreatitis (veterinary)</span> Medical condition

Pancreatitis is a common condition in cats and dogs. Pancreatitis is inflammation of the pancreas that can occur in two very different forms. Acute pancreatitis is sudden, while chronic pancreatitis is characterized by recurring or persistent form of pancreatic inflammation. Cases of both can be considered mild or severe. It is currently undecided whether chronic pancreatitis is a distinct disease or a form of acute pancreatitis. Other forms such as auto-immune and hereditary pancreatitis are presumed to occur but there existence has not been proven.

<span class="mw-page-title-main">Ductal cells</span>

Ductal cells refer to the epithelial cell lining of the pancreatic duct that deliver enzymes from the acinar cells to the duodenum. They have the essential function of producing bicarbonate-rich (HCO3-) secretion to neutralize stomach acidity. The hormone secretin stimulates ductal cells and is responsible for maintaining the duodenal pH and preventing duodenal injury from acidic chyme. Ductal cells mix their production with acinar cells to make up the pancreatic juice.

Lundh's test is a test of function of the exocrine function of the pancreas gland.

Type 3c diabetes is diabetes that comes secondary to pancreatic diseases, involving the exocrine and digestive functions of the pancreas. It also occurs following surgical removal of the pancreas.

<span class="mw-page-title-main">Dorsal pancreatic agenesis</span> Medical condition

Dorsal pancreatic agenesis is a congenital anomaly characterised by the absence of the duct of Santorini, tail and body of the pancreas. It is regarded as asymptomatic and the most common clinical manifestation is non-specific abdominal pain. While the cause is unclear, its mechanism is thought to be impaired dorsal buds or mutation of genes that regulate organogenesis during embryogenesis.

References

  1. ↑ "Pancrelipase Uses, Side Effects & Warnings".
  2. ↑ "Micrazym and associated names". European Medicines Agency. 21 March 2024. Retrieved 13 June 2024.
  3. 1 2 3 4 5 "Pancrelipase". The American Society of Health-System Pharmacists. Archived from the original on 18 January 2017. Retrieved 8 January 2017.
  4. ↑ "Pancreatin". The American Society of Health-System Pharmacists. Archived from the original on 18 January 2017. Retrieved 8 January 2017.
  5. 1 2 3 4 5 British national formulary: BNF 69 (69 ed.). British Medical Association. 2015. pp. 82–83. ISBN   978-0-85711-156-2.
  6. ↑ Stuhan MA (2013). Understanding Pharmacology for Pharmacy Technicians. ASHP. p. 597. ISBN   978-1-58528-360-6. Archived from the original on 14 September 2017.
  7. ↑ Banik SP, Khowala S, Pal C, Mukherjee S (2015). "Proteomic approaches to identify novel therapeutics and nutraceuticals from filamentous fungi: prospects and challenges". In Bagchi D, Swaroop A, Bagchi M (eds.). Genomics, Proteomics and Metabolomics in Nutraceuticals and Functional Foods. John Wiley & Sons. p. 274. ISBN   978-1-118-93046-5. Archived from the original on 18 September 2017.
  8. ↑ World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl:10665/325771. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
  9. ↑ "The Top 300 of 2022". ClinCalc. Archived from the original on 30 August 2024. Retrieved 30 August 2024.
  10. ↑ "Pancrelipase Amylase; Pancrelipase Lipase; Pancrelipase Protease Drug Usage Statistics, United States, 2013 - 2022". ClinCalc. Retrieved 30 August 2024.
  11. 1 2 Whitehead AM (February 1988). "Study to compare the enzyme activity, acid resistance and dissolution characteristics of currently available pancreatic enzyme preparations". Pharmaceutisch Weekblad. Scientific Edition. 10 (1): 12–16. doi:10.1007/BF01966429. PMID   2451209. S2CID   41763055.
  12. ↑ Löhr JM, Hummel FM, Pirilis KT, Steinkamp G, Körner A, Henniges F (September 2009). "Properties of different pancreatin preparations used in pancreatic exocrine insufficiency". European Journal of Gastroenterology & Hepatology. 21 (9): 1024–1031. doi:10.1097/MEG.0b013e328328f414. PMID   19352190. S2CID   13480750.
  13. ↑ Thorat V, Reddy N, Bhatia S, Bapaye A, Rajkumar JS, Kini DD, et al. (September 2012). "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". Alimentary Pharmacology & Therapeutics. 36 (5): 426–436. doi: 10.1111/j.1365-2036.2012.05202.x . PMC   3528066 . PMID   22762290. PDF version
  14. ↑ Smith RS (August 1965). "Iron Deficiency and Iron Overload". Archives of Disease in Childhood. 40 (212): 343–363. doi:10.1136/adc.40.212.343. PMC   2019287 . PMID   14329251.
  15. ↑ Baines MG, Cai F, Backman HA (November 1990). "Adsorption and removal of protein bound to hydrogel contact lenses". Optometry and Vision Science. 67 (11): 807–810. doi:10.1097/00006324-199011000-00003. PMID   2250887. S2CID   29228849.
  16. ↑ Lloyd-Still JD, Beno DW, Kimura RM (June 1999). "Cystic fibrosis colonopathy". Current Gastroenterology Reports. 1 (3): 231–237. doi:10.1007/s11894-999-0040-4. PMID   10980955. S2CID   37595322.
  17. ↑ Schibli S, Durie PR, Tullis ED (November 2002). "Proper usage of pancreatic enzymes". Current Opinion in Pulmonary Medicine. 8 (6): 542–546. doi:10.1097/00063198-200211000-00010. PMID   12394164. S2CID   8935747.
  18. ↑ "CREON® (pancrelipase) Delayed-Release Capsule | Official Website". www.creon.com. Retrieved 10 October 2019.
  19. 1 2 3 U.S. Food and Drug Administration (7 May 2009). "FDA Approves Pancreatic Enzyme Replacement Product for Marketing in United States: Creon designed to help those with cystic fibrosis, others with exocrine pancreatic insufficiency". News & Events, FDA News Release. Retrieved 20 July 2014.
  20. ↑ Adams B (12 March 2018). "Anthera's Sollpura canned after phase 3 flop, shares plunge". Fierce Biotech. Retrieved 23 October 2021.
  21. ↑ "FDA Committee Declines to Recommend Liprotamase for EPI". The Boomer Esiason Foundation. 19 March 2019. Retrieved 22 May 2021.
  22. ↑ "Ultresa - Search results. Page 1 of about 39 results". Drugs.com. Retrieved 22 May 2021.
  23. ↑ "Zenpep: Uses, Dosage & Side Effects Information". Drugs.com. Retrieved 22 May 2021.
  24. ↑ "Pfizer Completes Transaction to Combine Its Upjohn Business with Mylan". Pfizer. 16 November 2020. Retrieved 17 June 2024– via Business Wire.
  25. ↑ "Brands". Viatris. 16 November 2020. Retrieved 17 June 2024.
  26. ↑ Pancreatic cancer action (21 April 2020). "Temporary shortage of Creon (Pancreatin) 25k". Pancreatic cancer news. Retrieved 15 July 2020.
  27. ↑ Mylan (1 February 2019). "Pancreatin - Cambridgeshire and Peterborough CCG" (PDF). Archived from the original on 28 August 2021. Retrieved 15 July 2020.
  28. ↑ Greater Glasgow and Clyde Medicines (July 2016). "Medicines Update Primary Care". Archived from the original on 15 July 2020. Retrieved 15 July 2020.
  29. ↑ Layer P, Keller J (January 2003). "Lipase supplementation therapy: standards, alternatives, and perspectives". Pancreas. 26 (1): 1–7. doi:10.1097/00006676-200301000-00001. PMID   12499909. S2CID   12365426.
  30. ↑ Roxas M (December 2008). "The role of enzyme supplementation in digestive disorders". Alternative Medicine Review. 13 (4): 307–314. PMID   19152478.
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