Pancrelipase, a combination of lipase, protease, and amylase, has benefited patients with exocrine pancreatic insufficiency. The FDA-approved conditions that are associated with pancreatic insufficiency that may require supplementation with pancrelipase include chronic pancreatitis, obstructive pancreatic tumors, post-procedure loss of pancreatic tissue or ductal occlusion, insufficient mixing of chyme with pancreatic enzymes because of rapid gastric emptying, small bowel resection with inadequate secretion of cholecystokinin-pancreozymin and secretin, and lymph node dissection leading to decreased pancreatic stimulation. Also approved are genetic disorders including cystic fibrosis, Schwachman Diamond syndrome, hereditary hemochromatosis, Zollinger-Ellison syndrome, celiac disease, and Crohn disease. There are also non-FDA-approved indications as well. This activity outlines the indications, mechanism of action, methods of administration, significant adverse effects, contraindications, monitoring, and toxicity of pancrelipase so providers can direct patient therapy to optimal outcomes in conditions where pancrelipase has benefit. Objectives:
Pancrelipase, a combination of lipase, protease, and amylase, has been shown to benefit patients with exocrine pancreatic insufficiency.[1] The different conditions that are associated with pancreatic insufficiency that may require supplementation with pancrelipase are: FDA-Approved
Non-FDA Approved
The alkaline pH of the duodenum activates the components of pancrelipase, which then helps with digestion.[8][9] Lipase
Amylase
Protease
It, therefore, acts as the digestive enzymes inherently secreted by the pancreas in the absence of insufficiency. Various factors affect the efficacy of this supplementation, for example:
Pharmacokinetics
Oral Administration The oral preparation should not be kept in the mouth for prolonged periods as it tends to cause mucosal irritation and stomatitis. Various pancrelipase products are not interchangeable; clinicians should not switch between products without verifying dosing. For exocrine pancreatic insufficiency, the typical dosing is 500 to 2,500 lipase units with each meal or snack. Different formulations are not dose-transferable, so the prescriber should consult the drug information for each formulation when starting or switching agents. Tablets
Enteric-Coated Capsules
Other Routes of Administration
Mild Adverse Reactions
Moderate Adverse Reactions
Severe Adverse Reactions
Although pancreatic enzyme replacement therapy does have any absolute contraindications per se, a careful analysis of the underlying risks is necessary for the following conditions.[10][11] Diabetes Mellitus Pancrelipase affects glycemic control. Hence patients diagnosed with diabetes mellitus or patients at risk for abnormal blood sugar levels should have strict glucose monitoring while taking pancrelipase. Immunocompromised States Pancrelipase derives from the pancreatic tissue of swine. Although rigorous measures are in place to ensure no risk of transmitting viral infections to the patient, there is a theoretical risk from unknown viruses in the swine. Therefore, patients who are immunocompromised/immunodeficient are at an increased risk of contracting infections while on this medication. Hyperuricemia and Renal Impairment As this medication is porcine-derived, it contains certain nucleic acids that tend to increase blood uric acid levels. Patients with pre-existing hyperuricemia or gout and patients with decreased renal functions are to be closely monitored when on the drug. Dysphagia As mentioned earlier, patients with a tendency to retain the contents of the medications higher up in the gastrointestinal tract may develop mucosal irritation and mucositis. Care is necessary while administering the drug to patients with esophageal strictures and dysphagia. Meconium Ileus, Intestinal Obstruction, Inflammatory Bowel Disease, and Surgery Patients younger than 12 years of age, patients who have taken more than 6000 lipase units/kg per meal for more than six months, or patients with a history of meconium ileus, intestinal obstruction, inflammatory bowel disease, or abdominal surgery have the highest risk for developing fibrosing colonopathy. It is a rare but serious complication of enzyme replacement characterized by GI obstruction, bloody diarrhea, abdominal pain, and poor weight gain. Therefore, it has been recommended by the Cystic Fibrosis Foundation Consensus Conference Guidelines that the efficacy of lipase supplementation more than 2500 units/kg per meal be confirmed by a 3-day fecal-fat measure that indicated an increased fat absorption coefficient. The dose is then to be adjusted accordingly. Pregnancy There are not adequate numbers of human and animal reproduction studies for this drug. Therefore, its use in pregnancy should be limited to those patients with exocrine pancreatic insufficiency who have inadequate maternal weight gain; this may adversely affect fetal growth, and hence supplementation is justified. Breastfeeding All breastfeeding mothers should contact their healthcare provider before taking pancrelipase. Some proteins present in the product may undergo systemic absorption along with the dietary protein. There is no data available about the uptake of these substances into breast milk; it is only recommended when it is necessary to support the mother's nutritional status. Porcine Protein Sensitivity There are reports of anaphylactic reactions, hives, asthma, urticaria, and pruritus in patients with prior hypersensitivity to porcine protein. Caution is necessary for all these patients. The maximum dosage of pancrelipase is as follows: Adults The recommendation is a maximum of 10,000 lipase units per kg per day orally (PO) or less than 4,000 lipase units per gram of dietary fat per day. Geriatric The recommendation is a maximum of 10,000 lipase units per kg per day PO or less than 4,000 lipase units per gram of dietary fat per day. Adolescents The recommendation is a maximum of 10,000 lipase units per kg per day PO or less than 4,000 lipase units per gram of dietary fat per day. But at no time should the maximum dosage exceed 2,500 lipase units per kg per meal. Infant Dosage Infant dosages are product-specific. But the maximum dosage is not to exceed 4,000 lipase units per gram of ingested fat per day or 10,000 lipase units/kg per day. Neonates Neonatal dosages are product-specific. There are no dosage adjustments required for renal and hepatic impairment. Drug Interactions That May Require Dosage Adjustments
Chronic, high-dose pancreatic enzyme replacement can cause colonic strictures and fibrosing colonopathy.[12] Fibrosing colonopathy is a condition in which there is a narrowing of the lumen of a long segment of the colon. This condition occurs due to submucosal widening due to the deposition of mature collagen. Most commonly seen in children with cystic fibrosis as they require long-term high-dose pancreatic enzyme replacement. The administration of pancreatic enzyme replacement therapy requires the efficient functioning of an interprofessional team to ensure the best benefit to the patient. The team usually comprises a clinician, nurse practitioner, pharmacist, nutritionist/dietician, physiotherapist, and nurses. The primary provider may additionally involve physicians from oncology, gastroenterology, surgery, pulmonology, or pediatrics, depending on the etiology of the enzyme insufficiency. The primary care provider is involved in the diagnosis of insufficiency. The PCP is then responsible for managing the symptoms, deciding the supplementation requirements of the patients, monitoring progress, and managing any side effects that might result thereof. Nurse practitioners are required to alternate with physicians to monitor patient progress with the medications. Pharmacists should provide patients and families with information on the drug, side effects, precautions, and contraindications. They are also responsible for dose alterations as the case demands. Dieticians and nutritionists should assess the patient's nutritional status and determine the calorie requirement. They are also required to determine the need for vitamin supplements, growth hormone, and appetite stimulants. Physiotherapists are required to help with the ambulation of patients with chronic illnesses like pancreatic cancer and chronic pancreatitis. They should also be on board when dealing with cases of cystic fibrosis. Nurses are an integral part of the team, especially in the inpatient setting, to ensure that all orders are executed. They are also an essential link in communication between physicians and patients. No evidence is available for the effectiveness of an interprofessional approach to pancreatic enzyme replacement therapy. Various studies have shown the benefit of involving an interprofessional team for patients with cystic fibrosis.[13] Review Questions1. Durie P, Baillargeon JD, Bouchard S, Donnellan F, Zepeda-Gomez S, Teshima C. Diagnosis and management of pancreatic exocrine insufficiency (PEI) in primary care: consensus guidance of a Canadian expert panel. Curr Med Res Opin. 2018 Jan;34(1):25-33. [PubMed: 28985688] 2.Min M, Patel B, Han S, Bocelli L, Kheder J, Vaze A, Wassef W. Exocrine Pancreatic Insufficiency and Malnutrition in Chronic Pancreatitis: Identification, Treatment, and Consequences. Pancreas. 2018 Sep;47(8):1015-1018. [PMC free article: PMC6462188] [PubMed: 30074926] 3.Saito T, Nakai Y, Isayama H, Hirano K, Ishigaki K, Hakuta R, Takeda T, Saito K, Umefune G, Akiyama D, Watanabe T, Takagi K, Takahara N, Hamada T, Uchino R, Mizuno S, Mouri D, Yagioka H, Kogure H, Togawa O, Matsubara S, Ito Y, Yamamoto N, Tada M, Koike K. A Multicenter Open-Label Randomized Controlled Trial of Pancreatic Enzyme Replacement Therapy in Unresectable Pancreatic Cancer. Pancreas. 2018 Aug;47(7):800-806. [PubMed: 29851751] 4.Domínguez-Muñoz JE. Pancreatic enzyme replacement therapy: exocrine pancreatic insufficiency after gastrointestinal surgery. HPB (Oxford). 2009 Dec;11 Suppl 3:3-6. [PMC free article: PMC2798169] [PubMed: 20495625] 5.Antonini F, Crippa S, Falconi M, Macarri G, Pezzilli R. Pancreatic enzyme replacement therapy after gastric resection: An update. Dig Liver Dis. 2018 Jan;50(1):1-5. [PubMed: 29170072] 6.Giguere-Rich C, Mathew A, Reid E, Autore K, Guill MF. Use of an In-line Digestive Cartridge With Enteral Nutrition Improves the Weight Trajectory of 2 Children With Cystic Fibrosis Complicated by Another Medical Diagnosis. Nutr Clin Pract. 2018 Apr;33(2):286-294. [PubMed: 29658186] 7.Stumpf JL, Kurian RM, Vuong J, Dang K, Kraft MD. Efficacy of a Creon delayed-release pancreatic enzyme protocol for clearing occluded enteral feeding tubes. Ann Pharmacother. 2014 Apr;48(4):483-7. [PubMed: 24436458] 8.JAKOVCIC S, HSIA DY. Studies on mechanism for decreased lipoprotein lipase in cystic fibrosis of the pancrease. J Pediatr. 1963 Jan;62:25-30. [PubMed: 13964519] 9.Ferrone M, Raimondo M, Scolapio JS. Pancreatic enzyme pharmacotherapy. Pharmacotherapy. 2007 Jun;27(6):910-20. [PubMed: 17542772] 10.Lindkvist B. Diagnosis and treatment of pancreatic exocrine insufficiency. World J Gastroenterol. 2013 Nov 14;19(42):7258-66. [PMC free article: PMC3831207] [PubMed: 24259956] 11.Nakajima K, Oshida H, Muneyuki T, Kakei M. Pancrelipase: an evidence-based review of its use for treating pancreatic exocrine insufficiency. Core Evid. 2012;7:77-91. [PMC free article: PMC3426252] [PubMed: 22936895] 12.Dodge JA. Pancreatic enzymes and Fibrosing Colonopathy. J Cyst Fibros. 2015 Jan;14(1):153. [PubMed: 25242743] 13.Collins S. Nutritional management of cystic fibrosis - an update for the 21st century. Paediatr Respir Rev. 2018 Mar;26:4-6. [PubMed: 28420572] |