Pancrelipase


Article Author:
Nihaal Karnik


Article Editor:
Arif Jan


Editors In Chief:
Melissa Max
Danyae Lee
Manouchkathe Cassagnol


Managing Editors:
Avais Raja
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Khalid Alsayouri
Trevor Nezwek
Radia Jamil
Patrick Le
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Hassam Zulfiqar
Steve Bhimji
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Sarosh Vaqar
Mark Pellegrini
James Hughes
Beata Beatty
Nazia Sadiq
Hajira Basit
Phillip Hynes
Tehmina Warsi


Updated:
5/17/2019 4:03:04 PM

Indications

Pancrelipase refers to a class of medications designed to treat malabsorption and abdominal pain secondary to exocrine pancreatic insufficiency. These agents serve as exogenous versions of digestive hormones and enzymes required for normal digestion. As discussed below, these enzymes are ingested with meals to improve digestion, absorption, and abdominal pain frequently seen in chronic pancreatitis and exocrine pancreatic insufficiency. Pancrelipase can be used in all age groups.

FDA Indications

Exocrine pancreatic insufficiency due to any of the following conditions:

  • Chronic pancreatitis 
  • Pancreatic surgery 
  • Cystic fibrosis

Non-FDA Indications

  • As a presumptive test for pancreatic insufficiency
  • Steatorrhea of post-gastrectomy syndrome
  • Pancreatic insufficiency due to pancreatic cancer[1]

Key Clinical Background Information

Exocrine pancreatic insufficiency (EPI) is a syndrome characterized by poor absorption of fats, proteins, and, to a lesser extent carbohydrates. This condition occurs primarily in patients with cystic fibrosis (CF) or chronic pancreatitis (CP). Clinicians can make the diagnosis of EPI by one of 3 criteria: fecal elastase test, fecal fat test, or a direct pancreatic function test.

Patient’s with EPI in CP have worse nutritional status, vitamin levels, and quality of life when compared to patients with CP without EPI.[2] Pancreatic enzyme products (PEPs) have been the standard of care for treatment of EPI in patients with CP for the past three decades. Treating patients with PEP improves in nutritional status, quality of life, symptoms, and life expectancy in patients with EPI.

Manufacturers developed most PEPs before current United States Food and Drug Administration (FDA) New Drug Approval (NDA) requirements were enacted. In 2005, the FDA requested that manufacturers of PEPs now submit an NDA for approval of these products.[3] A new wave of research is being conducted to discern the pharmacokinetic and pharmacodynamic profiles of PEP. For instance, this includes research concerning the bioavailability of PEP, the onset of action, and the improvement of fat absorption for this class of drugs.

Practitioners use the coefficient of fat absorption (CFA) to discern the efficacy of these drugs. In exocrine pancreatic insufficiency, many of the poor outcomes stem from the poor absorption of fats and fat-soluble vitamins. The administration of PEP enhances the absorption of fats and fat-soluble vitamins (A, D, E, K), and provides better outcomes for patients on therapy. Often, readers may encounter the term CFA. A simple way to understand the CFA is to know that the higher the CFA of any PEP, the better the drug will be at improving fat and fat-soluble vitamin absorption.

Some clinicians empirically begin patients on pancrelipase therapy when patients present with vitamin deficiencies, malabsorption, and poor nutritional status with risk factors for chronic pancreatitis, for example, chronic alcoholism. The reason for this stems from the actual difficulty that one may encounter to diagnose chronic pancreatitis or exocrine pancreatic insufficiency. As mentioned above, EPI requires stool fat testing or even direct pancreatic function testing. Some clinicians may prefer to treat empirically given the immediate or rapid benefit conferred with PEP therapy; others often defer testing as testing is invasive (direct pancreatic stimulation testing) or unavailable in certain areas.

Mechanism of Action

PEPs are porcine enzymes and contain mixtures of pancreatic lipase, amylase, and protease. Lipase is a digestive enzyme involved in the hydrolysis and degradation of fats. Impairments in lipase metabolism lead to malabsorption of fats. Amylase is a digestive enzyme involved in the hydrolysis and digestion of starches. Impairments in amylase metabolism lead to complex carbohydrates malabsorption. Proteases are enzymes involved in the breakdown of proteins and amino acids. Imbalances or insufficiency of proteases can lead to poor absorption of amino acids and breakdown of essential proteins.

PEPs are exogenous versions of these enzymes, derived from porcine pancreatic ducts; these enzymes then act locally to break down fats, proteins, and carbohydrates. The main site of action is the duodenum. The duodenum represents the first part of the small intestine where nutrient absorption and macromolecule degradation co-occurs.

Manufacturers developed newer formulations known as enteric-coated microspheres to protect enzymes against gastric acid and to provide better dispersion of enzymes in the chyme and therefore observed to provide consistent symptoms relief in CP compared to an older formulation.[4] Oral pancreatic enzymes appear to inhibit pancreatic exocrine secretion through a negative feedback mechanism involving intraduodenal proteases and exocrine pancreas.[5]

Administration

Patients should take this medication with meals; a general rule of thumb is to take half a dose of pancrelipase with snacks. 

Most manufacturers recommend beginning with a dose of 500 units of lipase/kg with each meal. Most manufacturers recommend not to exceed 10,000 units of lipase/kg per day.

Adverse Effects

The most common adverse effects are headache, oral irritation, abdominal pain, lymphadenopathy, nasal congestion, and neck pain.

Notably, a beta-hemolytic streptococcal infection has been seen with the use of pancrelipase.

Rare (less than 1%) but severe side effects include cancer recurrence, anaphylaxis, duodenitis, and distal intestinal obstruction syndrome.

Warnings include fibrosing colonopathy (especially when doses exceed 2500 lipase units/kg of body weight per meal or greater than 10,000 lipase units/kg of body weight per day) and hyperuricemia as porcine-derived pancreatic enzyme products contain purines that may increase blood uric acid levels.

Pancrelipase has a pregnancy risk factor C.

Contraindications

There are no known contraindications to pancrelipase.

Monitoring

No therapeutic levels exist concerning monitoring. Monitoring of the drug effect and adverse effect profile will be based on clinical symptoms and data including abdominal symptoms, nutritional intake, weight, growth (in children), stool character, fecal fat.

Toxicity

No known toxicity has been documented per a 2008 report from the Center for Drug Evaluation and Research.

Enhancing Healthcare Team Outcomes

One of the common topics when reviewing the literature concerns the use of proton pump inhibitors with pancrelipase. These enzymes are enteric coated to avoid the harsh conditions and low pH of the stomach. The goal of PEP therapy focuses on maximal drug delivery into the duodenum, which is where absorption occurs.

Given the known effect of low pH on enzyme delivery for PEP, previous groups have attempted to increase the efficacy of PEP. Previous preparations of PEP included supplements such as sodium bicarbonate as a neutralizing agent.[6] Other groups have looked at the effects of antacids to improve the efficacy of PEP.[7] Other researchers have studied the effect of H2 receptor blockers as well.[8] Research concerning the effect of H2 receptor blockers showed no improvements in outcomes.[8] Data demonstrate that antacids such as aluminum hydroxide and sodium bicarbonate tend to lower the efficacy of PEP.[8]

Proesmans et al. have shown that in patients with cystic fibrosis, concurrent administration of omeprazole improved steatorrhea when used with PEP therapy.[9]

The literature mentioned above may provide good clinical evidence for providers to begin PPI therapy in patients who are known hyper-secretors (produce too much stomach acid) or in patients who show minimal improvement with pancrelipase therapy with EPI.


Interested in Participating?

We are looking for contributors to author, edit, and peer review our vast library of review articles and multiple choice questions. In as little as 2-3 hours you can make a significant contribution to your specialty. In return for a small amount of your time, you will receive free access to all content and you will be published as an author or editor in eBooks, apps, online CME/CE activities, and an online Learning Management System for students, teachers, and program directors that allows access to review materials in over 500 specialties.

Improve Content - Become an Author or Editor

This is an academic project designed to provide inexpensive peer-reviewed Apps, eBooks, and very soon an online CME/CE system to help students identify weaknesses and improve knowledge. We would like you to consider being an author or editor. Please click here to learn more. Thank you for you for your interest, the StatPearls Publishing Editorial Team.

Pancrelipase - Questions

Take a quiz of the questions on this article.

Take Quiz
What instructions are given to a patient with pancreatic insufficiency who is receiving pancrelipase?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
When is the best time to take pancrelipase?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A patient has been referred to your practice. Her past medical history includes chronic pancreatitis, and now she has complaints of post-prandial abdominal pain, steatorrhea, and has been told she has certain vitamin deficiencies? What would be the best next test to make a diagnosis?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A patient of yours was recently diagnosed with exocrine pancreatic insufficiency related to chronic pancreatitis by her gastroenterologist. She was prescribed pancrelipase. Today, she presents to your office and asks, "When is the best time for me to take the pancrelipase?" What is the best response?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A patient of yours who is known to be a hypersecretor of stomach acid. He was diagnosed with exocrine pancreatic insufficiency in the past due to cystic fibrosis. He has had little relief with pancreatic enzyme product (PEP) therapy. What is the best next step?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A patient with a past social history of alcohol use disorder presents to your clinic. He states that he has had multiple hospitalizations in the past for pancreatitis. He has been sober for a year and aims to regain his health. He says he is interested in beginning pancreatic enzyme therapy. He denies abdominal pain, steatorrhea, post-prandial cramping, and fatigue. A thorough evaluation does not reveal a vitamin deficiency. When is the appropriate time to begin pancreatic enzyme therapy?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up

Pancrelipase - References

References

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     [PubMed]
Slaff J,Jacobson D,Tillman CR,Curington C,Toskes P, Protease-specific suppression of pancreatic exocrine secretion. Gastroenterology. 1984 Jul     [PubMed]
Owyang C,Louie DS,Tatum D, Feedback regulation of pancreatic enzyme secretion. Suppression of cholecystokinin release by trypsin. The Journal of clinical investigation. 1986 Jun     [PubMed]
Giuliano CA,Dehoorne-Smith ML,Kale-Pradhan PB, Pancreatic enzyme products: digesting the changes. The Annals of pharmacotherapy. 2011 May     [PubMed]
Damerla V,Gotlieb V,Larson H,Saif MW, Pancreatic enzyme supplementation in pancreatic cancer. The journal of supportive oncology. 2008 Nov-Dec     [PubMed]
VEEGER W,ABELS J,HELLEMANS N,NIEWEG HO, Effect of sodium bicarbonate and pancreatin on the absorption of vitamin B12 and fat in pancreatic insufficiency. The New England journal of medicine. 1962 Dec 27     [PubMed]
Gow R,Bradbear R,Francis P,Shepherd R, Comparative study of varying regimens to improve steatorrhoea and creatorrhoea in cystic fibrosis: Effectiveness of an enteric-coated preparation with and without antacids and cimetidine. Lancet (London, England). 1981 Nov 14     [PubMed]
Graham DY, Pancreatic enzyme replacement: the effect of antacids or cimetidine. Digestive diseases and sciences. 1982 Jun     [PubMed]
Proesmans M,De Boeck K, Omeprazole, a proton pump inhibitor, improves residual steatorrhoea in cystic fibrosis patients treated with high dose pancreatic enzymes. European journal of pediatrics. 2003 Nov     [PubMed]

Disclaimer

The intent of StatPearls is to provide practice questions and explanations to assist you in identifying and resolving knowledge deficits. These questions and explanations are not intended to be a source of the knowledge base of all of medicine, nor is it intended to be a board or certification review of Pharmacy-Pharmacotherapy. The authors or editors do not warrant the information is complete or accurate. The reader is encouraged to verify each answer and explanation in several references. All drug indications and dosages should be verified before administration.

StatPearls offers the most comprehensive database of free multiple-choice questions with explanations and short review chapters ever developed. This system helps physicians, medical students, dentists, nurses, pharmacists, and allied health professionals identify education deficits and learn new concepts. StatPearls is not a board or certification review system for Pharmacy-Pharmacotherapy, it is a learning system that you can use to help improve your knowledge base of medicine for life-long learning. StatPearls will help you identify your weaknesses so that when you are ready to study for a board or certification exam in Pharmacy-Pharmacotherapy, you will already be prepared.

Our content is updated continuously through a multi-step peer review process that will help you be prepared and review for a thorough knowledge of Pharmacy-Pharmacotherapy. When it is time for the Pharmacy-Pharmacotherapy board and certification exam, you will already be ready. Besides online study quizzes, we also publish our peer-reviewed content in eBooks and mobile Apps. We also offer inexpensive CME/CE, so our content can be used to attain education credits while you study Pharmacy-Pharmacotherapy.