Becoming an “exPERT” on Pancreatic Enzyme Replacement Therapy

As part of its exocrine functions, the pancreas produces several important digestive enzymes including amylase, protease, and lipase, which are secreted into the small intestine shortly after ingesting a meal. These enzymes begin the process of digestion of the macronutrients from our meal – carbohydrates, proteins, and lipids, respectively. If pancreatic exocrine function is altered or insufficient, pancreatic enzyme replacement therapy (PERT), can be a crucial tool in avoiding malabsorption and ultimately reducing the risk of malnutrition. 

What is PERT? 

PERT involves patients taking prescribed pancreatic enzymes when eating a meal. (There are also options for patients who are enterally fed.) PERT medications generally include amylase, protease, and lipase. While amylase and protease can be compensated in other portions of the gastrointestinal system, lipase secretion is minimal through extra-pancreatic mechanisms. As a result, most pancreatic enzyme formulations will have a larger proportion of lipase with amylase and protease present in smaller amounts.

Who needs PERT? 

In general, patients require PERT when they have exocrine pancreatic insufficiency (EPI)? This means a patient’s pancreas is not able to effectively manufacture and release pancreatic enzymes. These patients typically present with symptoms or suspicion of malabsorption. Common conditions that require PERT include:  

Pancreatic disorders: 

• Acute or chronic pancreatitis 
• Pancreatic surgery or resection 
• Unresectable pancreatic cancer 
• Benign pancreatic tumor
• Shwachman–Diamond syndrome
• Cystic fibrosis  

Extra-pancreatic disorders: 

• Type 1 or Type 2 diabetes  
• Celiac disease
• Gastrointestinal surgery
• Bariatric surgery
• Total pancreatectomy
• HIV
• Sjogren’s syndrome
• Aging 

The signs and symptoms of EPI include:

• Steatorrhea (characterized by large- volume, foul-smelling stools) 
• Diarrhea (often shortly after consuming a meal)
• Weight loss
• Gas and bloating
• Abdominal pain
• May have low serum levels of fat-soluble vitamins (A, D, E, and K) 

How do you diagnose EPI?

The gold standard for diagnosing EPI is a 72-hour fecal fat quantification. However, the use of this test is often limited due to the high fat consumption required (>100 grams of fat daily for three days) and is often not realistic for the patient. Fecal elastase is a simpler and reliable alternative that is less invasive or time consuming to conduct for EPI evaluation. The fecal elastase level is not affected by enzyme replacement therapy. If the stool sample is too diluted by watery diarrhea, it may be inaccurate and require a new sample. Serum pancreatic enzymes are not considered a reliable tool to diagnose pancreatic insufficiency.  

Depending on which test is ordered, below are guidelines on interpreting results: 

• 72-hour fecal fat quantification: Less than 7 g of fat per 24 hours is considered “normal” 
• Fecal elastase 
• A “low” level indicates EPI 
• Depending on the lab cut points – Moderate pancreatic insufficiency is defined at 100 to 200 μg/mL, and severe pancreatic insufficiency as <100 μg/mL

How do you dose PERT?

Pancreatic enzymes are dosed in units of lipase but do also contain protease and amylase in small amounts depending on the manufacturer. Adults generally require 500 to 4,000 lipase units per gram of fat ingested or 500 to 2,500 lipase units/kg/meal and 250 to 1,250 lipase units/kg/snack. The maximum dose of pancreatic enzymes is 10,000 units of lipase/kg/day. This has been recommended due to the risk of fibrosing colonopathy associated with very high doses of PERT in patients with cystic fibrosis. While this has not been seen as commonly in other patient populations, the maximum dosing may affect the amount of enzymes insurance companies will provide.  

Other PERTinent tips: 

• Appropriate administration of PERT is vital to the effectiveness of the medication. Patients should be instructed to take their pancreatic enzymes with meals. If your patient is taking multiple capsules of pancreatic enzymes at mealtimes, separating the capsules up throughout the meal can be helpful to maximize effectiveness.  
• Provide education to your patient on meal sizes and how it relates to their prescribed dosing. This can help preserve the number of capsules of enzymes they have per month. While it is not necessarily harmful to take more enzymes at one time, it may not be necessary and can be wasteful and pricey, as PERT can be an expensive medication.  
• Monitor stool frequency and consistency in relation to meals when adjusting dosing. Taking too many pancreatic enzymes can sometimes lead to constipation. Monitoring bowel habits when introducing or adjusting a PERT regimen is most helpful in finding a dosing that works best.  

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References:  

Cologne, Germany: Institute for Quality and Efficiency in Health Care (IQWiG); 2006-. How does the pancreas work? 2009 Nov 11 [Updated 2018 Sep 6]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK279306/ 

Ghodeif AO, Azer SA. Pancreatic Insufficiency. 2022 May 1. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan–. PMID: 32310386. 

Perbtani Y, Forsmark CE. Update on the diagnosis and management of exocrine pancreatic insufficiency. F1000Res. 2019;8:F1000 Faculty Rev-1991. Published 2019 Nov 26. doi:10.12688/f1000research.20779.1 

Capurso G, Traini M, Piciucchi M, Signoretti M, Arcidiacono PG. Exocrine pancreatic insufficiency: prevalence, diagnosis, and management. Clin Exp Gastroenterol. 2019 Mar 21;12:129-139. doi: 10.2147/CEG.S168266. PMID: 30962702; PMCID: PMC6432881. 

Chaudhary A, Domínguez-Muñoz JE, Layer P, Lerch MM. Pancreatic Exocrine Insufficiency as a Complication of Gastrointestinal Surgery and the Impact of Pancreatic Enzyme Replacement Therapy. Dig Dis. 2020;38(1):53-68. doi:10.1159/000501675 

MedlinePlus [Internet]. Bethesda (MD): National Library of Medicine (US); [updated 2023 Jan 4]. Fecal Fat; [updated/reviewed 2020 July 16; cited 2023 Jan 16]; [5:00PM] Available from: https://medlineplus.gov/ency/article/003588.htm 

Vanga RR, Tansel A, Sidiq S, El-Serag HB, Othman MO. Diagnostic Performance of Measurement of Fecal Elastase-1 in Detection of Exocrine Pancreatic Insufficiency: Systematic Review and Meta-analysis. Clin Gastroenterol Hepatol. 2018 Aug;16(8):1220-1228.e4. doi: 10.1016/j.cgh.2018.01.027. Epub 2018 Jan 31. PMID: 29374614; PMCID: PMC6402774. 

Schwarzenberg, Sarah Jane. “Pancreatic Enzymes Clinical Care Guidelines.” Cystic Fibrosis Foundation, 1 Jul. 2021, www.cff.org/medical-professionals/pancreatic-enzymes-clinical-care-guidelines#pancreatic-enzymes-clinical-care-guidelines-executive-summary. Accessed 17 Jan. 2023.