What is the diagnosis and treatment for exocrine pancreatic insufficiency (EPI)?

From the Guidelines

Exocrine pancreatic insufficiency (EPI) should be diagnosed and treated with pancreatic enzyme replacement therapy (PERT) and dietary modifications to improve morbidity, mortality, and quality of life. The diagnosis of EPI should be suspected in patients with high-risk clinical conditions, such as chronic pancreatitis, relapsing acute pancreatitis, pancreatic ductal adenocarcinoma, cystic fibrosis, and previous pancreatic surgery 1. The fecal elastase test is the most appropriate initial test for diagnosing EPI, and a level <100 mg/g of stool provides good evidence of EPI 1.

Diagnosis and Treatment

• EPI diagnosis should be based on clinical features, such as steatorrhea with or without diarrhea, weight loss, bloating, excessive flatulence, fat-soluble vitamin deficiencies, and protein-calorie malnutrition 1.
• PERT formulations are all derived from porcine sources and are equally effective at equivalent doses, with a typical starting dose of at least 40,000 USP units of lipase during each meal in adults 1.
• PERT should be taken during the meal, with the initial treatment adjusted based on the meal size and fat content, and H2 or proton pump inhibitor therapy may be needed with non–enteric-coated preparations 1.
• Dietary modifications include a low-moderate fat diet with frequent smaller meals, avoiding very-low-fat diets, and supplementation of fat-soluble vitamins (A, D, E, K) 1.

Monitoring and Follow-up

• Measures of successful treatment with PERT include reduction in steatorrhea and associated gastrointestinal symptoms, gain of weight, muscle mass, and muscle function, and improvement in fat-soluble vitamin levels 1.
• Baseline measurements of nutritional status should be obtained, including body mass index, quality-of-life measure, and fat-soluble vitamin levels, and a baseline dual-energy x-ray absorptiometry scan should be obtained and repeated every 1–2 years 1.
• Patients with EPI should be monitored for nutritional deficiencies, and annual updates of measurements of fat-soluble vitamins and serum markers of malnutrition are reasonable 1.

From the FDA Drug Label

FULL PRESCRIBING INFORMATION 1 INDICATIONS AND USAGE CREON® is indicated for the treatment of exocrine pancreatic insufficiency in adult and pediatric patients.

2 DOSAGE AND ADMINISTRATION 2. 1 Important Dosing Information CREON is a mixture of enzymes including lipases, proteases, and amylases.

The diagnosis of exocrine pancreatic insufficiency (EPI) is not directly stated in the label, but the treatment for EPI is with pancrelipase (CREON), a mixture of enzymes including lipases, proteases, and amylases.

• The recommended oral initial starting dosage is:
  • 500 lipase units/kg/meal for adult and pediatric patients 4 years of age and older
  • 500 to 1,000 lipase units/kg/meal for adult patients with chronic pancreatitis or pancreatectomy
  • 1,000 lipase units/kg/meal for pediatric patients greater than 12 months to less than 4 years of age
• If signs and symptoms of malabsorption persist, increase the dosage, with a maximum of 2,500 lipase units/kg/meal, 10,000 lipase units/kg/day, or 4,000 lipase units/gram of fat ingested/day 2

From the Research

Diagnosis of Exocrine Pancreatic Insufficiency (EPI)

• The diagnosis of EPI can be estimated based on symptoms, signs of malnutrition in blood tests, fecal elastase 1 levels, and signs of morphologically severe chronic pancreatitis on imaging 3.
• Fecal fat quantification and the (13)C-mixed triglycerides test are the most accurate tests for pancreatic exocrine insufficiency 3.
• Fecal elastase is the most clinically useful test for the diagnosis of EPI 4.
• Concentration of fecal elastase is a commonly employed indirect, noninvasive test for EPI diagnosis 5.

Treatment of Exocrine Pancreatic Insufficiency (EPI)

• Treatment for pancreatic exocrine insufficiency includes support to stop smoking and alcohol consumption, dietary consultation, enzyme replacement therapy, and a structured follow-up of nutritional status and the effect of treatment 3.
• Pancreatic enzyme replacement therapy is administered in the form of enteric-coated minimicrospheres during meals, with a dose proportional to the fat content of the meal 3.
• The dose of pancreatic enzyme replacement therapy should be 40-50,000 lipase units per main meal, and half the dose is required for a snack 3.
• In cases that do not respond to initial treatment, the doses can be doubled, and proton inhibitors can be added to the treatment 3.
• Administration of pancreatic enzymes replacement therapy remains the mainstay of EPI treatment 5.

Management and Monitoring of EPI

• Monitoring and prevention of complications of EPI, such as osteopenia and osteoporosis, are increasingly important 4.
• In patients who fail to respond to treatment, coexistent small intestinal bacterial overgrowth should be considered 4.
• Augmenting clinical judgement with pancreatic imaging and repeat FE1 testing could improve the rate of PERT prescription and inform the approach to non-response, particularly in cases where there is diagnostic doubt 6.