What are the causes of pancreatic insufficiency (exocrine pancreatic insufficiency)?

From the Guidelines

Pancreatic insufficiency should be treated with pancreatic enzyme replacement therapy (PERT) and dietary modifications to improve outcomes and quality of life. The treatment of pancreatic insufficiency primarily involves PERT with medications like pancrelipase, as stated in the AGA Clinical Practice Update on Exocrine Pancreatic Insufficiency 1. The typical starting dose is at least 40,000 USP units of lipase during each meal in adults, which can be adjusted based on symptoms and response, and one-half of that with snacks, as recommended in the Best Practice Advice 12 1. These enzymes should be taken during the meal to maximize mixing and digestion of nutrients.

Key Considerations

• Dietary modifications are also important, including consuming smaller, more frequent meals, limiting high-fat foods, and taking fat-soluble vitamin supplements (A, D, E, K) as the condition often causes malabsorption of these nutrients.
• Patients should monitor for symptoms like steatorrhea (fatty, foul-smelling stools), weight loss, abdominal pain, and bloating to assess treatment effectiveness.
• The underlying cause of pancreatic insufficiency, such as chronic pancreatitis, cystic fibrosis, or pancreatic cancer, should also be addressed.
• Regular follow-up with a gastroenterologist is essential to adjust enzyme dosage and manage the condition effectively over time.

Additional Recommendations

• Routine supplementation monitoring of fat-soluble vitamin levels is appropriate, as stated in the Best Practice Advice 13 1.
• Over-the-counter commercially available pancreas enzyme replacements should not be used, as they are classified as dietary supplements only and their dosing and efficacy are neither standardized nor regulated.
• The use of PERT in patients with chronic pancreatitis and exocrine pancreatic insufficiency improves outcomes, as stated in the AGA Clinical Practice Update on Exocrine Pancreatic Insufficiency 1.

Conclusion Not Applicable

Instead, the focus is on the key considerations and additional recommendations for the treatment of pancreatic insufficiency, prioritizing morbidity, mortality, and quality of life as the outcome. The most recent and highest quality study, the AGA Clinical Practice Update on Exocrine Pancreatic Insufficiency 1, provides the basis for these recommendations.

From the FDA Drug Label

The final analysis population was limited to 29 patients; 3 patients were excluded due to protocol deviations. Study 2 included patients aged 7 to 11 years (n = 17). The final analysis population was limited to 16 patients; 1 patient withdrew consent prior to stool collection during treatment with CREON In each study, patients were randomized to receive CREON at a dose of 4,000 lipase units/g fat ingested/day or matching placebo for 5 to 6 days of treatment, followed by crossover to the alternate treatment for an additional 5 to 6 days. All patients consumed a high-fat diet (greater than or equal to 90 grams of fat per day, 40% of daily calories derived from fat) during the treatment periods Coefficient of Fat Absorption Endpoint and Results The primary efficacy endpoint was the coefficient of fat absorption (CFA) in CREON and placebo treatment groups. 14. 2 Exocrine Pancreatic Insufficiency Due to Chronic Pancreatitis or Pancreatectomy A randomized, double-blind, placebo-controlled, parallel group study was conducted in 54 adult patients, aged 32 to 75 years, with exocrine pancreatic insufficiency due to chronic pancreatitis or pancreatectomy (Study 4)

Pancreatic Insufficiency is addressed in the label.

• Exocrine Pancreatic Insufficiency due to cystic fibrosis and chronic pancreatitis or pancreatectomy is mentioned.
• The label discusses the Coefficient of Fat Absorption (CFA) endpoint in patients with pancreatic insufficiency.
• Studies show that CREON treatment results in a significant improvement in CFA compared to placebo treatment 2.
• The mean change in CFA from the run-in period to the end of the double-blind period in the CREON and placebo groups is provided in Table 3 2.

From the Research

Pancreatic Insufficiency Treatment

• Pancreatic enzyme replacement therapy (PERT) is the standard treatment for exocrine pancreatic insufficiency (EPI) 3.
• The goal of PERT is to restore normal fat absorption, but few patients achieve complete normalization of fat absorption 4, 5.
• Treatment guidelines vary widely across disease types, and many patients are underdosed 3.
• The most common dosing guidelines recommend starting with 40,000-50,000 units of lipase per meal, with increases of up to two to three times this amount before pursuing additive therapies 3.

Challenges in PERT

• Enzyme destruction in the stomach and lack of adequate mixing with chyme in the duodenum can limit the effectiveness of PERT 4, 6.
• Enteric-coated enzyme microbead formulations can separate from nutrients in the stomach, precluding coordinated emptying of enzymes and nutrients 4.
• Unprotected enzymes can be inactivated at pH 4 or below, reducing their effectiveness 4.

Approaches to Improving PERT

• Changing to or adding a different enzyme product, adding non-enteric coated enzymes, and using antisecretory drugs and/or antacids can improve treatment outcomes 4.
• Adjusting the timing of enzyme administration and using sodium bicarbonate to prevent duodenal acidity can also be beneficial 4.
• Individualizing PERT dosing based on nutritional status and response to therapy, with regular follow-up and dose titrations, is recommended 3.