Treatment of Pancreatic Insufficiency

Treatment of exocrine pancreatic insufficiency by oral enzyme replacement usually corrects steatorrhea, but steatorrhea is difficult to correct completely. This is due to variability of lipase activity in different commercial preparations, inadequate dosage, incorrect timing of doses, lipase inactivation by gastric acid, and the observation that chymotrypsin in the enzyme preparation digests and thus inactivates lipase. In enzyme supplements, the true lipase activity has been shown to be as much as twice the labeled amount. Pancrease, Creon, Ultrase, and Panceacarb are the preparations most widely used. These products are enteric-coated preparations that resist gastric acid inactivation. Generic enzyme preparations are less effective and should be avoided.

The dosage of pancreatic replacement for children depends on the amount of food eaten and is established by trial and error. Because these products contain excess protease compared with lipase, the dosage is estimated from the lipase requirement of 500–1,500 IU/kg/meal. An adequate dose is one that is followed by the return of the stools to normal fat content, size, color, and odor. Enzyme replacement should be given at the beginning of and with the meal. Tablets should be chewed; powder and granules can be mixed with a small quantity of food. Enzymes must also be given with snacks. Increasing enzyme supplements beyond the recommended dose does not improve absorption, may retard growth, and may cause fibrosing colonopathy.

When adequate fat absorption is not achieved, gastric acid neutralization with an H2-receptor antagonist or a proton pump inhibitor decreases enzyme inactivation by gastric acid and improves delivery of lipase into the intestine. The coating of enteric-coated preparations also protects lipase from acid inactivation.

Side effects:
Untoward effects secondary to pancreatic enzyme replacement therapy include allergic reactions, increased uric acid levels, and kidney stones. Fibrosing colonopathy, consisting of colonic fibrosis and strictures, occurs 7–12 mo after high-dose pancreatic supplement therapy (ranging from 6,500 to 58,000 IU lipase/kg/meal).