Exocrine pancreatic insufficiency (EPI) results when the production or delivery of pancreatic digestive enzymes is disrupted. It typically occurs as a consequence of pancreatic tissue destruction or blocked pancreatic ducts. The condition is not a rare disease but is often observed in patients with rare genetic diseases, such as cystic fibrosis and Shwachman-Diamond syndrome. It also presents in patients with chronic pancreatitis or who have undergone a pancreatectomy. Patients with EPI typically experience steatorrhea, frequent bowel movements, gas, bloating, stomach pain, and weight loss. Treatment of patients with EPI focuses on managing their underlying condition, which can alleviate some EPI symptoms and prevent additional damage to pancreatic tissue, and improving digestion by replacing the missing pancreatic enzymes, known as pancreatic enzyme replacement therapy
PERT is achieved through pharmacological agents that contain most of the pancreatic enzymes needed for digestion, including proteases, lipase, and amylase, which break down proteins, fats, and carbohydrates, respectively. One commonly prescribed agent is pancrelipase, which is available in 6 Food and Drug Administration (FDA)–approved formulations: Creon, Zenpep, Pancreaze, Ultresa, Pertzye, and Viokace. All of these agents except for Viokace are enteric-coated and indicated for the treatment of EPI due to cystic fibrosis or other conditions in adults and pediatric patients. Viokace is indicated in adults for the treatment of EPI due to chronic pancreatitis or pancreatectomy, and it must be administered in combination with a proton pump inhibitor to prevent it from breaking down in the stomach.
Creon was the first FDA approved combination of porcine-derived lipases, proteases, and amylases for EPI, and it is the most commonly prescribed pancrelipase. Creon is taken as an oral capsule with food. The capsules may not be crushed or chewed. As the capsules dissolve in the stomach, enteric-coated spheres sized between 0.7 mm and 1.6 mm in diameter are released. These spheres carry the digestive enzymes from the stomach through the pylorus into the small intestine, where the high pH environment dissolves the spheres, releasing the enzymes.
Treatment with Creon should be initiated at the lowest recommended dose and gradually increased based on a patient’s clinical symptoms and weight, degree of steatorrhea, and amount of dietary fat consumed. Caution is warranted in patients with cystic fibrosis who are taking high-dose PERT (>2500 lipase units per kg of body weight per meal or >10,000 lipase units per kg of body weight per day) and in those who are known to be allergic to pork products.
The most recently approved pancrelipase is Pertzye, which received approval in May 2012. Unlike the other pancerelipases on the market, this formulation contains bicarbonate-buffered enteric-coated microspheres. The addition of the bicarbonate, while an inactive ingredient, is meant to simulate normal pancreatic function, as pancreatic juice is composed of two secretory products critical to proper digestion: digestive enzymes and bicarbonate.
Although all pancrelipases contain the same digestive enzymes (ie, lipases, proteases, amylases), the FDA warns that these agents are not interchangeable at the pharmacy. Furthermore, patients receiving one of the many unapproved pancreatic enzyme products on the market should be switched to an approved product. In a postmarket safety statement, the FDA notes, “Several years ago, the FDA became aware that unapproved [pancreatic enzyme products] contained variable amounts of the therapeutic enzymes (lipase, amylase, and protease), which were causing patients to notice changes in their ability to digest food due to under-dosing, or adverse events due to overdosing.”
Did you know…
In patients with cystic fibrosis, pancreatic insufficiency is the most common gastrointestinal complication, affecting approximately 85% of patients at some point during their lifetime.
Shwachman-Diamond syndrome is the second most common cause of inherited pancreatic insufficiency after cystic fibrosis.
All currently available pancrelipases are classified as a category C medication during pregnancy and should be prescribed with caution.