warnings and cautions
5 WARNINGS AND PRECAUTIONS Fibrosing colonopathy is associated with high-dose use of pancreatic enzyme replacement. Exercise caution when doses of PANCRELIPASE exceed 2,500 lipase units/kg of body weight per meal (or greater than 10,000 lipase units/kg of body weight per day). ( 5.1 ) To avoid irritation of oral mucosa, do not chew PANCRELIPASE or retain in the mouth. ( 5.2 ) Exercise caution when prescribing PANCRELIPASE to patients with gout, renal impairment, or hyperuricemia. ( 5.3 ) There is theoretical risk of viral transmission with all pancreatic enzyme products including PANCRELIPASE. ( 5.4 ) Exercise caution when administering PANCRELIPASE to a patient with a known allergy to proteins of porcine origin. ( 5.5 ) 5.1 Fibrosing Colonopathy Fibrosing colonopathy has been reported following treatment with different pancreatic enzyme products. Fibrosing colonopathy is a rare serious adverse reaction initially described in association with high-dose pancreatic enzyme use, usually with use over a prolonged period of time and most commonly reported in pediatric patients with cystic fibrosis. The underlying mechanism of fibrosing colonopathy remains unknown. Doses of pancreatic enzyme products exceeding 6,000 lipase units/kg of body weight per meal have been associated with colonic strictures in children less than 12 years of age. 1 Patients with fibrosing colonopathy should be closely monitored because some patients may be at risk of progressing to stricture formation. It is uncertain whether regression of fibrosing colonopathy occurs. It is generally recommended, unless clinically indicated, that enzyme doses should be less than 2,500 lipase units/kg of body weight per meal (or less than 10,000 lipase units/kg of body weight per day) or less than 4,000 lipase units/g fat ingested per day [see Dosage and Administration (2.1 )] . Doses greater than 2,500 lipase units/kg of body weight per meal (or greater than 10,000 lipase units/kg of body weight per day) should be used with caution and only if they are documented to be effective by 3-day fecal fat measures that indicate a significantly improved coefficient of fat absorption. Patients receiving higher doses than 6,000 lipase units/kg of body weight per meal should be examined and the dosage either immediately decreased or titrated downward to a lower range. 5.2 Potential for Irritation to Oral Mucosa Care should be taken to ensure that no drug is retained in the mouth. PANCRELIPASE should not be crushed or chewed or mixed in foods having a pH greater than 4.5. These actions can disrupt the protective enteric coating resulting in early release of enzymes, irritation of oral mucosa, and/or loss or enzyme activity [see Dosage and Administration ( 2.2 ) and Patient Counseling Information ( 17.1 )] . For patients who are unable to swallow intact capsules, the capsules may be carefully opened and the contents added to a small amount of acidic soft food with a pH of 4.5 or less, such as applesauce. The PANCRELIPASE-soft food mixture should be swallowed immediately and followed with water or juice to ensure complete ingestion. 5.3 Potential for Risk of Hyperuricemia Caution should be exercised when prescribing PANCRELIPASE to patients with gout, renal impairment, or hyperuricemia. Porcine-derived pancreatic enzyme products contain purines that may increase blood uric acid levels. 5.4 Potential Viral Exposure from the Product Source PANCRELIPASE is sourced from pancreatic tissue from swine used for food consumption. Although the risk that PANCRELIPASE will transmit an infectious agent to humans has been reduced by testing for certain viruses during manufacturing and by inactivating certain viruses during manufacturing, there is a theoretical risk for transmission of viral disease, including diseases caused by novel or unidentified viruses. Thus, the presence of porcine viruses that might infect humans cannot be definitely excluded. However, no cases of transmission of an infectious illness associated with the use of porcine pancreatic extracts have been reported. 5.5 Allergic Reactions Caution should be exercised when administering PANCRELIPASE to a patient with a known allergy to proteins of porcine origin. Rarely, severe allergic reactions including anaphylaxis, asthma, hives, and pruritus, have been reported with other pancreatic enzyme products with different formulations of the same active ingredient (pancrelipase). The risks and benefits of continued PANCRELIPASE treatment in patients with severe allergy should be taken into consideration with the overall clinical needs of the patient.