11. Pancrelipase is a pancreatic enzyme product consisting of a mixture of enzymes including lipases, proteases, and amylases, and is an extract derived from porcine pancreatic glands. VIOKACE (pancrelipase) tablets are for oral administration and available as follows: 10,440 USP units of lipase; 39,150 USP units of protease; and 39,150 USP units of amylase as a tan, round biconvex tablet and have VIO9111 engraved on one side and 9111 on the other side. 20,880 USP units of lipase; 78,300 USP units of protease; and 78,300 USP units of amylase as a tan, oval, biconvex tablet with V 16 engraved on one side and 9116 on the other side. Inactive ingredients in VIOKACE include colloidal silicon dioxide, croscarmellose sodium, lactose monohydrate, microcrystalline cellulose, stearic acid and talc.

1. VIOKACE, in combination with a proton pump inhibitor, is indicated for the treatment of exocrine pancreatic insufficiency due to chronic pancreatitis or pancreatectomy in adults. VIOKACE, in combination with a proton pump inhibitor, is indicated for the treatment of exocrine pancreatic insufficiency due to chronic pancreatitis or pancreatectomy in adults.

3. Tablets are available in the following strengths: 10,440 USP units of lipase; 39,150 USP units of protease; and 39,150 USP units of amylase as a tan, round, biconvex tablet with VIO9111 engraved on one side and 9111 on the other side. 20,880 USP units of lipase; 78,300 USP units of protease; and 78,300 USP units of amylase as a tan, oval, biconvex tablet with V 16 engraved on one side and 9116 on the other side. Tablets: 10,440 USP units of lipase; 39,150 USP units of protease; and 39,150 USP units of amylase 20,880 USP units of lipase; 78,300 USP units of protease; and 78,300 USP units of amylase

2. Important Dosing Information VIOKACE is a mixture of enzymes including lipases, proteases, and amylases and dosing is based on lipase units. Dosing scheme based on actual body weight or fat ingestion. Individualize the dosage based on clinical symptoms, the degree of steatorrhea present, and the fat content of the diet. Do not exceed 2,500 lipase units/kg/meal, 10,000 lipase units/kg/day, or 4,000 lipase units/g fat ingested/day without further investigation. The total daily dosage should reflect approximately three meals plus two or three snacks per day. With each snack, administer approximately half the prescribed dose for a meal. Do not substitute other pancreatic enzyme products for VIOKACE. When switching from another pancreatic enzyme product to VIOKACE, monitor patients for clinical symptoms of exocrine pancreatic insufficiency and titrate the dosage as needed. Recommended Dosage Adult Patients : The recommended initial starting dosage is 500 lipase units/kg/meal. Titrate the dosage to 2,500 lipase units/kg/meal, 10,000 lipase units/kg/day, or 4,000 lipase units/g fat ingested/day. Higher dosages may be administered if documented effective by fecal fat measures or improvement in malabsorption. Preparation and Administration Instructions Swallow tablets whole; do not crush or chew VIOKACE tablets. Consume sufficient liquids to ensure complete swallowing of VIOKACE tablets. 2.1. Important Dosing Information VIOKACE is a mixture of enzymes including lipases, proteases, and amylases. VIOKACE dosing is based on lipase units. Administer VIOKACE with a proton pump inhibitor. Use either an actual body weight or fat ingestion-based dosing scheme. Start at the lowest recommended dosage and individualize the dosage based on clinical symptoms, the degree of steatorrhea present, and the fat content of the diet. Changes in dosage may require an adjustment period of several days. Do not exceed 2,500 lipase units/kg/meal, 10,000 lipase units/kg/day, or 4,000 lipase units/g fat ingested/day without further investigation . Higher dosages may be administered if they are documented to be effective by fecal fat measures or an improvement in signs or symptoms of malabsorption including measures of nutritional status. The total daily dosage should reflect approximately three meals plus two or three snacks per day. With each snack, administer approximately half the prescribed VIOKACE dose for a meal. Do not substitute other pancreatic enzyme products for VIOKACE. When switching from another pancreatic enzyme product to VIOKACE, monitor patients for clinical symptoms of exocrine pancreatic insufficiency and titrate the dosage as needed. 2.2. Recommended Dosage Adult Patients: The recommended oral initial starting dosage of VIOKACE is 500 lipase units/kg/meal. If signs and symptoms of malabsorption persist, increase the dosage. Titrate to a maximum of either 2,500 lipase units/kg/meal, 10,000 lipase units/kg/day, or 4,000 lipase units/grams of fat ingested/day. 2.3. Preparation and Administration Instructions Adult Patients: Take VIOKACE with meals or snacks. If a dose is missed, take the next dose with the next meal or snack. Swallow tablets whole. Do not crush or chew VIOKACE tablets. Consume sufficient liquids (water) to ensure complete swallowing of VIOKACE tablets .

5. Fibrosing Colonopathy : Associated with high doses, usually over prolonged use and in pediatric patients with cystic fibrosis. Colonic stricture reported in pediatric patients less than 12 years of age with dosages exceeding 6,000 lipase units/kg/meal. Monitor during treatment for progression of preexisting disease. Do not exceed the recommended dosage, unless clinically indicated. Irritation of the Oral Mucosa : May occur if tablets are crushed or chewed. Hyperuricemia : Reported with high dosages, consider monitoring blood uric acid levels in patients with gout, renal impairment, or hyperuricemia. Risk of Viral Transmission : The presence of porcine viruses that might infect humans cannot be definitely excluded. Hypersensitivity Reactions : Monitor patients with known reactions to proteins of porcine origin. If symptoms occur, initiate appropriate medical management; consider the risks and benefits of continued treatment. Potential for Exacerbation of Symptoms of Lactose Intolerance : tablets contain lactose monohydrate. Patients who have lactose intolerance may not be able to tolerate VIOKACE. 5.1. Fibrosing Colonopathy Fibrosing colonopathy has been reported following treatment with pancreatic enzyme products. Fibrosing colonopathy is a rare, serious adverse reaction initially described in association with use of high-dose pancreatic enzyme products, usually over a prolonged period of time and most commonly reported in pediatric patients with cystic fibrosis. Pancreatic enzyme products exceeding 6,000 lipase units/kg/meal have been associated with colonic stricture, a complication of fibrosing colonopathy, in pediatric patients less than 12 years of age. The underlying mechanism of fibrosing colonopathy remains unknown. If there is a history of fibrosing colonopathy, monitor patients during treatment with VIOKACE because some patients may be at risk of progressing to colonic stricture formation. It is uncertain whether regression of fibrosing colonopathy occurs. Do not exceed the recommended dosage of either 2,500 lipase units/kg/meal, 10,000 lipase units/kg/day, or 4,000 lipase units/g fat ingested/day without further investigation . Higher dosages may be administered if they are documented to be effective by fecal fat measures or an improvement in signs or symptoms of malabsorption including measures of nutritional status. Patients receiving dosages higher than 6,000 lipase units/kg/meal should frequently monitored for symptoms of fibrosing colonopathy and the dosage decreased or titrated downward to a lower range if clinically appropriate . 5.2. Irritation of the Oral Mucosa Crushing or chewing VIOKACE tablets can result in irritation of the oral mucosa, and/or loss of enzyme activity. Instruct the patient to swallow tablets whole. Do not crush or chew VIOKACE tablets. Consume sufficient liquids immediately following administration of VIOKACE to ensure complete swallowing . 5.3. Hyperuricemia Pancreatic enzyme products contain purines that may increase blood uric acid levels. High dosages have been associated with hyperuricosuria and hyperuricemia . Consider monitoring blood uric acid levels in patients with gout, renal impairment, or hyperuricemia during treatment with VIOKACE. 5.4. Risk of Viral Transmission VIOKACE is sourced from pancreatic tissue from pigs used for food consumption. Although the risk that VIOKACE 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. Hypersensitivity Reactions Severe hypersensitivity reactions including anaphylaxis, asthma, hives, and pruritus have been reported with pancreatic enzyme products . If symptoms occur, initiate appropriate medical management. Monitor patients with a known hypersensitivity reaction to proteins of porcine origin for hypersensitivity reactions during treatment with VIOKACE. The risks and benefits of continued VIOKACE treatment in patients with severe hypersensitivity reactions should be taken into consideration with the overall clinical needs of the patient. 5.6. Potential for Exacerbation of Symptoms of Lactose Intolerance VIOKACE tablets contain lactose monohydrate . Patients who have lactose intolerance may not be able to tolerate VIOKACE.