PANCREAZE

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. The enteric-coated microtablets in PANCREAZE are formulated to release pancreatic enzymes at an approximate pH of 5.5 or greater. PANCREAZE (pancrelipase) delayed-release capsules are for oral administration and include a two-piece shell containing enteric-coated microtablets that are each approximately 2 mm in diameter and are available as follows: 2,600 USP units of lipase ; 8,800 USP units of protease; and 15,200 USP units of amylase; delayed-release capsules have a light orange opaque body and clear cap imprinted with "VIVUS" and "MT 2". The shells contain hypromellose, titanium dioxide, yellow iron oxide, red iron oxide and imprint ink contains black iron oxide, shellac, propylene glycol, strong ammonia solution, potassium hydroxide. 4,200 USP units of lipase ; 14,200 USP units of protease; and 24,600 USP units of amylase; delayed-release capsules have a yellow opaque body and clear cap imprinted with "VIVUS" and "MT 4". The shells contain hypromellose, titanium dioxide, yellow iron oxide, and imprint ink contains black iron oxide, shellac-glaze-45%, ammonium hydroxide, propylene glycol. 10,500 USP units of lipase; 35,500 USP units of protease; and 61,500 USP units of amylase; delayed-release capsules have a flesh opaque body and clear cap imprinted with "VIVUS" and "MT 10". The shells contain hypromellose, titanium dioxide, red iron oxide, and imprint ink contains black iron oxide, shellac-glaze-45%, ammonium hydroxide, propylene glycol. 16,800 USP units of lipase; 56,800 USP units of protease; 98,400 USP units of amylase; delayed-release capsules have a flesh opaque body and clear cap imprinted with "VIVUS" and "MT 16". The shells contain hypromellose, titanium dioxide, red iron oxide, yellow iron oxide, and imprint ink contains black iron oxide, shellac-glaze-45%, ammonium hydroxide, propylene glycol. 21,000 USP units of lipase; 54,700 USP units of protease; and 83,900 USP units of amylase; delayed-release capsules have a white opaque body and cap imprinted with "VIVUS" and "MT 20". The shells contain hypromellose, titanium dioxide, and imprint ink contains yellow iron oxide, shellac, strong ammonia solution, propylene glycol. 37,000 USP units of lipase; 97,300 USP units of protease; and 149,900 USP units of amylase; delayed-release capsules have an iron grey opaque body and white opaque cap imprinted with "VIVUS" and "MT 37". The shells contain hypromellose, titanium dioxide, black iron oxide and imprint ink contains black iron oxide, shellac-glaze-45%, ammonium hydroxide, propylene glycol. PANCREAZE (pancrelipase) delayed-release capsules include the following inactive ingredients: colloidal silicon dioxide, crospovidone, magnesium stearate, methacrylic acid ethyl acrylate copolymer, microcrystalline cellulose, montan glycol wax, simethicone emulsion, talc and triethyl citrate.

PANCREAZE is indicated for the treatment of exocrine pancreatic insufficiency in adult and pediatric patients. PANCREAZE ® is indicated for the treatment of exocrine pancreatic insufficiency in adult and pediatric patients. ( 1 )

Important Dosing Information ( 2.1 ) PANCREAZE 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 in adult and pediatric patients greater than 12 months of age without further investigation. ( 5.1 ) The total daily dosage in adult and pediatric patients greater than 12 months of age 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 PANCREAZE. When switching from another pancreatic enzyme product to PANCREAZE, monitor patients for clinical symptoms of exocrine pancreatic insufficiency and titrate the dosage as needed. Recommended Dosage ( 2.2 ): Adult and Pediatric Patients Greater than 12 Months : The recommended initial starting dosage is: 500 lipase units/kg/meal for adult and pediatric patients 4 years and older. 1,000 lipase units/kg/meal for pediatric patients greater than 12 months to less than 4 years. Titrate the dosage to either 2,500 lipase units/kg/meal, 10,000 lipase units/kg/day, or less than 4,000 lipase units/g fat ingested/day. Higher dosages may be administered if documented effective by fecal fat measures or improvement in malabsorption. Pediatric Patients Birth to 12 Months: The recommended dosage is 2,600 lipase units (one capsule) per 120 mL of formula or per breastfeeding. Preparation and Administration Instructions ( 2.3 ) Swallow capsules whole. For patients unable to swallow intact capsule(s), the capsule contents may be sprinkled on soft acidic food (e.g., applesauce). Do not crush or chew PANCREAZE capsules or capsule contents. Consume sufficient liquids to ensure complete swallowing of PANCREAZE. ( 5.2 ) See the full prescribing information for additional information on administering to pediatric patients birth to 12 months. 2.1 Important Dosing Information PANCREAZE is a mixture of enzymes including lipases, proteases, and amylases. PANCREAZE dosing is based on lipase units. 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 in adult and pediatric patients greater than 12 months of age without further investigation [see Warnings and Precautions (5.1) ] . The total daily dosage in adult and pediatric patients greater than 12 months of age should reflect approximately three meals plus two or three snacks per day. With each snack, administer approximately half the prescribed PANCREAZE dose for a meal. Do not substitute other pancreatic enzyme products for PANCREAZE. When switching from another pancreatic enzyme product to PANCREAZE, monitor patients for clinical symptoms of exocrine pancreatic insufficiency and titrate the dosage as needed. 2.2 Recommended Dosage Adult and Pediatric Patients Greater than 12 Months of Age The recommended oral initial starting dosage is: 500 lipase units/kg/meal for adult and pediatric patients 4 years of age and older. 1,000 lipase units/kg/meal for pediatric patients greater than 12 months to less than 4 years of age. If signs and symptoms of malabsorption persist, increase the dosage. Titrate to either 2,500 lipase units/kg/meal, 10,000 lipase units/kg/day, or less than 4,000 lipase units/grams of fat ingested/day. Higher dosages may be administered if they are documented to be effective by fecal fat measures or an improvement in signs and symptoms of malabsorption including measures of nutritional status. Pediatric Patients Birth to 12 Months of Age The recommended oral dosage is 2,600 lipase units per 120 mL of formula or per breast-feeding. 2.3 Preparation and Administration Instructions Instruct adult and pediatric patients greater than 12 months of age, or their caregivers, of the following: Take PANCREAZE with meals or snacks. If a dose is missed, take the next dose with the next meal or snack. Swallow capsules whole. For patients who are unable to swallow intact capsules, carefully open the capsules and sprinkle the entire contents on a small amount of acidic soft food with a pH of 4.5 or less (e.g., applesauce). Consume the entire mixture immediately. Do not crush or chew PANCREAZE capsules or capsule contents. Consume sufficient liquids (water or juice) to ensure complete swallowing of PANCREAZE capsules [see Warnings and Precautions (5.2) ] . Instruct caregivers of pediatric patients birth to 12 months of age of the following: Immediately prior to each breast-feeding session or each administration of 120 mL of formula, carefully open one PANCREAZE capsule (containing 2,600 USP units of lipase) and administer the entire contents using one of the following two methods: Sprinkle on a small amount of acidic soft food with a pH of 4.5 or less (e.g., applesauce) being careful not to crush the capsule contents. The entire mixture should be given to the infant immediately. Sprinkle the capsule contents directly into the infant's mouth. Immediately administer additional breast milk or formula after PANCREAZE to ensure complete swallowing of the capsule contents. Do not mix PANCREAZE capsule contents directly into a bottle of breast milk or formula. Do not crush PANCREAZE capsule contents, and visually inspect the infant's mouth to ensure that no drug is retained in the mouth [see Warnings and Precautions (5.2) ] . If a dose is missed, administer the next dose with the next feeding.

None. None.

The following serious or otherwise important adverse reactions are described elsewhere in the labeling: Fibrosing Colonopathy [see Warnings and Precautions (5.1) ] Irritation of the Oral Mucosa [see Warnings and Precautions (5.2) ] Hyperuricemia [see Warnings and Precautions (5.3) ] Risk of Viral Transmission [see Warnings and Precautions (5.4) ] Hypersensitivity Reactions [see Warnings and Precautions (5.5) ] The data described below reflect exposure to PANCREAZE in 57 adult and pediatric patients with exocrine pancreatic insufficiency due to cystic fibrosis in two clinical trials. Study 1 was conducted in 40 patients, aged 8 years to 57 years; Study 2 was conducted in 17 pediatric patients, aged 6 months to 30 months [see Clinical Studies (14) ] . The most common adverse reactions were gastrointestinal, including diarrhea and vomiting. The following adverse reactions have been identified during post-approval use of PANCREAZE or other pancreatic enzyme products. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Most common adverse reactions are gastrointestinal, including nausea and vomiting. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact VIVUS LLC at 1-888-998-4887 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch Eye Disorders blurred vision Gastrointestinal Disorders fibrosing colonopathy, distal intestinal obstruction syndrome abdominal pain, flatulence, constipation, and nausea Immune System Disorders anaphylaxis, asthma, hives, and pruritus Investigations asymptomatic elevations of liver enzymes Musculoskeletal System myalgia, muscle spasm Skin and Subcutaneous Tissue Disorders urticaria and rash

Storage and Handling Store PANCREAZE at room temperature between 15ºC and 25ºC (59°F to 77°F), excursion permitted up to 40ºC (104°F) for 24 hours. After opening, keep bottle tightly closed between uses to protect from moisture. All PANCREAZE bottles contain a desiccant canister. Store and dispense PANCREAZE in the original container.