PERTZYE

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 microspheres in PERTZYE are formulated to release pancreatic enzymes at an approximate pH of 5.5 or greater. PERTZYE (pancrelipase) delayed-release capsules are for oral administration, include a two-piece hard gelatin shell containing light tan/cream-colored bicarbonate-buffered enteric-coated microspheres ranging in size from 0.8 to 1.4 mm in diameter for 4,000 USP units of lipase and 0.8 to 2.2 mm in diameter for 8,000, 16,000, and 24,000 USP units of lipase, and are available as follows: 4,000 USP units of lipase ; 14,375 USP units of protease; and 15,125 USP units of amylase; delayed-release capsules have a clear body printed in green with "4" and a clear cap printed with a green circular stripe and "DCI". The imprinting ink on the capsule contains FD&C Blue #1, D&C Yellow #10, black iron oxide, dehydrated alcohol, isopropyl alcohol, butyl alcohol, propylene glycol, shellac, and ammonium hydroxide. 8,000 USP units of lipase ; 28,750 USP units of protease; and 30,250 USP units of amylase; delayed-release capsules have a clear body printed in blue with "8" and a clear cap printed with a blue circular stripe and "DCI". The imprinting ink on the capsule contains FD&C Blue #1, ethanol, methanol, n-butyl alcohol, propylene glycol, shellac, and ammonium hydroxide. 16,000 USP units of lipase ; 57,500 USP units of protease; and 60,500 USP units of amylase; delayed-release capsules have a clear body printed in red with "16" and a clear cap printed with a red circular stripe and "DCI". The imprinting ink on the capsule contains FD&C Red #40, povidone, titanium dioxide, dehydrated alcohol, sodium hydroxide, butyl alcohol, propylene glycol, isopropyl alcohol, and shellac. 24,000 USP units of lipase ; 86,250 USP units of protease; and 90,750 USP units of amylase; delayed-release capsules have a clear body printed in purple with "24" and a clear cap printed with a purple circular stripe and "DCI". The imprinting ink on the capsule contains FD&C Blue #2, D&C Red #7, titanium dioxide, strong ammonia solution, propylene glycol, butyl alcohol, isopropyl alcohol, dehydrated alcohol, and shellac. PERTZYE (pancrelipase) delayed-release capsules include the following inactive ingredients: cellulose acetate phthalate, diethyl phthalate, polyvinylpyrrolidone, sodium bicarbonate, sodium carbonate, sodium starch glycolate, talc, and ursodiol.

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

Important Dosing Information ( 2.1 ) PERTZYE 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 PERTZYE. When switching from another pancreatic enzyme product to PERTZYE, monitor patients for clinical symptoms of exocrine pancreatic insufficiency and titrate the dosage as needed. Recommended Dosage ( 2.2 ) Adults 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 of age and older. 1,000 lipase units/kg/meal for pediatric patients greater than 12 months to less than 4 years of age. Titrate the dosage to either 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 to be effective by fecal fat measures or improvement in malabsorption. Pediatric Patients Birth to 12 Months: The recommended dosage is 4,000 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). The 4,000 USP lipase unit capsule may be administered with applesauce via gastrostomy tube (14 French or larger). The contents of no more than two capsules may be administered at a time. Do not crush or chew PERTZYE capsules or capsule contents. Consume sufficient liquids to ensure complete swallowing of PERTZYE. ( 5.2 ) See the full prescribing information for additional information on administering to pediatric patients birth to 12 months of age. 2.1 Important Dosing Information PERTZYE is a mixture of enzymes including lipases, proteases, and amylases. PERTZYE 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 PERTZYE dose for a meal. Do not substitute other pancreatic enzyme products for PERTZYE. When switching from another pancreatic enzyme product to PERTZYE, monitor patients for clinical symptoms of exocrine pancreatic insufficiency and titrate the dosage as needed. 2.2 Recommended Dosage Adults 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 4,000 lipase units/gram 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 or symptoms of malabsorption including measures of nutritional status. Pediatric Patients Birth to 12 Months of Age The recommended oral dosage is 4,000 lipase units per 120 mL of formula or per breastfeeding. 2.3 Preparation and Administration Instructions Adult and Pediatric Patients Greater than 12 Months of Age Instruct adult and pediatric patients greater than 12 months of age, or their caregivers, of the following: Take PERTZYE with meals or snacks. If a dose is missed, take the next dose with the next meal or snack. Swallow capsules whole. For patients unable to swallow intact capsules, the capsule contents may be sprinkled on a small amount of soft acidic food with a pH of 4.5 or less (e.g., applesauce). The 4,000 USP lipase unit capsule may also be administered with applesauce via gastrostomy tube 14 French or larger. Do not crush or chew PERTZYE capsules or capsule contents. Consume sufficient liquids (water or juice) to ensure complete swallowing of PERTZYE [see Warnings and Precautions (5.2) ] . Oral Administration for Patients Unable to Swallow Intact Capsules Carefully open the capsules and sprinkle the entire contents on a small amount of acidic soft food (approximately 10 mL) with a pH of 4.5 or less (e.g., applesauce). Mix the capsule contents with the acidic soft food (e.g., applesauce) being careful not to crush the contents. Consume the entire mixture immediately. Do not save the mixture for later use. Consume sufficient fluids to ensure complete swallowing of the PERTZYE food mixture. Gastrostomy Tube Administration (14 French Gastrostomy Tube or Larger) Only perform gastrostomy tube administration with the contents of the 4,000 USP lipase unit capsule of PERTZYE. The contents of no more than two capsules may be administered at a time in the gastrostomy tube. Transfer a minimum of 10 mL of applesauce into a small bowl or medicine cup. Carefully open one or two PERTZYE 4,000 lipase unit capsules. Mix the capsule contents thoroughly with the transferred applesauce to create a uniform suspension being careful not to crush the contents. Once mixed, administer the suspension immediately. Remove the plunger from a 35 mL slip tip syringe. Cover the tip of the syringe with your finger. Transfer the PERTZYE-applesauce mixture into the syringe. Replace the plunger partially back into the syringe. Shake or tap the syringe lightly with the syringe tip facing upward so that the PERTZYE-applesauce mixture will move towards the plunger. Carefully push the plunger slowly until the residual air is removed from the syringe tip. Once the residual air is removed, connect the syringe directly into the gastrostomy tube feeding port. Push the syringe contents into the gastrostomy tube feeding port using steady pressure until empty. Draw up approximately 10 mL of water with the slip tip syringe and flush the gastrostomy tube feeding port with the water. Discard any unused portion of the PERTZYE-applesauce mixture. Do not save for later use. If dose requires more than two capsules, repeat steps 1-9 until prescribed dose is reached. Pediatric Patients Birth to 12 Months of Age: Instruct caregivers of pediatric patients birth to 12 months of age of the following: Immediately prior to each breastfeeding session or each administration of 120 mL of formula, carefully open one PERTZYE capsule (containing 4,000 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 breast milk or formula after PERTZYE to ensure complete swallowing of the PERTZYE capsule contents. Do not crush PERTZYE 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. ( 4 )

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) ] Most common adverse reactions (≥ 10%) are: diarrhea, dyspepsia, and cough. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Digestive Care Inc. at 1-877-882-5950 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to the rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. The data described below reflect exposure to PERTZYE in 21 patients, aged 8 to 43 years, with exocrine pancreatic insufficiency due to cystic fibrosis in a placebo-controlled clinical trial [see Clinical Studies (14) ] . Table 1 enumerates adverse reactions that occurred in at least 2 patients (greater than or equal to 10%) treated with PERTZYE at a higher rate than with placebo. Table 1. Adverse Reactions Reported in at least 2 PERTZYE-treated patients (≥10%) and at a higher rate than placebo-treated patients in a Clinical Trial of Adult and Pediatric Patients 8 Years of Age and Older with Exocrine Pancreatic Insufficiency Due to Cystic Fibrosis Adverse Reaction PERTZYE N=21 (%) Placebo N=24 (%) Diarrhea 10% 4% Dyspepsia 10% 4% Cough 10% 4% 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of PERTZYE 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. 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 PERTZYE at room temperature 20°C to 25°C (68°F to 77°F), excursions permitted to 15°C to 40°C (59°F to 104°F) for up to 30 days. PERTZYE hard gelatin capsules should be stored in a dry place in the original container or equivalent airtight container. After opening, keep the container tightly closed between uses to protect from moisture. PERTZYE is dispensed in bottles containing a desiccant.