Pancrelipase

1 INDICATIONS AND USAGE CREON ® is indicated for the treatment of exocrine pancreatic insufficiency in adult and pediatric patients. CREON is indicated for the treatment of exocrine pancreatic insufficiency in adult and pediatric patients.

2 DOSAGE AND ADMINISTRATION Important Dosing Information ( 2.1 ) CREON 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 CREON. When switching from another pancreatic enzyme product to CREON, 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. 500 to 1,000 lipase units/kg/meal for adult patients with chronic pancreatitis or pancreatectomy. 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 4,000 lipase units/g fat ingested/day. Higher dosages may be administered if documented effective by fecal fat measures or improvement of malabsorption. Pediatric Patients Birth to 12 Months : The recommended dosage is 3,000 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, bananas, plain Greek yogurt). Do not crush or chew CREON capsules or capsule contents. Consume sufficient liquids to ensure complete swallowing of CREON. ( 5.2 ) See the full prescribing information for additional information on administering to pediatric patients birth to 12 months. 2.1 Important Dosing Information CREON is a mixture of enzymes including lipases, proteases, and amylases. CREON 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 CREON dose for a meal. Do not substitute other pancreatic enzyme products for CREON. When switching from another pancreatic enzyme product to CREON, 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. 500 to 1,000 lipase units/kg/meal for adult patients with chronic pancreatitis or pancreatectomy. 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 3,000 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 CREON during meals and 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, bananas, plain Greek yogurt). Consume the entire mixture immediately. Do not crush or chew CREON capsules or capsule contents. Consume sufficient liquids (water or juice) to ensure complete swallowing of CREON [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 CREON capsule (containing 3,000 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, bananas, plain Greek yogurt) 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 CREON to ensure complete swallowing of the capsule contents. Do not mix CREON capsule contents directly into a bottle of breast milk or formula. Do not crush CREON 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.

6 ADVERSE REACTIONS 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 R eactions ( 6.1 ) C ystic fibrosis adult and pediatric patients : 7 years and older (≥4%): vomiting, dizziness, cough. 4 months to 6 years (6%): vomiting, irritability, decreased appetite. C hronic pancreatitis or pancreatectomy patient s: Adults (≥ 4%): hyperglycemia, hypoglycemia, abdominal pain, abnormal feces, flatulence, frequent bowel movements, nasopharyngitis. To report SUSPECTED ADVERSE REACTIONS, contact AbbVie Inc. at 1-800-633-9110 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 practice. The data described below reflect exposure to CREON in 92 patients: 67 patients aged 4 months to 43 years with exocrine pancreatic insufficiency due to cystic fibrosis (Studies 1, 2, and 3) and 25 adults with exocrine pancreatic insufficiency due to chronic pancreatitis or pancreatectomy (Study 4) [see Use in Specific Populations ( 8.4 ) and Clinical Studies ( 14.1 , 14.2 )] . Exocrine Pancreatic Insufficiency Due to Cystic Fibrosis in Adult and Pediatric Patients Adult and Pediatric Patients 7 Years of Age and Older The most common adverse reactions, reported in at least 2 CREON-treated patients (greater than or equal to 4%) and at a higher rate than in placebo-treated patients in Studies 1 and 2, are shown in Table 1. Table 1: Adverse Reactions* in Clinical Trials of Adult and Pediatric Patients 7 Years of Age and Older with Exocrine Pancreatic Insufficiency due to Cystic Fibrosis (Studies 1 and 2) Adverse Reaction CREON N = 49 n (%) Placebo N = 47 n (%) Vomiting 3 (6%) 1 (2%) Dizziness 2 (4%) 1 (2%) Cough 2 (4%) 0 (0%) * Reported in at least 2 CREON-treated patients (greater than or equal to 4%) and at a higher rate than placebo-treated patients. In Study 1, one patient experienced duodenitis and gastritis of moderate severity 16 days after completing treatment with CREON. Transient neutropenia without clinical sequelae was observed as an abnormal laboratory finding in one patient receiving CREON and a macrolide antibiotic. Pediatric Patients 4 Months to 6 Years of Age Adverse reactions reported in 18 CREON-treated pediatric patients aged 4 months to 6 years in Study 3 were vomiting, irritability, and decreased appetite, each occurring in 6% of patients [see Use in Specific Populations ( 8.4 )] . Exocrine Pancreatic Insufficiency Due to Chronic Pancreatitis or Pancreatectomy in Adults Adverse reactions reported in at least 1 adult CREON-treated patient (greater than or equal to 4%) and at a higher rate than in placebo-treated patients in Study 4 is shown in Table 2. Table 2: Adverse Reactions* in a Clinical Trial of Adult Patients with Exocrine Pancreatic Insufficiency Due to Chronic Pancreatitis or Pancreatectomy (Study 4) Adverse Reaction CREON N = 25 n (%) Placebo N = 29 n (%) Hyperglycemia 2 (8%) 2 (7%) Hypoglycemia 1 (4%) 1 (3%) Abdominal Pain 1 (4%) 1 (3%) Abnormal Feces 1 (4%) 0 (0%) Flatulence 1 (4%) 0 (0%) Frequent Bowel Movements 1 (4%) 0 (0%) Nasopharyngitis 1 (4%) 0 (0%) * Reported in at least 1 CREON-treated patient (greater than or equal to 4%) and at a higher rate than placebo-treated patients. 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of CREON 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 D isorders fibrosing colonopathy and distal intestinal obstruction syndrome abdominal pain, diarrhea, 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

12.3 Pharmacokinetics Following oral administration, the lipases, proteases, and amylases released from CREON are not absorbed from the gastrointestinal tract in appreciable amounts. Drug Interactions The lipases, proteases, and amylases of CREON are not substrates of CYP enzymes or transporters. CYP enzymes or transporters mediated drug interactions are not expected.