Viokace

1. INDICATIONS AND USAGE 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. ( 1 )

2. DOSAGE AND ADMINISTRATION Important Dosing Information ( 2.1 ) 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. ( 5.1 ) 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. ( 2.3 ) Consume sufficient liquids to ensure complete swallowing of VIOKACE tablets. ( 2.3 , 5.2 ) 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 [see Warnings and Precautions (5.1) ] . 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 [see Warnings and Precautions (5.2) ] .

3. DOSAGE FORMS AND STRENGTHS 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 ( 3 ): 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

4. CONTRAINDICATIONS None. None. ( 4 )

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) ] Potential for Exacerbation of Symptoms of Lactose Intolerance [see Warnings and Precautions (5.6) ] Most common adverse reactions (≥7%) are: anal pruritus and biliary tract stones. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Aimmune Therapeutics, Inc at 1-833-AIM2KNO (1-833-246-2566) 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 VIOKACE in 30 adult patients with exocrine pancreatic insufficiency due to chronic pancreatitis or pancreatectomy in a single, multicenter, randomized, parallel, placebo-controlled, double-blind study [see Clinical Studies (14) ] . Adverse reactions that were reported in at least 2 VIOKACE-treated patients (greater than or equal to 7%) are shown in Table 1. There were no adverse reactions reported in two or more patients in the placebo group (N=20). Table 1: Adverse Reactions Reported in at least 2 VIOKACE-treated patients (greater than or equal to 7%) and at a higher rate than placebo-treated patients. in a Clinical Trial of Adult Patients with Exocrine Pancreatic Insufficiency Due to Chronic Pancreatitis or Pancreatectomy Adverse Reaction VIOKACE N = 30 (%) Anal pruritus 2 (7%) Biliary tract stones 2 (7%) The following adverse reactions were reported in one VIOKACE-treated patient each: anemia, abdominal pain, ascites, flatulence, headache, hydocholecystis, peripheral edema, rash, renal cyst, and viral infection. 6.2. Postmarketing Experience The following adverse reactions have been identified during post-approval use of VIOKACE 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 and distal intestinal obstruction syndrome abdominal pain, diarrhea, flatulence, constipation, and nausea Immune System Disorders anaphylaxis, asthma, hives and pruritis Investigations asymptomatic elevations of liver enzymes Musculoskeletal System myalgia, muscle spasm Skin and Subcutaneous Tissue Disorders urticaria and rash

8. USE IN SPECIFIC POPULATIONS Pediatrics: VIOKACE use in pediatric patients may result in suboptimal weight gain, malnutrition and/or need for larger doses. The safety and effectiveness of VIOKACE in pediatric patients have not been established. ( 8.4 ) 8.1. Pregnancy Risk Summary Published data from case reports with pancrelipase use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes. Pancrelipase is minimally absorbed systematically; therefore, maternal use is not expected to result in fetal exposure to the drug. Animal reproduction studies have not been conducted with pancrelipase. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. 8.2. Lactation Risk Summary There are no data on the presence of pancrelipase in either human or animal milk, the effects on the breastfed infant, or the effects on milk production. Pancrelipase is minimally absorbed systemically following oral administration, therefore maternal use is not expected to result in clinically relevant exposure of breastfed infants to the drug. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for VIOKACE and any potential adverse effects on the breastfed child from VIOKACE or from the underlying maternal conditions. 8.4. Pediatric Use The safety and effectiveness of VIOKACE in pediatric patients have not been established. Use of VIOKACE in pediatric patients may increase the risk of inadequate treatment of pancreatic insufficiency and result in suboptimal weight gain, malnutrition and/or need for larger doses of pancreatic enzyme replacement due to tablet degradation in the gastric environment of the stomach. High dosages of pancreatic enzyme products have been associated with fibrosing colonopathy and colonic strictures in pediatric patients less than 12 years of age [see Warnings and Precautions (5.1) ] . 8.5. Geriatric Use Clinical studies of VIOKACE did not include sufficient numbers of patients aged 65 years and over to determine whether they respond differently from younger patients. Other reported clinical experience has not identified differences in responses between patients aged 65 years and over and younger adult patients.

12.1. Mechanism of Action Pancreatic enzyme products contain a mixture of lipases, proteases, and amylases that catalyze the hydrolysis of fats to monoglycerides, glycerol and free fatty acids, proteins into peptides and amino acids, and starches into dextrins and short chain sugars such as maltose and maltriose in the duodenum and proximal small intestine, thereby acting like digestive enzymes physiologically secreted by the pancreas.

11. DESCRIPTION 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.

10. OVERDOSAGE Chronic high dosages of pancreatic enzyme products have been associated with fibrosing colonopathy and colonic strictures [see Warnings and Precautions (5.1) ] . High dosages of pancreatic enzyme products have been associated with hyperuricosuria and hyperuricemia [see Warnings and Precautions (5.3) ] .

16. HOW SUPPLIED/STORAGE AND HANDLING VIOKACE (pancrelipase) tablets are supplied as follows: Strength Description Supplied As NDC Number 10,440 USP units of lipase; 39,150 USP units of protease; 39,150 USP units of amylase tan, round, biconvex tablet with VIO9111 engraved on one side and 9111 on the other side bottles of 100 73562-104-10 20,880 USP units of lipase; 78,300 USP units of protease; 78,300 USP units of amylase tan, oval, biconvex tablet with V 16 engraved on one side and 9116 on the other side bottles of 100 73562-208-10 Storage and Handling Store VIOKACE at room temperature 20°C to 25°C (68°F to 77°F), and protect from moisture. Brief excursions permitted up to 40°C (104°F) for 24 hours. After opening, keep the container tightly closed between uses to protect from moisture . Store and dispense VIOKACE in the original container. VIOKACE is dispensed in bottles containing a desiccant.