Pertzye Drug Information

® 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.

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 . 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.

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.

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 . 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 . If a dose is missed, administer the next dose with the next feeding.

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 . 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%

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

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 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.

Pediatric Use The safety and effectiveness of PERTZYE for the treatment of exocrine pancreatic insufficiency have been established in pediatric patients. Use of PERTZYE for this indication is supported by a randomized, double-blind, placebo-controlled, crossover study of 24 pediatric patients, 8 years and older with exocrine pancreatic insufficiency due to cystic fibrosis. The safety in pediatric patients was similar to that observed in adult patients . Dosages exceeding 6,000 lipase units/kg/meal have been reported postmarketing to be associated with fibrosing colonopathy and colonic strictures in pediatric patients less than 12 years of age.

If there is a history of fibrosing colonopathy, monitor patients during treatment with PERTZYE because some patients may be at risk of progressing to stricture formation. 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 in pediatric patients greater than 12 months of age without further investigation . Crushing or chewing PERTZYE capsules or mixing the capsule contents in foods having a pH greater than 4.5 can disrupt the protective enteric coating on the capsule contents and result in early release of enzymes, irritation of the oral mucosa, and/or loss of enzyme activity. Instruct the patient or caregiver of the following: consume sufficient liquids (juice, water, breast milk, or formula) to ensure complete swallowing, and visually inspect the mouth of pediatric patients less than 12 months of age to ensure that no drug is retained in the mouth and irritation of the oral mucosa has not occurred .

Chronic high dosages of pancreatic enzyme products have been associated with fibrosing colonopathy and colonic strictures . High dosages of pancreatic enzyme products have been associated with hyperuricosuria and hyperuricemia .