Zenpep

ZENPEP^® is indicated for the treatment of exocrine pancreatic insufficiency in adult and pediatric patients.

• ZENPEP 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 Fibrosing Colonopathy

  Fibrosing colonopathy has been reported following treatment with pancreatic enzyme products. Fibrosing colonopathy is a rare serious adverse reaction initially described in association with use of high-dose pancreatic enzyme products, usually with use over a prolonged period of time and most commonly reported in pediatric patients with cystic fibrosis. Pancreatic enzyme products exceeding 6,000 lipase units/kg/meal have been associated with colonic stricture, a complication of fibrosing colonopathy, in pediatric patients less than 12 years of age. The underlying mechanism of fibrosing colonopathy remains unknown.

  If there is a history of fibrosing colonopathy, monitor patients during treatment with ZENPEP because some patients may be at risk of progressing to colonic stricture formation. It is uncertain whether regression of fibrosing colonopathy occurs. 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 adult and pediatric patients greater than 12 months of age without further investigation

  .

  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. Patients receiving dosages higher than 6,000 lipase units/kg/meal should be frequently monitored for symptoms of fibrosing colonopathy and the dosage decreased or titrated downward to a lower range if clinically appropriate

  [see Dosage and Administration (2.1)]

  .
  )
• 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 ZENPEP. When switching from another pancreatic enzyme product to ZENPEP, monitor patients for clinical symptoms of exocrine pancreatic insufficiency and titrate the dosage as needed. 

• 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 of age to less than 4 years of age.

• Titrate 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 in malabsorption.

• 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, pears).
• Do not crush or chew ZENPEP capsules or capsule contents.
• Consume sufficient liquids to ensure complete swallowing of ZENPEP. (
  5.2 Irritation of the Oral Mucosa

  Crushing or chewing ZENPEP 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:

  • Swallow capsules whole. For patients who cannot swallow the capsules whole, the capsules can be opened, and the contents sprinkled on a small amount of acidic soft food with a pH of 4.5 or less (e.g., commercially available preparations of applesauce, bananas or pears).
  • Do not crush or chew ZENPEP capsules or capsule contents.
  • Consume sufficient liquids (juice, water, breast milk, or formula) immediately following administration of ZENPEP to ensure complete swallowing.
  • Visually inspect the mouth of pediatric patients less than 12 months of age and of patients who are unable to swallow intact capsules to ensure no drug is retained in the mouth and irritation of the oral mucosa has not occurred
    [see Dosage and Administration (2.3)]
    .
  )
• See the full prescribing information for additional information on administering to pediatric patients birth to 12 months. (
  2.3 Preparation and Administration Instructions

  Instruct adult and pediatric patients greater than 12 months of age, or their caregivers, of the following:

  • Take ZENPEP during 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., commercially available preparations of applesauce, bananas, or pears). Consume the entire mixture immediately.
  • Do not crush or chew ZENPEP capsules or capsule contents.
  • Consume sufficient liquids (water or juice) to ensure complete swallowing of ZENPEP
    [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 ZENPEP 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., commercially available preparations of applesauce, bananas or pears) 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 ZENPEP to ensure complete swallowing of the capsule contents.
  • Do not mix the ZENPEP capsule contents directly into a bottle of breast milk or formula.
  • Do not crush ZENPEP 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.
  )

Delayed-release capsules are available in the following strengths:

• 3,000 USP units of lipase; 10,000 USP units of protease; and 14,000 USP units of amylase in a two‑piece hypromellose capsule with a white opaque cap and white opaque body, and red imprint with "APTALIS 3"
• 5,000 USP units of lipase; 17,000 USP units of protease; and 24,000 USP units of amylase in a two‑piece hypromellose capsule with a white opaque cap and white opaque body, and blue imprint with "APTALIS 5"
• 10,000 USP units of lipase; 32,000 USP units of protease; and 42,000 USP units of amylase in a two-piece hypromellose capsule with a yellow opaque cap and white opaque body, and blue imprint with "APTALIS 10"
• 15,000 USP units of lipase; 47,000 USP units of protease; and 63,000 USP units of amylase in a two-piece hypromellose capsule with a red opaque cap and white opaque body, and blue imprint with "APTALIS 15"
• 20,000 USP units of lipase; 63,000 USP units of protease; and 84,000 USP units of amylase in a two-piece hypromellose capsule with a green opaque cap and white opaque body, and blue imprint with "APTALIS 20"
• 25,000 USP units of lipase; 79,000 USP units of protease; and 105,000 USP units of amylase in a two-piece hypromellose capsule with a blue opaque cap and white opaque body, and blue imprint with "APTALIS 25"
• 40,000 USP units of lipase; 126,000 USP units of protease; and 168,000 USP units of amylase in a two-piece hypromellose capsule with an orange opaque cap and white opaque body, and blue imprint with "APTALIS 40"
• 60,000 USP units of lipase; 189,600 USP units of protease; 252,600 USP units of amylase. Capsules have a powder blue opaque cap with two black stripes and white opaque body, black imprint with "APTALIS
  60
  "

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.

• Fibrosing Colonopathy
  : Associated with high doses, usually over prolonged use and in pediatric patients with cystic fibrosis. Colonic stricture reported in pediatric patients less than 12 years of age with dosages exceeding 6,000 lipase units/kg/meal. Monitor during treatment for progression of preexisting disease. Do not exceed the recommended dosage, unless clinically indicated. (
  2.1 Important Dosing Information

  ZENPEP is a mixture of enzymes including lipases, proteases, and amylases. ZENPEP 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 ZENPEP dose for a meal.
  • Do not substitute other pancreatic enzyme products for ZENPEP. When switching from another pancreatic enzyme product to ZENPEP, monitor patients for clinical symptoms of exocrine pancreatic insufficiency and titrate the dosage as needed.
  ,
  5.1 Fibrosing Colonopathy

  Fibrosing colonopathy has been reported following treatment with pancreatic enzyme products. Fibrosing colonopathy is a rare serious adverse reaction initially described in association with use of high-dose pancreatic enzyme products, usually with use over a prolonged period of time and most commonly reported in pediatric patients with cystic fibrosis. Pancreatic enzyme products exceeding 6,000 lipase units/kg/meal have been associated with colonic stricture, a complication of fibrosing colonopathy, in pediatric patients less than 12 years of age. The underlying mechanism of fibrosing colonopathy remains unknown.

  If there is a history of fibrosing colonopathy, monitor patients during treatment with ZENPEP because some patients may be at risk of progressing to colonic stricture formation. It is uncertain whether regression of fibrosing colonopathy occurs. 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 adult and pediatric patients greater than 12 months of age without further investigation

  .

  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. Patients receiving dosages higher than 6,000 lipase units/kg/meal should be frequently monitored for symptoms of fibrosing colonopathy and the dosage decreased or titrated downward to a lower range if clinically appropriate

  [see Dosage and Administration (2.1)]

  .
  )
• Irritation of the Oral Mucosa
  : May occur due to loss of protective enteric coating on the capsule contents. (
  2.3 Preparation and Administration Instructions

  Instruct adult and pediatric patients greater than 12 months of age, or their caregivers, of the following:

  • Take ZENPEP during 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., commercially available preparations of applesauce, bananas, or pears). Consume the entire mixture immediately.
  • Do not crush or chew ZENPEP capsules or capsule contents.
  • Consume sufficient liquids (water or juice) to ensure complete swallowing of ZENPEP
    [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 ZENPEP 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., commercially available preparations of applesauce, bananas or pears) 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 ZENPEP to ensure complete swallowing of the capsule contents.
  • Do not mix the ZENPEP capsule contents directly into a bottle of breast milk or formula.
  • Do not crush ZENPEP 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.
  ,
  5.2 Irritation of the Oral Mucosa

  Crushing or chewing ZENPEP 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:

  • Swallow capsules whole. For patients who cannot swallow the capsules whole, the capsules can be opened, and the contents sprinkled on a small amount of acidic soft food with a pH of 4.5 or less (e.g., commercially available preparations of applesauce, bananas or pears).
  • Do not crush or chew ZENPEP capsules or capsule contents.
  • Consume sufficient liquids (juice, water, breast milk, or formula) immediately following administration of ZENPEP to ensure complete swallowing.
  • Visually inspect the mouth of pediatric patients less than 12 months of age and of patients who are unable to swallow intact capsules to ensure no drug is retained in the mouth and irritation of the oral mucosa has not occurred
    [see Dosage and Administration (2.3)]
    .
  )
• Hyperuricemia
  : Reported with high dosages; consider monitoring blood uric acid levels in patients with gout, renal impairment, or hyperuricemia. (
  5.3 Hyperuricemia

  Pancreatic enzyme products contain purines that may increase blood uric acid levels. High dosages have been associated with hyperuricosuria and hyperuricemia

  [see Overdosage (10)].

  Consider monitoring blood uric acid levels in patients with gout, renal impairment, or hyperuricemia during treatment with ZENPEP.
  )
• Risk of Viral Transmission
  : The presence of porcine viruses that might infect humans cannot be definitely excluded. (
  5.4 Risk of Viral Transmission

  ZENPEP is sourced from pancreatic tissue from swine used for food consumption. Although the risk that ZENPEP will transmit an infectious agent to humans has been reduced by testing for certain viruses during manufacturing and by inactivating certain viruses during manufacturing, there is a theoretical risk for transmission of viral disease, including diseases caused by novel or unidentified viruses. Thus, the presence of porcine viruses that might infect humans cannot be definitely excluded. However, no cases of transmission of an infectious illness associated with the use of porcine pancreatic extracts have been reported.
  )
• Hypersensitivity Reactions
  : Monitor patients with known reactions to proteins of porcine origin. If symptoms occur, initiate appropriate medical management; consider the risks and benefits of continued treatment. (
  5.5 Hypersensitivity Reactions

  Severe hypersensitivity reactions including anaphylaxis, asthma, hives, and pruritus have been reported with pancreatic enzyme products

  [see Adverse Reactions (6.2)]

  . If symptoms occur, initiate appropriate medical management.

  Monitor patients with a known hypersensitivity reaction to proteins of porcine origin for hypersensitivity reactions during treatment with ZENPEP. The risks and benefits of continued ZENPEP treatment in patients with severe hypersensitivity reactions should be taken into consideration with the overall clinical needs of the patient.
  )