Clinical Context

In the United States, approximately 200,000 patients have pancreatic insufficiency. Many pancreatic enzyme products (PEPs) have been available and are used to treat pancreatic insufficiency, but the US Food and Drug Administration (FDA) asked manufacturers of unapproved products to cease distribution by April 28, 2010. There are currently 3 FDA-approved PEPs on the market: Creon, Zenpep, and Pancreaze. The FDA has now approved 2 new PEPs: Ultresa delayed-release capsules and Viokace tablets, which are both combinations of porcine-derived lipases, proteases, and amylases.

Study Synopsis and Perspective

The FDA has approved 2 new PEPs to aid food digestion: pancrelipase delayed-release capsules (Ultresa, Aptalis Pharma) and pancrelipase tablets (Viokace, Aptalis Pharma).

Ultresa is indicated for the treatment of exocrine pancreatic insufficiency due to cystic fibrosis (CF) or other conditions. Viokace, in combination with a proton pump inhibitor, is indicated for the treatment of exocrine pancreatic insufficiency from chronic pancreatitis or pancreatectomy.

"The approvals of Ultresa and Viokace, along with the other approved pancreatic enzyme products, allow health care providers to prescribe the product that is most appropriate for the estimated 200,000 patients in the United States who have pancreatic insufficiency," said Julie Beitz, MD, the director of the Office of Drug Evaluation III in FDA's Center for Drug Evaluation and Research.

Although many PEPs are available, the FDA established that makers of these products should stop manufacturing and distributing unapproved products by April 28, 2010.

The two new products add to 3 approved PEPs: Creon (Abbott Laboratories), Zenpep (Aptalis), and Pancreaze (Janssen Pharmaceuticals, Inc).

At an FDA Pediatric Advisory Committee Meeting held January 30, 2012, the 3 forms of pancrelipase were recommended for return to routine monitoring during an abbreviated review that indicated no new safety signals in pediatric patients.

A manufacturer press release states that the 2 newly approved products will be launched in the United States in the near future.

Common Adverse Effects and Cautions for PEPs

The most common (> 7%) adverse reactions in patients treated with Ultresa were headache, pharyngolaryngeal pain, and epistaxis, whereas with Viokace, the most common effects were biliary tract stones and anal pruritus.

The manufacturer recommends that Ultresa not be chewed or retained in the mouth, to avoid irritation of oral mucosa. The maker adds that caution should be exercised with use of Ultresa in patients with gout, renal impairment, or hyperuricemia. The manufacturer also warns of a theoretic risk for viral transmission with all PEPs, including Ultresa and Viokace. High-dose use of pancreatic enzyme replacement has also been linked to fibrosing colonopathy.

The FDA notes that PEPs are not approved for administration via gastrostomy tubes, but "a small number of patients may require PEPs to be given through this route. Manufacturers of approved PEPs are currently conducting tests to evaluate the feasibility of administering PEPs via gastrostomy tubes."

They also suggest to healthcare professionals that, when switching a patient to another PEP, they should start with a similar amount of lipase enzyme, then adjust the dose according to the patient's response. They should also recognize that it may take 1 to 2 weeks for a patient to adjust to the dose of the new PEP.

Individual patient response should be monitored when a patient is switched from an unapproved PEP to an approved one.

Viokace Dosage and Administration

The specific dosage and administration information for Viokace tablets requires that the drug be swallowed whole. Pancrelipase products are not interchangeable with each other. Dosing should not exceed the maximal dosage specified in the Cystic Fibrosis Foundation Consensus Conferences Guidelines and should be individualized based on clinical symptoms, the amount of steatorrhea, and dietary fat content. Starting dose should be 500 lipase units/kg of body weight per meal, to a maximum of 2500 lipase units/kg of body weight per meal or 10,000 lipase units/kg of body weight per day.

Viokace Warnings and Precautions

Like Ultresa, Viokace should not be chewed or retained in the mouth (to avoid irritation of oral mucosa), and caution is needed in patients with gout, renal impairment, or hyperuricemia.

Patients with known allergy to porcine proteins of origin require that the clinician prescribing pancrelipase exercise caution.

In pediatric patients, the safety and efficacy of Viokace have not been determined. Because of tablet degradation in the gastric environment, children taking Viokace may have suboptimal growth. Pediatric patients in whom pancreatic enzymes are indicated should generally use delayed-release (enteric-coated) capsules.

Dosing Information for Ultresa

In pediatric patients, use of Ultresa is limited by the available capsule dosage strengths and their ability to deliver the recommended dose based on age and weight. The capsules should be swallowed whole and not crushed or chewed, but for children or patients unable to swallow intact capsules, the contents may be sprinkled on applesauce, yogurt, or other acidic soft food with a pH of 4.5 or less.

Dosing should not exceed the maximal dosage recommended by the Cystic Fibrosis Foundation Consensus Conferences Guidelines. Children 1 to 4 years old and weighing at least 14 kg should begin with 1000 lipase units/kg of body weight per meal and should not exceed 2500 lipase units/kg of body weight per meal, or 10,000 lipase units/kg of body weight per day, or 4000 lipase units/g fat ingested per day.

For children at least 4 years old and weighing at least 28 kg, and for adults, the starting dose should be 500 lipase units/kg of body weight per meal. The maximal dose should be 2500 lipase units/kg of body weight per meal, or not exceeding 10,000 lipase units/kg of body weight per day or 4000 lipase units/g fat ingested per day. Dividing the capsule contents into small fractions to deliver small doses of lipase is not recommended.

More information on the PEPs Ultresa and Viokace is available on the FDA Web site.

Laurie Barclay, MD, has contributed to this article.

Clinical Implications

• Ultresa delayed-release capsules are approved by the FDA to treat exocrine pancreatic insufficiency caused by CF or other conditions. Viokace tablets, in combination with a proton pump inhibitor, are FDA approved to treat exocrine pancreatic insufficiency caused by chronic pancreatitis or pancreatectomy.
• Viokace should be swallowed whole and not chewed or retained in the mouth. Caution is needed in patients with gout, renal impairment, hyperuricemia, or known allergy to porcine proteins. The safety and efficacy of Viokace have not been determined in pediatric patients, and pancrelipase products are not interchangeable with each other. Dosing should be individualized based on clinical symptoms, the amount of steatorrhea, and dietary fat content.
• Use of Ultresa in pediatric patients is limited by the available capsule dosage strengths and their ability to deliver the recommended dose based on age and weight. The capsules should be swallowed whole and not crushed or chewed, but the contents of the capsules may be sprinkled on acidic soft food. However, dividing the capsule contents into small fractions to deliver small doses of lipase is not recommended.

CME Test