Pharmacology Update

Pancrelipase Tablets (Viokace™)

By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD. Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente; and Assistant Professor of Medicine, University of California, San Francisco. Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA. Drs. Elliott and Chan report no financial relationships relevant to this field of study.

The FDA has approved a new pancreatic enzyme preparation for the treatment of pancreatic insufficiency. Pancrelipase contains porcine derived lipases, proteases, and amylases. It is marketed by Aptalis Pharma U.S. Inc. as Viokace.

Indications

Pancrelipase in indicated for use in adults with exocrine pancreatic insufficiency due to chronic pancreatitis or pancreatectomy.1

Dosage

The initial dose is 500 lipase units/kg of body weight per meal taken with a proton pump inhibitor.1 The dose may be increased to a maximum of 2500 lipase units/kg based on symptoms, the degree of steatorrhea, and the fat content of the diet. The dose, however, should be ≤ 10,000 lipase units/kg per day or < 4000 lipase unit/g fat ingested per day.1 One-half of the full dose should be given for snacks. The dose should be taken with a proton pump inhibitor.

Pancrelipase is available as two strengths:

• 10,440 USP units of lipase, 39,150 USP units of protease, and 39,150 USP units of amylase; and

• 20,880 USP units of lipase, 78,300 USP units of pro tease, and 78,300 USP units of amylase.

Both strengths should be administered with a proton pump inhibitor.

Potential Advantage

Viokace does not offer any advantages over currently available pancrelipase products.

Potential Disadvantages

The efficacy and safety of Viokace has not been established in children. Fibrosing colonopathy (colonic stricture) is a rare condition that may be associated with high-dose pancreatic enzyme use of long duration.1 This adverse reaction was most commonly seen in pediatric cystic fibrosis patients. The porcine origin of the enzymes may lead to allergic reaction in patients with allergy to porcine protein, increase uric acid level due to purine contents of the product, and result in unknown viral exposure.1 The most common adverse events (7% [2/30] vs 0% for placebo) were anal pruritus and biliary tract stones.1

Comments

In 2004, the FDA required new drug applications for all pancreatic extract drug products. This was due to evidence of substantial variation in drug potency of currently marketed products. The short-term safety and efficacy was assessed in a randomized, double-blind, placebo-controlled, parallel group study (n = 50).1 Adult patients with exocrine pancreatic insufficiency (pancreatitis or pancreatectomy) were randomized, after a washout period (6-7 days) to pancrelipase (22 tablets per day) or placebo coadministered with a proton pump inhibitor. Patients were maintained on a controlled high-fat diet of 100 g per day. The primary endpoint was the coefficient of fat absorption (CFA) based on a 72-hour stool collection. After a treatment of 6-7 days, the mean CFA was 86% compared to a washout period mean of 48% for pancrealipase. For placebo, CFA was 58% after treatment and a mean of 57% at washout. The mean difference CFA was 28% (95% confidence interval, 21, 37) in favor of pancrelipase.

Clinical Implications

Viokace is the fifth pancrelipase product to be approved. It is the only one that is not formulated as a delayed-release product. Pancrelipase requires coadministration with a proton pump inhibitor and is not approved for cystic fibrosis patients. Other approved pancrelipase products are Creon®, Zenpep®, Pancreaze®, and Ultresa®. The magnitude of mean differences in CFA compared to placebo are similar among these products: 28% for Viokace, 21% for Creon, 26% for Zenpep, and 35% for Ultresa.3-5

While the prescribing information for each product states that the pancrelipase products are not interchangeable, the maximum doses for each product are identical, as they are set forth by the Cystic Fibrosis Foundation Consensus Conference Guidelines.6

References

1. Viokace Prescribing Information. Birmingham, AL: Aptalis Pharma US Inc.; March 2012.

2. http://www.fda.gov/cder/drug/infopage/pancreatic_drugs/default.htm. Accessed April 5, 2012.

3. Creon Prescribing Information. Abbott Park, IL: Abbott Laboratories; July 2011.

4. Zenpep Prescribing Information. Yardley, PA: Eurand Pharmaceuticals; June 2011.

5. Ultresa Prescribing Information. Birmingham, AL: Aptalis Pharma US Inc.; March 2012.

6. Borowitz DS, et al. Consensus report on nutrition for pediatric patients with cystic fibrosis. J Pediatr Gastroenterol Nutr 2002;35:246-259.