General Information

The pancreatic enzymes in Zenpep catalyze the hydrolysis of fats to monoglycerol, glycerol and fatty acids, protein into peptides and amino acids, and starch into dextrins and short chain sugars in the duodenum and proximal small intestine, thereby acting like digestive enzymes physiologically secreted by the pancreas.

Zenpep is specifically indicated for the treatment of exocrine pancreatic insufficiency due to cystic fibrosis or other conditions.

Zenpep is supplied as a capsule for oral administration. The recommended initial dose of the drug is as follows:

Infants (up to 12 months)

2,000 to 4,000 lipase units per 120 mL of formula or per breast-feeding. Do not mix Zenpep capsule contents directly into formula or breast milk prior to administration.

Children Older than 12 Months and Younger than 4 Years

1,000 lipase units/kg of body weight per meal for children less than age 4 years to a maximum of 2,500 lipase units/kg of body weight per meal (or less than or equal to 10,000 lipase units/kg of body weight per day), or less than 4,000 lipase units/g fat ingested per day.

Children 4 Years and Older and Adults

dosing should begin with 500 lipase units/kg of body weight per meal for those older than age 4 years to a maximum of 2,500 lipase units/kg of body weight per meal (or less than or equal to 10,000 lipase units/kg of body weight per day), or less than 4,000 lipase units/g fat ingested per day.

Zenpep should be taken during meals or snacks, with sufficient fluid. Zenpep capsules and capsule contents should not be crushed or chewed.

Limitations on Dosing: Doses greater than 2,500 lipase units/kg of body weight per meal (or greater than 10,000 lipase units/kg of body weight per day) should be used with caution and only if they are documented to be effective by 3-day fecal fat measures that indicate a significantly improved coefficient of fat absorption.

Mechanism of Action

Clinical Trial Results

The FDA approval of Zenpep was based on the results of two clinical studies in patients with exocrine pancreatic insufficiency (EPI) associated with cystic fibrosis (CF).

Study One
This randomized, double-blind, placebo-controlled, crossover study enrolled 34 patients, ages 7 to 23 years. Results are from 32 subjects who completed both double-blind treatment periods, and were included in the efficacy analysis population. The subjects were randomized to receive Zenpep or matching placebo for 6 to 7 days of treatment, followed by crossover to the alternate treatment for an additional 6 to 7 days. The mean dose during the controlled treatment periods ranged from a mean dose of 3,900 lipase units per kilogram per day to 5,700 lipase units per kilogram per day. All patients consumed a high-fat diet (greater than or equal to 100 grams of fat per day) during the treatment period. The primary efficacy endpoint was the mean difference in the coefficient of fat absorption (CFA) between Zenpep and placebo treatment. Mean CFA was 88% with Zenpep treatment compared to 63% with placebo treatment. The mean difference in CFA was 26 percentage points in favor of Zenpep treatment (p<0.001). Subgroup analyses of the CFA results showed that mean change in CFA was greater in patients with lower no-treatment (placebo) CFA values than in patients with higher no-treatment (placebo) CFA values.

Study Two
All subjects in this study were transitioned to Zenpep from their usual PEP treatment. After a 4-14 days screening period on the current PEP, subjects received Zenpep at individually titrated doses ranging between 2,300 and 10,000 lipase units per kg body weight per day, with a mean of approximately 5000 lipase units per kg body weight per day (not to exceed 2,500 lipase units per kilogram per meal) for 14 days. There was no wash-out period. Overall, patients showed similar control of fat malabsorption by spot fecal fat testing when switched to Zenpep treatment at similar doses.