36,000 USP units of lipase; 114,000 USP units of protease; 180,000 USP units of amylase delayed-release capsules have a blue opaque cap with imprint “Creon 1236” and a colorless transparent body. The shells contain gelatin, titanium dioxide, FD&C Blue No. 2 and sodium lauryl sulfate.

Creon - Clinical Pharmacology
Mechanism of Action
The pancreatic enzymes in Creon catalyze the hydrolysis of fats to monoglyceride, glycerol and free fatty acids, proteins into peptides and amino acids, and starches into dextrins and short chain sugars such as maltose and maltriose in the duodenum and proximal small intestine, thereby acting like digestive enzymes physiologically secreted by the pancreas.

Pharmacokinetics
The pancreatic enzymes in Creon are enteric-coated to minimize destruction or inactivation in gastric acid. Creon is designed to release most of the enzymes in vivo at an approximate pH of 5.5 or greater. Pancreatic enzymes are not absorbed from the gastrointestinal tract in appreciable amounts.

Nonclinical Toxicology
Carcinogenesis, Mutagenesis, Impairment of Fertility
Carcinogenicity, genetic toxicology, and animal fertility studies have not been performed with pancrelipase.

Clinical Studies
The short-term efficacy of Creon was eva luated in three studies conducted in 103 patients with exocrine pancreatic insufficiency (EPI). Two studies were conducted in 49 patients with EPI due to cystic fibrosis (CF); one study was conducted in 54 patients with EPI due to chronic pancreatitis or pancreatectomy.

Cystic Fibrosis
Studies 1 and 2 were randomized, double-blind, placebo-controlled, crossover studies in 49 patients, ages 7 to 43 years, with exocrine pancreatic insufficiency due to cystic fibrosis. Study 1 included patients aged 12 to 43 years (n = 32). The final analysis population was limited to 29 patients; 3 patients were excluded due to protocol deviations. Study 2 included patients aged 7 to 11 years (n = 17). The final analysis population was limited to 16 patients; 1 patient withdrew consent prior to stool collection during treatment with Creon. In each study, patients were randomized to receive Creon at a dose of 4,000 lipase units/g fat ingested per day or matching placebo for 5 to 6 days of treatment, followed by crossover to the alternate treatment for an additional 5 to 6 days. All patients consumed a high-fat diet (greater than or equal to 90 grams of fat per day, 40% of daily calories derived from fat) during the treatment periods.

The coefficient of fat absorption (CFA) was determined by a 72-hour stool collection during both treatments, when both fat excretion and fat ingestion were measured. Each patient's CFA during placebo treatment was used as their no-treatment CFA value.

In Study 1, mean CFA was 89% with Creon treatment compared to 49% with placebo treatment. The mean difference in CFA was 41 percentage points in favor of Creon treatment with 95% CI: (34, 47) and p<0.001.

In Study 2, mean CFA was 83% with Creon treatment compared to 47% with placebo treatment. The mean difference in CFA was 35 percentage points in favor of Creon treatment with 95% CI: (27, 44) and p<0.001.

Subgroup analyses of the CFA results in Studies 1 and 2 showed that mean change in CFA with Creon treatment was great