tiple enzyme classes, including porcine-derived lipases, proteases, and amylases.
Pancrelipase is a beige-white amorphous powder. It is miscible in water and practically insoluble or insoluble in alcohol and ether.
Each delayed-release capsule for oral administration contains enteric-coated spheres (0.71–1.60 mm in diameter).
The active ingredient eva luated in clinical trials is lipase. CREON is dosed by lipase units.
Other active ingredients include protease and amylase.
CREON contains the following inactive ingredients: cetyl alcohol, dimethicone, hypromellose phthalate, polyethylene glycol, and triethyl citrate. The imprinting ink on the capsule contains dimethicone, 2-ethoxyethanol, shellac, soya lecithin, and titanium dioxide.
6,000 USP units of lipase; 19,000 USP units of protease; 30,000 USP units of amylase capsules have a Swedish-orange opaque cap with imprint “CREON 1206” and a blue opaque body. The shells contain FD&C Blue No. 2, gelatin, red iron oxide, sodium lauryl sulfate, titanium dioxide, and yellow iron oxide.
12,000 USP units of lipase; 38,000 USP units of protease; 60,000 USP units of amylase capsules have a brown opaque cap with imprint “CREON 1212” and a colorless transparent body. The shells contain black iron oxide, gelatin, red iron oxide, sodium lauryl sulfate, titanium dioxide, and yellow iron oxide.
24,000 USP units of lipase; 76,000 USP units of protease; 120,000 USP units of amylase capsules have a Swedish-orange opaque cap with imprint “CREON 1224” and a colorless transparent body. The shells contain gelatin, red iron oxide, sodium lauryl sulfate, titanium dioxide, and yellow iron oxide.
12 CLINICAL PHARMACOLOGY
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12.1 Mechanism of Action
The pancreatic enzymes in CREON are enteric-coated to resist destruction or inactivation in gastric acid, and to release most of the enzymes in vivo in the duodenum at a pH greater than 5.5. In the duodenum and proximal small intestine, the enzymes 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, thereby acting as a replacement for digestive enzymes physiologically secreted by the pancreas.
Pancreatic enzymes are not absorbed from the gastrointestinal tract in any appreciable amount, and are not systemically active.
13 NONCLINICAL TOXICOLOGY
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13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
Carcinogenicity, genetic toxicology, and animal fertility studies have not been performed.
14 CLINICAL STUDIES
The short-term efficacy and safety of CREON were eva luated in one double-blind, placebo-controlled, crossover study in 32 patients, ages 12 to 43 years, with exocrine pancreatic insufficiency due to cystic fibrosis. The final analysis population was limited to 29 patients; 3 patients were excluded due to protocol deviations. 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 100 grams of fat per day) during the treatment periods. The primary efficacy endpoint was the mean difference in the coefficient of fat absorption (CFA) between CREON and placebo treatment. The CFA was determined b |
