Rx Product News Profile: A Closer Look at New FDA Actions: Creon

Ms. Domenici and Ms. Patel are both pharmacists at Brigham and Women's Hospital, Boston, Massachusetts. Mr. DeCosta and Ms. Viscusi are both sixth-year pharmacy students at Massachusetts College of Pharmacy in Boston, Massachusetts.

Solvay Pharmaceuticals' Creon (pancrelipase) Delayed-Release Capsules

On May 1, 2009, the FDA announced the approval of Solvay Pharmaceuticals Inc's Creon (pancrelipase) delayed-re lease capsules for the treatment of exocrine pancreatic insufficiency (EPI) due to cystic fibrosis (CF) or other conditions.¹ Creon is the first pancreatic enzyme product (PEP) to receive FDA approval under new guidelines for the class.¹

Clinical Pharmacology

Creon contains pancreatic enzymes that are enteric-coated to resist destruction or inactivation at gastric pH. 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. Thus, Creon acts as a replacement for the digestive enzymes normally secreted by the pancreas.

Pharmacokinetics

Pancrelipase products are not interchangeable. Creon is not absorbed following oral administration because pancreatic enzymes are not absorbed from the gastrointestinal (GI) tract in any appreciable amount and are not systemically active.² The enzymes exert their action locally in the GI tract. Excretion occurs via the feces.³

Dose recommendations should follow the Cystic Fibrosis Foundation Consensus Conference Guidelines. Patients can be dosed on a schedule based on fat ingestion or actual body weight. It is recommended that doses be initiated as low as possible and gradually increased. Dose adjustments should be based on clinical response, fat content of diet, and presence of steatorrhea.²

Clinical Trials

In order to obtain FDA approval, efficacy was determined in a randomized, double-blind, placebo-controlled, crossover trial of 32 patients with exocrine pancreatic insufficiency due to CF (aged 12-43 years). The subjects received pancrelipase (4000 lipase units/g fat ingested per day) or placebo once daily for 5 to 6 days, followed by crossover to the alternate treatment for an additional 5 to 6 days. The primary end point was the mean difference in the coefficient of fat absorption (CFA) between Creon and placebo treatment.²

CFA was determined by a 72-hour stool collection during treatment with either active drug or placebo. Both fat ingestion and fat excretion were measured. The mean CFA reduction from baseline to day 5 or 6 was 89% for the Creon treatment, compared with 49% for the placebo treatment.²

No significant differences were found in patient response between men and women, nor between younger and older patients.²

Precautions

Creon should be used with caution during pregnancy (Category C). Although no conclusive data in humans exists of Creon being excreted in breast milk, nursing mothers should use caution while using this product.³

Fibrosing colonopathy has been associated with use of high-dose pancreatic enzyme replacement therapy in CF patients. The fibrotic changes may occur with use of Creon doses exceeding 2500 lipase units/kg of body weight per meal or greater than 10,000 lipase units/kg of body weight per day.¹

Creon should not be chewed, crushed, or mixed in foods with a pH less than 4, as there is a potential for irritation of the oral mucosa. ²

Creon is a porcine-derived product containing purines that may result in an increase of blood uric acid levels. Thus, patients with gout, renal impairment, and/or hyperuricemia should use caution when taking Creon.² Patients who are allergic to porcine products should avoid the use of Creon. There is a theoretical risk for transmission of viral disease, including diseases caused by novel or unidentified viruses. The presence of porcine viruses that may cross-infect humans cannot be definitively excluded; however, no cases have been reported.³

• Solvay Pharmaceuticals Press Release http://www.prnewswire.com/mnr/solvay/37345/.
• Creon (Pancrelipase) Delayed Release Capsules Package Insert
• Uloric. In DRUGDEX System [Internet database]. Greenwood Village, Colorado: Thomson Reuters (Healthcare) Inc. Updated periodically.Assessed 29 March 2009.