PRESCRIBING INFORMATION

DESCRIPTION

CREON® 20 Capsules are orally administered and contain 497 mg of delayed-release MINIMICROSPHERES® of pancrelipase, which is of porcine pancreatic origin. Each CREON® 20 Capsule contains lipase 20,000 USP Units, protease 75,000 USP Units and amylase 66,400 USP Units.

Inactive ingredients include dibutyl phthalate, dimethicone, hydroxypropylmethylcellulose phthalate, light mineral oil and polyethylene glycol. The capsule shells contain gelatin, red iron oxide, titanium dioxide and yellow iron oxide. The capsule imprinting ink contains dimethicone, 2-ethoxyethanol, shellac, soya lecithin, and titanium dioxide.

CLINICAL PHARMACOLOGY

The pancreatic enzymes in CREON® 20 Capsules are enteric-coated to resist gastric destruction or inactivation. The pancreatic enzymes catalyze the hydrolysis of fats to glycerol and fatty acids, protein into proteoses and derived substances and starch into dextrins and short chain sugars.

INDICATIONS

CREON® 20 Capsules are indicated for patients with pancreatic exocrine insufficiency as is often associated with:

• cystic fibrosis
• chronic pancreatitis
• post-pancreatectomy
• post-gastrointestinal bypass surgery (e.g., Billroth II gastroenterostomy)
• ductal obstruction from neoplasm (e.g., of the pancreas or common bile duct)

CONTRAINDICATIONS

CREON® 20 Capsules are contraindicated in the early stages of acute pancreatitis or in patients who are known to be hypersensitive to pork protein.

WARNINGS

Should symptoms of hypersensitivity appear, discontinue medication and initiate symptomatic and supportive therapy if necessary.

Strictures in the ileo-cecal region and/or ascending colon have been reported in cystic fibrosis patients treated with high doses of high-potency pancreatic enzyme supplements containing 20,000 or greater USP units of lipase per capsule. The underlying mechanism is unknown, but caution should be exercised when doses in excess of 6,000 USP units lipase per kg per meal fail to resolve symptoms, especially in patients with a history of intestinal complications such as meconium ileus equivalent, short bowel syndrome, surgery or Crohn's disease. If symptoms suggestive of gastrointestinal obstruction occur, the possibility of bowel stricture should be investigated including evaluation of pancreatic enzyme therapy.

PRECAUTIONS

CREON® 20 Capsules MINIMICROSPHERES® SHOULD NOT BE CRUSHED OR CHEWED or placed on foods having a pH greater than 5.5. These can dissolve the protective enteric coating resulting in early release of enzymes, irritation of oral mucosa, and/or loss of enzyme activity.

Information for Patients

CREON® 20 Capsules are a pancreatic enzyme product prescribed to promote improved digestion of foods, especially fat. The prescribed dosage should be taken with each meal and snack or as directed by the physician. The capsules can be swallowed whole, or the contents poured on soft, bland food. Care should be taken to avoid chewing or crushing of the capsule contents, which can result in early release of enzymes, irritation of oral mucosa, and/or loss of enzyme activity. Patients should maintain adequate fluid intake. The prescribed dose range should not be exceeded without calling your doctor.

The most common adverse reactions involve the stomach and intestine including diarrhea, nausea, vomiting, bloating, constipation, stomach cramps or pain. If these symptoms are persistent, contact your doctor.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term studies in animals have not been performed to evaluate carcinogenic potential.

Pregnancy, Category C

Animal reproduction studies have not been conducted with pancrelipase. It is also not known whether pancrelipase can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. CREON® 20 Capsules should be given to a pregnant woman only if clearly needed.

Nursing Mothers

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when CREON® 20 Capsules are administered to a nursing mother.

ADVERSE REACTIONS

The most frequently reported adverse reactions to pancreatic enzyme-containing products are gastrointestinal in nature which may include nausea, vomiting, bloating, cramping, constipation or diarrhea. Less frequently, allergic-type reactions have also been observed. Very high doses of pancreatin have been associated with hyperuricosuria and hyperuricemia.

DOSAGE AND ADMINISTRATION

Clinical experience should dictate initial starting dose. Doses should be taken during meals or snacks, not before or after. Do not take without food.

Adults and Children Over 6 Years Old

Usual initial starting dosage is one CREON® 20 Capsule per meal or snack.

Children Under 6 Years Old

The exact dosage of CREON® 20 Capsules should be selected based on clinical experience for this age group.

For cystic fibrosis patients, typical doses are 1,500-3,000 USP lipase units/kg/meal. Dosage should be adjusted according to the severity of the disease, control of steatorrhea and maintenance of good nutritional status. Doses in excess of 6,000 USP lipase units/kg/meal are not recommended.

Dose increases, if required, should occur with careful monitoring of body weight and stool fat content. When changing strengths of pancreatic enzyme products, care should be taken to maintain equivalent lipase units for each divided dosage.

It is important to ensure adequate hydration of patients at all times while taking pancreatic enzymes.

Where swallowing of capsules is difficult, the capsules may be carefully opened and the MINIMICROSPHERES® added to a small amount of soft food, with a pH less than 5.5. The soft food should be swallowed immediately without chewing and followed with a glass of water or juice to insure swallowing.

HOW SUPPLIED

CREON® 20 MINIMICROSPHERES® (Pancrelipase Delayed-release Capsules, USP) are available in a two-piece gelatin capsule (orange opaque top half, natural transparent bottom half) imprinted in white with "SOLVAY" and "1220". Each capsule contains tan-colored delayed-release MINIMICROSPHERES® of pancrelipase supplied in bottles of:

CREON® 20 Capsules must be stored at 25°C (77°F); excursions permitted to 15°-30°C (59°-86°F). [See USP Controlled Room Temperature.] PROTECT FROM MOISTURE. DO NOT REFRIGERATE. Dispense in tight, light-resistant containers. For human consumption only.

Manufactured By:

Solvay Pharmaceuticals GmbH,

Hannover, Germany

Marketed by:

Solvay

Pharmaceuticals, Inc.

Marietta, GA 30062

500199 Rev Nov 2004

© 2004 Solvay Pharmaceuticals, Inc.