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CLINICAL PHARMACOLOGY The buffer-stabilized pancreatic enzymes in PANCRECARB® (pancrelipase) Delayed-Release are enteric-coated with a gastric acid resistant polymer to protect the enzymes during gastric transit into the duodenum. After being swallowed, the gelatin capsules dissolve in the gastric juice within minutes and the released microspheres disperse with food in the stomach. Upon passing into the duodenum, the enteric-coated PANCRECARB® (pancrelipase) microspheres are activated at approximately pH 5.5, discharge their digestive enzymes and the released digestive enzymes help to re-establish the natural digestive conditions in the intestine. The digestive enzymes in PANCRECARB® (pancrelipase) act locally in the gastrointestinal tract. The digestive enzymes hydrolyze fats into glycerol and fatty acids, proteins into peptides and amino acids, and starch into dextrins and maltrose. Once the digestive enzymes accomplish their catalytic function to hydrolyze food, the digestive enzymes may be inactivated by anti-enzymes which are secreted by the intestinal mucosa or digested by proteases. The digested enzyme fragments may be absorbed from the intestine and subsequently excreted into the urine. The inactivated enzymes are excreted in the feces.

PANCRECARB (pancrelipase) Delayed-Release Capsules, Buffered and Enteric-Coated Microspheres. DESCRIPTION PANCRECARB® (pancrelipase) contain buffered pancreatic enzymes: lipase, amylase and protease, isolated and concentrated from porcine pancreatic glands. The enzyme containing microspheres are coated with a pH sensitive enteric-coating to provide protection against gastric inactivation of the buffer-stabilized enzymes during gastric passage. EACH PANCRECARB® (pancrelipase) CONTAINS: MS-4 MS-8 Lipase 4,000 U.S.P. Units 8,000 U.S.P. Units Amylase 25,000 U.S.P. Units 40,000 U.S.P. Units Protease 25,000 U.S.P. Units 45,000 U.S.P. Units Inactive ingredients include sodium carbonate, sodium bicarbonate, cellulose acetate phthalate, diethyl phthalate, gelatin, sodium carboxymethyl starch, polyvinylpyrrolidone, talc, ursodiol, and other trace ingredients.

INDICATIONS PANCRECARB® (pancrelipase) Delayed-Release Capsules, Buffered and Enteric-Coated Microspheres are indicated for patients with exocrine pancreatic enzyme insufficiency such as: cystic fibrosis, chronic pancreatitis due to alcohol use or other causes, post-pancreatectomy and post-gastrointestinal bypass surgery (e.g. Billroth II gastroenterostomy). DOSAGE AND ADMINISTRATION Dosing, Duration Of Therapy Dosage should be individualized and adjusted according to fat intake, severity of steatorrhea and the severity of the exocrine pancreatic insufficiency. Begin therapy with one or two capsules with meals or snacks and adjust dosage according to symptoms. Dose increases, if required, should be made slowly, with careful monitoring of response and symptomatology. It is important to ensure adequate hydration of patients at all times while taking PANCRECARB® (pancrelipase) . Patients with pancreatic enzyme insufficiency should consume a high-caloric diet with unrestricted fat intake, which is appropriate for age and clinical symptomology. HOW SUPPLIED PANCRECARB® (pancrelipase) are supplied as follows: PANCRECARB® (pancrelipase) MS-4 (clear, hard gelatin capsule imprinted in blue with "DCI" and "PANCRECARB® (pancrelipase) MS-4") in bottles of 100 (NDC 59767-002-01). PANCRECARB® (pancrelipase) MS-8 (clear, hard gelatin capsule imprinted in blue with "DCI" and "PANCRECARB® (pancrelipase) MS-8") in bottles of 100 (NDC 59767-001-01). PANCRECARB® (pancrelipase) MS-16 (clear, hard gelatin capsule imprinted in blue with "DCI" and "PANCRECARB® (pancrelipase) MS-16") in bottles of 100 (NDC 59767-003-01). Storage Store at controlled room temperature 25ºC (77ºF) in a dry place. Do not refrigerate. Do not expose capsules to humid air. Keep bottle tightly closed. Dispense capsules in a tight container. Manufacturer information. n/a. FDA rev date: n/a

OVERDOSE No information provided. CONTRAINDICATIONS PANCRECARB® (pancrelipase) Delayed-Release Capsules, Buffered and Enteric-Coated Microspheres are contraindicated in patients known to be hypersensitive to pork protein or any other ingredient of this product.

SIDE EFFECTS The most frequently reported adverse reactions to pancrelipase-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. Extremely high doses of exogenous pancreatic enzymes have been reported to be associated with hyperuricosuria and hyperuricemia. High strength pancrelipase preparation (i.e., those labeled as containing more than 20,000 lipase units per capsule) has been associated with colonic strictures. DRUG INTERACTIONS No information provided.

WARNINGS Should hypersensitivity occur during the course of treatment, discontinue medication and treat symptomatically. Cases of intestinal stricture and blockage requiring surgical decompression have been reported in cystic fibrosis patients, especially in patients with a history of intestinal complications such as meconium ileus equivalent, short bowel syndrome, surgery or Crohn's disease, who were taking high potency lipase pancreatic enzyme preparations (i.e., those labeled as containing more than 20,000 lipase units per capsule). If symptoms suggestive of gastrointestinal obstruction occur, the possibility of bowel strictures should be considered including the evaluation of pancreatic enzyme therapy. Patients receiving lipase dose of > 2,500 USP units per kilogram per meal should be re-evaluated and the lipase dose either be reduced by 50% or titrated down gradually to the lowest clinically effective dose as determined by 72-hour fecal fat excretion. PRECAUTIONS GENERAL - TO PROTECT ENTERIC COATING, MICROSPHERES SHOULD NOT BE CRUSHED OR CHEWED. The microsphere-containing capsules should be swallowed with liquids at the start of a meal. Where swallowing of capsules is difficult, the capsules may be carefully opened and the microspheres shaken into a small quantity of soft food such as applesauce, jelly, jello, etc., which does not require chewing, and swallowed immediately, followed by a glass of water or juice to ensure complete swallowing. Prolonged contact of the microspheres with foods having a pH greater than 5.5 can weaken the integrity of the protective enteric coat and compromise the potency of the enzymes. Carcinogenesis, Mutagenesis, Impairment of Fertility Long-term studies in animals have not been performed with PANCRECARB® (pancrelipase) delayed-release capsules. Pregnancy/Reproduction Pregnancy Category C. Diethylphthalate, an enteric coating component of PANCRECARB® (pancrelipase) have been shown to be teratogenic in rats following high intraperitoneal dosing. When this coating was given orally to rats up to 100 times the human dose, however, no teratogenic or embryocidal effects were observed.