ZENPEP DR 5,000 UNIT CAPSULE

Uses Advice to Patients Dosage and Administration Cautions Drug Interactions Pharmacokinetics

Uses

Pancrelipase is used as replacement therapy in the symptomatic treatment of malabsorption syndrome caused by established pancreatic insufficiency of organic origin, as in cystic fibrosis of the pancreas, chronic pancreatitis, pancreatectomy, GI bypass surgery (e.g., Billroth II gastroenterostomy), cancer of the pancreas, or other conditions in which pancreatic insufficiency impairs fat digestion. Pancreatic exocrine replacement therapy should not delay or supplant treatment of the primary disorder.

Although pancrelipase has been used in treating steatorrhea of postgastrectomy syndrome and bowel resection, pancreatic extracts are less likely to be effective in this condition and in cases of malabsorption associated with ileitis, tuberculosis, or lymphomas. Pancrelipase is not effective in the treatment of functional digestive disorders unrelated to pancreatic insufficiency.

Pancrelipase may be used as a presumptive test for pancreatic funtion (e.g., pancreatic insufficiency associated with chronic pancreatitis).

Dosage and Administration

Administration

Pancrelipase is administered orally with meals or snacks. Pancrelipase delayed-release capsules containing enteric-coated spheres, microspheres, or microtablets may be opened and the contents administered with liquids or mixed with soft food; care should be taken so that the powder is not inhaled. Following administration, the patient should drink a glass of water or juice to ensure that the spheres or microtablets are swallowed.

To avoid destruction of the enteric coating, the contents should not be chewed or crushed. Contact with food that has a pH greater than 5.5-6 will dissolve the enteric coating.

Patients receiving pancreatic enzymes should be adequately hydrated.

Dosage

Dosage of pancrelipase depends on the condition being treated and the digestive requirements as related to the diet of the patient. Considerable variation in dosage exists, in part, because of the susceptibility of pancrelipase to acid-peptic inactivation of enzyme activity in the stomach and duodenum. Delayed-release preparations (i.e., capsules containing enteric-coated spheres, microspheres, or microtablets of the drug) are reportedly less susceptible to acid-peptic inactivation since they are designed to disintegrate at a relatively high GI pH (e.g., greater than 5.5-6). Concomitant administration of conventional pancrelipase preparations and antacids or a histamine H₂-receptor antagonist (e.g., cimetidine) has been used to decrease the inactivation of enzyme activity.

It has been suggested that pancrelipase dosage be determined by the fat content of the diet and that approximately 8000 USP units of lipase activity be given for each 17 g of dietary fat. The usual initial adult dosage of pancrelipase is approximately 4000-33,000 USP units of lipase activity before or with each meal or snack. Dosage may be increased as necessary and then reduced as symptomatic improvement occurs. For the treatment of severe deficiency, one manufacturer states that the dose may be increased to 88,000 USP units of lipase activity with each meal or the dosing interval may be increased to hourly if necessary and if nausea, cramping, and/or diarrhea do not occur.

Dosage for children younger than 6 months of age has not been established. Children 6 months to younger than 1 year of age have responded to 2000 USP units of lipase activity given with each meal. Children 1 to younger than 7 years of age may receive 4000-8000 USP units of lipase activity with each meal and 4000 USP units of lipase with each snack. Children younger than 6 years of age receiving the delayed-release capsules may receive 5000-10,000 USP units of lipase activity with each meal or snack. Children 7-12 years of age have received 4000-12,000 USP units of lipase activity with each meal or snack; this dosage may be increased if needed. Children 6 years of age and older receiving the delayed-release capsules may receive an initial dosage of 10,000-20,000 USP units of lipase activity with each meal or snack. Growth curves have been used as end points to aid in the assessment of response in children.

When used for symptomatic treatment of malabsorption syndrome caused by cystic fibrosis in children younger than 6 years of age, pancrelipase may be given at a dosage of 1500-3000 USP units of lipase activity per kg per meal (units/kg per meal). Dosage should be adjusted according to severity of disease, control of steatorrhea, and nutritional status. Doses exceeding 6000 USP units of lipase activity per kg per meal (units/kg per meal) are not recommended. If dosage needs to be increased, body weight and stool fat content should be monitored carefully. If the patient is switched to a pancrelipase preparation of different strength, care should be taken to ensure that the new regimen provides an equivalent number of lipase units per dose.

Cautions

Adverse Effects

Nausea, vomiting, cramping, diarrhea, constipation, and bloating have been reported. Extremely high doses of exogenous pancreatic enzymes have been associated with hyperuricosuria and hyperuricemia.

Precautions and Contraindications

Pancrelipase should be used with extreme caution, if at all, in patients with known hypersensitivity to pork protein. If a hypersensitivity reaction occurs during pancrelipase therapy, the drug should be discontinued and symptomatic and supportive therapy initiated if necessary. Inhalation of pancrelipase powder should be avoided, since it is irritating to the nasal mucosa and respiratory tract and may precipitate bronchospasm in patients sensitized to pancreatic enzyme concentrates.

Strictures in the ileocecal region and/or ascending colon have been reported in patients with cystic fibrosis receiving high doses of high-potency pancreatic enzyme supplements (containing 20,000 USP units or more of lipase per capsule). Although the underlying mechansim has not been elucidated, caution should be used when dosages exceeding 6000 USP units of lipase per kg per meal do not resolve symptoms, especially in patients with a history of intestinal complications (e.g., short bowel syndrome, meconium ileus equivalent, surgery, Crohn's disease).

If symptoms suggestive of GI obstruction occur, the possibility of intestinal stricture should be considered and pancreatic enzyme therapy should be evaluated.

Pancrelipase may decrease serum iron response to oral iron therapy.

Pancrelipase is contraindicated in patients with acute pancreatitis or with acute exacerbations of chronic pancreatitis.

Geriatric Precautions

Clinical studies of pancrelipase did not include sufficient numbers of patients 65 years of age and older to determine whether geriatric patients respond differently than younger patients. Drug dosage generally should be titrated carefully in geriatric patients, usually initiating therapy at the low end of the dosage range. The greater frequency of decreased hepatic, renal, and/or cardiac function and of concomitant disease and drug therapy observed in the elderly also should be considered.

Pregnancy

Although there are no adequate and controlled studies to date in humans, diethylphthalate, a component of the enteric coating of Pancrease and Pancrecarb microspheres, has been shown to be teratogenic in rats when administered intraperitoneally in high doses; no teratogenic or embryocidal effects were observed in rats when given up to 100 times the usual human dose of the coating orally. Pancrease, Pancrease MT, Pancrecarb, or Viokase should be used during pregnancy only when the potential benefits justify the possible risks to the fetus.