CREON (pancrelipase) delayed-release capsules

CREON (pancrelipase) delayed-release capsules

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CREON (pancrelipase) delayed-release capsules

CREON is a pancreatic enzyme preparation consisting of pancrelipase, an extract derived from porcine pancreatic glands. Pancrelipase contains multiple 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 evaluated 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.

Indications and usage

CREON is a combination of porcine-derived lipases, proteases, and amylases indicated for the treatment of exocrine pancreatic insufficiency due to cystic fibrosis, chronic pancreatitis, pancreatectomy, or other conditions

Mechanism of Action

The pancreatic enzymes in CREON catalyze the hydrolysis of fats to monoglyceride, glycerol and free fatty acids, proteins into peptides and amino acids, and starches into dextrins and short chain sugars such as maltose and maltriose in the duodenum and proximal small intestine, thereby acting like digestive enzymes physiologically secreted by the pancreas.

Dosage and administration

CREON is not interchangeable with other pancrelipase products.

CREON is orally administered. Therapy should be initiated at the lowest recommended dose and gradually increased. The dosage of CREON should be individualized based on clinical symptoms, the degree of steatorrhea present, and the fat content of the diet

Infants (up to 12 months): CREON should be administered to infants immediately prior to each feeding, using a dosage of 3,000 lipase units per 120 mL of formula or prior to breast-feeding. Contents of the capsule may be administered directly to the mouth or with a small amount of applesauce. Administration should be followed by breast milk or formula. Contents of the capsule should not be mixed directly into formula or breast milk as this may diminish efficacy. Care should be taken to ensure that CREON is not crushed or chewed or retained in the mouth, to avoid irritation of the oral mucosa.

Children and Adults: CREON should be taken during meals or snacks, with sufficient fluid. CREON capsules and capsule contents should not be crushed or chewed. Capsules should be swallowed whole.

Dosage

Dosage recommendations for pancreatic enzyme replacement therapy were published following the Cystic Fibrosis Foundation Consensus Conferences. CREON should be administered in a manner consistent with the recommendations of the Cystic Fibrosis Foundation Consensus Conferences (also known as Conferences) provided in the following paragraphs, except for infants. Although the Conferences recommend doses of 2,000 to 4,000 lipase units in infants up to 12 months, CREON is available in a 3,000 lipase unit capsule. Therefore, the recommended dose of CREON in infants up to 12 months is 3,000 lipase units per 120 mL of formula or per breast-feeding. Patients may be dosed on a fat ingestion-based or actual body weight-based dosing scheme.

Infants (up to 12 months): CREON is available in the strength of 3,000 USP units of lipase thus infants may be given 3,000 lipase units (one capsule) per 120 mL of formula or per breast-feeding. Do not mix CREON capsule contents directly into formula or breast milk prior to administration

Children Older than 12 Months and Younger than 4 Years: Enzyme dosing should begin with 1,000 lipase units/kg of body weight per meal for children less than age 4 years to a maximum of 2,500 lipase units/kg of body weight per meal (or less than or equal to 10,000 lipase units/kg of body weight per day), or less than 4,000 lipase units/g fat ingested per day.

Children 4 Years and Older and Adults: Enzyme dosing should begin with 500 lipase units/kg of body weight per meal for those older than age 4 years to a maximum of 2,500 lipase units/kg of body weight per meal (or less than or equal to 10,000 lipase units/kg of body weight per day), or less than 4,000 lipase units/g fat ingested per day.

Usually, half of the prescribed CREON dose for an individualized full meal should be given with each snack. The total daily dose should reflect approximately three meals plus two or three snacks per day.

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Contraindications

None

Warnings and precautions

Fibrosing Colonopathy: Fibrosing colonopathy has been reported following treatment with different pancreatic enzyme products. Fibrosing colonopathy is a rare, serious adverse reaction initially described in association with high-dose pancreatic enzyme use, usually over a prolonged period of time and most commonly reported in pediatric patients with cystic fibrosis.

Doses greater than 2,500 lipase units/kg of body weight per meal (or greater than 10,000 lipase units/kg of body weight per day) should be used with caution and only if they are documented to be effective by 3-day fecal fat measures that indicate a significantly improved coefficient of fat absorption. Patients receiving higher doses than 6,000 lipase units/kg of body weight per meal should be examined and the dosage either immediately decreased or titrated downward to a lower range.

Potential for Irritation to Oral Mucosa: Care should be taken to ensure that no drug is retained in the mouth. CREON should not be crushed or chewed or mixed in foods having a pH greater than 4.5. These actions can disrupt the protective enteric coating resulting in early release of enzymes, irritation of oral mucosa, and/or loss of enzyme activity

Potential for Risk of Hyperuricemia: Caution should be exercised when prescribing CREON to patients with gout, renal impairment, or hyperuricemia. Porcine-derived pancreatic enzyme products contain purines that may increase blood uric acid levels.

Potential Viral Exposure from the Product Source: CREON is sourced from pancreatic tissue from swine used for food consumption. Although the risk that CREON will transmit an infectious agent to humans has been reduced by testing for certain viruses during manufacturing and by inactivating certain viruses during manufacturing, there is a theoretical risk for transmission of viral disease, including diseases caused by novel or unidentified viruses. Thus, the presence of porcine viruses that might infect humans cannot be definitely excluded. However, no cases of transmission of an infectious illness associated with the use of porcine pancreatic extracts have been reported.

Allergic Reactions: Caution should be exercised when administering pancrelipase to a patient with a known allergy to proteins of porcine origin. Rarely, severe allergic reactions including anaphylaxis, asthma, hives, and pruritus, have been reported with other pancreatic enzyme products with different formulations of the same active ingredient (pancrelipase).

Drug interactions

No drug interactions have been identified. No formal interaction studies have been conducted.

Use in specific populations

Pregnancy

Teratogenic effects

Pregnancy Category C

It is not known whether pancrelipase can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. CREON should be given to a pregnant woman only if clearly needed. The risk and benefit of pancrelipase should be considered in the context of the need to provide adequate nutritional support to a pregnant woman with exocrine pancreatic insufficiency. Adequate caloric intake during pregnancy is important for normal maternal weight gain and fetal growth. Reduced maternal weight gain and malnutrition can be associated with adverse pregnancy outcomes.

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 is administered to a nursing woman. The risk and benefit of pancrelipase should be considered in the context of the need to provide adequate nutritional support to a nursing mother with exocrine pancreatic insufficiency.

Geriatric Use: Clinical studies of CREON did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients.

Overdosage

There have been no reports of overdose in clinical trials or postmarketing surveillance with this formulation of CREON. Chronic high doses of pancreatic enzyme products have been associated with fibrosing colonopathy and colonic strictures. High doses of pancreatic enzyme products have been associated with hyperuricosuria and hyperuricemia, and should be used with caution in patients with a history of hyperuricemia, gout, or renal impairment.

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