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Special Alerts
Pancreatic Enzyme Replacement Products: Pancreaze™ to Replace Pancrease® MT
July 2010
Pancreaze™ delayed-release capsules (pancrelipase) received FDA approval as a pancreatic enzyme replacement product (PEP) in April 2010 and became available in July 2010. Patients currently receiving the non-FDA-approved product Pancrease® MT should be transitioned to the FDA-approved product, Pancreaze™. Pharmacies should not dispense Pancrease® MT after July 31, 2010, and should return any remaining inventory of Pancrease® MT to the manufacturer.
Unapproved PEPs are no longer allowed to be distributed in the U.S. There are three PEPs with FDA approval commercially available in the U.S.: Creon®, Pancreaze™, and Zenpep™. PEPs are not interchangeable, and patients will require new prescriptions when changing from one product to another. However, Pancrelipase™ lipase 5000 units strength (manufactured by Eurand Pharmaceuticals and distributed by X-Gen Pharmaceuticals) is an authorized generic which may be used interchangeably with the Zenpep™ lipase 5000 units product (manufactured by Eurand Pharmaceuticals).
For additional information, please refer to the following websites:
http://www.ashp.org/Import/PRACTICEANDPOLICY/PracticeResourceCenters/DrugShortages/GettingStarted/CurrentShortages/Bulletin.aspx?id=619
http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm204745.htm
Pronunciation
(pan kre LYE pase)
Generic Available (U.S.)
Yes
Index Terms
Medication Guide
An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:
Creon®: http://www.fda.gov/downloads/Drugs/DrugSafety/UCM152847.pdf
Pancreaze™: http://www.fda.gov/downloads/Drugs/DrugSafety/UCM208531.pdf
Zenpep™: http://www.fda.gov/downloads/Drugs/DrugSafety/UCM180714.pdf
REMS Components
Medication Guide
U.S. Brand Names
Canadian Brand Names
Pharmacologic Category
Use: Labeled Indications
Treatment of exocrine pancreatic insufficiency (EPI) due to conditions such as cystic fibrosis (Creon®, Pancreaze™, Zenpep™); chronic pancreatitis (Creon®); or pancreatectomy (Creon®)
Pregnancy Risk Factor
C
Pregnancy Considerations
Reproduction studies have not been conducted. Nutrition should be optimized in pregnancy; in cystic fibrosis patients with malabsorption, pancreatic enzyme replacement is not considered to cause a risk to the pregnancy.
Lactation
Excretion in breast milk unknown/use caution
Breast-Feeding Considerations
Systemic absorption and concentration into the breast milk is unlikely, but unknown.
Contraindications
There are no contraindications listed in the manufacturer's labeling.
Warnings/Precautions
Concerns related to adverse effects:
• Fibrosing colonopathy: Fibrosing colonopathy advancing to colonic strictures have been reported with doses of lipase >6000 units/kg/meal over long periods of time in children <12 years of age. Patients taking doses of lipase >6000 units/kg/meal should be examined and the dose decreased. Doses of lipase >2500 units/kg/meal (or lipase >10,000 units/kg/day) should be used with caution and only with documentation of 3-day fecal fat measures.
• Mucosal irritation: Crushing or chewing the contents of the capsules, or mixing the contents with foods outside of product labeling, may cause early release of the enzymes, causing irritation of the oral mucosa and/or loss of enzyme activity. When mixing the contents of capsules with food, the mixture should be swallowed immediately and followed with water or juice to ensure complete ingestion.
Disease-related concerns:
• Gout, hyperuricemia: Use caution in patients with gout or hyperuricemia; products contain purines which may increase uric acid concentrations.
• Renal impairment: Use caution in patients with renal impairment; products contain purines which may increase uric acid concentrations.
Dosage form specific issues:
• Brand interchangeability: Available products are not interchangeable.
• Pork: Products are derived from porcine pancreatic glands. Severe, allergic reactions (rare) have been observed; use with caution in patients hypersensitive to pork proteins. Transmission of porcine viruses is theoretically a risk; however, testing and/or inactivation or removal of certain viruses, reduces the risk. There have been no cases of transmission of an infectious illness reported.
Adverse Reactions
The following adverse reactions were reported in a short-term safety studies; actual frequency varies with different products; adverse events, particularly gastrointestinal events, were often greater with placebo:
10%:
Central nervous system: Headache (6% to 15%)
Gastrointestinal: Abdominal pain (4% to 18%)
1% to 10%:
Central nervous system: Dizziness (6%)
Endocrine & metabolic: Diabetes mellitus exacerbation (4%), hyperglycemia (4%), hypoglycemia (4%)
Gastrointestinal: Flatulence (4% to 9%), early satiety (6%), weight loss (3% to 6%), upper abdominal pain (≤5%), diarrhea (≤4%), feces abnormal (≤4%)
Respiratory: Cough (6%), nasopharyngitis (4%)
<1%, postmarketing, and/or case reports (reported with various formulations of pancrelipase): Allergic reactions (severe), anaphylaxis, asthma, carcinoma recurrence, constipation, distal intestinal obstruction syndrome (DIOS), duodenitis, fibrosing colonopathy, gastritis, hives, hyperuricemia, muscle spasm, myalgia, nausea, neutropenia (transient), pruritus, rash, transaminases increased (asymptomatic), urticaria, vision blurred
Drug Interactions
Iron Salts: Pancrelipase may decrease the absorption of Iron Salts. Exceptions: Ferumoxytol; Iron Dextran Complex; Iron Sucrose. Risk C: Monitor therapy
Ethanol/Nutrition/Herb Interactions
Food: Avoid placing contents of opened capsules on alkaline food; pancrelipase may impair absorption of oral iron.
Storage
Creon®: Store at room temperature of 25°C (77°F); excursions permitted between 25°C to 40°C (77°F to 104°F) for ≤30 days. Protect from moisture, and discard if moisture conditions are >70%. Keep bottle tightly closed.
Pancreaze™: Store at ≤25°C (77°F). Protect from moisture; keep bottle tightly closed.
Zenpep™: Store at room temperature 20°C to 25°C (68°F to 77°F). Protect from moisture; keep bottle tightly closed after opening.
Mechanism of Action
Pancrelipase is a natural product harvested from the porcine pancreatic glands. It contains a combination of lipase, amylase, and protease. Products are formulated to dissolve in the more basic pH of the duodenum so that they may act locally to break down fats, protein, and starch.
Pharmacodynamics/Kinetics
Absorption: None; acts locally in GI tract
Excretion: Feces
Dosage
Oral: Note: Adjust dose based on body weight, clinical symptoms, and stool fat content. Allow several days between dose adjustments. Total daily dose reflects ~3 meals/day and 2-3 snacks/day, with half the mealtime dose given with a snack. Doses of lipase >2500 units/kg/meal (or lipase >10,000 units/kg/day) should be used with caution and only with documentation of 3-day fecal fat measures. Doses of lipase >6000 units/kg/meal are associated with colonic stricture and should be decreased.
Pancreatic insufficiency:
Children:
≤1 year: Lipase 2000-4000 units per 120 mL of formula or breast milk
>1 and <4 years: Initial dose: Lipase 1000 units/kg/meal. Dosage range: Lipase 1000-2500 units/kg/meal. Maximum dose: Lipase 10,000 units/kg/day or lipase 4000 units/g of fat per day
≥4 years: Refer to adult dosing
Adults: Initial: Lipase 500 units/kg/meal. Dosage range: Lipase 500-2500 units/kg/meal. Maximum dose: Lipase 10,000 units/kg/day or lipase 4000 units/g of fat per day
Pancreatic insufficiency due to chronic pancreatitis or pancreatectomy (Creon®): Adults: Lipase 72,000 units/meal while consuming ≥100 g of fat per day; alternatively, lower initial doses of lipase 500 units/kg/meal with individualized dosage titrations have also been used
Administration: Oral
Administer with meals or snacks and swallow whole with a generous amount of liquid. Do not crush or chew; retention in the mouth before swallowing may cause mucosal irritation and stomatitis. If necessary, capsules may also be opened and contents added to a small amount of an acidic food (pH ≤4), such as applesauce. The food should be at room temperature and swallowed immediately after mixing. The contents of the capsule should not be crushed or chewed. Follow with water or juice to ensure complete ingestion and that no medication remains in the mouth.
Creon®: Capsules contain enteric coated spheres which are 0.71-1.6 mm in diameter
Pancreaze™: Capsules contain enteric coated microtablets which are ~2 mm in diameter
Zenpep™: Capsules contain enteric coated beads which are 1.8-2.5 mm in diameter
When administering to infants <1 year of age, do not mix with breast milk or infant formula. Open capsule and place the contents directly into the mouth or mix with a small amount of applesauce, commercially prepared pears, or bananas baby food. Administer immediately after mixing (or within 15 minutes of mixing using Pancreaze™). Follow with water or infant formula to ensure complete ingestion and that no medication remains in the mouth.
Monitoring Parameters
Abdominal symptoms, nutritional intake, weight, growth (in children), stool character, fecal fat
Dietary Considerations
Take with meals or snacks and swallow whole with a generous amount of liquid. Vitamin supplementation should be per current guidelines for patients with cystic fibrosis.
Patient Education
Take right before or with foods, and swallow whole with a generous amount of liquid. Dairy products may have a high pH and should not be taken together with this medication. Do not crush or chew the contents of the capsules. Delayed-release capsules containing enteric-coated microspheres or microtablets may be opened and the contents sprinkled on soft food; do not chew. Report unusual rash, persistent GI upset, or respiratory difficulty.
Geriatric Considerations
No special considerations are necessary since drug is dosed to response; however, drug-induced diarrhea can result in unwanted side effects (eg, confusion, hypotension, lethargy, fluid and electrolyte loss).
Additional Information
Pancreatic enzyme replacement products (PEP) may not be used interchangeably; however, Pancrelipase™ lipase 5000 units strength manufactured by Eurand Pharmaceuticals and distributed by X-Gen Pharmaceuticals is an authorized generic which may be used interchangeably with the Zenpep™ lipase 5000 units product (manufactured by Eurand Pharmaceuticals).
Dental Health: Effects on Dental Treatment
No significant effects or complications reported
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
None reported
Mental Health: Effects on Psychiatric Treatment
None reported
Nursing: Physical Assessment/Monitoring
Dosing and administration depend on purpose for use and formulation (available products are not interchangeable).
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, delayed release, enteric coated beads [porcine derived]:
Pancrelipase™: Lipase 5000 units, protease 17,000 units, amylase 27,000 units
Zenpep™: Lipase 5000 units, protease 17,000 units, amylase 27,000 units
Zenpep™: Lipase 10,000 units, protease 34,000 units, amylase 55,000 units
Zenpep™: Lipase 15,000 units, protease 51,000 units, amylase 82,000 units
Zenpep™: Lipase 20,000 units, protease 68,000 units, amylase 109,000 units
Capsule, delayed release, enteric coated microspheres [new formulation; porcine derived]:
Creon®: Lipase 6000 units, protease 19,000 units, and amylase 30,000 units
Creon®: Lipase 12000 units, protease 38,000 units, and amylase 60,000 units
Creon®: Lipase 24,000 units, protease 76,000 units, and amylase 120,000 units
Capsule, delayed release, enteric coated microtablets [porcine derived]:
Pancreaze™: Lipase 4200 units, protease 10,000 units, and amylase 17,500 units
Pancreaze™: Lipase 10,500 units, protease 25,000 units, and amylase 43,750 units
Pancreaze™: Lipase 16,800 units, protease 40,000 units, and amylase 70,000 units
Pancreaze™: Lipase 21,000 units, protease 37,000 units, and amylase 61,000 units
Pricing: U.S. (www.drugstore.com)
Capsule, enteric pellets (Creon 10)
33.2-10-37.5 units (100): $134.93
Capsule, enteric pellets (Creon 20)
66.4-20-75 units (100): $243.78
Capsule, enteric pellets (Creon 5)
16.6-5-18.75 units (100): $86.14
References
Baker SS, “Delayed Release Pancrelipase for the Treatment of Pancreatic Exocrine Insufficiency Associated With Cystic Fibrosis,” Ther Clin Risk Manag, 2008, 4(5):1079-84.
Borowitz D, Baker RD, and Stallings V, “Consensus Report on Nutrition for Pediatric Patients With Cystic Fibrosis,” J Pediatr Gastroenterol Nutr, 2002, 35(3):246-5.
Borowitz DS, Grand RJ, and Durie PR, “Use of Pancreatic Enzyme Supplements for Patients With Cystic Fibrosisin the Context of Fibrosing Colonopathy. Consensus Committee,” J Pediatr, 1995, 127(5):681-4.
Edenborough FP, Borgo G, Knoop C, et al, “Guidelines for the Management of Pregnancy in Women With Cystic Fibrosis,” J Cyst Fibros, 2008, 7 Suppl 1:2-32.
FitzSimmons SC, Burkhart GA, Borowitz D, et al, “High-Dose Pancreatic-Enzyme Supplements and Fibrosing Colonopathy in Children With Cystic Fibrosis,” N Engl J Med, 1997, 336(18):1283-9.
Pettei MJ, Leonidas JC, Levinne JJ, et al, “Pancolonic Disease in Cystic Fibrosis and High-Dose Pancreatic Enzyme Therapy,” J Pediatr, 1994, 125(4):587-9.
Stallings VA, Stark LJ, Robinson KA, et al, “Evidence-Based Practice Recommendations for Nutrition-Related Management of Children and Adults With Cystic Fibrosis and Pancreatic Insufficiency: Results of a Systematic Review,” J Am Diet Assoc, 2008, 108(5):832-9.
Taylor CG, “Colonic Strictures in Cystic Fibrosis,” Lancet, 1994, 343(8898):615-6.
International Brand Names
Lexi-Comp.com
Last full review/revision May 2011
Content last modified May 2011
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