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Special Alerts
Pancreatic Enzyme Replacement Products
In May 2009, the U.S. Food and Drug Administration (FDA) announced that it approved Creon® (pancrelipase) as a pancreatic enzyme replacement product (PEP). This is the first product approved since the FDA notified manufacturers that new drug applications (NDAs) would be required to continue their marketing of these products in the United States. Although some formulations have been on the market prior to the Federal Food, Drug, and Cosmetic Act of 1938, an FDA review found that variations in their manufacturing process resulted in differences in potency which could affect safety and effectiveness.
PEPs are not interchangeable. The recently approved Creon® product is not interchangeable with Creon® formulations previously available, and patients will require new prescriptions to continue taking this medication. All currently marketed PEPs will need FDA approval by April 2010.
For additional information, refer to the following FDA websites:
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm149579.htm
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2004/ucm108289.htm
Medication Safety Issues
Sound-alike/look-alike issues:
Pancrease® may be confused with Pentasa®
Pangestyme™ may be confused with Pentasa®
Viokase® may be confused with Viokase® 8
Viokase® 8 may be confused with Viokase®
Pronunciation
(pan kre LYE pase)
U.S. Brand Names
Index Terms
Generic Available
No
Canadian Brand Names
Pharmacologic Category
Use: Labeled Indications
Treatment of exocrine pancreatic insufficiency (EPI) due to conditions such as cystic fibrosis
Use: Unlabeled/Investigational
Treatment of occluded feeding tubes
Pregnancy Risk Factor
B/C (product specific)
Pregnancy Considerations
Reproduction studies have not been conducted with all products currently marketed (category C). When conducted, adverse events were not observed in animal reproduction studies at doses close to the maximum recommended human dose (category B). 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
Specific products may be contraindicated with hypersensitivity to pork protein or any component of the formulation; acute pancreatitis or acute exacerbations of chronic pancreatic disease
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 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 having a pH >4, 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 levels.
• Renal impairment: Use caution in patients with renal impairment; products contain purines which may increase uric acid levels.
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 and some products are specifically contraindicated in patients hypersensitive to pork proteins. Transmission of porcine viruses is a risk but has not been reported.
• Powder: Avoid inhalation of powder; may cause nasal and respiratory tract irritation.
Adverse Reactions
The following adverse reactions were reported in a short-term safety study with Creon® [new formulation]; gastrointestinal adverse events were greater with placebo:
1% to 10%:
Central nervous system: Dizziness (6%), headache (6%)
Gastrointestinal: Abdominal pain (9%), flatulence (9%), feces abnormal (3%), weight loss (3%), duodenitis, gastritis
Hematologic: Neutropenia
Respiratory: Cough (6%)
Adverse reactions reported with various formulations of pancrelipase products: Allergic reactions (severe), anaphylaxis, asthma, carcinoma recurrence, distal intestinal obstruction syndrome (DIOS), fibrosing colonopathy, hives, nausea, pruritus, rash, urticaria
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® [new formulation]: 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.
Pancrease® MT: Store in a tightly closed container and in a dry place at ?25°C (77°F); do not refrigerate.
Ultrase®, Ultrase® MT: Store at room temperature of 15°C to 25°C (59°F to 77°F) in a dry place; do not refrigerate.
Viokase®: Store in a tightly closed container and in a dry place at ?25°C (77°F).
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:
Malabsorption: 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 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.
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
Elderly: Older patients may need fewer lipase units/kg due to increased weight, but decreased ingestion of fat/kg.
Occluded feeding tubes (unlabeled use): Adults: One tablet of Viokase® crushed with one 325 mg tablet of sodium bicarbonate (to activate the Viokase®) in 5 mL of water can be instilled into the nasogastric tube and clamped for 5 minutes; then, flushed with 50 mL of tap water
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.
Creon® [new formulation]: When administering to infants <1 year, do not mix with breast milk or baby formula. Open capsule and place the contents directly into the mouth, or mix with a small amount of applesauce. Ensure that contents of capsule are not crushed, chewed or retained in the mouth. When used by children and adults, capsules should be swallowed whole, not crushed or chewed. If necessary, capsules may also be opened and the 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.
Pancrease® MT: Delayed-release capsules containing enteric-coated microtablets may also be opened and the contents sprinkled on soft food with a low pH (<7.3) that does not require chewing, such as applesauce, gelatin; apricot, banana, or sweet potato baby food. Dairy products such as milk, custard, or ice cream may have a high pH and should be avoided.
Ultrase®, Ultrase® MT: Foods with a pH >5.5 may dissolve the protective enteric shell and should be avoided.
Viokase®: Avoid inhalation of powder, may cause nasal and respiratory tract irritation.
Monitoring Parameters
Abdominal symptoms, nutritional intake, weight, growth (in children), stool character, fecal fat
Dietary Considerations
Should be used as part of a high-calorie diet, appropriate for age and clinical status. Administer 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
Do not take any new medication during therapy unless approved by prescriber. Take right before or with foods and swallow whole with a generous amount of liquid. Dairy products, such as milk, custard, or ice cream, may have a high pH and should not taken together with this medication. Do not crush or chew tablets or regular capsules. Delayed-release capsules containing enteric coated microspheres or microtablets may be opened and the contents sprinkled on soft food with a low pH such as applesauce, gelatin, apricot, banana, or sweet potato baby food (refer to specific product labeling). Powder: If powder spills on skin, wash off immediately, do not inhale powder when preparing. You may experience some gastric discomfort. Report unusual rash, persistent GI upset; or respiratory difficulty. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to become pregnant. Consult prescriber if breast-feeding.
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).
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 depends on purpose for use. Use caution preparing powder. If powder spills on skin, wash off immediately. Do not inhale powder. Teach patient possible side effects/appropriate interventions and adverse symptoms to report.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Capsule, delayed release, enteric coated granules [porcine derived]:
Pangestyme™ CN-10: Lipase 10,000 units, protease 37,500 units, amylase 33,200 units [DSC]
Pangestyme™ CN-20: Lipase 20,000 units, protease 75,000 units, amylase 66,400 units [DSC]
Pangestyme™ EC: Lipase 4500 units, protease 25,000 units, and amylase 20,000 units [DSC]
Pangestyme™ MT16: Lipase 16,000 units, protease 48,000 units, and amylase 48,000 units [DSC]
Pangestyme™ UL 12: Lipase 12,000 units, protease 39,000 units, and amylase 39,000 units [DSC]
Pangestyme™ UL 18: Lipase 18,000 units, protease 58,500 units, and amylase 58,500 units [DSC]
Pangestyme™ UL 20: Lipase 20,000 units, protease 65,000 units, and amylase 65,000 units [DSC]
Capsule, delayed release, enteric coated microspheres [porcine derived]: Lipase 4500 units, protease 25,000 units, and amylase 20,000 units; Lipase 10,000 units, protease 30,000 units, and amylase 30,000 units; Lipase 16,000 units, protease 48,000 units, and amylase 48,000 units; Lipase 20,000 units, protease 44,000 units, and amylase 56,000 units
Creon® 5: Lipase 5000 units, protease 18,750 units, and amylase 16,600 units [DSC]
Creon® 10: Lipase 10,000 units, protease 37,500 units, and amylase 33,200 units [DSC]
Creon® 20: Lipase 20,000 units, protease 75,000 units, and amylase 66,400 units [DSC]
Pancrecarb MS-4®: Lipase 4000 units, protease 25,000 units, and amylase 25,000 units [buffered]
Pancrecarb MS-8®: Lipase 8000 units, protease 45,000 units, and amylase 40,000 units [buffered]
Pancrecarb MS-16® Lipase 16,000 units, protease 52,000 units, and amylase 52,000 units [buffered]
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, enteric coated microspheres [porcine derived]:
Ultrase®: Lipase 4500 units, protease 25,000 units, and amylase 20,000 units
Capsule, enteric coated microtablets [porcine derived]:
Pancrease® MT 4: Lipase 4000 units, protease 12,000 units, and amylase 12,000 units
Pancrease® MT 10: Lipase 10,000 units, protease 30,000 units, and amylase 30,000 units
Pancrease® MT 16: Lipase 16,000 units, protease 48,000 units, and amylase 48,000 units
Pancrease® MT 20: Lipase 20,000 units, protease 44,000 units, and amylase 56,000 units
Capsule, enteric coated minitablets [porcine derived]:
Ultrase® MT12: Lipase 12,000 units, protease 39,000 units, and amylase 39,000 units
Ultrase® MT18: Lipase 18,000 units, protease 58,500 units, and amylase 58,500 units
Ultrase® MT20: Lipase 20,000 units, protease 65,000 units, and amylase 65,000 units
Powder [porcine derived]:
Viokase®: Lipase 16,800 units, protease 70,000 units, and amylase 70,000 units per 0.7 g (227 g)
Tablet [porcine derived]:
Plaretase™ 8000: Lipase 8000 units, protease 30,000 units, and amylase 30,000 units [DSC]
Viokase® 8: Lipase 8000 units, protease 30,000 units, and amylase 30,000 units
Viokase® 16: Lipase 16,000 units, protease 60,000 units, and amylase 60,000 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
Capsule, enteric pellets (Pancrease MT 10)
30-10-30 units (100): $112.22
Capsule, enteric pellets (Pancrease MT 16)
48-16-48 units (30): $53.68
Capsule, enteric pellets (Pancrease MT 20)
56-20-44 units (30): $66.86
Capsule, enteric pellets (Pancrelipase 16000)
48-16-48 units (100): $119.99
Capsule, enteric pellets (Pangestyme CN 20)
66.4-20-75 units (100): $173.53
Capsule, enteric pellets (Pangestyme EC)
4500 unit (100): $43.08
4500 unit (250): $85.33
Capsule, enteric pellets (Pangestyme MT 16)
48-16-48 units (30): $37.01
Capsule, enteric pellets (Ultrase)
4500 unit (100): $70.70
Capsule, enteric pellets (Ultrase MT 12)
39-12-39 units (100): $145.75
Capsule, enteric pellets (Ultrase MT 18)
58.5-18-58.5 units (100): $234.02
Capsule, enteric pellets (Ultrase MT 20)
65-20-65 units (100): $258.76
Powder (Viokase)
70-16.8-70 units (227): $259.64
Tablets (Viokase 16)
60-16-60 units (30): $59.88
Tablets (Viokase 8)
30-8-30 units (100): $72.12
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.
Marcuard SP and Stegall KS, “Unclogging Feeding Tubes With Pancreatic Enzyme,” JPEN J Parenter Enteral Nutr, 1990, 14(2):198-200.
Marcuard SP, Stegall KL, and Trogdon S., “Clearing Obstructed Feeding Tubes,” JPEN J Parenter Enteral Nutr, 1989, 13(1):81-3.
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 July 2009
Content last modified July 2009
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