1. Pancrelipase (DB00085) Approved and Investigational Drug
Chemical Formula: C5850H8902N1606O1739S49
Molecular Weight:
Pancrelipase is an enzyme mixture isolated from porcine or bovine pancreas, sometimes called pancreatin. It contains 3 enzymes: amylase, lipase, and a protease (chymotrypsin). Pancrelipase is marketed under several brand names such as Ultresa and Viokace
Indication/Usage
For treatment of exocrine pancreatic insufficiency in cystic fibrosis (Ultresa), chronic pancreatitis (Viokace in combination with a proton pump inhibitor), and pancreatectomy (Viokace in combination with a proton pump inhibitor).
Pharmacodynamics
Used in the treatment of cystic fibrosis or pancreatic dysfunction, pancrelipase helps improve fat digestion in the small intestine. Specifically, the lipase, protease and amylase components break down fat, protein, and starches, respectively, in the small intestine. Lipase hydrolyzes fats into glycerol and fatty acids. Protease converts proteins into proteoses and derived substances, while amylase converts starches into dextrins and sugars. Pancreatic enzymes are used to correct maldigestion, malabsorption and pain associated with pancreatic insufficiency. The major maldigestion/malabsorption problems arise from incomplete fat digestion. Exogenous pancrelipase reduces the amount of nitrogen and fat excreted in the stool.

2. Volume of Distribution
Mechanism of Action
The lipase, protease and amylase components of pancrelipase break down fat, protein, and starches, respectively, in the small intestine. Lipase hydrolyzes fats into glycerol and fatty acids. Protease converts proteins into proteoses and derived substances, while amylase converts starches into dextrins and sugars.
Toxicity
Overdose symptoms may include diarrhea or stomach upset. The most common adverse reactions seen are ear, neck, and abdominal pain; headache, nasal congestion, and beta-hemolytic streptococcal infection.
Metabolism
Pancrelipase acts locally, so there is minimal metabolism.
Absorption
Pancrelipase is not significantly absorbed from the gastrointestinal tract.
Half-Life
Pancrelipase is not significantly absorbed from the gastrointestinal tract and acts locally, so there is no terminal elimination half life.
Route of Elimnation
Pancrelipase is eliminated in the feces.
Volume of Distribution
Pancrelipase acts locally, so there is no volume of distribution.
Clearence
Pancrelipase is not significantly absorbed, so there is minimal clearance from the body.
Category
Gastrointestinal Agents and Enzyme Replacement Agents

3. Affected Organisms Food Interactions Drug Interactions Sequence
Human and other Mammals
Food Interactions
Delayed release capsules should not be broken or crushed, but for those patients who cannot swallow the capsules, sprinkle the contents of the capsule onto soft acidic foods (pH of 4.5). Alkaline foods with a higher pH will promote early release of pancrelipase followed by enzyme inactivation in the stomach.Multivitamins/minerals which have vitamins ADEK, folate, or iron: If pancrelipase is used in combination with multivitamins/minerals that have vitamins ADEK, folate, or iron then monitor therapy because pancrelipase may decrease absorption of iron in these multivitamin/mineral products.Take pancrelipase with meals and a sufficient amount of water.
Drug Interactions
DB01592 (Iron): If pancrelipase and iron salts are used in combination then monitor therapy. Pancrelipase may decrease the absorption of iron salts except for ferumoxytol, iron dextran complex, and iron sucrose.
Sequence
Pancreatic alpha amylase:
QYSPNTQQGRTSIVHLFEWRWVDIALECERYLAPKGFGGVQVSPPNENVAIYNPFRPWWERYQPVSYKLCTRSGNEDEFRNMVTRCNNVGVRIYVDAVINHMCGNAVSAGTSSTCGSYFNPGSRDFPAVPYSGWDFNDGKCKTGSGDIENYNDATQVRDCRLTGLLDLALEKDYVRSKIAEYMNHLIDIGVAGFRLDASKHMWPGDIKAILDKLHNLNSNWFPAGSKPFIYQEVIDLGGEPIKSSDYFGNGRVTEFKYGAKLGTVIRKWNGEKMSYLKNWGEGWGFVPSDRALVFVDNHDNQRGHGAGGASILTFWDARLYKMAVGFMLAHPYGFTRVMSSYRWPRQFQNGNDVNDWVGPPNNNGVIKEVTINPDTTCGNDWVCEHRWRQIRNMVIFRNVVDGQPFTNWYDNGSNQVAFGRGNRGFIVFNNDDWSFSLTLQTGLPAGTYCDVISGDKINGNCTGIKIYVSDDGKAHFSISNSAEDPFIAIHAESKL

4. Experimental Properties
Chymotrypsin:
BGVPAIHPVLSGLSRIVNGEDAVPGSWPWQVSLQDKTGFHFCGGSLISEDWVVTAAHCGVRTSDVVVAGEFDQGSDEENIQVLKIAKVFKNPKFSILTVNNDITLLKLATPARFSQTVSAVCLPSADDDFPAGTLCATTGWGKTKYNANKTPDKLQQAALPLLSNAECKKSWGRRITDVMICAGASGVSSCMGDSGGPLVCQKDGAWTLVGIVSWGSDTCSTSSPGVYARVTKLIPWVQKILAAN
Pancreatic triacylglycerol lipase:
MLPLWTLSLLLGAVAGKEVCYERLGCFSDDSPWSGITERPLHILPWSPKDVNTRFLLYTNENPNNFQEVAADSSSISGSNFKTNRKTRFIIHGFIDKGEENWLANVCKNLFKVESVNCICVDWKGGSRTGYTQASQNIRIVGAEVAYFVEFLQSAFGYSPSNVHVIGHSLGAHAAGEAGRRTNGTIGRITGLDPAEPCFQGTPELVRLDPSDAKFVDVIHTDGAPIVPNLGFGMSQVVGHLDFFPNGGVEMPGCKKNILSQIVDIDGIWEGTRDFAACNHLRSYKYYTDSIVNPDGFAGFPCASYNVFTANKCFPCPSGGCPQMGHYADRYPGKTNDVGQKFYLDTGDASNFARWRYKVSVTLSGKKVTGHILVSLFGNKGNSKQYEIFKGTLKPDSTHSNEFDSDVDVGDLQMVKFIWYNNVINPTLPRVGASKIIVETNVGKQFNFCSPETVREEVLLTLTPC
Experimental Properties
Melting Point: °C
Isoelectric Point: 6.44
Targets
Dietary fat, Dietary protein, Dietary starch
Brands
Pancrecarb - Digestive care US, Inc.
Viokace - Aptalis Pharma US, Inc.
ULTRESA- Aptalis Pharma US, Inc.
Pertzye - Digestive care US, Inc.
ULTRASE- Axcan Pharma
ZENPEP - Aptalis Pharma US, Inc.

5. PANCRECARB Formulation Used/Prescribed for Dosage Contraindications
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. Delayed-Release Capsules, Buffered and Enteric-Coated Microspheres to be taken orally
Formulation
it is formulated as Delayed-Release Capsules, Buffered and Enteric-Coated Microspheres.It contains Lipase :4000 to 8000 U.S.P. units, Amylase: to U.S.P. units, Protease: to U.S.P. units.nactive ingredients include sodium carbonate, sodium bicarbonate, cellulose acetate phthalate, diethyl phthalate, gelatin, sodium carboxymethyl starch, polyvinylpyrrolidone, talc, ursodiol, and other trace ingredients.
Used/Prescribed for
PANCRECARB® (pancrelipase) Delayed-Release Capsules, Buffered andEnteric-Coated Microspheres are indicated for patients with exocrinepancreatic enzyme insufficiency such as: cystic fibrosis, chronic pancreatitisdue to alcohol use or other causes, post-pancreatectomy and post-gastrointestinal bypass surgery .
Dosage
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.
Contraindications
PANCRECARB® (pancrelipase) Delayed-Release Capsules, Buffered andEnteric-Coated Microspheres are contraindicated in patients known to be hypersensitive to pork protein or any other ingredient of this product.

6. Side- effects Drug Interactions References
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 exogenouspancreatic 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
References

7. Viokace Formulation Used/Prescribed for Dosage Contraindications
VIOKACE is a pancreatic enzyme preparation for oral administration consisting of pancrelipase, an extract derived from porcine pancreatic glands. Pancrelipase contains multiple enzyme classes, including porcine-derived lipases, amylases, and proteases. Pancrelipase is a beige-white amorphous powder. It is miscible in water and practically insoluble in alcohol and converted to tablet form for oral administration
Formulation
10,440 USP units of lipase; 39,150 USP units of protease; 39,150 USP units of amylase tablets are tan, round biconvex and have VIO9111 engraved on one side and 9111 on the other side.Inactive ingredients in VIOKACE include: colloidal silicon dioxide, crosscarmellose sodium, lactose monohydrate, microcrystalline cellulose, stearic acid and talc.
Used/Prescribed for
VIOKACE (pancrelipase) tablets, in combination with a proton pump inhibitor, is indicated in adults for the treatment of exocrine paencratic insufficiencydue to chronic pancreatitis or pancreatectomy.
Dosage
Enzyme dosing should begin with 500 lipase units/kg of body weight per meal 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.
Contraindications
None
Side- effects
The most serious adverse reactions reported with different pancreatic enzyme products of the same active ingredient (pancrelipase) that are described elsewhere in the label include fibrosing colonopathy, hyperuricemia and allergic reactions

8. Drug Interactions References
No drug interactions have been identified. No formal interaction studies have been conducted.
References

9. Ultressa
ULTRESA is a pancreatic enzyme preparation consisting of pancrelipase, an extract derived from porcine pancreatic glands. Pancrelipase contains multiple enzyme classes, including porcine-derived lipases, amylases, and proteases. Pancrelipase is a beige-white amorphous powder. It is miscible in water and practically insoluble or insoluble in alcohol and ether and converted to Delayed-Release Capsules for oral route.
Formulation
Each delayed-release capsule for oral administration contains enteric-coatedbeads (1.7 mm in diameter and 1.9 mm thick for 4,000 USP lipase units, approximately 2.0 mm in diameter and 2.0 – 2.4 mm thick for 13,800, 20,700, and 23,000 USP lipase units). it also contains colloidal silicon dioxide, croscarmellose sodium, hydrogenated castor oil, hypromellose phthalate, magnesium stearate, microcrystalline cellulose, talc, and triethyl citrate.
Used/Prescribed for
ULTRESA (pancrelipase) is indicated for the treatment of exocrinepancreatic insufficiency due to cystic fibrosis or other conditions.
Dosage
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.
Contraindications
None

10. Side- effects Drug Interactions References
The most serious adverse reactions reported with different pancreatic enzyme products of the same active ingredient (pancrelipase) that are described elsewhere in the label include fibrosing colonopathy, hyperuricemia and allergic reactions
Drug Interactions
No drug interactions have been identified. No formal interaction studies have been conducted.
References

11. Pertzye
PERTZYE 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 and converted to Delayed-Release Capsules for oral route.
Formulation
Each PERTZYE delayed-release capsule for oral administration contains bicarbonatebuffered enteric-coated microspheres ranging in size from 0.8 – 2.2 mm in diameter.8,000 USP units of lipase; 28,750 USP units of protease; 30,250 USP units of amylase. it also contains odium bicarbonate, sodium carbonate, cellulose acetate phthalate, sodium starch glycolate, diethyl phthalate, ursodiol, polyvinylpyrrolidone, and talc and are contained in hard gelatin capsules.
Used/Prescribed for
PERTZYE (pancrelipase) is indicated for the treatment of exocrinepancreatic insufficiency due to cystic fibrosis or other conditions.
Dosage
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.
Contraindications
None

12. Side- effects Drug Interactions References
The most serious adverse reactions reported with different pancreatic enzyme products of the same active ingredient (pancrelipase) that are described elsewhere in the label include fibrosing colonopathy, hyperuricemia and allergic reactions
Drug Interactions
No drug interactions have been identified. No formal interaction studies have been conducted.
References

13. Ultrase
ULTRASE® (pancrelipase) Capsules are orally administered and contain 250 mg of enteric-coated microspheres of porcine pancreatic enzymeconcentrate, predominantly pancreatic lipase, amylase, and protease. These are Capsules Enteric-Coated Microspheres to be administered orally
Formulation
Each ULTRASE® (pancrelipase) Capsule contains 4500 USP units of lipase; USP units of protease; USP units of amylase. It contains povidone, talc, sugar, methacrylic acid copolymer (Type C), triethyl citrate, simethicone emulsion.
Used/Prescribed for
ULTRASE® (pancrelipase) Capsules are indicated for patients with partial or complete exocrine pancreatic insufficiency caused by cystic fibrosis, Chronic pancreatitis due to alcohol, Obstruction, Other pancreatic disease, Poor mixing.
Dosage
Initial dosing of pancreatic enzyme supplements should begin with 500 lipase U/kg/meal using enteric-coated microsphere products.
Contraindications
Pancrelipase capsules are contraindicated in patients known to be hypersensitive to pork protein. Pancrelipase capsules are contraindicated in patients with acute pancreatitis or with acute exacerbations of chronicpancreatic diseases.

14. Side- effects Drug Interactions References
Extremely high doses of exogenouspancreatic enzymes have been associated with hyperuricosuria andhyperuricemia
Drug Interactions
No information.
References

15. Zenpep
ZENPEP 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. Delayed release capsules to be administered orally.
Formulation
Each capsule for oral administration contains enteric-coated beads ( mm for 3,000 and 5,000 USP units of lipase, mm for 10,000, 15,000, 20,000, 25,000, and 40,000 USP units of lipase). ZENPEP include colloidal silicon dioxide, croscarmellose sodium, hydrogenated castor oil, hypromellose phthalate, magnesium stearate, microcrystalline cellulose, talc, and triethyl citrate and are contained in hypromellose capsules. The imprinting red ink on the 3,000 capsules strength contains, antifoam DC 1510, industrial methylated spirit, iron oxide red C.I E172, n-butyl alcohol, shellac and soya lecithin.
Used/Prescribed for
ZENPEP (pancrelipase) is indicated for the treatment of exocrinepancreatic insufficiency due to cystic fibrosis or other conditions.
Dosage
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.
Contraindications
None

16. Side- effects Drug Interactions References
The most serious adverse reactions reported with different pancreatic enzyme products of the same active ingredient (pancrelipase) that are described elsewhere in the label include fibrosing colonopathy,hyperuricemia and allergic reactions
Drug Interactions
No drug interactions have been identified. No formal interaction studies have been conducted.
References