Note: Dosing should not exceed recommended maximum dosage set forth by the Cystic Fibrosis Foundation Consensus Conferences Guidelines. Adjust dose based on body weight, clinical symptoms, stool fat content, and the fat content of the diet. Allow several days between dose adjustments. Total daily dose reflects ~3 meals per day and 2 to 3 snacks per day, with half the mealtime dose given with a snack. Doses of lipase >2,500 units/kg/meal, lipase >10,000 units/kg/day, or lipase >4,000 units/g fat daily should be used with caution and only with documentation of effectiveness by 3-day fecal fat measures indicating a significantly improved coefficient of fat absorption. Doses of lipase >6,000 units/kg/meal are associated with colonic stricture and should be decreased.
Pancreatic insufficiency due to conditions such as cystic fibrosis: Oral (Creon, Pancreaze, Pertzye, Zenpep): Initial: Lipase 500 units/kg/meal. Dosage range: Lipase 500 to 2,500 units/kg/meal. Maximum: Lipase ≤2,500 units/kg/meal or lipase ≤10,000 units/kg/day or lipase <4,000 units/g of fat daily.
Pancreatic insufficiency due to chronic pancreatitis or pancreatectomy: Oral:
Creon: Initial: Lipase 500 units/kg/meal with individualized dosage titrations. In one clinical trial, 72,000 units/meal while consuming ≥100 g of fat daily was used. Usually, half the prescribed dose for an individualized full meal should be given with each snack. Maximum: Lipase ≤2,500 units/kg/meal or lipase ≤10,000 units/kg/day or lipase <4,000 units/g of fat daily.
Viokace (administer in combination with a proton pump inhibitor): Initial: Lipase 500 units/kg/meal with individualized dosage titration. In one clinical trial, 125,280 units/meal while consuming ≥100 g of fat daily was used. Usually, half the prescribed dose for an individualized full meal should be given with each snack. Maximum: Lipase ≤2,500 units/kg/meal or lipase ≤10,000 units/kg/day or lipase <4,000 units/g of fat daily.
Pancreatic insufficiency (exocrine) due to pancreatic cancer (off-label dosing): Oral: Initial: 25,000 to 50,000 units (lipase) per meal or 1,000 units (lipase)/kg/day or 4,000 units/5 to 7 g fat at each meal; escalate dose based on relief of symptoms; maximum dose: 2,500 units (lipase)/kg/meal (Damerla 2008).
There are no dosage adjustments provided in the manufacturer’s labeling. Use with caution.
There are no dosage adjustments provided in the manufacturer’s labeling.
(For additional information see "Pancrelipase: Pediatric drug information")
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 to 3 snacks/day, with half the mealtime dose given with a snack. Doses of lipase >2,500 units/kg/meal should be used with caution and only with documentation of 3-day fecal fat measures. Doses of lipase >6,000 units/kg/meal are associated with colonic stricture and should be decreased.
Pancreatic insufficiency due to cystic fibrosis:
General dosing recommendations:
Infants: Oral: Lipase 2,000 to 5,000 units per feeding of formula, breast milk, or per breastfeeding. Maximum daily dose: Lipase 10,000 units/kg/day up to 2,500 units/kg/feeding (Borowitz 2009). Note: A review of data from the CF Foundation Patient Registry suggests that the maximum daily dose may be insufficient in young infants with CF; however, the optimal dose is not established (Borowitz 2013).
Children 1 to <2 years: Note: Dosage requirements may fluctuate as diet transitions to more solid foods. Oral: Initial dose: Lipase 1,000 units/kg/meal. Dosage range: Lipase 1,000 to 2,500 units/kg/meal. Maximum daily dose: Lipase 10,000 units/kg/day or lipase 4,000 units/g of fat/day. Higher dosing similar to infant dosing (Lipase: 2,000 to 5,000 units per feeding of formula, breast milk, or per breastfeeding) may be necessary in some patients (Borowitz 2009).
Children ≥2 to <4 years: Oral: Initial dose: Lipase 1,000 units/kg/meal. Dosage range: Lipase 1,000 to 2,500 units/kg/meal. Maximum daily dose: Lipase 10,000 units/kg/day or lipase 4,000 units/g of fat/day.
Children ≥4 years and Adolescents: Oral: Initial dose: Lipase 500 units/kg/meal. Dosage range: Lipase 500 to 2,500 units/kg/meal. Maximum daily dose: Lipase 10,000 units/kg/day or lipase 4,000 units per g of fat/day.
Pancreatic enzyme supplementation, enteral tube feedings: Infants, Children, and Adolescents: Limited data available: Note: With low-fat or elemental enteral formulas, pancreatic enzyme supplementation may not be necessary (Ferrie 2011).
Continuous enteral feeding: Oral: Lipase 1,000 units/g of fat provided by the daily amount of feeds administered in divided doses every 2 to 3 hours (Ferrie 2011)
Overnight enteral feeding: Oral: Administer premeal dose at beginning of feeding; additional dose may be given midway through or at the end of a feeding (Borowitz 2002). Some centers recommend using 1,000 units/g of fat provided by the overnight feed administered in 2 divided doses with the first dose as 50% of requirement or enough to cover 3 hours of feeds and the additional dose given if patient awakens at night or at the end of a feeding (Ferrie 2011).
There are no dosage adjustments provided in the manufacturer's labeling. Use with caution; enzymes contain purines that may increase blood uric acid levels.
There are no dosage adjustments provided in the manufacturer’s labeling.
Refer to adult dosing.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, delayed release, bicarbonate buffered enteric coated microspheres, oral [porcine derived]:
Pertzye: Lipase 4,000 USP units, protease 14,375 USP units, and amylase 15,125 USP units
Pertzye: Lipase 8,000 USP units, protease 28,750 USP units, and amylase 30,250 USP units
Pertzye: Lipase 16,000 USP units, protease 57,500 USP units, and amylase 60,500 USP units
Pertzye: Lipase 24,000 USP units, protease 86,250 USP units, and amylase 90,750 USP units
Capsule, delayed release, enteric-coated beads, oral [porcine derived]:
Zenpep: Lipase 3,000 USP units, protease 10,000 USP units, and amylase 14,000 USP units
Zenpep: Lipase 5,000 USP units, protease 17,000 USP units, and amylase 24,000 USP units
Zenpep: Lipase 10,000 USP units, protease 32,000 USP units, and amylase 42,000 USP units
Zenpep: Lipase 15,000 USP units, protease 47,000 USP units, and amylase 63,000 USP units
Zenpep: Lipase 20,000 USP units, protease 63,000 USP units, and amylase 84,000 USP units
Zenpep: Lipase 25,000 USP units, protease 79,000 USP units, and amylase 105,000 USP units
Zenpep: Lipase 40,000 USP units, protease 126,000 USP units, and amylase 168,000 USP units
Zenpep: Lipase 40,000 USP units, protease 136,000 USP units, and amylase 218,000 USP units [DSC]
Capsule, delayed release, enteric coated microspheres, oral [porcine derived]:
Creon: Lipase 3000 USP units, protease 9500 USP units, and amylase 15,000 USP units
Creon: Lipase 6000 USP units, protease 19,000 USP units, and amylase 30,000 USP units
Creon: Lipase 12,000 USP units, protease 38,000 USP units, and amylase 60,000 USP units
Creon: Lipase 24,000 USP units, protease 76,000 USP units, and amylase 120,000 USP units
Creon: Lipase 36,000 USP units, protease 114,000 USP units, and amylase 180,000 USP units
Capsule, delayed release, enteric coated microtablets, oral [porcine derived]:
Pancreaze: Lipase 2600 USP units, protease 8800 USP units, and amylase 15,200 USP units
Pancreaze: Lipase 4200 USP units, protease 14,200 USP units, and amylase 24,600 USP units
Pancreaze: Lipase 10,500 USP units, protease 35,500 USP units, and amylase 61,500 USP units
Pancreaze: Lipase 16,800 USP units, protease 56,800 USP units, and amylase 98,400 USP units
Pancreaze: Lipase 21,000 USP units, protease 54,700 USP units, and amylase 83,900 USP units
Pancreaze: Lipase 37,000 USP units, protease 97,300 USP units, and amylase 149,900 USP units
Tablet, oral [porcine derived]:
Viokace: Lipase 10,440 USP units, protease 39,150 USP units, and amylase 39,150 USP units
Viokace: Lipase 20,880 USP units, protease 78,300 USP units, and amylase 78,300 USP units
No
An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:
Creon: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020725s026lbl.pdf#page=16
Pancreaze: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/022523s013lbl.pdf#page=16
Pertzye: http://www.fda.gov/downloads/Drugs/DrugSafety/UCM306861.pdf
Viokace: http://www.fda.gov/downloads/Drugs/DrugSafety/UCM296222.pdf
Zenpep: http://www.fda.gov/downloads/Drugs/DrugSafety/UCM180714.pdf
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. Usually half the prescribed dose for an individualized full meal should be given with each snack. The total daily dose should reflect ~3 meals plus 2 or 3 snacks per day.
Capsules, delayed release: If necessary, capsules may be opened and contents added to a small amount (~10 mL) of soft acidic food (pH ≤4.5), such as applesauce; do not crush microspheres when mixing. The food should be swallowed immediately after mixing; do not chew. The food should be at room temperature (Creon). Follow with water or juice to ensure complete ingestion and that no medication remains in the mouth.
Tablets: Viokace: Tablets are not enteric coated and should be taken with a proton pump inhibitor.
Administration via gastrostomy (G) tube:
Creon: An in vitro study demonstrated that Creon delayed-release capsules sprinkled onto a small amount of baby food (pH <4.5; applesauce or bananas manufactured by both Gerber and Beech-Nut) stirred gently and after 15 minutes was administered through the following G-tubes without significant loss of lipase activity: Kimberly-Clark MIC Bolus size 18 French, Kimberly-Clark MIC-KEY size 16 French, Bard Tri-Funnel size 18 French, and Bard Button size 18 French (Shlieout 2011).
Pertzye: May administer up to two 4,000 unit capsules via G-tube with a diameter of 14 French or larger diameter tube. Thoroughly mix contents of one or two 4,000 unit capsules in ≥10 mL applesauce to create a uniform suspension; do not crush microspheres. Administer via a 35 mL slip tip syringe; flush with ~10 mL of water. Administer immediately after mixing; do not save for later use. If dose requires > two 4,000 unit capsules, repeat.
Administer with meals or snacks and swallow capsules or tablets whole with a generous amount of liquid, water, or juice. Do not crush or chew; retention in the mouth before swallowing may cause mucosal irritation and stomatitis.
Oral:
Capsules: If necessary, capsules may also be opened and contents added to a small amount of an acidic food (pH ≤4.5), 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 to 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 to 2.5 mm in diameter. Pertzye capsules contain bicarbonate buffered enteric-coated microspheres which are 0.8 to 2.2 mm in diameter.
Infants <1 year: Avoid mixing with breast milk or infant formula. Open capsule and place the contents directly into the mouth or mix with a small amount of acidic soft food (pH ≤4.5) such as applesauce, or other commercially prepared baby food (pears or bananas) at room temperature. Administer immediately after mixing (or within 15 minutes of mixing using Pancreaze). Follow with infant formula or breast milk to ensure complete ingestion and that no medication remains in the mouth.
Tablets (Viokace): Adults: Tablets are not enteric coated and should be taken with a proton pump inhibitor.
Enteral feeding tube: Capsules: An in vitro study demonstrated that Creon delayed-release capsules sprinkled on a small amount of baby food (pH<4.5; applesauce or bananas manufactured by both Gerber and Beech-Nut) may be administered through the following G-tubes without significant loss of lipase activity: Kimberly-Clark MIC Bolus size 18 Fr, Kimberly-Clark MIC-KEY size 16 Fr, Bard Tri-Funnel size 18 Fr, and Bard Button size 18 Fr (Shlieout 2011). Sodium bicarbonate has also been used to dissolve the beads before administering into feeding tube, although optimal regimen has not been described; may cause increase in serum bicarbonate, monitor closely (Boullata 2015; Ferrie 2011; Nicolo 2013).
Pancreatic insufficiency (exocrine): Treatment of exocrine pancreatic insufficiency caused by cystic fibrosis or other conditions. Creon is also approved for patients with chronic pancreatitis or pancreatectomy. Viokace, in combination with a proton-pump inhibitor, is approved for use in adults with exocrine pancreatic insufficiency caused by chronic pancreatitis or pancreatectomy.
Note: Viokace must be administered with a proton pump inhibitor (PPI) since it is not enteric coated.
Pancrelipase may be confused with pancreatin
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. 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 (3% to 15%)
Gastrointestinal: Abdominal pain (3% to 18%)
Hematologic & oncologic: Lymphadenopathy (11%)
Infection: Streptococcal infection (beta-hemolytic streptococcus: 11%)
Neuromuscular & skeletal: Neck pain (14%)
Otic: Otalgia (11%)
Respiratory: Nasal congestion (14%)
1% to 10%:
Cardiovascular: Peripheral edema (3%)
Central nervous system: Dizziness (4% to 6%)
Dermatologic: Skin rash (3%)
Endocrine & metabolic: Hyperglycemia (4% to 8%), weight loss (3% to 6%), exacerbation of diabetes mellitus (4%), hypoglycemia (4%)
Gastrointestinal: Dyspepsia (10%), diarrhea (≤10%), flatulence (3% to 9%), choledocholithiasis (7%), pruritus ani (7%), early satiety (6%), vomiting (6%), upper abdominal pain (≤5%), abnormal stools (≤4%)
Hematologic & oncologic: Anemia (3%)
Hepatic: Ascites (3%), hydrocholecystis (3%)
Infection: Viral infection (3%)
Renal: Renal cyst (3%)
Respiratory: Cough (4% to 10%), epistaxis (7%), pharyngolaryngeal pain (7%), nasopharyngitis (4%)
<1%, postmarketing, and/or case reports (reported with various formulations of pancrelipase): Anaphylaxis, asthma, blurred vision, carcinoma (recurrence), constipation, duodenitis, fibrosing colonopathy, gastritis, hyperuricemia, increased serum transaminases (asymptomatic), intestinal obstruction (distal intestinal obstruction syndrome [DIOS]), muscle spasm, myalgia, nausea, neutropenia (transient), pruritus, severe hypersensitivity, urticaria
There are no contraindications listed in the US labeling.
Canadian labeling: Hypersensitivity to pancrelipase or any component of the formulation; acute pancreatitis; acute exacerbation of chronic pancreatitis.
Concerns related to adverse effects:
• Fibrosing colonopathy: Fibrosing colonopathy, advancing to colonic strictures, has been reported (rarely). Risk may be increased with high doses, prolonged use, and in pediatric patients with cystic fibrosis; however, the mechanism is unknown. Doses of lipase >6,000 units/kg/meal have been associated with colonic stricture in children <12 years. Patients taking doses of lipase >6,000 units/kg/meal should be examined and the dose decreased. Doses of lipase >2,500 units/kg/meal, lipase >10,000 units/kg/day, or lipase >4,000 units/g fat daily should be used with caution and only with documentation of effectiveness by 3-day fecal fat measures indicating a significantly improved coefficient of fat absorption.
• Hypersensitivity: Severe, allergic reactions (eg anaphylaxis, asthma, hives, pruritus) have rarely been observed; use with caution in patients hypersensitive to pork proteins, taking into consideration the patient's overall clinical needs.
• Mucosal irritation: Crushing or chewing the contents of the capsules or tablets, or mixing the capsule 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. Pancrelipase should not be mixed in foods with pH >4.5.
• Pork: Products are derived from porcine pancreatic glands. Transmission of porcine viruses, and diseases caused by novel or unidentified 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.
Disease-related concerns:
• Gout, hyperuricemia: Use caution in patients with gout or hyperuricemia; porcine-derived products contain purines which may increase uric acid concentrations.
• Pancreatic cancer: According to guidelines from the American Society of Clinical Oncology, patients with pancreatic cancer (potentially curable, locally advanced, or metastatic) who experience exocrine pancreatic insufficiency may require pancreatic enzyme replacement therapy to improve digestion and nutrient absorption (Balaban 2016; Khorana 2016; Sohal 2016). A retrospective study in patients with metastatic pancreatic cancer suggests that pancreatic enzyme replacement therapy is underutilized (Landers 2016).
• Renal impairment: Use caution in patients with renal impairment; porcine-derived products contain purines which may increase uric acid concentrations.
Dosage form specific issues:
• Brand interchangeability: Available brand products are not interchangeable.
• Lactose: Viokace tablets may contain lactose; use with caution in patients with lactose intolerance.
None known.
There are no known significant interactions.
Delayed release capsules: Enteric coated contents of delayed release capsules opened and sprinkled on alkaline foods may result in early release of pancrelipase followed by enzyme inactivation by gastric acid in the stomach after swallowing. Management: Avoid placing contents of opened capsules on alkaline food (using soft acidic foods with a pH of ≤4.5 is recommended for patients who cannot swallow capsules).
Systemic absorption of pancrelipase is limited; significant fetal exposure is not expected following maternal use.
Pancrelipase is considered compatible for use during pregnancy (Edenborough 2008; Panchaud 2016).
It is not known if pancrelipase is present in breast milk.
Systemic absorption of pancrelipase is limited; significant exposure to the breastfed infant is not expected following maternal use. According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother. Maternal use of pancrelipase is considered compatible with breastfeeding (Edenborough 2008; Panchaud 2016).
Take with meals or snacks and swallow whole with a generous amount of liquid. Capsule contents may be sprinkled on a soft acidic food with pH <4.5. Vitamin supplementation should be per current guidelines for patients with cystic fibrosis.
Abdominal symptoms, nutritional intake, weight, growth (in children), stool character, fecal fat
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.
Absorption: None; acts locally in GI tract
Excretion: Feces
Capsule, enteric pellets (Creon Oral)
3000-9500 unit (per each): $1.91
6000-19000 unit (per each): $2.26
12000-38000 unit (per each): $4.52
24000-76000 unit (per each): $8.96
36000-114000 unit (per each): $13.61
Capsule, enteric pellets (Pancreaze Oral)
2600-8800 unit (per each): $0.89
4200-14200 unit (per each): $1.44
10500-35500 unit (per each): $3.60
16800-56800 unit (per each): $5.79
21000-54700 unit (per each): $7.21
37000-97300 unit (per each): $16.43
Capsule, enteric pellets (Pertzye Oral)
4000-14375 unit (per each): $2.02
8000-28750 unit (per each): $3.02
16000-57500 unit (per each): $6.04
24000-86250 unit (per each): $9.06
Capsule, enteric pellets (Zenpep Oral)
3000-10000 unit (per each): $2.43
5000-24000 unit (per each): $2.31
10000-32000 unit (per each): $4.58
15000-47000 unit (per each): $6.61
20000-63000 unit (per each): $8.98
25000-79000 unit (per each): $11.11
40000-126000 unit (per each): $17.72
Tablets (Viokace Oral)
10440-39150 unit (per each): $4.23
20880-78300 unit (per each): $8.34
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
