pancrelipase (Creon, Pancreaze, Pertzye, Ultresa, Viokace, Zenpep)

Dosing and uses of Creon, Pancreaze (pancrelipase)

• Adult
• Pediatric

 

Adult dosage forms and strengths

lipase/protease/amylase

(KU=1000 units)

capsule, delayed-release (contains enteric-coated microspheres)

• Creon
• 6KU/19KU/30KU
• 12KU/38KU/60KU
• 24KU/76KU/120KU
• 36KU/114KU/180KU

capsule, delayed-release (contains enteric-coated microtablets)

• Pancreaze
• 4.2KU/10KU/17.5KU
• 10.5KU/25KU/43.75KU
• 16.8KU/40KU/70KU
• 21KU/37KU/61KU

capsule, delayed-release (contains enteric-coated minitablets)

• Ultresa
• 13.8KU/27.6KU/27.6KU
• 20.7KU/41.4KU/41.4KU
• 23KU/46KU/46KU

tablet

• Viokace
• 10.44KU/39.15KU/39.15KU  
• 20.88KU/78.3KU/78.3KU

capsule, delayed-release (contains enteric-coated microspheres)

• Pertzye
• 8KU/28.75KU/30.25KU
• 16KU/57.5KU/60.5KU

capsule, delayed-release (contains enteric-coated beads)

• Zenpep
• 5KU/17KU/27KU
• 10KU/34KU/55KU
• 15KU/51KU/82KU
• 20KU/68KU/109KU
• 25KU/85KU/136KU

 

Exocrine Pancreatic Insufficiency

Creon, Ultresa, Pertzye, Zenpep, Pancreaze are indicated for pancreatic insufficiency due to cystic fibrosis, pancreatitis, pancreatectomy, or other conditions

• Cystic fibrosis guidelines: Generally, start 500 lipase units/kg PO per meal; can titrate up to 2500 units/kg/meal based on response; not to exceed 10,000 lipase units/kg/day or <4000 lipase units/g fat ingested per day
• Administer 50% of meal dose with snacks
• High-dose Creon: In 1 clinical trial described in the prescribing information, adults received a dose of 72,000 lipase units/meal while consuming at least 100 g of fat/day for chronic pancreatitis or pancreatectomy; lower starting doses (ie, 500 lipase units/kg/meal) are consistent with Cystic Fibrosis guidelines

Viokace

• Only indicated in adults for the treatment of exocrine pancreatic insufficiency due to chronic pancreatitis or pancreatectomy (and not cystic fibrosis)
• Generally, start 500 lipase units/kg PO per meal; can titrate up to 2500 units/kg/meal based on response; not to exceed 10,000 lipase units/kg/day or <4000 lipase units/g fat ingested per day
• Administer 50% of meal dose with snacks
• Viokace should be administered with a PPI

 

Pediatric dosage forms and strengths

lipase/protease/amylase

(KU=1000 units)

capsule, delayed-release (enteric-coated microspheres)

• Creon
• 3KU/9.5KU/15KU
• 6KU/19KU/30KU
• 12KU/38KU/60KU
• 24KU/76KU/120KU

capsule, delayed-release (enteric-coated microtablets)

• Pancreaze
• 4.2KU/10KU/17.5KU
• 10.5KU/25KU/43.75KU
• 16.8KU/40KU/70KU
• 21KU/37KU/61KU

capsule, delayed-release (contains enteric-coated minitablets)

• Ultresa
• 13.8KU/27.6KU/27.6KU
• 20.7KU/41.4KU/41.4KU
• 23KU/46KU/46KU

tablet

• Viokace
• 10.44KU/39.15KU/39.15KU  
• 20.88KU/78.3KU/78.3KU

capsule, delayed-release (contains enteric-coated microspheres)

• Pertzye
• 4KU/14.375KU/15.125KU
• 8KU/28.75KU/30.25KU
• 16KU/57.5KU/60.5KU

capsule, delayed-release (contains enteric-coated beads)

• Zenpep
• 3KU/10KU/16KU
• 5KU/17KU/27KU
• 10KU/34KU/55KU
• 15KU/51KU/82KU
• 20KU/68KU/109KU
• 25KU/85KU/136KU

 

Exocrine Pancreatic Insufficiency

Creon, Ultresa, Pertzye, Zenpep, Pancreaze are indicated for pancreatic insufficiency due to cystic fibrosis, pancreatitis, pancreatectomy, or other conditions

Creon/Zenpep

• ≤12 months: 3000 lipase units/kg/120 mL of formula or per breastfeeding; administer prior to feeding; capsule contents should not be mixed directly in formula or breast milk
• 1-3 years: Initiate at 1000 lipase units/kg/meal; not to exceed 2500 lipase units/kg/meal (or 10000 lipase units/kg/day) or <4000 lipase units/g fat ingested per day
• ≥4 years: Initiate at 500 lipase units/kg/meal; not to exceed 2500 lipase units/kg/meal (or 10,000 lipase units/kg/day) or <4000 lipase units/g fat ingested per day

Pancreaze

• ≤12 months: 2000-4000 lipase units/kg/120 mL of formula or per breastfeeding; administer prior to feeding; capsule contents should not be mixed directly in formula or breast milk
• 1-3 years: Initiate at 1000 lipase units/kg/meal; not to exceed 2500 lipase units/kg/meal (or 10,000 lipase units/kg/day) or <4000 lipase units/g fat ingested per day
• ≥4 years: Initiate at 500 lipase units/kg/meal; not to exceed 2500 lipase units/kg/meal (or 10,000 lipase units/kg/day) or <4000 lipase units/g fat ingested per day
• Not to exceed 10,000 unit lipase/kg/day or <4,000 lipase unites/g fat ingested daily

Pertzye

• ≤12 months: 4000 lipase units/kg/120 mL of formula or per breastfeeding; administer prior to feeding; capsule contents should not be mixed directly in formula or breast milk
• 1-4 years and weight ≥8 kg: Initiate at 1000 lipase units/kg/meal; not to exceed 2500 lipase units/kg/meal (or 10,000 lipase units/kg/day) or <4000 lipase units/g fat ingested per day
• ≥4 years and weight ≥16 kg: Initiate at 500 lipase units/kg per meal; not to exceed 2500 lipase units/kg/meal (or 10,000 lipase units/kg/day) or <4000 lipase units/g fat ingested per day

Ultresa

• 1-4 years and weight >14 kg: Initiate at 1000 lipase units/kg/meal; not to exceed 2500 lipase units/kg/meal (or 10,000 lipase units/kg/day) or <4000 lipase units/g fat ingested per day
• ≥4 years and weight >28 kg: Initiate at 500 lipase units/kg/meal; not to exceed 2500 lipase units/kg/meal (or 10,000 lipase units/kg/day) or <4000 lipase units/g fat ingested per day

Viokace

• Safety and effectiveness not established

Recommendations from Cystic Fibrosis Foundation Consensus Report

• Infants <2 years is 2000-5000 lipase units/120 mL feeding; as infant grows, adjust dose not to exceed 2500 lipase units/kg/feeding (or 10,000 lipase units/kg/day)
• In general, daily requirements of 500-4000 lipase units/g of fat are required
• J Pediatr 2009;155(6 Suppl):S73-S93

 

Creon, Pancreaze (pancrelipase) adverse (side) effects

>10%

Abdominal pain/cramping (3-18% )

Headache (3-15% )

 

1-10%

Dyspepsia (10%)

Cough (4-10%)

Diarrhea (0-10%)

Hyperglycemia (8%)

Pharyngolaryngeal pain (7%)

Epistaxis (7%)

Anal pruritus (7%)

Biliary tract stones (7%)

Vomiting (6%)

Contusion (6%)

Weight loss (6%)

Early satiety (6%)

Flatulence (5-6%)

Dizziness (4%)

Hypoglycemia (4%)

Abnormal Feces (4%)

Frequent bowel movements (4%)

Nasopharyngitis (4%)

Anemia (3%)

Ascites (3%)

Flatulence (3%)

Peripheral edema (3%)

Hydrocholecystis (3%)

Viral infection (3%)

Renal cyst (3%)

Rash (3%)

 

Postmarketing Reports

Severe allergic reactions including anaphylaxis, asthma and hives

Skin disorders including pruritus, rash and urticaria

Asymptomatic elevations of liver enzymes

Gastrointestinal disorders: Abdominal distension, abdominal pain, diarrhea, flatulence, constipation and nausea; rare reports of fibrosing colonopathy and distal intestinal obstruction syndrome

Endocrine: May affect glycemic control in susceptible individuals

 

Warnings

Contraindications

Documented hypersensitivity

 

Cautions

Avoid exceeding maximum dose due to risk of fibrosing colonopathy; ≥6,000 lipase units/kg per meal associated with colonic stricture, indicative of fibrosing colonopathy, particularly in children ≤12 years

Swallow pills as chewing or retaining in mouth may cause oral mucosa irritation; do not chew, crush or mixed in foods having a pH ≥4.5

Monitor uric acid levels in patients with gout, hyperuricemia or renal impairment due to risk of hyperuricemia

Caution in patients with known allergy or porcine proteins

Do not exceed ≥2,500 units/kg per meal (or ≥10,000 lipase units/kg per day or ≥ 4000 lipase units/g fat ingested per day)

Avoid inhalation of powder

Theoretical risk of viral transmission

 

Pregnancy and lactation

Pregnancy category: C

Lactation: unknown

 

Pregnancy categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

 

Pharmacology of Creon, Pancreaze (pancrelipase)

Mechanism of action

Product contains a combination of lipase, protease, and amylase that replace endogenous pancreatic enzymes and catalyze the hydrolysis of starches into dextrins and short chain sugars such as maltose and maltotriose, fats to monoglycerides, glycerol and free fatty acids and proteins into peptides and amino acids in the duodenum and proximal small intestine

 

Pharmacokinetics

Absorption: not absorbed, acts locally in GI tract

Excretion: feces

 

Administration

Oral Administration

Pancrelipase products are not interchangeable

Initiate therapy at lowest recommended dose and increase gradualL

Individualize therapy based on symptoms, degree of steatorrhea, fat content of diet, and patient response

Children and adults

• Usually, 50% of the full meal dose should be administered with snacks; total daily dosage should reflect approximately 3 meals plus 2-3 snacks per day
• Decrease dose in geriatric patients as, on average, they weigh more but tend to ingest less fat per kilogram of body weight
• Capsule should be swallowed whole with sufficient fluid; do not crush, chew, or retain in the mouth, to avoid irritation of the oral mucosa
• Unable to swallow capsule: Capsule contents may be sprinkled on applesauce, yogurt, or acidic soft food with pH <4.5

Infants ≤12 months

• Do not mix capsule contents directly into formula or breast milk (may decrease efficacy)
• Administered to infants immediately prior to each feeding
• Capsule contents may be mixed with soft acidic food with a pH ≤4.5 (eg, applesauce) or directly to the mouth
• Administration should be followed by breast milk or formula
• Contents of the capsule should not be mixed directly into
• Do not crush, chew, or retain in the mouth, to avoid irritation of the oral mucosa