What is Creon (pancreatic enzyme replacement medication)?

What is Creon?

Creon is an FDA-approved pancreatic enzyme replacement therapy (PERT) derived from porcine pancreas that contains lipase, amylase, and proteases in enteric-coated delayed-release capsules, used to treat exocrine pancreatic insufficiency (EPI) in conditions such as cystic fibrosis, chronic pancreatitis, and pancreatic surgery. 1, 2

Composition and Formulation

• Creon contains three digestive enzymes extracted from porcine pancreas: lipase (for fat digestion), proteases (for protein digestion), and amylases (for carbohydrate digestion) 1, 2
• The product is labeled based on its USP lipase content, which is the primary enzyme needed for fat digestion 1
• Creon uses enteric-coated mini-microspheres (1.0-1.2 mm) that protect the enzymes from gastric acid degradation and release them in the duodenum at pH >5.5 1
• These mini-microspheres have demonstrated higher therapeutic efficacy compared to larger microspheres 1

FDA Approval Status

• Creon was the first PERT product to gain FDA approval in the United States in 2009, following an FDA mandate requiring all pancreatic enzyme manufacturers to submit new drug applications 2, 3
• It has been available in Europe since 1984 and in the USA since 1987, with the new formulation approved in 2009 3
• All FDA-approved PERT products in the United States (including Creon, Zenpep, Pancreaze, Pertzye, and Viokace) are of porcine origin, making porcine-derived enzymes the only approved source for treating pancreatic insufficiency 1

Clinical Indications

• Creon treats exocrine pancreatic insufficiency (EPI) regardless of etiology, including cystic fibrosis, chronic pancreatitis, pancreatectomy, and pancreatic surgery 1, 2, 3
• Untreated EPI results in maldigestion symptoms, nutritional deficiencies, poor quality of life, and increased mortality 1

Proven Efficacy

• Clinical trials demonstrate that Creon significantly improves the coefficient of fat absorption (CFA) from 49.6% with placebo to 88.6% with treatment, and coefficient of nitrogen absorption (CNA) from 49.9% to 85.1% 4
• Treatment results in statistically significant weight gain (mean 2.7 kg over 6 months), reduced stool frequency (mean decrease of 1.0 stools/day), and improvements in abdominal pain, flatulence, and stool consistency 5
• Success is measured by reduction in steatorrhea, weight gain, improvement in muscle mass and function, and normalization of fat-soluble vitamin levels 1

Dosing Principles

• Initial PERT dosing should be at least 40,000 USP units of lipase during each meal in adults and half that amount with snacks 1
• Doses can be increased up to a maximum of 2,500 units/kg/meal if symptoms persist 6
• The daily maximum is 10,000 units/kg/day 6
• Creon should be taken during meals (not before or after) to maximize mixing with food and digestion of nutrients 1, 6
• When using multiple capsules, they should be distributed throughout the meal rather than taken all at once 6

Safety Profile

• Creon is well tolerated with very few withdrawals due to adverse events and a low frequency of treatment-related adverse events 3
• The most commonly reported adverse events are gastrointestinal disorders (including diarrhea, frequent bowel movements) and allergic skin reactions 7, 3
• In pediatric studies, respiratory tract infections, rhinitis, stomatitis, and nasopharyngitis were also common, though none were serious or led to discontinuation 7

Available Formulations

• Creon is available in multiple lipase unit strengths, including Creon 24,000-unit capsules for adults and Creon Micro (5000 lipase units/spoon) for young children 7, 5
• The different FDA-approved porcine enzyme products are generally considered equipotent at similar lipase dosages 1

Important Clinical Considerations

• Adding a proton pump inhibitor or H2-blocker can enhance enzyme activity, even though Creon is enteric-coated 6
• Routine monitoring of fat-soluble vitamin levels (A, D, E, K) is essential, as deficiencies can persist even with adequate PERT 1, 6
• Over-the-counter enzyme supplements should never be used as substitutes, as they are classified as dietary supplements with unstandardized dosing, unregulated efficacy, and unknown safety 1, 6