What is pancrelipase, a medication used to treat pancreatic insufficiency in patients with a history of pancreatic surgery, chronic pancreatitis, cystic fibrosis, or other conditions affecting the pancreas?

What is Pancrelipase?

Pancrelipase is a prescription pancreatic enzyme replacement therapy (PERT) consisting of porcine-derived digestive enzymes—lipases, proteases, and amylases—used to treat exocrine pancreatic insufficiency (EPI) by replacing the enzymes that the pancreas fails to produce adequately. 1

Composition and Formulation

Pancrelipase is extracted from porcine (pig) pancreatic glands and contains three primary enzyme types that mirror human pancreatic enzymes 1:

• Lipases: Break down fats into monoglycerides, glycerol, and free fatty acids
• Proteases: Break down proteins into peptides and amino acids
• Amylases: Break down starches into dextrins and short-chain sugars like maltose 1

All FDA-approved pancrelipase products in the United States are porcine-derived, making this the only approved source for treating pancreatic insufficiency. 2 Available FDA-approved brands include Creon, Zenpep, Pancreaze, Pertzye, and Viokace. 2

The medication comes as enteric-coated microspheres or microtablets within delayed-release capsules, designed to protect the enzymes from destruction by stomach acid and release them in the duodenum at pH >5.5, where they can function optimally. 3, 1 Mini-microspheres (1.0-1.2 mm diameter) demonstrate higher therapeutic efficacy compared to larger microspheres. 3

Clinical Indications

Pancrelipase treats exocrine pancreatic insufficiency caused by 3, 4:

• Chronic pancreatitis (most common indication in adults)
• Cystic fibrosis (most common indication in children)
• Pancreatic surgery or pancreatectomy
• Pancreatic cancer
• Acute pancreatitis (severe or recurrent)

Mechanism of Action and Clinical Effects

Pancrelipase works by catalyzing the hydrolysis of nutrients in the duodenum and proximal small intestine, functioning as replacement for the digestive enzymes normally secreted by a healthy pancreas. 1 The enzymes are not absorbed systemically but act locally in the gastrointestinal tract. 1

Without treatment, EPI leads to 3, 4:

• Steatorrhea (fatty, bulky stools that are difficult to flush)
• Maldigestion and malabsorption of fats, proteins, and carbohydrates
• Weight loss and malnutrition
• Fat-soluble vitamin deficiencies (A, D, E, K)
• Increased mortality and poor quality of life 3

Pancrelipase reverses these complications by improving fat and nitrogen absorption, controlling gastrointestinal symptoms, and correcting nutritional deficiencies. 4, 5

Dosing Guidelines

For adults, the typical starting dose is 40,000 USP units of lipase per main meal and 20,000 USP units per snack. 3, 6 The maximum recommended dose is 2,500 units of lipase per kg per meal or 10,000 units per kg per day. 3, 1

Pancrelipase must be taken during meals—not before or after—to ensure proper mixing with food and optimal enzyme-nutrient contact. 6 For larger meals requiring multiple capsules, spread the capsules throughout the meal rather than taking all at once. 6

Products are labeled based on their USP lipase content, which ranges from 3,000 to 40,000 USP units per capsule, as lipase is the rate-limiting enzyme for fat digestion. 2, 1

Important Safety Considerations

Chronic high doses of pancrelipase (exceeding 6,000 lipase units/kg/meal in children under 12 years) have been associated with fibrosing colonopathy and colonic strictures. 1 Do not exceed recommended maximum doses. 1

Never crush or chew pancrelipase capsules, as this destroys the protective enteric coating, leading to oral mucosa irritation and loss of enzyme activity. 1 For patients unable to swallow capsules, the contents can be mixed with acidic foods (pH <4.5) like applesauce, but never with alkaline foods or added directly to infant formula. 3

High doses may also cause hyperuricosuria and hyperuricemia. 1

Monitoring Effectiveness

Treatment success is measured by 3, 6:

• Reduction or resolution of steatorrhea
• Weight gain and improved muscle mass
• Normalization of fat-soluble vitamin levels
• Improvement in gastrointestinal symptoms (reduced stool frequency, improved consistency, decreased abdominal pain and bloating)

Monitor growth and nutritional status at every clinic visit for infants, every 3 months for children and adolescents, and every 6 months for adults. 3

Critical Distinction from Over-the-Counter Products

Over-the-counter pancreatic enzyme supplements should never be used to treat EPI, as they lack standardized dosing, have unverified and inconsistent enzymatic activity between batches, and are classified as dietary supplements only. 2, 6 Only FDA-approved prescription pancrelipase products have demonstrated efficacy and safety for treating pancreatic insufficiency. 2