What are the recommended uses and dosages of pancreatic enzyme replacement therapy (PERT) and ox bile in patients with pancreatic insufficiency?

Pancreatic Enzyme Replacement Therapy (PERT) and Ox Bile for Pancreatic Insufficiency

For patients with pancreatic insufficiency, pancreatic enzyme replacement therapy (PERT) should be administered at an initial dose of 40,000 USP units of lipase with each main meal and 20,000 USP units with snacks in adults, with dosage adjustments based on clinical response and meal fat content. 1

Diagnosis of Pancreatic Insufficiency

• Pancreatic insufficiency should be suspected in high-risk conditions including chronic pancreatitis, relapsing acute pancreatitis, pancreatic cancer, cystic fibrosis, and previous pancreatic surgery 1
• Clinical features include steatorrhea, weight loss, bloating, excessive flatulence, fat-soluble vitamin deficiencies, and protein-calorie malnutrition 1
• Fecal elastase test is the most appropriate initial diagnostic test, with levels <100 μg/g of stool providing good evidence of exocrine pancreatic insufficiency (EPI) 1
• Fecal elastase testing can be performed while on pancreatic enzyme replacement therapy without affecting results 1

Pancreatic Enzyme Replacement Therapy (PERT)

Recommended Dosing

• Initial adult dosing: 40,000 USP units of lipase with each main meal and 20,000 USP units with snacks 1
• Initial pediatric dosing (>12 months to <4 years): 1,000 lipase units/kg/meal 2
• Initial pediatric dosing (≥4 years): 500 lipase units/kg/meal 2
• Infants (birth to 12 months): 3,000 lipase units per 120 mL of formula or per breastfeeding 2
• Dosage can be titrated up to 2,500 lipase units/kg/meal, 10,000 lipase units/kg/day, or 4,000 lipase units/g fat ingested/day 1, 2

Administration Guidelines

• PERT must be taken during the meal to maximize mixing and digestion of nutrients, not before or after 1
• Capsules should be swallowed whole; for patients unable to swallow intact capsules, contents may be sprinkled on soft acidic food (e.g., applesauce) 2
• Do not crush or chew capsules or capsule contents 2
• For enteral tube feedings, enzymes should be administered as bolus doses through the feeding tube, not mixed with the feed 1

FDA-Approved PERT Formulations

Brand	Type	Available Lipase Strengths (USP)
Creon	Enteric-coated microspheres	3,000/6,000/12,000/24,000/36,000
Zenpep	Enteric-coated beads	3,000/5,000/10,000/15,000/20,000/25,000/40,000
Pancreaze	Enteric-coated microtablets	2,600/4,200/10,500/16,800/21,000/37,000
Pertzye	Enteric-coated microspheres	4,000/8,000/16,000/24,000
Viokace	Non-enteric-coated tablets	10,444/20,880
Relizorb	In-line lipase cartridge	For enteral feeding formulas
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Ox Bile Supplements

• Unlike PERT, ox bile supplements are not FDA-approved medications and are classified as dietary supplements 1
• Over-the-counter commercially available pancreas enzyme replacements and ox bile supplements should not be used as they are neither standardized nor regulated, with unknown utility and safety 1

Optimizing PERT Effectiveness

• For inadequate response to initial PERT dosage, consider:
  1. Increasing PERT dosage 1
  2. Adding a proton pump inhibitor (PPI) or H2 receptor antagonist 1
  3. Investigating for small intestinal bacterial overgrowth (SIBO) if the above measures fail 1
• Non-enteric-coated PERT formulations require concurrent acid-suppression therapy with PPIs or H2 blockers 1
• All FDA-approved PERT formulations are derived from porcine sources and are equally effective at equivalent doses 1

Monitoring Treatment Response

• Assess for reduction in steatorrhea and associated gastrointestinal symptoms 1
• Monitor for weight gain, improved muscle mass and function 1
• Check fat-soluble vitamin levels (A, D, E, K) regularly 1
• Perform baseline and follow-up dual-energy x-ray absorptiometry scans every 1-2 years 1
• For children: monitor growth at every clinic visit for infants, every 3 months for older children and adolescents 1
• For adults: assess nutritional status every 6 months 1

Dietary Recommendations

• Recommend low-moderate fat diet with frequent smaller meals 1
• Avoid very-low-fat diets as they may compromise essential fatty acid intake 1
• Routine supplementation of fat-soluble vitamins is appropriate 1

Common Pitfalls to Avoid

• Taking enzymes before or after meals instead of during meals 1
• Using over-the-counter enzyme or ox bile supplements instead of FDA-approved PERT 1
• Inadequate dosing or failing to adjust dosage based on meal fat content 1
• Not considering acid suppression therapy when response to PERT is suboptimal 1
• Overlooking other causes of malabsorption such as SIBO when PERT appears ineffective 1
• Relying solely on symptomatic improvement without objective monitoring of nutritional status 1