Pancreatic Enzyme Replacement Therapy

Pancreatic enzyme replacement therapy supplies lipase, protease and amylase of porcine origin to replace deficient exocrine pancreatic secretion. It treats fat and protein maldigestion in chronic pancreatitis, cystic fibrosis, pancreatic resection, pancreatic cancer and after gastric surgery.

Pharmacokinetics. Preparations are enteric-coated microspheres that resist gastric acid and release enzymes at pH above 5.5 in the duodenum. Enzymes act in the gut lumen and are not absorbed.

• Pancrelipase capsules by lipase content, usual 10,000, 25,000 or 40,000 units.
• Adults: 25,000 to 50,000 units of lipase with each main meal and 10,000 to 25,000 units with snacks.
• Maximum 10,000 units/kg of lipase daily or 2,500 units/kg with each meal.
• Children: 1,000 units/kg with each meal under 4 years and 500 units/kg from 4 years, with half the dose with snacks.

Differences. Preparations differ in lipase content and release, so doses are not interchangeable between products.

• Indication: symptomatic steatorrhoea, weight loss or deficiency of fat-soluble vitamins with proven exocrine insufficiency (faecal elastase under 200 microgram/g; under 100 microgram/g is severe).
• Dosing: swallow capsules whole during, not before, the meal. Capsules may be opened and the granules mixed with acidic soft food such as apple sauce, not crushed or chewed.
• Titration: increase the dose every few days until stool and weight improve, up to the maximum.
• Inadequate response: check adherence and timing, add a proton pump inhibitor (omeprazole 20 to 40 mg daily) to protect enzymes from acid, and exclude small bowel bacterial overgrowth, coeliac disease and other causes.

Selection. Diet should not restrict fat; adjust the enzyme dose to the meal's fat content.

Contraindications. Hypersensitivity to porcine protein. Acute pancreatitis in the early phase.

Adverse effects. Abdominal pain, bloating, nausea, constipation, hyperuricosuria with high doses. Fibrosing colonopathy in children with cystic fibrosis at high doses (over 6,000 units/kg for each meal). Perianal or oral irritation if granules are held in the mouth. Porcine origin may be unacceptable to some patients on religious grounds; counsel before starting.

Interactions. Acarbose and miglitol reduce enzyme activity. Folate and iron absorption may fall.

Special groups.

• Pregnancy: acceptable; the enzymes are not absorbed.
• Breastfeeding: acceptable.
• Children: lipase 1,000 units/kg with each meal under 4 years and 500 units/kg from 4 years; cystic fibrosis units give specialist dosing.
• Older adults and kidney or liver impairment: no adjustment.

Monitoring. Weight, stool frequency and character, fat-soluble vitamins (A, D, E, K) and vitamin B12 yearly, glycaemia (pancreatogenic diabetes), and bone density.

Referral and escalation. Persistent steatorrhoea or weight loss at the maximum dose with a proton pump inhibitor, new abdominal pain or jaundice (suspect pancreatic cancer or stricture), or colonic strictures in cystic fibrosis.