Pancrelipase

Pancrelipase is a mixture of porcine pancreatic enzymes (lipase, protease and amylase) given by mouth to replace missing pancreatic secretion. It treats exocrine pancreatic insufficiency from chronic pancreatitis, cystic fibrosis, pancreatic surgery or pancreatic cancer, where fat malabsorption causes steatorrhoea, weight loss and deficiency of fat-soluble vitamins.

Classification. Pancreatic enzyme replacement; digestive enzyme.

Mechanism. Lipase hydrolyses dietary triglycerides to fatty acids and monoglycerides, protease digests protein and amylase digests starch. Enteric-coated microspheres resist stomach acid and release enzymes in the duodenum at pH above 5.5.

Pharmacodynamics. Improves fat and protein absorption, reduces stool frequency, steatorrhoea and abdominal pain, and supports weight gain. Effect is immediate with each meal.

Pharmacokinetics. Not absorbed; acts in the gut lumen and is digested like other dietary protein.

Metabolism. Degraded in the gut; no systemic metabolism.

Doses are expressed as units of lipase. Adult oral doses unless stated.

Exocrine pancreatic insufficiency (chronic pancreatitis, pancreatic surgery, pancreatic cancer).

• Start 25,000 to 40,000 units of lipase with each main meal.

• Give half that dose (10,000 to 25,000 units) with each snack.

• Increase gradually every few days using steatorrhoea, weight and symptoms.

• Usual maximum 10,000 units/kg daily, or 4,000 units for each gram of dietary fat; avoid exceeding 2,500 units/kg with each meal.

• Doses over these limits need specialist review.

Cystic fibrosis.

• Children under 4 years: 1,000 units/kg with each meal; children 4 years and over: 500 units/kg with each meal.

• Maximum 2,500 units/kg with each meal, 10,000 units/kg daily or 4,000 units for each gram of fat daily.

• Snacks: about half the meal dose.

• Infants: 2,000 to 4,000 units for each 120 mL of formula or each breastfeed.

Pancreatic enzyme replacement with total pancreatectomy. Higher doses may be needed; specialist directed.

Kidney and liver adjustment. None.

Contraindications. Hypersensitivity to pork protein; acute pancreatitis or acute flare of chronic pancreatitis.

Common adverse effects. Abdominal pain, nausea, bloating, flatulence, constipation or diarrhoea.

Serious adverse effects.

• Fibrosing colonopathy, with colonic strictures, in children with cystic fibrosis taking high doses (above 10,000 units/kg daily).

• Hyperuricaemia and hyperuricosuria at high doses.

• Irritation of the mouth and perianal skin if granules are chewed or spilt.

• Allergic reactions to pork protein and inhalation sensitivity in care staff.

• Distal intestinal obstruction syndrome in cystic fibrosis.

Major interactions.

• Acid suppressants (proton pump inhibitors, H2 blockers): improve enzyme release; useful when response is poor.

• Calcium or magnesium antacids: may reduce effect.

• Iron: absorption may be reduced by large doses of enzymes.

• Acarbose and miglitol: reduce the amylase effect.

Special groups.

• Pregnancy: acceptable; continue treatment to maintain nutrition.

• Breastfeeding: compatible.

• Children: dose by weight and fat intake.

• Older adults: no adjustment.

• Kidney impairment: no adjustment.

• Liver impairment: no adjustment.

• Religious and dietary: porcine source; discuss with patients who avoid pork.

• Regional: cost and supply limit access in East Africa, and storage in hot climates reduces potency.

Formulations. Enteric-coated capsules 5,000, 10,000, 25,000 and 40,000 units lipase; sachets of granules for infants and patients who cannot swallow capsules.

Administration.

• Take with or immediately after the first bite of a meal or snack, and spread across the meal if it is long.

• Swallow capsules whole with fluid.

• If swallowing is hard, open the capsule and sprinkle the granules on a small amount of acidic soft food (apple puree, yoghurt), swallow at once without chewing, then drink water.

• Do not mix with milk or alkaline food, which dissolve the coating.

• Store tightly closed, at room temperature, away from heat and moisture.

Baseline. Weight, stool pattern, faecal elastase, fat-soluble vitamin levels (A, D, E and K), glucose.

Monitoring.

• Weight, stool frequency and steatorrhoea.

• Fat-soluble vitamins annually and bone density.

• Dose in units/kg in cystic fibrosis.

• Persistent symptoms: adjust dose, add an acid suppressant, and check for other causes such as bacterial overgrowth.

Therapeutic drug monitoring. Not applicable.

Stopping. Treatment is lifelong in established insufficiency. Stop for severe allergy.

Referral and escalation. Refer to a specialist for persistent steatorrhoea on maximum doses, suspected fibrosing colonopathy, weight loss or diabetes.