Introduction
Zenpep (pancrelipase) is a prescription pancreatic enzyme replacement therapy (PERT) containing a standardized mixture of digestive enzymes including lipase, protease, and amylase. It is derived from porcine pancreatic glands and is designed to compensate for deficient exocrine pancreatic secretion in various malabsorption conditions.
Mechanism of Action
Zenpep works by delivering active pancreatic enzymes to the duodenum where they facilitate the digestion of fats, proteins, and carbohydrates. The enteric-coated microtablets are designed to protect the enzymes from gastric acid degradation, releasing them in the more neutral pH environment of the small intestine. Lipase hydrolyzes triglycerides to monoglycerides and fatty acids, protease cleaves proteins into amino acids and peptides, and amylase converts carbohydrates to dextrins and sugars.
Indications
Zenpep is FDA-approved for the treatment of exocrine pancreatic insufficiency (EPI) due to:
- Cystic fibrosis
- Chronic pancreatitis
- Pancreatectomy
- Other conditions resulting in pancreatic insufficiency
Dosage and Administration
Dosing: Individualized based on clinical symptoms, degree of steatorrhea, and fat content of diet- Initial adult dose: 500-2,500 lipase units per kg body weight per meal
- Initial pediatric dose: 500-4,000 lipase units per kg body weight per meal
- Half the prescribed meal dose should be given with snacks
- Take with meals and snacks
- Swallow whole with plenty of liquid; do not crush or chew
- For patients unable to swallow capsules, contents may be sprinkled on soft, acidic foods (pH ≤4.5) like applesauce
- Do not mix with alkaline foods or milk-based products
- Geriatric: No specific dosage adjustment recommended
- Renal/Hepatic impairment: No formal recommendations available
Pharmacokinetics
Absorption: Enzymes act locally in the gastrointestinal tract; systemic absorption of intact enzymes is minimal Distribution: Acts within the lumen of the gastrointestinal tract Metabolism: Enzymes are metabolized like dietary proteins Elimination: Excreted in feces as partially digested enzymesContraindications
- Known hypersensitivity to pork proteins or any component of the formulation
- History of fibrosing colonopathy associated with high-dose pancreatic enzyme replacement therapy
Warnings and Precautions
Fibrosing Colonopathy: Rare but serious adverse reaction associated with high-dose pancreatic enzyme use, particularly in cystic fibrosis patients. Risk increases with high doses and prolonged use. Hyperuricemia: May occur due to purine content in pancreatic extracts Allergic Reactions: Possible hypersensitivity reactions in patients with pork protein allergy Irritation: May cause irritation if released in the mouth Pregnancy Category C: Use during pregnancy only if potential benefit justifies potential riskDrug Interactions
- May reduce absorption of iron supplements (separate administration by several hours)
- May reduce efficacy of acarbose and miglitol
- Theoretical interaction with proton pump inhibitors (may affect enteric coating performance)
Adverse Effects
Common:- Abdominal pain
- Flatulence
- Headache
- Constipation
- Diarrhea
- Nausea
- Fibrosing colonopathy
- Hyperuricemia
- Allergic reactions (rash, urticaria, anaphylaxis)
- Irritation/perforation with improper administration
Monitoring Parameters
- Clinical response (reduction in steatorrhea symptoms)
- Nutritional status (weight gain, growth parameters in children)
- Stool frequency and consistency
- Adverse effects (particularly abdominal symptoms)
- Uric acid levels in patients at risk
- Signs of fibrosing colonopathy (abdominal pain, distension, vomiting)
Patient Education
- Take with every meal and snack containing fat
- Swallow capsules whole with plenty of liquid
- Do not crush or chew capsules
- For sprinkling administration, use immediately and consume entire portion
- Report any abdominal pain, vomiting, or changes in bowel habits
- Store at room temperature in original container
- Keep out of reach of children
- Inform all healthcare providers about Zenpep use
- Follow prescribed dietary recommendations
References
1. FDA Prescribing Information: Zenpep (pancrelipase) capsules. Revised 2022. 2. American Gastroenterological Association medical position statement on pancreatic enzyme replacement therapy. Gastroenterology. 2020;159(2):723-727. 3. Struyvenberg MR, Martin CR, Freedman SD. Practical guide to exocrine pancreatic insufficiency. Pancreas. 2017;46(8):1035-1042. 4. Singh VK, Schwarzenberg SJ. Pancreatic insufficiency in cystic fibrosis. J Cyst Fibros. 2017;16 Suppl 2:S70-S78. 5. Lohr JM, et al. Properties of different pancreatic preparations used in pancreatic exocrine insufficiency. Eur J Gastroenterol Hepatol. 2019;31(1):1-7.