Pancrelipase

Mechanism of Action

PEPs are porcine enzymes and contain mixtures of pancreatic lipase, amylase, and protease. Lipase is a digestive enzyme involved in the hydrolysis and degradation of fats. Impairments in lipase metabolism lead to the malabsorption of fats. Amylase is a digestive enzyme involved in the hydrolysis and digestion of starches. Impairments in amylase metabolism lead to complex carbohydrates malabsorption. Proteases are enzymes involved in the breakdown of proteins and amino acids. Imbalances or insufficiency of proteases can lead to poor absorption of amino acids and breakdown of essential proteins.

PEPs are exogenous versions of these enzymes derived from porcine pancreatic ducts; these enzymes then act locally to break down fats, proteins, and carbohydrates. The main site of action is the duodenum. The duodenum represents the initial part of the small intestine where nutrient absorption and macromolecule degradation co-occurs. The drug has minimal systemic absorption.

Manufacturers developed newer formulations known as enteric-coated microspheres to protect enzymes against breakdown by gastric acid and provide better dispersion of enzymes in the chyme and, therefore, observed to provide consistent symptoms relief in CP compared to the older formulation.[4] Oral pancreatic enzymes appear to inhibit pancreatic exocrine secretion through a negative feedback mechanism involving intraduodenal proteases and exocrine pancreas.[5]

Administration

Different products have differing lipase/protease/amylase ratios; pancrelipase products are not interchangeable; patients should not switch between products.[6]

Patients should take this medication with meals; a general rule of thumb is to take half a dose of pancrelipase with snacks. 

Adult dosing for exocrine pancreatic insufficiency:

• 500 to 2500 lipase units/kg/dose orally with each meal or snack. 

Pediatric dosing for exocrine pancreatic insufficiency:

• Ages 1 to 3: 1000 to 2500 lipase units/kg/dose orally with each meal or snack; start with 1000 lipase units/kg with each meal or snack. The maximum dose is 6000 lipase units/kg/meal.
• Ages 4 to 11: 500 to 2500 lipase units/kg/dose orally with each meal or snack; start with 500 lipase units/kg/ with each meal or snack. The maximum dose is 6000 lipase units/kg/meal.
• Ages 12 and over: 500 to 2500 lipase units/kg/dose orally with each meal or snack; start with 500 lipase units/kg/meal.

Caps may be opened and sprinkled on soft food with a pH of 4.5 or lower, but patients must not crush or chew the contents. Doses exceeding 2500 lipase units/kg/meal, over 4000 lipase units per gram of fat ingested daily, or more than 10,000 lipase units/kg/day require objective evidence of improved therapeutic efficacy.

Most manufacturers recommend that patients not exceed 10,000 units of lipase/kg per day.

Adverse Effects

The most common adverse effects are headache, oral irritation, abdominal pain, lymphadenopathy, nasal congestion, and neck pain.

Notably, a beta-hemolytic streptococcal infection has been seen with the use of pancrelipase.

Rare (less than 1%) but severe side effects include cancer recurrence, anaphylaxis, duodenitis, and distal intestinal obstruction syndrome.

Warnings include fibrosing colonopathy (especially when doses exceed 2500 lipase units/kg of body weight per meal or greater than 10,000 lipase units/kg of body weight per day) and hyperuricemia as porcine-derived pancreatic enzyme products contain purines that may increase blood uric acid levels.

Pancrelipase has a pregnancy risk factor C; it can be used during pregnancy and breastfeeding. There is inadequate human data, but fetal/infant harm is not expected due to minimal maternal systemic absorption.[7]

Since these are porcine-derived products, there is a theoretical risk of viral transmission with their use; this risk is minimized by adhering to proper dosing instructions. Long-term pancreatic enzyme replacement products (PERPs), some of which had been available for over 100 years, fell under a 2006  US FDA directive that porcine-derived PERP products required the pharmaceutical manufacturer to submit a new drug application s(NDA) for each of these products, the first of the commercial PERP products approved following the FDA requirement received approval in 2009.[8]

Contraindications

Contraindications to pancrelipase include hypersensitivity to the drug or components of the formulation or hypersensitivity to pork protein.[9]

Caution is indicated in some conditions, including hyperuricemia or gout, a history of recurrent GI obstruction, meconium ileus, a history of short bowel syndrome, Crohn disease, or hypoglycemia/hyperglycemia.[10][11][12]

Pancrelipase can interact with certain drugs such as acarbose and calcium or magnesium salts; clinicians should consider alternative therapeutic choices.

Monitoring

No therapeutic levels exist concerning monitoring. Monitoring of the drug effect and adverse effect profile will be based on clinical symptoms and data, including abdominal symptoms, nutritional intake, weight, growth (in children), stool character, fecal fat. Glucose monitoring is advised if the patient has hypoglycemia or hyperglycemia risk.

Toxicity

No known toxicity has been documented per a 2008 report from the Center for Drug Evaluation and Research.

Enhancing Healthcare Team Outcomes

One of the common topics when reviewing the literature concerns the use of proton pump inhibitors with pancrelipase. These enzymes are enteric-coated to avoid the harsh conditions and low pH of the stomach. The goal of PEP therapy focuses on maximal drug delivery into the duodenum, which is where absorption occurs.[13]

Given the known effect of low pH on enzyme delivery for PEP, previous groups have attempted to increase the efficacy of PEP. Previously, preparations of PEP included supplements such as sodium bicarbonate as a neutralizing agent.[14] Other groups have looked at the effects of antacids to improve the efficacy of PEP.[15] Other researchers have studied the effect of H2 receptor blockers as well.[16] Research concerning the effect of H2 receptor blockers showed no improvements in outcomes.[16] Data demonstrate that antacids such as aluminum hydroxide and sodium bicarbonate tend to lower the efficacy of PEP.[16]

Proesmans et al. have shown that concurrent omeprazole administration improved steatorrhea when used with PEP therapy in patients with cystic fibrosis.[17]

The above-referenced literature may provide good clinical evidence for providers to begin PPI therapy in patients who are known hyper-secretors (produce too much stomach acid) or in patients who show minimal improvement with pancrelipase therapy for exocrine pancreatic insufficiency.

When using pancrelipase therapy for indicated conditions, the interprofessional healthcare team strategy will yield the best results. This team, comprised of clinicians, specialists, mid-level practitioners, nurses, and pharmacists, can oversee the therapy, monitor for therapeutic results and adverse events, and provide patient counseling to optimize treatment. With open collaboration and communication, the interprofessional team can achieve the best patient outcomes with the lowest incidence of adverse events. [Level 5]