Pancrelipase refers to a class of medications designed to treat malabsorption and abdominal pain secondary to exocrine pancreatic insufficiency. These agents serve as exogenous versions of digestive hormones and enzymes required for normal digestion. As discussed below, these enzymes are ingested with meals to improve digestion, absorption, and abdominal pain frequently seen in chronic pancreatitis and exocrine pancreatic insufficiency. Pancrelipase can be used in all age groups.
Exocrine pancreatic insufficiency due to any of the following conditions:
Key Clinical Background Information
Exocrine pancreatic insufficiency (EPI) is a syndrome characterized by poor absorption of fats, proteins, and, to a lesser extent carbohydrates. This condition occurs primarily in patients with cystic fibrosis (CF) or chronic pancreatitis (CP). Clinicians can make the diagnosis of EPI by one of 3 criteria: fecal elastase test, fecal fat test, or a direct pancreatic function test.
Patient’s with EPI in CP have worse nutritional status, vitamin levels, and quality of life when compared to patients with CP without EPI. Pancreatic enzyme products (PEPs) have been the standard of care for treatment of EPI in patients with CP for the past three decades. Treating patients with PEP improves in nutritional status, quality of life, symptoms, and life expectancy in patients with EPI.
Manufacturers developed most PEPs before current United States Food and Drug Administration (FDA) New Drug Approval (NDA) requirements were enacted. In 2005, the FDA requested that manufacturers of PEPs now submit an NDA for approval of these products. A new wave of research is being conducted to discern the pharmacokinetic and pharmacodynamic profiles of PEP. For instance, this includes research concerning the bioavailability of PEP, the onset of action, and the improvement of fat absorption for this class of drugs.
Practitioners use the coefficient of fat absorption (CFA) to discern the efficacy of these drugs. In exocrine pancreatic insufficiency, many of the poor outcomes stem from the poor absorption of fats and fat-soluble vitamins. The administration of PEP enhances the absorption of fats and fat-soluble vitamins (A, D, E, K), and provides better outcomes for patients on therapy. Often, readers may encounter the term CFA. A simple way to understand the CFA is to know that the higher the CFA of any PEP, the better the drug will be at improving fat and fat-soluble vitamin absorption.
Some clinicians empirically begin patients on pancrelipase therapy when patients present with vitamin deficiencies, malabsorption, and poor nutritional status with risk factors for chronic pancreatitis, for example, chronic alcoholism. The reason for this stems from the actual difficulty that one may encounter to diagnose chronic pancreatitis or exocrine pancreatic insufficiency. As mentioned above, EPI requires stool fat testing or even direct pancreatic function testing. Some clinicians may prefer to treat empirically given the immediate or rapid benefit conferred with PEP therapy; others often defer testing as testing is invasive (direct pancreatic stimulation testing) or unavailable in certain areas.
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 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 first part of the small intestine where nutrient absorption and macromolecule degradation co-occurs.
Manufacturers developed newer formulations known as enteric-coated microspheres to protect enzymes against gastric acid and to provide better dispersion of enzymes in the chyme and therefore observed to provide consistent symptoms relief in CP compared to an older formulation. Oral pancreatic enzymes appear to inhibit pancreatic exocrine secretion through a negative feedback mechanism involving intraduodenal proteases and exocrine pancreas.
Patients should take this medication with meals; a general rule of thumb is to take half a dose of pancrelipase with snacks.
Most manufacturers recommend beginning with a dose of 500 units of lipase/kg with each meal. Most manufacturers recommend not to exceed 10,000 units of lipase/kg per day.
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.
There are no known contraindications to pancrelipase.
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.
No known toxicity has been documented per a 2008 report from the Center for Drug Evaluation and Research.
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.
Given the known effect of low pH on enzyme delivery for PEP, previous groups have attempted to increase the efficacy of PEP. Previous preparations of PEP included supplements such as sodium bicarbonate as a neutralizing agent. Other groups have looked at the effects of antacids to improve the efficacy of PEP. Other researchers have studied the effect of H2 receptor blockers as well. Research concerning the effect of H2 receptor blockers showed no improvements in outcomes. Data demonstrate that antacids such as aluminum hydroxide and sodium bicarbonate tend to lower the efficacy of PEP.
Proesmans et al. have shown that in patients with cystic fibrosis, concurrent administration of omeprazole improved steatorrhea when used with PEP therapy.
The literature mentioned above 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 with EPI.
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