The most serious adverse reactions reported with different pancreatic enzyme products of the same active ingredient (pancrelipase) include fibrosing colonopathy, hyperuricemia and allergic reactions [see WARNINGS AND PRECAUTIONS].
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to the rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
The short-term safety of PERTZYE was assessed in a randomized, double-blind, placebocontrolled, crossover study of 24 patients, ages 8 to 43 years, with exocrine pancreatic insufficiency due to cystic fibrosis. In this study, patients were randomized to receive PERTZYE at individually titrated doses (not to exceed 2,500 lipase units per kilogram per meal) or matching placebo for 6 to 8 days of treatment, followed by crossover to the alternate treatment for an additional 6 to 8 days. The length of exposure to PERTZYE during this study was 20-28 days, including the treatment period of 6 to 8 days, and the open label titration and transition periods of 7 to 10 days.
The most common adverse reactions ( ≥ 10%) were diarrhea, dyspepsia, and cough. Table 1 enumerates adverse reactions that occurred in at least 2 patients (greater than or equal to 10%) treated with PERTZYE at a higher rate than with placebo.
Table 1: Adverse Reactions Occurring in at Least 2 Patients ( ≥ 10%)
|Diarrhea||2 (10%)||1 (4%)|
|Dyspepsia||2 (10%)||1 (4%)|
|Cough||2 (10%)||1 (4%)|
The following adverse reactions have been identified during post approval use of PERTZYE. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
This formulation of PERTZYE has been marketed since 2004 under the trademark PANCRECARB®. Two product complaints relating to an adverse drug reaction were reported. A mild allergic reaction (itching and red, blotchy rash on face) was reported by a patient with a known history of allergy to another pancrelipase product, and a dull headache was reported by another patient taking concomitant ursodeoxycholic acid. Both events resolved without sequelae after discontinuation of treatment.
Delayed- and immediate-release pancreatic enzyme products with different formulations of the same active ingredient (pancrelipase) have been used for the treatment of patients with exocrine pancreatic insufficiency due to cystic fibrosis and other conditions, such as chronic pancreatitis. The long-term safety profile of these products has been described in the medical literature. The most serious adverse events include fibrosing colonopathy, distal intestinal obstruction syndrome (DIOS), recurrence of pre-existing carcinoma, and severe allergic reactions including anaphylaxis, asthma, hives, and pruritus. The most commonly reported adverse events were gastrointestinal disorders, including abdominal pain, diarrhea, flatulence, constipation and nausea, and skin disorders, including pruritus, urticaria and rash.