l clinical needs of the patient.
6 ADVERSE REACTIONS
The most serious adverse reactions reported with different pancreatic enzyme products of the same active ingredient (pancrelipase) include fibrosing colonopathy [see Warnings and Precautions (5.1)], hyperuricemia [see Warnings and Precautions (5.3)] and allergic reactions [see Warnings and Precautions (5.5)].
6.1 Adverse Reactions in Clinical Trials
The short-term safety of CREON was assessed in a single, randomized, double-blind, placebo-controlled, crossover study of 32 patients, ages 12 to 43 years, with exocrine pancreatic insufficiency due to cystic fibrosis. In this study, patients were randomized to receive CREON at a dose of 4,000 lipase units/g fat ingested per day or matching placebo for 5 to 6 days of treatment, followed by crossover to the alternate treatment for an additional 5 to 6 days. The mean exposure to CREON during this study was 5 days.
One patient experienced duodenitis and gastritis of moderate severity reported as a serious adverse event 16 days after completing treatment with CREON.
Transient neutropenia without clinical sequelae was observed as an abnormal laboratory finding in one patient receiving CREON and a macrolide antibiotic.
The incidence of adverse events (regardless of causality) was higher during placebo treatment (71%) than during CREON treatment (50%). Adverse events reported during the study were predominantly gastrointestinal complaints, and the type and incidence of adverse events were similar in adolescents (12 to 18 years) and adults (greater than 18 years).
Because clinical trials are conducted under controlled conditions, the observed adverse event rates may not reflect the rates observed in clinical practice.
Table 1 enumerates treatment-emergent adverse events that occurred in at least 2 patients (greater than or equal to 6%) treated with either CREON or placebo in the clinical study. Adverse events were classified by Medical Dictionary for Regulatory Activities (MedDRA) terminology.
Table 1: Treatment-Emergent Adverse Events Occurring in at least 2 Patients (greater than or equal to 6%) in Either Treatment Group of the Placebo-Controlled, Crossover Clinical Study of CREON MedDRA Primary System Organ Class Preferred Term CREON Capsules
n = 32 (%) Placebo
n = 31 (%)
Gastrointestinal Disorders
Abnormal Feces 1 (3) 6 (19)
Flatulence 3 (9) 8 (26)
Abdominal Pain 3 (9) 8 (26)
Abdominal Pain Upper 0 3 (10)
Investigations
Weight Decreased 1 (3) 2 (6)
Nervous System Disorders
Headache 2 (6) 8 (26)
Dizziness 2 (6) 0
Respiratory, Thoracic and Mediastinal Disorders
Cough 2 (6) 0
6.2 Postmarketing Experience
There is no postmarketing experience with this formulation of CREON.
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 included fibrosing colonopathy, distal intestinal obstruction syndrome (DIOS), recurrence of pre-existing carcinoma, and severe allergic |
