CREON Safety Data

Review safety data collected from clinical trials of CREON in various patient populations.

Adults with EPI due to
chronic pancreatitis (CP)
or
pancreatectomy Children and adults with
EPI
due to cystic fibrosis (CF) Short-term data in infants and
children
with EPI due to CF

Adverse reactions reported in clinical studies of patients with EPI due to chronic pancreatitis (CP) or pancreatectomy^1,2

CREON vs Placebo	CREON n=25 (%)	Placebo n=29 (%)
Hyperglycemia	2 (8%)	2 (7%)
Hypoglycemia	1 (4%)	1 (3%)
Abdominal pain	1 (4%)	1 (3%)
Abnormal feces	1 (4%)	0 (0%)
Flatulence	1 (4%)	0 (0%)
Frequent bowel movements	1 (4%)	0 (0%)
Nasopharyngitis	1 (4%)	0 (0%)

Adverse reactions reported in at least 1 patient (≥4%) treated with CREON at a higher rate than placebo in the Chronic Pancreatitis and Pancreatectomy Study
The most common adverse reactions reported in this study were related to glycemic control and were reported more commonly with CREON treatment than with placebo treatment

Whitcomb Study Design

Randomized, double-blind, multicenter, placebo-controlled, parallel-group study of CREON in patients aged 32 to 75 years with EPI due to chronic pancreatitis or pancreatectomy. Patients entered a 5-day placebo run-in period, followed by pancreatic enzyme replacement therapy as directed by the investigator for 16 days. Only patients with a coefficient of fat absorption (CFA) <80% in the run-in period were randomized to the double-blind period. A total of 54 patients were randomized to receive CREON 12,000 lipase unit capsules, at 72,000 lipase units per main meal (3 main meals) and 36,000 lipase units per snack (2 snacks), or matching placebo for 7 days. Patients consumed ≥100 grams of fat per day during the treatment period. The primary endpoint was CFA and the secondary endpoint was the coefficient of nitrogen absorption (CNA). The final analysis population was limited to 52 patients; 2 patients were excluded due to protocol violations.

Adverse reactions reported in combined clinical studies of patients with EPI due to cystic fibrosis^1,3,4

CREON vs Placebo	CREON n=49 (%)	Placebo n=47 (%)
Vomiting	3 (6%)	1 (2%)
Dizziness	2 (4%)	1 (2%)
Cough	2 (4%)	0 (0%)

Adverse reactions reported in at least 2 patients (≥4%) treated with CREON at a higher rate than placebo in adult and pediatric CF studies combined

Trapnell Study Design

Randomized, double-blind, multicenter, placebo-controlled, 2-period crossover study of CREON in 32 patients aged 12 to 43 with confirmed diagnosis of EPI and CF. Patients were randomized to receive CREON 24,000 lipase unit capsules, at a dose of 4,000 lipase units per gram of fat per day, or matching placebo for 5 to 6 days, followed by crossover to the alternate treatment for 5 to 6 days. Patients consumed ≥90 grams of fat per day during treatment periods. A washout period of 3 to 14 days was included between crossover periods to return patients to baseline conditions. The primary endpoint was the coefficient of fat absorption (CFA) and the secondary endpoint was coefficient of nitrogen absorption (CNA). The final analysis population was limited to 29 patients; 3 patients were excluded due to protocol deviations.

Graff Study Design

Randomized, double-blind, multicenter, placebo-controlled, 2-period crossover study of CREON in children aged 7 to 11 with confirmed EPI and CF. A total of 17 patients were randomized to receive CREON 12,000 lipase unit capsules, at a dose of 4,000 lipase units per gram of fat per day, or matching placebo for 5 to 6 days, followed by crossover to the alternate treatment for 5 to 6 days. Patients consumed ≥90 grams of fat per day during treatment periods. A washout period of 3 to 14 days was included between crossover periods to return patients to baseline conditions. The primary endpoint was the coefficient of fat absorption (CFA) and the secondary endpoint was coefficient of nitrogen absorption (CNA). One patient in the pancrelipase/placebo treatment sequence withdrew and was not included in the efficacy analysis.

An open-label, single-arm study
assessed the short-term safety and
tolerability of CREON in 18 infants
and children with EPI due to CF^1,5

The primary objective of this study was to observe the safety and tolerability profile of CREON compared with the standard PERT therapy in children under 7
This study included patients with a confirmed diagnosis of EPI due to CF aged 4 months to 6 years, the youngest population studied for PERT use
Adverse reactions that occurred in patients during treatment with CREON in this open-label study were vomiting, irritability, and decreased appetite, each occurring in 6% of patients

Open-label Study Design

Open-label, multicenter, single-arm, short-term study of CREON in 18 infants and children aged 4 months to 6 years of age with EPI due to CF. Patients received their usual pancreatic enzyme replacement therapy (mean dose of 7,000 lipase units/kg/day for a mean duration of 18.2 days) followed by CREON (mean dose of 7,500 lipase units/kg/day for a mean duration of 12.6 days). The mean daily fat intake was 48 grams during treatment with usual pancreatic enzyme replacement therapy and 47 grams during treatment with CREON. The primary objective of this study was to observe the short-term safety and tolerability of CREON compared with the standard PERT therapy in children less than 7 years of age with EPI due to CF.

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Indications and Important
Safety Information

Indications¹

CREON^® (pancrelipase) Delayed-Release Capsules is a pancrelipase which is a combination of porcine-derived lipases, proteases, and amylases indicated for the treatment of exocrine pancreatic insufficiency due to cystic fibrosis, chronic pancreatitis, pancreatectomy, or other conditions.

Important Safety Information

Fibrosing colonopathy is associated with high-dose use of pancreatic enzyme replacement in the treatment
of cystic fibrosis patients. Exercise caution when doses of CREON exceed 2,500 lipase units/kg of body weight
per meal (or greater than 10,000 lipase units/kg of body weight per day).
To avoid irritation of oral mucosa, care should be taken to ensure that CREON is not crushed, chewed, or retained in the mouth. CREON should always be taken with food.
Porcine-derived pancreatic enzyme products contain purines. Caution should be exercised when prescribing CREON to patients with gout, renal impairment, or hyperuricemia.
There is theoretical risk of viral transmission with all pancreatic enzyme products including CREON.
Exercise caution when administering pancrelipase to a patient with a known allergy to proteins of porcine origin.
Adverse reactions that occurred in at least 2 cystic fibrosis patients (greater than or equal to 4%) receiving CREON were vomiting, dizziness, and cough.
Adverse reactions that occurred in at least 1 chronic pancreatitis or pancreatectomy patient (greater than or equal to 4%) receiving CREON were hyperglycemia, hypoglycemia, abdominal pain, abnormal feces, flatulence, frequent bowel movements, and nasopharyngitis.
CREON is not interchangeable with any other pancrelipase product.