Creon Information
Creon (Pancreatic) Indications And Usage
Creon (Pancreatic) (pancrelipase) is indicated for the treatment of exocrine pancreatic insufficiency due to cystic fibrosis, chronic pancreatitis, pancreatectomy, or other conditions.
Creon (Pancreatic) Dosage And Administration
Creon (Pancreatic) is not interchangeable with other pancrelipase products.
Creon (Pancreatic) is orally administered. Therapy should be initiated at the lowest recommended dose and gradually increased. The dosage of Creon (Pancreatic) should be individualized based on clinical symptoms, the degree of steatorrhea present, and the fat content of the diet as described in the Limitations on Dosing below .
Creon (Pancreatic) Dosage Forms And Strengths
The active ingredient in Creon (Pancreatic) evaluated in clinical trials is lipase. Creon (Pancreatic) is dosed by lipase units.
Other active ingredients include protease and amylase. Each Creon (Pancreatic) delayed-release capsule strength contains the specified amounts of lipase, protease, and amylase as follows:
Creon (Pancreatic) Contraindications
Creon (Pancreatic) Warnings And Precautions
Fibrosing colonopathy has been reported following treatment with different pancreatic enzyme products. Fibrosing colonopathy is a rare, serious adverse reaction initially described in association with high-dose pancreatic enzyme use, usually over a prolonged period of time and most commonly reported in pediatric patients with cystic fibrosis. The underlying mechanism of fibrosing colonopathy remains unknown. Doses of pancreatic enzyme products exceeding 6,000 lipase units/kg of body weight per meal have been associated with colonic stricture in children less than 12 years of age. Patients with fibrosing colonopathy should be closely monitored because some patients may be at risk of progressing to stricture formation. It is uncertain whether regression of fibrosing colonopathy occurs. It is generally recommended, unless clinically indicated, that enzyme doses should be less than 2,500 lipase units/kg of body weight per meal (or less than 10,000 lipase units/kg of body weight per day) or less than 4,000 lipase units/g fat ingested per day
Doses greater than 2,500 lipase units/kg of body weight per meal (or greater than 10,000 lipase units/kg of body weight per day) should be used with caution and only if they are documented to be effective by 3-day fecal fat measures that indicate a significantly improved coefficient of fat absorption. Patients receiving higher doses than 6,000 lipase units/kg of body weight per meal should be examined and the dosage either immediately decreased or titrated downward to a lower range.
Creon (Pancreatic) Adverse Reactions
The most serious adverse reactions reported with different pancreatic enzyme products of the same active ingredient (pancrelipase) that are described elsewhere in the label include fibrosing colonopathy, hyperuricemia and allergic reactions .
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 practice.
The short-term safety of Creon (Pancreatic) was assessed in clinical trials conducted in 121 patients with exocrine pancreatic insufficiency (EPI): 67 patients with EPI due to cystic fibrosis (CF) and 25 patients with EPI due to chronic pancreatitis or pancreatectomy were treated with Creon (Pancreatic) .
Postmarketing data from this formulation of Creon (Pancreatic) have been available since 2009. The following adverse reactions have been identified during post approval use of this formulation of Creon (Pancreatic) . 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.
Gastrointestinal disorders (including abdominal pain, diarrhea, flatulence, constipation and nausea), skin disorders (including pruritus, urticaria and rash), blurred vision, myalgia, muscle spasm, and asymptomatic elevations of liver enzymes have been reported with this formulation of Creon (Pancreatic) .
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 reactions included fibrosing colonopathy, distal intestinal obstruction syndrome (DIOS), recurrence of pre-existing carcinoma, and severe allergic reactions including anaphylaxis, asthma, hives, and pruritus.
Creon (Pancreatic) Drug Interactions
No drug interactions have been identified. No formal interaction studies have been conducted.
Creon (Pancreatic) Use In Specific Populations
The short-term safety and effectiveness of Creon (Pancreatic) were assessed in two randomized, double-blind, placebo-controlled, crossover studies of 49 patients with EPI due to cystic fibrosis, 25 of whom were pediatric patients. Study 1 included 8 adolescents between 12 and 17 years of age. Study 2 included 17 children between 7 and 11 years of age. The safety and efficacy in pediatric patients in these studies were similar to adult patients .
An open-label, single-arm, short-term study of Creon (Pancreatic) was conducted in 18 infants and children, ages 4 months to six years of age, with EPI due to cystic fibrosis. 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 (Pancreatic) (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 (Pancreatic) . When patients were switched from their usual pancreatic enzyme replacement therapy to Creon (Pancreatic) , they demonstrated similar spot fecal fat testing results; the clinical relevance of spot fecal fat testing has not been demonstrated. Adverse reactions that occurred in patients during treatment with Creon (Pancreatic) were vomiting, irritability, and decreased appetite .
The safety and efficacy of pancreatic enzyme products with different formulations of pancrelipase consisting of the same active ingredient (lipases, proteases, and amylases) for treatment of children with exocrine pancreatic insufficiency due to cystic fibrosis have been described in the medical literature and through clinical experience.
Dosing of pediatric patients should be in accordance with recommended guidance from the Cystic Fibrosis Foundation Consensus Conferences . Doses of other pancreatic enzyme products exceeding 6,000 lipase units/kg of body weight per meal have been associated with fibrosing colonopathy and colonic strictures in children less than 12 years of age .
Creon (Pancreatic) Overdosage
There have been no reports of overdose in clinical trials or postmarketing surveillance with this formulation of Creon (Pancreatic) . Chronic high doses of pancreatic enzyme products have been associated with fibrosing colonopathy and colonic strictures . High doses of pancreatic enzyme products have been associated with hyperuricosuria and hyperuricemia, and should be used with caution in patients with a history of hyperuricemia, gout, or renal impairment .
Creon (Pancreatic) Description
Creon (Pancreatic) is a pancreatic enzyme preparation consisting of pancrelipase, an extract derived from porcine pancreatic glands. Pancrelipase contains multiple enzyme classes, including porcine-derived lipases, proteases, and amylases.
Pancrelipase is a beige-white amorphous powder. It is miscible in water and practically insoluble or insoluble in alcohol and ether.
Each delayed-release capsule for oral administration contains enteric-coated spheres (0.71–1.60 mm in diameter).
The active ingredient evaluated in clinical trials is lipase. Creon (Pancreatic) is dosed by lipase units.
Other active ingredients include protease and amylase.
Creon (Pancreatic) contains the following inactive ingredients: cetyl alcohol, dimethicone, hypromellose phthalate, polyethylene glycol, and triethyl citrate.
Creon (Pancreatic) Clinical Studies
The short-term efficacy of Creon (Pancreatic) was evaluated in three studies conducted in 103 patients with exocrine pancreatic insufficiency (EPI). Two studies were conducted in 49 patients with EPI due to cystic fibrosis (CF); one study was conducted in 54 patients with EPI due to chronic pancreatitis or pancreatectomy.
Studies 1 and 2 were randomized, double-blind, placebo-controlled, crossover studies in 49 patients, ages 7 to 43 years, with exocrine pancreatic insufficiency due to cystic fibrosis. Study 1 included patients aged 12 to 43 years (n = 32). The final analysis population was limited to 29 patients; 3 patients were excluded due to protocol deviations. Study 2 included patients aged 7 to 11 years (n = 17). The final analysis population was limited to 16 patients; 1 patient withdrew consent prior to stool collection during treatment with Creon (Pancreatic) . In each study, patients were randomized to receive Creon (Pancreatic) 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. All patients consumed a high-fat diet (greater than or equal to 90 grams of fat per day, 40% of daily calories derived from fat) during the treatment periods.
The coefficient of fat absorption (CFA) was determined by a 72-hour stool collection during both treatments, when both fat excretion and fat ingestion were measured. Each patient's CFA during placebo treatment was used as their no-treatment CFA value.
In Study 1, mean CFA was 89% with Creon (Pancreatic) treatment compared to 49% with placebo treatment. The mean difference in CFA was 41 percentage points in favor of Creon (Pancreatic) treatment with 95% CI: (34, 47) and p
In Study 2, mean CFA was 83% with Creon (Pancreatic) treatment compared to 47% with placebo treatment. The mean difference in CFA was 35 percentage points in favor of Creon (Pancreatic) treatment with 95% CI: (27, 44) and p
Subgroup analyses of the CFA results in Studies 1 and 2 showed that mean change in CFA with Creon (Pancreatic) treatment was greater in patients with lower no-treatment (placebo) CFA values than in patients with higher no-treatment (placebo) CFA values. There were no differences in response to Creon (Pancreatic) by age or gender, with similar responses to Creon (Pancreatic) observed in male and female patients, and in younger (under 18 years of age) and older patients.
The coefficient of nitrogen absorption (CNA) was determined by a 72-hour stool collection during both treatments, when nitrogen excretion was measured and nitrogen ingestion from a controlled diet was estimated (based on the assumption that proteins contain 16% nitrogen). Each patient's CNA during placebo treatment was used as their no-treatment CNA value.
In Study 1, mean CNA was 86% with Creon (Pancreatic) treatment compared to 49% with placebo treatment. The mean difference in CNA was 37 percentage points in favor of Creon (Pancreatic) treatment with 95% CI: (31, 42) and p
In Study 2, mean CNA was 80% with Creon (Pancreatic) treatment compared to 45% with placebo treatment. The mean difference in CNA was 35 percentage points in favor of Creon (Pancreatic) treatment with 95% CI: (26, 45) and p
A randomized, double-blind, placebo-controlled, parallel group study was conducted in 54 adult patients, ages 32 to 75 years, with EPI due to chronic pancreatitis or pancreatectomy. The final analysis population was limited to 52 patients; 2 patients were excluded due to protocol violations. Ten patients had a history of pancreatectomy (7 were treated with Creon (Pancreatic) ). In this study, patients received placebo for 5 days (run-in period), followed by pancreatic enzyme replacement therapy as directed by the investigator for 16 days; this was followed by randomization to Creon (Pancreatic) or matching placebo for 7 days of treatment (double-blind period). Only patients with CFA less than 80% in the run-in period were randomized to the double-blind period. The dose of Creon (Pancreatic) during the double-blind period was 72,000 lipase units per main meal (3 main meals) and 36,000 lipase units per snack (2 snacks). All patients consumed a high-fat diet (greater than or equal to 100 grams of fat per day) during the treatment period.
The CFA was determined by a 72-hour stool collection during the run-in and double-blind treatment periods, when both fat excretion and fat ingestion were measured. The mean change in CFA from the run-in period to the end of the double-blind period in the Creon (Pancreatic) and Placebo groups is shown in .
Subgroup analyses of the CFA results showed that mean change in CFA was greater in patients with lower run-in period CFA values than in patients with higher run-in period CFA values. Only 1 of the patients with a history of total pancreatectomy was treated with Creon (Pancreatic) in the study. That patient had a CFA of 26% during the run-in period and a CFA of 73% at the end of the double-blind period. The remaining 6 patients with a history of partial pancreatectomy treated with Creon (Pancreatic) on the study had a mean CFA of 42% during the run-in period and a mean CFA of 84% at the end of the double-blind period.
Creon (Pancreatic) How Supplied/storage And Handling
3,000 USP units of lipase; 9,500 USP units of protease; 15,000 USP units of amylase
Each Creon (Pancreatic) capsule is available as a two piece hypromellose capsule with a white opaque cap with imprint “Creon (Pancreatic) 1203” and a white opaque body that contains tan colored, delayed-release pancrelipase supplied in bottles of:
6,000 USP units of lipase; 19,000 USP units of protease; 30,000 USP units of amylase
Each Creon (Pancreatic) capsule is available as a two-piece gelatin capsule with orange opaque cap with imprint “Creon (Pancreatic) 1206” and a blue opaque body that contains tan-colored, delayed-release pancrelipase supplied in bottles of:
12,000 USP units of lipase; 38,000 USP units of protease; 60,000 USP units of amylase
Each Creon (Pancreatic) capsule is available as a two-piece gelatin capsule with a brown opaque cap with imprint “Creon (Pancreatic) 1212” and a colorless transparent body that contains tan-colored, delayed-release pancrelipase supplied in bottles of:
24,000 USP units of lipase; 76,000 USP units of protease; 120,000 USP units of amylase
Each Creon (Pancreatic) capsule is available as a two-piece gelatin capsule with orange opaque cap with imprint “Creon (Pancreatic) 1224” and a colorless transparent body that contains tan-colored, delayed-release pancrelipase supplied in bottles of:
Creon (Pancreatic) must be stored at room temperature up to 25°C (77°F) and protected from moisture. Temperature excursions are permitted between 25°C to 40°C (77°F and 104°F) for up to 30 days. Product should be discarded if exposed to higher temperature and moisture conditions higher than 70%. between uses to .
Bottles of Creon (Pancreatic) 3,000 USP units of lipase must be stored and dispensed in the original container.
Creon (Pancreatic) Patient Counseling Information
See FDA-approved patient labeling (Medication Guide)
Manufactured by:
Marketed By:
1055216 12E Rev Jul 2011
© 2011 Abbott Laboratories
Creon (Pancreatic)
Creon (Pancreatic)
