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Pharmacotherapeutic group: Multienzymes (amylase, lipase, protease). ATC code: A09A A02.
Pharmacology: Pharmacodynamics: Creon contains porcine pancreatin formulated as enteric-coated (acid-resistant) pellets within gelatine capsules.
The capsules dissolve rapidly in the stomach releasing plenty of pellets, a multi-dose principle which is designed to achieve good mixing with the chyme, emptying from the stomach together with the chyme and after release, good distribution of enzymes within the chyme.
When the pellets reach the small intestine the coating rapidly disintegrates (at pH >5.5) to release enzymes with lipolytic, amylolytic and proteolytic activity to ensure the digestion of fats, starches and proteins. The products of pancreatic digestion are then either absorbed directly, or following further hydrolysis by intestinal enzymes.
Clinical efficacy: Overall 30 studies investigating the efficacy of Creon in patients with pancreatic exocrine insufficiency have been conducted. Ten of these were either placebo-controlled studies performed in patients with cystic fibrosis, chronic pancreatitis or post-surgical conditions.
In all randomized, placebo-controlled, efficacy studies, the pre-defined primary objective was to show superiority of Creon over placebo on the primary efficacy parameter, the coefficient of fat absorption (CFA).
The coefficient of fat absorption determines the percentage of fat that is absorbed into the body taking into account fat intake and fecal fat excretion. In the placebo-controlled PEI studies, the mean CFA (%) was higher with Creon treatment (83.0%) as compared to placebo (62.6%). In all studies, irrespective of the design, the mean CFA (%) at the end of the treatment period with Creon was similar to the mean CFA values for Creon in the placebo-controlled studies.
Treatment with Creon markedly improves the symptoms of pancreatic exocrine insufficiency including stool consistency, abdominal pain, flatulence and stool frequency, independent of the underlying disease.
Paediatric population: In cystic fibrosis (CF), the efficacy of Creon was demonstrated in 288 paediatric patients covering an age range from newborns to adolescents. In all studies, the mean end-of-treatment CFA values exceeded 80% on Creon comparably in all paediatric age groups.
Pharmacokinetics: Animal studies showed no evidence for absorption of intact enzymes and therefore classical pharmacokinetic studies have not been performed. Pancreatic enzyme supplements do not require absorption to exert their effects.
On the contrary, their full therapeutic activity is exerted from within the lumen of the gastrointestinal tract. Furthermore, they are proteins, and as such undergo proteolytic digestion while passing along the gastrointestinal tract before being absorbed as peptides and amino acids.
Toxicology: Preclinical Safety Data: Preclinical data show no relevant acute, subchronic or chronic toxicity. Studies on genotoxicity, carcinogenicity or toxicity to reproduction have not been performed.
