Creon 10000

This hard capsule with gastro-resistant pellets is a bicolor capsule with brown cap and transparent body.
One hard capsule with gastro-resistant pellets contains 150 mg pancreas powder, made from pig pancreas tissue, corresponding to: Amylolytic activity 8,000 Ph.Eur. units; Lipolytic activity 10,000 Ph.Eur. units; Proteolytic activity 600 Ph.Eur. units.
Excipients/Inactive Ingredients: Cetyl alcohol, triethyl citrate, dimethicone 1000, macrogol 4000, hypromellose phthalate, gelatin, sodium dodecyl sulphate, titanium dioxide (E171), anhydrous iron (III) oxide (E172), hydrated iron (III) oxide (E172), iron (II, III) oxide (E172).
Note: Creon contains no sugar and is therefore also suitable for diabetics.

Pharmacotherapeutic group: Digestion products, multi-enzymes. ATC code: A09AA02.
Pharmacology: Pharmacodynamics: Creon 10000 capsules contain pancreatin powder produced from porcine pancreas tissue in the form of gastro-resistant pellets in hard gelatin capsules.
Pancreatin contains the excretory pancreatic enzymes lipase, alpha-amylase, trypsin, chymotrypsin and other enzymes. Pancreatin also contains additional excipients devoid of enzymatic activity. The non-absorbed portion is broken down and denatured by gastric juices or bacteria. Gastrointestinal availability is determined by enzyme activity and the pharmaceutical form. Lipase enzyme activity and trypsin content are crucial whereas amylolytic activity is significant only in the treatment of cystic fibrosis since food polysaccharides continue to be broken down undisturbed even in cases of chronic pancreatitis.
Pancreatic lipase breaks down the fatty acids in positions 1 and 3 from a triacylglyceride molecule. The free fatty acids and 2-monoglycerides thus released are mainly rapidly absorbed from the upper small intestine with the aid of bile acids. Animal pancreatic lipase is unstable in acids, just like human lipase. Its lipolytic activity is therefore inactivated to an increasingly irreversible extent at pH <4.
Trypsin is activated from trypsinogen autocatalytically or by small intestine enterokinase, and is broken down as endopeptidase peptide compounds involving lysine and arginine. Based on recent research, trypsin-mediated feedback inhibition of stimulated pancreatic secretion by active trypsin in the upper small intestine is assumed. The analgesic effect of pancreatin preparations described in a few studies is attributed to this effect.
Alpha-amylase very rapidly breaks down glucose-containing polysaccharides as endoamylase such that its activity is still sufficient even in cases where the secretory activity of the pancreas is considerably reduced due to disease.
The galenical principle of Creon guarantees optimum use of the enzymatic activities of pancreatin for the digestion of food. The gastro-resistant micropellets containing a mixture of all the pancreatic enzymes are enclosed in readily soluble hard gelatine capsules. The capsules dissolve within 2 to 3 minutes in the stomach, regardless of pH, and release numerous micropellets. This multi-dosing principle has been developed in order to mix the micropellets thoroughly with the chyme. This facilitates the entire removal of the micropellets with the chyme from the stomach to the duodenum and effective distribution of the enzymes in the chyme post-release. As soon as the micropellets reach the small intestine, the protective film quickly dissolves (at pH >5.5) and the enzymes are released. The breakdown of the chyme can then begin as in the physiological digestion process since the breaking down and absorption of nutrients is limited in terms of time and space. The degradation products are either absorbed directly or further hydrolysed by intestinal enzymes.
Due to the galenical preparation, activity losses are avoided with Creon due to a strongly acidic gastric pH. Enzyme availability is pH-dependent.
Clinical efficacy: Overall, 30 studies have been carried out to establish the clinical efficacy of Creon in patients with exocrine pancreatic insufficiency. These include 10 studies versus placebo involving patients with cystic fibrosis, chronic pancreatitis or following surgery.
In all randomised, placebo-controlled efficacy studies, the primary objective was to demonstrate the superiority of Creon over placebo for the primary efficacy parameter, the fat absorption coefficient (CFA). The CFA refers to the percentage of fat absorbed in relation to the total fat intake.
In PEI studies versus placebo, the mean CFA during Creon treatment was higher than that observed with placebo (83% versus 62.6%). In all trials, regardless of design, the mean CFA value at the end of Creon treatment was comparable to that recorded in the placebo-controlled studies.
Creon treatment substantially improves the symptoms of exocrine pancreatic insufficiency including stool consistency, abdominal pain, distension and bowel movements, regardless of the underlying condition.
Paediatric population: The efficacy of Creon in cystic fibrosis was confirmed in 288 paediatric patients ranging from new-born infants to adulthood. In all studies, the mean CFA value on completion of Creon treatment was over 80%, regardless of age group.
Pharmacokinetics: Since animal studies have not highlighted intact enzyme absorption, no conventional pharmacokinetic studies were carried out. Pancreatic enzymes do not have to be absorbed in order to be effective. However, their full therapeutic activity is apparent in the intestinal lumen. As proteins, pancreatic enzymes are mainly digested in the intestine by autolysis or proteolysis as they pass through the gastrointestinal tract and are absorbed as peptides and amino acids.
Toxicology: Preclinical safety data: There is no evidence of relevant acute, subchronic or chronic toxicity in the preclinical data. No genotoxicity, carcinogenicity or reproduction toxicity studies have been conducted. Pancreatin is not expected to have systemic toxic effects following oral administration.

Disorders of exocrine pancreas function, accompanied by maldigestion. In case of cystic fibrosis to support insufficient pancreatic function.

Dosage: The dosage depends on the individual requirements and the severity of pancreatic insufficiency and the composition of the meal.
Dosage in children: In children aged under 4 years the weight-based dose should begin with 1,000 Ph.Eur. lipase units/kg body weight/meal, in children over 4 years with a dose of 500 Ph.Eur lipase units/kg body weight/meal.
Dose for adolescents and adults: The dose should be adjusted for the individual patient, depending on the severity of the maldigestion and the fat content of the meal. As a general guide dose a lipase content per meal of between 20,000 and 80,000 Ph.Eur units (corresponding to 2 to 8 capsules of Creon 10000 capsules) is recommended. The required dose may however be considerably higher depending on the severity of the digestion weakness.
Recommended maximum daily dose: Particularly in patients with cystic fibrosis the dose taking into account the quantity and composition of the meals should not exceed the enzyme dose necessary for adequate fat absorption. The dose should only be increased under medical supervision and should aim at improving the symptoms (e.g. steatorrhoea, abdominal pain).
A daily enzyme dose of 15,000-20,000 PH. Eur. Lipase units/kilogram body weight or of 4,000 PH. Eur. Lipase units/gram of fat intake should not be exceeded.
Method of administration: The capsules should be taken unopened and without chewing with or immediately after a meal or a snack with sufficient fluid. Should it be difficult to swallow the capsules (e.g. small children, elderly patients), the capsules may be carefully opened and the pellets added to soft food (pH<5.5), which does not require chewing (e.g. apple puree) or the pellets may be taken with sufficient fluid.
All mixtures of pellets with food or fluids should be used immediately and not stored. Crushing or chewing the pellets or mixing with food or fluids with a pH higher than 5.5 may destroy the gastro-resistant coating of the pellets. As a result the enzymes may be released prematurely in the oral cavity, their efficacy reduced, and the mucous membrane there damaged. Care should be taken that no product residues remain in the oral cavity. Make sure sufficient fluid is taken.

Extremely high doses of pancreatin may be linked to elevated uric acid levels in the serum and urine, particularly in cystic fibrosis patients.

Creon 10000 capsules must not be taken by patients with proven hypersensitivity to pork (pork allergy) or to any of the excipients of Creon 10000 capsules listed in Description.

Strictures in the ileocaecal region and the ascending colon (fibrosing colonopathy) have been reported in cystic fibrosis patients receiving high doses of pancreatin preparations. As a precautionary measure, medical advice should be sought in the event of unusual abdominal discomfort or a change in the clinical picture in order to rule out the possibility of fibrosing colonopathy. This applies in particular to patients taking over 10,000 Ph. Eur. lipase units per kg body weight per day.
Effects on ability to drive and use machines: Creon has no effect or a negligible effect on the ability to drive and use machines.

No adequate data are available on the use of Creon in pregnant women. Only insufficient data from animal studies are available regarding the effects on pregnancy, embryonal/foetal development, childbirth or postnatal development. The potential risk to humans is therefore not known. Thus Creon should not be taken during pregnancy or while breast-feeding unless it is absolutely necessary.

Over 900 patients have been treated with Creon in clinical studies. The most commonly reported adverse events were mostly mild to moderate gastrointestinal disorders.
The following adverse reactions were observed during clinical studies.
The following categories are used to assess the frequency of adverse reactions: Very common: can affect more than 1 in 10 of those treated; Common: can affect up to 1 in 10 of those treated; Uncommon: can affect up to 1 in 100 of those treated; Rare: can affect up to 1 in 1,000 of those treated; Very rare: can affect up to 1 in 10,000 of those treated; Not known: frequency cannot be estimated from the available data. (See table.)

Click on icon to see table/diagram/image

Strictures in the ileocaecal region and the ascending colon (fibrosing colonopathy) have been reported in cystic fibrosis patients receiving high doses of pancreatin preparations - see Precautions.
Periodic Safety Update Reports have highlighted allergic reactions limited mainly, but not exclusively, to the skin.
Paediatric population: No specific adverse reactions have been observed in the paediatric population. The frequency, nature and severity of the adverse reactions in children with cystic fibrosis were similar to those documented in adults.
Reporting of suspected adverse reactions: Reporting of suspected adverse reactions after authorization of the medicinal product is important. It allowed continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions to Drug Office, Department of Health via link http://www.drugoffice.gov.hk/eps/do/en/healthcare_providers/adr_reporting/adr_report_form.html.

No interaction studies have been carried out.

Incompatibilities: Not applicable.

Digestives

A09AA02 - multienzymes (lipase, protease etc.) ; Belongs to the class of enzyme preparations used as digestives.

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