Creon®chic

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT KREON®CHICK (KREON®CHICK)

Composition:

Active substance: pancreatin;

1 dose (100 mg) contains 60.12 mg of pancreatin in gastroresistant granules (mini-microspheres) with enzymatic activity: lipase 5000 IU Ph. Eur., amylase 3600 IU Ph. Eur., protease 200 IU Ph. Eur.;

Excipients: macrogol 4000, hypromellose phthalate, cetyl alcohol, triethyl citrate, dimethicone 1000.

Pharmaceutical form. Gastroresistant granules.

Main physicochemical characteristics: brownish granules.

Pharmacotherapeutic group. Digestive enzymes and other agents that improve digestion. Pancreatic enzyme preparations. ATC code A09AA02.

Pharmacological Properties

Pharmacodynamics

CREON®CHIK contains pancreatic powder (pancreatin) of porcine origin in the form of granules coated with an enteric coating.

Pancreatic powder contains exocrine enzymes of the pancreas: lipase, alpha-amylase, trypsin, chymotrypsin, and other enzymes. The pancreatic powder also contains other components that do not have enzymatic activity. These components, which are not absorbed, are degraded and denatured by digestive juices or bacteria.

Digestive capacity is determined by enzyme activity and galenic formulation. Key factors are the enzymatic activity of lipase and the content of trypsin, whereas amylolytic activity is relevant only in the treatment of cystic fibrosis, since even in chronic pancreatitis, the breakdown of dietary polysaccharides continues unimpeded.

Pancreatic lipase hydrolyzes fatty acids at positions 1 and 3 of the triacylglycerol molecule. The released fatty acids and 2-monoglycerides are rapidly absorbed, primarily in the upper segments of the small intestine, with the help of bile acids. Pancreatic lipase of animal origin, like human lipase, is acid-labile; therefore, its lipolytic activity is progressively and irreversibly inactivated at pH < 4.

Trypsin is activated via autocatalysis from trypsinogen or by enteropeptidase of the small intestine and, as an endopeptidase, cleaves peptide bonds involving lysine and arginine. According to recent research, trypsin is considered a feedback inhibitor of stimulated pancreatic secretion induced by active trypsin in the upper segments of the small intestine. In several studies, the analgesic effect of pancreatic enzyme preparations has been attributed to this activity.

Alpha-amylase rapidly breaks down glucose-containing polysaccharides as an endoamylase, so its activity is sufficient even in cases of significantly reduced pancreatic secretory activity due to disease.

The galenic design of the preparation ensures optimal utilization of the enzymatic activity of pancreatic powder in the digestion of food.

Gastro-resistant granules containing a mixture of all pancreatic enzymes represent a multi-dose formulation designed to ensure thorough mixing of granules with chyme, so that they exit the stomach together with chyme into the duodenum, and after their release, enzymes are properly distributed within the chyme.

As soon as the granules enter the small intestine, the protective film dissolves rapidly (at pH > 5.5), releasing the enzymes. Subsequent digestion of chyme proceeds exactly as in physiological digestion, since digestion and absorption of nutrients are spatially and temporally limited processes. Digestion products are either absorbed directly or further hydrolyzed by intestinal enzymes.

Due to the galenic formulation, enzyme activity is not reduced by the highly acidic pH environment in the stomach. Enzyme availability depends on pH levels.

Clinical efficacy.

Overall, 30 clinical efficacy studies have been conducted. Among them, 10 were placebo-controlled studies involving patients with cystic fibrosis, chronic pancreatitis, or postoperative patients.

In all randomized, placebo-controlled efficacy studies, the pre-defined primary objective was to demonstrate superior efficacy of CREON®CHIK compared to placebo based on the primary efficacy endpoint—the coefficient of fat absorption (CFA). The coefficient of fat absorption indicates the percentage of fat absorbed by the body relative to total fat intake.

In placebo-controlled studies involving patients with exocrine pancreatic insufficiency, the mean CFA value was higher in patients receiving the medication (83%) compared to the placebo group (62.6%).

Across all studies, regardless of study design, mean CFA values at the end of the treatment period with the medication were similar to mean CFA values observed in placebo-controlled studies.

Treatment with CREON®CHIK significantly reduces symptoms caused by impaired exocrine pancreatic function, including stool consistency, abdominal pain, flatulence, and stool frequency, regardless of the underlying disease.

Children.

The efficacy of the medication has been demonstrated in 288 patients with cystic fibrosis across all age groups—from newborns to adults. In all studies, mean CFA values at the end of the treatment period exceeded 80%, regardless of age group.

Pharmacokinetics

Animal studies did not reveal evidence of absorption of enzymes in their unchanged form, and therefore classical pharmacokinetic studies were not conducted. Pancreatic enzymes are not intended to be absorbed to achieve their effect. On the contrary, their full therapeutic action occurs within the intestinal lumen. Moreover, as proteins, pancreatic enzymes are primarily degraded through autolysis or proteolysis as they pass through the gastrointestinal tract before being absorbed in the form of peptides and amino acids.

Clinical characteristics.

Indications.

Exocrine pancreatic insufficiency associated with digestive disturbances.

Support of insufficient pancreatic function in patients with cystic fibrosis.

Contraindications.

Should not be used in cases of proven hypersensitivity to the active substance or to pork (pork allergy), or to any other component of the medicinal product.

Interaction with other medicinal products and other forms of interactions.

Interaction studies have not been conducted.

Special precautions for use.

In patients with cystic fibrosis who have taken high doses of pancreatin preparations, narrowing of the ileocecal region of the intestine and colon (fibrosing colonopathy) has been observed.

As a precautionary measure, it is recommended that if unusual abdominal symptoms occur or changes in symptoms appear, medical advice should be sought to rule out the possibility of fibrosing colonopathy. This is particularly relevant for patients receiving more than 10,000 IU of lipase per kg of body weight per day.

Use during pregnancy or breastfeeding.

There are insufficient data on the use of the medicinal product in pregnant women. Data on effects on pregnancy, embryonic/fetal development, labour or postnatal development obtained from animal studies are limited. Therefore, the potential risk in humans is unknown. Hence, the product should not be used during pregnancy or breastfeeding, except in cases of extreme necessity.

Ability to affect reaction speed when driving vehicles or operating machinery.

The effect of the medicinal product CREON®CHIK on the ability to drive vehicles or operate machinery is negligible or absent.

Method of Administration and Dosage

Dosing

The dosage of the medicinal product is based on individual patient needs and depends on the severity of pancreatic insufficiency and the composition of food.

The amount of the drug is measured with the dosing spoon provided in the package. 100 mg of gastroresistant granules corresponds to 5000 units of lipase (1 measuring spoon).

Dosing for Children

Generally, the dose for newborns is 100 mg of gastroresistant granules, corresponding to 5000 units of lipase (1 measuring spoon) per dose.

For children under 4 years of age, the dose is calculated according to body weight and starts at 1000 IU Ph. Eur. (PhEur) lipase/kg body weight/dose. For children aged 4 years and older, dosing starts at 500 IU PhEur lipase/kg body weight/dose.

Dosing for Adolescents and Adults

Dosage should be individually adjusted for each patient depending on the degree of digestive impairment and fat content in the diet. Generally, a dose of 20000 to 80000 IU PhEur lipase per meal is recommended, corresponding to 4–16 measuring spoons of the drug. The required dose may be significantly higher depending on the severity of digestive impairment.

Maximum Recommended Daily Dose

Particularly for patients with cystic fibrosis, considering the quantity and composition of food, the dose should not exceed the amount of enzymes necessary for adequate fat absorption. The dose should be increased only under medical supervision, and dose escalation should aim to alleviate symptoms (e.g., steatorrhea, abdominal pain).

The daily dose of lipase should not exceed 15000–20000 IU PhEur per kilogram of body weight or 4000 IU PhEur lipase per gram of ingested fat.

Method of Administration

The special dosage form of the drug with very small granules is suitable for administration to infants and children who cannot swallow capsules.

The dose of CREON®CHIK can be individually adjusted when low doses of lipase are required for treatment of children.

The granules may be added to small amounts of soft food with an acidic environment (pH < 5.5) that does not require chewing (e.g., apple puree), or to liquids with an acidic environment (pH < 5.5).

Alternatively, the granules may be mixed with a small amount of milk in a feeding spoon and immediately administered to the child. Granules should not be added to a bottle containing infant formula.

Any mixture of the drug with food or liquid should be swallowed immediately and not stored. The granules should be swallowed whole without chewing and should not be retained in the oral cavity. Crushing or chewing the granules, or mixing them with food or liquid with pH > 5.5, may destroy the gastroresistant coating of the granules. This could lead to premature release of enzymes in the oral cavity, reduced efficacy of the drug, and irritation of mucous membranes.

It is recommended to rinse any residual drug from the oral cavity with liquid.

Gastroresistant granules may also be administered via a gastric feeding tube.

Children

CREON®CHIK can be used in children.

Overdose

It has been reported that ingestion of extremely high doses of pancreatin, including in patients with cystic fibrosis, may be associated with increased levels of uric acid in blood serum and urine.

Adverse Reactions

The effect of the medicinal product CREON®CHIK was studied in more than 1000 patients during clinical trials. Gastrointestinal disorders, mostly mild to moderate in severity, were the most commonly reported.

The adverse reactions observed during clinical trials and their frequency are listed below.

The frequency of adverse reactions is defined according to the following classification:

very common (≥ 1/10),
common (from ≥ 1/100 to < 1/10),
uncommon (from ≥ 1/1000 to < 1/100),
rare (from ≥ 1/10000 to < 1/1000),
very rare (< 1/10000),
frequency not known (cannot be estimated from available data).

Gastrointestinal disorders: very common — abdominal pain*; common — nausea, vomiting, constipation, diarrhea*, bloating; frequency not known — narrowing of the ileocecal region and colon (fibrosing colonopathy).

*Gastrointestinal disorders are primarily related to the underlying disease. Diarrhea and abdominal pain were reported at a frequency similar to or lower than that with placebo.

Skin and subcutaneous tissue disorders: uncommon — rash; frequency not known — pruritus, urticaria.

Immune system disorders: frequency not known — hypersensitivity (anaphylactic reactions).

Cases of narrowing of the ileocecal region and colon (fibrosing colonopathy) have been reported in patients with cystic fibrosis who were taking high doses of pancreatin-containing products (see section "Special precautions for use").

Allergic reactions, predominantly (but not exclusively) manifesting as skin reactions, have been identified as adverse reactions during post-marketing use. Since reports of these reactions were spontaneous and received from an undefined number of patients, the exact frequency of these reactions cannot be determined.

Children

No specific adverse reactions have been identified in children. The frequency, type, and severity of adverse reactions in children with cystic fibrosis were similar to those in adults.

Reporting suspected adverse reactions after marketing authorization is highly important. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals, pharmacists, patients, and their legal representatives are encouraged to report all suspected adverse reactions and lack of efficacy via the Automated Information System for Pharmacovigilance at: https://aisf.dec.gov.ua.

Shelf life.

3 years. Shelf life after first opening — 3 months.

Storage conditions.

Store at temperatures not exceeding 25 °C in tightly closed packaging. Keep out of reach of children.

Packaging.

20 g of gastro-resistant granules in a glass bottle. 1 bottle with a measuring spoon in a cardboard box.

Availability.

Over-the-counter (without prescription).

Manufacturer.

Abbott Laboratories GmbH, Germany.

Manufacturer's address and location of operations.

Abbott Laboratories, Plant Neustadt, Justus-von-Liebig-Str. 33, 31535 Neustadt a. Rbge., Germany.