Crezanta 10 000 pH. Eur. units, gastro-resistant hard capsules – Summary of Product Characteristics (SmPC) for healthcare professionals

1 NAME OF THE MEDICINAL PRODUCT

Crezanta 10,000 Ph. Eur. units, gastro-resistant hard capsules

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each gastro-resistant capsule contains pancreatin (as pancreas powder) * corresponding to:

Amylase 8,000 Ph. Eur. units

Lipase 10,000 Ph. Eur. units

Protease 600 Ph. Eur. units

*Produced from porcine pancreatic tissue.

For the full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Gastro-resistant capsule, hard

Hard gelatin capsules of size 2 (length 17.8 ± 0.4 mm) with a brown cap and transparent body, filled with cylindrical, spherical or irregularly shaped gastro-resistant pellets (micro pellets) of light brown to brown colour.

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

For the treatment of exocrine pancreatic insufficiency.

4.2 Posology and method of administration

Adults (including the elderly) and children:

Initially one or two capsules during or immediately after each meal. Dose increases, if required, should be added slowly, with careful monitoring of response and symptomatology.

Method of administration

The capsules can be swallowed whole, or for ease of administration they may be opened and the granules taken with acidic fluid or soft food, but without chewing.

This could be apple sauce or yoghurt or any fruit juice with a pH less than 5.5, e.g. apple, orange or pineapple juice. If the granules are mixed with fluid or food it is important that they are taken immediately and the mixture not stored, otherwise dissolution of the enteric coating may result. In order to protect the enteric coating, it is important that the granules are not crushed or chewed. Crushing and chewing of the minimicrospheres or mixing with food or fluid with a pH greater than 5.5 can disrupt the protective enteric coating. This can result in early release of enzymes in the oral cavity and may lead to reduced efficacy and irritation of the mucous membranes. Care should be taken to ensure that no product is retained in the mouth.

It is important to ensure adequate hydration of patients at all times whilst dosing Crezanta.

Fibrosing colonopathy has been reported in patients with cystic fibrosis taking in excess of 10,000 units of lipase kg/day (see section 4.4).

4.3 Contraindications

Hypersensitivity to the pancreatin of porcine origin or to any of the excipients listed in section 6.1.

4.4 Special warnings and precautions for use

Fibrosing colonopathy

Strictures of the ileo-caecum and large bowel (fibrosing colonopathy) have been reported in patients with cystic fibrosis taking high doses of pancreatin preparations. As a precaution, unusual abdominal symptoms or changes in abdominal symptoms should be medically assessed to exclude the possibility of fibrosing colonopathy, especially if the patient is taking in excess of 10,000 units of lipase/per kilogram bodyweight per day.

Anaphylactic reactions

Rarely, anaphylactic reactions have been reported with pancreatic enzyme products with different formulations of the same active ingredient (pancreas powder). If this reaction occurs, patients should be advised to discontinue treatment immediately and seek urgent medical assistance.

To reduce the risk of adverse reactions due to hypersensitivity, caution is advised in patients with allergy to porcine proteins.

Potential for irritation to oral mucosa

Care should be taken to ensure that no medicinal product is retained in the mouth. This medicine should not be crushed or chewed or kept too long in the mouth and/or mixed in foods having a pH greater than 5.5. These actions can disrupt the protective gastro-resistant coating resulting in early release of enzymes, oral pain, irritation of oral mucosa, bleeding, ulcer formation in the mouth and/or loss of enzyme activity (see section 4.2).

Rinsing the mouth and drinking of a glass of water may help if there are preliminary signs of mouth irritation.

Traceability

In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.

This medicine is essentially 'sodium-free'.

Alcohol

Use of this medicine concomitantly with heavy alcohol is not recommended for all the proposed strengths (see section 5.2).

4.5 Interaction with other medicinal products and other forms of interaction

No interaction studies have been performed.

4.6 Fertility, pregnancy and lactation

Pregnancy

There are no or limited amount of data (less than 300 pregnancy outcomes) from the use of porcine pancreatic enzymes in pregnant women. There are no data from animal studies with respect to reproductive toxicity (see section 5.3), but animal studies show no evidence for any absorption of porcine pancreatic enzymes. Therefore, no reproductive or developmental toxicity is to be expected. This medicinal product can be used during pregnancy if necessary, to provide adequate nutritional support to a pregnant woman with exocrine pancreatic insufficiency.

Breastfeeding

No effects on the breastfed newborn/infant are anticipated since the systemic exposure of the breast-feeding woman to porcine pancreatic enzymes is negligible. Pancreatic enzymes can be used during breastfeeding.

Fertility

No effects on fertility are anticipated since pancreatic enzymes are not absorbed from the gastrointestinal tract.

4.7 Effects on ability to drive and use machines

This medicine has no or negligible influence on the ability to drive and use machines.

4.8 Undesirable effects

The most important serious adverse reactions observed with pancreatic enzyme medicinal products are anaphylactic reactions (see section 4.4) and fibrosing colonopathy (see section 4.4).

In clinical trials, more than 1 000 patients were exposed to pancreatin. The most commonly reported adverse reactions were gastrointestinal disorders and were primarily mild or moderate in severity.

The following adverse reactions have been observed with the below indicated frequencies:

* The following symptoms of hypersensitivity have been observed during post-approval use:

generalised rash, angioedema, lips swelling, oral mucosa and face swelling, burning and swelling around the eyes, asthmatic complaints. In addition, tachycardia and hypotension have been reported in the condition of an anaphylactic shock.

** Gastrointestinal disorders are mainly associated with the underlying disease. Similar or lower incidences compared to placebo were reported for abdominal pain and diarrhoea.

Strictures of the ileo-caecum and large bowel (fibrosing colonopathy) have been reported in patients with cystic fibrosis taking high doses of pancreatin preparations, see section 4.4 Special warnings and precautions for use.

Paediatric population

No specific adverse reactions were identified in the paediatric population. Frequency, type and severity of adverse reactions were similar in children with cystic fibrosis as compared to adults.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via Yellow Card Scheme Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9 Overdose

Chronic high doses of pancreatic enzyme products have been associated with fibrosing colonopathy and as a result in some cases colonic strictures (see sections 4.2 and 4.4).

Extremely high doses of pancreatin have been reported to be associated with hyperuricosuria and hyperuricaemia.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Digestives, incl. enzymes; Enzyme preparations, ATC code: A09AA02

Mechanism of action

This medicine contains porcine pancreatin formulated as enteric-coated (acid-resistant) pellets within gelatin 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.

Clinical efficacy

Overall, 33 studies investigating the efficacy of pancreatin in patients with pancreatic exocrine insufficiency have been conducted. Eleven of these were 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 pancreatin 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 pancreatin treatment (83.0%) as compared to placebo (59.1%). In all studies, irrespective of the design, the mean CFA (%) at the end of the treatment period with Pancreatin was similar to the mean CFA values for pancreatin in the placebo-controlled studies.

Treatment with pancreatin 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 pancreatin was demonstrated in 340 paediatric patients covering an age range from newborns to adolescents. In all studies, the mean end-of-treatment CFA values exceeded 80% on pancreatin comparably in all paediatric age groups.

5.2 Pharmacokinetic properties

Alcohol

An in vitro study showed significant increases of pancreatin release from pancreatin capsules at 2 hours to approximately 48% of the label claim in the presence of 20 % alcohol. The effect of 5 % and 10 % alcohol on pancreatin release was observed at 2 hours to approximately 4 % and 6% of the label claim.

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.

5.3 Preclinical safety data

Preclinical data show no relevant repeated dose toxicity. Animal studies show no evidence for absorption of porcine pancreatic enzymes from the gastrointestinal tract after oral administration. Studies on genotoxicity, carcinogenicity or toxicity to reproduction have not been performed.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Pellets:

cetyl alcohol, poloxamer.

Gastro-resistant coating:

methacrylic acid - ethyl acrylate copolymer (1:1) dispersion 30 %, macrogol-4000, talc, simeticone, methyl cellulose, sorbic acid.

Gelatin capsules, hard

gelatin, yellow iron oxide (E172), black iron oxide (E172), red iron oxide (E172) , titanium dioxide (E171).

6.2 Incompatibilities

Not applicable

6.3 Shelf life

24 months

6.4 Special precautions for storage

Store below 25 °C. After opening use within 3 months.

Keep the bottle tightly closed in order to protect from moisture.

6.5 Nature and contents of container

This medicine is available in a 75 ml white HDPE bottle with a white PP screw cap containing a coloured white insert block made of low density polyethylene with desiccant inside (silica gel). Each bottle contains 100 capsules and is overpacked in a carton box.

Not all pack sizes may be marketed

6.6 Special precautions for disposal

No special requirements.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

7 MARKETING AUTHORISATION HOLDER

Aspire Pharma Ltd

Unit 4 Rotherbrook Court

Bedford Road

Petersfield

Hampshire

GU32 3QG

United Kingdom

8 MARKETING AUTHORISATION NUMBER(S)

PL 35533/0206

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE

AUTHORISATION

06/07/2026

10 DATE OF REVISION OF THE TEXT

06/07/2026