4.1. Therapeutic indications

For the treatment of pancreatic exocrine insufficiency.

4.2. Posology and method of administration

Initially 100 mg (5000 lipase units) of gastro-resistant granules (one measure) should be taken with each feed or meal or immediately after. Dose increases, if required, should be added slowly, with careful monitoring of response and symptomatology. The maximum daily dosage should not exceed 10,000 units lipase/kg/day. The required quantity of gastro-resistant granules should be dispensed using the measuring scoop contained in the pack which holds 100 mg.

In young infants, Creon Micro granules should be mixed with a small amount of apple juice and given from a spoon directly before the feed. In weaned infants, granules should be taken with acidic liquids or soft foods (e.g. mixed with apple juice or apple puree), but without chewing, directly before the meal. When giving Creon Micro to young or weaned infants the apple juice should not be diluted. Alternatively, the granules can be mixed with a small amount of milk on a spoon and administered to the infant immediately. The granules should not be added to the baby's bottle.

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 with Creon.

Fibrosing colonopathy has been reported in patients with cystic fibrosis taking in excess of 10000 units of lipase/kg/day (see section 4.4).

4.3. Contraindications

Hypersensitivity to pancreatin of porcine origin or to any of the excipients.

4.4. Special warnings and precautions for use

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/kg/day.

Creon is essentially 'sodium free' as it contains less than 1 mmol sodium (23 mg) per dose (2 mg).

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.

4.5. Interaction with other medicinal products and other forms of interaction

No interaction studies have been performed.

4.6. Pregnancy and lactation

Pregnancy

For pancreatic enzymes no clinical data on exposed pregnancies are available. Animal studies show no evidence for any absorption of porcine pancreatic enzymes. Therefore, no reproductive or developmental toxicity is to be expected. Caution should be exercised when prescribing to pregnant women.

Lactation

No effects on the suckling child are anticipated since animal studies suggest no systemic exposure of the breastfeeding woman to pancreatic enzymes. Pancreatic enzymes can be used during breastfeeding.

If required during pregnancy or lactation Creon should be used in doses sufficient to provide adequate nutritional status

4.7. Effects on ability to drive and use machines

Creon has no or negligible influence on the ability to drive or use machines.

4.8. Undesirable effects

In clinical trials, more than 900 patients with were exposed to Creon. The most commonly reported adverse reactions were gastrointestinal disorders and were primarily mild or moderate in severity.

The following adverse reactions have been observed during clinical trials with the below indicated frequencies

Organ system

Very common

≥ 1/10

Common

≥ 1/100 to < 1/10

Uncommon

≥ 1/1000 to < 1/100

Frequency not known

Gastrointestinal disorders

abdominal pain*

nausea, vomiting, constipation, abdominal distention, diarrhoea*

strictures of the ileo-caecum and large bowel (fibrosing colonopathy)

Skin and subcutaneous tissue disorders

rash

pruritus, urticaria

Immune system disorders

hypersensitivity (anaphylactic reactions).

*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.

Allergic reactions mainly but not exclusively limited to the skin have been observed and identified as adverse reactions during post-approval use. Because these reactions were reported spontaneously from a population of uncertain size, it is not possible to reliably estimate their frequency.

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 directly via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.

4.9. Overdose

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

Supportive measures including stopping enzyme therapy and ensuring adequate rehydration are recommended.