Creon^® Micro Pancreatin 60.12 mg Gastro-resistant Granules

Each 100 mg of gastro-resistant granules (equivalent to one measuring spoonful) contains 60.12mg of pancreatin, containing the following pancreatic enzymes:

For excipients, see 6.1.

Gastro-resistant granules.

Round, light brown gastro-resistant granules.

For the treatment of pancreatic exocrine insufficiency.

Initially 100 mg (5000 lipase units) of gastro-resistant granules (one measure) should be taken with each feed or meal. 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.

If the granules are mixed with fluid or food it is important that they are taken immediately, 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.

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).

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

Strictures of the ileo-caecum and large bowel (fibrosing colonopathy) have been reported in patients with cystic fibrosis taking high doses of pancreatin preparations. Case control studies did not reveal evidence for an association between Creon and the appearance of fibrosing colonopathy. 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.

As with all currently marketed porcine pancreatin products, Creon Micro is sourced from pancreatic tissue from swine used for food consumption. Although the risk that Creon Micro will transmit an infectious agent to humans has been reduced by the testing and inactivation of certain viruses during manufacturing, there is a theoretical risk for transmission of viral disease, including diseases caused by novel or unidentified viruses. The presence of porcine viruses that might infect humans cannot be definitely excluded. However, no cases of transmission of an infectious illness associated with the use of porcine pancreatic extracts have been reported, whereas they have been used for a long time.

No interaction studies have been performed.

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

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

In clinical trials, more than 600 patients with pancreatic exocrine insufficiency, due to cystic fibrosis, chronic pancreatitis, and pancreatic surgery 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 placebo-controlled clinical trials with the below indicated frequencies

Gastrointestinal disorders

Common (1/100, <1/10): nausea, vomiting, constipation, diarrhoea and abdominal distension

Gastrointestinal disorders are mainly associated with the underlying disease. Similar or lower incidences compared to placebo were reported for abdominal pain (very common, 1/10).

Skin and subcutaneous tissue disorders

Uncommon(1/1,000, 1/100): rash

Frequency not known: pruritus, urticaria

Immune System Disorders:

Frequency not known: Hypersensitivity (anaphylactic reactions).

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.

Multiple clinical trials were conducted in other patient populations: HIV, acute pancreatitis, diabetes mellitus. No additional adverse drug reactions were identified compared to the above three patient groups.

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.

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.

The ATC code is A09A A (Enzyme preparations).

Replacement therapy in pancreatic enzyme deficiency states. The enzymes have hydrolytic activity on fat, carbohydrates and proteins.

Pharmacokinetic data are not available as the enzymes act locally in the gastro-intestinal tract. After exerting their action, the enzymes are digested themselves in the intestine.

None stated.

Hypromellose phthalate

Macrogol 4000

Dimeticone

Cetyl alcohol

Triethyl citrate

Not applicable.

2 years. 12 weeks after first opening.

Do not store above 30°C.

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

Glass bottle with LDPE stopper. Containers hold 20 g of gastro-resistant granules.

No special requirements.

Abbott Healthcare Products Limited

Mansbridge Road

West End

Southampton

SO18 3JD

United Kingdom

PL 00512/0179

August 2004

06 March 2012

P