Creon^® 40000 Capsules

Each capsule contains pancreatin PhEur 400 mg equivalent to:

Capsules.

Brown/clear size 00 capsules containing light brown, gastro-resistant granules.

For the treatment of pancreatic exocrine insufficiency.

Adults (including the elderly) and children:

Creon 40000 should only be used if the patient requires equal to or more than 40,000 lipase units per meal or snack. Creon 40000 should only be used in patients in whom the minimum effective dose has already been determined using lower strength pancreatic enzyme products.

Initially one or two capsules with meals. The capsules should be swallowed whole. Dose increases, if required, should be added slowly, with careful monitoring of response and symptomatology.

It is important to ensure adequate hydration of patients at all times whilst dosing Creon 40000.

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).

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.

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

Pruritus and urticaria have been additionally 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.

Granules:

Macrogol 4000

Hypromellose phthalate

Dimeticone

Cetyl alcohol

Triethyl citrate

Capsules:

Gelatin

Anhydrous iron (III) oxide (E172)

Hydrated iron (III) oxide (E172)

Iron (II, III) oxide (E172)

Titanium dioxide E171

Sodium lauryl sulphate

3 years.

Do not store above 25°C. Keep container tightly closed.

HDPE container with tamper-evident PP cap. Each container contains 100 capsules.

Solvay Healthcare Limited

Mansbridge Road

West End

Southampton

SO18 3JD

United Kingdom

PL 00512/0177

25/02/2009

28/09/2009

POM