Creon^® 10000 Capsules

Each capsule contains:

Brown/clear capsules containing gastro-resistant granules.

For the treatment of pancreatic exocrine insufficiency.

Adults (including the elderly) and children:

Initially one to two capsules with each meal. 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.

The capsules can be swallowed whole, or for ease of administration they may be opened and the granules taken with fluid or soft food, but without chewing. If the granules are mixed with food it is important that they are taken immediately, otherwise dissolution of the enteric coating may result.

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.

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

Capsule shell:

Gelatin,

Anhydrous iron (III) oxide, E172

Hydrated iron (III) oxide, E172

Iron (II, III) oxide (E172)

Titanium dioxide (E171)

Sodium lauryl sulphate

Not applicable.

2 years.

Do not store above 30°C.

HDPE container with tamper-evident PP cap. Containers hold 100, 250 or 300 capsules.

No special instructions.

Solvay Healthcare Limited

Mansbridge Road

West End

Southampton

SO18 3JD

United Kingdom

PL 00512/0149

01 January 2001

28/09/2009