Section 4.8: Undesirable effects
From:
Diarrhoea, constipation, gastric discomfort, nausea and skin reactions have been reported occasionally in patients receiving enzyme replacement therapy.
Rarely cases of hyper-uricosuria and hyper-uricaemia have been reported with very high doses of pancreatin.
Stricture of the ileo-caecum and large bowel and colitis has been reported in children with cystic fibrosis taking high doses of pancreatic enzyme supplements. To date, Creon has not been implicated in the development of colonic damage. However, unusual abdominal symptoms or changes in abdominal symptoms should be reviewed to exclude the possibility of colonic damage - especially if the patient is taking in excess of 10,000 units of lipase/kg/day.
To:
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.
Section 4.9: Overdose
From:
Most cases respond to supportive measures including stopping enzyme therapy, ensuring adequate rehydration.
To:
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.
