A 2-year post-authorization safety study of high-strength pancreatic enzyme replacement therapy (pancreatin 40,000) in cystic fibrosis

Abstract

Objective: At the request of the Medicines and Healthcare Regulatory Agency and in agreement with the appropriate authorities, an observational, multi-center, non-interventional, post-authorization safety study of high-strength pancreatic enzymes was conducted.

Research design and methods: Patients with exocrine pancreatic insufficiency due to cystic fibrosis (CF) who had previously taken high doses of pancreatic enzymes received pancreatin 40,000 capsules (Creon 40,000 Minimicrospheres, Abbott GmbH, Hanover, Germany) as part of their normal treatment for up to 2 years. Initial doses were calculated to match previous established doses in lipase units, with adjustment if required.

Main outcome measures: Safety focused on serious suspected adverse drug reactions. Maldigestion symptoms and body weight were also monitored. Patients were managed according to general guidelines common to all major CF units in the UK, although minor variations were expected. The coefficient of fat absorption was not assessed as this was a safety rather than an efficacy study.

Results: Sixty-four patients were enrolled at nine UK centers. Two deaths occurred during the study, which were considered unrelated to therapy by investigators. There were no further serious suspected adverse drug reactions related to pancreatin 40,000 and no cases of fibrosing colonopathy. Daily lipase doses were reduced by 11% after switching to pancreatin 40,000. Maldigestion symptoms improved and mean body weight increased from baseline to last observation (mean + 6.1 kg in patients < 18 years old).

Conclusions: No safety concerns were identified with pancreatin 40,000 therapy for up to 2 years. Daily lipase doses were not increased when switching to pancreatin 40,000.

Keywords::

• cystic fibrosis
• exocrine pancreatic insufficiency
• high-dose
• pancreatic enzymes
• pancreatin
• safety

Acknowledgements

The authors thank all participating centers for their contribution: Papworth Hospital NHS Trust, Papworth Everard, Cambridge, CV3 8RE; D Bilton, H Watson, C Haworth, R Hartley, Gartnavel General Hospital, 1053 Great Western Road, Glasgow, G12 0YN; P Henderson, S Sriram, North Staffordshire Hospital, Newcastle Road, Stoke on Trent, ST4 6QC; C Pantin, W Lenney, S Bell, Southampton General Hospital, Tremona Road, Southampton, SO16 6YD; J Legg, G Connett, P Brammer, C Parker, C Pearson, T Brown, Addenbrookes Hospital, Hills Road, Cambridge, CB2 2QQ; R Iles, K Robinson, Northern General Hospital, Herries Road, Sheffield, S5 7AU; S Brennan, S Thornton, F Edenborough, Birmingham Heartlands Hospital, Bordesley Green East, Birmingham, B9 5SS; S Williams, D Stableforth, London Chest Hospital, Banner Road, London, E2 9JX; M Powell, D Empey, Norfolk & Norwich NHS Trust, Colney Lane, Norwich, NR4 7UZ; and C Culligan, E van Tonder.

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