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

Expert Opin Drug Saf. 2011 Mar;10(2):197-203. doi: 10.1517/14740338.2011.552499.

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.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Body Weight / drug effects
  • Child
  • Cystic Fibrosis / drug therapy*
  • Cystic Fibrosis / physiopathology
  • Dose-Response Relationship, Drug
  • Female
  • Gastrointestinal Agents / administration & dosage
  • Gastrointestinal Agents / adverse effects*
  • Gastrointestinal Agents / therapeutic use
  • Humans
  • Lipase / administration & dosage
  • Lipase / therapeutic use
  • Male
  • Microspheres
  • Pancreatin / administration & dosage
  • Pancreatin / adverse effects*
  • Pancreatin / therapeutic use
  • Young Adult

Substances

  • Gastrointestinal Agents
  • Pancreatin
  • Lipase