Real-life evaluations of compliance with mandatory drug safety monitoring exemplified with tolcapone in Parkinson's disease

Eur Neurol. 2008;60(3):122-6. doi: 10.1159/000144081. Epub 2008 Jul 14.

Abstract

Background/aims: In 1998, the European Medicines Agency suspended the approval for tolcapone in Parkinson's disease (PD) with motor complications due to the drug's implication in fulminant liver failure and the consequent death of 3 patients. Clinical data obtained by ongoing use of tolcapone in other countries proved that adequate safety can be achieved if liver enzymes are strictly monitored. In 2005, tolcapone was relaunched in the European Union under the prerequisite of biweekly liver enzyme monitoring. The objective of this study was to evaluate the compliance with mandatory drug safety monitoring under real-life conditions.

Methods: Twenty-one Parkinson's disease patients receiving tolcapone were analyzed with regard to their compliance in performing and reporting the required laboratory tests.

Results: Tolcapone was effective and well tolerated. Yet, less than 25% of the patients regularly performed and reported the required laboratory tests and the compliance declined when comparing the first and second half-years of therapy.

Conclusions: Our data shed light on the incongruity between requirements of postmarketing drug surveillance and every-day reality. The depicted noncompliance is most likely a general problem in postmarketing drug surveillance with an impact for physicians, manufacturers and legal authorities. Practical, legal and ethical aspects will be discussed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adverse Drug Reaction Reporting Systems
  • Aged
  • Alanine Transaminase / blood
  • Antiparkinson Agents / adverse effects*
  • Aspartate Aminotransferases / blood
  • Benzophenones / adverse effects*
  • Drug Monitoring* / methods
  • Drug Monitoring* / standards
  • Drug Monitoring* / statistics & numerical data
  • Drug-Related Side Effects and Adverse Reactions
  • European Union
  • Female
  • Humans
  • Male
  • Middle Aged
  • Nitrophenols / adverse effects*
  • Parkinson Disease / drug therapy*
  • Patient Compliance / statistics & numerical data*
  • Tolcapone

Substances

  • Antiparkinson Agents
  • Benzophenones
  • Nitrophenols
  • Tolcapone
  • Aspartate Aminotransferases
  • Alanine Transaminase