Real-life evaluations of compliance with mandatory drug safety monitoring exemplified with tolcapone in Parkinson's disease.
OBJECTIVE
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.
Unger
Marcus M
MM
Department of Neurology, Philipps Universitat Marburg, and Competence Network Parkinson Syndrome, Marburg, Germany.
Reese
Jens P
JP
Oertel
Wolfgang H
WH
Eggert
Karla M
KM
D016907:Adverse Drug Reaction Reporting Systems; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D000978:Antiparkinson Agents / Q000009:adverse effects*; D001219:Aspartate Aminotransferases / Q000097:blood; D001577:Benzophenones / Q000009:adverse effects*; D016903:Drug Monitoring / Q000379:methods / Q000592:standards / Q000706:statistics & numerical data; D064420:Drug-Related Side Effects and Adverse Reactions; D005062:European Union; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009596:Nitrophenols / Q000009:adverse effects*; D010300:Parkinson Disease / Q000188:drug therapy*; D010349:Patient Compliance / Q000706:statistics & numerical data*; D000077867:Tolcapone
D000978:Antiparkinson Agents; D001577:Benzophenones; D009596:Nitrophenols; D000077867:Tolcapone; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase