Results from a 2-year centralized tolcapone liver enzyme monitoring program.

Objectives: Tolcapone, administered with levodopa/carbidopa to patients with Parkinson disease, is an effective and generally well-tolerated adjunctive therapy. However, 4 early cases of hepatotoxicity causing 3 deaths in patients not properly monitored gave rise to more rigorous liver function test monitoring guidelines and a liver function test monitoring program in which blood samples from tolcapone-treated patients were tested and results were collected in a central database. We analyzed these results to determine the percentages of patients with at least 1 aspartate aminotransferase (AST) or alanine aminotransferase (ALT) elevation above the upper limit of normal (ULN) and at least 1 elevation greater than 2 times the ULN.

Methods: This retrospective, observational analysis included all AST and ALT values recorded in the database from 11,883 samples from patients who received tolcapone for up to 2 years or longer (January 1999-January 2001).

Results: Of 1725 patients who had at least 1 AST or ALT measurement, 3.9% (n = 67) had elevations above the ULN. Less than 1% (15/1725) of patients had AST or ALT elevations greater than 2 times the ULN. Most values returned to normal during continued tolcapone treatment. In 472 patients monitored biweekly while receiving tolcapone for 20 to 114 consecutive weeks, only 0.6% (n = 3) had an AST or ALT value greater than 2 times the ULN; no significant elevations occurred in the remaining 469 (99.4%).

Conclusions: This analysis of results from the central monitoring program suggests that significant transaminase elevations are rare, typically transient, and may return to normal in the face of continued tolcapone therapy in most patients.