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Tasmar-Liver Warning 24 November 1998 Thanks to the alert and resourceful Judith Richards, we now have the letter sent 16 Nov by Roche (makers of Tasmar) to U.S. doctors, containing at least partial answers to some of my questions and, pending decisive advice from my neurologist, I'm very reluctantly inclined to quit taking that drug. The situation in brief: During its customary and extensive trials, tolcapone (Tasmar) proved to be outstandingly effective and safe, as a valuable adjunct to levodopa (Sinemet) treatment for PD. But, besides the single death reported during the trials and described in the official product description leaflet, there have been two additional deaths from fulminant hepatitis, and an unknown number of other cases averted in time, among the 100,000 or so PD patients who began taking Tasmar after it was approved and introduced a year ago. As a result, periodic monitoring of liver function was first recommended, then required, for those taking Tasmar. Now its approval has been withdrawn in France and Germany, and restrictive warnings issued in the U.S. and Canada. The problem in deciding whether to continue using or prescribing Tasmar is the scarcity of convincing data. Fulminant hepatitis is very rare, thought to be caused by the hepatitis A virus (HAV) or another as yet unidentified virus, and characterized by very rapid (within a few hours) onset, and death shortly after. Apparently, it wasn't even recognized in the first case above. The letter says, its incidence (3 per 100,000 or so Tasmar users so far) may be "10- to 100-fold" higher than in the general population. But clearly there aren't enough cases to establish that for sure, or to pinpoint Tasmar as the cause. Nor is it clear, whether Tasmar alone may be at fault, or if any other COMT inhibitor will present a similar risk. The liver function monitoring is advocated as a precaution, but without "robust evidence" that it will detect fulminant hepatitis in time for protection. The liver is subject to a wide variety of threats, nearly all of which, for example alcohol, are slowly progressive. When distressed, the liver emits one or two enzymes whose level in the blood can be measured: Serum Glutamic-Pyruvic Transaminase (SGPT), now called ALanine aminoTransferase (ALT); and Serum Glutamic-Oxaloacetic Transaminase (SGOT), now called ASpartate aminoTransferase (AST). These are routine blood tests familiar to every clinic and hospital, and elevated level indicates either pre-existing liver damage or increased vulnerability to one or more liver toxins. But it can be seen, even at the now recommended frequency of every two weeks for the first year after starting or increasing Tasmar, that their value in predicting a sudden onslaught such as fulminant hepatitis may be dubious, and mainly psychological. Cheers, Joe -- J. R. Bruman (818) 789-3694 3527 Cody Road Sherman Oaks, CA 91403-5013