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Tasmar And Liver Failure 18 Nov 1998 (Readers Beware: The Following Does NOT Substitute For Professional Medical Advice- Obtain That From Your Doctor!) Recent news about unforeseen risk of fatal liver injury from the COMT inhibitor tolcapone (Tasmar) has prompted a flurry of official reaction as well as warnings of concern to many Parkinsn listmembers who have been taking Tasmar as part of their PD medication. My own reaction, based partly on undeniable benefit since I began taking Tasmar in June of this year, has been to look for more detailed info about the risk, in hopes of finding a rationale to continue its use if it looks safe enough. As usual, I turned first to my trusty Merck Manual (1992) for background. The liver seems to be the body's busiest chemical laboratory, as well as the most vulnerable. Many foreign compounds, such as drugs and including tolcapone, are converted in the liver to innocuous forms which then can be excreted by the kidneys in urine. But the liver is subject to an astonishing variety of threats. Merck's index contains nearly two dozen different causes of hepatitis (the general term for liver trouble). We've all heard of alcohol's effects, and viruses such as Hepatitis A Virus (HAV), HBV, and HCV, but maybe not NANB (unknown, but Not A, Not B). And there is a whole chapter about drugs (medications) and the liver. The syndrome that has been connected with Tasmar is rare and usually caused by acute HBV or NANB infection, but "drugs" is also mentioned. It's called "fulminant hepatitis" because of its swift onset: coma and signs of bleeding may develop within hours, followed by kidney failure and usually, a fatal outcome. On autopsy, massive necrosis and atrophy of the liver are seen. All this makes some sense if a virus is the villain; but the sudden unpredictable onset, from a drug which may have been taken for months without noticable ill effect, is harder to understand. And the rarity of the disease in connection with Tasmar, currently about 3 cases among 60,000 PWP taking the drug, is even more puzzling. One wonders how authorities can be so sure that Tasmar was the cause, or if they are only being cautious. Another question pertains to the monitoring protocol recommended by Roche (and practiced by Kaiser), which is only to measure a single enzyme, alanine aminotransferase (ALT) every 6 weeks for 3 months, then monthly for the next 3 months. Elevated ALT is a signal of several kinds of liver distress, but it's hard to see how a 6-weekly or monthly test can detect something as sudden and unpredictable as fulminant hepatitis. Does an acceptable level of ALT during the first 6 months indicate that there is nothing further to fear? Or is the monitoring protocol just a bit of window dressing, for lack of anything better? Could Tasmar somehow have made those victims more vulnerable to a virus (HBV or NANB)? Stay tuned. Cheers, Joe -- J. R. Bruman (818) 789-3694 3527 Cody Road Sherman Oaks, CA 91403-5013