TASMAR REDUX 17 January 1999
PD patients and prescribing physicians who have elected to
continue using tolcapone (Tasmar) despite the recent concern
over a possible but unproven association with fulminant liver
failure will be pleased to know that, at least in the U.S., it's
still aggressively marketed by its makers, Roche Laboratories.
At yesterday's short symposium on the occasion of opening an
APDA-supported Parkinson's Information and Referral Center at
Cedars-Sinai Medical Center in Los Angeles, Roche Labs had a
table where I gathered promotional material including a video
cassette for PD patients, a diskette which will add the site
http://www.tasmar.com
to your internet Bookmarks file, and a re-written product
information (package insert) leaflet. Substantive changes
mostly reflect the letter from Roche Labs dated 16 Nov 1998,
circulated widely to U.S. doctors and discussed in numerous
postings to this forum, but I'll review the main ones:
-In about 40,000 patient-years of experience among the 60,000
Tasmar users, there have been 3 deaths from fulminant liver
failure, and possibly others unreported. This incidence may
be 10- to 100-fold higher than in the general population(1).
-Tasmar should be prescribed only where fluctuating motor
symptoms have not responded to other therapy, and only to
patients without pre-existing liver disease or injury. Tasmar
should be stopped if therapeutic benefit does not appear
within 3 weeks.
-The enzymes serum glutamic-pyruvic transaminase, or alanine
aminotransferase (SGPT/ALT) and serum glutamic-oxaloacetic
transaminase, or aspartate aminotransferase (SGOT/AST) should
be monitored biweekly for the first year after starting
Tasmar or increasing its dosage rate(2). Tasmar should be
stopped if either level exceeds the upper limit of normal range
(ULN). Earlier advice was to test monthly for the first three
months, and stop Tasmar if either level exceeds 5 times ULN.
-It is not clear that the recommended enzyme monitoring will
enable detection of fulminant liver failure in time to prevent
a fatal outcome(3).
-Cases of severe rhabdomyolysis, with one case of multiorgan
system failure rapidly progressing to death, have been
reported. It is impossible to tell if Tasmar was to blame(4).
Notes:
1. One cannot be certain whether such rare events were related
to Tasmar, or only to coincidence.
2. Both enzymes, especially ALT, become elevated on occurrence
of liver damage, but the "normal" range is loosely defined.
3. The defining feature of fulminant liver failure is its very
rapid progression, sometimes in less than a day, from a
normal condition to a life-threatening one. It may have an
incubation period up to 8 or 10 weeks long, but transaminase
elevation during that period has not been confirmed.
4. This disease is so rare that it is not even mentioned in the
Merck Manual. Its name is a compound of 3 Greek words meaning
"rod","muscle", and "dissolution", i.e., "disintegration of
skeletal muscle". It is so complicated that association with
Tasmar cannot be ascertained, but severe prolonged motor
activity such as dyskinesia may play a role.
The new package insert has the warnings above collected in a
boldface boxed section, as well as a sample of the very strict
Patient Consent form that is offered separately.
Cheers,
Joe
--
J. R. Bruman (818) 789-3694
3527 Cody Road
Sherman Oaks, CA 91403-5013
