TASMAR ALERT ! (from Jan-Feb issue)
Tasmar brand of tolcapone, the most recently F.D.A. approved drug for
treating Parkinson's disease, has caused some severe side effects,
in particular a very rapid inflammation of the liver which is known to
have resulted in at least three deaths. Some say that the death count
may be understated since many people who have Parkinson's and die are
not autopsied. It is known that there were many non-fatal cases of liver
inflammation among people who took Tasmar.
The news of the problem with Tasmar was made public by
Hoffman-LaRoche [Roche Laboratories,Inc.], the maker of Tasmar,
November 16, 1998, the day the November Parkinson's Newsletter was
printed. The November Parkinson's Newsletter did not include Tasmar
in its listing of Parkinson's drugs, since there had been rumors about
severe Tasmar side effects. Tasmar is the only  COMT inhibitor F.D.A.
approved in the United States.
Roche Laboratories sent warning notices to neurologists, the most likely
prescribers of the product. The APDA sent notices to its chapter
presidents. There were many notices posted on the Internet. The product
was withdrawn from most countries in Europe.  Tasmar is still available
in the U.S., but many prescribing neurologists, including the Parkinson's
Disease Clinic at Johns Hopkins, are limiting Tasmar prescriptions only
to patients for whom other drugs do not work, who sign a waiver of
liability recognizing the danger in Tasmar, and get a liver function test
every two weeks.
Tasmar is still available in at least some local pharmacies. On January
14, I checked with Super G Deep Discount Drug in Salisbury to see if
they still carried Tasmar. They had received no notice of any problem
with Tasmar and have it in stock at $217.69 per 100 for the 100 mg
caplets and at $235.47 per 100 for the 200 mg caplets. Tasmar has
been a very useful drug for some PD patients. According to theory,
Tasmar blocks the breakdown of levodopa (the active ingredient in
Sinemet) by catechol-O-methyl transferase, a natural and normally
useful enzyme, found in all humans, which has an affinity for levodopa.
If this is the actual situation, Tasmar could be replaced by simply taking
a little more Sinemet. The benefits reported by many users indicate that
it may be doing more.
One European group questioned the wisdom of using Tasmar earlier,
claiming that a COMT inhibitor could hasten neuronal cell death in the
brain, but this was not widely believed. I have been taking another
COMT inhibitor, entacapone from Orion Farma of Finland, for several
years as a participant in its drug trials. Entacapone is expected to be
sold
as Comtan in the U.S. after receiving F.D.A. approval some time in
1999. No liver problems have been reported with entacapone, but the
Tasmar scare may delay or halt approval.
The neurologist in charge of my testing of entacapone said she thought
Tasmar was a more effective product than entacapone. There is one
major difference between entacapone and Tasmar. Tasmar can cross the
blood/brain barrier, providing more complete protection for the
levodopa. Entacapone does not cross the blood/brain barrier.
Carbidopa, the decarboxylase enzyme inhibitor and first number in
describing Sinemet strength, also does not cross the blood/brain barrier.
Once the levodopa is converted to dopamine, Eldepryl, [also known as
Deprenyl, Jumex, or seligeline] which also crosses the blood/brain
barrier, can be used to slow the monamine oxidase enzyme's attack on
dopamine. Tasmar provides some protection for the levodopa between
the time it crosses the blood/brain barrier and the time it is converted
to dopamine in the brain. Entacapone does not provide this protection.
Tasmar now is now recommended only for those patents who are not
able to get satisfactory relief from the symptoms of PD from other
drugs. There is no other product providing protection for the levodopa
after it has crossed into the brain. The general feeling of the experts I
have talked with is that Tasmar should be used as a last resort, only
when nothing else works. Only three known deaths out of the many
taking the product may mean that the danger is over stated.




Will Johnnston
A.P.D.A. DelMarVA Chapter Pres.
4049 Oakland School Road
Salisbury MD 21804 USA 410-543-0110