A number of questions about Tasmar and its dosage have
been raised in recent messages. Those questions are
answered in the excellent "An Algorithm (decision tree)
for the Management of Parkinson's Disease: Treatment
Guidelines" by C. Warren Olanow and William C. Koller
in _Neurology_ March,1998;50, Suppl 3 pp s1-s57.
Tasmar is not prescribed by itself, it is used in con-
junction with levodopa in treating PD. COMT inhibitors
such as entacapone (Comtan) and tolcapone (Tasmar) increase
the "availability and transfer of levodopa into the brain."
It works with either regular or sustained relief Sinemet.
Tasmar makes more levodopa available to the brain smoothly
and thus avoiding the concentration of levodopa causing motor
complications. Quoting directly:
Clinically, the COMT inhibitors have been
shown to enhance the antiparkinson effect of levo-
dopa in both fluctuating and nonfluctuating PD
patients .163,165-167 Because COMT inhibitors increase
levodopa availability to the CNS, they are associated
with an increased incidence of dopaminergic side ef-
fects (dyskinesia and, less often, neuropsychiatric
problems) that may require a reduction in levodopa
dose of 29 to 30%. Typically, the COMT inhibitor is
added to levodopa and the patient is advised that
increasing dyskinesia may ensue and may necessi-
tate a reduction in levodopa dosage within the first 1
to 2 days.
With reference to dosage Dr. Olanow and Dr. Koller say:
The relatively short elimination half-lives
of the COMT inhibitors necessitate multiple daily
dosing. Tolcapone is usually administered in doses of
100 or 200 mg tid. The 200-mg dose provides greater
efficacy than the 100-mg dose in virtually all studies
and is the preferred dose because it provides more
complete enzyme inhibition. Patients can be started
directly on this dose and side effects can be ad-
dressed if they occur. Entacapone is usually adminis-
tered at the same time as each dose of levodopa,1-
and dopaminergic side effects are managed in a sim-
ilar fashion to those of tolcapone.
The authors go on to report on several clinical studies:
A placebo-controlled study was performed compar-
ing 4-week courses of entacapone or placebo as an
adjunct to levodopa/carbidopa. This study demon-
strated that entacapone-treated patients had a 34-
ninute increase in the mean duration of "on" time
after a single dose of levodopa and a 2.5-hour in-
crease in daily "on" time. This benefit was associated
with a 16% reduction in the mean daily dose of levo-
dopa (from 860 to 720 mg per day).'" Similarly, in
levodopa-treated PD patients who experienced motor
fluctuations, tolcapone treatment decreased the du-
ration of "off" time by 26 to 50% and the daily dose of
levodopa by 29 to 40% .
The benefits of COMT inhibitors have also been
observed in nonfluctuating patients. A double-blind,
placebo-controlled study in PD patients who experi-
enced a stable response to levodopa demonstrated
that patients randomized to receive tolcapone ther-
apy had significantly improved ADL and motor
scores, and required lower levodopa doses compared
with placebo-treated patients.
Clinical trials in patients with early PD are under
way to assess the possibility that administration of
levodopa with a COMT inhibitor may reduce the risk
of developing motor complications. This possibility is
based on the capacity of a COMT inhibitor to smooth
the plasma levodopa concentration curve and dimin-
ish the likelihood that dopamine receptors will be
exposed to pulsatile dopamine stimulation.
But, now the down side. The authors observe that:
In general, the COMT inhibitors are well tolerated
and easy to administer. The most common side effect
is dyskinesia, which reflects increased central do-
paminergic: activity. It is usually a problem only in
patients who already have dyskinesia, and it can be
satisfactorily controlled by a 20 to 30% reduction in
levodopa dose. Physicians should be aware that this
side effect tends to occur within 24 hours after initi-
ation of a COMT inhibitor and may require an imme-
diate dose adjustment. Severe diarrhea is a therapy-
limiting side effect in 5 to 6% of tolcapone treated
patients, and may require discontinuation of treat-
ment.
And, because up to 3% of Tasmar treated patients may have
an increase in liver transaminase, a periodic monitoring
of the liver is mandated.
(Still another superb treatment of Tasmar can be found in
the National Parkinson's Foundation quarterly _The Parkinson
Report_ in an article by William J. Weiner, "New Approach
to Parkinson's Disease Treatment:Tasmar (Tolcapone)"
Spring, 1998 pages 10-11.)
__________
Sid Roberts 68/3 <[log in to unmask] > Youngstown, Ohio
