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