(tolcapone) Tablets
Tasmar (tolcapone) is indicated as an adjunct to levodopa and carbidopa for the treatment of the signs and symptoms
of
idiopathic Parkinson's disease. It is used in combination with levodopa and carbidopa for patients with severe
Parkinson's disease who are experiencing symptom functions and are not responding satisfactorily to, or are not
appropriate candidates for, other adjunct therapies.
The biology of Parkinson's disease and its treatment involves the complicated interaction of brain chemicals and
enzymes. When patients first start on levodopa or levodopa/carbidopa combination therapy, their improvement is often
dramatic. However, after a few years, this therapy becomes less and less effective, which leads to an increase in
symptoms (this is called "wearing off").
Tasmar (tolcapone) inhibits catechol-O-methyltransferase (COMT), an enzyme that catalyzes the metabolization of
levodopa into 3-O-methyldopa. This provides a prolonged maintenance of serum levodopa levels, which may provide a longer
clinical response to levodopa treatments.
Therefore, Tasmar is most effectively prescribed to prolong the effectiveness of levodopa and carbidopa treatments
after their clinical effectiveness has been reduced due to the progression of the disease. It can also be prescribed if
a patient is not responding well to, or is not an appropriate candidate for, other adjunctive therapies.
Most patients experience significant results from taking Tasmar. The average Tasmar patient has an increase in
"ON"
time, otherwise known as the time symptoms are controlled. In a 16-hour waking day, it increases "ON" time an average of
1.7-2.9 hours, and decreases "OFF" time anywhere from between 1.6 to 3.2 hours.
The Tasmar TASK (Tasmar Adjunctive Study in Parkinson's) trial is a multi-center study enrolling patients with Parkinson's Disease, who receive Tasmar as adjunctive therapy to L-dopa for a 30 day treatment period.
Named after Dr. James Parkinson, a London physician who first described the disease in 1817, Parkinson's disease (PD) is
a chronic, progressive disorder of the central nervous system. Once you get PD, it does not go away and the symptoms get
worse over time. In general, tremor is followed by stiffness, slowness of movement (bradykinesia), and in the later
stages, lack of balance. Emotional symptoms such as depression and anxiety are also characteristic of Parkinson's
disease.
Although the exact cause of PD is unknown, many of the symptoms occur when certain brain cells, called neurons, die or
become damaged. Neurons produce a chemical substance called dopamine that is important in the control of movement. Over
time, the dopamine level in the brain decreases and a chemical imbalance is caused that makes movement more difficult
and less fluid. By the time characteristics of Parkinson's disease like tremor and stiffness are visible, the normal
level of dopamine has been greatly reduced.
Perhaps the biggest adjustment PD patients will have to make is learning to live with the "ON-OFF" cycle. This is the
back and forth between periods of time with and without symptoms. During "ON" times patients report that they feel
relatively fluid, clear, and in control of their movements. On the contrary, during "OFF" periods, patients experience
stiffness, lack of muscular coordination and pain. Most patients have visible symptoms. Typically, patients cycle
between "ON" and "OFF" periods 3 - 4 times every day.
Detecting PD in its early stages can be difficult, but most skilled practitioners can usually diagnose PD accurately.
If you think you might have Parkinson's disease, or if your doctor suspects that you may, he will perform an assessment
to detect Parkinson's disease that consists of
- Taking your medical history
- Questions about things you do at home on a regular basis such as dressing, showering, bathing, walking, and
eating
- A special exam by a neurologist
More sophisticated tests are available if a diagnosis is uncertain, but these are generally not used due to their cost
and the overall strength of the standard exam.
TASMAR SHOULD NOT BE USED BY PATIENTS UNTIL THERE HAS BEEN A COMPLETE DISCUSSION OF THE RISKS AND PATIENT HAS PROVIDED WRITTEN ACKNOWLEDGEMENT THAT THE RISKS HAVE BEEN EXPLAINED (SEE PATIENT ACKNOWLEDGEMENT OF RISKS SECTION).
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WARNING: Due to the risk of potentially fatal, acute fulminant liver failure, TASMAR should ordinarily be used in patients with Parkinson’s disease on levodopa/carbidopa who have symptom fluctuations and are not responding satisfactorily to or who are not appropriate for other adjunctive therapies (see INDICATIONS and DOSAGE AND ADMINISTRATION).
TASMAR should not be initiated in patients with clinical evidence of liver disease or two SGPT/ALT or SGOT/AST values >ULN and should be discontinued if substantial clinical benefit is not seen within 3 weeks.
Patients with severe dyskinesia or dystonia should be treated with caution (see PRECAUTIONS: Rhabdomyolysis).
Laboratory monitoring is recommended (see PRECAUTIONS: Laboratory Tests for the recommended schedule). Liver monitoring may not prevent liver failure; however, early detection and immediate drug withdrawal are believed to enhance the likelihood for recovery. Patients should be advised to self-monitor for signs of liver disease. Discontinue TASMAR if hepatic enzymes exceed 2 times (2X) ULN or patient exhibits signs of liver failure.
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TASMAR is contraindicated in patients with liver disease, in patients who were withdrawn from TASMAR because of evidence of TASMAR-induced hepatocellular injury or who have demonstrated hypersensitivity to the drug or its ingredients. TASMAR is also contraindicated in patients with a history of non-traumatic rhabdomyolysis or hyperpyrexia and confusion possibly related to medication.
In clinical trials, adverse events reported at a frequency of >10% when TASMAR was administered in combination with levodopa/carbidopa were dyskinesia, nausea, sleep disorder, dystonia, anorexia, diarrhea, somnolence, excessive dreaming, muscle cramps, orthostatic complaints, dizziness, headache, and confusion. The majority of these effects are dopaminergic and may be reduced by decreasing the dose of levodopa; however, some may persist despite levodopa dosage adjustment.
Diarrhea was the adverse event that most commonly led to discontinuation.
The following notable dopaminergic effects occurred but infrequently led to the discontinuation of TASMAR therapy: symptomatic hypotension (approximately 0.7% of patients withdrew); hallucinations (1.0% to 1.4%); dyskinesia (0.3% to 1.0%).
Cases of severe rhabdomyolysis have been reported; it is impossible to determine what role, if any, TASMAR played in the pathogenesis. Rare cases of hyperpyrexia and confusion have been reported similar to those reported in association with dose reduction or abrupt withdrawal of other dopaminergic drugs. It is difficult to determine what role TASMAR may have played. The postmarketing cases involved concomitant administration of several medications affecting brain monoaminergic and anticholinergic systems.
TASMAR should not be given in conjunction with nonselective MAO inhibitors such as phenelzine and tranylcypromine. TASMAR can be given concomitantly with a selective MAO-B inhibitor (eg, selegiline).
Patients should be advised not to drive a car or operate complex machinery until they have gained sufficient experience on TASMAR to know how it affects them
Please see full Prescribing Information, including BOXED WARNING at www.tasmar.com.
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