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| |  ICPD: Comtan/Comtess (Entacapone) May Reduce Severity Of Levodopa Complications HELSINKI, FINLAND -- July 30, 2001 -- "Many Parkinson’s disease (PD) patients are not receiving optimal treatment for their condition" said Cheryl Waters, Professor of Neurology at New York’s Columbia University, talking at the XIV International Congress on Parkinson’s Disease in Helsinki, Finland. "Simple measures such as using a COMT-inhibitor [catechol O-methyltransferase inhibitor] to provide a smoother, more continuous delivery of levodopa to the brain, can reduce the disabling effects of wearing-off symptoms as this wearing-off appears to be correlated to the intermittent or pulsatile nature of levodopa delivery," Dr. Waters added. Introduced as a miracle drug in the 1960s, levodopa represents the mainstay treatment for Parkinson’s disease and, with the exception of very early phase PD, all patients will eventually be treated with it. However, it is now well-known that patients experience reduced effect from the drug over time. Physicians are increasingly concerned that long-term pulsatile levodopa delivery may be in part responsible for the development of dyskinesias, motor and non-motor fluctuations. This means that patients experience periods of on-time when they are responding to the medication and periods of off-time, when they do not. For patients themselves it may be difficult to distinguish between levodopa wearing-off effects or end-of dose deterioration and the disease process. Motor fluctuations, for example, can include a return of parkinsonian-type symptoms such as tremor and slowness or involuntary, often painful, muscle contractions. Non-motor fluctuations, which can be even more disabling to patients, include anxiety, hallucinations, pain and drenching sweats. This wearing-off phenomenon may occur as early as two-three years after levodopa therapy is initiated. Since patients often do not recognize these symptoms for what they are, they may not discuss their appearance with their physicians. Neurologists, on the other hand, often rely on patients’ description of symptoms for guidance when deciding what to prescribe. Research indicates that changes in levodopa dose are very frequent. This is a sign that levodopa efficacy has started to wear-off. Since patients do not recognize these symptoms for what they are, they may not speak readily with their physicians, who in turn may not systematically explore these with them. It is worth noting that a majority of patients see their neurologist no more than twice a year and 80% of the visits are considered "routine" by physicians. According to David Brooks, Professor of Neurology at London’s Imperial College, also speaking at the Helsinki meeting, many of these wearing-off effects are treatable through the use of a more continuous rather than pulsatile dopamingeric stimulation. "Historically, it was thought that the classic model of the basal ganglia would provide answers to levodopa motor complications, however current thinking is that the loss of dopaminergic terminals may also play a major role leading to pulsatile swings in synaptic dopamine levels. There is now a growing body of evidence to support the view that the pulsatile dopaminergic stimulation leads to abnormal internalisation of dopamine receptors and changes in downstream neurotransmitter levels resulting in motor fluctuations and involuntary movements." He continued, "early use of the COMT inhibitor Comtan® /Comtess® (entacapone) may delay late motor complications by achieving continuous rather than pulsatile dopaminergic stimulation. Based on over 100,000 patient exposures, Comtan/Comtess is an effective medication with a good safety profile, which when added to each dose of levodopa, provides fluctuating patients around an extra one and a half hours of daily on-time, improving their quality of life." Professor Brooks added, "even in patients without motor complications, Comtan/Comtess can improve activities of daily living". Not only are there clear benefits in receiving levodopa in a smoother and more continuous fashion for patients already experiencing motor fluctuations, there is increasing interest in providing continuous dopamine stimulation from as early as possible in the management of PD. Currently Comtan/Comtess, is licensed for use in patients experiencing end-of-dose wearing-off. However, there is growing belief that administering a COMT-inhibitor from the first dose of levodopa -- by reducing pulsatile stimulation -- will decrease the risk of motor complications. Administration of Comtan/Comtess and levodopa will be even easier when the triple combination tablet containing levodopa, carbidopa and Comtan becomes available.
SOURCE: Orion Pharma
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