Curbing 'off' episodes in advanced Parkinson's.
This injectable dopamine agonist, known as Apokyn, recently won Food and Drug Administration approval as the first and only acute or rescue therapy for off episodes in Parkinson's disease patients. Apokyn, which has orphan drug status, is distributed through a specialty pharmacy network, a spokesperson for Mylan Laboratories said.
Patients with Parkinson's disease consider off episodes to be among the most disturbing aspects of the disease. (See story on p. 29.) Off episodes, which occur in about 50% of patients after 5 years of levodopa therapy, become increasingly frequent with disease progression.
These debilitating periods of loss of motor control are of two types: those occurring when a patient's oral Parkinson's disease medication wears off at the end of a dose, and those that occur unpredictably, explained Dr. Koller of Mt. Sinai Medical Center, New York.
Off episodes occur because of a shortage of dopamine in movement centers in the brain. They respond to oral dopamine agonists, but only after a roughly 90-minute delay during which patients may encounter great difficulty in walking, eating, and talking.
An alternative to Apokyn in approaching the problem of off episodes is rasagiline, a potent once-daily second-generation MAO type-B inhibitor that reduces the frequency of such episodes by blocking dopamine breakdown, although it's not useful as rescue therapy during an episode.
In randomized trials, rasagiline significantly improved motor function in general, and the disabling symptom known as freezing of gait in particular, in patients with advanced Parkinson's disease, said Dr. Nir Giladi of Tel Aviv University.
Teva Neuroscience has filed a new drug application with the FDA seeking two indications for rasagiline: as monotherapy for patients with early Parkinson's disease and as an adjunct to levodopa for patients with moderate to advanced disease.
Dr. Giladi reported on 454 levodopa-treated patients with advanced Parkinson's disease and motor fluctuations who participated in a double-blind, randomized 18-week trial of 1 mg/day rasagiline, 200 mg entacapone taken three to eight times daily as an active comparator, or placebo.
The primary study end point was change in the Freezing of Gait Questionnaire from baseline to week 10. The rasagiline group showed a significant mean 1.17-point improvement from a baseline of 11.9 on the 24-point scale; improvements in the entacapone group were not significant.
The study was part of a larger trial in which the addition of 1 mg/day of rasagiline in levodopa-treated patients reduced the total daily time that Parkinson's symptoms weren't controlled by 1.2 hours, or 21%. Postural hypotension was the only adverse event more common with rasagiline than placebo, he added.
Dr. Koller reported on 51 patients with advanced Parkinson's disease of a mean 11 years' duration who had multiple daily off episodes. After pretreatment with trimethobenzamide, an antiemetic, they were randomized to treatment of an acute off episode using 4 mg of apomorphine or a placebo injection, then crossed over to the other study arm for treatment of another episode on a separate day.
Scores on the Unified Parkinson's Disease Rating Scale motor score at 20, 40, and 90 minutes were significantly better in the apomorphine group. Side effects more common with Apokyn were yawning, dizziness, nausea, sleepiness, and dyskinesias, all of which were mostly mild to moderate in intensity. The sole serious complication involved a patient who experienced syncope and sinus arrest 16 minutes after receiving Apokyn.
BY BRUCE JANCIN
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|Publication:||Internal Medicine News|
|Date:||Sep 15, 2004|
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