For the first time, a transdermal drug delivery system is available for treating Parkinson's disease patients, a treatment option that provides both practical and theoretical benefits for this population, according to experts not involved in clinical trials of the product.
Last month, the Food and Drug Administration approved a transdermal patch containing rotigotine, a nonergotamine dopamine agonist previously not available in any form in the United States, for the signs and symptoms of early-stage idiopathic Parkinson's. Approval was based on three randomized, double-blind, placebo-controlled studies of 1,154 patients with early Parkinson's, who were not on other drugs for Parkinson's. The patch will be marketed as Neupro by the German company Schwarz Pharma LLC and should be available by June 22–30. At press time, price was not available.
A transdermal delivery system is one clear advantage for patients already taking many pills, said Dr. David Standaert, professor of neurology and director of the division of movement disorders at the University of Alabama at Birmingham. The pharmacology of rotigotine is a little different from that of the most widely used dopamine agonists, pramipexole and ropinirole, but the main difference is the transdermal system, he said in an interview.
Another advantage is that the continuous delivery of medication over 24 hours provides a stable blood level, he said. Research suggests the peaks and troughs with conventional dopaminergic drugs may cause some of the problems associated with oral therapy—end of the dose “wearing off” and dyskinesia—and possibly hallucinations and neuropsychiatric effects. However, there is no evidence that the steady level provided by the patch will translate into long-term clinical benefits. Dr. Standaert, who also is the director of the university's Center for Neurodegeneration and Experimental Therapeutics, was not involved in rotigotine studies. He has no financial ties to the manufacturer but has consulted on the pharmacologic properties of rotigotine to UCB, the U.S. pharmaceutical company that is in the process of acquiring Schwarz Pharma.
“There are a lot of both theoretical and practical advantages to finally having patch therapy for Parkinson's,” agreed Dr. Michael Pourfar, a neurologist in the division of movement disorders, at North Shore University Hospital, Manhasset, N.Y. Because there are effective dopamine agonists available for Parkinson's, he said he would not want patients to feel like they must switch medications. “But I do think this is something that will improve quality of life for many,” he added in an interview, noting that for some, the patch could replace as many as six pills per day. He has not been involved in trials of rotigotine and has no financial ties to the maker.
Rotigotine is delivered continuously though the silicone-based patch that is applied to clean, dry intact skin and is replaced every 24 hours. It is available in three strengths: 2 mg, 4 mg, and 6 mg/24 hr. The recommended dosing is to start at 2 mg. When additional therapeutic effects are needed, the dose may be increased weekly by 2 mg/24 hours if tolerated, according to the package insert. In studies, the lowest effective dose was 4 mg/24 hours, and in dose-ranging studies, doses above 6 mg/24 hours were not more effective and were tied to a higher rate of adverse reactions.
The patch should be applied to the front of the abdomen, thigh, hip, flank, shoulder, or upper arm at about the same time every day, avoiding same-site reapplication more than once every 14 days.
The change from baseline for the combined scores for the activities of daily living and motor components of the Unified Parkinson's Disease Rating Scale (UPDRS) was the primary outcome in the three studies, which enrolled early-stage Parkinson's disease patients not on dopamine agonist treatment, whose mean age was 60–63 years.
In one trial, a 28-week multicenter North American study, 277 patients received up to a 6 g/24 hours dose of rotigotine or placebo. The mean reduction in the combined UPDRS score from baseline was 4.0, versus a mean 1.39 increase from baseline among those on placebo, a statistically significant difference of 5.3. The most common side effects were dizziness, nausea, vomiting, drowsiness, and insomnia, “most of which are typical for this class of drugs,” said the FDA. Nearly 40% had application site reactions—mostly mild or moderate—versus 14% of those on a placebo patch. The delivery system contains a sulfite that may cause allergic reactions in sulfite-sensitive people.
The patch is not yet approved for advanced disease, but in a recently published, placebo-controlled, 24-week study of 351 patients with advanced Parkinson's, those treated with two doses of the patch had significant reductions in daily “off” time than those on placebo (Neurology 2007;68:1262–7).