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Rotigotine Transdermal System (Neupro®)
By William T. Elliott, MD, FACP, and James Chan, PhD, PharmD, Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente; Assistant Clinical Professor of Medicine, University of California, San Francisco; Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA. Drs. Chan and Elliott report no financial relationship to this field of study.
The FDA has approved a transdermal patch for the treatment of early Parkinson's disease. Rotigotine is a non-ergoline, D3/D2/D1 dopamine receptor agonist. It is marketed by Schwarz Bioscience as Neupro.
Rotigotine is indicated for the treatment of the signs and symptoms of early stage idiopathic Parkinson's disease.1
The recommended initial dose is 2 mg/24 hours. It may be titrated by 2 mg/24 hours weekly to maximum dose of 6 mg/24 hours. No dosage adjustment is required for moderate hepatic dysfunction or mild to severe renal dysfunction. The patch should be applied to clean, dry, healthy skin on the stomach, thigh, hip, flank, shoulder or upper arm.1
Rotigotine transdermal system is available as 2 mg/24 hours, 4 mg/24 hours and 6 mg/24 hours.
Rotigoline provides a once daily application that delivers a constant level of drug over 24 hours without regard to meals. In comparison, oral formulations tend to have inconsistent absorption, which may lead to variable pharmacological effects.2 Rotigoline has low potential for drug-drug interactions involving CYP isoenzymes.3
Some patients may experience sudden excessive drowsiness without warning that may occur one year after initiation of treatment. The transdermal formulation contains sodium metabisulfite that may cause an allergic reaction (anaphylactic type) in certain susceptible individuals. The most common adverse event is application site reactions (37% vs 14% for placebo) and nausea (38% vs 15%). Other adverse events include syncope, weight gain, peripheral edema, and hypotension.1
Rotigotine is a potent nonergoline dopamine agonist similar to ropinirole and pramipexole. The efficacy of rotigoline was demonstrated in 3 randomized, double-blind placebo controlled parallel studies in patients with early Parkinson's disease, not currently taking levodopa or a dopamine agonist. The primary outcome was change from baseline for Part II (activity of daily living) and III (motor component) of the Unified Parkinson's Disease Rating Scale (UPDRS). Doses of 6 to 8 mg/24 hours showed a difference from placebo in the combined Parts II and III of -4.5 to -5.3 over a period of 11 to 37 weeks.1,4 Baseline UPDRS ranged from 27.1 to 33.2. The reduction in score represents a 14% to 18% change. In patients with advanced disease, rotigoline added to levodopa decreased mean "off" time by an additional 1.8 hours (8 mg/24 hours) from a baseline 6.7 hours compared to placebo.5 Fifty seven percent of patients showed a 30% or greater reduction in "off" time compared to 34% for placebo. Common adverse events include application site reactions, nausea, vomiting, and somnolence. Serious adverse events include falling asleep during daily activity. Comparative studies with other dopamine agonists, levodopa, or MAO inhibitors (selegiline) have not been published. The product information indicated that one arm of a foreign study included an active oral comparator but it was not identified. The cost of rotigoline transdermal systems was not available at the time of this review.
Rotigotine transdermal is a new delivery system for an antiparkinson drug. It appears to offer some potential advantages over oral formulations such as more consistent delivery of the drug. Pulsatile stimulation of the striatal dopamine receptors resulting from short acting dopaminergic drugs may contribute to motor complications of Parkinson's disease.6 Long-acting dopamine agonists such as cabergoline have been shown to reduce the frequency and delay the occurrence of motor complications.7 Whether rotigotine offers a clear clinical advantage over existing agents remains to be established.
1. Neupro Product Information. Schwarz Pharma, LLC. May 2007.
2. Poewe W, Leussi F. Neurology. 2003;65 (suppl 1): S11 -S14.
3. Reynolds NA, et al. CNS Drugs. 2005;19(11):973-981.
4. Watts RL, et al. Neurology. 2007;68:272-276.
5. LeWitt PA, et al. Neurology. 2007;68:1262-1267.
6. Linazasaro G. Arch Neurol. 2007;64:137-140.
7. Bracco F, et al. CNS Drugs. 2004:18(1):733-746.