Rotigotine

Some of the views expressed in the following notes on newly approved products should be regarded as preliminary, as there may have been limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Executive Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.

Neupro (UCB Pharma)
Transdermal patches releasing 2 mg, 4 mg, 6 mg or 8 mg per 24 hours
Approved indication: Parkinson's disease
Australian Medicines Handbook section 16.2

Parkinson's disease is characterised by a progressive loss of dopaminergic neurons in the brain, causing patients to develop tremor, rigidity and bradykinesia. Symptomatic treatment using drugs such as levodopa and dopamine agonists (Aust Prescr 2001;24:92–5) aims to restore dopaminergic stimulation of the striatal neurons.

Rotigotine is a new non-ergot dopamine agonist which acts at dopamine receptors D3, D2 and D1. In Australia, it has been approved as a monotherapy or in combination with levodopa for early to advanced Parkinson's disease.

This drug comes in the form of a skin patch which is applied once a day. About 45% of the rotigotine in the patch is released within 24 hours and steady state plasma concentrations are reached by 1–2 days. After being extensively metabolised, rotigotine is mainly excreted in the urine as metabolites. Once the patch is removed, plasma concentrations decrease with a terminal half-life of 5–7 hours.

In an eleven week dose-finding trial of 242 patients with early Parkinson's disease, there was a significant improvement in activities of daily living and motor function of patients who received rotigotine 6 mg/24 hours or 8 mg/24 hours compared to placebo.¹ In a six month study of 272 similar patients, the proportion of participants who had a 20% improvement was higher with rotigotine (2 mg, 4 mg or 6 mg/24 hours) than with placebo (48% vs 19%). ²

Rotigotine has been compared with ropinirole in 561 patients with early Parkinson's disease. Ropinirole is also a dopamine agonist, but is not currently approved for Parkinson's disease in Australia. Although rotigotine was better than placebo (with 52% vs 30% of patients responding), it did not appear to be as effective as ropinirole (to which 68% of patients responded).³

Rotigotine has also been tested in patients with advanced Parkinson's disease who were already taking levodopa (≥ 200 mg/day) and had poorly controlled symptoms with at least 2.5 hours of 'off' time a day.⁴ , ⁵ After 24 weeks of maintenance treatment, there were more responders (patients with 30% or more reduction in 'off' time) with rotigotine (8 mg/24 hours or 12 mg/24 hours) than with placebo (56% vs 35%).⁴ In another trial, rotigotine (up to 16 mg/24 hours) appeared to be as effective as pramipexole (up to 4.5 mg/day orally) after 16 weeks of maintenance treatment. Responder rates were 60% for rotigotine (120 of 201 patients), 67% for pramipexole (134 of 200 patients) and 35% for placebo (35 of 100 patients).⁵

Rotigotine's safety profile is generally typical of a dopamine agonist. In a trial of early Parkinson's disease, the most commonly reported adverse events with doses of 2–8 mg/24 hours were nausea (47% of patients), application-site reactions (39%), dizziness (24%), somnolence (22%), insomnia (19%), headache (17%), vomiting (16%) and fatigue (15%). Nausea, application-site reactions, somnolence and insomnia appeared to be dose-related.⁵ Approximately 13% of 649 patients receiving rotigotine discontinued treatment because of adverse events. The most common reasons were application site reaction (5%), nausea (2%) and vomiting (1%). When tested as an adjuvant to levodopa in patients with advanced Parkinson's disease, rotigotine was associated with an increase in hallucinations and dyskinesia compared to

Patients should be warned about the potential sedating effects of rotigotine, which include somnolence and falling asleep suddenly. Some patients have reported sudden sleep or loss of consciousness while driving. Compulsive behaviours such as pathological gambling and increased sexual urges have occurred in patients taking rotigotine.

Rotigotine can elevate heart rate and blood pressure and cause orthostatic hypotension. Monitoring of blood pressure is advisable, especially at the beginning of treatment. Peripheral oedema has been reported in some patients on rotigotine. Patients should be monitored for skin cancers because of an increased risk of melanoma. Cardiac valvulopathy and retinal degeneration may also be a risk with rotigotine.

Dopamine antagonists such as antipsychotics or metoclopramide could potentially reduce the effectiveness of rotigotine and should be avoided.

Rotigotine should be started at 2 mg/24 hours for early Parkinson's disease and 4 mg/24 hours for advanced disease. The dose should be increased weekly depending on the clinical response and tolerability. Likewise, when stopping treatment the dose of rotigotine should be decreased gradually to avoid precipitating neuroleptic malignant syndrome. After removal, the patch is to be folded over so that it sticks to itself before being disposed of safely, and patients or carers should wash their hands to remove any drug.

Rotigotine offers another treatment option for patients with Parkinson's disease. A once-a-day skin patch may be preferable to taking tablets for some patients.

manufacturer provided the product information

The Transparency Score ( ) is explained in New drugs: transparency', Vol 37 No 1, Aust Prescr 2014;37:27.