Neupro: Rotigotine transdermal system recently approved by FDA as new molecular entity

Rotigotine transdermal system is now approved by FDA as a nonergoline dopamine agonist for the treatment of for the treatment of signs and symptoms of early-stage idiopathic Parkinson disease.

Key Points

Neupro
Rotigotine transdermal system
SCHWARZNonergoline dopamine agonist approved for the treatment of the signs and symptoms of early-stage idiopathic Parkinson disease
This nonergoline D3/D2/D1 dopamine agonist is thought to help in the treatment of Parkinson disease (PD) by stimulating dopamine D2 receptors within the caudate-putamen in the brain. Rotigotine was approved on May 9, 2007, for the treatment of the signs and symptoms of early-stage idiopathic PD. Rotigotine is the first transdermal patch approved for this indication.

Efficacy. The efficacy of rotigotine was evaluated in 3 studies. The primary outcome assessment was the change from baseline in the combined scores on parts II and III of the Unified Parkinson's Disease Rating Scale (UPDRS). In the first randomized, double-blind, multicenter, multinational study, 316 patients with early-stage PD were randomized to treatment with either placebo or rotigotine (2 mg, 4 mg, 6 mg, or 8 mg every 24 h) administered as one, two, three, or four 2-mg patches for ≤11 weeks. Doses were titrated weekly over 4 weeks so that the target dose was achieved for all groups after 3 weeks; the target dose was administered during the fourth week of the titration phase and then during a 7-week maintenance period. Patients treated with rotigotine demonstrated improvements in UPDRS parts II and III scores compared with patients treated with placebo (difference from placebo: 2 mg, –2.1; 4 mg, –3.1; 6 mg, –4.9; 8 mg, –5.0). In another randomized, double-blind, multinational study, 277 patients with early-stage PD were randomized 2:1 to receive either rotigotine or placebo for ≤28 weeks. Doses were titrated weekly over 3 weeks to a maximal dose of 6 mg/24 h depending on efficacy and tolerability; treatment was continued during a 24-week maintenance phase. Patients treated with rotigotine ≤6 mg/24 h experienced a statistically significant improvement of –5.3 in UPDRS parts II and III scores relative to placebo. The third study was a randomized, double-blind, multinational, 3-arm, parallel-group trial that enrolled 561 patients with early-stage PD. Patients were assigned 1:2:2 to receive placebo, rotigotine, or active oral comparator. Treatment continued for ≤39 weeks. Rotigotine doses were titrated weekly to a maximal daily dose of 8 mg/24 h. After a 13-week titration period, patients received treatment during a 24-week maintenance phase. Patients treated with rotigotine ≤8 mg/24 h demonstrated a statistically significant improvement of –4.5 in UPDRS parts II and III scores relative to placebo.

Safety. Patients treated with rotigotine have reported falling asleep during activities of daily living, including driving. Occasionally, these events have been reported as late as 1 year after treatment initiation. Somnolence is a common occurrence in patients treated with rotigotine. In clinical trials, patients treated with rotigotine have experienced hallucinations, sometimes of sufficient severity to cause discontinuation of treatment. Dopamine agonists have been associated with postural hypotension and syncope. Patients treated with rotigotine have experienced a higher incidence of systolic blood pressure >180 mmHg and diastolic blood pressure >105 mmHg, as well as a higher incidence of substantial weight gain than patients taking placebo. Rotigotine may cause and/or exacerbate pre-existing dyskinesia. Rapid dose reduction, withdrawal of, or changes in antiparkinsonian therapy have been associated with a symptom complex similar to neuroleptic malignant syndrome. Cases of retroperitoneal fibrosis, pulmonary infiltrates, pleural effusion, pleural thickening, pericarditis, and cardiac valvulopathy have occasionally been reported in patients treated with ergot-derived dopaminergic agents. The most common adverse events associated with rotigotine treatment include somnolence, application-site reactions, nausea, dizziness, headache, fatigue, extremity edema, back pain, and insomnia.