Rotigotine Transdermal System

Parkinson's Disease (PD)

Neupro (Rotigotine Transdermal System) is indicated for the treatment of the signs and symptoms of idiopathic Parkinson's disease.

The effectiveness of Neupro was demonstrated in randomized, controlled trials in patients with early-stage Parkinson's disease who were not receiving concomitant levodopa therapy as well as in patients with advanced-stage Parkinson's disease on concomitant levodopa.

Restless Legs Syndrome (RLS)

Neupro (Rotigotine Transdermal System) is indicated for the treatment of moderate-to-severe primary restless legs syndrome.

Dosage Forms And Strengths

Transdermal System: 1 mg, 2 mg, 3 mg, 4 mg, 6 mg and 8 mg rotigotine per 24 hours.

Storage And Handling

Each transdermal system is packaged in a separate pouch.

Each strength is available in cartons of 30 transdermal systems.

1 mg/24 hours 30 transdermal systems NDC #50474-801-03
2 mg/24 hours 30 transdermal systems NDC #50474-802-03
3 mg/24 hours 30 transdermal systems NDC #50474-803-03
4 mg/24 hours 30 transdermal systems NDC #50474-804-03
6 mg/24 hours 30 transdermal systems NDC #50474-805-03
8 mg/24 hours 30 transdermal systems NDC #50474-806-03

Store at 20° - 25°C (68° - 77°F); excursions permitted between 15° - 30°C (59° - 86°F). [See USP Controlled Room Temperature]

Neupro should be stored in the original pouch. Do not store outside of pouch.

Apply the transdermal system immediately upon removal from the pouch. Discard used systems in household trash in a manner that prevents accidental application or ingestion by children, pets or others.

Manufactured for: UCB, Inc. Smyrna, GA 30080 Made in Germany 1E. Revised: 04/2012

The following adverse reactions are discussed in more detail in the WARNINGS AND PRECAUTIONS section of labeling.

• Sulfite Sensitivity [see WARNINGS AND PRECAUTIONS]
• Falling Asleep During Activities of Daily Living and Somnolence [see WARNINGS AND PRECAUTIONS]
• Hallucinations / Other Psychiatric Disorders [see WARNINGS AND PRECAUTIONS]
• Symptomatic Hypotension [see WARNINGS AND PRECAUTIONS]
• Syncope [see WARNINGS AND PRECAUTIONS]
• Impulse Control / Compulsive Behaviors [see WARNINGS AND PRECAUTIONS]
• Elevation of Blood Pressure and Heart Rate [see WARNINGS AND PRECAUTIONS]
• Weight Gain and Fluid Retention [see WARNINGS AND PRECAUTIONS]
• Dyskinesia [see WARNINGS AND PRECAUTIONS]
• Application Site Reactions [see WARNINGS AND PRECAUTIONS]
• Melanoma [see WARNINGS AND PRECAUTIONS]
• Augmentation and Rebound in RLS [see WARNINGS AND PRECAUTIONS]
• Heat Application [see WARNINGS AND PRECAUTIONS]
• Withdrawal-Emergent-Hyperpyrexia and Confusion [see WARNINGS AND PRECAUTIONS]
• Fibrotic Complications [see WARNINGS AND PRECAUTIONS]

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, the incidence of adverse reactions (number of unique patients experiencing an adverse reaction associated with treatment / total number of patients treated) observed in the clinical trials of a drug cannot be directly compared to incidence of adverse reactions in the clinical trials of another drug and may not reflect the incidence of adverse reactions observed in practice.

Adverse Reactions Incidence in Controlled Clinical Studies in Early-Stage Parkinson's Disease

The safety of Neupro was evaluated in a total of 649 early-stage Parkinson's disease patients who participated in three double-blind, placebo-controlled studies with durations of 3 to 9 months. Additional safety information was collected in short term studies, and two open-label extension studies in patients with early-stage Parkinson's disease.

The incidence of adverse reactions in a randomized, double-blinded, placebo-controlled, fixed-dose trial is shown in Table 1. Incidences for the non-recommended 8 mg/24 hour dose are also shown.

In the double-blind, placebo-controlled, Dose-Response study in patients with early-stage Parkinson's disease, the most commonly observed adverse reactions (> 5 % greater than placebo) for the highest recommended dose of Neupro (6 mg/24 hours) were nausea, vomiting, somnolence, application site reactions, dizziness, anorexia, hyperhidrosis, and insomnia.

In this trial, 12% of patients treated with the highest, recommended Neupro dose (6 mg/24 hours) discontinued treatment because of adverse reactions, compared with 6% of patients who received placebo.

Table 1 : Incidence of Treatment-Emergent Adverse Reactions in Placebo-Controlled, Trial of Patients with Early-Stage Parkinson's Disease (Dose-Response Study) Where Incidence Was ≥ 2 % in 6 mg/24 hours Neupro Group and Greater Than the Incidence in Placebo-Treated Patients

The incidence of certain adverse reactions with Neupo treatment was notably increased compared to placebo treatment (i.e., Neupro % - placebo % = ≥5 %) in either the titration or maintenance phases of the Dose-Response trial. During the titration phase, an increased incidence ( in descending order of % treatment difference) was observed for nausea, somnolence, vomiting, application site reactions (ASRs), dizziness, sweating increased, anorexia and vision abnormal. During the maintenance phase, an increased incidence was observed for nausea, and ASRs. Some adverse reactions developing in the titration phase persisted ( ≥7 days) into the maintenance phase. These “persistent” adverse reactions included ASRs, anorexia, somnolence, nausea, and vision abnormal.

Adverse Reactions Incidence in Controlled Clinical Studies in Advanced-Stage Parkinson's Disease

The safety evaluation of Neupro was based on a total of 672 Neupro-treated subjects with advanced-stage Parkinson's disease who participated in 3 double-blind, placebo-controlled studies (2 fixed-dose trials and one flexible dose trial) with durations of 3 to 7 months. Patients received concomitant levodopa in these studies. Additional safety information was collected in earlier short-term studies, and 2 open-label extension studies in subjects with advanced-stage Parkinson's disease.

The incidence of adverse reactions in a randomized, double-blinded, placebo-controlled, fixed-dose trial is shown in Table 2. Incidences for the non-recommended 12 mg/24 hour dose are also shown.

In the Dose-Response, placebo controlled trial for advanced-stage Parkinson's disease, the most common adverse reactions (> 5 % greater than placebo) for the highest recommended dose of Neupro (8 mg) were application site reactions, nausea, somnolence, and headache.

In this trial, approximately 15 % of patients treated with the highest, recommended Neupro dose (8 mg/24 hours) discontinued treatment because of adverse reactions, compared with 9 % of patients who received placebo.

Table 2: Incidence of Treatment-Emergent Adverse Reactions in Placebo-Controlled, Trial of Patients with Advanced-Stage Parkinson's Disease (Dose-Response Study) Where Incidence Was ≥ 2 % in 8 mg/24 hours Neupro Group and Greater Than the Incidence in Placebo-Treated Patients

The incidence of certain adverse reactions with Neupo treatment was notably increased compared to placebo treatment (i.e., Neupro % - placebo % = ≥ 5 %) in either the titration or maintenance phases of the Dose-Response trial. During the titration phase, an increased incidence (in descending order of % treatment difference) was observed for nausea, hallucinations, constipation, dyskinesia, dizziness. During the maintenance phase, an increased incidence was observed for ASRs, peripheral edema, and dyskinesia. Some adverse reactions developing in the titration phase persisted ( ≥ 7 days) into the maintenance phase. A notably “persistent” adverse reaction was ASRs.

Adverse Reactions Incidence in Controlled Clinical Studies in Restless Legs Syndrome

The safety evaluation of rotigotine was based on a total of 745 Neupro-treated subjects with RLS who participated in 2 double-blind, placebo-controlled studies with maintenance durations of 6 months. Additional safety information was collected in earlier short term studies, and 3 open-label extension studies in subjects with RLS.

The incidence of adverse reactions in two randomized, double-blinded, placebo-controlled, fixed-dose trials are shown in Table 3.

In the two randomized, double-blinded, placebo-controlled, fixed-dose trials for RLS, the most common adverse reactions (> 5 % greater than placebo) for the highest recommended dose of Neupro (3 mg) were application site reactions, nausea, somnolence, and headache.

In the two Dose-Response, placebo controlled trials, 24 % of Neupro-treated patients treated with the highest recommended dose (3 mg) discontinued treatment because of adverse reactions, compared with 3 % of patients who received placebo.

Table 3 : Incidence of Treatment-Emergent Adverse Reactions in Placebo-Controlled, Trial of Patients with Restless Legs Syndrome (North American and Foreign Multinational Studies) Where Incidence Was ≥ 2 % in 2 mg or 3 mg/24 hours Neupro Groups and Greater Than the Incidence in Placebo-Treated Patients

The incidence of certain adverse reactions with Neupo treatment was notably increased compared to placebo treatment (i.e., Neupro % - placebo % = ≥5 %) in either the titration or maintenance phases of the Dose-Response trial. During the titration phase, an increased incidence (in descending order of % treatment difference) was observed for ASRs, and disturbances in initiating and/or maintaining sleep. During the maintenance phase, an increased incidence was observed for ASRs. Some adverse reactions developing in the titration phase persisted (> 7 days) into the maintenance phase. These “persistent” adverse reactions were ASRs, nausea, and disturbances in initiating and/or maintaining sleep.

Laboratory Changes

Some clinical laboratory analytes were abnormal for patients treated with the highest recommended Neupro dose in the dose-response trials for patients with early-stage and advanced-stage Parkinson's disease and with RLS.

There was a treatment difference (Neupro % - placebo %) of 6 % for decreased hemoglobin (below the normal reference range) and of 3 % for decreased hematocrit (below the normal reference range) in patients with early-stage Parkinson's disease. There was a treatment difference of 4 % for a decreased hemoglobin (below the normal reference range) and of 3 % for decreased hematocrit (below the normal reference range) in patients with advanced-stage Parkinson's disease. There was a treatment difference of 3 % for a decreased hemoglobin (below the normal reference range) in patients with RLS. There was also a treatment difference of 2 % for markedly decreased hemoglobin and hematocrit in patients with advanced Parkinson's disease and of 1 % for markedly decreased hematocrit in patients with RLS.

There was a treatment difference of 9 % for increased serum BUN (above the normal reference range) in patients with early-stage Parkinson's disease. There was a treatment difference of 1 % for markedly increased serum BUN in patients with advanced-stage Parkinson's disease.

There was a treatment difference of 9 % for decreased serum glucose (below the normal reference range) in patients with early-stage Parkinson's disease and of 3 % in patients with advanced-stage Parkinson's disease. There was a treatment difference of 1 % for markedly decreased serum glucose in patients with advanced-stage Parkinson's disease.

Included as part of the PRECAUTIONS section.