Ropiniroleside effects

The following adverse reactions are described in more detail in other sections of the label:

Hypersensitivity

Falling asleep during activities of daily living and somnolence

Syncope

Hypotension/orthostatic hypotension

Hallucinations/psychotic-like behavior

Dyskinesia

Impulse control/compulsive behaviors

Withdrawal-emergent hyperpyrexia and confusion

Withdrawal Symptoms

Augmentation and early-morning rebound in RLS

Fibrotic complications

Retinal pathology Most common adverse reactions (incidence with ropinirole at least 5% greater than placebo) in the respective indications were: Early PD: Nausea, somnolence, dizziness, syncope, asthenic condition, viral infection, leg edema, vomiting, and dyspepsia. Advanced PD: Dyskinesia, somnolence, nausea, dizziness, confusion, hallucinations, sweating, and headache. RLS: Nausea, vomiting, somnolence, dizziness, and asthenic condition. To report SUSPECTED ADVERSE REACTIONS, contact Bionpharma Inc. at 1-888-235-BION or 1-888-235-2466 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1 Clinical

Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug (or of another development program of a different formulation of the same drug) and may not reflect the rates observed in practice. Parkinson's Disease During the premarketing development of ropinirole, patients received ropinirole either without L-dopa (early Parkinson's disease trials) or as concomitant therapy with L-dopa (advanced Parkinson's disease trials). Because these 2 populations may have differential risks for various adverse reactions, this section will in general present adverse reaction data for these 2 populations separately. Early Parkinson's Disease (without L-dopa): In the double-blind, placebo-controlled trials in patients with early-stage Parkinson's disease, the most commonly observed adverse reactions in patients treated with ropinirole (incidence at least 5% greater than placebo) were nausea, somnolence, dizziness, syncope, asthenic condition (i.e., asthenia, fatigue, and/or malaise), viral infection, leg edema, vomiting, and dyspepsia. Approximately 24% of patients treated with ropinirole who participated in the double-blind, placebo-controlled early Parkinson's disease (without L-dopa) trials discontinued treatment due to adverse reactions compared with 13% of patients who received placebo. The most common adverse reactions in patients treated with ropinirole (incidence at least 2% greater than placebo) of sufficient severity to cause discontinuation were nausea and dizziness. Table 3 lists treatment-emergent adverse reactions that occurred in at least 2% of patients with early Parkinson's disease (without L-dopa) treated with ropinirole participating in the double-blind, placebo-controlled trials and were numerically more common than the incidence for placebo-treated patients. In these trials, either ropinirole or placebo was used as early therapy (i.e., without L-dopa). Table 3. Treatment-Emergent Adverse Reaction Incidence in Double-blind, Placebo-Controlled Early Parkinson's Disease (without L-dopa) Trials (Events ≥2% of Patients Treated with Ropinirole and Numerically More Frequent than the Placebo Group) a Body System/Adverse Reaction Ropinirole (n = 157) (%) Placebo (n = 147) (% Autonomic nervous system Flushing Dry mouth Increased sweating 3 5 6 1 3 4 Body as a whole Asthenic condition b Chest pain Dependent edema Leg edema Pain 16 4 6 7 8 5 2 3 1 4 Cardiovascular general Hypertension Hypotension Orthostatic symptoms Syncope 5 2 6 12 3 0 5 1 Central/peripheral nervous system Dizziness Hyperkinesia Hypesthesia Vertigo 40 2 4 2 22 1 2 0 Gastrointestinal Abdominal pain Anorexia Dyspepsia Flatulence Nausea Vomiting 6 4 10 3 60 12 3 1 5 1 22 7 Heart rate/rhythm Extrasystoles Atrial fibrillation Palpitation Tachycardia 2 2 3 2 1 0 2 0 Metabolic/nutritional Increased alkaline phosphatase 3 1 Psychiatric Amnesia Impaired concentration Confusion Hallucination Somnolence Yawning 3 2 5 5 40 3 1 0 1 1 6 0 Reproductive male Impotence 3 1 Resistance mechanism Viral infection 11 3 Respiratory Bronchitis Dyspnea Pharyngitis Rhinitis Sinusitis 3 3 6 4 4 1 0 4 3 3 Urinary Urinary tract infection 5 4 Vascular extracardiac Peripheral ischemia 3 0 Vision Eye abnormality Abnormal vision Xerophthalmia 3 6 2 1 3 0 a Patients may have reported multiple adverse reactions during the trial or at discontinuation; thus, patients may be included in more than one category. b Asthenic condition (i.e., asthenia, fatigue, and/or malaise). Advanced Parkinson's Disease (with L-dopa): In the double-blind, placebo-controlled trials in patients with advanced-stage Parkinson's disease, the most commonly observed adverse reactions in patients treated with ropinirole (incidence at least 5 % greater than placebo) were dyskinesia, somnolence, nausea, dizziness, confusion, hallucinations, increased sweating, and headache. Approximately 24% of patients who received ropinirole in the double-blind, placebo-controlled advanced Parkinson's disease (with L-dopa) trials discontinued treatment due to adverse reactions compared with 18% of patients who received placebo. The most common adverse reaction in patients treated with ropinirole (incidence at least 2% greater than placebo) of sufficient severity to cause discontinuation was dizziness. Table 4 lists treatment-emergent adverse reactions that occurred in at least 2% of patients with advanced Parkinson's disease (with L-dopa) treated with ropinirole who participated in the double-blind, placebo-controlled trials and were numerically more common than the incidence for placebo-treated patients. In these trials, either ropinirole or placebo was used as an adjunct to L-dopa. Table 4. Treatment-Emergent Adverse Reaction Incidence in Double-blind, Placebo-Controlled Advanced Parkinson's Disease (with L-dopa) Trials (Events ≥2% of Patients Treated with Ropinirole and Numerically More Frequent than the Placebo Group) a Body System/Adverse Reaction Ropinirole (n = 208) (%) Placebo (n = 120) (%) Autonomic nervous system Dry mouth Increased sweating 5 7 1 2 Body as a whole Increased drug level Pain 7 5 3 3 Cardiovascular general Hypotension Syncope 2 3 1 2 Central/peripheral nervous system Dizziness Dyskinesia Falls Headache Hypokinesia Paresis Paresthesia Tremor 26 34 10 17 5 3 5 6 16 13 7 12 4 0 3 3 Gastrointestinal Abdominal pain Constipation Diarrhea Dysphagia Flatulence Nausea Increased saliva Vomiting 9 6 5 2 2 30 2 7 8 3 3 1 1 18 1 4 Metabolic/nutritional Weight decrease 2 1 Musculoskeletal Arthralgia Arthritis 7 3 5 1 Psychiatric Amnesia Anxiety Confusion Abnormal dreaming Hallucination Nervousness Somnolence 5 6 9 3 10 5 20 1 3 2 2 4 3 8 Red blood cell Anemia 2 0 Resistance mechanism Upper respiratory tract infection 9 8 Respiratory Dyspnea 3 2 Urinary Pyuria Urinary incontinence Urinary tract infection 2 2 6 1 1 3 Vision Diplopia 2 1 a Patients may have reported multiple adverse reactions during the trial or at discontinuation; thus, patients may be included in more than one category. Restless Legs Syndrome In the double-blind, placebo-controlled trials in patients with RLS, the most commonly observed adverse reactions in patients treated with ropinirole (incidence at least 5% greater than placebo) were nausea, vomiting, somnolence, dizziness, and asthenic condition (i.e., asthenia, fatigue, and/or malaise). Approximately 5% of patients treated with ropinirole who participated in the double-blind, placebo-controlled trials in the treatment of RLS discontinued treatment due to adverse reactions compared with 4% of patients who received placebo. The most common adverse reaction in patients treated with ropinirole (incidence at least 2% greater than placebo) of sufficient severity to cause discontinuation was nausea. Table 5 lists treatment-emergent adverse reactions that occurred in at least 2% of patients with RLS treated with ropinirole participating in the 12 week, double-blind, placebo-controlled trials and were numerically more common than the incidence for placebo-treated patients. Table 5. Treatment-Emergent Adverse Reaction Incidence in Double-blind, Placebo-Controlled Restless Legs Syndrome Trials (Events ≥2% of Patients Treated with Ropinirole and Numerically More Frequent than the Placebo Group) a Body System/Adverse Reaction Ropinirole (n = 496) (%) Placebo (n = 500) (%) Ear and labyrinth Vertigo 2 1 Gastrointestinal Nausea Vomiting Diarrhea Dyspepsia Dry mouth Abdominal pain upper 40 11 5 4 3 3 8 2 3 3 2 1 General disorders and administration site conditions Asthenic condition b Edema peripheral 9 2 4 1 Infections and infestations Nasopharyngitis Influenza 9 3 8 2 Musculoskeletal and connective tissue Arthralgia Muscle cramps Pain in extremity 4 3 3 3 2 2 Nervous system Somnolence Dizziness Paresthesia 12 11 3 6 5 1 Respiratory, thoracic, and mediastinal Cough Nasal congestion 3 2 2 1 Skin and subcutaneous tissue Hyperhidrosis 3 1 a Patients may have reported multiple adverse reactions during the trial or at discontinuation; thus, patients may be included in more than one category. b Asthenic condition (i.e., asthenia, fatigue, and/or malaise).

6.2 Postmarketing

Experience The following adverse reactions have been identified during postapproval use of ropinirole. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. General Disorders and Administration Site Conditions Withdrawal symptoms