FDA label 88c5b939-a658-4972-b849-e5c00a447b53

WARNINGS Falling Asleep During Activities of Daily Living: Patients treated with ropinirole hydrochloride have reported falling asleep while engaged in activities of daily living, including the operation of motor vehicles, which sometimes resulted in accidents. Although many of these patients reported somnolence while on ropinirole hydrochloride, some perceived that they had no warning signs such as excessive drowsiness, and believed that they were alert immediately prior to the event. Some of these events have been reported as late as 1 year after initiation of treatment. In controlled clinical trials, somnolence was a common occurrence in patients receiving ropinirole hydrochloride and is more frequent in Parkinson’s disease (up to 40% ropinirole hydrochloride, 6% placebo) than in Restless Legs Syndrome (12% ropinirole hydrochloride, 6% placebo). Many clinical experts believe that falling asleep while engaged in activities of daily living always occurs in a setting of preexisting somnolence, although patients may not give such a history. For this reason, prescribers should continually reassess patients for drowsiness or sleepiness, especially since some of the events occur well after the start of treatment. Prescribers should also be aware that patients may not acknowledge drowsiness or sleepiness until directly questioned about drowsiness or sleepiness during specific activities. Before initiating treatment with ropinirole hydrochloride, patients should be advised of the potential to develop drowsiness and specifically asked about factors that may increase the risk with ropinirole hydrochloride such as concomitant sedating medications, the presence of sleep disorders (other than Restless Legs Syndrome), and concomitant medications that increase ropinirole plasma levels (e.g., ciprofloxacin-see PRECAUTIONS : Drug Interactions ). If a patient develops significant daytime sleepiness or episodes of falling asleep during activities that require active participation (e.g., conversations, eating, etc.), ropinirole hydrochloride should ordinarily be discontinued (see DOSAGE AND ADMINISTRATION for guidance in discontinuing ropinirole hydrochloride). If a decision is made to continue ropinirole hydrochloride, patients should be advised to not drive and to avoid other potentially dangerous activities. There is insufficient information to establish that dose reduction will eliminate episodes of falling asleep while engaged in activities of daily living. Syncope: Syncope, sometimes associated with bradycardia, was observed in association with ropinirole in both Parkinson’s disease patients and RLS patients. In the 2 double-blind, placebo-controlled studies of ropinirole hydrochloride in patients with Parkinson’s disease who were not being treated with L-dopa, 11.5% (18 of 157) of patients on ropinirole hydrochloride had syncope compared to 1.4% (2 of 147) of patients on placebo. Most of these cases occurred more than 4 weeks after initiation of therapy with ropinirole hydrochloride, and were usually associated with a recent increase in dose. Of 208 patients being treated with both L-dopa and ropinirole hydrochloride in placebo-controlled advanced Parkinson’s disease trials, there were reports of syncope in 6 (2.9%) compared to 2 of 120 (1.7%) of placebo/L-dopa patients. In patients with RLS, of 496 patients treated with ropinirole hydrochloride in 12-week placebo-controlled trials, there were reports of syncope in 5 (1.0%) compared with 1 of 500 (0.2%) patients treated with placebo. Because the studies of ropinirole hydrochloride excluded patients with significant cardiovascular disease, it is not known to what extent the estimated incidence figures apply to either Parkinson’s disease or RLS patients in clinical practice. Therefore, patients with severe cardiovascular disease should be treated with caution. Two of 47 Parkinson’s disease patient volunteers enrolled in phase 1 studies had syncope following a 1-mg dose. In 2 studies in RLS patients that used a forced titration regimen and orthostatic challenge with intensive blood pressure monitoring, 1 of 55 RLS patients treated with ropinirole hydrochloride compared with 0 of 27 patients receiving placebo reported syncope. In phase 1 studies including 110 healthy volunteers, 1 patient developed hypotension, bradycardia, and sinus arrest of 26 seconds accompanied by syncope; the patient recovered spontaneously without intervention. One other healthy volunteer reported syncope. Symptomatic Hypotension: Dopamine agonists, in clinical studies and clinical experience, appear to impair the systemic regulation of blood pressure, with resulting postural hypotension, especially during dose escalation. Parkinson’s disease patients, in addition, appear to have an impaired capacity to respond to a postural challenge. For these reasons, Parkinson’s patients being treated with dopaminergic agonists ordinarily (1) require careful monitoring for signs and symptoms of postural hypotension, especially during dose escalation, and (2) should be informed of this risk (see PRECAUTIONS : Information for Patients ). Although the clinical trials were not designed to systematically monitor blood pressure, there were individual reported cases of postural hypotension in early Parkinson’s disease (without L-dopa) in patients treated with ropinirole hydrochloride. Most of these cases occurred more than 4 weeks after initiation of therapy with ropinirole hydrochloride and were usually associated with a recent increase in dose. In 12-week placebo-controlled trials of patients with RLS, the adverse event orthostatic hypotension was reported by 4 of 496 patients (0.8%) treated with ropinirole hydrochloride compared with 2 of 500 patients (0.4%) receiving placebo. In two phase 2 studies in patients with RLS that used a forced-titration regimen and orthostatic challenges with intensive blood pressure monitoring, 14 of 55 patients (25%) receiving ropinirole hydrochloride experienced an adverse event of hypotension or postural hypotension. As described above, one additional patient was noted to have an episode of vasovagal syncope (although no blood pressure recording was documented). None of the 27 patients receiving placebo had a similar adverse event. In these studies, 11 of the 55 patients (20%) receiving ropinirole hydrochloride and 3 of the 26 patients (12%) who had post-dose blood pressure assessments following placebo, experienced an orthostatic blood pressure decrease of at least 40 mm Hg systolic and/or at least 20 mm Hg diastolic; not all of these changes were associated with clinical symptoms. Except for its forced nature these studies used a similar titration schedule as those in the phase 3 efficacy trials. In phase 1 studies of ropinirole hydrochloride that included 110 healthy volunteers, 9 subjects had documented symptomatic postural hypotension. These episodes appeared mainly at doses above 0.8 mg and these doses are higher than the starting doses recommended for either Parkinson’s disease patients or RLS patients. In 8 of these 9 individuals, the hypotension was accompanied by bradycardia, but did not develop into syncope (see Syncope subsection). None of these events resulted in death or hospitalization. One of 47 Parkinson’s disease patient volunteers enrolled in phase 1 studies had documented hypotension following a 2-mg dose on 2 occasions. Hallucinations: In double-blind, placebo-controlled, early-therapy studies in patients with Parkinson’s disease who were not treated with L-dopa, 5.2% (8 of 157) of patients treated with ropinirole hydrochloride reported hallucinations, compared to 1.4% of patients on placebo (2 of 147). Among those patients receiving both ropinirole hydrochloride and L-dopa in advanced Parkinson’s disease (with L-dopa) studies, 10.1% (21 of 208) were reported to experience hallucinations, compared to 4.2% (5 of 120) of patients treated with placebo and L-dopa. Hallucinations were of sufficient severity to cause discontinuation of treatment in 1.3% of the early Parkinson’s disease (without L-dopa) patients and 1.9% of the advanced Parkinson’s disease (with L-dopa) patients, compared to 0% and 1.7% of placebo patients, respectively. In patients with RLS, hallucinations were reported by 0% of patients treated with ropinirole hydrochloride (0 of 496) compared with 0.2% of patients who received placebo (1 of 500) in the 12-week placebo-controlled trials; in premarketing long-term open-label studies, 0.5% of patients reported hallucinations during therapy with ropinirole hydrochloride (2 of 390) but did not discontinue treatment and symptoms resolved.

ADVERSE REACTIONS Parkinson’s Disease: During the premarketing development of ropinirole hydrochloride, patients received ropinirole hydrochloride either without L-dopa (early Parkinson’s disease studies) or as concomitant therapy with L-dopa (advanced Parkinson’s disease studies). Because these 2 populations may have differential risks for various adverse events, this section will, in general, present adverse event data for these 2 populations separately. Early Parkinson’s Disease (Without L-dopa): The most commonly observed adverse events (>5%) in the double-blind, placebo-controlled early Parkinson’s disease trials associated with the use of ropinirole hydrochloride (n = 157) not seen at an equivalent frequency among the placebo-treated patients (n = 147) were, in order of decreasing incidence: nausea, dizziness, somnolence, headache, vomiting, syncope, fatigue, dyspepsia, viral infection, constipation, pain, increased sweating, asthenia, dependent/leg edema, orthostatic symptoms, abdominal pain, pharyngitis, confusion, hallucinations, urinary tract infections, and abnormal vision. Approximately 24% of 157 patients treated with ropinirole hydrochloride who participated in the double-blind, placebo-controlled early Parkinson’s disease (without L-dopa) trials discontinued treatment due to adverse events compared to 13% of 147 patients who received placebo. The adverse events most commonly causing discontinuation of treatment by patients treated with ropinirole hydrochloride were: nausea (6.4%), dizziness (3.8%), aggravated Parkinson’s disease (1.3%), hallucinations (1.3%), somnolence (1.3%), vomiting (1.3%), and headache (1.3%). Of these, hallucinations appear to be dose-related. While other adverse events leading to discontinuation may be dose-related, the titration design utilized in these trials precluded an adequate assessment of the dose response. For example, in the larger of the 2 trials described in CLINICAL PHARMACOLOGY : Clinical Trials , the difference in the rate of discontinuations emerged only after 10 weeks of treatment, suggesting, although not proving, that the effect could be related to dose. Adverse Event Incidence in Controlled Clinical Studies: Table 2 lists treatment-emergent adverse events that occurred in ≥2% of patients with early Parkinson’s disease (without L-dopa) treated with ropinirole hydrochloride participating in the double-blind, placebo-controlled studies and were numerically more common in the group treated with ropinirole hydrochloride. In these studies, either ropinirole hydrochloride or placebo was used as early therapy (i.e., without L-dopa). The prescriber should be aware that these figures cannot be used to predict the incidence of adverse events in the course of usual medical practice where patient characteristics and other factors differ from those that prevailed in the clinical studies. Similarly, the cited frequencies cannot be compared with figures obtained from other clinical investigations involving different treatments, uses, and investigators. However, the cited figures do provide the prescribing physician with some basis for estimating the relative contribution of drug and non-drug factors to the adverse-events incidence rate in the population studied. Table 2Treatment-Emergent Adverse Event Patients may have reported multiple adverse experiences during the study or at discontinuation; thus, patients may be included in more than one category. Incidence in Double-Blind, Placebo-Controlled Early Parkinson’s Disease (Without L-dopa) Trials (Events ≥2% of Patients Treated with Ropinirole Hydrochloride and Numerically More Frequent Than the Placebo Group) Adverse Experience Ropinirole Hydrochloride ( n = 157 ) (%) Placebo ( n = 147 ) (%) Autonomic nervous system Flushing 3 1 Dry mouth 5 3 Increased sweating 6 4 Body as a whole Asthenia 6 1 Chest pain 4 2 Dependent edema 6 3 Leg edema 7 1 Fatigue 11 4 Malaise 3 1 Pain 8 4 Cardiovascular general Hypertension 5 3 Hypotension 2 0 Orthostatic symptoms 6 5 Syncope 12 1 Central / peripheral nervous system Dizziness 40 22 Hyperkinesia 2 1 Hypesthesia 4 2 Vertigo 2 0 Gastrointestinal system Abdominal pain 6 3 Anorexia 4 1 Dyspepsia 10 5 Flatulence 3 1 Nausea 60 22 Vomiting 12 7 Heart rate / rhythm Extrasystoles 2 1 Atrial fibrillation 2 0 Palpitation 3 2 Tachycardia 2 0 Metabolic / nutritional Increased alkaline phosphatase 3 1 Psychiatric Amnesia 3 1 Impaired concentration 2 0 Confusion 5 1 Hallucination 5 1 Somnolence 40 6 Yawning 3 0 Reproductive male Impotence 3 1 Resistance mechanism Viral infection 11 3 Respiratory system Bronchitis 3 1 Dyspnea 3 0 Pharyngitis 6 4 Rhinitis 4 3 Sinusitis 4 3 Urinary system Urinary tract infection 5 4 Vascular extracardiac Peripheral ischemia 3 0 Vision Eye abnormality 3 1 Abnormal vision 6 3 Xerophthalmia 2 0 Other events reported by 1% or more of early Parkinson’s disease (without L-dopa) patients treated with ropinirole hydrochloride, but that were equally or more frequent in the placebo group, were: headache, upper respiratory infection, insomnia, arthralgia, tremor, back pain, anxiety, dyskinesias, aggravated Parkinsonism, depression, falls, myalgia, leg cramps, paresthesias, nervousness, diarrhea, arthritis, hot flushes, weight loss, rash, cough, hyperglycemia, muscle spasm, arthrosis, abnormal dreams, dystonia, increased salivation, bradycardia, gout, basal cell carcinoma, gingivitis, hematuria, and rigors. Among the treatment-emergent adverse events in patients treated with ropinirole hydrochloride, hallucinations appear to be dose-related. The incidence of adverse events was not materially different between women and men. Advanced Parkinson’s Disease (With L-dopa): The most commonly observed adverse events (>5%), in the double-blind, placebo-controlled advanced Parkinson’s disease (with L-dopa) trials associated with the use of ropinirole hydrochloride (n = 208) as an adjunct to L-dopa not seen at an equivalent frequency among the placebo-treated patients (n = 120) were, in order of decreasing incidence: dyskinesias, nausea, dizziness, aggravated Parkinsonism, somnolence, headache, insomnia, injury, hallucinations, falls, abdominal pain, upper respiratory infection, confusion, increased sweating, vomiting, viral infection, increased drug level, arthralgia, tremor, anxiety, urinary tract infection, constipation, dry mouth, pain, hypokinesia, and paresthesia. Approximately 24% of 208 patients who received ropinirole hydrochloride in the double-blind, placebo-controlled advanced Parkinson’s disease (with L-dopa) trials discontinued treatment due to adverse events compared to 18% of 120 patients who received placebo. The events most commonly (≥1%) causing discontinuation of treatment by patients treated with ropinirole hydrochloride were: dizziness (2.9%), dyskinesias (2.4%), vomiting (2.4%), confusion (2.4%), nausea (1.9%), hallucinations (1.9%), anxiety (1.9%), and increased sweating (1.4%). Of these, hallucinations and dyskinesias appear to be dose-related. Adverse Event Incidence in Controlled Clinical Studies: Table 3 lists treatment-emergent adverse events that occurred in ≥2% of patients with advanced Parkinson’s disease (with L-dopa) treated with ropinirole hydrochloride who participated in the double-blind, placebo-controlled studies and were numerically more common in the group treated with ropinirole hydrochloride. In these studies, either ropinirole hydrochloride or placebo was used as an adjunct to L-dopa. Adverse events were usually mild or moderate in intensity. The prescriber should be aware that these figures cannot be used to predict the incidence of adverse events in the course of usual medical practice where patient characteristics and other factors differ from those that prevailed in the clinical studies. Similarly, the cited frequencies cannot be compared with figures obtained from other clinical investigations involving different treatments, uses, and investigators. However, the cited figures do provide the prescribing physician with some basis for estimating the relative contribution of drug and non-drug factors to the adverse events incidence rate in the population studied. Table 3Treatment-Emergent Adverse Event Patients may have reported multiple adverse experiences during the study or at discontinuation; thus, patients may be included in more than one category. Incidence in Double-Blind, Placebo-Controlled Advanced Parkinson’s Disease (With L-dopa) Trials (Events ≥2% ofPatients Treated with Ropinirole Hydrochloride and Numerically More Frequent Than the Placebo Group) Ropinirole Hydrochloride Placebo ( n = 208 ) ( n = 120 ) Adverse Experience (%) (%) Autonomic nervous system Dry mouth 5 1 Increased sweating 7 2 Body as a whole Increased drug level 7 3 Pain 5 3 Cardiovascular general Hypotension 2 1 Syncope 3 2 Central / peripheral nervous system Dizziness 26 16 Dyskinesia 34 13 Falls 10 7 Headache 17 12 Hypokinesia 5 4 Paresis 3 0 Paresthesia 5 3 Tremor 6 3 Gastrointestinal system Abdominal pain 9 8 Constipation 6 3 Diarrhea 5 3 Dysphagia 2 1 Flatulence 2 1 Nausea 30 18 Increased saliva 2 1 Vomiting 7 4 Metabolic / nutritional Weight decrease 2 1 Musculoskeletal system Arthralgia 7 5 Arthritis 3 1 Psychiatric Amnesia 5 1 Anxiety 6 3 Confusion 9 2 Abnormal dreaming 3 2 Hallucinations 10 4 Nervousness 5 3 Somnolence 20 8 Red blood cell Anemia 2 0 Resistance mechanism Upper respiratory tract infection 9 8 Respiratory system Dyspnea 3 2 Urinary system Pyuria 2 1 Urinary incontinence 2 1 Urinary tract infection 6 3 Vision Diplopia 2 1 Other events reported by 1% or more of patients treated with both ropinirole hydrochloride and L-dopa, but equally or more frequent in the placebo/L-dopa group, were: myocardial infarction, orthostatic symptoms, virus infections, asthenia, dyspepsia, myalgia, back pain, depression, leg cramps, fatigue, rhinitis, chest pain, hematuria, vertigo, tinnitus, leg edema, hot flushes, abnormal gait, hyperkinesia, and pharyngitis. Among the treatment-emergent adverse events in patients treated with ropinirole hydrochloride, hallucinations and dyskinesias appear to be dose-related. Restless Legs Syndrome: The most commonly observed adverse events (>5%) in the 12-week double-blind, placebo-controlled trials in the treatment of Restless Legs Syndrome with ropinirole hydrochloride (n = 496) and at least twice the rate for placebo-treated patients (n = 500) were, in order of decreasing incidence: nausea, somnolence, vomiting, dizziness, and fatigue (see Table 4 ). Occurrences of nausea in clinical trials were generally mild to moderate in intensity (see also DOSAGE AND ADMINISTRATION : General Dosing Considerations ). Approximately 5% of 496 patients treated with ropinirole hydrochloride who participated in the double-blind, placebo-controlled trials in the treatment of RLS discontinued treatment due to adverse events compared to 4% of 500 patients who received placebo. The adverse events most commonly causing discontinuation of treatment by patients treated with ropinirole hydrochloride were: nausea (1.6%), dizziness (0.8 %), and headache (0.8%). Adverse Event Incidence in Controlled Clinical Studies: Table 4 lists treatment-emergent adverse events that occurred in ≥2% of patients with RLS treated with ropinirole hydrochloride participating in the 12-week double-blind, placebo-controlled studies and were numerically more common in the group treated with ropinirole hydrochloride. The prescriber should be aware that these figures cannot be used to predict the incidence of adverse events in the course of usual medical practice where patient characteristics and other factors differ from those that prevailed in the clinical studies. Similarly, the cited frequencies cannot be compared with figures obtained from other clinical investigations involving different treatments, uses, and investigators. However, the cited figures do provide the prescribing physician with some basis for estimating the relative contribution of drug and non-drug factors to the adverse-events incidence rate in the population studied. Table 4Treatment-Emergent Adverse Event Incidence in Double-Blind, Placebo-Controlled RLS Trials (Events ≥2% of Patients Treated with Ropinirole Hydrochloride and Numerically More Frequent Than the Placebo Group) Adverse Experience Ropinirole Hydrochloride ( n = 496 ) (%) Placebo ( n = 500 ) (%) Ear and labyrinth disorders Vertigo 2 1 Gastrointestinal disorders Nausea 40 8 Vomiting 11 2 Diarrhea 5 3 Dyspepsia 4 3 Dry mouth 3 2 Abdominal pain upper 3 1 General disorders and administration site conditions Fatigue 8 4 Edema peripheral 2 1 Infections and infestations Nasopharyngitis 9 8 Influenza 3 2 Musculoskeletal and connective tissue disorders Arthralgia 4 3 Muscle cramps 3 2 Pain in extremity 3 2 Nervous system disorders Somnolence 12 6 Dizziness 11 5 Paresthesia 3 1 Respiratory , thoracic , and mediastinal disorders Cough 3 2 Nasal congestion 2 1 Skin and subcutaneous tissue disorders Hyperhidrosis 3 1 Other events reported by 2% or more of patients treated with ropinirole hydrochloride, but equally or more frequent in the placebo group, were headache, insomnia, restless legs syndrome, upper respiratory tract infection, back pain, and sinusitis. Other Adverse Events Observed During All Phase 2/3 Clinical Trials for Parkinson’s Disease: Ropinirole hydrochloride has been administered to 1,599 individuals in clinical trials. During these trials, all adverse events were recorded by the clinical investigators using terminology of their own choosing. To provide a meaningful estimate of the proportion of individuals having adverse events, similar types of events were grouped into a smaller number of standardized categories using modified WHOART dictionary terminology. These categories are used in the listing below. The frequencies presented represent the proportion of the 1,599 individuals exposed to ropinirole hydrochloride who experienced events of the type cited on at least 1 occasion while receiving ropinirole hydrochloride. All reported events that occurred at least twice (or once for serious or potentially serious events), except those already listed above, trivial events, and terms too vague to be meaningful, are included without regard to determination of a causal relationship to ropinirole hydrochloride, except that events very unlikely to be drug-related have been deleted. Events are further classified within body system categories and enumerated in order of decreasing frequency using the following definitions: frequent adverse events are defined as those occurring in at least 1/100 patients and infrequent adverse events are those occurring in 1/100 to 1/1,000 patients and rare events are those occurring in fewer than 1/1,000 patients. Body as a Whole: Infrequent: Cellulitis, peripheral edema, fever, influenza-like symptoms, enlarged abdomen, precordial chest pain, and generalized edema. Rare: Ascites. Cardiovascular: Infrequent: Cardiac failure, bradycardia, tachycardia, supraventricular tachycardia, angina pectoris, bundle branch block, cardiac arrest, cardiomegaly, aneurysm, mitral insufficiency. Rare: Ventricular tachycardia. Central/Peripheral Nervous System: Frequent: Neuralgia. Infrequent: Involuntary muscle contractions, hypertonia, dysphonia, abnormal coordination, extrapyramidal disorder, migraine, choreoathetosis, coma, stupor, aphasia, convulsions, hypotonia, peripheral neuropathy, paralysis. Rare: Grand mal convulsions, hemiparesis, hemiplegia. Endocrine: Infrequent: Hypothyroidism, gynecomastia, hyperthyroidism. Rare: Goiter, SIADH. Gastrointestinal: Infrequent: Increased hepatic enzymes, bilirubinemia, cholecystitis, cholelithiasis colitis, dysphagia, periodontitis, fecal incontinence, gastroesophageal reflux, hemorrhoids, toothache, eructation, gastritis, esophagitis, hiccups, diverticulitis, duodenal ulcer, gastric ulcer, melena, duodenitis, gastrointestinal hemorrhage, glossitis, rectal hemorrhage, pancreatitis, stomatitis and ulcerative stomatitis, tongue edema. Rare: Biliary pain, hemorrhagic gastritis, hematemesis, salivary duct obstruction. Hematologic: Infrequent: Purpura, thrombocytopenia, hematoma, Vitamin B12 deficiency, hypochromic anemia, eosinophilia, leukocytosis, leukopenia, lymphocytosis, lymphopenia, lymphedema. Metabolic/Nutritional: Frequent: Increased BUN. Infrequent: Hypoglycemia, increased alkaline phosphatase, increased LDH, weight increase, hyperphosphatemia, hyperuricemia, diabetes mellitus, glycosuria, hypokalemia, hypercholesterolemia, hyperkalemia, acidosis, hyponatremia, thirst, increased CPK, dehydration. Rare: Hypochloremia. Musculoskeletal: Infrequent: Aggravated arthritis, tendonitis, osteoporosis, bursitis, polymyalgia rheumatica, muscle weakness, skeletal pain, torticollis. Rare: Dupuytren’s contracture requiring surgery. Neoplasm: Infrequent: Malignant breast neoplasm. Rare: Bladder carcinoma, benign brain neoplasm, esophageal carcinoma, malignant laryngeal neoplasm, lipoma, rectal carcinoma, uterine neoplasm. Psychiatric: Infrequent: Increased libido, agitation, apathy, impaired concentration, depersonalization, paranoid reaction, personality disorder, euphoria, delirium, dementia, delusion, emotional lability, decreased libido, manic reaction, somnambulism, aggressive reaction, neurosis. Rare: Suicide attempt. Genitourinary: Infrequent: Amenorrhea, vaginal hemorrhage, penile disorder, prostatic disorder, balanoposthitis, epididymitis, perineal pain, dysuria, micturition frequency, albuminuria, nocturia, polyuria, renal calculus. Rare: Breast enlargement, mastitis, uterine hemorrhage, ejaculation disorder, Peyronie’s disease, pyelonephritis, acute renal failure, uremia. Resistance Mechanism: Infrequent: Herpes zoster, otitis media, sepsis, abscess, herpes simplex, fungal infection, genital moniliasis. Respiratory: Infrequent: Asthma, epistaxis, laryngitis, pleurisy, pulmonary edema. Skin/Appendage: Infrequent : Pruritus, dermatitis, eczema, skin ulceration, alopecia, skin hypertrophy, skin discoloration, urticaria, fungal dermatitis, furunculosis, hyperkeratosis, photosensitivity reaction, psoriasis, maculopapular rash, psoriaform rash, seborrhea. Special Senses: Infrequent: Tinnitus, earache, decreased hearing, abnormal lacrimation, conjunctivitis, blepharitis, glaucoma, abnormal accommodation, blepharospasm, eye pain, photophobia. Rare: Scotoma. Vascular Extracardiac: Infrequent: Varicose veins, phlebitis, peripheral gangrene. Rare: Limb embolism, pulmonary embolism, gangrene, subarachnoid hemorrhage, deep thrombophlebitis, leg thrombophlebitis, thrombosis. Falling Asleep During Activities of Daily Living: Patients treated with ropinirole hydrochloride have reported falling asleep while engaged in activities of daily living, including operation of a motor vehicle which sometimes resulted in accidents (see bolded WARNING ). Other Adverse Events Observed During Phase 2/3 Clinical Trials for RLS: Ropinirole hydrochloride has been administered to 911 individuals in clinical trials. During these trials, all adverse events were recorded by the clinical investigators using terminology of their own choosing. To provide a meaningful estimate of the proportion of individuals having adverse events, similar types of events were grouped into a smaller number of standardized categories using MedDRA dictionary terminology. These categories are used in the listing below. The frequencies presented represent the proportion of the 911 individuals exposed to ropinirole hydrochloride who experienced events of the type cited on at least one occasion while receiving ropinirole hydrochloride. All reported events that occurred at least twice (or once for serious or potentially serious events), except those already listed, trivial events, and terms too vague to be meaningful, are included without regard to determination of a causal relationship to ropinirole hydrochloride, except that events very unlikely to be drug-related have been deleted. Events are further classified within body system categories and enumerated in order of decreasing frequency using the following definitions: frequent adverse events are defined as those occurring in at least 1/100 patients and infrequent adverse events are those occurring in 1/100 to 1/1,000 patients. Blood and Lymphatic System Disorders: Infrequent: Anemia, lymphadenopathy. Cardiac Disorders: Frequent: Palpitations. Infrequent: Acute coronary syndrome, angina pectoris, angina unstable, bradycardia, cardiac failure, cardiovascular disorder, coronary artery disease, myocardial infarction, sick sinus syndrome, tachycardia. Congenital, Familial, and Genetic Disorders: Infrequent: Pigmented nevus. Ear and Labyrinth Disorders: Infrequent: Ear pain, middle ear effusion, tinnitus. Endocrine Disorders: Infrequent: Goiter, hypothyroidism. Eye Disorders: Infrequent: Blepharitis, conjunctival hemorrhage, conjunctivitis, eye irritation, eye pain, keratoconjunctivitis sicca, vision blurred, visual acuity reduced, visual disturbance. Gastrointestinal Disorders: Frequent: Abdominal pain, constipation, gastroesophageal reflux disease, stomach discomfort, toothache. Infrequent: Abdominal adhesions, abdominal discomfort, abdominal distension, abdominal pain lower, duodenal ulcer, dysphagia, eructation, flatulence, gastric disorder, gastric hemorrhage, gastric polyps, gastric ulcer, gastritis, gastrointestinal pain, hematemesis, hemorrhoids, hiatus hernia, intestinal obstruction, irritable bowel syndrome, loose stools, mouth ulceration, pancreatitis acute, peptic ulcer, rectal hemorrhage, reflux esophagitis. General Disorders and Administration Site Conditions: Frequent: Asthenia, chest pain, influenza-like illness, rigors. Infrequent: Chest discomfort, feeling cold, feeling hot, hunger, lethargy, malaise, edema, pain, pyrexia. Hepatobiliary Disorders: Infrequent: Cholecystitis, cholelithiasis, ischemic hepatitis. Immune System Disorders: Infrequent: Hypersensitivity. Infections and Infestations: Frequent: Bronchitis, gastroenteritis, gastroenteritis viral, lower respiratory tract infection, rhinitis, tooth abscess, urinary tract infection. Infrequent: Appendicitis, bacterial infection, bladder infection, bronchitis acute, candidiasis, cellulitis, cystitis, diarrhea infectious, diverticulitis, ear infection, folliculitis, fungal infection, gastrointestinal infection, herpes simplex, infected cyst, laryngitis, localized infection, mastitis, otitis externa, otitis media, pharyngitis, pneumonia, postoperative infection, respiratory tract infection, tonsillitis, tooth infection, vaginal candidiasis, vaginal infection , vaginal mycosis, viral infection, viral upper respiratory tract infection, wound infection. Injury, Poisoning, and Procedural Complications: Infrequent: Concussion, lower limb fracture, post procedural hemorrhage, road traffic accident. Investigations: Infrequent: Blood cholesterol increased, blood iron decreased, blood pressure increased, blood urine present, hemoglobin decreased, heart rate increased, protein urine present, weight decreased, weight increased. Metabolism and Nutrition Disorders: Infrequent: Anorexia, decreased appetite, diabetes mellitus non-insulin-dependent, fluid retention, gout, hypercholesterolemia. Musculoskeletal and Connective Tissue Disorders: Frequent: Muscle spasms, musculoskeletal stiffness, myalgia, neck pain, osteoarthritis, tendonitis. Infrequent: Arthritis, aseptic necrosis bone, bone pain, bone spur, bursitis, groin pain, intervertebral disc degeneration, intervertebral disc protrusion, joint stiffness, joint swelling, localized osteoarthritis, monoarthritis, muscle contracture, muscle tightness, muscle twitching, osteoporosis, rotator cuff syndrome, sacroiliitis, synovitis. Neoplasms Benign, Malignant, and Unspecified: Infrequent: Anaplastic thyroid cancer, angiomyolipoma, basal cell carcinoma, breast cancer, gastric cancer, gastrointestinal stromal tumor, malignant melanoma, prostate cancer, skin papilloma, squamous cell carcinoma, uterine leiomyoma. Nervous System Disorders: Frequent: Hypoesthesia, migraine. Infrequent: Amnesia, aphasia, ataxia, balance disorder, benign intracranial hypertension, burning sensation, carpal tunnel syndrome, disturbance in attention, dizziness postural, dysgeusia, dyskinesia, head discomfort, hyperesthesia, hypersomnia, lethargy, loss of consciousness, memory impairment, migraine with aura, migraine without aura, neuralgia, sciatica, sedation, sinus headache, sleep apnea syndrome, syncope vasovagal, tension headache, transient ischemic attack, tremor. Psychiatric Disorders: Frequent: Anxiety, depression, irritability, sleep disorder. Infrequent: Abnormal dreams, agitation, bruxism, confusional state, depressed mood, disorientation, early morning awakening, libido decreased, loss of libido, mood swings, nervousness, nightmare, panic attack, stress symptoms, tension. Renal and Urinary Disorders: Infrequent: Dysuria, hematuria, hypertonic bladder, micturition disorder, nephrolithiasis, nocturia, pollakiuria, proteinuria, urinary retention. Reproductive System and Breast Disorders: Frequent: Erectile dysfunction. Infrequent: Breast cyst, dysmenorrhea, menorrhagia, pelvic peritoneal adhesions, postmenopausal hemorrhage, premenstrual syndrome, prostatitis. Respiratory, Thoracic and Mediastinal Disorders: Frequent: Asthma, pharyngolaryngeal pain. Infrequent: Dry throat, dyspnea, epistaxis, hemoptysis, hoarseness, interstitial lung disease, nasal mucosal disorder, nasal polyps, respiratory tract congestion, rhinorrhea, sinus congestion, sneezing, wheezing, yawning. Skin and Subcutaneous Tissue Disorders: Frequent: Night sweats, rash. Infrequent: Acne, actinic keratosis, alopecia, cold sweat, dermatitis, dermatitis allergic, dermatitis contact, eczema, exanthem, face edema, photosensitivity reaction, pruritus, psoriasis, rash pruritic, skin lesion, urticaria. Vascular Disorders: Frequent: Hot flush, hypertension, hypotension. Infrequent: Atherosclerosis, circulatory collapse, flushing, hematoma, thrombosis, varicose vein. Postmarketing Reports: Psychiatric Disorders: Impulse control symptoms, pathological gambling, increased libido including hypersexuality.

<table ID="id_901fa928-1acc-4a1a-961c-ca7a0912acb8"> <caption ID="id_7e52e24d-75c3-44f6-b7fb-69a259894d06">Table 2Treatment-Emergent Adverse Event<footnote ID="id-acd57067-6910-43d0-8755-b1d5b355b2f0">Patients may have reported multiple adverse experiences during the study or at discontinuation; thus, patients may be included in more than one category.</footnote> Incidence in Double-Blind, Placebo-Controlled Early Parkinson&#x2019;s Disease (Without L-dopa) Trials (Events &#x2265;2% of Patients Treated with Ropinirole Hydrochloride and Numerically More Frequent Than the Placebo Group)</caption> <col width="51%"/> <col width="24%"/> <col width="24%"/> <thead> <tr ID="id_9d0f2a95-9315-4706-b17d-f81e1567a821"> <td align="left" valign="top" styleCode="Lrule Botrule Rrule"> <content styleCode="bold"> </content> <content styleCode="bold">Adverse </content> <content styleCode="bold">Experience</content> <content styleCode="bold"> </content> </td> <td align="center" valign="top" styleCode="Rrule"> <content styleCode="bold">Ropinirole </content> <content styleCode="bold">Hydrochloride</content> <content styleCode="bold"> </content> <content styleCode="bold">(</content> <content styleCode="bold">n </content> <content styleCode="bold">= </content> <content styleCode="bold">157</content> <content styleCode="bold">)</content> <content styleCode="bold"> </content> <content styleCode="bold">(%)</content> <content styleCode="bold"> </content> </td> <td align="center" valign="top" styleCode="Botrule Rrule"> <content styleCode="bold">Placebo</content> <content styleCode="bold"> </content> <content styleCode="bold">(</content> <content styleCode="bold">n </content> <content styleCode="bold">= </content> <content styleCode="bold">147</content> <content styleCode="bold">)</content> <content styleCode="bold"> </content> <content styleCode="bold">(%)</content> <content styleCode="bold"> </content> </td> </tr> </thead> <tbody> <tr ID="id_daba6a1e-e5b6-48c3-90fc-9fb19dacf50e"> <td align="left" valign="top" styleCode="Lrule Toprule Rrule"> <content styleCode="bold">Autonomic </content> <content styleCode="bold">nervous </content> <content styleCode="bold">system</content> <content styleCode="bold"> </content> </td> <td align="center" valign="top" styleCode="Rrule"> </td> <td align="center" valign="top" styleCode="Rrule"> </td> </tr> <tr ID="id_2a3f1d70-3ca2-4a2b-91ff-bd3ba19fe668"> <td align="left" valign="top" styleCode="Lrule Rrule"> Flushing </td> <td align="center" valign="top" styleCode="Rrule">3 </td> <td align="center" valign="top" styleCode="Rrule">1 </td> </tr> <tr ID="id_d4d97923-0eff-4869-920f-9e30d93f54de"> <td align="left" valign="top" styleCode="Lrule Rrule"> Dry mouth </td> <td align="center" valign="top" styleCode="Rrule">5 </td> <td align="center" valign="top" styleCode="Rrule">3 </td> </tr> <tr ID="id_8ca7ae1e-1038-485b-99ba-539bece07038"> <td align="left" valign="top" styleCode="Lrule Botrule Rrule"> Increased sweating </td> <td align="center" valign="top" styleCode="Botrule Rrule">6 </td> <td align="center" valign="top" styleCode="Botrule Rrule">4 </td> </tr> <tr ID="id_7b5c7be2-3ba5-487b-90d3-937fe76b9bb5"> <td align="left" valign="top" styleCode="Lrule Rrule"> <content styleCode="bold">Body </content> <content styleCode="bold">as </content> <content styleCode="bold">a </content> <content styleCode="bold">whole</content> <content styleCode="bold"> </content> </td> <td align="center" valign="top" styleCode="Rrule"> </td> <td align="center" valign="top" styleCode="Rrule"> </td> </tr> <tr ID="id_d29451de-7f33-45bf-a019-137bd255c2f1"> <td align="left" valign="top" styleCode="Lrule Rrule"> Asthenia </td> <td align="center" valign="top" styleCode="Rrule">6 </td> <td align="center" valign="top" styleCode="Rrule">1 </td> </tr> <tr ID="id_57c72e62-b3e8-477b-ba2c-f31c584548ba"> <td align="left" valign="top" styleCode="Lrule Rrule"> Chest pain </td> <td align="center" valign="top" styleCode="Rrule">4 </td> <td align="center" valign="top" styleCode="Rrule">2 </td> </tr> <tr ID="id_76b30032-f2e9-405c-8478-3d73e20ace5e"> <td align="left" valign="top" styleCode="Lrule Rrule"> Dependent edema </td> <td align="center" valign="top" styleCode="Rrule">6 </td> <td align="center" valign="top" styleCode="Rrule">3 </td> </tr> <tr ID="id_f3eb2eed-1a8c-481d-97bd-2c953bf32d48"> <td align="left" valign="top" styleCode="Lrule Rrule"> Leg edema </td> <td align="center" valign="top" styleCode="Rrule">7 </td> <td align="center" valign="top" styleCode="Rrule">1 </td> </tr> <tr ID="id_fd1e8af1-ad6d-432e-b96b-cb04cc8f51df"> <td align="left" valign="top" styleCode="Lrule Rrule"> Fatigue </td> <td align="center" valign="top" styleCode="Rrule">11 </td> <td align="center" valign="top" styleCode="Rrule">4 </td> </tr> <tr ID="id_8bf2d0e1-77c5-4222-b8d0-dbae733015e1"> <td align="left" valign="top" styleCode="Lrule Rrule"> Malaise </td> <td align="center" valign="top" styleCode="Rrule">3 </td> <td align="center" valign="top" styleCode="Rrule">1 </td> </tr> <tr ID="id_e3871ddb-a851-477c-9c32-a128dd4cdcb7"> <td align="left" valign="top" styleCode="Lrule Botrule Rrule"> Pain </td> <td align="center" valign="top" styleCode="Botrule Rrule">8 </td> <td align="center" valign="top" styleCode="Botrule Rrule">4 </td> </tr> <tr ID="id_95971507-86d8-405c-aeb8-ba1ae63f68f0"> <td align="left" valign="top" styleCode="Lrule Rrule"> <content styleCode="bold">Cardiovascular </content> <content styleCode="bold">general</content> <content styleCode="bold"> </content> </td> <td align="center" valign="top" styleCode="Rrule"> </td> <td align="center" valign="top" styleCode="Rrule"> </td> </tr> <tr ID="id_a2c21cb3-dcc6-47f7-8d45-f341d9da6d7a"> <td align="left" valign="top" styleCode="Lrule Rrule"> Hypertension </td> <td align="center" valign="top" styleCode="Rrule">5 </td> <td align="center" valign="top" styleCode="Rrule">3 </td> </tr> <tr ID="id_20feb8a5-5dd0-4d51-b557-04a3957ef4ae"> <td align="left" valign="top" styleCode="Lrule Rrule"> Hypotension </td> <td align="center" valign="top" styleCode="Rrule">2 </td> <td align="center" valign="top" styleCode="Rrule">0 </td> </tr> <tr ID="id_e1d92a3e-d11d-4442-82c1-da44993b5d29"> <td align="left" valign="top" styleCode="Lrule Rrule"> Orthostatic symptoms </td> <td align="center" valign="top" styleCode="Rrule">6 </td> <td align="center" valign="top" styleCode="Rrule">5 </td> </tr> <tr ID="id_f99b9633-835d-492b-bada-2ab3bca5e66b"> <td align="left" valign="top" styleCode="Lrule Botrule Rrule"> Syncope </td> <td align="center" valign="top" styleCode="Botrule Rrule">12 </td> <td align="center" valign="top" styleCode="Botrule Rrule">1 </td> </tr> <tr ID="id_e287bcba-e42a-4d37-9c7d-61dc1c7a730b"> <td align="left" valign="top" styleCode="Lrule Rrule"> <content styleCode="bold">Central</content> <content styleCode="bold">/</content> <content styleCode="bold">peripheral </content> <content styleCode="bold">nervous </content> <content styleCode="bold">system</content> <content styleCode="bold"> </content> </td> <td align="center" valign="top" styleCode="Rrule"> </td> <td align="center" valign="top" styleCode="Rrule"> </td> </tr> <tr ID="id_c5beed20-d042-4b8d-ab54-066fe282c9ea"> <td align="left" valign="top" styleCode="Lrule Rrule"> Dizziness </td> <td align="center" valign="top" styleCode="Rrule">40 </td> <td align="center" valign="top" styleCode="Rrule">22 </td> </tr> <tr ID="id_246e4ba6-6fae-40b2-9ba2-a47ea845d2bd"> <td align="left" valign="top" styleCode="Lrule Rrule"> Hyperkinesia </td> <td align="center" valign="top" styleCode="Rrule">2 </td> <td align="center" valign="top" styleCode="Rrule">1 </td> </tr> <tr ID="id_1c8ca2e1-d615-4421-98c6-098e31937386"> <td align="left" valign="top" styleCode="Lrule Rrule"> Hypesthesia </td> <td align="center" valign="top" styleCode="Rrule">4 </td> <td align="center" valign="top" styleCode="Rrule">2 </td> </tr> <tr ID="id_17b17178-be74-41ea-ae0f-181802fbc169"> <td align="left" valign="top" styleCode="Lrule Botrule Rrule"> Vertigo </td> <td align="center" valign="top" styleCode="Botrule Rrule">2 </td> <td align="center" valign="top" styleCode="Botrule Rrule">0 </td> </tr> <tr ID="id_60c54fde-78b0-4fb7-8ca6-fd363a9899a8"> <td align="left" valign="top" styleCode="Lrule Rrule"> <content styleCode="bold">Gastrointestinal </content> <content styleCode="bold">system</content> <content styleCode="bold"> </content> </td> <td align="center" valign="top" styleCode="Rrule"> </td> <td align="center" valign="top" styleCode="Rrule"> </td> </tr> <tr ID="id_d6c31f55-cb8a-4974-a6d3-9c40d5866941"> <td align="left" valign="top" styleCode="Lrule Rrule"> Abdominal pain </td> <td align="center" valign="top" styleCode="Rrule">6 </td> <td align="center" valign="top" styleCode="Rrule">3 </td> </tr> <tr ID="id_fe848681-3604-480c-b3bd-baa0066f7b49"> <td align="left" valign="top" styleCode="Lrule Rrule"> Anorexia </td> <td align="center" valign="top" styleCode="Rrule">4 </td> <td align="center" valign="top" styleCode="Rrule">1 </td> </tr> <tr ID="id_eaaf5753-0b25-4228-843d-7d0b4aa24fc2"> <td align="left" valign="top" styleCode="Lrule Rrule"> Dyspepsia </td> <td align="center" valign="top" styleCode="Rrule">10 </td> <td align="center" valign="top" styleCode="Rrule">5 </td> </tr> <tr ID="id_38d8499f-2888-4429-b674-f4cd5209ddaa"> <td align="left" valign="top" styleCode="Lrule Rrule"> Flatulence </td> <td align="center" valign="top" styleCode="Rrule">3 </td> <td align="center" valign="top" styleCode="Rrule">1 </td> </tr> <tr ID="id_b1d111ef-ea5a-477d-97f6-de470ff003cf"> <td align="left" valign="top" styleCode="Lrule Rrule"> Nausea </td> <td align="center" valign="top" styleCode="Rrule">60 </td> <td align="center" valign="top" styleCode="Rrule">22 </td> </tr> <tr ID="id_f3928ad4-7015-489c-a933-e81f53b72eb5"> <td align="left" valign="top" styleCode="Lrule Botrule Rrule"> Vomiting </td> <td align="center" valign="top" styleCode="Botrule Rrule">12 </td> <td align="center" valign="top" styleCode="Botrule Rrule">7 </td> </tr> <tr ID="id_33a9345e-ac8d-480d-b215-480aef73bd68"> <td align="left" valign="top" styleCode="Lrule Rrule"> <content styleCode="bold">Heart </content> <content styleCode="bold">rate</content> <content styleCode="bold">/</content> <content styleCode="bold">rhythm</content> <content styleCode="bold"> </content> </td> <td align="center" valign="top" styleCode="Rrule"> </td> <td align="center" valign="top" styleCode="Rrule"> </td> </tr> <tr ID="id_3c9c0ed1-22fc-43e5-b1b8-4b5daf457378"> <td align="left" valign="top" styleCode="Lrule Rrule"> Extrasystoles </td> <td align="center" valign="top" styleCode="Rrule">2 </td> <td align="center" valign="top" styleCode="Rrule">1 </td> </tr> <tr ID="id_1b52ed5c-f57f-4e0c-bcb0-215b4ff2195a"> <td align="left" valign="top" styleCode="Lrule Rrule"> Atrial fibrillation </td> <td align="center" valign="top" styleCode="Rrule">2 </td> <td align="center" valign="top" styleCode="Rrule">0 </td> </tr> <tr ID="id_e2596700-8c96-4da8-bffb-9cd5300360ff"> <td align="left" valign="top" styleCode="Lrule Rrule"> Palpitation </td> <td align="center" valign="top" styleCode="Rrule">3 </td> <td align="center" valign="top" styleCode="Rrule">2 </td> </tr> <tr ID="id_3e6a8596-e39c-49e7-bd80-f9833c22128b"> <td align="left" valign="top" styleCode="Lrule Botrule Rrule"> Tachycardia </td> <td align="center" valign="top" styleCode="Botrule Rrule">2 </td> <td align="center" valign="top" styleCode="Botrule Rrule">0 </td> </tr> <tr ID="id_26fc822e-bcb6-41bd-888f-1e0b3d7e8c27"> <td align="left" valign="top" styleCode="Lrule Rrule"> <content styleCode="bold">Metabolic</content> <content styleCode="bold">/</content> <content styleCode="bold">nutritional</content> <content styleCode="bold"> </content> </td> <td align="center" valign="top" styleCode="Rrule"> </td> <td align="center" valign="top" styleCode="Rrule"> </td> </tr> <tr ID="id_39e84ffa-8dbc-4825-99f1-9ee2241d634a"> <td align="left" valign="top" styleCode="Lrule Botrule Rrule"> Increased alkaline phosphatase </td> <td align="center" valign="top" styleCode="Botrule Rrule">3 </td> <td align="center" valign="top" styleCode="Botrule Rrule">1 </td> </tr> <tr ID="id_24c32ba5-e26d-49f7-b008-07168ff36e91"> <td align="left" valign="top" styleCode="Lrule Rrule"> <content styleCode="bold">Psychiatric</content> <content styleCode="bold"> </content> </td> <td align="center" valign="top" styleCode="Rrule"> </td> <td align="center" valign="top" styleCode="Rrule"> </td> </tr> <tr ID="id_58dc9f48-bf7b-4b19-9fa2-4601e90ca974"> <td align="left" valign="top" styleCode="Lrule Rrule"> Amnesia </td> <td align="center" valign="top" styleCode="Rrule">3 </td> <td align="center" valign="top" styleCode="Rrule">1 </td> </tr> <tr ID="id_05c02fbd-f525-49b2-800d-9c7bf7fa8f74"> <td align="left" valign="top" styleCode="Lrule Rrule"> Impaired concentration </td> <td align="center" valign="top" styleCode="Rrule">2 </td> <td align="center" valign="top" styleCode="Rrule">0 </td> </tr> <tr ID="id_14da114f-27fb-420a-8aed-d508dea88381"> <td align="left" valign="top" styleCode="Lrule Rrule"> Confusion </td> <td align="center" valign="top" styleCode="Rrule">5 </td> <td align="center" valign="top" styleCode="Rrule">1 </td> </tr> <tr ID="id_281b1ffc-92a8-44de-a211-2daf1397d6c0"> <td align="left" valign="top" styleCode="Lrule Rrule"> Hallucination </td> <td align="center" valign="top" styleCode="Rrule">5 </td> <td align="center" valign="top" styleCode="Rrule">1 </td> </tr> <tr ID="id_92a4dd58-87a8-4b8d-bbad-3145c25bd824"> <td align="left" valign="top" styleCode="Lrule Rrule"> Somnolence </td> <td align="center" valign="top" styleCode="Rrule">40 </td> <td align="center" valign="top" styleCode="Rrule">6 </td> </tr> <tr ID="id_1dff65b0-5e09-480d-ae15-65814d9a657e"> <td align="left" valign="top" styleCode="Lrule Botrule Rrule"> Yawning </td> <td align="center" valign="top" styleCode="Botrule Rrule">3 </td> <td align="center" valign="top" styleCode="Botrule Rrule">0 </td> </tr> <tr ID="id_7e0342fb-6bc6-4aa5-9ca7-21e133ea41e4"> <td align="left" valign="top" styleCode="Lrule Rrule"> <content styleCode="bold">Reproductive </content> <content styleCode="bold">male</content> <content styleCode="bold"> </content> </td> <td align="center" valign="top" styleCode="Rrule"> </td> <td align="center" valign="top" styleCode="Rrule"> </td> </tr> <tr ID="id_e2d41743-8d92-4871-a0c8-f5d97e0227fe"> <td align="left" valign="top" styleCode="Lrule Botrule Rrule"> Impotence </td> <td align="center" valign="top" styleCode="Botrule Rrule">3 </td> <td align="center" valign="top" styleCode="Botrule Rrule">1 </td> </tr> <tr ID="id_ca8e4fe0-6ec4-4a48-9195-e0469dc77e30"> <td align="left" valign="top" styleCode="Lrule Rrule"> <content styleCode="bold">Resistance </content> <content styleCode="bold">mechanism</content> <content styleCode="bold"> </content> </td> <td align="center" valign="top" styleCode="Rrule"> </td> <td align="center" valign="top" styleCode="Rrule"> </td> </tr> <tr ID="id_62a6e365-0b3b-4006-a267-aa9d07680828"> <td align="left" valign="top" styleCode="Lrule Botrule Rrule"> Viral infection </td> <td align="center" valign="top" styleCode="Botrule Rrule">11 </td> <td align="center" valign="top" styleCode="Botrule Rrule">3 </td> </tr> <tr ID="id_94e051de-0d32-4f85-a269-fb528c7d809d"> <td align="left" valign="top" styleCode="Lrule Rrule"> <content styleCode="bold">Respiratory </content> <content styleCode="bold">system</content> <content styleCode="bold"> </content> </td> <td align="center" valign="top" styleCode="Rrule"> </td> <td align="center" valign="top" styleCode="Rrule"> </td> </tr> <tr ID="id_01fb0704-5e4a-4d8c-86f9-44274b5ca084"> <td align="left" valign="top" styleCode="Lrule Rrule"> Bronchitis </td> <td align="center" valign="top" styleCode="Rrule">3 </td> <td align="center" valign="top" styleCode="Rrule">1 </td> </tr> <tr ID="id_6bdef8df-6268-4399-8594-58fb2119f1a7"> <td align="left" valign="top" styleCode="Lrule Rrule"> Dyspnea </td> <td align="center" valign="top" styleCode="Rrule">3 </td> <td align="center" valign="top" styleCode="Rrule">0 </td> </tr> <tr ID="id_a104a1bc-7ed7-4b68-8f48-a7521d908f5f"> <td align="left" valign="top" styleCode="Lrule Rrule"> Pharyngitis </td> <td align="center" valign="top" styleCode="Rrule">6 </td> <td align="center" valign="top" styleCode="Rrule">4 </td> </tr> <tr ID="id_3e33c67c-d46b-4db0-90cf-2d7e030e44b1"> <td align="left" valign="top" styleCode="Lrule Rrule"> Rhinitis </td> <td align="center" valign="top" styleCode="Rrule">4 </td> <td align="center" valign="top" styleCode="Rrule">3 </td> </tr> <tr ID="id_85df2fd4-3447-4fac-9b40-2e6071b2d1e7"> <td align="left" valign="top" styleCode="Lrule Botrule Rrule"> Sinusitis </td> <td align="center" valign="top" styleCode="Botrule Rrule">4 </td> <td align="center" valign="top" styleCode="Botrule Rrule">3 </td> </tr> <tr ID="id_a725d8fc-35e9-4385-b3ea-7abc68768c17"> <td align="left" valign="top" styleCode="Lrule Rrule"> <content styleCode="bold">Urinary </content> <content styleCode="bold">system</content> <content styleCode="bold"> </content> </td> <td align="center" valign="top" styleCode="Rrule"> </td> <td align="center" valign="top" styleCode="Rrule"> </td> </tr> <tr ID="id_6b78453a-3050-4220-8266-e731c80e8aad"> <td align="left" valign="top" styleCode="Lrule Botrule Rrule"> Urinary tract infection </td> <td align="center" valign="top" styleCode="Botrule Rrule">5 </td> <td align="center" valign="top" styleCode="Botrule Rrule">4 </td> </tr> <tr ID="id_23326453-7a00-461f-aef5-15977a8c8dd9"> <td align="left" valign="top" styleCode="Lrule Rrule"> <content styleCode="bold">Vascular </content> <content styleCode="bold">extracardiac</content> <content styleCode="bold"> </content> </td> <td align="center" valign="top" styleCode="Rrule"> </td> <td align="center" valign="top" styleCode="Rrule"> </td> </tr> <tr ID="id_226f4fd4-6e77-4b82-a07a-628e20d6c47e"> <td align="left" valign="top" styleCode="Lrule Botrule Rrule"> Peripheral ischemia </td> <td align="center" valign="top" styleCode="Botrule Rrule">3 </td> <td align="center" valign="top" styleCode="Botrule Rrule">0 </td> </tr> <tr ID="id_f98bc309-63f1-43ef-8678-e311e9ff8076"> <td align="left" valign="top" styleCode="Lrule Rrule"> <content styleCode="bold">Vision</content> <content styleCode="bold"> </content> </td> <td align="left" valign="top" styleCode="Rrule"> </td> <td align="left" valign="top" styleCode="Rrule"> </td> </tr> <tr ID="id_7c231bed-3349-43fd-b911-f6e2622214eb"> <td align="left" valign="top" styleCode="Lrule Rrule"> Eye abnormality </td> <td align="center" valign="top" styleCode="Rrule">3 </td> <td align="center" valign="top" styleCode="Rrule">1 </td> </tr> <tr ID="id_541672f3-2ffb-4338-b866-a09c700f966b"> <td align="left" valign="top" styleCode="Lrule Rrule"> Abnormal vision </td> <td align="center" valign="top" styleCode="Rrule">6 </td> <td align="center" valign="top" styleCode="Rrule">3 </td> </tr> <tr ID="id_3cef6601-3a21-4872-8786-436b88931f5f"> <td align="left" valign="top" styleCode="Lrule Botrule Rrule"> Xerophthalmia </td> <td align="center" valign="top" styleCode="Rrule">2 </td> <td align="center" valign="top" styleCode="Botrule Rrule">0 </td> </tr> </tbody> </table>

<table ID="id_ac896ccc-2925-4065-bbab-1fad7a0a8508"> <caption ID="id_183f34fd-30da-4784-a2c0-e2690ad97937">Table 3Treatment-Emergent Adverse Event<footnote ID="id-929d9641-392d-40a8-9447-73885a5854d5">Patients may have reported multiple adverse experiences during the study or at discontinuation; thus, patients may be included in more than one category.</footnote> Incidence in Double-Blind, Placebo-Controlled Advanced Parkinson&#x2019;s Disease (With L-dopa) Trials (Events &#x2265;2% ofPatients Treated with Ropinirole Hydrochloride and Numerically More Frequent Than the Placebo Group)</caption> <col width="51%"/> <col width="25%"/> <col width="24%"/> <thead> <tr ID="id_c135af63-5840-40c1-baa3-6e5c4500511d"> <td align="left" valign="top" styleCode="Lrule Toprule Rrule"> </td> <td align="center" valign="top" styleCode="Botrule Rrule"> <content styleCode="bold">Ropinirole </content> <content styleCode="bold">Hydrochloride</content> <content styleCode="bold"> </content> </td> <td align="center" valign="top" styleCode="Botrule Rrule"> <content styleCode="bold">Placebo</content> <content styleCode="bold"> </content> </td> </tr> <tr ID="id_d16d1371-5d3f-4bf7-912e-5bddefbd94d4"> <td align="left" valign="top" styleCode="Lrule Botrule Rrule"> </td> <td align="center" valign="top" styleCode="Botrule Rrule"> <content styleCode="bold">(</content> <content styleCode="bold">n </content> <content styleCode="bold">= </content> <content styleCode="bold">208</content> <content styleCode="bold">)</content> <content styleCode="bold"> </content> </td> <td align="center" valign="top" styleCode="Botrule Rrule"> <content styleCode="bold">(</content> <content styleCode="bold">n </content> <content styleCode="bold">= </content> <content styleCode="bold">120</content> <content styleCode="bold">)</content> <content styleCode="bold"> </content> </td> </tr> <tr ID="id_44079e3b-90d7-4dfa-897d-bb41523ec53f"> <td align="left" valign="top" styleCode="Lrule Botrule Rrule"> <content styleCode="bold">Adverse </content> <content styleCode="bold">Experience</content> <content styleCode="bold"> </content> </td> <td align="center" valign="top" styleCode="Rrule"> <content styleCode="bold">(%)</content> <content styleCode="bold"> </content> </td> <td align="center" valign="top" styleCode="Botrule Rrule"> <content styleCode="bold">(%)</content> <content styleCode="bold"> </content> </td> </tr> </thead> <tbody> <tr ID="id_7ca3edff-52b7-4c2b-ac5a-ff10a6e2f598"> <td align="left" valign="top" styleCode="Lrule Toprule Rrule"> <content styleCode="bold">Autonomic </content> <content styleCode="bold">nervous </content> <content styleCode="bold">system</content> <content styleCode="bold"> </content> </td> <td align="center" valign="top" styleCode="Rrule"> </td> <td align="center" valign="top" styleCode="Rrule"> </td> </tr> <tr ID="id_1bc8e8bf-6c35-4356-bab5-4ed83396da00"> <td align="left" valign="top" styleCode="Lrule Rrule"> Dry mouth </td> <td align="center" valign="top" styleCode="Rrule">5 </td> <td align="center" valign="top" styleCode="Rrule">1 </td> </tr> <tr ID="id_b1c8b8eb-0f95-4b43-8f68-290dac3d9877"> <td align="left" valign="top" styleCode="Lrule Botrule Rrule"> Increased sweating </td> <td align="center" valign="top" styleCode="Botrule Rrule">7 </td> <td align="center" valign="top" styleCode="Botrule Rrule">2 </td> </tr> <tr ID="id_efc14148-f756-4193-9b62-f9c4f630a432"> <td align="left" valign="top" styleCode="Lrule Rrule"> <content styleCode="bold">Body </content> <content styleCode="bold">as </content> <content styleCode="bold">a </content> <content styleCode="bold">whole</content> <content styleCode="bold"> </content> </td> <td align="center" valign="top" styleCode="Rrule"> </td> <td align="center" valign="top" styleCode="Rrule"> </td> </tr> <tr ID="id_3cbed9c6-f4a6-42c3-b133-11201fd81966"> <td align="left" valign="top" styleCode="Lrule Rrule"> Increased drug level </td> <td align="center" valign="top" styleCode="Rrule">7 </td> <td align="center" valign="top" styleCode="Rrule">3 </td> </tr> <tr ID="id_73de2541-93f0-418a-b4b1-6eebb86f0753"> <td align="left" valign="top" styleCode="Lrule Botrule Rrule"> Pain </td> <td align="center" valign="top" styleCode="Botrule Rrule">5 </td> <td align="center" valign="top" styleCode="Botrule Rrule">3 </td> </tr> <tr ID="id_b9dcbd57-ef97-4e23-89c3-b8d7b7ee79c1"> <td align="left" valign="top" styleCode="Lrule Rrule"> <content styleCode="bold">Cardiovascular </content> <content styleCode="bold">general</content> <content styleCode="bold"> </content> </td> <td align="center" valign="top" styleCode="Rrule"> </td> <td align="center" valign="top" styleCode="Rrule"> </td> </tr> <tr ID="id_d01bac45-1dd6-4c8f-8ef2-bf45927d5ee2"> <td align="left" valign="top" styleCode="Lrule Rrule"> Hypotension </td> <td align="center" valign="top" styleCode="Rrule">2 </td> <td align="center" valign="top" styleCode="Rrule">1 </td> </tr> <tr ID="id_b157df35-a10b-426f-a44d-47f6416bc04c"> <td align="left" valign="top" styleCode="Lrule Botrule Rrule"> Syncope </td> <td align="center" valign="top" styleCode="Botrule Rrule">3 </td> <td align="center" valign="top" styleCode="Botrule Rrule">2 </td> </tr> <tr ID="id_c8662acd-9c96-4449-957a-db4ae955f7ae"> <td align="left" valign="top" styleCode="Lrule Rrule"> <content styleCode="bold">Central</content> <content styleCode="bold">/</content> <content styleCode="bold">peripheral </content> <content styleCode="bold">nervous </content> <content styleCode="bold">system</content> <content styleCode="bold"> </content> </td> <td align="center" valign="top" styleCode="Rrule"> </td> <td align="center" valign="top" styleCode="Rrule"> </td> </tr> <tr ID="id_99300f29-2a8a-487b-b851-e43dafd87c7c"> <td align="left" valign="top" styleCode="Lrule Rrule"> Dizziness </td> <td align="center" valign="top" styleCode="Rrule">26 </td> <td align="center" valign="top" styleCode="Rrule">16 </td> </tr> <tr ID="id_dc333db4-59fc-4281-9a71-7d56fc3093f8"> <td align="left" valign="top" styleCode="Lrule Rrule"> Dyskinesia </td> <td align="center" valign="top" styleCode="Rrule">34 </td> <td align="center" valign="top" styleCode="Rrule">13 </td> </tr> <tr ID="id_2bfbca74-ca17-4905-85d4-187fce1998d5"> <td align="left" valign="top" styleCode="Lrule Rrule"> Falls </td> <td align="center" valign="top" styleCode="Rrule">10 </td> <td align="center" valign="top" styleCode="Rrule">7 </td> </tr> <tr ID="id_df462ef1-b25d-406c-b76d-3f56addba55d"> <td align="left" valign="top" styleCode="Lrule Rrule"> Headache </td> <td align="center" valign="top" styleCode="Rrule">17 </td> <td align="center" valign="top" styleCode="Rrule">12 </td> </tr> <tr ID="id_22b28f0d-05ae-4955-86ec-13b444912205"> <td align="left" valign="top" styleCode="Lrule Rrule"> Hypokinesia </td> <td align="center" valign="top" styleCode="Rrule">5 </td> <td align="center" valign="top" styleCode="Rrule">4 </td> </tr> <tr ID="id_37512e6b-1571-4f19-85b2-22d1082bf08d"> <td align="left" valign="top" styleCode="Lrule Rrule"> Paresis </td> <td align="center" valign="top" styleCode="Rrule">3 </td> <td align="center" valign="top" styleCode="Rrule">0 </td> </tr> <tr ID="id_6d31cb54-89fc-4c40-a868-e2054b004455"> <td align="left" valign="top" styleCode="Lrule Rrule"> Paresthesia </td> <td align="center" valign="top" styleCode="Rrule">5 </td> <td align="center" valign="top" styleCode="Rrule">3 </td> </tr> <tr ID="id_b83c8114-d8f2-41e6-92cd-6bf5d04d0d57"> <td align="left" valign="top" styleCode="Lrule Botrule Rrule"> Tremor </td> <td align="center" valign="top" styleCode="Botrule Rrule">6 </td> <td align="center" valign="top" styleCode="Botrule Rrule">3 </td> </tr> <tr ID="id_7b9d013d-af73-41e1-93f3-824bf8dd39fd"> <td align="left" valign="top" styleCode="Lrule Rrule"> <content styleCode="bold">Gastrointestinal </content> <content styleCode="bold">system</content> <content styleCode="bold"> </content> </td> <td align="center" valign="top" styleCode="Rrule"> </td> <td align="center" valign="top" styleCode="Rrule"> </td> </tr> <tr ID="id_e2437b6d-4488-4cc9-89f7-de9941d01303"> <td align="left" valign="top" styleCode="Lrule Rrule"> Abdominal pain </td> <td align="center" valign="top" styleCode="Rrule">9 </td> <td align="center" valign="top" styleCode="Rrule">8 </td> </tr> <tr ID="id_3aacd938-84ba-471d-a017-349771b7eaba"> <td align="left" valign="top" styleCode="Lrule Rrule"> Constipation </td> <td align="center" valign="top" styleCode="Rrule">6 </td> <td align="center" valign="top" styleCode="Rrule">3 </td> </tr> <tr ID="id_cab71e46-2a94-4ee7-a891-996f45b406e2"> <td align="left" valign="top" styleCode="Lrule Rrule"> Diarrhea </td> <td align="center" valign="top" styleCode="Rrule">5 </td> <td align="center" valign="top" styleCode="Rrule">3 </td> </tr> <tr ID="id_336fd4f0-15df-459b-95ff-6a62955e46ac"> <td align="left" valign="top" styleCode="Lrule Rrule"> Dysphagia </td> <td align="center" valign="top" styleCode="Rrule">2 </td> <td align="center" valign="top" styleCode="Rrule">1 </td> </tr> <tr ID="id_794b7c62-c6f4-4e6a-a04e-85160a026111"> <td align="left" valign="top" styleCode="Lrule Rrule"> Flatulence </td> <td align="center" valign="top" styleCode="Rrule">2 </td> <td align="center" valign="top" styleCode="Rrule">1 </td> </tr> <tr ID="id_77ed7cb6-0722-4c76-9a2f-ef23f95f7acd"> <td align="left" valign="top" styleCode="Lrule Rrule"> Nausea </td> <td align="center" valign="top" styleCode="Rrule">30 </td> <td align="center" valign="top" styleCode="Rrule">18 </td> </tr> <tr ID="id_991504fb-f83e-4504-a212-5bd396d126dd"> <td align="left" valign="top" styleCode="Lrule Rrule"> Increased saliva </td> <td align="center" valign="top" styleCode="Rrule">2 </td> <td align="center" valign="top" styleCode="Rrule">1 </td> </tr> <tr ID="id_9b0da0f6-1a2c-49c7-95fe-dcd70c9bf53b"> <td align="left" valign="top" styleCode="Lrule Botrule Rrule"> Vomiting </td> <td align="center" valign="top" styleCode="Botrule Rrule">7 </td> <td align="center" valign="top" styleCode="Botrule Rrule">4 </td> </tr> <tr ID="id_e1ddbc95-9b71-4ccd-ab68-356de2249f4c"> <td align="left" valign="top" styleCode="Lrule Rrule"> <content styleCode="bold">Metabolic</content> <content styleCode="bold">/</content> <content styleCode="bold">nutritional</content> <content styleCode="bold"> </content> </td> <td align="center" valign="top" styleCode="Rrule"> </td> <td align="center" valign="top" styleCode="Rrule"> </td> </tr> <tr ID="id_816863f6-7f35-47b9-baec-ecf204bd7cdc"> <td align="left" valign="top" styleCode="Lrule Botrule Rrule"> Weight decrease </td> <td align="center" valign="top" styleCode="Botrule Rrule">2 </td> <td align="center" valign="top" styleCode="Botrule Rrule">1 </td> </tr> <tr ID="id_5f2c23b4-858c-45ee-91ec-9e0597ee325f"> <td align="left" valign="top" styleCode="Lrule Rrule"> <content styleCode="bold">Musculoskeletal </content> <content styleCode="bold">system</content> <content styleCode="bold"> </content> </td> <td align="center" valign="top" styleCode="Rrule"> </td> <td align="center" valign="top" styleCode="Rrule"> </td> </tr> <tr ID="id_79bae07d-3c4f-4d9c-9dfa-202b117ce451"> <td align="left" valign="top" styleCode="Lrule Rrule"> Arthralgia </td> <td align="center" valign="top" styleCode="Rrule">7 </td> <td align="center" valign="top" styleCode="Rrule">5 </td> </tr> <tr ID="id_0464216f-41a7-4c43-a170-62e928cee7a4"> <td align="left" valign="top" styleCode="Lrule Botrule Rrule"> Arthritis </td> <td align="center" valign="top" styleCode="Botrule Rrule">3 </td> <td align="center" valign="top" styleCode="Botrule Rrule">1 </td> </tr> <tr ID="id_394bec5c-6425-4156-8346-a91dc23daea5"> <td align="left" valign="top" styleCode="Lrule Rrule"> <content styleCode="bold">Psychiatric</content> <content styleCode="bold"> </content> </td> <td align="center" valign="top" styleCode="Rrule"> </td> <td align="center" valign="top" styleCode="Rrule"> </td> </tr> <tr ID="id_d10d54eb-46e9-48e0-83eb-436ae10d249c"> <td align="left" valign="top" styleCode="Lrule Rrule"> Amnesia </td> <td align="center" valign="top" styleCode="Rrule">5 </td> <td align="center" valign="top" styleCode="Rrule">1 </td> </tr> <tr ID="id_3e747489-45c4-4434-9be9-8781d75245e3"> <td align="left" valign="top" styleCode="Lrule Rrule"> Anxiety </td> <td align="center" valign="top" styleCode="Rrule">6 </td> <td align="center" valign="top" styleCode="Rrule">3 </td> </tr> <tr ID="id_0a7a16d4-cbc1-4834-b7d8-c678bd619b3d"> <td align="left" valign="top" styleCode="Lrule Rrule"> Confusion </td> <td align="center" valign="top" styleCode="Rrule">9 </td> <td align="center" valign="top" styleCode="Rrule">2 </td> </tr> <tr ID="id_f70887c6-4ee6-4047-a2df-d0c47ef68d0b"> <td align="left" valign="top" styleCode="Lrule Rrule"> Abnormal dreaming </td> <td align="center" valign="top" styleCode="Rrule">3 </td> <td align="center" valign="top" styleCode="Rrule">2 </td> </tr> <tr ID="id_772cb117-5db9-4a37-9a16-f653a1ac36fb"> <td align="left" valign="top" styleCode="Lrule Rrule"> Hallucinations </td> <td align="center" valign="top" styleCode="Rrule">10 </td> <td align="center" valign="top" styleCode="Rrule">4 </td> </tr> <tr ID="id_ab0b1589-4ea8-4ecf-9861-35f96e18a968"> <td align="left" valign="top" styleCode="Lrule Rrule"> Nervousness </td> <td align="center" valign="top" styleCode="Rrule">5 </td> <td align="center" valign="top" styleCode="Rrule">3 </td> </tr> <tr ID="id_6bc4236d-5b21-4d43-838b-27a0742ceb5b"> <td align="left" valign="top" styleCode="Lrule Botrule Rrule"> Somnolence </td> <td align="center" valign="top" styleCode="Botrule Rrule">20 </td> <td align="center" valign="top" styleCode="Botrule Rrule">8 </td> </tr> <tr ID="id_bddb729a-a431-4e2e-a76a-fadec6b03827"> <td align="left" valign="top" styleCode="Lrule Rrule"> <content styleCode="bold">Red </content> <content styleCode="bold">blood </content> <content styleCode="bold">cell</content> <content styleCode="bold"> </content> </td> <td align="left" valign="top" styleCode="Rrule"> </td> <td align="left" valign="top" styleCode="Rrule"> </td> </tr> <tr ID="id_0840c4e4-1518-4d85-b703-f5d85b3e4c5b"> <td align="left" valign="top" styleCode="Lrule Botrule Rrule"> Anemia </td> <td align="center" valign="top" styleCode="Botrule Rrule">2 </td> <td align="center" valign="top" styleCode="Botrule Rrule">0 </td> </tr> <tr ID="id_18193ecf-9d17-4bb8-8eb9-70a8511ccabf"> <td align="left" valign="top" styleCode="Lrule Rrule"> <content styleCode="bold">Resistance </content> <content styleCode="bold">mechanism</content> <content styleCode="bold"> </content> </td> <td align="center" valign="top" styleCode="Rrule"> </td> <td align="center" valign="top" styleCode="Rrule"> </td> </tr> <tr ID="id_e886bc84-25fd-4639-9453-fe843fedb511"> <td align="left" valign="top" styleCode="Lrule Botrule Rrule"> Upper respiratory tract infection </td> <td align="center" valign="top" styleCode="Botrule Rrule">9 </td> <td align="center" valign="top" styleCode="Botrule Rrule">8 </td> </tr> <tr ID="id_e267b81a-ed59-44b1-a2ff-997c1bf1cf1b"> <td align="left" valign="top" styleCode="Lrule Rrule"> <content styleCode="bold">Respiratory </content> <content styleCode="bold">system</content> <content styleCode="bold"> </content> </td> <td align="center" valign="top" styleCode="Rrule"> </td> <td align="center" valign="top" styleCode="Rrule"> </td> </tr> <tr ID="id_ce72e000-02ce-4f82-b29a-3b4f9a9435ef"> <td align="left" valign="top" styleCode="Lrule Botrule Rrule"> Dyspnea </td> <td align="center" valign="top" styleCode="Botrule Rrule">3 </td> <td align="center" valign="top" styleCode="Botrule Rrule">2 </td> </tr> <tr ID="id_4803f0ca-8630-40f4-8656-f014f30d2776"> <td align="left" valign="top" styleCode="Lrule Rrule"> <content styleCode="bold">Urinary </content> <content styleCode="bold">system</content> <content styleCode="bold"> </content> </td> <td align="center" valign="top" styleCode="Rrule"> </td> <td align="center" valign="top" styleCode="Rrule"> </td> </tr> <tr ID="id_df0075f6-92d5-4eb0-b4b5-466e92ad9192"> <td align="left" valign="top" styleCode="Lrule Rrule"> Pyuria </td> <td align="center" valign="top" styleCode="Rrule">2 </td> <td align="center" valign="top" styleCode="Rrule">1 </td> </tr> <tr ID="id_c14c3a93-2b54-4ad2-91e5-0b107873587c"> <td align="left" valign="top" styleCode="Lrule Rrule"> Urinary incontinence </td> <td align="center" valign="top" styleCode="Rrule">2 </td> <td align="center" valign="top" styleCode="Rrule">1 </td> </tr> <tr ID="id_d1e7e8b0-618d-4cab-a44f-12eddc7f9c63"> <td align="left" valign="top" styleCode="Lrule Botrule Rrule"> Urinary tract infection </td> <td align="center" valign="top" styleCode="Botrule Rrule">6 </td> <td align="center" valign="top" styleCode="Botrule Rrule">3 </td> </tr> <tr ID="id_65c233cf-be17-4dc4-accd-bf9d9d84e068"> <td align="left" valign="top" styleCode="Lrule Rrule"> <content styleCode="bold">Vision</content> <content styleCode="bold"> </content> </td> <td align="center" valign="top" styleCode="Rrule"> </td> <td align="center" valign="top" styleCode="Rrule"> </td> </tr> <tr ID="id_01c2fc06-f5b5-4ade-a6f9-1d62cc1e86f0"> <td align="left" valign="top" styleCode="Lrule Botrule Rrule"> Diplopia </td> <td align="center" valign="top" styleCode="Rrule">2 </td> <td align="center" valign="top" styleCode="Botrule Rrule">1 </td> </tr> </tbody> </table>

<table ID="id_6d2085c9-06ce-40c5-a555-be2f7643cfb0"> <caption ID="id_ba79f40a-6a87-4548-8df7-0ce66aa16b48">Table 4Treatment-Emergent Adverse Event Incidence in Double-Blind, Placebo-Controlled RLS Trials (Events &#x2265;2% of Patients Treated with Ropinirole Hydrochloride and Numerically More Frequent Than the Placebo Group)</caption> <col width="53%"/> <col width="24%"/> <col width="22%"/> <thead> <tr ID="id_884e2f19-d1a0-4ce2-ae93-1a40d5a8c511"> <td align="left" valign="top" styleCode="Lrule Botrule Rrule"> <content styleCode="bold"> </content> <content styleCode="bold">Adverse </content> <content styleCode="bold">Experience</content> <content styleCode="bold"> </content> </td> <td align="center" valign="top" styleCode="Rrule"> <content styleCode="bold">Ropinirole </content> <content styleCode="bold">Hydrochloride</content> <content styleCode="bold"> </content> <content styleCode="bold">(</content> <content styleCode="bold">n </content> <content styleCode="bold">= </content> <content styleCode="bold">496</content> <content styleCode="bold">)</content> <content styleCode="bold"> </content> <content styleCode="bold">(%)</content> <content styleCode="bold"> </content> </td> <td align="center" valign="top" styleCode="Botrule Rrule"> <content styleCode="bold">Placebo</content> <content styleCode="bold"> </content> <content styleCode="bold">(</content> <content styleCode="bold">n </content> <content styleCode="bold">=</content> <content styleCode="bold">500</content> <content styleCode="bold">)</content> <content styleCode="bold"> </content> <content styleCode="bold">(%)</content> <content styleCode="bold"> </content> </td> </tr> </thead> <tbody> <tr ID="id_4bd3d38f-ebe8-4c8b-bddf-02cb91b6b919"> <td align="left" valign="top" styleCode="Lrule Toprule Rrule"> <content styleCode="bold">Ear </content> <content styleCode="bold">and </content> <content styleCode="bold">labyrinth </content> <content styleCode="bold">disorders</content> <content styleCode="bold"> </content> </td> <td align="center" valign="top" styleCode="Rrule"> </td> <td align="center" valign="top" styleCode="Rrule"> </td> </tr> <tr ID="id_3d3dc5b9-397a-43ea-a7d5-91451d3f2346"> <td align="left" valign="top" styleCode="Lrule Botrule Rrule"> Vertigo </td> <td align="center" valign="top" styleCode="Botrule Rrule">2 </td> <td align="center" valign="top" styleCode="Botrule Rrule">1 </td> </tr> <tr ID="id_b881cbd3-083a-4663-a15d-7b378c8cd093"> <td align="left" valign="top" styleCode="Lrule Rrule"> <content styleCode="bold">Gastrointestinal </content> <content styleCode="bold">disorders</content> <content styleCode="bold"> </content> </td> <td align="center" valign="top" styleCode="Rrule"> </td> <td align="center" valign="top" styleCode="Rrule"> </td> </tr> <tr ID="id_c27f68d4-90f8-4e98-8542-8ea3df99a5f0"> <td align="left" valign="top" styleCode="Lrule Rrule"> Nausea </td> <td align="center" valign="top" styleCode="Rrule">40 </td> <td align="center" valign="top" styleCode="Rrule">8 </td> </tr> <tr ID="id_cbb67aad-d096-40ea-8ad2-177fa8bf17f4"> <td align="left" valign="top" styleCode="Lrule Rrule"> Vomiting </td> <td align="center" valign="top" styleCode="Rrule">11 </td> <td align="center" valign="top" styleCode="Rrule">2 </td> </tr> <tr ID="id_4db3325d-c48d-4d3d-adc2-1394609938d4"> <td align="left" valign="top" styleCode="Lrule Rrule"> Diarrhea </td> <td align="center" valign="top" styleCode="Rrule">5 </td> <td align="center" valign="top" styleCode="Rrule">3 </td> </tr> <tr ID="id_ce9f55be-3b8c-4459-8772-80d49e3a281b"> <td align="left" valign="top" styleCode="Lrule Rrule"> Dyspepsia </td> <td align="center" valign="top" styleCode="Rrule">4 </td> <td align="center" valign="top" styleCode="Rrule">3 </td> </tr> <tr ID="id_41092079-a3e8-49f7-930c-52b0836d91eb"> <td align="left" valign="top" styleCode="Lrule Rrule"> Dry mouth </td> <td align="center" valign="top" styleCode="Rrule">3 </td> <td align="center" valign="top" styleCode="Rrule">2 </td> </tr> <tr ID="id_6e9efb57-544b-40de-92ba-0bcc89fc6764"> <td align="left" valign="top" styleCode="Lrule Botrule Rrule"> Abdominal pain upper </td> <td align="center" valign="top" styleCode="Botrule Rrule">3 </td> <td align="center" valign="top" styleCode="Botrule Rrule">1 </td> </tr> <tr ID="id_355a4373-c7a2-403a-98f4-67aacd304cb0"> <td align="left" valign="top" styleCode="Lrule Rrule"> <content styleCode="bold">General </content> <content styleCode="bold">disorders </content> <content styleCode="bold">and </content> <content styleCode="bold">administration </content> <content styleCode="bold">site</content> <content styleCode="bold"> </content> </td> <td align="center" valign="top" styleCode="Rrule"> </td> <td align="center" valign="top" styleCode="Rrule"> </td> </tr> <tr ID="id_1ccdfe88-c5fb-4085-834b-be73d54a8fe3"> <td align="left" valign="top" styleCode="Lrule Rrule"> <content styleCode="bold">conditions</content> <content styleCode="bold"> </content> </td> <td align="center" valign="top" styleCode="Rrule"> </td> <td align="center" valign="top" styleCode="Rrule"> </td> </tr> <tr ID="id_400e0e81-6d56-4989-a2ab-6895630fcec6"> <td align="left" valign="top" styleCode="Lrule Rrule"> Fatigue </td> <td align="center" valign="top" styleCode="Rrule">8 </td> <td align="center" valign="top" styleCode="Rrule">4 </td> </tr> <tr ID="id_411657f1-4c98-41aa-be63-6e9758fb8007"> <td align="left" valign="top" styleCode="Lrule Botrule Rrule"> Edema peripheral </td> <td align="center" valign="top" styleCode="Botrule Rrule">2 </td> <td align="center" valign="top" styleCode="Botrule Rrule">1 </td> </tr> <tr ID="id_57653c60-a319-49f4-a57e-8dd5be0b1d3b"> <td align="left" valign="top" styleCode="Lrule Rrule"> <content styleCode="bold">Infections </content> <content styleCode="bold">and </content> <content styleCode="bold">infestations</content> <content styleCode="bold"> </content> </td> <td align="center" valign="top" styleCode="Rrule"> </td> <td align="center" valign="top" styleCode="Rrule"> </td> </tr> <tr ID="id_403732a1-9caf-4fbd-b484-8d1f8bbe4383"> <td align="left" valign="top" styleCode="Lrule Rrule"> Nasopharyngitis </td> <td align="center" valign="top" styleCode="Rrule">9 </td> <td align="center" valign="top" styleCode="Rrule">8 </td> </tr> <tr ID="id_37b2604c-5bf3-4b4e-9dff-9de5bae8d068"> <td align="left" valign="top" styleCode="Lrule Botrule Rrule"> Influenza </td> <td align="center" valign="top" styleCode="Botrule Rrule">3 </td> <td align="center" valign="top" styleCode="Botrule Rrule">2 </td> </tr> <tr ID="id_8f5af059-753d-4a74-80aa-5431ca8ca219"> <td align="left" valign="top" styleCode="Lrule Rrule"> <content styleCode="bold">Musculoskeletal </content> <content styleCode="bold">and </content> <content styleCode="bold">connective </content> <content styleCode="bold">tissue</content> <content styleCode="bold"> </content> </td> <td align="center" valign="top" styleCode="Rrule"> </td> <td align="center" valign="top" styleCode="Rrule"> </td> </tr> <tr ID="id_da43712a-bd57-4262-9411-61f7ea5affa5"> <td align="left" valign="top" styleCode="Lrule Rrule"> <content styleCode="bold">disorders</content> <content styleCode="bold"> </content> </td> <td align="center" valign="top" styleCode="Rrule"> </td> <td align="center" valign="top" styleCode="Rrule"> </td> </tr> <tr ID="id_6906f549-63ab-4fda-ae81-8350d5a1f240"> <td align="left" valign="top" styleCode="Lrule Rrule"> Arthralgia </td> <td align="center" valign="top" styleCode="Rrule">4 </td> <td align="center" valign="top" styleCode="Rrule">3 </td> </tr> <tr ID="id_98960fdf-ea7f-4079-8848-9247aea2e77e"> <td align="left" valign="top" styleCode="Lrule Rrule"> Muscle cramps </td> <td align="center" valign="top" styleCode="Rrule">3 </td> <td align="center" valign="top" styleCode="Rrule">2 </td> </tr> <tr ID="id_ae9827eb-68a9-4713-985f-ad61bc8fa371"> <td align="left" valign="top" styleCode="Lrule Botrule Rrule"> Pain in extremity </td> <td align="center" valign="top" styleCode="Botrule Rrule">3 </td> <td align="center" valign="top" styleCode="Botrule Rrule">2 </td> </tr> <tr ID="id_0f802a34-1b3e-47a6-bbf0-41f31e754a9c"> <td align="left" valign="top" styleCode="Lrule Rrule"> <content styleCode="bold">Nervous </content> <content styleCode="bold">system </content> <content styleCode="bold">disorders</content> <content styleCode="bold"> </content> </td> <td align="center" valign="top" styleCode="Rrule"> </td> <td align="center" valign="top" styleCode="Rrule"> </td> </tr> <tr ID="id_28ab8c29-a31d-4a8c-8bb7-ba9d9f881e92"> <td align="left" valign="top" styleCode="Lrule Rrule"> Somnolence </td> <td align="center" valign="top" styleCode="Rrule">12 </td> <td align="center" valign="top" styleCode="Rrule">6 </td> </tr> <tr ID="id_b0beafa9-f105-401e-9105-dc54145a9b0a"> <td align="left" valign="top" styleCode="Lrule Rrule"> Dizziness </td> <td align="center" valign="top" styleCode="Rrule">11 </td> <td align="center" valign="top" styleCode="Rrule">5 </td> </tr> <tr ID="id_f64558d3-780f-452a-b132-5ff2909a628c"> <td align="left" valign="top" styleCode="Lrule Botrule Rrule"> Paresthesia </td> <td align="center" valign="top" styleCode="Botrule Rrule">3 </td> <td align="center" valign="top" styleCode="Botrule Rrule">1 </td> </tr> <tr ID="id_98b11245-8110-4efc-867b-41e82d2b94ec"> <td align="left" valign="top" styleCode="Lrule Rrule"> <content styleCode="bold">Respiratory</content> <content styleCode="bold">, </content> <content styleCode="bold">thoracic</content> <content styleCode="bold">, </content> <content styleCode="bold">and </content> <content styleCode="bold">mediastinal</content> <content styleCode="bold"> </content> </td> <td align="center" valign="top" styleCode="Rrule"> </td> <td align="center" valign="top" styleCode="Rrule"> </td> </tr> <tr ID="id_f0ba494c-9384-4822-8497-51c72f5f6c3d"> <td align="left" valign="top" styleCode="Lrule Rrule"> <content styleCode="bold">disorders</content> <content styleCode="bold"> </content> </td> <td align="center" valign="top" styleCode="Rrule"> </td> <td align="center" valign="top" styleCode="Rrule"> </td> </tr> <tr ID="id_525f0922-2178-455f-a73d-e517149e725f"> <td align="left" valign="top" styleCode="Lrule Rrule"> Cough </td> <td align="center" valign="top" styleCode="Rrule">3 </td> <td align="center" valign="top" styleCode="Rrule">2 </td> </tr> <tr ID="id_a1461a59-9abc-4823-8d5a-74f10a04c984"> <td align="left" valign="top" styleCode="Lrule Botrule Rrule"> Nasal congestion </td> <td align="center" valign="top" styleCode="Botrule Rrule">2 </td> <td align="center" valign="top" styleCode="Botrule Rrule">1 </td> </tr> <tr ID="id_068b9cdd-9e96-4ef2-83c3-c27a694a0da8"> <td align="left" valign="top" styleCode="Lrule Rrule"> <content styleCode="bold">Skin </content> <content styleCode="bold">and </content> <content styleCode="bold">subcutaneous </content> <content styleCode="bold">tissue </content> <content styleCode="bold">disorders</content> <content styleCode="bold"> </content> </td> <td align="center" valign="top" styleCode="Rrule"> </td> <td align="center" valign="top" styleCode="Rrule"> </td> </tr> <tr ID="id_25dd7861-7d6a-49fc-9334-26de266bcc2c"> <td align="left" valign="top" styleCode="Lrule Botrule Rrule"> Hyperhidrosis </td> <td align="center" valign="top" styleCode="Rrule">3 </td> <td align="center" valign="top" styleCode="Botrule Rrule">1 </td> </tr> </tbody> </table>