FDA label b5504316-3907-444c-b604-ec9a18cdcd6d

WARNINGS Falling Asleep During Activities of Daily Living Patients treated with Mirapex® (pramipexole dihydrochloride) tablets 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 MIRAPEX tablets, 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 had been reported as late as one year after the initiation of treatment. Somnolence is a common occurrence in patients receiving MIRAPEX tablets at doses above 1.5 mg/day (0.5 mg TID) for Parkinson’s disease. In controlled clinical trials in RLS, patients treated with MIRAPEX tablets at doses of 0.25-0.75 mg once a day, the incidence of somnolence was 6% compared to an incidence of 3% for placebo-treated patients (see ADVERSE EVENTS, Table 5 ). Many clinical experts believe that falling asleep while engaged in activities of daily living always occurs in a setting of pre-existing 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 MIRAPEX tablets, patients should be advised of the potential to develop drowsiness and specifically asked about factors that may increase the risk with MIRAPEX tablets such as concomitant sedating medications, the presence of sleep disorders, and concomitant medications that increase pramipexole plasma levels (e.g., cimetidine - 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.), MIRAPEX tablets should ordinarily be discontinued. If a decision is made to continue MIRAPEX tablets, patients should be advised to not drive and to avoid other potentially dangerous activities. While dose reduction clearly reduces the degree of somnolence, there is insufficient information to establish that dose reduction will eliminate episodes of falling asleep while engaged in activities of daily living. Symptomatic Hypotension Dopamine agonists, in clinical studies and clinical experience, appear to impair the systemic regulation of blood pressure, with resulting orthostatic hypotension, especially during dose escalation. Parkinson's disease patients, in addition, appear to have an impaired capacity to respond to an orthostatic challenge. For these reasons, both Parkinson's disease patients and RLS patients being treated with dopaminergic agonists ordinarily require careful monitoring for signs and symptoms of orthostatic hypotension, especially during dose escalation, and should be informed of this risk (see PRECAUTIONS, Information for Patients ). In clinical trials of pramipexole, however, and despite clear orthostatic effects in normal volunteers, the reported incidence of clinically significant orthostatic hypotension was not greater among those assigned to Mirapex® (pramipexole dihydrochloride) tablets than among those assigned to placebo. This result, especially with the higher doses used in Parkinson’s disease, is clearly unexpected in light of the previous experience with the risks of dopamine agonist therapy. While this finding could reflect a unique property of pramipexole, it might also be explained by the conditions of the study and the nature of the population enrolled in the clinical trials. Patients were very carefully titrated, and patients with active cardiovascular disease or significant orthostatic hypotension at baseline were excluded. Also, clinical trials in patients with RLS did not incorporate orthostatic challenges with intensive blood pressure monitoring done in close temporal proximity to dosing. Hallucinations In the three double-blind, placebo-controlled trials in early Parkinson's disease, hallucinations were observed in 9% (35 of 388) of patients receiving MIRAPEX tablets, compared with 2.6% (6 of 235) of patients receiving placebo. In the four double-blind, placebo-controlled trials in advanced Parkinson's disease, where patients received MIRAPEX tablets and concomitant levodopa, hallucinations were observed in 16.5% (43 of 260) of patients receiving MIRAPEX tablets compared with 3.8% (10 of 264) of patients receiving placebo. Hallucinations were of sufficient severity to cause discontinuation of treatment in 3.1% of the early Parkinson's disease patients and 2.7% of the advanced Parkinson's disease patients compared with about 0.4% of placebo patients in both populations. Age appears to increase the risk of hallucinations attributable to pramipexole. In the early Parkinson's disease patients, the risk of hallucinations was 1.9 times greater than placebo in patients younger than 65 years and 6.8 times greater than placebo in patients older than 65 years. In the advanced Parkinson's disease patients, the risk of hallucinations was 3.5 times greater than placebo in patients younger than 65 years and 5.2 times greater than placebo in patients older than 65 years. In the RLS clinical program, one pramipexole-treated patient (of 889) reported hallucinations; this patient discontinued treatment and the symptoms resolved.

ADVERSE EVENTS Parkinson's Disease During the premarketing development of pramipexole, patients with either early or advanced Parkinson's disease were enrolled in clinical trials. Apart from the severity and duration of their disease, the two populations differed in their use of concomitant levodopa therapy. Patients with early disease did not receive concomitant levodopa therapy during treatment with pramipexole; those with advanced Parkinson's disease all received concomitant levodopa treatment. Because these two populations may have differential risks for various adverse events, this section will, in general, present adverse-event data for these two populations separately. Because the controlled trials performed during premarketing development all used a titration design, with a resultant confounding of time and dose, it was impossible to adequately evaluate the effects of dose on the incidence of adverse events. Early Parkinson's Disease In the three double-blind, placebo-controlled trials of patients with early Parkinson's disease, the most commonly observed adverse events (>5%) that were numerically more frequent in the group treated with MIRAPEX tablets were nausea, dizziness, somnolence, insomnia, constipation, asthenia, and hallucinations. Approximately 12% of 388 patients with early Parkinson's disease and treated with MIRAPEX tablets who participated in the double-blind, placebo-controlled trials discontinued treatment due to adverse events compared with 11% of 235 patients who received placebo. The adverse events most commonly causing discontinuation of treatment were related to the nervous system (hallucinations [3.1% on MIRAPEX tablets vs 0.4% on placebo]; dizziness [2.1% on MIRAPEX tablets vs 1% on placebo]; somnolence [1.6% on MIRAPEX tablets vs 0% on placebo]; extrapyramidal syndrome [1.6% on MIRAPEX tablets vs 6.4% on placebo]; headache and confusion [1.3% and 1.0%, respectively, on Mirapex® (pramipexole dihydrochloride) tablets vs 0% on placebo]); and gastrointestinal system (nausea [2.1% on MIRAPEX tablets vs 0.4% on placebo]). Adverse-event Incidence in Controlled Clinical Studies in Early Parkinson's Disease Table 3 lists treatment-emergent adverse events that occurred in the double-blind, placebo-controlled studies in early Parkinson's disease that were reported by ≥1% of patients treated with MIRAPEX tablets and were numerically more frequent than in the placebo group. In these studies, patients did not receive concomitant levodopa. 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 nondrug factors to the adverse-event incidence rate in the population studied. Table 3 Treatment-Emergent Adverse-Event* Incidence in Double-Blind, Placebo-Controlled Trials in Early Parkinson's Disease (Events ≥1% of Patients Treated with MIRAPEX tablets and Numerically More Frequent than in the Placebo Group) Body System/ Adverse Event MIRAPEX N=388 Placebo N=235 *Patients may have reported multiple adverse experiences during the study or at discontinuation; thus, patients may be included in more than one category. Body as a Whole Asthenia 14 12 General edema 5 3 Malaise 2 1 Reaction unevaluable 2 1 Fever 1 0 Digestive System Nausea 28 18 Constipation 14 6 Anorexia 4 2 Dysphagia 2 0 Metabolic & Nutritional System Peripheral edema 5 4 Decreased weight 2 0 Nervous System Dizziness 25 24 Somnolence 22 9 Insomnia 17 12 Hallucinations 9 3 Confusion 4 1 Amnesia 4 2 Hypesthesia 3 1 Dystonia 2 1 Akathisia 2 0 Thinking abnormalities 2 0 Decreased libido 1 0 Myoclonus 1 0 Special Senses Vision abnormalities 3 0 Urogenital System Impotence 2 1 Other events reported by 1% or more of patients with early Parkinson's disease and treated with Mirapex® (pramipexole dihydrochloride) tablets but reported equally or more frequently in the placebo group were infection, accidental injury, headache, pain, tremor, back pain, syncope, postural hypotension, hypertonia, depression, abdominal pain, anxiety, dyspepsia, flatulence, diarrhea, rash, ataxia, dry mouth, extrapyramidal syndrome, leg cramps, twitching, pharyngitis, sinusitis, sweating, rhinitis, urinary tract infection, vasodilation, flu syndrome, increased saliva, tooth disease, dyspnea, increased cough, gait abnormalities, urinary frequency, vomiting, allergic reaction, hypertension, pruritis, hypokinesia, increased creatine PK, nervousness, dream abnormalities, chest pain, neck pain, paresthesia, tachycardia, vertigo, voice alteration, conjunctivitis, paralysis, accommodation abnormalities, tinnitus, diplopia, and taste perversions. In a fixed-dose study in early Parkinson's disease, occurrence of the following events increased in frequency as the dose increased over the range from 1.5 mg/day to 6 mg/day: postural hypotension, nausea, constipation, somnolence, and amnesia. The frequency of these events was generally 2-fold greater than placebo for pramipexole doses greater than 3 mg/day. The incidence of somnolence with pramipexole at a dose of 1.5 mg/day was comparable to that reported for placebo. Advanced Parkinson's Disease In the four double-blind, placebo-controlled trials of patients with advanced Parkinson's disease, the most commonly observed adverse events (>5%) that were numerically more frequent in the group treated with MIRAPEX tablets and concomitant levodopa were postural (orthostatic) hypotension, dyskinesia, extrapyramidal syndrome, insomnia, dizziness, hallucinations, accidental injury, dream abnormalities, confusion, constipation, asthenia, somnolence, dystonia, gait abnormality, hypertonia, dry mouth, amnesia, and urinary frequency. Approximately 12% of 260 patients with advanced Parkinson's disease who received Mirapex® (pramipexole dihydrochloride) tablets and concomitant levodopa in the double-blind, placebo-controlled trials discontinued treatment due to adverse events compared with 16% of 264 patients who received placebo and concomitant levodopa. The events most commonly causing discontinuation of treatment were related to the nervous system (hallucinations [2.7% on MIRAPEX tablets vs 0.4% on placebo]; dyskinesia [1.9% on MIRAPEX tablets vs 0.8% on placebo]; extrapyramidal syndrome [1.5% on MIRAPEX tablets vs 4.9% on placebo]; dizziness [1.2% on MIRAPEX tablets vs 1.5% on placebo]; confusion [1.2% on MIRAPEX tablets vs 2.3% on placebo]); and cardiovascular system (postural [orthostatic] hypotension [2.3% on MIRAPEX tablets vs 1.1% on placebo]). Adverse-event Incidence in Controlled Clinical Studies in Advanced Parkinson's Disease Table 4 lists treatment-emergent adverse events that occurred in the double-blind, placebo-controlled studies in advanced Parkinson's disease that were reported by ≥1% of patients treated with MIRAPEX tablets and were numerically more frequent than in the placebo group. In these studies, MIRAPEX tablets or placebo was administered to patients who were also receiving concomitant levodopa. 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 nondrug factors to the adverse-events incidence rate in the population studied. Table 4 Treatment-Emergent Adverse-Event* Incidence in Double-Blind, Placebo-Controlled Trials in Advanced Parkinson's Disease (Events ≥1% of Patients Treated with MIRAPEX tablets and Numerically More Frequent than in the Placebo Group) Body System/ Adverse Event MIRAPEX † (pramipexole dihydrochloride) N=260 Placebo † N=264 * Patients may have reported multiple adverse experiences during the study or at discontinuation; thus, patients may be included in more than one category. † Patients received concomitant levodopa. Body as a Whole Accidental injury 17 15 Asthenia 10 8 General edema 4 3 Chest pain 3 2 Malaise 3 2 Cardiovascular System Postural hypotension 53 48 Digestive System Constipation 10 9 Dry mouth 7 3 Metabolic & Nutritional System Peripheral edema 2 1 Increased creatine PK 1 0 Musculoskeletal System Arthritis 3 1 Twitching 2 0 Bursitis 2 0 Myasthenia 1 0 Nervous System Dyskinesia 47 31 Extrapyramidal syndrome 28 26 Insomnia 27 22 Dizziness 26 25 Hallucinations 17 4 Dream abnormalities 11 10 Confusion 10 7 Somnolence 9 6 Dystonia 8 7 Gait abnormalities 7 5 Hypertonia 7 6 Amnesia 6 4 Akathisia 3 2 Thinking abnormalities 3 2 Paranoid reaction 2 0 Delusions 1 0 Sleep disorders 1 0 Respiratory System Dyspnea 4 3 Rhinitis 3 1 Pneumonia 2 0 Skin & Appendages Skin disorders 2 1 Special Senses Accommodation abnormalities 4 2 Vision abnormalities 3 1 Diplopia 1 0 Urogenital System Urinary frequency 6 3 Urinary tract infection 4 3 Urinary incontinence 2 1 Other events reported by 1% or more of patients with advanced Parkinson's disease and treated with Mirapex® (pramipexole dihydrochloride) tablets but reported equally or more frequently in the placebo group were nausea, pain, infection, headache, depression, tremor, hypokinesia, anorexia, back pain, dyspepsia, flatulence, ataxia, flu syndrome, sinusitis, diarrhea, myalgia, abdominal pain, anxiety, rash, paresthesia, hypertension, increased saliva, tooth disorder, apathy, hypotension, sweating, vasodilation, vomiting, increased cough, nervousness, pruritus, hypesthesia, neck pain, syncope, arthralgia, dysphagia, palpitations, pharyngitis, vertigo, leg cramps, conjunctivitis, and lacrimation disorders. Restless Legs Syndrome MIRAPEX tablets for treatment of RLS have been evaluated for safety in 889 patients, including 427 treated for over six months and 75 for over one year. The overall safety assessment focuses on the results of three double-blind, placebo-controlled trials, in which 575 patients with RLS were treated with MIRAPEX tablets for up to 12 weeks. The most commonly observed adverse events with MIRAPEX tablets in the treatment of RLS (observed in > 5% of pramipexole-treated patients and at a rate at least twice that observed in placebo-treated patients) were nausea and somnolence. Occurrences of nausea and somnolence in clinical trials were generally mild and transient. Approximately 7% of 575 patients treated with MIRAPEX tablets during the double-blind periods of three placebo-controlled trials discontinued treatment due to adverse events compared to 5% of 223 patients who received placebo. The adverse event most commonly causing discontinuation of treatment was nausea (1%). Table 5 lists treatment-emergent events that occurred in three double-blind, placebo-controlled studies in RLS patients that were reported by ≥ 2% of patients treated with MIRAPEX tablets and were numerically more frequent than in the placebo group. 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 nondrug factors to the adverse-event incidence rate in the population studied. Table 5 Treatment-Emergent Adverse-Event* Incidence in Double-Blind, Placebo-Controlled Trials in Restless Legs Syndrome (Events ≥ 2% of Patients Treated with MIRAPEX tablets and Numerically More Frequent than in the Placebo Group) Body System/ Adverse Event MIRAPEX 0.125 – 0.75 mg/day (N=575) % Placebo (N=223) % *Patients may have reported multiple adverse experiences during the study or at discontinuation; thus, patients may be included in more than one category. Gastrointestinal disorders Nausea 16 5 Constipation 4 1 Diarrhea 3 1 Dry mouth 3 1 General disorders and administration site conditions Fatigue 9 7 Infections and infestations Influenza 3 1 Nervous system disorders Headache 16 15 Somnolence 6 3 Other events reported by 2% or more of RLS patients treated with Mirapex® (pramipexole dihydrochloride) tablets but equally or more frequently in the placebo group, were: vomiting, nasopharyngitis, back pain, pain in extremity, dizziness, and insomnia. Table 6 summarizes data for adverse events that appeared to be dose related in the 12-week fixed dose study. Table 6 Dose Related Adverse Events in a 12-Week Double-Blind, Placebo-Controlled Fixed Dose Study in Restless Legs Syndrome (Occurring in ≥5% of all Patients in the Treatment Phase) Body System/ Adverse Event MIRAPEX 0.25 mg (N=88) % MIRAPEX 0.5 mg (N=80) % MIRAPEX 0.75 mg (N=90) % Placebo (n=86) % Gastrointestinal disorders Nausea 11 19 27 5 Diarrhea 3 1 7 0 Dyspepsia 3 1 4 7 Infections and infestations Influenza 1 4 7 1 General disorders and administration site conditions Fatigue 3 5 7 5 Psychiatric disorders Insomnia 9 9 13 9 Abnormal dreams 2 1 8 2 Respiratory, thoracic and mediastinal disorders Nasal congestion 0 3 6 1 Musculoskeletal and connective tissue disorders Pain in extremity 3 3 7 1 General Adverse Events; Relationship to Age, Gender, and Race Among the treatment-emergent adverse events in patients treated with MIRAPEX tablets, hallucination appeared to exhibit a positive relationship to age in patients with Parkinson’s disease. Although no gender-related differences were observed in Parkinson’s disease patients, nausea and fatigue, both generally transient, were more frequently reported by female than male RLS patients. Less than 4% of patients enrolled were non-Caucasian, therefore, an evaluation of adverse events related to race is not possible. Other Adverse Events Observed During Phase 2 and 3 Clinical Trials MIRAPEX tablets have been administered to 1620 Parkinson’s disease patients and to 889 RLS patients in Phase 2 and 3 clinical trials. During these trials, all adverse events were recorded by the clinical investigators using terminology of their own choosing; 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. Adverse events which are not listed above but occurred on at least two occasions (one occasion if the event was serious) in the 2509 individuals exposed to MIRAPEX tablets are listed below. The reported events below are included without regard to determination of a causal relationship to MIRAPEX tablets. Blood and lymphatic system disorders: anemia, iron deficiency anemia, leukocytosis, leukopenia, lymphadenitis, lymphadenopathy, thrombocythaemia, thrombocytopenia Cardiac disorders: angina pectoris, arrhythmia supraventricular, atrial fibrillation, atrioventricular block first degree, atrioventricular block second degree, bradycardia, bundle branch block, cardiac arrest, cardiac failure, cardiac failure congestive, cardiomegaly, coronary artery occlusion, cyanosis, extrasystoles, left ventricular failure, myocardial infarction, nodal arrhythmia, sinus arrhythmia, sinus bradycardia, sinus tachycardia, supraventricular extrasystoles, supraventricular tachycardia, tachycardia, ventricular fibrillation, ventricular extrasystoles, ventricular hypertrophy Congenital, familial and genetic disorders: atrial septal defect, congenital foot malformation, spine malformation Ear and labyrinth disorders: deafness, ear pain, hearing impaired, hypoacusis, motion sickness, vestibular ataxia Endocrine disorders: goiter, hyperthyroidism, hypothyroidism Eye disorders: amaurosis fugax, blepharitis, blepharospasm, cataract, dacryostenosis acquired, dry eye, eye hemorrhage, eye irritation, eye pain, eyelid edema, eyelid ptosis, glaucoma, keratitis, macular degeneration, myopia, photophobia, retinal detachment, retinal vascular disorder, scotoma, vision blurred, visual acuity reduced, vitreous floaters Gastrointestinal disorders: abdominal discomfort, abdominal distension, aphthous stomatitis, ascites, cheilitis, colitis, colitis ulcerative, duodenal ulcer, duodenal ulcer hemorrhage, enteritis, eructation, fecal incontinence, gastric ulcer, gastric ulcer hemorrhage, gastritis, gastrointestinal hemorrhage, gastroesophageal reflux disease, gingivitis, haematemesis, haematochezia, hemorrhoids, hiatus hernia, hyperchlorhydria, ileus, inguinal hernia, intestinal obstruction, irritable bowel syndrome, esophageal spasm, esophageal stenosis, esophagitis, pancreatitis, periodontitis, rectal hemorrhage, reflux esophagitis, tongue edema, tongue ulceration, toothache, umbilical hernia General disorders: chest discomfort, chills, death, drug withdrawal syndrome, face edema, feeling cold, feeling hot, feeling jittery, gait disturbance, impaired healing, influenza-like illness, irritability, localized edema, edema, pitting edema, thirst Hepatobiliary disorders: biliary colic, cholecystitis, cholecystitis chronic, cholelithiasis Immune system disorders: drug hypersensitivity Infections and infestations: abscess, acute tonsillitis, appendicitis, bronchiolitis, bronchitis, bronchopneumonia, cellulitis, cystitis, dental caries, diverticulitis, ear infection, eye infection, folliculitis, fungal infection, furuncle, gangrene, gastroenteritis, gingival infection, herpes simplex, herpes zoster, hordeolum, intervertebral discitis, laryngitis, lobar pneumonia, nail infection, onychomycosis, oral candidiasis, orchitis, osteomyelitis, otitis externa, otitis media, paronychia, pyelonephritis, pyoderma, sepsis, skin infection, tonsillitis, tooth abscess, tooth infection, upper respiratory tract infection, urethritis, vaginal candidiasis, vaginal infection, viral infection, wound infection Injury, poisoning and procedural complications: accidental falls, drug toxicity epicondylitis, road traffic accident, sunburn, tendon rupture Metabolism and nutrition disorders: cachexia, decreased appetite, dehydration, diabetes mellitus, fluid retention, gout, hypercholesterolemia, hyperglycemia, hyperlipidemia, hyperuricemia, hypocalcemia, hypoglycemia, hypokalemia, hyponatremia, hypovitaminosis, increased appetite, metabolic alkalosis Musculoskeletal and connective tissue disorders: bone pain, fasciitis, flank pain, intervertebral disc disorder, intervertebral disc protrusion, joint effusion, joint stiffness, joint swelling, monarthritis, muscle rigidity, muscle spasms, musculoskeletal stiffness, myopathy, myositis, nuchal rigidity, osteoarthritis, osteonecrosis, osteoporosis, polymyalgia, rheumatoid arthritis, shoulder pain, spinal osteoarthritis, tendonitis, tenosynovitis Neoplasms benign, malignant and unspecified: abdominal neoplasm, adenocarcinoma, adenoma benign, basal cell carcinoma, bladder cancer, breast cancer, breast neoplasm, chronic lymphocytic leukemia, colon cancer, colorectal cancer, endometrial cancer, gallbladder cancer, gastric cancer, gastrointestinal neoplasm, hemangioma, hepatic neoplasm, hepatic neoplasm malignant, lip and/or oral cavity cancer, lung neoplasm malignant, lung cancer metastatic, lymphoma, malignant melanoma, melanocytic naevus, metastases to lung, multiple myeloma, oral neoplasm benign, neoplasm, neoplasm malignant, neoplasm prostate, neoplasm skin, neuroma, ovarian cancer, prostate cancer, prostatic adenoma, pseudo lymphoma, renal neoplasm, skin cancer, skin papilloma, squamous cell carcinoma, thyroid neoplasm, uterine leiomyoma Nervous system disorders: ageusia, akinesia, anticholinergic syndrome, aphasia, balance disorder, brain edema, carotid artery occlusion, carpal tunnel syndrome, cerebral artery embolism, cerebral hemorrhage, cerebral infarction, cerebral ischemia, chorea, cognitive disorder, coma, convulsion, coordination abnormal, dementia, depressed level of consciousness, disturbance in attention, dizziness postural, dysarthria, dysgraphia, facial palsy, grand mal convulsion, hemiplegia, hyperaesthesia, hyperkinesia, hyperreflexia, hyporeflexia, hypotonia, lethargy, loss of consciousness, memory impairment, migraine, muscle contractions involuntary, narcolepsy, neuralgia, neuropathy, nystagmus, parosmia, psychomotor hyperactivity, sciatica, sedation, sensory disturbance, sleep phase rhythm disturbance, sleep talking, stupor, syncope vasovagal, tension headache Psychiatric disorders: affect lability, aggression, agitation, bradyphrenia, bruxism, suicide, delirium, delusional disorder persecutory type, disorientation, dissociation, emotional distress, euphoric mood, hallucination auditory, hallucination visual, initial insomnia, libido increased, mania, middle insomnia, mood altered, nightmare, obsessive thoughts, obsessive-compulsive disorder, panic reaction, parasomnia, personality disorder, psychotic disorder, restlessness, sleep walking, suicidal ideation Renal and urinary disorders: chromaturia, dysuria, glycosuria, hematuria, urgency, nephrolithiasis, neurogenic bladder, nocturia, oliguria, pollakiuria, proteinuria, renal artery stenosis, renal colic, renal cyst, renal failure, renal impairment, urinary retention Reproductive system and breast disorders: amenorrhea, breast pain, dysmenorrhea, epididymitis, gynaecomastia, menopausal symptoms, menorrhagia, metrorrhagia, ovarian cyst, priapism, prostatitis, sexual dysfunction, uterine hemorrhage, vaginal discharge, vaginal hemorrhage Respiratory, thoracic and mediastinal disorders: apnea, aspiration, asthma, choking, chronic obstructive pulmonary disease, dry throat, dysphonia, dyspnea exertional, epistaxis, haemoptysis, hiccups, hyperventilation, increased bronchial secretion, laryngospasm, nasal dryness, nasal polyps, obstructive airways disorder, pharyngolaryngeal pain, pleurisy, pneumonia aspiration, pneumothorax, postnasal drip, productive cough, pulmonary embolism, pulmonary edema, respiratory alkalosis, respiratory distress, respiratory failure, respiratory tract congestion, rhinitis allergic, rhinorrhea, sinus congestion, sleep apnoea syndrome, sneezing, snoring, tachypnea, wheezing Skin and subcutaneous tissue disorders: acne, alopecia, cold sweat, dermal cyst, dermatitis, dermatitis bullous, dermatitis contact, dry skin, ecchymosis, eczema, erythema, hyperkeratosis, livedo reticularis, night sweats, periorbital edema, petechiae, photosensitivity allergic reaction, psoriasis, purpura, rash erythematous, rash maculo-papular, rash papular, rosacea, seborrhea, seborrheic dermatitis, skin burning sensation, skin discoloration, skin exfoliation, skin hyperpigmentation, skin hypertrophy, skin irritation, skin nodule, skin odor abnormal, skin ulcer, urticaria Vascular disorders: aneurysm, angiopathy, arteriosclerosis, circulatory collapse, deep vein thrombosis, embolism, hematoma, hot flush, hypertensive crisis, lymphoedema, pallor, phlebitis, Raynaud’s phenomenon, shock, thrombophlebitis, thrombosis, varicose vein Falling Asleep During Activities of Daily Living Patients treated with Mirapex® (pramipexole dihydrochloride) tablets 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 ). Post-Marketing Experience In addition to the adverse events reported during clinical trials, the following adverse reactions have been identified during post-approval use of MIRAPEX tablets, primarily in Parkinson’s disease patients. 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. Decisions to include these reactions in labeling are typically based on one or more of the following factors: (1) seriousness of the reaction, (2) frequency of reporting, or (3) strength of causal connection to pramipexole tablets. Similar types of events were grouped into a smaller number of standardized categories using the MedDRA dictionary: abnormal behavior, abnormal dreams, accidents (including fall), blackouts, compulsive shopping, fatigue, hallucinations (all kinds), headache, hypotension (including postural hypotension), increased eating (including binge eating, compulsive eating, and hyperphagia), libido disorders (including increased and decreased libido, and hypersexuality), pathological gambling, pruritus, syncope, vomiting, and weight increase.

<table width="0.000" ID="id_46ffd851-4b6d-4cd6-ba6e-4497b072eeb8"> <caption ID="id_2230206c-6a43-4929-ac36-1c00ca7a5e90">Table 3 Treatment-Emergent Adverse-Event* Incidence in Double-Blind, Placebo-Controlled Trials in Early Parkinson&apos;s Disease (Events &#x2265;1% of Patients Treated with MIRAPEX tablets and Numerically More Frequent than in the Placebo Group)</caption> <col/> <col/> <col/> <thead> <tr ID="id_869375eb-e99c-45fe-bbc6-138736b9e3c9" styleCode="Botrule"> <td align="left" valign="top" styleCode="Rrule">Body System/ Adverse Event</td> <td align="left" valign="top" styleCode="Rrule">MIRAPEX N=388 </td> <td align="left" valign="top">Placebo N=235 </td> </tr> </thead> <tfoot ID="id_9cc32a80-2639-4385-9d7a-7d661f5de178"> <tr> <td align="left" valign="top" colspan="3">*Patients may have reported multiple adverse experiences during the study or at discontinuation; thus, patients may be included in more than one category. </td> </tr> </tfoot> <tbody> <tr ID="id_41b97c21-ffcf-4266-8a1a-3d1519a4e475" styleCode="Toprule"> <td align="left" valign="top"> <content styleCode="bold"> <content styleCode="emphasis">Body as a Whole</content> </content> </td> <td align="left" valign="top" styleCode="Toprule"> </td> <td align="left" valign="top"> </td> </tr> <tr ID="id_8e5ee1d5-5a04-4dc1-b5b6-a27ab8272390"> <td align="left" valign="top"> Asthenia</td> <td align="left" valign="top">14</td> <td align="left" valign="top">12</td> </tr> <tr ID="id_8a4f5dde-c332-45c8-ba5e-f57859c09c95"> <td align="left" valign="top"> General edema</td> <td align="left" valign="top">5</td> <td align="left" valign="top">3</td> </tr> <tr ID="id_3818034f-7474-483a-ad0b-914305a99dae"> <td align="left" valign="top"> Malaise</td> <td align="left" valign="top">2</td> <td align="left" valign="top">1</td> </tr> <tr ID="id_da529f08-b7a9-43eb-8713-85b8dc0e0087"> <td align="left" valign="top"> Reaction unevaluable</td> <td align="left" valign="top">2</td> <td align="left" valign="top">1</td> </tr> <tr ID="id_c79ae72f-114c-47b9-acb5-54b61d5ef82e"> <td align="left" valign="top"> Fever</td> <td align="left" valign="top">1</td> <td align="left" valign="top">0</td> </tr> <tr ID="id_0df59af6-b280-4767-86ca-5eff38ea35be"> <td align="left" valign="top"> <content styleCode="bold"> <content styleCode="emphasis">Digestive System</content> </content> </td> <td align="left" valign="top"> </td> <td align="left" valign="top"> </td> </tr> <tr ID="id_3c04b1b5-e5d1-4cb9-a413-ef3c5a966bbc"> <td align="left" valign="top"> Nausea</td> <td align="left" valign="top">28</td> <td align="left" valign="top">18</td> </tr> <tr ID="id_5898c8b7-94e5-4a0a-bff3-d251a8fd2bac"> <td align="left" valign="top"> Constipation</td> <td align="left" valign="top">14</td> <td align="left" valign="top">6</td> </tr> <tr ID="id_e181c79c-f6b6-4c48-af48-e5c2f10057e1"> <td align="left" valign="top"> Anorexia</td> <td align="left" valign="top">4</td> <td align="left" valign="top">2</td> </tr> <tr ID="id_f323cc0b-0779-40a6-a26a-72e2a2239a57"> <td align="left" valign="top"> Dysphagia</td> <td align="left" valign="top">2</td> <td align="left" valign="top">0</td> </tr> <tr ID="id_336c8c1d-a641-41dc-be28-30889515dcad"> <td align="left" valign="top"> <content styleCode="bold"> <content styleCode="emphasis">Metabolic &amp; Nutritional System</content> </content> </td> <td align="left" valign="top"> </td> <td align="left" valign="top"> </td> </tr> <tr ID="id_c7696f8e-124f-44f8-82bb-9a342b71b369"> <td align="left" valign="top"> Peripheral edema</td> <td align="left" valign="top">5</td> <td align="left" valign="top">4</td> </tr> <tr ID="id_fc0f4e1d-1db9-4baf-a754-acecb9d75e9d"> <td align="left" valign="top"> Decreased weight</td> <td align="left" valign="top">2</td> <td align="left" valign="top">0</td> </tr> <tr ID="id_290ddafd-39a8-4da6-b602-af64e195c7df"> <td align="left" valign="top"> <content styleCode="bold"> <content styleCode="emphasis">Nervous System</content> </content> </td> <td align="left" valign="top"> </td> <td align="left" valign="top"> </td> </tr> <tr ID="id_27350154-7877-4e0a-91d0-9f054b656c04"> <td align="left" valign="top"> Dizziness</td> <td align="left" valign="top">25</td> <td align="left" valign="top">24</td> </tr> <tr ID="id_48df3e22-f966-4456-96f8-dafd4894c74d"> <td align="left" valign="top"> Somnolence</td> <td align="left" valign="top">22</td> <td align="left" valign="top">9</td> </tr> <tr ID="id_d892fa20-d772-4960-b5c6-e15a55afaca0"> <td align="left" valign="top"> Insomnia</td> <td align="left" valign="top">17</td> <td align="left" valign="top">12</td> </tr> <tr ID="id_4fdece1a-61e1-4c3e-b5dc-3edaaff3539f"> <td align="left" valign="top"> Hallucinations</td> <td align="left" valign="top">9</td> <td align="left" valign="top">3</td> </tr> <tr ID="id_c89dc9b4-7882-4046-8d98-16032b8203d2"> <td align="left" valign="top"> Confusion</td> <td align="left" valign="top">4</td> <td align="left" valign="top">1</td> </tr> <tr ID="id_b09a28eb-9e75-4439-9a21-8756ab8cea10"> <td align="left" valign="top"> Amnesia</td> <td align="left" valign="top">4</td> <td align="left" valign="top">2</td> </tr> <tr ID="id_ed9ebb13-f492-4f55-aede-5231029177fd"> <td align="left" valign="top"> Hypesthesia</td> <td align="left" valign="top">3</td> <td align="left" valign="top">1</td> </tr> <tr ID="id_d5e0bd0a-1b5c-486e-8526-59fb764c06a8"> <td align="left" valign="top"> Dystonia</td> <td align="left" valign="top">2</td> <td align="left" valign="top">1</td> </tr> <tr ID="id_b2eecb13-b34d-4352-84ec-5f55c70bd231"> <td align="left" valign="top"> Akathisia</td> <td align="left" valign="top">2</td> <td align="left" valign="top">0</td> </tr> <tr ID="id_8e0ee8b6-d460-46c4-aafb-2073f490b44a"> <td align="left" valign="top"> Thinking abnormalities</td> <td align="left" valign="top">2</td> <td align="left" valign="top">0</td> </tr> <tr ID="id_2c58d658-787b-4a0c-bc14-611081df4e23"> <td align="left" valign="top"> Decreased libido</td> <td align="left" valign="top">1</td> <td align="left" valign="top">0</td> </tr> <tr ID="id_8e22e05d-0891-4257-aee1-4dc050c5abbd"> <td align="left" valign="top"> Myoclonus</td> <td align="left" valign="top">1</td> <td align="left" valign="top">0</td> </tr> <tr ID="id_b86d321f-112b-4770-a711-b4ac5ec03bba"> <td align="left" valign="top"> <content styleCode="bold"> <content styleCode="emphasis">Special Senses</content> </content> </td> <td align="left" valign="top"> </td> <td align="left" valign="top"> </td> </tr> <tr ID="id_34bac2c7-eb23-427d-b1ab-a285184f42c0"> <td align="left" valign="top"> Vision abnormalities</td> <td align="left" valign="top">3</td> <td align="left" valign="top">0</td> </tr> <tr ID="id_cfa98c40-1844-4a0e-af8e-8b954c5b98d0"> <td align="left" valign="top"> <content styleCode="bold"> <content styleCode="emphasis">Urogenital System</content> </content> </td> <td align="left" valign="top"> </td> <td align="left" valign="top"> </td> </tr> <tr ID="id_87a4e54b-cdb5-4302-8933-dd5869f03126"> <td align="left" valign="top"> Impotence</td> <td align="left" valign="top">2</td> <td align="left" valign="top">1</td> </tr> </tbody> </table>

<table width="0.000" ID="id_37823b81-3acf-433d-9134-582de9d3bfa9"> <caption ID="id_87d30799-bfae-4ad8-a370-de56b951d6c1">Table 4 Treatment-Emergent Adverse-Event* Incidence in Double-Blind, Placebo-Controlled Trials in Advanced Parkinson&apos;s Disease (Events &#x2265;1% of Patients Treated with MIRAPEX tablets and Numerically More Frequent than in the Placebo Group) </caption> <col/> <col/> <col/> <thead> <tr ID="id_91007b67-900b-401d-ac22-f0ab635e530e" styleCode="Botrule"> <td align="left" valign="middle" styleCode="Rrule">Body System/ Adverse Event</td> <td align="left" valign="top" styleCode="Rrule">MIRAPEX^&#x2020; (pramipexole dihydrochloride) N=260 </td> <td align="left" valign="middle">Placebo^&#x2020; N=264 </td> </tr> </thead> <tfoot ID="id_b53818f8-c2aa-48b7-8183-1b78c56bddcf"> <tr> <td align="left" valign="top" colspan="3">* Patients may have reported multiple adverse experiences during the study or at discontinuation; thus, patients may be included in more than one category.</td> </tr> <tr> <td align="left" valign="top" colspan="3">&#x2020; Patients received concomitant levodopa.</td> </tr> </tfoot> <tbody> <tr ID="id_97f046d8-1484-4b2c-bc7a-dc63a78bb9c7" styleCode="Toprule"> <td align="left" valign="top"> <content styleCode="bold"> <content styleCode="emphasis">Body as a Whole</content> </content> </td> <td align="left" valign="top" styleCode="Toprule"> </td> <td align="left" valign="top"> </td> </tr> <tr ID="id_0f8db6cb-d018-4a0f-96e6-f2b5005f56b8"> <td align="left" valign="top"> Accidental injury</td> <td align="left" valign="top">17</td> <td align="left" valign="top">15</td> </tr> <tr ID="id_39a77bc6-dd99-479a-9a81-a576a08b0d20"> <td align="left" valign="top"> Asthenia</td> <td align="left" valign="top">10</td> <td align="left" valign="top">8</td> </tr> <tr ID="id_6211e586-9660-42fc-8ea3-df7ebd3efda4"> <td align="left" valign="top"> General edema</td> <td align="left" valign="top">4</td> <td align="left" valign="top">3</td> </tr> <tr ID="id_0782cb85-524a-4a34-a75e-1d4b9c0b19da"> <td align="left" valign="top"> Chest pain</td> <td align="left" valign="top">3</td> <td align="left" valign="top">2</td> </tr> <tr ID="id_31f38fb9-5bff-4d92-9016-6b6907e66bc8"> <td align="left" valign="top"> Malaise</td> <td align="left" valign="top">3</td> <td align="left" valign="top">2</td> </tr> <tr ID="id_ca4075b1-7cab-4f2e-9c7b-3f949036dcfc"> <td align="left" valign="top"> <content styleCode="bold"> <content styleCode="emphasis">Cardiovascular System</content> </content> </td> <td align="left" valign="top"> </td> <td align="left" valign="top"> </td> </tr> <tr ID="id_4cbff3bc-c134-4e22-aa88-c956be98bbf6"> <td align="left" valign="top"> Postural hypotension</td> <td align="left" valign="top">53</td> <td align="left" valign="top">48</td> </tr> <tr ID="id_811e0bfe-2499-4b08-b6cc-3e130f85bbe5"> <td align="left" valign="top"> <content styleCode="bold"> <content styleCode="emphasis">Digestive System</content> </content> </td> <td align="left" valign="top"> </td> <td align="left" valign="top"> </td> </tr> <tr ID="id_af5b4177-fe62-45ea-b1a3-52f023d5493f"> <td align="left" valign="top"> Constipation</td> <td align="left" valign="top">10</td> <td align="left" valign="top">9</td> </tr> <tr ID="id_f022183e-b5ea-4071-a7fd-3f09380746e9"> <td align="left" valign="top"> Dry mouth</td> <td align="left" valign="top">7</td> <td align="left" valign="top">3</td> </tr> <tr ID="id_e87f4518-760c-4120-a598-07890898dfe1"> <td align="left" valign="top"> <content styleCode="bold"> <content styleCode="emphasis">Metabolic &amp; Nutritional System</content> </content> </td> <td align="left" valign="top"> </td> <td align="left" valign="top"> </td> </tr> <tr ID="id_f75edb30-8cea-4bd4-ac97-f93d95fe187d"> <td align="left" valign="top"> Peripheral edema</td> <td align="left" valign="top">2</td> <td align="left" valign="top">1</td> </tr> <tr ID="id_2c58c1ae-6bdb-475e-b38a-291e57eb16ac"> <td align="left" valign="top"> Increased creatine PK</td> <td align="left" valign="top">1</td> <td align="left" valign="top">0</td> </tr> <tr ID="id_4d1b0144-cd12-405d-a60d-f0cf7d6ddb2c"> <td align="left" valign="top"> <content styleCode="bold"> <content styleCode="emphasis">Musculoskeletal System</content> </content> </td> <td align="left" valign="top"> </td> <td align="left" valign="top"> </td> </tr> <tr ID="id_46278cd4-c530-4dd1-922d-28dbf0985cfd"> <td align="left" valign="top"> Arthritis</td> <td align="left" valign="top">3</td> <td align="left" valign="top">1</td> </tr> <tr ID="id_8b7fb53b-36d8-47aa-8c5d-5deaece61e6e"> <td align="left" valign="top"> Twitching</td> <td align="left" valign="top">2</td> <td align="left" valign="top">0</td> </tr> <tr ID="id_17b9d140-c9e7-42d3-ab16-a6a4d01ab150"> <td align="left" valign="top"> Bursitis</td> <td align="left" valign="top">2</td> <td align="left" valign="top">0</td> </tr> <tr ID="id_29771ae2-0b96-4a52-8373-29538e298e72"> <td align="left" valign="top"> Myasthenia</td> <td align="left" valign="top">1</td> <td align="left" valign="top">0</td> </tr> <tr ID="id_4ab4f0db-b480-4045-b902-c840bea50a77"> <td align="left" valign="top"> <content styleCode="bold"> <content styleCode="emphasis">Nervous System</content> </content> </td> <td align="left" valign="top"> </td> <td align="left" valign="top"> </td> </tr> <tr ID="id_28f4a673-b733-480f-a10e-b3091c8571e7"> <td align="left" valign="top"> Dyskinesia </td> <td align="left" valign="top">47</td> <td align="left" valign="top">31</td> </tr> <tr ID="id_c294a525-3a5b-420f-9d4f-605badeded7c"> <td align="left" valign="top"> Extrapyramidal syndrome</td> <td align="left" valign="top">28</td> <td align="left" valign="top">26</td> </tr> <tr ID="id_6a8dc806-b0d9-454b-a9b4-707ad8f39884"> <td align="left" valign="top"> Insomnia</td> <td align="left" valign="top">27</td> <td align="left" valign="top">22</td> </tr> <tr ID="id_330e74d0-809b-45a0-9572-58ee7f4741af"> <td align="left" valign="top"> Dizziness</td> <td align="left" valign="top">26</td> <td align="left" valign="top">25</td> </tr> <tr ID="id_8fc6d9af-c916-48d2-914f-2da8bbac9e0a"> <td align="left" valign="top"> Hallucinations</td> <td align="left" valign="top">17</td> <td align="left" valign="top">4</td> </tr> <tr ID="id_8b8a2c9e-e604-466c-abb9-08b3cb7855e3"> <td align="left" valign="top"> Dream abnormalities</td> <td align="left" valign="top">11</td> <td align="left" valign="top">10</td> </tr> <tr ID="id_0a2a0fd3-1386-4562-9785-03d23c3fb326"> <td align="left" valign="top"> Confusion</td> <td align="left" valign="top">10</td> <td align="left" valign="top">7</td> </tr> <tr ID="id_a3fbbf48-b12f-4512-945b-bf8c921dbf48"> <td align="left" valign="top"> Somnolence</td> <td align="left" valign="top">9</td> <td align="left" valign="top">6</td> </tr> <tr ID="id_cb0d4564-81af-4d91-b17d-c768a81244a3"> <td align="left" valign="top"> Dystonia</td> <td align="left" valign="top">8</td> <td align="left" valign="top">7</td> </tr> <tr ID="id_3e365cd7-0629-4c75-8d14-d7df6d95e1b8"> <td align="left" valign="top"> Gait abnormalities</td> <td align="left" valign="top">7</td> <td align="left" valign="top">5</td> </tr> <tr ID="id_4d8df33b-7576-42f8-8bc0-fc55adf52ed3"> <td align="left" valign="top"> Hypertonia</td> <td align="left" valign="top">7</td> <td align="left" valign="top">6</td> </tr> <tr ID="id_33880d75-d15a-489b-8954-c487170053a2"> <td align="left" valign="top"> Amnesia</td> <td align="left" valign="top">6</td> <td align="left" valign="top">4</td> </tr> <tr ID="id_fea70dcd-e426-43ff-a66a-bb0b502e64ec"> <td align="left" valign="top"> Akathisia</td> <td align="left" valign="top">3</td> <td align="left" valign="top">2</td> </tr> <tr ID="id_d97fafe6-88e0-4ad5-89c1-5a00aed65b86"> <td align="left" valign="top"> Thinking abnormalities</td> <td align="left" valign="top">3</td> <td align="left" valign="top">2</td> </tr> <tr ID="id_2417e8be-6773-4cd3-9de3-9637c52f3ff2"> <td align="left" valign="top"> Paranoid reaction</td> <td align="left" valign="top">2</td> <td align="left" valign="top">0</td> </tr> <tr ID="id_18fc1971-bea8-4d3e-bbc3-7bc11e61ad7e"> <td align="left" valign="top"> Delusions</td> <td align="left" valign="top">1</td> <td align="left" valign="top">0</td> </tr> <tr ID="id_576b45c4-3d4d-4a60-ad39-9602bc816fa4"> <td align="left" valign="top"> Sleep disorders</td> <td align="left" valign="top">1</td> <td align="left" valign="top">0</td> </tr> <tr ID="id_a555648f-3d88-41dd-a1a7-91de138b759d"> <td align="left" valign="top"> <content styleCode="bold"> <content styleCode="emphasis">Respiratory System</content> </content> </td> <td align="left" valign="top"> </td> <td align="left" valign="top"> </td> </tr> <tr ID="id_8c79a6db-b067-49ea-8948-bb3bc83f827c"> <td align="left" valign="top"> Dyspnea</td> <td align="left" valign="top">4</td> <td align="left" valign="top">3</td> </tr> <tr ID="id_de3bd565-da4a-44e5-afb0-28dfa86a1d9d"> <td align="left" valign="top"> Rhinitis</td> <td align="left" valign="top">3</td> <td align="left" valign="top">1</td> </tr> <tr ID="id_80df09a4-dade-428b-915f-332e5e5f255d"> <td align="left" valign="top"> Pneumonia</td> <td align="left" valign="top">2</td> <td align="left" valign="top">0</td> </tr> <tr ID="id_c335ce8c-ab06-48d3-bf11-2ac3ecfb1a03"> <td align="left" valign="top"> <content styleCode="bold"> <content styleCode="emphasis">Skin &amp; Appendages</content> </content> </td> <td align="left" valign="top"> </td> <td align="left" valign="top"> </td> </tr> <tr ID="id_8d208b3c-774a-4301-8d53-24025e1698b8"> <td align="left" valign="top"> Skin disorders</td> <td align="left" valign="top">2</td> <td align="left" valign="top">1</td> </tr> <tr ID="id_ebec607b-c28a-4042-b4eb-d8a924ed63f4"> <td align="left" valign="top"> <content styleCode="bold"> <content styleCode="emphasis">Special Senses</content> </content> </td> <td align="left" valign="top"> </td> <td align="left" valign="top"> </td> </tr> <tr ID="id_87bb9f70-8bfa-4081-9124-14eaa82e13bc"> <td align="left" valign="top"> Accommodation abnormalities</td> <td align="left" valign="top">4</td> <td align="left" valign="top">2</td> </tr> <tr ID="id_f62da9da-ae27-4833-a5cb-007c2e671d91"> <td align="left" valign="top"> Vision abnormalities</td> <td align="left" valign="top">3</td> <td align="left" valign="top">1</td> </tr> <tr ID="id_9e2bdb9a-789d-4b10-bb4c-746f3aedeb67"> <td align="left" valign="top"> Diplopia</td> <td align="left" valign="top">1</td> <td align="left" valign="top">0</td> </tr> <tr ID="id_cd1acb9e-ece9-41df-a51d-2466c5cfb094"> <td align="left" valign="top"> <content styleCode="bold"> <content styleCode="emphasis">Urogenital System</content> </content> </td> <td align="left" valign="top"> </td> <td align="left" valign="top"> </td> </tr> <tr ID="id_13200f05-47c9-4027-9597-3bccfba0bafb"> <td align="left" valign="top"> Urinary frequency</td> <td align="left" valign="top">6</td> <td align="left" valign="top">3</td> </tr> <tr ID="id_dbaf3bb4-fc32-43a9-838b-6d725bc2a5f7"> <td align="left" valign="top"> Urinary tract infection</td> <td align="left" valign="top">4</td> <td align="left" valign="top">3</td> </tr> <tr ID="id_76d12b55-97e9-4c0f-b1da-c6a7eafe0596"> <td align="left" valign="top"> Urinary incontinence</td> <td align="left" valign="top">2</td> <td align="left" valign="top">1</td> </tr> </tbody> </table>

<table width="0.000" ID="id_e8eb0d61-2c8c-4f3d-a2c0-5c35f5a4cdf9"> <caption ID="id_48719a89-a7fe-4e09-ad08-971ad50517e1">Table 5 Treatment-Emergent Adverse-Event* Incidence in Double-Blind, Placebo-Controlled Trials in Restless Legs Syndrome (Events &#x2265; 2% of Patients Treated with MIRAPEX tablets and Numerically More Frequent than in the Placebo Group) </caption> <col/> <col/> <col/> <thead> <tr ID="id_834a49ea-8dfe-4b65-8d60-c0075fb765b3" styleCode="Botrule"> <td align="left" valign="top" styleCode="Rrule">Body System/ Adverse Event </td> <td align="center" valign="top" styleCode="Rrule">MIRAPEX 0.125 &#x2013; 0.75 mg/day (N=575) %</td> <td align="center" valign="top">Placebo (N=223) %</td> </tr> </thead> <tfoot ID="id_7a6025dd-4c12-49bc-a65b-a27b89e5d0b4"> <tr> <td align="left" valign="top" colspan="3">*Patients may have reported multiple adverse experiences during the study or at discontinuation; thus, patients may be included in more than one category. </td> </tr> </tfoot> <tbody> <tr ID="id_a18f546d-9e5b-469d-84b7-f5de0f9e5718" styleCode="Toprule"> <td align="left" valign="top" colspan="3" styleCode="Botrule"> <content styleCode="bold"> <content styleCode="emphasis">Gastrointestinal disorders </content> </content> </td> </tr> <tr ID="id_8513f84d-f919-41be-89b7-91d098fd25ba"> <td align="left" valign="top" styleCode="Botrule"> Nausea</td> <td align="center" valign="top" styleCode="Botrule">16</td> <td align="center" valign="top" styleCode="Botrule">5</td> </tr> <tr ID="id_c4b8d183-cc14-4045-81f5-005ad0316b02"> <td align="left" valign="top" styleCode="Botrule"> Constipation</td> <td align="center" valign="top" styleCode="Botrule">4</td> <td align="center" valign="top" styleCode="Botrule">1</td> </tr> <tr ID="id_f7fe48c0-cb89-4510-9f6e-b68719ef6b39"> <td align="left" valign="top" styleCode="Botrule"> Diarrhea</td> <td align="center" valign="top" styleCode="Botrule">3</td> <td align="center" valign="top" styleCode="Botrule">1</td> </tr> <tr ID="id_c2bbeadd-f2d7-47b0-87d8-4674a293a2ed"> <td align="left" valign="top" styleCode="Botrule"> Dry mouth</td> <td align="center" valign="top" styleCode="Botrule">3</td> <td align="center" valign="top" styleCode="Botrule">1</td> </tr> <tr ID="id_42edb255-1864-4d67-b559-9878e0a987d3"> <td align="left" valign="top" colspan="3" styleCode="Botrule"> <content styleCode="bold"> <content styleCode="emphasis">General disorders and administration site conditions </content> </content> </td> </tr> <tr ID="id_791399d4-586f-4f68-b2ca-0994b39b4d5e"> <td align="left" valign="top" styleCode="Botrule"> Fatigue</td> <td align="center" valign="top" styleCode="Botrule">9</td> <td align="center" valign="top" styleCode="Botrule">7</td> </tr> <tr ID="id_c91c4215-cc07-4ab5-9d56-3e64329b268e"> <td align="left" valign="top" colspan="3" styleCode="Botrule"> <content styleCode="bold"> <content styleCode="emphasis">Infections and infestations</content> </content> </td> </tr> <tr ID="id_a9b875d5-77d5-4455-9691-22d6760114f9"> <td align="left" valign="top" styleCode="Botrule"> Influenza</td> <td align="center" valign="top" styleCode="Botrule">3</td> <td align="center" valign="top" styleCode="Botrule">1</td> </tr> <tr ID="id_2f37c792-bb8b-44e6-b215-1976fa9f00bc"> <td align="left" valign="top" colspan="3" styleCode="Botrule"> <content styleCode="bold"> <content styleCode="emphasis">Nervous system disorders</content> </content> </td> </tr> <tr ID="id_d43b73a9-d22f-4b29-ac3a-6eda70b92274"> <td align="left" valign="top" styleCode="Botrule"> Headache</td> <td align="center" valign="top" styleCode="Botrule">16</td> <td align="center" valign="top" styleCode="Botrule">15</td> </tr> <tr ID="id_5692674a-8cc8-4527-92b0-4e2ccb1cc368"> <td align="left" valign="top"> Somnolence</td> <td align="center" valign="top">6</td> <td align="center" valign="top">3</td> </tr> </tbody> </table>