FDA label 57245b67-39dc-eb29-e063-6294a90a82da

5 WARNINGS AND PRECAUTIONS May cause hypertension (including severe hypertensive syndromes) at recommended doses ( 5.1 ) May cause serotonin syndrome when used with antidepressants ( 5.2 ) May cause falling asleep during activities of daily living, daytime drowsiness, and somnolence ( 5.3 ) May cause hypotension, especially orthostatic ( 5.6 ) May cause or exacerbate dyskinesia. Decreasing the levodopa dose may lessen or eliminate this side effect ( 5.7 ) May cause hallucinations and psychotic-like behavior ( 5.8 ) May cause impulse control/compulsive behaviors ( 5.9 ) May cause withdrawal-emergent hyperpyrexia and confusion ( 5.10 ) Increased risk of melanoma: monitor patients for melanoma on a regular basis ( 5.11 ) 5.1 Hypertension Exacerbation of hypertension may occur during treatment with AZILECT. Medication adjustment may be necessary if elevation of blood pressure is sustained. Monitor patients for new onset hypertension or hypertension that is not adequately controlled after starting AZILECT. In Study 3, AZILECT (1 mg/day) given in conjunction with levodopa, produced an increased incidence of significant blood pressure elevation (systolic > 180 or diastolic > 100 mm Hg) of 4% compared to 3% for placebo [see Adverse Reactions ( 6.1 )] . When used as an adjunct to levodopa (Studies 3 and 4), the risk for developing post-treatment high blood pressure (e.g., systolic > 180 or diastolic >100 mm Hg) combined with a significant increase from baseline (e.g., systolic > 30 or diastolic > 20 mm Hg) was higher for AZILECT (2%) compared to placebo (1%). Dietary tyramine restriction is not required during treatment with recommended doses of AZILECT. However, certain foods that may contain very high amounts (i.e., more than 150 mg) of tyramine that could potentially cause severe hypertension because of tyramine interaction (including various clinical syndromes referred to as hypertensive urgency, crisis, or emergency) in patients taking AZILECT, even at the recommended doses, due to increased sensitivity to tyramine. Patients should be advised to avoid foods containing a very large amount of tyramine while taking recommended doses of AZILECT because of the potential for large increases in blood pressure including clinical syndromes referred to as hypertensive urgency, crisis, or emergency. AZILECT is a selective inhibitor of MAO-B at the recommended doses of 0.5 or 1 mg daily. Selectivity for inhibiting MAO-B diminishes in a dose-related manner as the dose is progressively increased above the recommended daily doses. 5.2 Serotonin Syndrome Serotonin syndrome has been reported with concomitant use of an antidepressant (e.g., selective serotonin reuptake inhibitors-SSRIs, serotonin-norepinephrine reuptake inhibitors-SNRIs, tricyclic antidepressants, tetracyclic antidepressants, triazolopyridine antidepressants) and a nonselective MAOI (e.g., phenelzine, tranylcypromine) or selective MAO-B inhibitors, such as selegiline (Eldepryl) and rasagiline (AZILECT). Serotonin syndrome has also been reported with concomitant use of AZILECT with meperidine, tramadol, methadone, or propoxyphene. AZILECT is contraindicated for use with meperidine, tramadol, methadone, propoxyphene and MAO inhibitors (MAOIs), including other selective MAO-B inhibitors [see Contraindications ( 4 ) and Drug Interactions ( 7.1 , 7.2 , 7.3 )]. In the postmarketing period, potentially life-threatening serotonin syndrome has been reported in patients treated with antidepressants concomitantly with AZILECT. Concomitant use of AZILECT with one of many classes of antidepressants (e.g., SSRIs, SNRIs, triazolopyridine, tricyclic or tetracyclic antidepressants) is not recommended [see Drug Interactions ( 7.5 )] . The symptoms of serotonin syndrome have included behavioral and cognitive/mental status changes (e.g., confusion, hypomania, hallucinations, agitation, delirium, headache, and coma), autonomic effects (e.g., syncope, shivering, sweating, high fever/hyperthermia, hypertension, tachycardia, nausea, diarrhea), and somatic effects (e.g., muscular rigidity, myoclonus, muscle twitching, hyperreflexia manifested by clonus, and tremor). Serotonin syndrome can result in death. AZILECT clinical trials did not allow concomitant use of fluoxetine or fluvoxamine with AZILECT, and the potential drug interaction between AZILECT and antidepressants has not been studied systematically. Although a small number of AZILECT-treated patients were concomitantly exposed to antidepressants (tricyclics n=115; SSRIs n=141), the exposure, both in dose and number of subjects, was not adequate to rule out the possibility of an untoward reaction from combining these agents. At least 14 days should elapse between discontinuation of AZILECT and initiation of treatment with a SSRI, SNRI, tricyclic, tetracyclic, or triazolopyridine antidepressant. Because of the long half-lives of certain antidepressants (e.g., fluoxetine and its active metabolite), at least five weeks (perhaps longer, especially if fluoxetine has been prescribed chronically and/or at higher doses) should elapse between discontinuation of fluoxetine and initiation of AZILECT [see Drug Interactions ( 7.5 )] . 5.3 Falling Asleep During Activities of Daily Living and Somnolence It has been reported 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 monitor patients for drowsiness or sleepiness, because some of the events occur well after initiation of treatment with dopaminergic medication. Prescribers should also be aware that patients may not acknowledge drowsiness or sleepiness until directly questioned about drowsiness or sleepiness during specific activities. Cases of patients treated with AZILECT and other dopaminergic medications 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 AZILECT with other dopaminergic medications, 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 more than 1-year after initiation of treatment. In Study 3, somnolence was a common occurrence in patients receiving AZILECT and was more frequent in patients with Parkinson’s disease receiving AZILECT than in respective patients receiving placebo (6% AZILECT compared to 4% Placebo) [see Adverse Reactions ( 6.1 )] . Before initiating treatment with AZILECT, patients should be advised of the potential to develop drowsiness and specifically asked about factors that may increase the risk with AZILECT such as concomitant sedating medications, the presence of sleep disorders, and concomitant medications that increase rasagiline plasma levels (e.g., ciprofloxacin ) [see Drug Interactions ( 7.6 )] . If a patient develops significant daytime sleepiness or episodes of falling asleep during activities that require active participation (e.g., driving a motor vehicle, conversations, eating), AZILECT should ordinarily be discontinued. If a decision is made to continue these patients on AZILECT, advise them to avoid driving and 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. 5.4 Ciprofloxacin or Other CYP1A2 Inhibitors Rasagiline plasma concentrations may increase up to 2 fold in patients using concomitant ciprofloxacin and other CYP1A2 inhibitors. Patients taking concomitant ciprofloxacin or other CYP1A2 inhibitors should not exceed a dose of AZILECT 0.5 mg once daily [see Dosage and Administration ( 2.2 ), Drug Interactions ( 7.6 ), and Clinical Pharmacology ( 12.3 )] . 5.5 Hepatic Impairment Rasagiline plasma concentration may increase in patients with hepatic impairment. Patients with mild hepatic impairment should be given the dose of AZILECT 0.5 mg once daily. AZILECT should not be used in patients with moderate or severe hepatic impairment [see Dosage and Administration ( 2.3 ) and Clinical Pharmacology ( 12.3 )] . 5.6 Hypotension / Orthostatic Hypotension In Study 3, the incidence of orthostatic hypotension consisting of a systolic blood pressure decrease (≥ 30 mm Hg) or a diastolic blood pressure decrease (> 20 mm Hg) after standing was 13% with AZILECT (1 mg/day) compared to 9% with placebo [see Adverse Reactions ( 6.1 )] . At the 1 mg dose, the frequency of orthostatic hypotension (at any time during the study) was approximately 44% for AZILECT vs 33% for placebo for mild to moderate systolic blood pressure decrements (> 20 mm Hg), 40% for AZILECT vs 33% for placebo for mild to moderate diastolic blood pressure decrements (> 10 mm Hg), 7% for AZILECT vs 3% for placebo for severe systolic blood pressure decrements (> 40 mm Hg), and 9% for AZILECT vs 6% for placebo for severe diastolic blood pressure decrements (≥ 20 mm Hg). There was also an increased risk for some of these abnormalities at the lower 0.5 mg daily dose and for an individual patient having mild to moderate or severe orthostatic hypotension for both systolic and diastolic blood pressure. In Study 2 where AZILECT was given as an adjunct therapy in patients not taking concomitant levodopa, there were 5 reports of orthostatic hypotension in patients taking AZILECT 1 mg (3.1%) and 1 report in patients taking placebo (0.6%) [see Adverse Reactions ( 6.1 )] . Clinical trial data further suggest that orthostatic hypotension occurs most frequently in the first two months of AZILECT treatment and tends to decrease over time. Some patients treated with AZILECT experienced a mildly increased risk for significant decreases in blood pressure unrelated to standing but while supine. The risk for post-treatment hypotension (e.g., systolic < 90 or diastolic < 50 mm Hg) combined with a significant decrease from baseline (e.g., systolic > 30 or diastolic > 20 mm Hg) was higher for AZILECT 1 mg (3.2%) compared to placebo (1.3%). There was no clear increased risk for lowering of blood pressure or postural hypotension associated with AZILECT 1 mg/day as monotherapy. When used as an adjunct to levodopa, postural hypotension was also reported as an adverse reaction in approximately 6% of patients treated with AZILECT 0.5 mg, 9% of patients treated with AZILECT 1 mg and 3% of patients treated with placebo. Postural hypotension led to drug discontinuation and premature withdrawal from clinical trials in one (0.7%) patient treated with AZILECT 1 mg/day, no patients treated with AZILECT 0.5 mg/day and no placebo-treated patients. 5.7 Dyskinesia When used as an adjunct to levodopa, AZILECT may cause dyskinesia or potentiate dopaminergic side effects and exacerbate pre-existing dyskinesia. In Study 3, the incidence of dyskinesia was 18% for patients treated with 0.5 mg or 1 mg AZILECT as an adjunct to levodopa and 10% for patients treated with placebo as an adjunct to levodopa. Decreasing the dose of levodopa may mitigate this side effect [see Adverse Reactions ( 6.1 )] . 5.8 Hallucinations / Psychotic-Like Behavior In the monotherapy study (Study 1), the incidence of hallucinations reported as an adverse event was 1.3% in patients treated with AZILECT 1 mg and 0.7% in patients treated with placebo. In Study 1, the incidence of hallucinations reported as an adverse reaction and leading to drug discontinuation and premature withdrawal was 1.3% in patients treated with AZILECT 1 mg and 0% in placebo-treated patients. When studied as an adjunct therapy without levodopa (Study 2), hallucinations were reported as an adverse reaction in 1.2% of patients treated with 1 mg/day AZILECT and 1.8% of patients treated with placebo. Hallucinations led to drug discontinuation and premature withdrawal from the clinical trial in 0.6% of patients treated with AZILECT 1 mg/day and in none of the placebo-treated patients. When studied as an adjunct to levodopa (Study 3), the incidence of hallucinations was approximately 5% in patients treated with AZILECT 0.5 mg/day, 4% in patients treated with AZILECT 1 mg/day, and 3% in patients treated with placebo. The incidence of hallucinations leading to drug discontinuation and premature withdrawal was about 1% in patients treated with 0.5 mg AZILECT and 1 mg AZILECT/day, and 0% in placebo-treated patients [see Adverse Reactions ( 6.1 )]. Postmarketing reports indicate that patients may experience new or worsening mental status and behavioral changes, which may be severe, including psychotic-like behavior during treatment with AZILECT or after starting or increasing the dose of AZILECT. Other drugs prescribed to improve the symptoms of Parkinson’s disease can have similar effects on thinking and behavior. This abnormal thinking and behavior can consist of one or more of a variety of manifestations including paranoid ideation, delusions, hallucinations, confusion, psychotic-like behavior, disorientation, aggressive behavior, agitation, and delirium. Patients should be informed of the possibility of developing hallucinations and instructed to report them to their health care provider promptly should they develop. Patients with a major psychotic disorder should ordinarily not be treated with AZILECT because of the risk of exacerbating the psychosis with an increase in central dopaminergic tone. In addition, many treatments for psychosis that decrease central dopaminergic tone may decrease the effectiveness of AZILECT [ see Drug Interactions ( 7.8 ) ]. Consider dose reduction or stopping the medication if a patient develops hallucinations or psychotic like behaviors while taking AZILECT. 5.9 Impulse Control / Compulsive Behaviors Case reports suggest that patients can experience intense urges to gamble, increased sexual urges, intense urges to spend money, binge eating, and/or other intense urges, and the inability to control these urges while taking one or more of the medications, including AZILECT, that increase central dopaminergic tone and that are generally used for the treatment of Parkinson’s disease. In some cases, although not all, these urges were reported to have stopped when the dose was reduced or the medication was discontinued. Because patients may not recognize these behaviors as abnormal, it is important for prescribers to specifically ask patients or their caregivers about the development of new or increased gambling urges, sexual urges, uncontrolled spending or other urges while being treated with AZILECT. Consider dose reduction or stopping the medication if a patient develops such urges while taking AZILECT. 5.10 Withdrawal-Emergent Hyperpyrexia and Confusion A symptom complex resembling neuroleptic malignant syndrome (characterized by elevated temperature, muscular rigidity, altered consciousness, and autonomic instability), with no other obvious etiology, has been reported in association with rapid dose reduction, withdrawal of, or changes in drugs that increase central dopaminergic tone. 5.11 Melanoma Epidemiological studies have shown that patients with Parkinson’s disease have a higher risk (2- to approximately 6-fold higher) of developing melanoma than the general population. Whether the increased risk observed was due to Parkinson’s disease or other factors, such as drugs used to treat Parkinson’s disease, is unclear. For the reasons stated above, patients and providers are advised to monitor for melanomas frequently and on a regular basis. Ideally, periodic skin examinations should be performed by appropriately qualified individuals (e.g., dermatologists).

6 ADVERSE REACTIONS The following adverse reactions are described in more detail in the Warnings and Precautions section of the label: Hypertension [ see Warnings and Precautions ( 5.1 ) ] Serotonin Syndrome [ see Warnings and Precautions ( 5.2 ) ] Falling Asleep During Activities of Daily Living and Somnolence [ see Warnings and Precautions ( 5.3 ) ] Hypotension / Orthostatic Hypotension [ see Warnings and Precautions ( 5.6 ) ] Dyskinesia [ see Warnings and Precautions ( 5.7 ) ] Hallucinations / Psychotic-Like Behavior [ see Warnings and Precautions ( 5.8 ) ] Impulse Control /Compulsive Behaviors [ see Warnings and Precautions ( 5.9 ) ] Withdrawal-Emergent Hyperpyrexia and Confusion [ see Warnings and Precautions ( 5.10 ) ] Melanoma [ see Warnings and Precautions ( 5.11 ) ] Most common adverse reactions (incidence 3% or greater than placebo): AZILECT monotherapy: flu syndrome, arthralgia, depression, dyspepsia ( 6.1 ) AZILECT used as adjunct without levodopa: peripheral edema, fall, arthralgia, cough, and insomnia ( 6.1 ) AZILECT used as adjunct to levodopa: dyskinesia, accidental injury, weight loss, postural hypotension, vomiting, anorexia, arthralgia, abdominal pain, nausea, constipation, dry mouth, rash, abnormal dreams, fall, and tenosynovitis ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact TEVA at 1-800-221-4026 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to the incidence of adverse reactions in the clinical trials of another drug and may not reflect the rates of adverse reactions observed in practice. During the clinical development of AZILECT, Parkinson’s disease patients received AZILECT as initial monotherapy (Study 1) and as adjunct therapy (Study 2, Study 3, Study 4). As the populations in these studies differ, not only in the adjunct use of dopamine agonists or levodopa during AZILECT treatment, but also in the severity and duration of their disease, the adverse reactions are presented separately for each study. Monotherapy Use of AZILECT In Study 1, approximately 5% of the 149 patients treated with AZILECT discontinued treatment due to adverse reactions compared to 2% of the 151 patients who received placebo. The only adverse reaction that led to the discontinuation of more than one patient was hallucinations. The most commonly observed adverse reactions in Study 1 (incidence in AZILECT-treated patients 3% or greater than the incidence in placebo-treated patients) included flu syndrome, arthralgia, depression, and dyspepsia. Table 1 lists adverse reactions that occurred in 2% or greater of patients receiving AZILECT as monotherapy and were numerically more frequent than in the placebo group in Study 1. Table 1: Adverse Reactions* in Study 1 AZILECT 1 mg (N=149) Placebo (N=151) % of Patients % of Patients Headache 14 12 Arthralgia 7 4 Dyspepsia 7 4 Depression 5 2 Fall 5 3 Flu syndrome 5 1 Conjunctivitis 3 1 Fever 3 1 Gastroenteritis 3 1 Rhinitis 3 1 Arthritis 2 1 Ecchymosis 2 0 Malaise 2 0 Neck Pain 2 0 Paresthesia 2 1 Vertigo 2 1 *Incidence 2% or greater in AZILECT 1 mg group and numerically more frequent than in placebo group There were no significant differences in the safety profile based on age or gender. Adjunct Use of AZILECT AZILECT was studied as an adjunct therapy without levodopa (Study 2), or as an adjunct therapy to levodopa, with some patients also taking dopamine agonists, COMT inhibitors, anticholinergics, or amantadine (Study 3 and Study 4). In Study 2, approximately 8% of the 162 patients treated with AZILECT discontinued treatment due to adverse reactions compared to 4% of the 164 patients who received placebo. Adverse reactions that led to the discontinuation of more than one patient were nausea and dizziness. The most commonly observed adverse reactions in Study 2 (incidence in AZILECT-treated patients 3% or greater than incidence in placebo-treated patients) included peripheral edema, fall, arthralgia, cough, and insomnia. Table 2 lists adverse reactions that occurred in 2% or greater in patients receiving AZILECT as adjunct therapy without levodopa and numerically more frequent than in the placebo group in Study 2. Table 2: Adverse Reactions* in Study 2 AZILECT 1 mg (N=162) Placebo (N=164) % of Patients % of Patients Dizziness 7 6 Peripheral edema 7 4 Headache 6 4 Nausea 6 4 Fall 6 1 Arthralgia 5 2 Back pain 4 3 Cough 4 1 Insomnia 4 1 Upper respiratory tract infection 4 2 Orthostatic hypotension 3 1 *Incidence 2% or greater in AZILECT 1 mg group and numerically more frequent than in placebo group There were no significant differences in the safety profile based on age or gender. In Study 3, adverse event reporting was considered more reliable than Study 4; therefore, only the adverse event data from Study 3 are presented below. In Study 3, approximately 9% of the 164 patients treated with AZILECT 0.5 mg/day and 7% of the 149 patients treated with AZILECT 1 mg/day discontinued treatment due to adverse reactions, compared to 6% of the 159 patients who received placebo. The adverse reactions that led to discontinuation of more than one AZILECT-treated patient were diarrhea, weight loss, hallucination, and rash. The most commonly observed adverse reactions in Study 3 (incidence in AZILECT-treated patients 3% or greater than the incidence in placebo-treated patients) included dyskinesia, accidental injury, weight loss, postural hypotension, vomiting, anorexia, arthralgia, abdominal pain, nausea, constipation, dry mouth, rash, abnormal dreams, fall and tenosynovitis. Table 3 lists adverse reactions that occurred in 2% or greater of patients treated with AZILECT 1 mg/day and that were numerically more frequent than the placebo group in Study 3. Table 3: Adverse Reactions* in Study 3 AZILECT 1 mg (N=149) AZILECT 0.5 mg (N=164) Placebo (N=159) % of patients % of patients % of patients Dyskinesia 18 18 10 Accidental injury 12 8 5 Nausea 12 10 8 Headache 11 8 10 Fall 11 12 8 Weight loss 9 2 3 Constipation 9 4 5 Postural hypotension 9 6 3 Arthralgia 8 6 4 Vomiting 7 4 1 Dry mouth 6 2 3 Rash 6 3 3 Somnolence 6 4 4 Abdominal pain 5 2 1 Anorexia 5 2 1 Diarrhea 5 7 4 Ecchymosis 5 2 3 Dyspepsia 5 4 4 Paresthesia 5 2 3 Abnormal dreams 4 1 1 Hallucinations 4 5 3 Ataxia 3 6 1 Dyspnea 3 5 2 Infection 3 2 2 Neck pain 3 1 1 Sweating 3 2 1 Tenosynovitis 3 1 0 Dystonia 3 2 1 Gingivitis 2 1 1 Hemorrhage 2 1 1 Hernia 2 1 1 Myasthenia 2 2 1 *Incidence 2% or greater in AZILECT 1 mg group and numerically more frequent than in placebo group Several of the more common adverse reactions seemed dose-related, including weight loss, postural hypotension, and dry mouth. There were no significant differences in the safety profile based on age or gender. During all Parkinson’s disease phase 2/3 clinical trials, the long-term safety profile was similar to that observed with shorter duration exposure.

<table width="100%"><caption>Table 1: Adverse Reactions* in Study 1</caption><col width="33%"/><col width="28%"/><col width="31%"/><tbody><tr><td styleCode="Rrule Botrule Lrule Toprule "/><td styleCode="Rrule Botrule Lrule Toprule "><paragraph><content styleCode="bold">AZILECT 1 mg (N=149)</content></paragraph></td><td styleCode="Rrule Botrule Lrule Toprule "><paragraph><content styleCode="bold">Placebo (N=151)</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule "/><td styleCode="Rrule Lrule Toprule Botrule "><paragraph><content styleCode="bold">% of Patients</content></paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph><content styleCode="bold">% of Patients</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule "><paragraph>Headache</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>14</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>12</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule "><paragraph>Arthralgia</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>7</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>4</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule "><paragraph>Dyspepsia</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>7</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>4</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule "><paragraph>Depression</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>5</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>2</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule "><paragraph>Fall</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>5</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>3</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule "><paragraph>Flu syndrome</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>5</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>1</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule "><paragraph>Conjunctivitis</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>3</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>1</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule "><paragraph>Fever</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>3</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>1</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule "><paragraph>Gastroenteritis</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>3</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>1</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule "><paragraph>Rhinitis</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>3</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>1</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule "><paragraph>Arthritis</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>2</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>1</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule "><paragraph>Ecchymosis</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>2</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>0</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule "><paragraph>Malaise</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>2</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>0</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule "><paragraph>Neck Pain</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>2</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>0</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule "><paragraph>Paresthesia</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>2</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>1</paragraph></td></tr><tr><td styleCode="Rrule Botrule Lrule Toprule "><paragraph>Vertigo</paragraph></td><td styleCode="Rrule Botrule Lrule Toprule "><paragraph>2</paragraph></td><td styleCode="Rrule Botrule Lrule Toprule "><paragraph>1</paragraph></td></tr></tbody></table>

<table width="100%"><caption>Table 2: Adverse Reactions* in Study 2</caption><col width="33%"/><col width="28%"/><col width="31%"/><tbody><tr><td styleCode="Rrule Botrule Lrule Toprule " valign="middle"/><td styleCode="Rrule Botrule Lrule Toprule " valign="bottom"><paragraph><content styleCode="bold">AZILECT 1 mg (N=162)</content></paragraph></td><td styleCode="Rrule Botrule Lrule Toprule " valign="bottom"><paragraph><content styleCode="bold">Placebo</content></paragraph><paragraph><content styleCode="bold">(N=164)</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule "/><td styleCode="Rrule Lrule Toprule Botrule " valign="bottom"><paragraph><content styleCode="bold">% of Patients</content></paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="bottom"><paragraph><content styleCode="bold">% of Patients</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule "><paragraph>Dizziness</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="bottom"><paragraph>7</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="bottom"><paragraph>6</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule "><paragraph>Peripheral edema</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="bottom"><paragraph>7</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="bottom"><paragraph>4</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule "><paragraph>Headache</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="bottom"><paragraph>6</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="bottom"><paragraph>4</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule "><paragraph>Nausea</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="bottom"><paragraph>6</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="bottom"><paragraph>4</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule "><paragraph>Fall</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="bottom"><paragraph>6</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="bottom"><paragraph>1</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule "><paragraph>Arthralgia</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="bottom"><paragraph>5</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="bottom"><paragraph>2</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule "><paragraph>Back pain</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="bottom"><paragraph>4</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="bottom"><paragraph>3</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule "><paragraph>Cough</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="bottom"><paragraph>4</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="bottom"><paragraph>1</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule "><paragraph>Insomnia</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="bottom"><paragraph>4</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="bottom"><paragraph>1</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule "><paragraph>Upper respiratory tract infection</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="bottom"><paragraph>4</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="bottom"><paragraph>2</paragraph></td></tr><tr><td styleCode="Rrule Botrule Lrule Toprule "><paragraph>Orthostatic hypotension</paragraph></td><td styleCode="Rrule Botrule Lrule Toprule " valign="bottom"><paragraph>3</paragraph></td><td styleCode="Rrule Botrule Lrule Toprule " valign="bottom"><paragraph>1</paragraph></td></tr></tbody></table>

<table width="100%"><caption>Table 3: Adverse Reactions* in Study 3</caption><col width="25%"/><col width="25%"/><col width="25%"/><col width="25%"/><tbody><tr><td styleCode="Rrule Botrule Lrule Toprule "/><td styleCode="Rrule Botrule Lrule Toprule " valign="middle"><paragraph><content styleCode="bold">AZILECT 1 mg</content></paragraph><paragraph><content styleCode="bold">(N=149)</content></paragraph></td><td styleCode="Rrule Botrule Lrule Toprule "><paragraph><content styleCode="bold">AZILECT 0.5 mg (N=164)</content></paragraph></td><td styleCode="Rrule Botrule Lrule Toprule "><paragraph><content styleCode="bold">Placebo (N=159) </content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule "/><td styleCode="Rrule Lrule Toprule Botrule "><paragraph><content styleCode="bold">% of patients</content></paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph><content styleCode="bold">% of patients</content></paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph><content styleCode="bold">% of patients</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule "><paragraph>Dyskinesia</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>18</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>18</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>10</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule "><paragraph>Accidental injury</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>12</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>8</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>5</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule "><paragraph>Nausea</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>12</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>10</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>8</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule "><paragraph>Headache</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>11</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>8</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>10</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule "><paragraph>Fall</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>11</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>12</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>8</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule "><paragraph>Weight loss</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>9</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>2</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>3</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule "><paragraph>Constipation</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>9</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>4</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>5</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule "><paragraph>Postural hypotension</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>9</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>6</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>3</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule "><paragraph>Arthralgia</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>8</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>6</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>4</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule "><paragraph>Vomiting</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>7</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>4</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>1</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule "><paragraph>Dry mouth</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>6</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>2</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>3</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule "><paragraph>Rash</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>6</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>3</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>3</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule "><paragraph>Somnolence</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>6</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>4</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>4</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule "><paragraph>Abdominal pain</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>5</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>2</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>1</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule "><paragraph>Anorexia</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>5</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>2</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>1</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule "><paragraph>Diarrhea</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>5</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>7</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>4</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule "><paragraph>Ecchymosis</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>5</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>2</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>3</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule "><paragraph>Dyspepsia</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>5</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>4</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>4</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule "><paragraph>Paresthesia</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>5</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>2</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>3</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule "><paragraph>Abnormal dreams</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>4</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>1</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>1</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule "><paragraph>Hallucinations</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>4</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>5</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>3</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule "><paragraph>Ataxia</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>3</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>6</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>1</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule "><paragraph>Dyspnea</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>3</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>5</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>2</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule "><paragraph>Infection</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>3</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>2</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>2</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule "><paragraph>Neck pain</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>3</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>1</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>1</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule "><paragraph>Sweating</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>3</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>2</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>1</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule "><paragraph>Tenosynovitis</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>3</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>1</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>0</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule "><paragraph>Dystonia</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>3</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>2</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>1</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule "><paragraph>Gingivitis</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>2</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>1</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>1</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule "><paragraph>Hemorrhage</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>2</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>1</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>1</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule "><paragraph>Hernia</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>2</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>1</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule "><paragraph>1</paragraph></td></tr><tr><td styleCode="Rrule Botrule Lrule Toprule "><paragraph>Myasthenia</paragraph></td><td styleCode="Rrule Botrule Lrule Toprule "><paragraph>2</paragraph></td><td styleCode="Rrule Botrule Lrule Toprule "><paragraph>2</paragraph></td><td styleCode="Rrule Botrule Lrule Toprule "><paragraph>1</paragraph></td></tr></tbody></table>