Levetiracetam

5 WARNINGS AND PRECAUTIONS Psychiatric Symptoms: Behavioral abnormalities including psychotic symptoms, suicidal ideation, irritability, and aggressive behavior have been observed. Monitor patients for psychiatric signs and symptoms ( 5.1 ) Suicidal Behavior and Ideation: Monitor patients for new or worsening depression, suicidal thoughts/behavior, and/or unusual changes in mood or behavior ( 5.2 ) Somnolence and Fatigue: Monitor patients for these symptoms and advise patients not to drive or operate machinery until they have gained sufficient experience on levetiracetam tablets ( 5.3 ) Withdrawal Seizures: Levetiracetam tablets must be gradually withdrawn ( 5.6 ) 5.1 Psychiatric Reactions In some patients levetiracetam tablets causes behavioral abnormalities. The incidences of behavioral abnormalities in the myoclonic and primary generalized tonic-clonic seizure studies were comparable to those of the adult and pediatric partial onset seizure studies. A total of 13.3% of adult levetiracetam tablets -treated patients and 37.6% of pediatric levetiracetam tablets-treated patients (4 to 16 years of age) compared to 6.2% and 18.6% of adult and pediatric placebo patients respectively, experienced non-psychotic behavioral symptoms (reported as aggression, agitation, anger, anxiety, apathy, depersonalization, depression, emotional lability, hostility, hyperkinesias, irritability, nervousness, neurosis, and personality disorder). A randomized double-blind, placebo-controlled study was performed to assess the neurocognitive and behavioral effects of levetiracetam tablets as adjunctive therapy in pediatric patients (4 to 16 years of age). The results from an exploratory analysis indicated a worsening in levetiracetam tablets-treated patients on aggressive behavior (one of eight behavior dimensions) as measured in a standardized and systematic way using a validated instrument, the Achenbach Child Behavior Checklist (CBCL/6 to18). In pediatric patients 1 month to < 4 years of age, irritability was reported in 11.7% of the levetiracetam tablets-treated patients compared to 0% of placebo patients. A total of 1.7% of adult levetiracetam tablets -treated patients discontinued treatment due to behavioral adverse events, compared to 0.2% of placebo patients. The treatment dose was reduced in 0.8% of adult levetiracetam tablets -treated patients and in 0.5% of placebo patients. Overall, 10.9% of levetiracetam tablets -treated pediatric patients experienced behavioral symptoms associated with discontinuation or dose reduction, compared to 6.2% of placebo patients. One percent of adult levetiracetam tablets -treated patients, 2% of children 4 to 16 years of age, and 17% of children 1 month to <4 years of age experienced psychotic symptoms, compared to 0.2%, 2%, and 5% respectively, in the placebo patients. In the controlled study that assessed the neurocognitive and behavioral effects of levetiracetam tablets in pediatric patients 4 to 16 years of age, 1 (1.6%) levetiracetam tablets -treated patient experienced paranoia compared to no placebo patients. There were 2 (3.1%) levetiracetam tablets -treated patients that experienced confusional state compared to no placebo patients [ see Use in Specific Populations (8.4) ]. Two (0.3%) adult levetiracetam tablets -treated patients were hospitalized and their treatment was discontinued due to psychosis. Both events, reported as psychosis, developed within the first week of treatment and resolved within 1 to 2 weeks following treatment discontinuation. There was no difference between drug and placebo-treated patients in the incidence of the pediatric patients who discontinued treatment due to psychotic and non-psychotic adverse reactions. The above psychiatric signs and symptoms should be monitored. 5.2 Suicidal Behavior and Ideation Antiepileptic drugs (AEDs), including levetiracetam tablets, increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Patients treated with any AED for any indication should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior. Pooled analyses of 199 placebo-controlled clinical trials (mono- and adjunctive therapy) of 11 different AEDs showed that patients randomized to one of the AEDs had approximately twice the risk (adjusted Relative Risk 1.8, 95% CI:1.2, 2.7) of suicidal thinking or behavior compared to patients randomized to placebo. In these trials, which had a median treatment duration of 12 weeks, the estimated incidence rate of suicidal behavior or ideation among 27,863 AED-treated patients was 0.43%, compared to 0.24% among 16,029 placebo-treated patients, representing an increase of approximately one case of suicidal thinking or behavior for every 530 patients treated. There were four suicides in drug-treated patients in the trials and none in placebo-treated patients, but the number is too small to allow any conclusion about drug effect on suicide. The increased risk of suicidal thoughts or behavior with AEDs was observed as early as one week after starting drug treatment with AEDs and persisted for the duration of treatment assessed. Because most trials included in the analysis did not extend beyond 24 weeks, the risk of suicidal thoughts or behavior beyond 24 weeks could not be assessed. The risk of suicidal thoughts or behavior was generally consistent among drugs in the data analyzed. The finding of increased risk with AEDs of varying mechanisms of action and across a range of indications suggests that the risk applies to all AEDs used for any indication. The risk did not vary substantially by age (5 to100 years) in the clinical trials analyzed. Table 2 shows absolute and relative risk by indication for all evaluated AEDs. Table 2: Risk by Indication for Antiepileptic Drugs in the Pooled Analysis Indication Placebo Patients with Events Per 1000 Patients Drug Patients with Events Per 1000 Patients Relative Risk: Incidence of Events in Drug Patients/Incide nce in Placebo Patients Risk Difference: Additional Drug Patients with Events Per 1000 Patients Epilepsy 1.0 3.4 3.5 2.4 Psychiatric 5.7 8.5 1.5 2.9 Other 1.0 1.8 1.9 0.9 Total 2.4 4.3 1.8 1.9 The relative risk for suicidal thoughts or behavior was higher in clinical trials for epilepsy than in clinical trials for psychiatric or other conditions, but the absolute risk differences were similar for the epilepsy and psychiatric indications. Anyone considering prescribing levetiracetam tablets or any other AED must balance the risk of suicidal thoughts or behaviors with the risk of untreated illness. Epilepsy and many other illnesses for which AEDs are prescribed are themselves associated with morbidity and mortality and an increased risk of suicidal thoughts and behavior. Should suicidal thoughts and behavior emerge during treatment, the prescriber needs to consider whether the emergence of these symptoms in any given patient may be related to the illness being treated. Patients, their caregivers, and families should be informed that AEDs increase the risk of suicidal thoughts and behavior and should be advised of the need to be alert for the emergence or worsening of the signs and symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts, behavior, or thoughts about self-harm. Behaviors of concern should be reported immediately to healthcare providers. 5.3 Somnolence and Fatigue In some patients, levetiracetam tablets causes somnolence and fatigue. The incidences of somnolence and fatigue provided below are from controlled adult partial onset seizure studies. In general, the incidences of somnolence and fatigue in the pediatric partial onset seizure studies, and in pediatric and adult myoclonic and primary generalized tonic-clonic seizure studies were comparable to those of the adult partial onset seizure studies. In controlled trials of adult patients with epilepsy experiencing partial onset seizures, 14.8% of levetiracetam tablets -treated patients reported somnolence, compared to 8.4% of placebo patients. There was no clear dose response up to 3000 mg/day. In a study where there was no titration, about 45% of patients receiving 4000 mg/day reported somnolence. The somnolence was considered serious in 0.3% of the treated patients, compared to 0% in the placebo group. About 3% of levetiracetam tablets -treated patients discontinued treatment due to somnolence, compared to 0.7% of placebo patients. In 1.4% of treated patients and in 0.9% of placebo patients the dose was reduced, while 0.3% of the treated patients were hospitalized due to somnolence. In controlled trials of adult patients with epilepsy experiencing partial onset seizures, 14.7% of levetiracetam tablets -treated patients reported asthenia, compared to 9.1% of placebo patients. Treatment was discontinued due to asthenia in 0.8% of treated patients as compared to 0.5% of placebo patients. In 0.5% of treated patients and in 0.2% of placebo patients the dose was reduced due to asthenia. Somnolence and asthenia occurred most frequently within the first 4 weeks of treatment. Patients should be monitored for these signs and symptoms and advised not to drive or operate machinery until they have gained sufficient experience on levetiracetam tablets to gauge whether it adversely affects their ability to drive or operate machinery. 5.4 Serious Dermatological Reactions Serious dermatological reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), have been reported in both children and adults treated with levetiracetam. The median time of onset is reported to be 14 to 17 days, but cases have been reported at least four months after initiation of treatment. Recurrence of the serious skin reactions following rechallenge with levetiracetam has also been reported. Levetiracetam tablets should be discontinued at the first sign of a rash, unless the rash is clearly not drug-related. If signs or symptoms suggest SJS/TEN, use of this drug should not be resumed and alternative therapy should be considered. 5.5 Coordination Difficulties Coordination difficulties were only observed in the adult partial onset seizure studies. A total of 3.4% of adult levetiracetam tablets -treated patients experienced coordination difficulties, (reported as either ataxia, abnormal gait, or incoordination) compared to 1.6% of placebo patients. A total of 0.4% of patients in controlled trials discontinued levetiracetam tablets treatment due to ataxia, compared to 0% of placebo patients. In 0.7% of treated patients and in 0.2% of placebo patients the dose was reduced due to coordination difficulties, while one of the treated patients was hospitalized due to worsening of pre-existing ataxia. These events occurred most frequently within the first 4 weeks of treatment. Patients should be monitored for these signs and symptoms and advised not to drive or operate machinery until they have gained sufficient experience on levetiracetam tablets to gauge whether it could adversely affect their ability to drive or operate machinery. 5.6 Withdrawal Seizures Antiepileptic drugs, including levetiracetam tablets, should be withdrawn gradually to minimize the potential of increased seizure frequency. 5.7 Hematologic Abnormalities Partial Onset Seizures Adults Minor, but statistically significant, decreases compared to placebo in total mean RBC count (0.03 x 10 6 /mm 3 ), mean hemoglobin (0.09 g/dL), and mean hematocrit (0.38%), were seen in levetiracetam tablets -treated patients in controlled trials. A total of 3.2% of treated and 1.8% of placebo patients had at least one possibly significant (≤2.8 x 10 9 /L) decreased WBC, and 2.4% of treated and 1.4% of placebo patients had at least one possibly significant (≤1.0 x 10 9 /L) decreased neutrophil count. Of the treated patients with a low neutrophil count, all but one rose towards or to baseline with continued treatment. No patient was discontinued secondary to low neutrophil counts. Pediatric Patients 4 Years to < 16 Years Statistically significant decreases in WBC and neutrophil counts were seen in levetiracetam tablets -treated patients as compared to placebo. The mean decreases from baseline in the levetiracetam tablets -treated group were -0.4 × 10 9 /L and -0.3 × 10 9 /L, respectively, whereas there were small increases in the placebo group. Mean relative lymphocyte counts increased by 1.7% in levetiracetam tablets -treated patients, compared to a decrease of 4% in placebo patients (statistically significant). In the controlled trial, more levetiracetam tablets -treated patients had a possibly clinically significant abnormally low WBC value (3.0% levetiracetam tablets -treated versus 0% placebo), however, there was no apparent difference between treatment groups with respect to neutrophil count (5.0% levetiracetam tablets -treated versus 4.2% placebo). No patient was discontinued secondary to low WBC or neutrophil counts. In the controlled cognitive and neuropsychological safety study, two subjects (6.1%) in the placebo group and 5 subjects (8.6%) in the levetiracetam tablets -treated group had high eosinophil count values that were possibly clinically significant (≥10% or ≥0.7 × 10 9 /L). Juvenile Myoclonic Epilepsy Although there were no obvious hematologic abnormalities observed in patients with JME, the limited number of patients makes any conclusion tentative. The data from the partial seizure patients should be considered to be relevant for JME patients. 5.8 Blood Pressure Increases In a randomized, placebo-controlled study in patients aged 1 month to <4 years of age, a significantly higher risk of at least one measured increase in diastolic blood pressure was observed in the levetiracetam tablets -treated patients (17%) compared to the placebo-treated patients (2%). There was no overall difference in mean diastolic blood pressure between the treatment groups. This disparity between the levetiracetam tablets and placebo treatment groups was not observed in the studies of older children or in adults. 5.9 Seizure Control During Pregnancy Physiological changes may gradually decrease plasma levels of levetiracetam throughout pregnancy. This decrease is more pronounced during the third trimester. It is recommended that patients be monitored carefully during pregnancy. Close monitoring should continue through the postpartum period especially if the dose was changed during pregnancy.

<table> <col width="17%"/> <col width="21%"/> <col width="21%"/> <col width="21%"/> <col width="21%"/> <tbody> <tr> <td align="justify" valign="top" styleCode=" Botrule Toprule Lrule Rrule "> Indication </td> <td valign="top" styleCode=" Botrule Toprule Lrule Rrule "> Placebo Patients with Events Per 1000 Patients </td> <td valign="top" styleCode=" Botrule Toprule Lrule Rrule "> Drug Patients with Events Per 1000 Patients </td> <td valign="top" styleCode=" Botrule Toprule Lrule Rrule "> Relative Risk: Incidence of Events in Drug Patients/Incide nce in Placebo Patients </td> <td valign="top" styleCode=" Botrule Toprule Lrule Rrule "> Risk Difference: Additional Drug Patients with Events Per 1000 Patients </td> </tr> <tr> <td align="justify" styleCode=" Botrule Toprule Lrule Rrule "> Epilepsy </td> <td align="justify" styleCode=" Botrule Toprule Lrule Rrule "> 1.0 </td> <td align="justify" styleCode=" Botrule Toprule Lrule Rrule "> 3.4 </td> <td align="justify" styleCode=" Botrule Toprule Lrule Rrule "> 3.5 </td> <td align="justify" styleCode=" Botrule Toprule Lrule Rrule "> 2.4 </td> </tr> <tr> <td align="justify" styleCode=" Botrule Toprule Lrule Rrule "> Psychiatric </td> <td align="justify" styleCode=" Botrule Toprule Lrule Rrule "> 5.7 </td> <td align="justify" styleCode=" Botrule Toprule Lrule Rrule "> 8.5 </td> <td align="justify" styleCode=" Botrule Toprule Lrule Rrule "> 1.5 </td> <td align="justify" styleCode=" Botrule Toprule Lrule Rrule "> 2.9 </td> </tr> <tr> <td align="justify" styleCode=" Botrule Toprule Lrule Rrule "> Other </td> <td align="justify" styleCode=" Botrule Toprule Lrule Rrule "> 1.0 </td> <td align="justify" styleCode=" Botrule Toprule Lrule Rrule "> 1.8 </td> <td align="justify" styleCode=" Botrule Toprule Lrule Rrule "> 1.9 </td> <td align="justify" styleCode=" Botrule Toprule Lrule Rrule "> 0.9 </td> </tr> <tr> <td align="justify" styleCode=" Botrule Toprule Lrule Rrule "> Total </td> <td align="justify" styleCode=" Botrule Toprule Lrule Rrule "> 2.4 </td> <td align="justify" styleCode=" Botrule Toprule Lrule Rrule "> 4.3 </td> <td align="justify" styleCode=" Botrule Toprule Lrule Rrule "> 1.8 </td> <td align="justify" styleCode=" Botrule Toprule Lrule Rrule "> 1.9 </td> </tr> </tbody> </table>

6 ADVERSE REACTIONS Most common adverse reactions (incidence in levetiracetam tablets -treated patients is ≥ 5% more than in placebo-treated patients) include: Adult patients: somnolence, asthenia, infection and dizziness ( 6.1 ) Pediatric patients: fatigue, aggression, nasal congestion, decreased appetite, and irritability ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Exelan Pharmaceuticals, Inc. at 1-855-295-7455 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. The following adverse reactions are discussed in more details in other sections of labeling: Psychiatric Symptoms [ see Warnings and Precautions (5.1) ] Suicidal Behavior and Ideation [ see Warnings and Precautions (5.2) ] Somnolence and Fatigue [ see Warnings and Precautions (5.3) ] Serious Dermatological Reactions [ see Warnings and Precautions (5.4) ] Coordination Difficulties [ see Warnings and Precautions (5.5) ] Withdrawal Seizures [ see Warnings and Precautions (5.6) ] Hematologic Abnormalities [ see Warnings and Precautions (5.7) ] Blood Pressure Increases [see Warnings and Precautions (5.8) ] Seizure Control During Pregnancy [ see Warnings and Precautions (5.9) ] 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 rates in the clinical trials of another drug and may not reflect the rates observed in practice. The prescriber should be aware that the adverse reaction incidence figures in the following tables, obtained when levetiracetam tablets was added to concurrent AED therapy, cannot be used to predict the frequency of adverse reactions in the course of usual medical practice where patient characteristics and other factors may differ from those prevailing during clinical trials. Similarly, the cited frequencies cannot be directly compared with figures obtained from other clinical investigations involving different treatments, uses, or investigators. An inspection of these frequencies, however, does provide the prescriber with one basis to estimate the relative contribution of drug and non-drug factors to the adverse reaction incidences in the population studied. Partial Onset Seizures Adults In controlled clinical studies in adults with partial onset seizures, the most frequently reported adverse reactions in patients receiving levetiracetam tablets in combination with other AEDs, for events with rates greater than placebo, were somnolence, asthenia, infection and dizziness. Of the most frequently reported adverse reactions in adults experiencing partial onset seizures, asthenia, somnolence and dizziness appeared to occur predominantly during the first 4 weeks of treatment with levetiracetam tablets. Table 3 lists adverse reactions that occurred in at least 1% of adult epilepsy patients treated with levetiracetam tablets participating in placebo-controlled studies and were numerically more common than in patients treated with placebo. In these studies, either levetiracetam tablets or placebo was added to concurrent AED therapy. Adverse reactions were usually mild to moderate in intensity. Table 3: Incidence (%) Of Adverse Reactions In Placebo-Controlled, Add-On Studies In Adults Experiencing Partial Onset Seizures By Body System (Adverse Reactions Occurred In At Least 1% Of levetiracetam tablets -Treated Patients And Occurred More Frequently Than Placebo-Treated Patients) Body System / Adverse Reaction Levetiracetam ( N = 769 ) % Placebo ( N = 439 ) % Body as a Whole Asthenia 15 9 Headache 14 13 Infection 13 8 Pain 7 6 Digestive System Anorexia 3 2 Nervous System Somnolence 15 8 Dizziness 9 4 Depression 4 2 Nervousness 4 2 Ataxia 3 1 Vertigo 3 1 Amnesia 2 1 Anxiety 2 1 Hostility 2 1 Paresthesia 2 1 Emotional Lability 2 0 Respiratory System Pharyngitis 6 4 Rhinitis 4 3 Cough Increased 2 1 Sinusitis 2 1 Special Senses Diplopia 2 1 In controlled adult clinical studies, 15% of patients receiving levetiracetam tablets and 12% receiving placebo either discontinued or had a dose reduction as a result of an adverse reaction. Table 4 lists the most common (>1%) adverse reactions that resulted in discontinuation or dose reduction and that occurred more frequently in levetiracetam tablets -treated patients than in placebo-treated patients Table 4: Adverse Reactions That Most Commonly Resulted In Discontinuation Or Dose Reduction That Occurred More Frequently In levetiracetam -Treated Patients In Placebo-Controlled Studies In Adult Patients Experiencing Partial Onset Seizures Adverse Reaction Levetiracetam ( N = 769 ) % Placebo ( N = 439 ) % Dizziness 1 0 Somnolence 4 2 Pediatric Patients 4 Years to <16 Years The adverse reaction data presented below was obtained from a pooled analysis of two controlled pediatric clinical studies in children 4 to 16 years of age with partial onset seizures. The adverse reactions most frequently reported with the use of levetiracetam tablets in combination with other AEDs, for events with rates greater than placebo, were fatigue, aggression, nasal congestion, decreased appetite, and irritability. Table 5 lists adverse reactions from the pooled pediatric controlled studies (4 to 16 years of age) that occurred in at least 2% of pediatric levetiracetam tablets -treated patients and were numerically more common than in pediatric patients treated with placebo. In these studies, either levetiracetam tablets or placebo was added to concurrent AED therapy. Adverse reactions were usually mild to moderate in intensity. Table 5: Incidence (%) Of Adverse Reactions In Pooled Placebo-Controlled, Add-On Studies In Pediatric Patients Ages 4 to 16 Years Experiencing Partial Onset Seizures By Body System (Adverse Reactions Occurred In At Least 2% Of levetiracetam -Treated Patients And Occurred More Frequently Than Placebo-Treated Patients) Body System / Adverse Reaction Levetiracetam ( N = 165 ) % Placebo ( N = 131 ) % Ear and Labyrinth Disorders Ear Pain 2 1 Eye Disorders Conjunctivitis 2 0 Gastrointestinal Disorders Vomiting 15 12 Abdominal Pain Upper 9 8 Diarrhea 6 5 Constipation 3 1 General Disorders and Administration Site Conditions Fatigue 11 5 Infections and Infestations Nasopharyngitis 15 12 Influenza 3 1 Gastroenteritis 2 0 Rhinitis 2 0 Injury , Poisoning and Procedural Complications Head Injury 4 0 Contusion 3 1 Fall 3 2 Joint Sprain 2 1 Metabolism and Nutrition Disorders Decreased Appetite 8 2 Anorexia 4 3 Musculoskeletal and Connective Tissue Disorders Arthralgia 2 0 Neck Pain 2 1 Nervous System Headache 19 15 Somnolence 13 9 Dizziness 7 5 Lethargy 6 2 Sedation 2 1 Psychiatric Disorders Aggression 10 5 Abnormal Behavior 7 4 Irritability 7 1 Insomnia 5 3 Agitation 4 1 Depression 3 1 Mood Altered 3 1 Affect Lability 2 1 Anxiety 2 1 Confusional State 2 0 Mood Swings 2 1 Respiratory , Thoracic and Mediastinal Disorders Cough 9 5 Nasal Congestion 9 2 Pharyngolaryngeal Pain 7 4 In the well-controlled pooled pediatric clinical studies in patients 4 to16 years of age, 7% of patients receiving levetiracetam tablets and 9% receiving placebo discontinued as a result of an adverse event. Adverse reaction information in pediatric patients less than 4 years of age as adjunctive therapy in the treatment of partial onset seizures is approved for UCB, Inc.’s levetiracetam tablets and oral solution. However, due to UCB Inc.’s marketing exclusivity rights, this drug product is not labeled with that pediatric information. Myoclonic Seizures Although the pattern of adverse reactions in this study seems somewhat different from that seen in patients with partial seizures, this is likely due to the much smaller number of patients in this study compared to partial seizure studies. The adverse reaction pattern for patients with JME is expected to be essentially the same as for patients with partial seizures. In the well-controlled clinical study that included both adolescent (12 to 16 years of age) and adult patients with myoclonic seizures, the most frequently reported adverse reactions in patients using levetiracetam tablets in combination with other AEDs, for events with rates greater than placebo, were somnolence, neck pain, and pharyngitis. Table 7 lists adverse reactions that occurred in at least 5% of juvenile myoclonic epilepsy patients experiencing myoclonic seizures treated with levetiracetam tablets and were numerically more common than in patients treated with placebo. In this study, either levetiracetam tablets or placebo was added to concurrent AED therapy. Adverse reactions were usually mild to moderate in intensity. Table 7: Incidence (%) Of Adverse Reactions In A Placebo-Controlled, Add-On Study In Patients 12 Years Of Age And Older With Myoclonic Seizures By Body System (Adverse Reactions Occurred In At Least 5% Of levetiracetam -Treated Patients And Occurred More Frequently Than Placebo-Treated Patients) Body System / Adverse Reaction Levetiracetam ( N = 60 ) % Placebo ( N = 60 ) % Ear and labyrinth disorders Vertigo 5 3 Infections and infestations Pharyngitis 7 0 Influenza 5 2 Musculoskeletal and connective tissue disorders Neck pain 8 2 Nervous system disorders Somnolence 12 2 Psychiatric disorders Depression 5 2 In the placebo-controlled study, 8% of patients receiving levetiracetam tablets and 2% receiving placebo either discontinued or had a dose reduction as a result of an adverse reaction. The adverse reactions that led to discontinuation or dose reduction and that occurred more frequently in levetiracetam tablets -treated patients than in placebo-treated patients are presented in Table 8. Table 8:Adverse Reactions That Resulted In Discontinuation Or Dose Reduction That Occurred More Frequently in levetiracetam -Treated Patients In The Placebo-Controlled Study In Patients With Juvenile Myoclonic Epilepsy Adverse Reaction Levetiracetam ( N = 60 ) % Placebo ( N = 60 ) % Anxiety 3 2 Depressed mood 2 0 Depression 2 0 Diplopia 2 0 Hypersomnia 2 0 Insomnia 2 0 Irritability 2 0 Nervousness 2 0 Somnolence 2 0 Primary Generalized Tonic-Clonic Seizures Although the pattern of adverse reactions in this study seems somewhat different from that seen in patients with partial seizures, this is likely due to the much smaller number of patients in this study compared to partial seizure studies. The adverse reaction pattern for patients with PGTC seizures is expected to be essentially the same as for patients with partial seizures. In the controlled clinical study that included patients 4 years of age and older with primary generalized tonic-clonic (PGTC) seizures, the most frequently reported adverse reaction in patients using levetiracetam tablets in combination with other AEDs, for events with rates greater than placebo, was nasopharyngitis. Table 9 lists adverse reactions that occurred in at least 5% of idiopathic generalized epilepsy patients experiencing PGTC seizures treated with levetiracetam tablets and were numerically more common than in patients treated with placebo. In this study, either levetiracetam tablets or placebo was added to concurrent AED therapy. Adverse reactions were usually mild to moderate in intensity. Table 9: Incidence (%) Of Adverse Reactions In A Placebo-Controlled, Add-On Study In Patients 4 Years Of Age And Older With PGTC Seizures By MedDRA System Organ Class (Adverse Reactions Occurred In At Least 5% Of levetiracetam -Treated Patients And Occurred More Frequently Than Placebo-Treated Patients) Body System / Adverse Reaction Levetiracetam ( N = 79 ) % Placebo ( N = 84 ) % Gastrointestinal disorders Diarrhea 8 7 General disorders and administration site conditions Fatigue 10 8 Infections and infestations Nasopharyngitis 14 5 Psychiatric disorders Irritability 6 2 Mood Swings 5 1 In the placebo-controlled study, 5% of patients receiving levetiracetam tablets and 8% receiving placebo either discontinued or had a dose reduction during the treatment period as a result of an adverse reaction. This study was too small to adequately characterize the adverse reactions that could be expected to result in discontinuation of treatment in this population. It is expected that the adverse reactions that would lead to discontinuation in this population would be similar to those resulting in discontinuation in other epilepsy trials (see tables 4 and 8). In addition, the following adverse reactions were seen in other well-controlled adult studies of levetiracetam tablets: balance disorder, disturbance in attention, eczema, memory impairment, myalgia, and vision blurred. Comparison of Gender, Age and Race The overall adverse reaction profile of levetiracetam tablets was similar between females and males. There are insufficient data to support a statement regarding the distribution of adverse experience reports by age and race. 6.2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of levetiracetam tablets. 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. In addition to the adverse reactions listed above, [ see Adverse Reactions (6.1) ], the following adverse events have been reported in patients receiving marketed levetiracetam tablets worldwide. The listing is alphabetized: abnormal liver function test, choreoathetosis, dyskinesia, erythema multiforme, hepatic failure, hepatitis, hyponatremia leukopenia, muscle weakness, neutropenia, pancreatitis, pancytopenia (with bone marrow suppression identified in some of these cases), panic attack, thrombocytopenia, and weight loss. Alopecia has been reported with levetiracetam tablets use; recovery was observed in majority of cases where levetiracetam tablets was discontinued.

<table> <col width="44%"/> <col width="36%"/> <col width="20%"/> <tbody> <tr> <td styleCode=" Botrule Toprule Lrule Rrule "> <content styleCode="bold">Body </content> <content styleCode="bold">System</content> <content styleCode="bold">/ </content> <content styleCode="bold">Adverse </content> <content styleCode="bold">Reaction</content> <content styleCode="bold"> </content> </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> <content styleCode="bold">Levetiracetam </content> <content styleCode="bold">(</content> <content styleCode="bold">N</content> <content styleCode="bold">=</content> <content styleCode="bold">769</content> <content styleCode="bold">) </content> <content styleCode="bold">%</content> <content styleCode="bold"> </content> </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> <content styleCode="bold">Placebo </content> <content styleCode="bold">(</content> <content styleCode="bold">N</content> <content styleCode="bold">=</content> <content styleCode="bold">439</content> <content styleCode="bold">) </content> <content styleCode="bold">%</content> <content styleCode="bold"> </content> </td> </tr> <tr> <td colspan="3" styleCode=" Botrule Toprule Lrule Rrule "> <content styleCode="bold">Body </content> <content styleCode="bold">as </content> <content styleCode="bold">a </content> <content styleCode="bold">Whole </content> </td> </tr> <tr> <td styleCode=" Botrule Toprule Lrule Rrule "> Asthenia </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 15 </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 9 </td> </tr> <tr> <td styleCode=" Botrule Toprule Lrule Rrule "> Headache </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 14 </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 13 </td> </tr> <tr> <td styleCode=" Botrule Toprule Lrule Rrule "> Infection </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 13 </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 8 </td> </tr> <tr> <td styleCode=" Botrule Toprule Lrule Rrule "> Pain </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 7 </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 6 </td> </tr> <tr> <td colspan="3" styleCode=" Botrule Toprule Lrule Rrule "> <content styleCode="bold">Digestive </content> <content styleCode="bold">System</content> </td> </tr> <tr> <td styleCode=" Botrule Toprule Lrule Rrule "> Anorexia </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 3 </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 2 </td> </tr> <tr> <td colspan="3" styleCode=" Botrule Toprule Lrule Rrule "> <content styleCode="bold">Nervous </content> <content styleCode="bold">System</content> </td> </tr> <tr> <td styleCode=" Botrule Toprule Lrule Rrule "> Somnolence </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 15 </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 8 </td> </tr> <tr> <td styleCode=" Botrule Toprule Lrule Rrule "> Dizziness </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 9 </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 4 </td> </tr> <tr> <td styleCode=" Botrule Toprule Lrule Rrule "> Depression </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 4 </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 2 </td> </tr> <tr> <td styleCode=" Botrule Toprule Lrule Rrule "> Nervousness </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 4 </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 2 </td> </tr> <tr> <td styleCode=" Botrule Toprule Lrule Rrule "> Ataxia </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 3 </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 1 </td> </tr> <tr> <td styleCode=" Botrule Toprule Lrule Rrule "> Vertigo </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 3 </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 1 </td> </tr> <tr> <td styleCode=" Botrule Toprule Lrule Rrule "> Amnesia </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 2 </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 1 </td> </tr> <tr> <td styleCode=" Botrule Toprule Lrule Rrule "> Anxiety </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 2 </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 1 </td> </tr> <tr> <td styleCode=" Botrule Toprule Lrule Rrule "> Hostility </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 2 </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 1 </td> </tr> <tr> <td styleCode=" Botrule Toprule Lrule Rrule "> Paresthesia </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 2 </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 1 </td> </tr> <tr> <td styleCode=" Botrule Toprule Lrule Rrule "> Emotional Lability </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 2 </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 0 </td> </tr> <tr> <td colspan="3" styleCode=" Botrule Toprule Lrule Rrule "> <content styleCode="bold">Respiratory </content> <content styleCode="bold">System </content> </td> </tr> <tr> <td styleCode=" Botrule Toprule Lrule Rrule "> Pharyngitis </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 6 </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 4 </td> </tr> <tr> <td styleCode=" Botrule Toprule Lrule Rrule "> Rhinitis </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 4 </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 3 </td> </tr> <tr> <td styleCode=" Botrule Toprule Lrule Rrule "> Cough Increased </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 2 </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 1 </td> </tr> <tr> <td styleCode=" Botrule Toprule Lrule Rrule "> Sinusitis </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 2 </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 1 </td> </tr> <tr> <td colspan="3" styleCode=" Botrule Toprule Lrule Rrule "> <content styleCode="bold">Special </content> <content styleCode="bold">Senses</content> </td> </tr> <tr> <td styleCode=" Botrule Toprule Lrule Rrule "> Diplopia </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 2 </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 1 </td> </tr> </tbody> </table>

<table> <col width="33%"/> <col width="39%"/> <col width="28%"/> <tbody> <tr> <td align="justify" valign="top" styleCode=" Botrule Toprule Lrule Rrule "> <content styleCode="bold">Adverse </content> <content styleCode="bold">Reaction </content> </td> <td align="center" valign="top" styleCode=" Botrule Toprule Lrule Rrule "> <content styleCode="bold">Levetiracetam </content> <content styleCode="bold">(</content> <content styleCode="bold">N</content> <content styleCode="bold">=</content> <content styleCode="bold">769</content> <content styleCode="bold">) </content> <content styleCode="bold"> </content> <content styleCode="bold">%</content> </td> <td align="center" valign="top" styleCode=" Botrule Toprule Lrule Rrule "> <content styleCode="bold">Placebo </content> <content styleCode="bold">(</content> <content styleCode="bold">N</content> <content styleCode="bold">=</content> <content styleCode="bold">439</content> <content styleCode="bold">)</content> <content styleCode="bold"> </content> <content styleCode="bold">%</content> </td> </tr> <tr> <td align="justify" styleCode=" Botrule Toprule Lrule Rrule "> Dizziness </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 1 </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 0 </td> </tr> <tr> <td align="justify" styleCode=" Botrule Toprule Lrule Rrule "> Somnolence </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 4 </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 2 </td> </tr> </tbody> </table>

<table> <col width="48%"/> <col width="33%"/> <col width="19%"/> <tbody> <tr> <td align="justify" valign="top" styleCode=" Botrule Toprule Lrule Rrule "> <content styleCode="bold">Body </content> <content styleCode="bold">System</content> <content styleCode="bold">/ </content> <content styleCode="bold"> </content> <content styleCode="bold">Adverse </content> <content styleCode="bold">Reaction </content> </td> <td align="center" valign="top" styleCode=" Botrule Toprule Lrule Rrule "> <content styleCode="bold">Levetiracetam </content> <content styleCode="bold">(</content> <content styleCode="bold">N</content> <content styleCode="bold">=</content> <content styleCode="bold">165</content> <content styleCode="bold">) </content> <content styleCode="bold"> </content> <content styleCode="bold">%</content> </td> <td align="center" valign="top" styleCode=" Botrule Toprule Lrule Rrule "> <content styleCode="bold">Placebo </content> <content styleCode="bold">(</content> <content styleCode="bold">N</content> <content styleCode="bold">=</content> <content styleCode="bold">131</content> <content styleCode="bold">) </content> <content styleCode="bold">%</content> </td> </tr> <tr> <td align="justify" colspan="3" styleCode=" Botrule Toprule Lrule Rrule "> <content styleCode="bold">Ear </content> <content styleCode="bold">and </content> <content styleCode="bold">Labyrinth </content> <content styleCode="bold">Disorders </content> </td> </tr> <tr> <td align="justify" styleCode=" Botrule Toprule Lrule Rrule "> Ear Pain </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 2 </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 1 </td> </tr> <tr> <td align="justify" colspan="3" styleCode=" Botrule Toprule Lrule Rrule "> <content styleCode="bold">Eye </content> <content styleCode="bold">Disorders</content> </td> </tr> <tr> <td align="justify" styleCode=" Botrule Toprule Lrule Rrule "> Conjunctivitis </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 2 </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 0 </td> </tr> <tr> <td align="justify" colspan="3" styleCode=" Botrule Toprule Lrule Rrule "> <content styleCode="bold">Gastrointestinal </content> <content styleCode="bold">Disorders</content> </td> </tr> <tr> <td align="justify" styleCode=" Botrule Toprule Lrule Rrule "> Vomiting </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 15 </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 12 </td> </tr> <tr> <td align="justify" styleCode=" Botrule Toprule Lrule Rrule "> Abdominal Pain Upper </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 9 </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 8 </td> </tr> <tr> <td align="justify" styleCode=" Botrule Toprule Lrule Rrule "> Diarrhea </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 6 </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 5 </td> </tr> <tr> <td align="justify" styleCode=" Botrule Toprule Lrule Rrule "> Constipation </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 3 </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 1 </td> </tr> <tr> <td colspan="3" styleCode=" Botrule Toprule Lrule Rrule "> <content styleCode="bold">General </content> <content styleCode="bold">Disorders </content> <content styleCode="bold">and </content> <content styleCode="bold"> </content> <content styleCode="bold">Administration </content> <content styleCode="bold">Site </content> <content styleCode="bold">Conditions</content> </td> </tr> <tr> <td align="justify" styleCode=" Botrule Toprule Lrule Rrule "> Fatigue </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 11 </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 5 </td> </tr> <tr> <td align="justify" colspan="3" styleCode=" Botrule Toprule Lrule Rrule "> <content styleCode="bold">Infections </content> <content styleCode="bold">and </content> <content styleCode="bold">Infestations</content> </td> </tr> <tr> <td align="justify" styleCode=" Botrule Toprule Lrule Rrule "> Nasopharyngitis </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 15 </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 12 </td> </tr> <tr> <td align="justify" styleCode=" Botrule Toprule Lrule Rrule "> Influenza </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 3 </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 1 </td> </tr> <tr> <td align="justify" styleCode=" Botrule Toprule Lrule Rrule "> Gastroenteritis </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 2 </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 0 </td> </tr> <tr> <td align="justify" styleCode=" Botrule Toprule Lrule Rrule "> Rhinitis </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 2 </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 0 </td> </tr> <tr> <td align="justify" colspan="3" styleCode=" Botrule Toprule Lrule Rrule "> <content styleCode="bold">Injury</content>, <content styleCode="bold">Poisoning </content> <content styleCode="bold">and </content> <content styleCode="bold"> </content> <content styleCode="bold">Procedural </content> <content styleCode="bold">Complications</content> </td> </tr> <tr> <td align="justify" styleCode=" Botrule Toprule Lrule Rrule "> Head Injury </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 4 </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 0 </td> </tr> <tr> <td align="justify" styleCode=" Botrule Toprule Lrule Rrule "> Contusion </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 3 </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 1 </td> </tr> <tr> <td align="justify" styleCode=" Botrule Toprule Lrule Rrule "> Fall </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 3 </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 2 </td> </tr> <tr> <td align="justify" styleCode=" Botrule Toprule Lrule Rrule "> Joint Sprain </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 2 </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 1 </td> </tr> <tr> <td align="justify" colspan="3" styleCode=" Botrule Toprule Lrule Rrule "> <content styleCode="bold">Metabolism </content> <content styleCode="bold">and </content> <content styleCode="bold">Nutrition </content> <content styleCode="bold"> </content> <content styleCode="bold">Disorders</content> </td> </tr> <tr> <td align="justify" styleCode=" Botrule Toprule Lrule Rrule "> Decreased Appetite </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 8 </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 2 </td> </tr> <tr> <td align="justify" styleCode=" Botrule Toprule Lrule Rrule "> Anorexia </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 4 </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 3 </td> </tr> <tr> <td align="justify" colspan="3" styleCode=" Botrule Toprule Lrule Rrule "> <content styleCode="bold">Musculoskeletal </content> <content styleCode="bold">and </content> <content styleCode="bold">Connective </content> <content styleCode="bold"> </content> <content styleCode="bold">Tissue </content> <content styleCode="bold">Disorders</content> </td> </tr> <tr> <td align="justify" styleCode=" Botrule Toprule Lrule Rrule "> Arthralgia </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 2 </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 0 </td> </tr> <tr> <td align="justify" styleCode=" Botrule Toprule Lrule Rrule "> Neck Pain </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 2 </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 1 </td> </tr> <tr> <td align="justify" colspan="3" styleCode=" Botrule Toprule Lrule Rrule "> <content styleCode="bold">Nervous </content> <content styleCode="bold">System</content> </td> </tr> <tr> <td align="justify" styleCode=" Botrule Toprule Lrule Rrule "> Headache </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 19 </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 15 </td> </tr> <tr> <td align="justify" styleCode=" Botrule Toprule Lrule Rrule "> Somnolence </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 13 </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 9 </td> </tr> <tr> <td align="justify" styleCode=" Botrule Toprule Lrule Rrule "> Dizziness </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 7 </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 5 </td> </tr> <tr> <td align="justify" styleCode=" Botrule Toprule Lrule Rrule "> Lethargy </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 6 </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 2 </td> </tr> <tr> <td align="justify" styleCode=" Botrule Toprule Lrule Rrule "> Sedation </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 2 </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 1 </td> </tr> <tr> <td align="justify" colspan="3" styleCode=" Botrule Toprule Lrule Rrule "> <content styleCode="bold">Psychiatric </content> <content styleCode="bold">Disorders</content> </td> </tr> <tr> <td align="justify" styleCode=" Botrule Toprule Lrule Rrule "> Aggression </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 10 </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 5 </td> </tr> <tr> <td align="justify" styleCode=" Botrule Toprule Lrule Rrule "> Abnormal Behavior </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 7 </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 4 </td> </tr> <tr> <td align="justify" styleCode=" Botrule Toprule Lrule Rrule "> Irritability </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 7 </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 1 </td> </tr> <tr> <td align="justify" styleCode=" Botrule Toprule Lrule Rrule "> Insomnia </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 5 </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 3 </td> </tr> <tr> <td align="justify" styleCode=" Botrule Toprule Lrule Rrule "> Agitation </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 4 </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 1 </td> </tr> <tr> <td align="justify" styleCode=" Botrule Toprule Lrule Rrule "> Depression </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 3 </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 1 </td> </tr> <tr> <td align="justify" styleCode=" Botrule Toprule Lrule Rrule "> Mood Altered </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 3 </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 1 </td> </tr> <tr> <td align="justify" styleCode=" Botrule Toprule Lrule Rrule "> Affect Lability </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 2 </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 1 </td> </tr> <tr> <td align="justify" styleCode=" Botrule Toprule Lrule Rrule "> Anxiety </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 2 </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 1 </td> </tr> <tr> <td align="justify" styleCode=" Botrule Toprule Lrule Rrule "> Confusional State </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 2 </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 0 </td> </tr> <tr> <td align="justify" styleCode=" Botrule Toprule Lrule Rrule "> Mood Swings </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 2 </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 1 </td> </tr> <tr> <td align="justify" colspan="3" styleCode=" Botrule Toprule Lrule Rrule "> <content styleCode="bold">Respiratory</content>, <content styleCode="bold">Thoracic </content> <content styleCode="bold">and </content> <content styleCode="bold"> </content> <content styleCode="bold">Mediastinal </content> <content styleCode="bold">Disorders</content> </td> </tr> <tr> <td align="justify" styleCode=" Botrule Toprule Lrule Rrule "> Cough </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 9 </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 5 </td> </tr> <tr> <td align="justify" styleCode=" Botrule Toprule Lrule Rrule "> Nasal Congestion </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 9 </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 2 </td> </tr> <tr> <td align="justify" styleCode=" Botrule Toprule Lrule Rrule "> Pharyngolaryngeal Pain </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 7 </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> 4 </td> </tr> </tbody> </table>