FDA label c7574abc-cd5e-4eed-9f92-1d091df78489

5 WARNINGS AND PRECAUTIONS Neuropsychiatric Adverse Reactions: Including: 1) Somnolence and fatigue, 2) Coordination difficulties and 3) Behavioral Abnormalities (e.g., psychotic symptoms, suicide ideation, and other abnormalities). (5.1) Withdrawal Seizures: Levetiracetam must be gradually withdrawn. (5.2) 5.1 Neuropsychiatric Adverse Reactions Partial Onset Seizures In some adults experiencing partial onset seizures, levetiracetam causes the occurrence of central nervous system adverse reactions that can be classified into the following categories: 1) somnolence and fatigue, 2) coordination difficulties, and 3) behavioral abnormalities. In controlled trials of adult patients with epilepsy experiencing partial onset seizures, 14.8% of levetiracetam-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-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 treated patients reported asthenia, compared to 9.1% of placebo patients. Treatment was discontinued 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. A total of 3.4% of levetiracetam-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 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. Somnolence, asthenia and coordination difficulties occurred most frequently within the first 4 weeks of treatment. In controlled trials of patients with epilepsy experiencing partial onset seizures, 5 (0.7%) of levetiracetam-treated patients experienced psychotic symptoms compared to 1 (0.2%) placebo patient. Two (0.3%) levetiracetam-treated patients were hospitalized and their treatment was discontinued. Both events, reported as psychosis, developed within the first week of treatment and resolved within 1 to 2 weeks following treatment discontinuation. Two other events, reported as hallucinations, occurred after 1-5 months and resolved within 2-7 days while the patients remained on treatment. In one patient experiencing psychotic depression occurring within a month, symptoms resolved within 45 days while the patient continued treatment. A total of 13.3% of levetiracetam patients experienced other behavioral symptoms (reported as aggression, agitation, anger, anxiety, apathy, depersonalization, depression, emotional lability, hostility, irritability, etc.) compared to 6.2% of placebo patients. Approximately half of these patients reported these events within the first 4 weeks. A total of 1.7% of treated patients discontinued treatment due to these events, compared to 0.2% of placebo patients. The treatment dose was reduced in 0.8% of treated patients and in 0.5% of placebo patients. A total of 0.8% of treated patients had a serious behavioral event (compared to 0.2% of placebo patients) and were hospitalized. In addition, 4 (0.5%) of treated patients attempted suicide compared to 0% of placebo patients. One of these patients completed suicide. In the other 3 patients, the events did not lead to discontinuation or dose reduction. The events occurred after patients had been treated for between 4 weeks and 6 months [ see Patient Counseling Information (17) ]. Myoclonic Seizures During clinical development, the number of patients with myoclonic seizures exposed to levetiracetam was considerably smaller than the number with partial seizures. Therefore, under-reporting of certain adverse reactions was more likely to occur in the myoclonic seizure population. In some patients experiencing myoclonic seizures, levetiracetam causes somnolence and behavioral abnormalities. It is expected that the events seen in partial seizure patients would occur in patients with JME. In the double-blind, controlled trial in patients with juvenile myoclonic epilepsy experiencing myoclonic seizures, 11.7% of levetiracetam-treated patients experienced somnolence compared to 1.7% of placebo patients. No patient discontinued treatment as a result of somnolence. In 1.7% of levetiracetam-treated patients and in 0% of placebo patients the dose was reduced as a result of somnolence. Non-psychotic behavioral disorders (reported as aggression and irritability) occurred in 5% of the levetiracetam-treated patients compared to 0% of placebo patients. Non-psychotic mood disorders (reported as depressed mood, depression, and mood swings) occurred in 6.7% of levetiracetam-treated patients compared to 3.3% of placebo patients. A total of 5.0% of levetiracetam-treated patients had a reduction in dose or discontinued treatment due to behavioral or psychiatric events (reported as anxiety, depressed mood, depression, irritability, and nervousness), compared to 1.7% of placebo patients. Primary Generalized Tonic-Clonic Seizures During clinical development, the number of patients with primary generalized tonic-clonic epilepsy exposed to levetiracetam was considerably smaller than the number with partial epilepsy, described above. As in the partial seizure patients, behavioral symptoms appeared to be associated with levetiracetam treatment. Gait disorders and somnolence were also described in the study in primary generalized seizures, but with no difference between placebo and levetiracetam treatment groups and no appreciable discontinuations. Although it may be expected that drug related events seen in partial seizure patients would be seen in primary generalized epilepsy patients (e.g. somnolence and gait disturbance), these events may not have been observed because of the smaller sample size. In some patients experiencing primary generalized tonic-clonic seizures, levetiracetam causes behavioral abnormalities. In the double-blind, controlled trial in patients with idiopathic generalized epilepsy experiencing primary generalized tonic-clonic seizures, irritability was the most frequently reported psychiatric adverse event occurring in 6.3% of levetiracetam-treated patients compared to 2.4% of placebo patients. Additionally, non-psychotic behavioral disorders (reported as abnormal behavior, aggression, conduct disorder, and irritability) occurred in 11.4% of the levetiracetam-treated patients compared to 3.6% of placebo patients. Of the levetiracetam-treated patients experiencing non-psychotic behavioral disorders, one patient discontinued treatment due to aggression. Non-psychotic mood disorders (reported as anger, apathy, depression, mood altered, mood swings, negativism, suicidal ideation, and tearfulness) occurred in 12.7% of levetiracetam-treated patients compared to 8.3% of placebo patients. No levetiracetam-treated patients discontinued or had a dose reduction as a result of these events. One levetiracetam-treated patient experienced suicidal ideation. One patient experienced delusional behavior that required the lowering of the dose of levetiracetam. In a long-term open label study that examined patients with various forms of primary generalized epilepsy, along with the non-psychotic behavioral disorders, 2 of 192 patients studied exhibited psychotic-like behavior. Behavior in one case was characterized by auditory hallucinations and suicidal thoughts and led to levetiracetam discontinuation. The other case was described as worsening of pre-existent schizophrenia and did not lead to drug discontinuation. 5.2 Withdrawal Seizures Antiepileptic drugs, including levetiracetam, should be withdrawn gradually to minimize the potential of increased seizure frequency. 5.3 Hematologic Abnormalities Partial Onset Seizures 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-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. 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. 5.4 Hepatic Abnormalities There were no meaningful changes in mean liver function tests (LFT) in controlled trials in adult patients; lesser LFT abnormalities were similar in drug and placebo treated patients in controlled trials (1.4%). No patients were discontinued from controlled trials for LFT abnormalities except for 1 (0.07%) adult epilepsy patient receiving open treatment. 5.5 Laboratory Tests Although most laboratory tests are not systematically altered with levetiracetam treatment, there have been relatively infrequent abnormalities seen in hematologic parameters and liver function tests.

6 ADVERSE REACTIONS Most common adverse reactions (difference in incidence rate is ≥5% between levetiracetam-treated patients and placebo-treated patients and occurred more frequently in levetiracetam-treated patients) include: somnolence, asthenia, infection, and dizziness (6.1) . Important behavioral adverse reactions (incidence of levetiracetam-treated patients > placebo-treated patients, but <5%) include depression, nervousness, anxiety, and emotional lability (6.1) . To report SUSPECTED ADVERSE REACTIONS, contact West-ward Pharmaceutical Corp. at 1-877-233-2001, or the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Studies 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 adverse reactions that result from levetiracetam injection use include all of those reported for levetiracetam tablets and oral solution. Equivalent doses of intravenous (IV) levetiracetam and oral levetiracetam result in equivalent C max , C min , and total systemic exposure to levetiracetam when the IV levetiracetam is administered as a 15 minute infusion. The prescriber should be aware that the adverse reaction incidence figures in the following tables, obtained when levetiracetam was added to concurrent AED therapy, cannot be used to predict the frequency of adverse experiences in the course of usual medical practice where patient characteristics and other factors may differ from those prevailing during clinical studies. 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 In well-controlled clinical studies using levetiracetam tablets in adults with partial onset seizures, the most frequently reported adverse reactions in patients receiving levetiracetam in combination with other AEDs, not seen at an equivalent frequency among placebo-treated patients, were somnolence, asthenia, infection and dizziness. Of the most frequently reported adverse reactions in placebo-controlled studies using levetiracetam tablets in adults experiencing partial onset seizures, asthenia, somnolence and dizziness appeared to occur predominantly during the first 4 weeks of treatment with levetiracetam. Table 3 lists treatment-emergent 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 or placebo was added to concurrent AED therapy. Adverse reactions were usually mild to moderate in intensity. Table 3: Incidence (%) of Treatment-Emergent 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-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 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 using levetiracetam tablets in patients with myoclonic seizures, the most frequently reported adverse reactions in patients using levetiracetam in combination with other AEDs, not seen at an equivalent frequency among placebo-treated patients, were somnolence, neck pain, and pharyngitis. Table 4 lists treatment-emergent 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 or placebo was added to concurrent AED therapy. Adverse reactions were usually mild to moderate in intensity. Table 4: Incidence (%) of Treatment-Emergent Adverse Reactions in a Placebo-Controlled, Add-On Study in Patients 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 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 well-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 associated with the use of levetiracetam in combination with other AEDs, not seen at an equivalent frequency among placebo-treated patients, was nasopharyngitis. Table 5 lists treatment-emergent adverse reactions that occurred in at least 5% of idiopathic generalized epilepsy patients experiencing PGTC seizures treated with levetiracetam and were numerically more common than in patients treated with placebo. In this study, either levetiracetam or placebo was added to concurrent AED therapy. Adverse reactions were usually mild to moderate in intensity. Table 5: Incidence (%) of Treatment-Emergent 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 Discontinuation or Dose Reduction in Well-Controlled Clinical Studies Partial Onset Seizures In well-controlled adult clinical studies using levetiracetam tablets, 15.0% of patients receiving levetiracetam and 11.6% receiving placebo either discontinued or had a dose reduction as a result of an adverse event. Table 6 lists the most common (>1%) adverse reactions that resulted in discontinuation or dose reduction and that occurred more frequently in levetiracetam-treated patients than in placebo-treated patients. Table 6: 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) n (%) Placebo (N=439) n (%) Asthenia 10 (1.3%) 3 (0.7%) Dizziness 11 (1.4%) 0 Somnolence 34 (4.4%) 7 (1.6%) Myoclonic Seizures In the placebo-controlled study using levetiracetam tablets, 8.3% of patients receiving levetiracetam and 1.7% receiving placebo either discontinued or had a dose reduction as a result of an adverse event. The adverse reactions that led to discontinuation or dose reduction in the well-controlled study and that occurred more frequently in levetiracetam-treated patients than in placebo-treated patients are presented in Table 7. Table 7: 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) n (%) Placebo (N=60) n (%) Anxiety 2 (3.3%) 1 (1.7%) Depressed mood 1 (1.7%) 0 Depression 1 (1.7%) 0 Diplopia 1 (1.7%) 0 Hypersomnia 1 (1.7%) 0 Insomnia 1 (1.7%) 0 Irritability 1 (1.7%) 0 Nervousness 1 (1.7%) 0 Somnolence 1 (1.7%) 0 Primary Generalized Tonic-Clonic Seizures In the placebo-controlled study, 5.1% of patients receiving levetiracetam and 8.3% receiving placebo either discontinued or had a dose reduction during the treatment period as a result of a treatment-emergent adverse reaction. This study was too small to adequately characterize the adverse reactions leading to discontinuation. 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 6 - 7). Comparison of Gender, Age and Race The overall adverse experience profile of levetiracetam 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 events have been identified during postapproval use of levetiracetam. Because these events 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 worldwide. The listing is alphabetized: abnormal liver function test, hepatic failure, hepatitis, leukopenia, neutropenia, pancreatitis, pancytopenia (with bone marrow suppression identified in some of these cases), thrombocytopenia and weight loss. Alopecia has been reported with levetiracetam use; recovery was observed in majority of cases where levetiracetam was discontinued. There have been reports of suicidal behavior (including completed suicide, suicide attempt and suicidal ideation) with marketed levetiracetam [ see Patient Counseling Information (17) ].

<table> <caption>Table 3: Incidence (%) of Treatment-Emergent 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-Treated Patients and Occurred More Frequently than Placebo-Treated Patients)</caption> <col/> <col/> <col/> <thead> <tr> <td valign="top"> <content styleCode="bold">Body System/ Adverse Reaction</content> </td> <td align="center"> <content styleCode="bold">Levetiracetam(N=769) %</content> </td> <td align="center"> <content styleCode="bold">Placebo (N=439) %</content> </td> </tr> </thead> <tbody> <tr> <td> <content styleCode="bold">Body as a Whole</content> </td> <td align="center"> <content styleCode="bold"> </content> </td> <td align="center"> <content styleCode="bold"> </content> </td> </tr> <tr> <td> Asthenia</td> <td align="center"> 15</td> <td align="center"> 9</td> </tr> <tr> <td> Headache</td> <td align="center"> 14</td> <td align="center"> 13</td> </tr> <tr> <td> Infection</td> <td align="center"> 13</td> <td align="center"> 8</td> </tr> <tr> <td> Pain</td> <td align="center"> 7</td> <td align="center"> 6</td> </tr> <tr> <td> <content styleCode="bold">Digestive System</content> </td> <td align="center"> <content styleCode="bold"> </content> </td> <td align="center"> <content styleCode="bold"> </content> </td> </tr> <tr> <td> Anorexia</td> <td align="center"> 3</td> <td align="center"> 2</td> </tr> <tr> <td> <content styleCode="bold">Nervous System</content> </td> <td align="center"> <content styleCode="bold"> </content> </td> <td align="center"> <content styleCode="bold"> </content> </td> </tr> <tr> <td> Somnolence</td> <td align="center"> 15</td> <td align="center"> 8</td> </tr> <tr> <td> Dizziness</td> <td align="center"> 9</td> <td align="center"> 4</td> </tr> <tr> <td> Depression</td> <td align="center"> 4</td> <td align="center"> 2</td> </tr> <tr> <td> Nervousness</td> <td align="center"> 4</td> <td align="center"> 2</td> </tr> <tr> <td> Ataxia</td> <td align="center"> 3</td> <td align="center"> 1</td> </tr> <tr> <td> Vertigo</td> <td align="center"> 3</td> <td align="center"> 1</td> </tr> <tr> <td> Amnesia</td> <td align="center"> 2</td> <td align="center"> 1</td> </tr> <tr> <td> Anxiety</td> <td align="center"> 2</td> <td align="center"> 1</td> </tr> <tr> <td> Hostility</td> <td align="center"> 2</td> <td align="center"> 1</td> </tr> <tr> <td> Paresthesia</td> <td align="center"> 2</td> <td align="center"> 1</td> </tr> <tr> <td> Emotional Lability</td> <td align="center"> 2</td> <td align="center"> 0</td> </tr> <tr> <td> <content styleCode="bold">Respiratory System</content> </td> <td align="center"> <content styleCode="bold"> </content> </td> <td align="center"> <content styleCode="bold"> </content> </td> </tr> <tr> <td> Pharyngitis</td> <td align="center"> 6</td> <td align="center"> 4</td> </tr> <tr> <td> Rhinitis</td> <td align="center"> 4</td> <td align="center"> 3</td> </tr> <tr> <td> Cough Increased</td> <td align="center"> 2</td> <td align="center"> 1</td> </tr> <tr> <td> Sinusitis</td> <td align="center"> 2</td> <td align="center"> 1</td> </tr> <tr> <td> <content styleCode="bold">Special Senses</content> </td> <td align="center"> <content styleCode="bold"> </content> </td> <td align="center"> <content styleCode="bold"> </content> </td> </tr> <tr> <td> Diplopia</td> <td align="center"> 2</td> <td align="center"> 1</td> </tr> </tbody> </table>

<table> <caption>Table 4: Incidence (%) of Treatment-Emergent Adverse Reactions in a Placebo-Controlled, Add-On Study in Patients 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)</caption> <col/> <col/> <col/> <thead> <tr> <td valign="top"> <content styleCode="bold">Body System/ Adverse Reaction</content> </td> <td align="center"> <paragraph> <content styleCode="bold">Levetiracetam </content> <content styleCode="bold">(N=60) %</content> </paragraph> </td> <td align="center"> <content styleCode="bold">Placebo (N=60) %</content> </td> </tr> </thead> <tbody> <tr> <td> <content styleCode="bold">Ear and labyrinth disorders</content> </td> <td align="center"> <content styleCode="bold"> </content> </td> <td align="center"> <content styleCode="bold"> </content> </td> </tr> <tr> <td> Vertigo</td> <td align="center"> 5</td> <td align="center"> 3</td> </tr> <tr> <td> <content styleCode="bold">Infections and infestations</content> </td> <td align="center"> <content styleCode="bold"> </content> </td> <td align="center"> <content styleCode="bold"> </content> </td> </tr> <tr> <td> Pharyngitis</td> <td align="center"> 7</td> <td align="center"> 0</td> </tr> <tr> <td> Influenza</td> <td align="center"> 5</td> <td align="center"> 2</td> </tr> <tr> <td> <content styleCode="bold">Musculoskeletal and connective tissue disorders</content> </td> <td align="center"> <content styleCode="bold"> </content> </td> <td align="center"> <content styleCode="bold"> </content> </td> </tr> <tr> <td> Neck pain</td> <td align="center"> 8</td> <td align="center"> 2</td> </tr> <tr> <td> <content styleCode="bold">Nervous system disorders</content> </td> <td align="center"> <content styleCode="bold"> </content> </td> <td align="center"> <content styleCode="bold"> </content> </td> </tr> <tr> <td> Somnolence</td> <td align="center"> 12</td> <td align="center"> 2</td> </tr> <tr> <td> <content styleCode="bold">Psychiatric disorders</content> </td> <td align="center"> <content styleCode="bold"> </content> </td> <td align="center"> <content styleCode="bold"> </content> </td> </tr> <tr> <td> Depression</td> <td align="center"> 5</td> <td align="center"> 2</td> </tr> </tbody> </table>

<table> <caption>Table 5: Incidence (%) of Treatment-Emergent 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)</caption> <col/> <col/> <col/> <thead> <tr> <td valign="top"> <content styleCode="bold">Body System/ Adverse Reaction</content> </td> <td align="center"> <paragraph> <content styleCode="bold">Levetiracetam </content> <content styleCode="bold">(N=79) %</content> </paragraph> </td> <td align="center"> <content styleCode="bold">Placebo (N=84) %</content> </td> </tr> </thead> <tbody> <tr> <td> <content styleCode="bold">Gastrointestinal disorders</content> </td> <td align="center"> <content styleCode="bold"> </content> </td> <td align="center"> <content styleCode="bold"> </content> </td> </tr> <tr> <td> Diarrhea</td> <td align="center"> 8</td> <td align="center"> 7</td> </tr> <tr> <td> <content styleCode="bold">General disorders and administration site conditions</content> </td> <td align="center"> <content styleCode="bold"> </content> </td> <td align="center"> <content styleCode="bold"> </content> </td> </tr> <tr> <td> Fatigue</td> <td align="center"> 10</td> <td align="center"> 8</td> </tr> <tr> <td> <content styleCode="bold">Infections and infestations</content> </td> <td align="center"> <content styleCode="bold"> </content> </td> <td align="center"> <content styleCode="bold"> </content> </td> </tr> <tr> <td> Nasopharyngitis</td> <td align="center"> 14</td> <td align="center"> 5</td> </tr> <tr> <td> <content styleCode="bold">Psychiatric disorders</content> </td> <td align="center"> <content styleCode="bold"> </content> </td> <td align="center"> <content styleCode="bold"> </content> </td> </tr> <tr> <td> Irritability</td> <td align="center"> 6</td> <td align="center"> 2</td> </tr> <tr> <td> Mood swings</td> <td align="center"> 5</td> <td align="center"> 1</td> </tr> </tbody> </table>