FDA label 6236abfb-1a85-404e-b19d-f67cf9c24725

5 WARNINGS AND PRECAUTIONS • Psychiatric Reactions: 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 extended-release tablets ( 5.3 ) • Withdrawal Seizures:Levetiracetam extended-release tablets must be gradually withdrawn ( 5.6 ) 5.1 Psychiatric Reactions Levetiracetam Extended-release Tablets: In some patients levetiracetam extended-release tablets cause behavioral abnormalities. A total of 6.5% of levetiracetam extended-release tablets-treated patients experienced non-psychotic behavioral disorders (reported as irritability and aggression) compared to 0% of placebo-treated patients. Irritability was reported in 6.5% of levetiracetam extended-release tablets-treated patients. Aggression was reported in 1.3% of levetiracetam extended-release tablets-treated patients. No patient discontinued treatment or had a dose reduction as a result of these adverse reactions. The number of patients exposed to levetiracetam extended-release tablets was considerably smaller than the number of patients exposed to immediate-release levetiracetam tablets in controlled trials. Therefore, certain adverse reactions observed in the immediate-release levetiracetam controlled trials will likely occur in patients receiving levetiracetam extended-release tablets. Immediate-Release Levetiracetam Tablets: A total of 13.3% of adult levetiracetam-treated patients compared to 6.2% of placebo patients experienced non-psychotic behavioral symptoms (reported as aggression, agitation, anger, anxiety, apathy, depersonalization, depression, emotional lability, hostility, irritability and nervousness). A total of 1.7% of adult levetiracetam-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-treated patients and in 0.5% of placebo patients. One percent of adult levetiracetam-treated patients experienced psychotic symptoms compared to 0.2% of placebo patients. Two (0.3%) adult levetiracetam-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. The above psychiatric signs and symptoms should be monitored. 5.2 Suicidal Behavior and Ideation Antiepileptic drugs (AEDs), including levetiracetam extended-release 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 to 100 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 1,000 Patients Drug Patients with Events Per 1,000 Patients Relative Risk: Incidence of Events in Drug Patients/Incidence in Placebo Patients Risk Difference: Additional Drug Patients with Events Per 1,000 Patients Epilepsy 1 3.4 3.5 2.4 Psychiatric 5.7 8.5 1.5 2.9 Other 1 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 extended-release tablets or any other AED must balance the risk of suicidal thoughts or behavior 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 Levetiracetam Extended-release Tablets: In the levetiracetam extended-release tablets double-blind, controlled trial in patients experiencing partial onset seizures, 7.8% of levetiracetam extended-release tablets-treated patients experienced somnolence compared to 2.5% of placebo-treated patients. No patient discontinued treatment or had a dose reduction as a result of these adverse reactions. The number of patients exposed to levetiracetam extended-release tablets was considerably smaller than the number of patients exposed to immediate-release levetiracetam tablets in controlled trials. Therefore, certain adverse reactions observed in the immediate-release levetiracetam controlled trials will likely occur in patients receiving levetiracetam extended-release tablets. Immediate-Release Levetiracetam Tablets: 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 levetiracetam-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 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 patients treated with levetiracetam. The median time of onset is reported to be 14 to 17 days, but cases have been reported at least 4 months after initiation of treatment. Recurrence of the serious skin reactions following rechallenge with levetiracetam has also been reported. Levetiracetam extended-release 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 not observed in the levetiracetam extended-release tablets controlled trial, however, the number of patients exposed to levetiracetam extended-release tablets was considerably smaller than the number of patients exposed to immediate-release levetiracetam tablets in controlled trials. However, adverse reactions observed in the immediate-release levetiracetam controlled trials may also occur in patients receiving levetiracetam extended-release tablets. Immediate-Release Levetiracetam Tablets: A total of 3.4% of adult 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 preexisting 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 to gauge whether it could adversely affect their ability to drive or operate machinery. 5.6 Withdrawal Seizures Antiepileptic drugs, including levetiracetam extended-release tablets, should be withdrawn gradually to minimize the potential of increased seizure frequency. 5.7 Hematologic Abnormalities Although there were no obvious hematologic abnormalities observed in treated patients in the levetiracetam extended-release tablets controlled study, the limited number of patients makes any conclusion tentative. The data from the partial seizure patients in the immediate-release levetiracetam controlled studies should be considered to be relevant for levetiracetam extended-release tablets-treated patients. In controlled trials of immediate-release levetiracetam tablets in patients experiencing 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 immediate-release levetiracetam-treated patients. 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 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. 5.8 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 ID="_Ref367886355"> <caption>Table 2: Risk by Indication for Antiepileptic Drugs in the Pooled Analysis</caption> <col width="13%"/> <col width="22%"/> <col width="21%"/> <col width="34%"/> <col width="26%"/> <tbody> <tr> <td styleCode="Botrule Toprule "> <paragraph>Indication</paragraph> </td> <td styleCode="Botrule Toprule "> <paragraph>Placebo Patients with Events Per 1,000 Patients</paragraph> </td> <td styleCode="Botrule Toprule "> <paragraph>Drug Patients with Events Per 1,000 Patients</paragraph> </td> <td styleCode="Botrule Toprule "> <paragraph>Relative Risk: Incidence of Events in Drug Patients/Incidence in Placebo Patients</paragraph> </td> <td styleCode="Botrule Toprule "> <paragraph>Risk Difference: Additional Drug Patients with Events Per 1,000 Patients</paragraph> </td> </tr> <tr> <td> <paragraph>Epilepsy</paragraph> </td> <td> <paragraph>1</paragraph> </td> <td> <paragraph>3.4</paragraph> </td> <td> <paragraph>3.5</paragraph> </td> <td> <paragraph>2.4</paragraph> </td> </tr> <tr> <td> <paragraph>Psychiatric</paragraph> </td> <td> <paragraph>5.7</paragraph> </td> <td> <paragraph>8.5</paragraph> </td> <td> <paragraph>1.5</paragraph> </td> <td> <paragraph>2.9</paragraph> </td> </tr> <tr> <td> <paragraph>Other</paragraph> </td> <td> <paragraph>1</paragraph> </td> <td> <paragraph>1.8</paragraph> </td> <td> <paragraph>1.9</paragraph> </td> <td> <paragraph>0.9</paragraph> </td> </tr> <tr> <td styleCode="Botrule "> <paragraph>Total</paragraph> </td> <td styleCode="Botrule "> <paragraph>2.4</paragraph> </td> <td styleCode="Botrule "> <paragraph>4.3</paragraph> </td> <td styleCode="Botrule "> <paragraph>1.8</paragraph> </td> <td styleCode="Botrule "> <paragraph>1.9</paragraph> </td> </tr> </tbody> </table>

6 ADVERSE REACTIONS The following adverse reactions are discussed in more details in other sections of labeling: • Psychiatric Reactions [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) ] • Seizure Control During Pregnancy [see Warnings and Precautions (5.8) ] • Most common adverse reactions (incidence in levetiracetam extended-release tablets-treated patients is ≥ 5% more than in placebo-treated patients) include: somnolence and irritability ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Mylan Pharmaceuticals Inc. at 1-877-446-3679 (1-877-4-INFO-RX) 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 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 table, obtained when levetiracetam extended-release tablets were 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. Levetiracetam Extended-release Tablets: In the controlled clinical study using levetiracetam extended-release tablets in patients with partial onset seizures, the most frequently reported adverse reactions in patients receiving levetiracetam extended-release tablets in combination with other AEDs, for events with rates greater than placebo, were irritability and somnolence. Table 3 lists adverse reactions that occurred in at least 5% of epilepsy patients treated with levetiracetam extended-release tablets participating in the placebo-controlled study and were numerically more common than in patients treated with placebo. In this study, either levetiracetam extended-release 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 the Placebo-Controlled, Add-on Study by Body System (Adverse Reactions Occurred in at Least 5% of Levetiracetam Extended-release Tablets-Treated Patients and Occurred More Frequently than Placebo-Treated Patients) Body System/Adverse Reaction Levetiracetam Extended-release Tablets (N = 77) % Placebo (N = 79) % Gastrointestinal Disorders Nausea 5 3 Infections and Infestations Influenza 8 4 Nasopharyngitis 7 5 Nervous System Disorders Somnolence 8 3 Dizziness 5 3 Psychiatric Disorders Irritability 7 0 Discontinuation or Dose Reduction in the Levetiracetam Extended-release Tablets Controlled Clinical Study: In the controlled clinical study using levetiracetam extended-release tablets, 5.2% of patients receiving levetiracetam extended-release tablets and 2.5% receiving placebo discontinued as a result of an adverse reaction. The adverse reactions that resulted in discontinuation and that occurred more frequently in levetiracetam extended-release tablets-treated patients than in placebo-treated patients were asthenia, epilepsy, mouth ulceration, rash and respiratory failure. Each of these adverse reactions led to discontinuation in a levetiracetam extended-release tablets-treated patient and no placebo-treated patients. Table 4 lists the adverse reactions seen in the controlled studies of immediate-release levetiracetam tablets in adult patients experiencing partial onset seizures. Although the pattern of adverse reactions in the levetiracetam extended-release tablets study seems somewhat different from that seen in partial onset seizure controlled studies for immediate-release levetiracetam tablets, this is possibly due to the much smaller number of patients in this study compared to the immediate-release tablet studies. The adverse reactions for levetiracetam extended-release tablets are expected to be similar to those seen with immediate-release levetiracetam tablets. Immediate-Release Levetiracetam Tablets: In controlled clinical studies of immediate-release levetiracetam tablets as adjunctive therapy to other AEDs in adults with partial onset seizures, the most frequently reported adverse reactions, for events with rates greater than placebo, were somnolence, asthenia, infection and dizziness. Table 4 lists adverse reactions that occurred in at least 1% of adult epilepsy patients treated with immediate-release levetiracetam tablets participating in placebo-controlled studies and were numerically more common than in patients treated with placebo. In these studies, either immediate-release levetiracetam tablets or placebo was added to concurrent AED therapy. Adverse reactions were usually mild to moderate in intensity. Table 4: 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 Immediate-Release Levetiracetam-Treated Patients and Occurred More Frequently than Placebo-Treated Patients) Body System/Adverse Reaction Immediate-release 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 addition, the following adverse reactions were seen in other well controlled studies of immediate-release levetiracetam tablets: balance disorder, disturbance in attention, eczema, hyperkinesia, memory impairment, myalgia, personality disorders, pruritus and vision blurred. Comparison of Gender, Age and Race: There are insufficient data for levetiracetam extended-release tablets to support a statement regarding the distribution of adverse experience reports by gender, age and race. 6.2 Post-Marketing Experience In addition to the adverse reactions listed above for immediate-release levetiracetam tablets [see Adverse Reactions (6.1) ] , the following adverse events have been identified during postapproval use of immediate-release 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. The listing is alphabetized: abnormal liver function test, choreoathetosis, dyskinesia, erythema multiforme, 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 immediate-release levetiracetam use; recovery was observed in majority of cases where immediate-release levetiracetam was discontinued.

<table ID="_Ref367879169"> <caption>Table 3: Incidence (%) of Adverse Reactions in the Placebo-Controlled, Add-on Study by Body System (Adverse Reactions Occurred in at Least 5% of Levetiracetam Extended-release Tablets-Treated Patients and Occurred More Frequently than Placebo-Treated Patients)</caption> <col width="33%"/> <col width="42%"/> <col width="10%"/> <tbody> <tr> <td align="center" styleCode="Rrule Botrule Lrule Toprule "> <paragraph> <content styleCode="bold">Body System/Adverse Reaction</content> </paragraph> </td> <td align="center" styleCode="Rrule Botrule Toprule "> <paragraph> <content styleCode="bold">Levetiracetam Extended-release Tablets </content> <content styleCode="bold">(N = 77)</content> <content styleCode="bold">%</content> </paragraph> </td> <td align="center" styleCode="Rrule Botrule Toprule "> <paragraph> <content styleCode="bold">Placebo</content> <content styleCode="bold">(N = 79)</content> <content styleCode="bold">%</content> </paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule "> <paragraph> <content styleCode="bold">Gastrointestinal Disorders</content> </paragraph> </td> <td styleCode="Rrule Botrule "/> <td styleCode="Rrule Botrule "/> </tr> <tr> <td styleCode="Rrule Lrule Botrule "> <paragraph> Nausea</paragraph> </td> <td align="center" styleCode="Rrule Botrule "> <paragraph>5</paragraph> </td> <td align="center" styleCode="Rrule Botrule "> <paragraph>3</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule "> <paragraph> <content styleCode="bold">Infections and Infestations</content> </paragraph> </td> <td styleCode="Rrule Botrule "/> <td styleCode="Rrule Botrule "/> </tr> <tr> <td styleCode="Rrule Lrule Botrule "> <paragraph> Influenza</paragraph> </td> <td align="center" styleCode="Rrule Botrule "> <paragraph>8</paragraph> </td> <td align="center" styleCode="Rrule Botrule "> <paragraph>4</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule "> <paragraph> Nasopharyngitis</paragraph> </td> <td align="center" styleCode="Rrule Botrule "> <paragraph>7</paragraph> </td> <td align="center" styleCode="Rrule Botrule "> <paragraph>5</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule "> <paragraph> <content styleCode="bold">Nervous System Disorders</content> </paragraph> </td> <td styleCode="Rrule Botrule "/> <td styleCode="Rrule Botrule "/> </tr> <tr> <td styleCode="Rrule Lrule Botrule "> <paragraph> Somnolence</paragraph> </td> <td align="center" styleCode="Rrule Botrule "> <paragraph>8</paragraph> </td> <td align="center" styleCode="Rrule Botrule "> <paragraph>3</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule "> <paragraph> Dizziness</paragraph> </td> <td align="center" styleCode="Rrule Botrule "> <paragraph>5</paragraph> </td> <td align="center" styleCode="Rrule Botrule "> <paragraph>3</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule "> <paragraph> <content styleCode="bold">Psychiatric Disorders</content> </paragraph> </td> <td styleCode="Rrule Botrule "/> <td styleCode="Rrule Botrule "/> </tr> <tr> <td styleCode="Rrule Botrule Lrule "> <paragraph> Irritability</paragraph> </td> <td align="center" styleCode="Rrule Botrule "> <paragraph>7</paragraph> </td> <td align="center" styleCode="Rrule Botrule "> <paragraph>0</paragraph> </td> </tr> </tbody> </table>

<table ID="_Ref367879219"> <caption>Table 4: 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 Immediate-Release Levetiracetam-Treated Patients and Occurred More Frequently than Placebo-Treated Patients)</caption> <col width="33%"/> <col width="35%"/> <col width="11%"/> <tbody> <tr> <td align="center" styleCode="Rrule Botrule Lrule Toprule "> <paragraph> <content styleCode="bold">Body System/Adverse Reaction</content> </paragraph> </td> <td align="center" styleCode="Rrule Botrule Toprule "> <paragraph> <content styleCode="bold">Immediate-release Levetiracetam </content> <content styleCode="bold">(N = 769)</content> <content styleCode="bold">%</content> </paragraph> </td> <td align="center" styleCode="Rrule Botrule Toprule "> <paragraph> <content styleCode="bold">Placebo</content> <content styleCode="bold">(N = 439)</content> <content styleCode="bold">%</content> </paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule "> <paragraph> <content styleCode="bold">Body as a Whole</content> </paragraph> </td> <td styleCode="Rrule Botrule "/> <td styleCode="Rrule Botrule "/> </tr> <tr> <td styleCode="Rrule Lrule Botrule "> <paragraph> Asthenia</paragraph> </td> <td align="center" styleCode="Rrule Botrule "> <paragraph>15</paragraph> </td> <td align="center" styleCode="Rrule Botrule "> <paragraph>9</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule "> <paragraph> Headache</paragraph> </td> <td align="center" styleCode="Rrule Botrule "> <paragraph>14</paragraph> </td> <td align="center" styleCode="Rrule Botrule "> <paragraph>13</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule "> <paragraph> Infection</paragraph> </td> <td align="center" styleCode="Rrule Botrule "> <paragraph>13</paragraph> </td> <td align="center" styleCode="Rrule Botrule "> <paragraph>8</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule "> <paragraph> Pain</paragraph> </td> <td align="center" styleCode="Rrule Botrule "> <paragraph>7</paragraph> </td> <td align="center" styleCode="Rrule Botrule "> <paragraph>6</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule "> <paragraph> <content styleCode="bold">Digestive System</content> </paragraph> </td> <td styleCode="Rrule Botrule "/> <td styleCode="Rrule Botrule "/> </tr> <tr> <td styleCode="Rrule Lrule Botrule "> <paragraph> Anorexia</paragraph> </td> <td align="center" styleCode="Rrule Botrule "> <paragraph>3</paragraph> </td> <td align="center" styleCode="Rrule Botrule "> <paragraph>2</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule "> <paragraph> <content styleCode="bold">Nervous System</content> </paragraph> </td> <td styleCode="Rrule Botrule "/> <td styleCode="Rrule Botrule "/> </tr> <tr> <td styleCode="Rrule Lrule Botrule "> <paragraph> Somnolence</paragraph> </td> <td align="center" styleCode="Rrule Botrule "> <paragraph>15</paragraph> </td> <td align="center" styleCode="Rrule Botrule "> <paragraph>8</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule "> <paragraph> Dizziness</paragraph> </td> <td align="center" styleCode="Rrule Botrule "> <paragraph>9</paragraph> </td> <td align="center" styleCode="Rrule Botrule "> <paragraph>4</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule "> <paragraph> Depression</paragraph> </td> <td align="center" styleCode="Rrule Botrule "> <paragraph>4</paragraph> </td> <td align="center" styleCode="Rrule Botrule "> <paragraph>2</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule "> <paragraph> Nervousness</paragraph> </td> <td align="center" styleCode="Rrule Botrule "> <paragraph>4</paragraph> </td> <td align="center" styleCode="Rrule Botrule "> <paragraph>2</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule "> <paragraph> Ataxia</paragraph> </td> <td align="center" styleCode="Rrule Botrule "> <paragraph>3</paragraph> </td> <td align="center" styleCode="Rrule Botrule "> <paragraph>1</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule "> <paragraph> Vertigo</paragraph> </td> <td align="center" styleCode="Rrule Botrule "> <paragraph>3</paragraph> </td> <td align="center" styleCode="Rrule Botrule "> <paragraph>1</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule "> <paragraph> Amnesia</paragraph> </td> <td align="center" styleCode="Rrule Botrule "> <paragraph>2</paragraph> </td> <td align="center" styleCode="Rrule Botrule "> <paragraph>1</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule "> <paragraph> Anxiety</paragraph> </td> <td align="center" styleCode="Rrule Botrule "> <paragraph>2</paragraph> </td> <td align="center" styleCode="Rrule Botrule "> <paragraph>1</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule "> <paragraph> Hostility</paragraph> </td> <td align="center" styleCode="Rrule Botrule "> <paragraph>2</paragraph> </td> <td align="center" styleCode="Rrule Botrule "> <paragraph>1</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule "> <paragraph> Paresthesia</paragraph> </td> <td align="center" styleCode="Rrule Botrule "> <paragraph>2</paragraph> </td> <td align="center" styleCode="Rrule Botrule "> <paragraph>1</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule "> <paragraph> Emotional Lability</paragraph> </td> <td align="center" styleCode="Rrule Botrule "> <paragraph>2</paragraph> </td> <td align="center" styleCode="Rrule Botrule "> <paragraph>0</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule "> <paragraph> <content styleCode="bold">Respiratory System</content> </paragraph> </td> <td styleCode="Rrule Botrule "/> <td styleCode="Rrule Botrule "/> </tr> <tr> <td styleCode="Rrule Lrule Botrule "> <paragraph> Pharyngitis</paragraph> </td> <td align="center" styleCode="Rrule Botrule "> <paragraph>6</paragraph> </td> <td align="center" styleCode="Rrule Botrule "> <paragraph>4</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule "> <paragraph> Rhinitis</paragraph> </td> <td align="center" styleCode="Rrule Botrule "> <paragraph>4</paragraph> </td> <td align="center" styleCode="Rrule Botrule "> <paragraph>3</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule "> <paragraph> Cough Increased</paragraph> </td> <td align="center" styleCode="Rrule Botrule "> <paragraph>2</paragraph> </td> <td align="center" styleCode="Rrule Botrule "> <paragraph>1</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule "> <paragraph> Sinusitis</paragraph> </td> <td align="center" styleCode="Rrule Botrule "> <paragraph>2</paragraph> </td> <td align="center" styleCode="Rrule Botrule "> <paragraph>1</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule "> <paragraph> <content styleCode="bold">Special Senses</content> </paragraph> </td> <td styleCode="Rrule Botrule "/> <td styleCode="Rrule Botrule "/> </tr> <tr> <td styleCode="Rrule Botrule Lrule "> <paragraph> Diplopia</paragraph> </td> <td align="center" styleCode="Rrule Botrule "> <paragraph>2</paragraph> </td> <td align="center" styleCode="Rrule Botrule "> <paragraph>1</paragraph> </td> </tr> </tbody> </table>