FDA label 6cfb8e78-e2ea-6603-e053-2991aa0aacb3

WARNING: SUICIDAL IDEATION IN CHILDREN AND ADOLESCENTS STRATTERA (atomoxetine) increased the risk of suicidal ideation in short-term studies in children or adolescents with Attention-Deficit/Hyperactivity Disorder (ADHD). Anyone considering the use of STRATTERA in a child or adolescent must balance this risk with the clinical need. Co-morbidities occurring with ADHD may be associated with an increase in the risk of suicidal ideation and/or behavior. Patients who are started on therapy should be monitored closely for suicidality (suicidal thinking and behavior), clinical worsening, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. STRATTERA is approved for ADHD in pediatric and adult patients. STRATTERA is not approved for major depressive disorder. Pooled analyses of short-term (6 to 18 weeks) placebo-controlled trials of STRATTERA in children and adolescents (a total of 12 trials involving over 2200 patients, including 11 trials in ADHD and 1 trial in enuresis) have revealed a greater risk of suicidal ideation early during treatment in those receiving STRATTERA compared to placebo. The average risk of suicidal ideation in patients receiving STRATTERA was 0.4% (5/1357 patients), compared to none in placebo-treated patients (851 patients). No suicides occurred in these trials [see Warnings and Precautions ( 5.1 )] . WARNING: SUICIDAL IDEATION IN CHILDREN AND ADOLESCENTS See full prescribing information for complete boxed warning. Increased risk of suicidal ideation in children or adolescents ( 5.1 ) No suicides occurred in clinical trials ( 5.1 ) Patients started on therapy should be monitored closely ( 5.1 )

5 WARNINGS AND PRECAUTIONS Suicidal Ideation – Monitor for suicidality, clinical worsening, and unusual changes in behavior. ( 5.1 ) Severe Liver Injury – Should be discontinued and not restarted in patients with jaundice or laboratory evidence of liver injury. ( 5.2 ) Serious Cardiovascular Events – Sudden death, stroke and myocardial infarction have been reported in association with atomoxetine treatment. Patients should have a careful history and physical exam to assess for presence of cardiovascular disease. STRATTERA generally should not be used in children or adolescents with known serious structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, or other serious cardiac problems that may place them at increased vulnerability to its noradrenergic effects. Consideration should be given to not using STRATTERA in adults with clinically significant cardiac abnormalities. ( 5.3 ) Emergent Cardiovascular Symptoms – Patients should undergo prompt cardiac evaluation. ( 5.3 ) Effects on Blood Pressure and Heart Rate – Increase in blood pressure and heart rate; orthostasis and syncope may occur. Use with caution in patients with hypertension, tachycardia, or cardiovascular or cerebrovascular disease. ( 5.4 ) Emergent Psychotic or Manic Symptoms – Consider discontinuing treatment if such new symptoms occur. ( 5.5 ) Bipolar Disorder – Screen patients to avoid possible induction of a mixed/manic episode. ( 5.6 ) Aggressive behavior or hostility should be monitored. ( 5.7 ) Possible allergic reactions, including anaphylactic reactions, angioneurotic edema, urticaria, and rash. ( 5.8 ) Effects on Urine Outflow – Urinary hesitancy and retention may occur. ( 5.9 ) Priapism – Prompt medical attention is required in the event of suspected priapism. ( 5.10 , 17.5 ) Growth – Height and weight should be monitored in pediatric patients. ( 5.11 ) Concomitant Use of Potent CYP2D6 Inhibitors or Use in patients known to be CYP2D6 PMs – Dose adjustment of STRATTERA may be necessary. ( 5.13 ) 5.1 Suicidal Ideation STRATTERA increased the risk of suicidal ideation in short-term studies in children and adolescents with Attention-Deficit/Hyperactivity Disorder (ADHD). Pooled analyses of short-term (6 to 18 weeks) placebo-controlled trials of STRATTERA in children and adolescents have revealed a greater risk of suicidal ideation early during treatment in those receiving STRATTERA. There were a total of 12 trials (11 in ADHD and 1 in enuresis) involving over 2200 patients (including 1357 patients receiving STRATTERA and 851 receiving placebo). The average risk of suicidal ideation in patients receiving STRATTERA was 0.4% (5/1357 patients), compared to none in placebo-treated patients. There was 1 suicide attempt among these approximately 2200 patients, occurring in a patient treated with STRATTERA. No suicides occurred in these trials. All reactions occurred in children 12 years of age or younger. All reactions occurred during the first month of treatment. It is unknown whether the risk of suicidal ideation in pediatric patients extends to longer-term use. A similar analysis in adult patients treated with STRATTERA for either ADHD or major depressive disorder (MDD) did not reveal an increased risk of suicidal ideation or behavior in association with the use of STRATTERA. All pediatric patients being treated with STRATTERA should be monitored appropriately and observed closely for clinical worsening, suicidality, and unusual changes in behavior, especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases. The following symptoms have been reported with STRATTERA: anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania and mania. Although a causal link between the emergence of such symptoms and the emergence of suicidal impulses has not been established, there is a concern that such symptoms may represent precursors to emerging suicidality. Thus, patients being treated with STRATTERA should be observed for the emergence of such symptoms. Consideration should be given to changing the therapeutic regimen, including possibly discontinuing the medication, in patients who are experiencing emergent suicidality or symptoms that might be precursors to emerging suicidality, especially if these symptoms are severe or abrupt in onset, or were not part of the patient's presenting symptoms. Families and caregivers of pediatric patients being treated with STRATTERA should be alerted about the need to monitor patients for the emergence of agitation, irritability, unusual changes in behavior, and the other symptoms described above, as well as the emergence of suicidality, and to report such symptoms immediately to healthcare providers. Such monitoring should include daily observation by families and caregivers. 5.2 Severe Liver Injury Postmarketing reports indicate that STRATTERA can cause severe liver injury. Although no evidence of liver injury was detected in clinical trials of about 6000 patients, there have been rare cases of clinically significant liver injury that were considered probably or possibly related to STRATTERA use in postmarketing experience. Rare cases of liver failure have also been reported, including a case that resulted in a liver transplant. Because of probable underreporting, it is impossible to provide an accurate estimate of the true incidence of these reactions. Reported cases of liver injury occurred within 120 days of initiation of atomoxetine in the majority of cases and some patients presented with markedly elevated liver enzymes [>20 X upper limit of normal (ULN)], and jaundice with significantly elevated bilirubin levels (>2 X ULN), followed by recovery upon atomoxetine discontinuation. In one patient, liver injury, manifested by elevated hepatic enzymes up to 40 X ULN and jaundice with bilirubin up to 12 X ULN, recurred upon rechallenge, and was followed by recovery upon drug discontinuation, providing evidence that STRATTERA likely caused the liver injury. Such reactions may occur several months after therapy is started, but laboratory abnormalities may continue to worsen for several weeks after drug is stopped. The patient described above recovered from his liver injury, and did not require a liver transplant. STRATTERA should be discontinued in patients with jaundice or laboratory evidence of liver injury, and should not be restarted. Laboratory testing to determine liver enzyme levels should be done upon the first symptom or sign of liver dysfunction (e.g., pruritus, dark urine, jaundice, right upper quadrant tenderness, or unexplained “flu like” symptoms) [see Warnings and Precautions ( 5.12 ); Patient Counseling Information ( 17.3 )] . 5.3 Serious Cardiovascular Events Sudden Death and Pre-existing Structural Cardiac Abnormalities or Other Serious Heart Problems Children and Adolescents — Sudden death has been reported in association with atomoxetine treatment at usual doses in children and adolescents with structural cardiac abnormalities or other serious heart problems. Although some serious heart problems alone carry an increased risk of sudden death, atomoxetine generally should not be used in children or adolescents with known serious structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, or other serious cardiac problems that may place them at increased vulnerability to the noradrenergic effects of atomoxetine. Adults — Sudden deaths, stroke, and myocardial infarction have been reported in adults taking atomoxetine at usual doses for ADHD. Although the role of atomoxetine in these adult cases is also unknown, adults have a greater likelihood than children of having serious structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, coronary artery disease, or other serious cardiac problems. Consideration should be given to not treating adults with clinically significant cardiac abnormalities. Assessing Cardiovascular Status in Patients being Treated with Atomoxetine Children, adolescents, or adults who are being considered for treatment with atomoxetine should have a careful history (including assessment for a family history of sudden death or ventricular arrhythmia) and physical exam to assess for the presence of cardiac disease, and should receive further cardiac evaluation if findings suggest such disease (e.g., electrocardiogram and echocardiogram). Patients who develop symptoms such as exertional chest pain, unexplained syncope, or other symptoms suggestive of cardiac disease during atomoxetine treatment should undergo a prompt cardiac evaluation. 5.4 Effects on Blood Pressure and Heart Rate STRATTERA should be used with caution in patients whose underlying medical conditions could be worsened by increases in blood pressure or heart rate such as certain patients with hypertension, tachycardia, or cardiovascular or cerebrovascular disease. It should not be used in patients with severe cardiac or vascular disorders whose condition would be expected to deteriorate if they experienced clinically important increases in blood pressure or heart rate [see Contraindications ( 4.5 )] . Pulse and blood pressure should be measured at baseline, following STRATTERA dose increases, and periodically while on therapy to detect possible clinically important increases. The following table provides short-term, placebo-controlled clinical trial data for the proportions of patients having an increase in: diastolic blood pressure ≥15 mm Hg; systolic blood pressure ≥20 mm Hg; heart rate greater than or equal to 20 bpm, in both the pediatric and adult populations ( see Table 1 ). Table 1 a a Abbreviations: bpm=beats per minute; DBP=diastolic blood pressure; HR=heart rate; mm Hg=millimeters mercury; SBP=systolic blood pressure. b Proportion of patients meeting threshold at any one time during clinical trial. Pediatric Acute Placebo-Controlled Adult Acute Placebo-Controlled Maximum b Endpoint Maximum b Endpoint Atomoxetine Placebo Atomoxetine Placebo Atomoxetine Placebo Atomoxetine Placebo % % % % % % % % DBP (≥15 mm Hg) 21.5 14.1 9.3 4.8 12.6 8.7 4.8 3.5 SBP (≥20 mm Hg) 12.5 8.7 4.9 3.3 12.4 7.8 4.2 3.2 HR (≥20 bpm) 23.4 11.5 12.2 3.8 22.4 8.3 10.2 2.0 In placebo-controlled registration studies involving pediatric patients, tachycardia was identified as an adverse event for 0.3% (5/1597) of these STRATTERA patients compared with 0% (0/934) of placebo patients. The mean heart rate increase in extensive metabolizer (EM) patients was 5.0 beats/minute, and in poor metabolizer (PM) patients 9.4 beats/minute. In adult clinical trials where EM/PM status was available, the mean heart rate increase in PM patients was significantly higher than in EM patients (11 beats/minute versus 7.5 beats/minute). The heart rate effects could be clinically important in some PM patients. In placebo-controlled registration studies involving adult patients, tachycardia was identified as an adverse event for 1.5% (8/540) of STRATTERA patients compared with 0.5% (2/402) of placebo patients. In adult clinical trials where EM/PM status was available, the mean change from baseline in diastolic blood pressure in PM patients was higher than in EM patients (4.21 versus 2.13 mm Hg) as was the mean change from baseline in systolic blood pressure (PM: 2.75 versus EM: 2.40 mm Hg). The blood pressure effects could be clinically important in some PM patients. Orthostatic hypotension and syncope have been reported in patients taking STRATTERA. In child and adolescent registration studies, 0.2% (12/5596) of STRATTERA-treated patients experienced orthostatic hypotension and 0.8% (46/5596) experienced syncope. In short-term child and adolescent registration studies, 1.8% (6/340) of STRATTERA-treated patients experienced orthostatic hypotension compared with 0.5% (1/207) of placebo-treated patients. Syncope was not reported during short-term child and adolescent placebo-controlled ADHD registration studies. STRATTERA should be used with caution in any condition that may predispose patients to hypotension, or conditions associated with abrupt heart rate or blood pressure changes. 5.5 Emergence of New Psychotic or Manic Symptoms Treatment emergent psychotic or manic symptoms, e.g., hallucinations, delusional thinking, or mania in children and adolescents without a prior history of psychotic illness or mania can be caused by atomoxetine at usual doses. If such symptoms occur, consideration should be given to a possible causal role of atomoxetine, and discontinuation of treatment should be considered. In a pooled analysis of multiple short-term, placebo-controlled studies, such symptoms occurred in about 0.2% (4 patients with reactions out of 1939 exposed to atomoxetine for several weeks at usual doses) of atomoxetine-treated patients compared to 0 out of 1056 placebo-treated patients. 5.6 Screening Patients for Bipolar Disorder In general, particular care should be taken in treating ADHD in patients with comorbid bipolar disorder because of concern for possible induction of a mixed/manic episode in patients at risk for bipolar disorder. Whether any of the symptoms described above represent such a conversion is unknown. However, prior to initiating treatment with STRATTERA, patients with comorbid depressive symptoms should be adequately screened to determine if they are at risk for bipolar disorder; such screening should include a detailed psychiatric history, including a family history of suicide, bipolar disorder, and depression. 5.7 Aggressive Behavior or Hostility Patients beginning treatment for ADHD should be monitored for the appearance or worsening of aggressive behavior or hostility. Aggressive behavior or hostility is often observed in children and adolescents with ADHD. In pediatric short-term controlled clinical trials, 21/1308 (1.6%) of atomoxetine patients versus 9/806 (1.1%) of placebo-treated patients spontaneously reported treatment emergent hostility-related adverse events (overall risk ratio of 1.33 [95% C.I. 0.67-2.64 – not statistically significant]). In adult placebo-controlled clinical trials, 6/1697 (0.35%) of atomoxetine patients versus 4/1560 (0.26%) of placebo-treated patients spontaneously reported treatment emergent hostility-related adverse events (overall risk ratio of 1.38 [95% C.I. 0.39-4.88 – not statistically significant]). Although this is not conclusive evidence that STRATTERA causes aggressive behavior or hostility, these behaviors were more frequently observed in clinical trials among children, adolescents, and adults treated with STRATTERA compared to placebo. 5.8 Allergic Events Although uncommon, allergic reactions, including anaphylactic reactions, angioneurotic edema, urticaria, and rash, have been reported in patients taking STRATTERA. 5.9 Effects on Urine Outflow from the Bladder In adult ADHD controlled trials, the rates of urinary retention (1.7%, 9/540) and urinary hesitation (5.6%, 30/540) were increased among atomoxetine subjects compared with placebo subjects (0%, 0/402 ; 0.5%, 2/402, respectively). Two adult atomoxetine subjects and no placebo subjects discontinued from controlled clinical trials because of urinary retention. A complaint of urinary retention or urinary hesitancy should be considered potentially related to atomoxetine. 5.10 Priapism Rare postmarketing cases of priapism, defined as painful and nonpainful penile erection lasting more than 4 hours, have been reported for pediatric and adult patients treated with STRATTERA. The erections resolved in cases in which follow-up information was available, some following discontinuation of STRATTERA. Prompt medical attention is required in the event of suspected priapism. 5.11 Effects on Growth Data on the long-term effects of STRATTERA on growth come from open-label studies, and weight and height changes are compared to normative population data. In general, the weight and height gain of pediatric patients treated with STRATTERA lags behind that predicted by normative population data for about the first 9-12 months of treatment. Subsequently, weight gain rebounds and at about 3 years of treatment, patients treated with STRATTERA have gained 17.9 kg on average, 0.5 kg more than predicted by their baseline data. After about 12 months, gain in height stabilizes, and at 3 years, patients treated with STRATTERA have gained 19.4 cm on average, 0.4 cm less than predicted by their baseline data ( see Figure 1 below). This growth pattern was generally similar regardless of pubertal status at the time of treatment initiation. Patients who were pre-pubertal at the start of treatment (girls ≤8 years old, boys ≤9 years old) gained an average of 2.1 kg and 1.2 cm less than predicted after three years. Patients who were pubertal (girls >8 to ≤13 years old, boys >9 to ≤14 years old) or late pubertal (girls >13 years old, boys >14 years old) had average weight and height gains that were close to or exceeded those predicted after three years of treatment. Growth followed a similar pattern in both extensive and poor metabolizers (EMs, PMs). PMs treated for at least two years gained an average of 2.4 kg and 1.1 cm less than predicted, while EMs gained an average of 0.2 kg and 0.4 cm less than predicted. In short-term controlled studies (up to 9 weeks), STRATTERA-treated patients lost an average of 0.4 kg and gained an average of 0.9 cm, compared to a gain of 1.5 kg and 1.1 cm in the placebo-treated patients. In a fixed-dose controlled trial, 1.3%, 7.1%, 19.3%, and 29.1% of patients lost at least 3.5% of their body weight in the placebo, 0.5, 1.2, and 1.8 mg/kg/day dose groups. Growth should be monitored during treatment with STRATTERA. Figure 1 5.12 Laboratory Tests Routine laboratory tests are not required. CYP2D6 metabolism — Poor metabolizers (PMs) of CYP2D6 have a 10-fold higher AUC and a 5-fold higher peak concentration to a given dose of STRATTERA compared with extensive metabolizers (EMs). Approximately 7% of a Caucasian population are PMs. Laboratory tests are available to identify CYP2D6 PMs. The blood levels in PMs are similar to those attained by taking strong inhibitors of CYP2D6. The higher blood levels in PMs lead to a higher rate of some adverse effects of STRATTERA [see Adverse Reactions ( 6.1 )] . 5.13 Concomitant Use of Potent CYP2D6 Inhibitors or Use in patients who are known to be CYP2D6 PMs Atomoxetine is primarily metabolized by the CYP2D6 pathway to 4-hydroxyatomoxetine. Dosage adjustment of STRATTERA may be necessary when coadministered with potent CYP2D6 inhibitors (e.g., paroxetine, fluoxetine, and quinidine) or when administered to CYP2D6 PMs. [See Dosage and Administration ( 2.4 ) and Drug Interactions ( 7.2 )] .

<table ID="t1" width="100%"> <caption>Table 1 ^a </caption> <col width="12.000%" align="left"/> <col width="10.323%" align="left"/> <col width="10.323%" align="left"/> <col width="10.323%" align="left"/> <col width="10.243%" align="left"/> <col width="10.323%" align="left"/> <col width="10.323%" align="left"/> <col width="10.323%" align="left"/> <col width="10.243%" align="left"/> <tfoot> <tr> <td colspan="9" align="left" valign="top"> <paragraph styleCode="footnote"> ^a Abbreviations: bpm=beats per minute; DBP=diastolic blood pressure; HR=heart rate; mm Hg=millimeters mercury; SBP=systolic blood pressure. </paragraph> <paragraph styleCode="footnote"> ^b Proportion of patients meeting threshold at any one time during clinical trial. </paragraph> </td> </tr> </tfoot> <tbody> <tr> <td rowspan="1" align="left" styleCode="Lrule Rrule" valign="top"/> <td colspan="4" align="center" styleCode="Toprule Botrule Rrule" valign="top"> <content styleCode="bold">Pediatric Acute Placebo-Controlled </content> </td> <td colspan="4" align="center" styleCode="Toprule Botrule Rrule" valign="top"> <content styleCode="bold">Adult Acute Placebo-Controlled </content> </td> </tr> <tr> <td rowspan="2" align="left" styleCode="Lrule Rrule" valign="top"/> <td colspan="2" align="center" styleCode="Toprule Botrule Rrule" valign="top"> <content styleCode="bold">Maximum ^b </content> </td> <td colspan="2" align="center" styleCode="Toprule Botrule Rrule" valign="top"> <content styleCode="bold">Endpoint</content> </td> <td colspan="2" align="center" styleCode="Toprule Botrule Rrule" valign="top"> <content styleCode="bold">Maximum ^b </content> </td> <td colspan="2" align="center" styleCode="Toprule Botrule Rrule" valign="top"> <content styleCode="bold">Endpoint</content> </td> </tr> <tr> <td align="center" styleCode="Botrule Rrule" valign="top"> <content styleCode="bold">Atomoxetine</content> </td> <td align="center" styleCode="Botrule Rrule" valign="top"> <content styleCode="bold">Placebo</content> </td> <td align="center" styleCode="Botrule Rrule" valign="top"> <content styleCode="bold">Atomoxetine</content> </td> <td align="center" styleCode="Botrule Rrule" valign="top"> <content styleCode="bold">Placebo</content> </td> <td align="center" styleCode="Botrule Rrule" valign="top"> <content styleCode="bold">Atomoxetine</content> </td> <td align="center" styleCode="Botrule Rrule" valign="top"> <content styleCode="bold">Placebo</content> </td> <td align="center" styleCode="Botrule Rrule" valign="top"> <content styleCode="bold">Atomoxetine</content> </td> <td align="center" styleCode="Botrule Rrule" valign="top"> <content styleCode="bold">Placebo</content> </td> </tr> <tr> <td align="left" styleCode="Botrule Lrule Rrule" valign="top"/> <td align="center" styleCode="Botrule Rrule" valign="top"> <content styleCode="bold">%</content> </td> <td align="center" styleCode="Botrule Rrule" valign="top"> <content styleCode="bold">%</content> </td> <td align="center" styleCode="Botrule Rrule" valign="top"> <content styleCode="bold">%</content> </td> <td align="center" styleCode="Botrule Rrule" valign="top"> <content styleCode="bold">%</content> </td> <td align="center" styleCode="Botrule Rrule" valign="top"> <content styleCode="bold">%</content> </td> <td align="center" styleCode="Botrule Rrule" valign="top"> <content styleCode="bold">%</content> </td> <td align="center" styleCode="Botrule Rrule" valign="top"> <content styleCode="bold">%</content> </td> <td align="center" styleCode="Botrule Rrule" valign="top"> <content styleCode="bold">%</content> </td> </tr> <tr> <td align="left" styleCode="Botrule Lrule Rrule" valign="top"> DBP (&#x2265;15 mm Hg) </td> <td align="center" styleCode="Botrule Rrule" valign="middle"> 21.5 </td> <td align="center" styleCode="Botrule Rrule" valign="middle"> 14.1 </td> <td align="center" styleCode="Botrule Rrule" valign="middle"> 9.3 </td> <td align="center" styleCode="Botrule Rrule" valign="middle"> 4.8 </td> <td align="center" styleCode="Botrule Rrule" valign="middle"> 12.6 </td> <td align="center" styleCode="Botrule Rrule" valign="middle"> 8.7 </td> <td align="center" styleCode="Botrule Rrule" valign="middle"> 4.8 </td> <td align="center" styleCode="Botrule Rrule" valign="middle"> 3.5 </td> </tr> <tr> <td align="left" styleCode="Botrule Lrule Rrule" valign="top"> SBP (&#x2265;20 mm Hg) </td> <td align="center" styleCode="Botrule Rrule" valign="middle"> 12.5 </td> <td align="center" styleCode="Botrule Rrule" valign="middle"> 8.7 </td> <td align="center" styleCode="Botrule Rrule" valign="middle"> 4.9 </td> <td align="center" styleCode="Botrule Rrule" valign="middle"> 3.3 </td> <td align="center" styleCode="Botrule Rrule" valign="middle"> 12.4 </td> <td align="center" styleCode="Botrule Rrule" valign="middle"> 7.8 </td> <td align="center" styleCode="Botrule Rrule" valign="middle"> 4.2 </td> <td align="center" styleCode="Botrule Rrule" valign="middle"> 3.2 </td> </tr> <tr> <td align="left" styleCode="Botrule Lrule Rrule" valign="top"> HR (&#x2265;20 bpm) </td> <td align="center" styleCode="Botrule Rrule" valign="middle"> 23.4 </td> <td align="center" styleCode="Botrule Rrule" valign="middle"> 11.5 </td> <td align="center" styleCode="Botrule Rrule" valign="middle"> 12.2 </td> <td align="center" styleCode="Botrule Rrule" valign="middle"> 3.8 </td> <td align="center" styleCode="Botrule Rrule" valign="middle"> 22.4 </td> <td align="center" styleCode="Botrule Rrule" valign="middle"> 8.3 </td> <td align="center" styleCode="Botrule Rrule" valign="middle"> 10.2 </td> <td align="center" styleCode="Botrule Rrule" valign="middle"> 2.0 </td> </tr> </tbody> </table>

6 ADVERSE REACTIONS Most common adverse reactions (≥5% and at least twice the incidence of placebo patients) Child and Adolescent Clinical Trials – Nausea, vomiting, fatigue, decreased appetite, abdominal pain, and somnolence. ( 6.1 ) Adult Clinical Trials – Constipation, dry mouth, nausea, decreased appetite, dizziness, erectile dysfunction, and urinary hesitation. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Eli Lilly and Company at 1-800-LillyRx (1-800-545-5979) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience STRATTERA was administered to 5382 children or adolescent patients with ADHD and 1007 adults with ADHD in clinical studies. During the ADHD clinical trials, 1625 children and adolescent patients were treated for longer than 1 year and 2529 children and adolescent patients were treated for over 6 months. 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. Child and Adolescent Clinical Trials Reasons for discontinuation of treatment due to adverse reactions in child and adolescent clinical trials — In acute child and adolescent placebo-controlled trials, 3.0% (48/1613) of atomoxetine subjects and 1.4% (13/945) placebo subjects discontinued for adverse reactions. For all studies, (including open-label and long-term studies), 6.3% of extensive metabolizer (EM) patients and 11.2% of poor metabolizer (PM) patients discontinued because of an adverse reaction. Among STRATTERA-treated patients, irritability (0.3%, N=5); somnolence (0.3%, N=5); aggression (0.2%, N=4); nausea (0.2%, N=4); vomiting (0.2%, N=4); abdominal pain (0.2%, N=4); constipation (0.1%, N=2); fatigue (0.1%, N=2); feeling abnormal (0.1%, N=2); and headache (0.1%, N=2) were the reasons for discontinuation reported by more than 1 patient. Seizures — STRATTERA has not been systematically evaluated in pediatric patients with seizure disorder as these patients were excluded from clinical studies during the product's premarket testing. In the clinical development program, seizures were reported in 0.2% (12/5073) of children whose average age was 10 years (range 6 to 16 years). In these clinical trials, the seizure risk among poor metabolizers was 0.3% (1/293) compared to 0.2% (11/4741) for extensive metabolizers. Commonly observed adverse reactions in acute child and adolescent, placebo-controlled trials — Commonly observed adverse reactions associated with the use of STRATTERA (incidence of 2% or greater) and not observed at an equivalent incidence among placebo-treated patients (STRATTERA incidence greater than placebo) are listed in Table 2 . Results were similar in the BID and the QD trial except as shown in Table 3 , which shows both BID and QD results for selected adverse reactions based on statistically significant Breslow-Day tests. The most commonly observed adverse reactions in patients treated with STRATTERA (incidence of 5% or greater and at least twice the incidence in placebo patients, for either BID or QD dosing) were: nausea, vomiting, fatigue, decreased appetite, abdominal pain, and somnolence ( see Tables 2 and 3 ). Additional data from ADHD clinical trials (controlled and uncontrolled) has shown that approximately 5 to 10% of pediatric patients experienced potentially clinically important changes in heart rate (≥20 beats per min) or blood pressure (≥15 to 20 mm Hg) [see Contraindications ( 4 ) and Warnings and Precautions ( 5 )] . Table 2: Common Treatment–Emergent Adverse Reactions Associated with the Use of STRATTERA in Acute (up to 18 weeks) Child and Adolescent Trials a Reactions reported by at least 2% of patients treated with atomoxetine, and greater than placebo. The following reactions did not meet this criterion but were reported by more atomoxetine-treated patients than placebo-treated patients and are possibly related to atomoxetine treatment: blood pressure increased, early morning awakening (terminal insomnia), flushing, mydriasis, sinus tachycardia, asthenia, palpitations, mood swings, constipation, and dyspepsia. The following reactions were reported by at least 2% of patients treated with atomoxetine, and equal to or less than placebo: pharyngolaryngeal pain, insomnia (insomnia includes the terms, insomnia, initial insomnia, middle insomnia). The following reaction did not meet this criterion but shows a statistically significant dose relationship: pruritus. b Abdominal pain includes the terms: abdominal pain upper, abdominal pain, stomach discomfort, abdominal discomfort, epigastric discomfort. c Somnolence includes the terms: sedation, somnolence. Adverse Reaction a Percentage of Patients Reporting Reaction STRATTERA (N=1597) Placebo (N=934) Gastrointestinal Disorders Abdominal pain b 18 10 Vomiting 11 6 Nausea 10 5 General Disorders and Administration Site Conditions Fatigue 8 3 Irritability 6 3 Therapeutic response unexpected 2 1 Investigations Weight decreased 3 0 Metabolism and Nutritional Disorders Decreased appetite 16 4 Anorexia 3 1 Nervous System Disorders Headache 19 15 Somnolence c 11 4 Dizziness 5 2 Skin and Subcutaneous Tissue Disorders Rash 2 1 Table 3: Common Treatment-Emergent Adverse Reactions Associated with the Use of STRATTERA in Acute (up to 18 weeks) Child and Adolescent Trials a Abdominal pain includes the terms: abdominal pain upper, abdominal pain, stomach discomfort, abdominal discomfort, epigastric discomfort. b Constipation didn't meet the statistical significance on Breslow-Day test but is included in the table because of pharmacologic plausibility. c Mood swings didn't meet the statistical significance on Breslow-Day test at 0.05 level but p-value was <0.1 (trend). Adverse Reaction Percentage of Patients Reporting Reaction from BID Trials Percentage of Patients Reporting Reaction from QD Trials STRATTERA (N=715) Placebo (N=434) STRATTERA (N=882) Placebo (N=500) Gastrointestinal Disorders Abdominal pain a 17 13 18 7 Vomiting 11 8 11 4 Nausea 7 6 13 4 Constipation b 2 1 1 0 General Disorders Fatigue 6 4 9 2 Psychiatric Disorders Mood swings c 2 0 1 1 The following adverse reactions occurred in at least 2% of child and adolescent CYP2D6 PM patients and were statistically significantly more frequent in PM patients compared with CYP2D6 EM patients: insomnia (11% of PMs, 6% of EMs); weight decreased (7% of PMs, 4% of EMs); constipation (7% of PMs, 4% of EMs); depression 1 (7% of PMs, 4% of EMs); tremor (5% of PMs, 1% of EMs); excoriation (4% of PMs, 2% of EMs); middle insomnia (3% of PMs, 1% of EMs); conjunctivitis (3% of PMs, 1% of EMs); syncope (3% of PMs, 1% of EMs); early morning awakening (2% of PMs, 1% of EMs); mydriasis (2% of PMs, 1% of EMs); sedation (4% of PMs, 2% of EMs). 1 Depression includes the following terms: depression, major depression, depressive symptoms, depressed mood, dysphoria. Adult Clinical Trials Reasons for discontinuation of treatment due to adverse reactions in acute adult placebo-controlled trials — In the acute adult placebo-controlled trials, 11.3% (61/541) atomoxetine subjects and 3.0% (12/405) placebo subjects discontinued for adverse reactions. Among STRATTERA-treated patients, insomnia (0.9%, N=5); nausea (0.9%, N=5); chest pain (0.6%, N=3); fatigue (0.6%, N=3); anxiety (0.4%, N=2); erectile dysfunction (0.4%, N=2); mood swings (0.4%, N=2); nervousness (0.4%, N=2); palpitations (0.4%, N=2); and urinary retention (0.4%, N=2) were the reasons for discontinuation reported by more than 1 patient. Seizures — STRATTERA has not been systematically evaluated in adult patients with a seizure disorder as these patients were excluded from clinical studies during the product's premarket testing. In the clinical development program, seizures were reported on 0.1% (1/748) of adult patients. In these clinical trials, no poor metabolizers (0/43) reported seizures compared to 0.1% (1/705) for extensive metabolizers. Commonly observed adverse reactions in acute adult placebo-controlled trials — Commonly observed adverse reactions associated with the use of STRATTERA (incidence of 2% or greater) and not observed at an equivalent incidence among placebo-treated patients (STRATTERA incidence greater than placebo) are listed in Table 4 . The most commonly observed adverse reactions in patients treated with STRATTERA (incidence of 5% or greater and at least twice the incidence in placebo patients) were: constipation, dry mouth, nausea, decreased appetite, dizziness, erectile dysfunction, and urinary hesitation ( see Table 4 ). Additional data from ADHD clinical trials (controlled and uncontrolled) has shown that approximately 5 to 10% of adult patients experienced potentially clinically important changes in heart rate (≥20 beats per min) or blood pressure (≥15 to 20 mm Hg) [see Contraindications ( 4 ) and Warnings and Precautions ( 5 )] . Table 4: Common Treatment-Emergent Adverse Reactions Associated with the Use of STRATTERA in Acute (up to 25 weeks) Adult Trials a Reactions reported by at least 2% of patients treated with atomoxetine, and greater than placebo. The following reactions did not meet this criterion but were reported by more atomoxetine-treated patients than placebo-treated patients and are possibly related to atomoxetine treatment: peripheral coldness, tachycardia, prostatitis, testicular pain, orgasm abnormal, flatulence, asthenia, feeling cold, muscle spasm, dysgeusia, agitation, restlessness, micturition urgency, pollakiuria, pruritus, urticaria, flushing, tremor, menstruation irregular, rash, and urinary retention. The following reactions were reported by at least 2% of patients treated with atomoxetine, and equal to or less than placebo: anxiety, diarrhea, back pain, headache, and oropharyngeal pain. b Abdominal pain includes the terms: abdominal pain upper, abdominal pain, stomach discomfort, abdominal discomfort, epigastric discomfort. c Somnolence includes the terms: sedation, somnolence. d Insomnia includes the terms: insomnia, initial insomnia, middle insomnia, and terminal insomnia. e Urinary hesitation includes the terms: urinary hesitation, urine flow decreased. f Based on total number of males (STRATTERA, N=943; placebo, N=869). g Based on total number of females (STRATTERA, N=754; placebo, N=691). Adverse Reaction a Percentage of Patients Reporting Reaction System Organ Class/Adverse Reaction STRATTERA (N=1697) Placebo (N=1560) Cardiac Disorders Palpitations 3 1 Gastrointestinal Disorders Dry mouth 20 5 Nausea 26 6 Constipation 8 3 Abdominal pain b 7 4 Dyspepsia 4 2 Vomiting 4 2 General Disorders and Administration Site Conditions Fatigue 10 6 Chills 3 0 Feeling jittery 2 1 Irritability 5 3 Thirst 2 1 Investigations Weight decreased 2 1 Metabolism and Nutritional Disorders Decreased appetite 16 3 Nervous System Disorders Dizziness 8 3 Somnolence c 8 5 Paraesthesia 3 0 Psychiatric Disorders Abnormal dreams 4 3 Insomnia d 15 8 Libido decreased 3 1 Sleep disorder 3 1 Renal and Urinary Disorders Urinary hesitation e 6 1 Dysuria 2 0 Reproductive System and Breast Disorders Erectile dysfunction f 8 1 Dysmenorrhea g 3 2 Ejaculation delayed f and/or ejaculation disorder f 4 1 Skin and Subcutaneous Tissue Disorders Hyperhidrosis 4 1 Vascular Disorders Hot flush 3 0 The following adverse events occurred in at least 2% of adult CYP2D6 poor metaboliser (PM) patients and were statistically significantly more frequent in PM patients compared to CYP2D6 extensive metaboliser (EM) patients: vision blurred (4% of PMs, 1% of EMs); dry mouth (35% of PMs, 17% of EMs); constipation (11% of PMs, 7% of EMs); feeling jittery (5% of PMs, 2% of EMs); decreased appetite (23% of PMs, 15% of EMs); tremor (5% of PMs, 1% of EMs); insomnia (19% of PMs, 11% of EMs); sleep disorder (7% of PMs, 3% of EMs); middle insomnia (5% of PMs, 3% of EMs); terminal insomnia (3% of PMs, 1% of EMs); urinary retention (6% of PMs, 1% of EMs); erectile dysfunction (21% of PMs, 9% of EMs); ejaculation disorder (6% of PMs, 2% of EMs); hyperhidrosis (15% of PMs, 7% of EMs); peripheral coldness (3% of PMs, 1% of EMs). Male and female sexual dysfunction — Atomoxetine appears to impair sexual function in some patients. Changes in sexual desire, sexual performance, and sexual satisfaction are not well assessed in most clinical trials because they need special attention and because patients and physicians may be reluctant to discuss them. Accordingly, estimates of the incidence of untoward sexual experience and performance cited in product labeling are likely to underestimate the actual incidence. Table 4 above displays the incidence of sexual side effects reported by at least 2% of adult patients taking STRATTERA in placebo-controlled trials. There are no adequate and well-controlled studies examining sexual dysfunction with STRATTERA treatment. While it is difficult to know the precise risk of sexual dysfunction associated with the use of STRATTERA, physicians should routinely inquire about such possible side effects. 6.2 Postmarketing Spontaneous Reports The following adverse reactions have been identified during post approval use of STRATTERA. Unless otherwise specified, these adverse reactions have occurred in adults and children and adolescents. 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. Cardiovascular system — QT prolongation, syncope. Peripheral vascular effects — Raynaud's phenomenon. General disorders and administration site conditions — Lethargy. Musculoskeletal System — Rhabdomyolysis. Nervous system disorders — Hypoaesthesia; paraesthesia in children and adolescents; sensory disturbances; tics. Psychiatric disorders — Depression and depressed mood; anxiety, libido changes. Seizures — Seizures have been reported in the postmarketing period. The postmarketing seizure cases include patients with pre-existing seizure disorders and those with identified risk factors for seizures, as well as patients with neither a history of nor identified risk factors for seizures. The exact relationship between STRATTERA and seizures is difficult to evaluate due to uncertainty about the background risk of seizures in ADHD patients. Skin and subcutaneous tissue disorders — Hyperhidrosis. Urogenital system — Male pelvic pain; urinary hesitation in children and adolescents; urinary retention in children and adolescents.

<table ID="t2" width="100%"> <caption>Table 2: Common Treatment&#x2013;Emergent Adverse Reactions Associated with the Use of STRATTERA in Acute (up to 18 weeks) Child and Adolescent Trials </caption> <col width="48.049%" align="left"/> <col width="25.975%" align="left"/> <col width="25.975%" align="left"/> <tfoot> <tr> <td colspan="3" align="left" valign="top"> <paragraph styleCode="footnote"> ^a Reactions reported by at least 2% of patients treated with atomoxetine, and greater than placebo. The following reactions did not meet this criterion but were reported by more atomoxetine-treated patients than placebo-treated patients and are possibly related to atomoxetine treatment: blood pressure increased, early morning awakening (terminal insomnia), flushing, mydriasis, sinus tachycardia, asthenia, palpitations, mood swings, constipation, and dyspepsia. The following reactions were reported by at least 2% of patients treated with atomoxetine, and equal to or less than placebo: pharyngolaryngeal pain, insomnia (insomnia includes the terms, insomnia, initial insomnia, middle insomnia). The following reaction did not meet this criterion but shows a statistically significant dose relationship: pruritus. </paragraph> </td> </tr> <tr> <td colspan="3" align="left" valign="top"> <paragraph styleCode="footnote"> ^b Abdominal pain includes the terms: abdominal pain upper, abdominal pain, stomach discomfort, abdominal discomfort, epigastric discomfort. </paragraph> </td> </tr> <tr> <td colspan="3" align="left" valign="top"> <paragraph styleCode="footnote"> ^c Somnolence includes the terms: sedation, somnolence. </paragraph> </td> </tr> </tfoot> <tbody> <tr> <td align="left" styleCode="Toprule Botrule Lrule Rrule" valign="top"> <content styleCode="bold">Adverse Reaction ^a </content> </td> <td colspan="2" align="center" styleCode="Toprule Botrule Rrule" valign="top"> <content styleCode="bold">Percentage of Patients Reporting Reaction</content> </td> </tr> <tr> <td align="left" styleCode="Botrule Lrule Rrule" valign="top"/> <td align="center" styleCode="Botrule Rrule" valign="top"> <content styleCode="bold">STRATTERA (N=1597) </content> </td> <td align="center" styleCode="Botrule Rrule" valign="top"> <content styleCode="bold">Placebo (N=934) </content> </td> </tr> <tr> <td align="left" styleCode="Botrule Lrule Rrule" valign="top"> <content styleCode="bold">Gastrointestinal Disorders</content> </td> <td align="center" styleCode="Botrule Rrule" valign="top"/> <td align="center" styleCode="Botrule Rrule" valign="top"/> </tr> <tr> <td align="left" styleCode="Botrule Lrule Rrule" valign="top"> Abdominal pain ^b </td> <td align="center" styleCode="Botrule Rrule" valign="top">18 </td> <td align="center" styleCode="Botrule Rrule" valign="top">10 </td> </tr> <tr> <td align="left" styleCode="Botrule Lrule Rrule" valign="top"> Vomiting </td> <td align="center" styleCode="Botrule Rrule" valign="top">11 </td> <td align="center" styleCode="Botrule Rrule" valign="top">6 </td> </tr> <tr> <td align="left" styleCode="Botrule Lrule Rrule" valign="top"> Nausea </td> <td align="center" styleCode="Botrule Rrule" valign="top">10 </td> <td align="center" styleCode="Botrule Rrule" valign="top">5 </td> </tr> <tr> <td align="left" styleCode="Botrule Lrule Rrule" valign="top"> <content styleCode="bold">General Disorders and Administration Site Conditions</content> </td> <td align="center" styleCode="Botrule Rrule" valign="top"/> <td align="center" styleCode="Botrule Rrule" valign="top"/> </tr> <tr> <td align="left" styleCode="Botrule Lrule Rrule" valign="top"> Fatigue </td> <td align="center" styleCode="Botrule Rrule" valign="top">8 </td> <td align="center" styleCode="Botrule Rrule" valign="top">3 </td> </tr> <tr> <td align="left" styleCode="Botrule Lrule Rrule" valign="top"> Irritability </td> <td align="center" styleCode="Botrule Rrule" valign="top">6 </td> <td align="center" styleCode="Botrule Rrule" valign="top">3 </td> </tr> <tr> <td align="left" styleCode="Botrule Lrule Rrule" valign="top"> Therapeutic response unexpected </td> <td align="center" styleCode="Botrule Rrule" valign="top">2 </td> <td align="center" styleCode="Botrule Rrule" valign="top">1 </td> </tr> <tr> <td align="left" styleCode="Botrule Lrule Rrule" valign="top"> <content styleCode="bold">Investigations</content> </td> <td align="center" styleCode="Botrule Rrule" valign="top"/> <td align="center" styleCode="Botrule Rrule" valign="top"/> </tr> <tr> <td align="left" styleCode="Botrule Lrule Rrule" valign="top"> Weight decreased </td> <td align="center" styleCode="Botrule Rrule" valign="top">3 </td> <td align="center" styleCode="Botrule Rrule" valign="top">0 </td> </tr> <tr> <td align="left" styleCode="Botrule Lrule Rrule" valign="top"> <content styleCode="bold">Metabolism and Nutritional Disorders</content> </td> <td align="center" styleCode="Botrule Rrule" valign="top"/> <td align="center" styleCode="Botrule Rrule" valign="top"/> </tr> <tr> <td align="left" styleCode="Botrule Lrule Rrule" valign="top"> Decreased appetite </td> <td align="center" styleCode="Botrule Rrule" valign="top">16 </td> <td align="center" styleCode="Botrule Rrule" valign="top">4 </td> </tr> <tr> <td align="left" styleCode="Botrule Lrule Rrule" valign="top"> Anorexia </td> <td align="center" styleCode="Botrule Rrule" valign="top">3 </td> <td align="center" styleCode="Botrule Rrule" valign="top">1 </td> </tr> <tr> <td align="left" styleCode="Botrule Lrule Rrule" valign="top"> <content styleCode="bold">Nervous System Disorders</content> </td> <td align="center" styleCode="Botrule Rrule" valign="top"/> <td align="center" styleCode="Botrule Rrule" valign="top"/> </tr> <tr> <td align="left" styleCode="Botrule Lrule Rrule" valign="top"> Headache </td> <td align="center" styleCode="Botrule Rrule" valign="top">19 </td> <td align="center" styleCode="Botrule Rrule" valign="top">15 </td> </tr> <tr> <td align="left" styleCode="Botrule Lrule Rrule" valign="top"> Somnolence ^c </td> <td align="center" styleCode="Botrule Rrule" valign="top">11 </td> <td align="center" styleCode="Botrule Rrule" valign="top">4 </td> </tr> <tr> <td align="left" styleCode="Botrule Lrule Rrule" valign="top"> Dizziness </td> <td align="center" styleCode="Botrule Rrule" valign="top">5 </td> <td align="center" styleCode="Botrule Rrule" valign="top">2 </td> </tr> <tr> <td align="left" styleCode="Botrule Lrule Rrule" valign="top"> <content styleCode="bold">Skin and Subcutaneous Tissue Disorders</content> </td> <td align="center" styleCode="Botrule Rrule" valign="top"/> <td align="center" styleCode="Botrule Rrule" valign="top"/> </tr> <tr> <td align="left" styleCode="Botrule Lrule Rrule" valign="top"> Rash </td> <td align="center" styleCode="Botrule Rrule" valign="top">2 </td> <td align="center" styleCode="Botrule Rrule" valign="top">1 </td> </tr> </tbody> </table>

<table ID="t3" width="100%"> <caption>Table 3: Common Treatment-Emergent Adverse Reactions Associated with the Use of STRATTERA in Acute (up to 18 weeks) Child and Adolescent Trials </caption> <col width="27.160%" align="left"/> <col width="16.920%" align="left"/> <col width="11.260%" align="left"/> <col width="16.920%" align="left"/> <col width="27.740%" align="left"/> <tfoot> <tr> <td colspan="5" align="left" valign="top"> <paragraph styleCode="footnote"> ^a Abdominal pain includes the terms: abdominal pain upper, abdominal pain, stomach discomfort, abdominal discomfort, epigastric discomfort. </paragraph> </td> </tr> <tr> <td colspan="5" align="left" valign="top"> <paragraph styleCode="footnote"> ^b Constipation didn&apos;t meet the statistical significance on Breslow-Day test but is included in the table because of pharmacologic plausibility. </paragraph> </td> </tr> <tr> <td colspan="5" align="left" valign="top"> <paragraph styleCode="footnote"> ^c Mood swings didn&apos;t meet the statistical significance on Breslow-Day test at 0.05 level but p-value was &lt;0.1 (trend). </paragraph> </td> </tr> </tfoot> <tbody> <tr> <td align="left" styleCode="Toprule Botrule Lrule Rrule" valign="top"> <content styleCode="bold">Adverse Reaction</content> </td> <td colspan="2" align="center" styleCode="Toprule Botrule Rrule" valign="top"> <content styleCode="bold">Percentage of Patients Reporting Reaction from BID Trials </content> </td> <td colspan="2" align="center" styleCode="Toprule Botrule Rrule" valign="top"> <content styleCode="bold">Percentage of Patients Reporting Reaction from QD Trials </content> </td> </tr> <tr> <td align="left" styleCode="Botrule Lrule Rrule" valign="top"/> <td align="center" styleCode="Botrule Rrule" valign="top"> <content styleCode="bold">STRATTERA (N=715) </content> </td> <td align="center" styleCode="Botrule Rrule" valign="top"> <content styleCode="bold">Placebo (N=434) </content> </td> <td align="center" styleCode="Botrule Rrule" valign="top"> <content styleCode="bold">STRATTERA (N=882) </content> </td> <td align="center" styleCode="Botrule Rrule" valign="top"> <content styleCode="bold">Placebo (N=500) </content> </td> </tr> <tr> <td align="left" styleCode="Botrule Lrule Rrule" valign="top"> <content styleCode="bold">Gastrointestinal Disorders</content> </td> <td align="center" styleCode="Botrule Rrule" valign="top"/> <td align="center" styleCode="Botrule Rrule" valign="top"/> <td align="center" styleCode="Botrule Rrule" valign="top"/> <td align="center" styleCode="Botrule Rrule" valign="top"/> </tr> <tr> <td align="left" styleCode="Botrule Lrule Rrule" valign="top"> Abdominal pain ^a </td> <td align="center" styleCode="Botrule Rrule" valign="top">17 </td> <td align="center" styleCode="Botrule Rrule" valign="top">13 </td> <td align="center" styleCode="Botrule Rrule" valign="top">18 </td> <td align="center" styleCode="Botrule Rrule" valign="top">7 </td> </tr> <tr> <td align="left" styleCode="Botrule Lrule Rrule" valign="top"> Vomiting </td> <td align="center" styleCode="Botrule Rrule" valign="top">11 </td> <td align="center" styleCode="Botrule Rrule" valign="top">8 </td> <td align="center" styleCode="Botrule Rrule" valign="top">11 </td> <td align="center" styleCode="Botrule Rrule" valign="top">4 </td> </tr> <tr> <td align="left" styleCode="Botrule Lrule Rrule" valign="top"> Nausea </td> <td align="center" styleCode="Botrule Rrule" valign="top">7 </td> <td align="center" styleCode="Botrule Rrule" valign="top">6 </td> <td align="center" styleCode="Botrule Rrule" valign="top">13 </td> <td align="center" styleCode="Botrule Rrule" valign="top">4 </td> </tr> <tr> <td align="left" styleCode="Botrule Lrule Rrule" valign="top"> Constipation ^b </td> <td align="center" styleCode="Botrule Rrule" valign="top">2 </td> <td align="center" styleCode="Botrule Rrule" valign="top">1 </td> <td align="center" styleCode="Botrule Rrule" valign="top">1 </td> <td align="center" styleCode="Botrule Rrule" valign="top">0 </td> </tr> <tr> <td align="left" styleCode="Botrule Lrule Rrule" valign="top"> <content styleCode="bold">General Disorders</content> </td> <td align="center" styleCode="Botrule Rrule" valign="top"/> <td align="center" styleCode="Botrule Rrule" valign="top"/> <td align="center" styleCode="Botrule Rrule" valign="top"/> <td align="center" styleCode="Botrule Rrule" valign="top"/> </tr> <tr> <td align="left" styleCode="Botrule Lrule Rrule" valign="top"> Fatigue </td> <td align="center" styleCode="Botrule Rrule" valign="top">6 </td> <td align="center" styleCode="Botrule Rrule" valign="top">4 </td> <td align="center" styleCode="Botrule Rrule" valign="top">9 </td> <td align="center" styleCode="Botrule Rrule" valign="top">2 </td> </tr> <tr> <td align="left" styleCode="Botrule Lrule Rrule" valign="top"> <content styleCode="bold">Psychiatric Disorders</content> </td> <td align="center" styleCode="Botrule Rrule" valign="top"/> <td align="center" styleCode="Botrule Rrule" valign="top"/> <td align="center" styleCode="Botrule Rrule" valign="top"/> <td align="center" styleCode="Botrule Rrule" valign="top"/> </tr> <tr> <td align="left" styleCode="Botrule Lrule Rrule" valign="top"> Mood swings ^c </td> <td align="center" styleCode="Botrule Rrule" valign="top">2 </td> <td align="center" styleCode="Botrule Rrule" valign="top">0 </td> <td align="center" styleCode="Botrule Rrule" valign="top">1 </td> <td align="center" styleCode="Botrule Rrule" valign="top">1 </td> </tr> </tbody> </table>

<table ID="t4" width="100%"> <caption>Table 4: Common Treatment-Emergent Adverse Reactions Associated with the Use of STRATTERA in Acute (up to 25 weeks) Adult Trials </caption> <col width="62.054%" align="left"/> <col width="18.973%" align="left"/> <col width="18.973%" align="left"/> <tfoot> <tr> <td colspan="3" align="left" valign="top"> <paragraph styleCode="footnote"> ^a Reactions reported by at least 2% of patients treated with atomoxetine, and greater than placebo. The following reactions did not meet this criterion but were reported by more atomoxetine-treated patients than placebo-treated patients and are possibly related to atomoxetine treatment: peripheral coldness, tachycardia, prostatitis, testicular pain, orgasm abnormal, flatulence, asthenia, feeling cold, muscle spasm, dysgeusia, agitation, restlessness, micturition urgency, pollakiuria, pruritus, urticaria, flushing, tremor, menstruation irregular, rash, and urinary retention. The following reactions were reported by at least 2% of patients treated with atomoxetine, and equal to or less than placebo: anxiety, diarrhea, back pain, headache, and oropharyngeal pain. </paragraph> </td> </tr> <tr> <td colspan="3" align="left" valign="top"> <paragraph styleCode="footnote"> ^b Abdominal pain includes the terms: abdominal pain upper, abdominal pain, stomach discomfort, abdominal discomfort, epigastric discomfort. </paragraph> </td> </tr> <tr> <td colspan="3" align="left" valign="top"> <paragraph styleCode="footnote"> ^c Somnolence includes the terms: sedation, somnolence. </paragraph> </td> </tr> <tr> <td colspan="3" align="left" valign="top"> <paragraph styleCode="footnote"> ^d Insomnia includes the terms: insomnia, initial insomnia, middle insomnia, and terminal insomnia. </paragraph> </td> </tr> <tr> <td colspan="3" align="left" valign="top"> <paragraph styleCode="footnote"> ^e Urinary hesitation includes the terms: urinary hesitation, urine flow decreased. </paragraph> </td> </tr> <tr> <td colspan="3" align="left" valign="top"> <paragraph styleCode="footnote"> ^f Based on total number of males (STRATTERA, N=943; placebo, N=869). </paragraph> </td> </tr> <tr> <td colspan="3" align="left" valign="top"> <paragraph styleCode="footnote"> ^g Based on total number of females (STRATTERA, N=754; placebo, N=691). </paragraph> </td> </tr> </tfoot> <tbody> <tr> <td align="left" styleCode="Toprule Botrule Lrule Rrule" valign="top"> <content styleCode="bold">Adverse Reaction</content> <content styleCode="bold"> ^a </content> </td> <td colspan="2" align="center" styleCode="Toprule Botrule Rrule" valign="top"> <content styleCode="bold">Percentage of Patients Reporting Reaction</content> </td> </tr> <tr> <td align="left" styleCode="Botrule Lrule Rrule" valign="top"> <content styleCode="bold"> System Organ Class/Adverse Reaction </content> </td> <td align="center" styleCode="Botrule Rrule" valign="top"> <content styleCode="bold">STRATTERA (N=1697) </content> </td> <td align="center" styleCode="Botrule Rrule" valign="top"> <content styleCode="bold">Placebo (N=1560) </content> </td> </tr> <tr> <td align="left" styleCode="Botrule Lrule Rrule" valign="top"> <content styleCode="bold">Cardiac Disorders</content> </td> <td align="center" styleCode="Botrule Rrule" valign="top"/> <td align="center" styleCode="Botrule Rrule" valign="top"/> </tr> <tr> <td align="left" styleCode="Botrule Lrule Rrule" valign="top"> Palpitations </td> <td align="center" styleCode="Botrule Rrule" valign="top">3 </td> <td align="center" styleCode="Botrule Rrule" valign="top">1 </td> </tr> <tr> <td align="left" styleCode="Botrule Lrule Rrule" valign="top"> <content styleCode="bold">Gastrointestinal Disorders</content> </td> <td align="center" styleCode="Botrule Rrule" valign="top"/> <td align="center" styleCode="Botrule Rrule" valign="top"/> </tr> <tr> <td align="left" styleCode="Botrule Lrule Rrule" valign="top"> Dry mouth </td> <td align="center" styleCode="Botrule Rrule" valign="top">20 </td> <td align="center" styleCode="Botrule Rrule" valign="top">5 </td> </tr> <tr> <td align="left" styleCode="Botrule Lrule Rrule" valign="top"> Nausea </td> <td align="center" styleCode="Botrule Rrule" valign="top">26 </td> <td align="center" styleCode="Botrule Rrule" valign="top">6 </td> </tr> <tr> <td align="left" styleCode="Botrule Lrule Rrule" valign="top"> Constipation </td> <td align="center" styleCode="Botrule Rrule" valign="top">8 </td> <td align="center" styleCode="Botrule Rrule" valign="top">3 </td> </tr> <tr> <td align="left" styleCode="Botrule Lrule Rrule" valign="top"> Abdominal pain ^b </td> <td align="center" styleCode="Botrule Rrule" valign="top">7 </td> <td align="center" styleCode="Botrule Rrule" valign="top">4 </td> </tr> <tr> <td align="left" styleCode="Botrule Lrule Rrule" valign="top"> Dyspepsia </td> <td align="center" styleCode="Botrule Rrule" valign="top">4 </td> <td align="center" styleCode="Botrule Rrule" valign="top">2 </td> </tr> <tr> <td align="left" styleCode="Botrule Lrule Rrule" valign="top"> Vomiting </td> <td align="center" styleCode="Botrule Rrule" valign="top">4 </td> <td align="center" styleCode="Botrule Rrule" valign="top">2 </td> </tr> <tr> <td align="left" styleCode="Botrule Lrule Rrule" valign="top"> <content styleCode="bold">General Disorders and Administration Site Conditions</content> </td> <td align="center" styleCode="Botrule Rrule" valign="top"/> <td align="center" styleCode="Botrule Rrule" valign="top"/> </tr> <tr> <td align="left" styleCode="Botrule Lrule Rrule" valign="top"> Fatigue </td> <td align="center" styleCode="Botrule Rrule" valign="top">10 </td> <td align="center" styleCode="Botrule Rrule" valign="top">6 </td> </tr> <tr> <td align="left" styleCode="Botrule Lrule Rrule" valign="top"> Chills </td> <td align="center" styleCode="Botrule Rrule" valign="top">3 </td> <td align="center" styleCode="Botrule Rrule" valign="top">0 </td> </tr> <tr> <td align="left" styleCode="Botrule Lrule Rrule" valign="top"> Feeling jittery </td> <td align="center" styleCode="Botrule Rrule" valign="top">2 </td> <td align="center" styleCode="Botrule Rrule" valign="top">1 </td> </tr> <tr> <td align="left" styleCode="Botrule Lrule Rrule" valign="top"> Irritability </td> <td align="center" styleCode="Botrule Rrule" valign="top">5 </td> <td align="center" styleCode="Botrule Rrule" valign="top">3 </td> </tr> <tr> <td align="left" styleCode="Botrule Lrule Rrule" valign="top"> Thirst </td> <td align="center" styleCode="Botrule Rrule" valign="top">2 </td> <td align="center" styleCode="Botrule Rrule" valign="top">1 </td> </tr> <tr> <td align="left" styleCode="Botrule Lrule Rrule" valign="top"> <content styleCode="bold">Investigations</content> </td> <td align="center" styleCode="Botrule Rrule" valign="top"/> <td align="center" styleCode="Botrule Rrule" valign="top"/> </tr> <tr> <td align="left" styleCode="Botrule Lrule Rrule" valign="top"> Weight decreased </td> <td align="center" styleCode="Botrule Rrule" valign="top">2 </td> <td align="center" styleCode="Botrule Rrule" valign="top">1 </td> </tr> <tr> <td align="left" styleCode="Botrule Lrule Rrule" valign="top"> <content styleCode="bold">Metabolism and Nutritional Disorders</content> </td> <td align="center" styleCode="Botrule Rrule" valign="top"/> <td align="center" styleCode="Botrule Rrule" valign="top"/> </tr> <tr> <td align="left" styleCode="Botrule Lrule Rrule" valign="top"> Decreased appetite </td> <td align="center" styleCode="Botrule Rrule" valign="top">16 </td> <td align="center" styleCode="Botrule Rrule" valign="top">3 </td> </tr> <tr> <td align="left" styleCode="Botrule Lrule Rrule" valign="top"> <content styleCode="bold">Nervous System Disorders</content> </td> <td align="center" styleCode="Botrule Rrule" valign="top"/> <td align="center" styleCode="Botrule Rrule" valign="top"/> </tr> <tr> <td align="left" styleCode="Botrule Lrule Rrule" valign="top"> Dizziness </td> <td align="center" styleCode="Botrule Rrule" valign="top">8 </td> <td align="center" styleCode="Botrule Rrule" valign="top">3 </td> </tr> <tr> <td align="left" styleCode="Botrule Lrule Rrule" valign="top"> Somnolence ^c </td> <td align="center" styleCode="Botrule Rrule" valign="top">8 </td> <td align="center" styleCode="Botrule Rrule" valign="top">5 </td> </tr> <tr> <td align="left" styleCode="Botrule Lrule Rrule" valign="top"> Paraesthesia </td> <td align="center" styleCode="Botrule Rrule" valign="top">3 </td> <td align="center" styleCode="Botrule Rrule" valign="top">0 </td> </tr> <tr> <td align="left" styleCode="Botrule Lrule Rrule" valign="top"> <content styleCode="bold">Psychiatric Disorders</content> </td> <td align="center" styleCode="Botrule Rrule" valign="top"/> <td align="center" styleCode="Botrule Rrule" valign="top"/> </tr> <tr> <td align="left" styleCode="Botrule Lrule Rrule" valign="top"> Abnormal dreams </td> <td align="center" styleCode="Botrule Rrule" valign="top">4 </td> <td align="center" styleCode="Botrule Rrule" valign="top">3 </td> </tr> <tr> <td align="left" styleCode="Botrule Lrule Rrule" valign="top"> Insomnia ^d </td> <td align="center" styleCode="Botrule Rrule" valign="top">15 </td> <td align="center" styleCode="Botrule Rrule" valign="top">8 </td> </tr> <tr> <td align="left" styleCode="Botrule Lrule Rrule" valign="top"> Libido decreased </td> <td align="center" styleCode="Botrule Rrule" valign="top">3 </td> <td align="center" styleCode="Botrule Rrule" valign="top">1 </td> </tr> <tr> <td align="left" styleCode="Botrule Lrule Rrule" valign="top"> Sleep disorder </td> <td align="center" styleCode="Botrule Rrule" valign="top">3 </td> <td align="center" styleCode="Botrule Rrule" valign="top">1 </td> </tr> <tr> <td align="left" styleCode="Botrule Lrule Rrule" valign="top"> <content styleCode="bold">Renal and Urinary Disorders</content> </td> <td align="center" styleCode="Botrule Rrule" valign="top"/> <td align="center" styleCode="Botrule Rrule" valign="top"/> </tr> <tr> <td align="left" styleCode="Botrule Lrule Rrule" valign="top"> Urinary hesitation ^e </td> <td align="center" styleCode="Botrule Rrule" valign="top">6 </td> <td align="center" styleCode="Botrule Rrule" valign="top">1 </td> </tr> <tr> <td align="left" styleCode="Botrule Lrule Rrule" valign="top"> Dysuria </td> <td align="center" styleCode="Botrule Rrule" valign="top">2 </td> <td align="center" styleCode="Botrule Rrule" valign="top">0 </td> </tr> <tr> <td align="left" styleCode="Botrule Lrule Rrule" valign="top"> <content styleCode="bold">Reproductive System and Breast Disorders</content> </td> <td align="center" styleCode="Botrule Rrule" valign="top"/> <td align="center" styleCode="Botrule Rrule" valign="top"/> </tr> <tr> <td align="left" styleCode="Botrule Lrule Rrule" valign="top"> Erectile dysfunction ^f </td> <td align="center" styleCode="Botrule Rrule" valign="top">8 </td> <td align="center" styleCode="Botrule Rrule" valign="top">1 </td> </tr> <tr> <td align="left" styleCode="Botrule Lrule Rrule" valign="top"> Dysmenorrhea ^g </td> <td align="center" styleCode="Botrule Rrule" valign="top">3 </td> <td align="center" styleCode="Botrule Rrule" valign="top">2 </td> </tr> <tr> <td align="left" styleCode="Botrule Lrule Rrule" valign="top"> Ejaculation delayed ^f and/or ejaculation disorder ^f </td> <td align="center" styleCode="Botrule Rrule" valign="top">4 </td> <td align="center" styleCode="Botrule Rrule" valign="top">1 </td> </tr> <tr> <td align="left" styleCode="Botrule Lrule Rrule" valign="top"> <content styleCode="bold">Skin and Subcutaneous Tissue Disorders</content> </td> <td align="center" styleCode="Botrule Rrule" valign="top"/> <td align="center" styleCode="Botrule Rrule" valign="top"/> </tr> <tr> <td align="left" styleCode="Botrule Lrule Rrule" valign="top"> Hyperhidrosis </td> <td align="center" styleCode="Botrule Rrule" valign="top">4 </td> <td align="center" styleCode="Botrule Rrule" valign="top">1 </td> </tr> <tr> <td align="left" styleCode="Botrule Lrule Rrule" valign="top"> <content styleCode="bold">Vascular Disorders</content> </td> <td align="center" styleCode="Botrule Rrule" valign="top"/> <td align="center" styleCode="Botrule Rrule" valign="top"/> </tr> <tr> <td align="left" styleCode="Botrule Lrule Rrule" valign="top"> Hot flush </td> <td align="center" styleCode="Botrule Rrule" valign="top">3 </td> <td align="center" styleCode="Botrule Rrule" valign="top">0 </td> </tr> </tbody> </table>