FDA label 6e0fd2d4-8fca-1967-e053-2a91aa0a1dd4

WARNING: DRUG DEPENDENCE Dexmethylphenidate hydrochloride extended-release capsules should be given cautiously to patients with a history of drug dependence or alcoholism. Chronic abusive use can lead to marked tolerance and psychological dependence with varying degrees of abnormal behavior. Frank psychotic episodes can occur, especially with parenteral abuse. Careful supervision is required during withdrawal from abusive use, since severe depression may occur. Withdrawal following chronic therapeutic use may unmask symptoms of the underlying disorder that may require follow-up. WARNING: DRUG DEPENDENCE See full prescribing information for complete boxed warning. Dexmethylphenidate hydrochloride extended-release capsules should be given cautiously to patients with a history of drug dependence or alcoholism. Chronic abusive use can lead to marked tolerance and psychological dependence, with varying degrees of abnormal behavior.

5 WARNINGS AND PRECAUTIONS Serious Cardiovascular Events: Sudden death has been reported in association with CNS stimulant treatment at usual doses in children and adolescents with structural cardiac abnormalities or other serious heart problems. Sudden death, stroke, and myocardial infarction have been reported in adults taking stimulant drugs at usual doses for ADHD. Stimulant products generally should not be used in patients with known structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, coronary artery disease, or other serious heart problems. ( 5.1 ) Increased Blood Pressure and Heart Rate: have been reported. Monitor patients for changes in blood pressure and heart rate. Caution should be exercised in treating patients whose underlying medical conditions might be compromised by increases in blood pressure or heart rate. ( 5.2 ) Assess Cardiovascular Status: prior to stimulant treatment, assess for cardiac disease with history and exam and, if suggested by findings, conduct further cardiac evaluation. Patients with emerging symptoms suggestive of cardiac disease should undergo a prompt cardiac evaluation. ( 5.3 ) Psychotic Symptoms: may be exacerbated in patients with psychotic disorders. ( 5.4 ) Bipolar Disorder: Use with particular care in ADHD patients with comorbid Bipolar Disorder. Before initiating stimulant therapy, obtain a detailed psychiatric history for patients with comorbid depressive symptoms, in order to determine risk for Bipolar Disorder. ( 5.5 ) Emergence of New Psychotic or Manic Symptoms: Treatment-emergent psychotic or manic symptoms without a prior history can be caused by stimulants at usual doses. Discontinuation of stimulant therapy may be indicated. ( 5.6 ) Aggression: Monitor for appearance of or worsening of aggressive behavior or hostility. ( 5.7 ) Long-Term Suppression of Growth: monitor height and weight in pediatric patients at appropriate intervals. Patients who are not growing or gaining weight as expected may need to have their treatment interrupted. ( 5.8 ) Seizures: The threshold for seizures may be lowered. In the presence of seizure, discontinue treatment. ( 5.9 ) Priapism: Cases of painful and prolonged penile erections and priapism have been reported with methylphenidate products. Immediate medical attention should be sought if signs or symptoms of prolonged penile erections or priapism are observed. ( 5.10 ) Peripheral Vasculopathy, including Raynaud’s phenomenon: Stimulants used to treat ADHD are associated with peripheral vasculopathy, including Raynaud’s phenomenon. Careful observation for digital changes is necessary during treatment with ADHD stimulants. ( 5.11 ) Visual Disturbance: difficulties with accommodation and blurring of vision have been reported with stimulant treatment. ( 5.12 ) Hematologic Monitoring: periodic monitoring of CBC with differential is advised during prolonged therapy. ( 5.14 ) 5.1 Sudden Death and Preexisting Structural Cardiac Abnormalities or Other Serious Heart Problems Children and Adolescents Sudden death has been reported in association with CNS stimulant 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, stimulant products 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 sympathomimetic effects of a stimulant drug. Adults Sudden death, stroke, and myocardial infarction have been reported in adults taking stimulant drugs at usual doses for ADHD. Although the role of stimulants 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. Adults with such abnormalities should also generally not be treated with stimulant drugs. 5.2 Hypertension and Other Cardiovascular Conditions Stimulant medications cause a modest increase in average blood pressure (about 2 to 4 mmHg) and average heart rate (about 3 to 6 bpm), and individuals may have larger increases. While the mean changes alone would not be expected to have short-term consequences, all patients should be monitored for larger changes in heart rate and blood pressure. Caution is indicated in treating patients whose underlying medical conditions might be compromised by increases in blood pressure or heart rate, e.g., those with preexisting hypertension, heart failure, recent myocardial infarction, or ventricular arrhythmia. 5.3 Assessing Cardiovascular Status in Patients being Treated with Stimulant Medications Children, adolescents, or adults who are being considered for treatment with stimulant medications 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 stimulant treatment should undergo a prompt cardiac evaluation. 5.4 Preexisting Psychosis Administration of stimulants may exacerbate symptoms of behavior disturbance and thought disorder in patients with a preexisting psychotic disorder. 5.5 Bipolar Illness Particular care should be taken in using stimulants to treat ADHD in patients with comorbid bipolar disorder because of concern for possible induction of a mixed/manic episode in such patients. Prior to initiating treatment with a stimulant, 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. 5.6 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 stimulants at usual doses. If such symptoms occur, consideration should be given to a possible causal role of the stimulant, and discontinuation of treatment may be appropriate. In a pooled analysis of multiple short-term, placebo-controlled studies, such symptoms occurred in about 0.1% (4 patients with events out of 3,482 exposed to methylphenidate or amphetamine for several weeks at usual doses) of stimulant-treated patients compared to 0 in placebo-treated patients. 5.7 Aggression Aggressive behavior or hostility is often observed in children and adolescents with ADHD, and has been reported in clinical trials and the postmarketing experience of some medications indicated for the treatment of ADHD. Although there is no systematic evidence that stimulants cause aggressive behavior or hostility, patients beginning treatment for ADHD should be monitored for the appearance of or worsening of aggressive behavior or hostility. 5.8 Long-Term Suppression of Growth Careful follow-up of weight and height in children ages 7 to 10 years who were randomized to either methylphenidate or non-medication treatment groups over 14 months, as well as in naturalistic subgroups of newly methylphenidate-treated and non-medication treated children over 36 months (to the ages of 10 to 13 years), suggests that consistently medicated children (i.e., treatment for 7 days per week throughout the year) have a temporary slowing in growth rate (on average, a total of about 2 cm less growth in height and 2.7 kg less growth in weight over 3 years), without evidence of growth rebound during this period of development. In the 7 week, double-blind, placebo-controlled study of dexmethylphenidate hydrochloride extended-release capsules, the mean weight gain was greater for patients receiving placebo (+0.4 kg) than for patients receiving dexmethylphenidate hydrochloride extended-release capsules (-0.5 kg). Published data are inadequate to determine whether chronic use of amphetamines may cause a similar suppression of growth, however, it is anticipated that they likely have this effect as well. Therefore, growth should be monitored during treatment with stimulants, and patients who are not growing or gaining height or weight as expected may need to have their treatment interrupted. 5.9 Seizures There is some clinical evidence that stimulants may lower the convulsive threshold in patients with prior history of seizures, in patients with prior EEG abnormalities in absence of seizures, and, very rarely, in patients without a history of seizures and no prior EEG evidence of seizures. In the presence of seizures, the drug should be discontinued. 5.10 Priapism Prolonged and painful erections, sometimes requiring surgical intervention, have been reported with methylphenidate products in both pediatric and adult patients. Priapism was not reported with drug initiation but developed after some time on the drug, often subsequent to an increase in dose. Priapism has also appeared during a period of drug withdrawal (drug holidays or during discontinuation). Patients who develop abnormally sustained or frequent and painful erections should seek immediate medical attention. 5.11 Peripheral Vasculopathy, Including Raynaud’s Phenomenon Stimulants, including dexmethylphenidate hydrochloride extended-release capsules, used to treat ADHD are associated with peripheral vasculopathy, including Raynaud’s phenomenon. Signs and symptoms are usually intermittent and mild; however, very rare sequelae include digital ulceration and/or soft tissue breakdown. Effects of peripheral vasculopathy, including Raynaud’s phenomenon, were observed in postmarketing reports at different times and at therapeutic doses in all age groups throughout the course of treatment. Signs and symptoms generally improve after reduction in dose or discontinuation of drug. Careful observation for digital changes is necessary during treatment with ADHD stimulants. Further clinical evaluation (e.g., rheumatology referral) may be appropriate for certain patients. 5.12 Visual Disturbance Difficulties with accommodation and blurring of vision have been reported with stimulant treatment. 5.13 Use in Children Under Six Years of Age Dexmethylphenidate hydrochloride extended-release capsules should not be used in children under 6 years of age, since safety and efficacy in this age group have not been established. 5.14 Hematologic Monitoring Periodic CBC, differential, and platelet counts are advised during prolonged therapy.

6 ADVERSE REACTIONS Dexmethylphenidate hydrochloride extended-release capsules were administered to 46 children and 7 adolescents with ADHD for up to 7 weeks and 206 adults with ADHD in clinical studies. During the clinical studies, 101 adult patients were treated for at least 6 months. Adverse events during exposure were obtained primarily by general inquiry and recorded by clinical investigators using terminology of their own choosing. Consequently, it is not possible to provide a meaningful estimate of the proportion of individuals experiencing adverse events without first grouping similar types of events into a smaller number of standardized event categories. In the tables and listings that follow, MedDRA terminology has been used to classify reported adverse events. The stated frequencies of adverse events represent the proportion of individuals who experienced, at least once, a treatment-emergent adverse event of the type listed. An event was considered treatment emergent if it occurred for the first time or worsened while receiving therapy following baseline evaluation. Most common adverse reactions (at least 5% and twice the incidence among placebo-treated patients) are dyspepsia, decreased appetite, headache, and anxiety for pediatric patients and dry mouth, dyspepsia, headache, and anxiety for adult patients. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact TEVA USA, PHARMACOVIGILANCE at 1-866-832-8537 or drug.safety@tevapharm.com; or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Adverse Events Associated with Discontinuation of Treatment in Acute Clinical Studies with Dexmethylphenidate Hydrochloride Extended-Release Capsules - Children Overall, 50 of 684 children treated with dexmethylphenidate hydrochloride immediate-release formulation (7.3%) experienced an adverse event that resulted in discontinuation. The most common reasons for discontinuation were twitching (described as motor or vocal tics), anorexia, insomnia, and tachycardia (approximately 1% each). None of the 53 dexmethylphenidate hydrochloride extended-release capsule-treated pediatric patients discontinued treatment due to adverse events in the 7 week, placebo-controlled study. 6.2 Adverse Events Occurring at an Incidence of 5% or More Among Dexmethylphenidate Hydrochloride Extended-Release Capsule-Treated Patients - Children Table 1 enumerates treatment-emergent adverse events for the placebo-controlled, parallel-group study in children and adolescents with ADHD at flexible dexmethylphenidate hydrochloride extended-release capsule doses of 5 to 30 mg/day. The table includes only those events that occurred in 5% or more of patients treated with dexmethylphenidate hydrochloride extended-release capsules and for which the incidence in patients treated with dexmethylphenidate hydrochloride extended-release capsules were at least twice the incidence in placebo-treated patients. The prescriber should be aware that these figures cannot be used to predict the incidence of adverse events in the course of usual medical practice where patient characteristics and other factors differ from those which prevailed in the clinical trials. Similarly, the cited frequencies cannot be compared with figures obtained from other clinical investigations involving different treatments, uses, and investigators. The cited figures, however, do provide the prescribing physician with some basis for estimating the relative contribution of drug and non-drug factors to the adverse event incidence rate in the population studied. Table 1. Treatment-Emergent Adverse Events Events, regardless of causality, for which the incidence for patients treated with dexmethylphenidate hydrochloride extended-release capsules was at least 5% and twice the incidence among placebo-treated patients. Incidence has been rounded to the nearest whole number. Occurring During Double-Blind Treatment–Pediatric Patients Dexmethylphenidate Hydrochloride Extended-Release Capsules N = 53 Placebo N = 47 No. of Patients with AEs Total 76% 57% Primary System Organ Class/ Adverse Event Preferred Term Gastrointestinal Disorders 38% 19% Dyspepsia 8% 4% Metabolism and Nutrition Disorders 34% 11% Decreased Appetite 30% 9% Nervous System Disorders 30% 13% Headache 25% 11% Psychiatric Disorders 26% 15% Anxiety 6% 0% Table 2 below enumerates the incidence of dose-related adverse events that occurred during a fixed-dose, double-blind, placebo-controlled trial of dexmethylphenidate hydrochloride extended-release capsules up to 30 mg/day versus placebo in children and adolescents with ADHD. Table 2. Dose-Related Adverse Events from a Fixed-dose Study of Double-Blind Treatment in Pediatric Patients by Organ-System and Preferred Term ADVERSE EVENT Dexmethylphenidate Hydrochloride Extended-Release Capsules Dexmethylphenidate Hydrochloride Extended-Release Capsules Dexmethylphenidate Hydrochloride Extended-Release Capsules Placebo 10 mg/d 20 mg/d 30 mg/d N = 64 N = 60 N = 58 N = 63 Gastrointestinal Disorders 22% 23% 29% 24% Vomiting 2% 8% 9% 0 Metabolism and Nutritional Disorders 16% 17% 22% 5% Anorexia 5% 5% 7% 0 Psychiatric Disorders 19% 20% 38% 8% Insomnia 5% 8% 17% 3% Depression 0 0 3% 0 Mood Swings 0 0 3% 2% Other Adverse Events Irritability 0 2% 5% 0 Nasal Congestion 0 0 5% 0 Pruritus 0 0 3% 0 6.3 Adverse Events Associated with Discontinuation of Treatment in Clinical Studies with Dexmethylphenidate Hydrochloride Extended-Release Capsules - Adults In the adult placebo-controlled study, 10.7% of the dexmethylphenidate hydrochloride extended-release capsule-treated patients and 7.5% of the placebo-treated patients discontinued for adverse events. Among dexmethylphenidate hydrochloride extended-release capsule-treated patients, insomnia (1.8%, n = 3), feeling jittery (1.8%, n = 3), anorexia (1.2%, n = 2), and anxiety (1.2%, n = 2) were the reasons for discontinuation reported by more than 1 patient. 6.4 Adverse Events Occurring at an Incidence of 5% or More Among Dexmethylphenidate Hydrochloride Extended-Release Capsule-Treated Patients - Adults Table 3 enumerates treatment-emergent adverse events for the placebo-controlled, parallel-group study in adults with ADHD at fixed dexmethylphenidate hydrochloride extended-release capsule doses of 20, 30, and 40 mg/day. The table includes only those events that occurred in 5% or more of patients in a dexmethylphenidate hydrochloride extended-release capsule dose group and for which the incidences in patients treated with dexmethylphenidate hydrochloride extended-release capsules appeared to increase with dose. The prescriber should be aware that these figures cannot be used to predict the incidence of adverse events in the course of usual medical practice where patient characteristics and other factors differ from those which prevailed in the clinical trials. Similarly, the cited frequencies cannot be compared with figures obtained from other clinical investigations involving different treatments, uses, and investigators. The cited figures, however, do provide the prescribing physician with some basis for estimating the relative contribution of drug and non-drug factors to the adverse event incidence rate in the population studied. Table 3. Treatment-Emergent Adverse Events Events, regardless of causality, for which the incidence was at least 5% in a dexmethylphenidate hydrochloride extended-release capsule group and which appeared to increase with randomized dose. Incidence has been rounded to the nearest whole number. Occurring During Double-Blind Treatment–Adults Dexmethylphenidate Hydrochloride Extended-Release Capsule, 20 mg Dexmethylphenidate Hydrochloride Extended-Release Capsule, 30 mg Dexmethylphenidate Hydrochloride Extended-Release Capsule, 40 mg Placebo N = 57 N = 54 N = 54 N = 53 No. of Patients with AEs Total 84% 94% 85% 68% Primary System Organ Class/ Adverse Event Preferred Term Gastrointestinal Disorders 28% 32% 44% 19% Dry Mouth 7% 20% 20% 4% Dyspepsia 5% 9% 9% 2% Nervous System Disorders 37% 39% 50% 28% Headache 26% 30% 39% 19% Psychiatric Disorders 40% 43% 46% 30% Anxiety 5% 11% 11% 2% Respiratory, Thoracic and Mediastinal Disorders 16% 9% 15% 8% Pharyngolaryngeal Pain 4% 4% 7% 2% Two other adverse reactions occurring in clinical trials with dexmethylphenidate hydrochloride extended-release capsules at a frequency greater than placebo, but which were not dose related were: feeling jittery (12% and 2%, respectively) and dizziness (6% and 2%, respectively). Table 4 summarizes changes in vital signs and weight that were recorded in the adult study (N = 218) of dexmethylphenidate hydrochloride extended-release capsules in the treatment of ADHD. Table 4. Changes (Mean ± SD) in Vital Signs and Weight by Randomized Dose During Double-Blind Treatment – Adults Dexmethylphenidate Hydrochloride Extended-Release Capsule, 20 mg (N = 57) Dexmethylphenidate Hydrochloride Extended-Release Capsule, 30 mg (N = 54) Dexmethylphenidate Hydrochloride Extended-Release Capsule, 40 mg (N = 54) Placebo (N = 53) Pulse (bpm) 3.1 ± 11.1 4.3 ± 11.7 6.0 ± 10.1 -1.4 ± 9.3 Diastolic BP (mmHg) -0.2 ± 8.2 1.2 ± 8.9 2.1 ± 8.0 0.3 ± 7.8 Weight (kg) -1.4 ± 2.0 -1.2 ± 1.9 -1.7 ± 2.3 -0.1 ± 3.9 6.5 Postmarketing Experience The following additional adverse reactions have been identified during postapproval use of dexmethylphenidate hydrochloride extended-release capsules. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency: Musculoskeletal: rhabdomyolysis Immune System Disorders: hypersensitivity reactions, including angioedema and anaphylaxis 6.6 Adverse Events with Other Methylphenidate HCl Dosage Forms Nervousness and insomnia are the most common adverse reactions reported with other methylphenidate products. In children, loss of appetite, abdominal pain, weight loss during prolonged therapy, insomnia, and tachycardia may occur more frequently; however, any of the other adverse reactions listed below may also occur. Other reactions include: Cardiac: angina, arrhythmia, palpitations, pulse increased or decreased, tachycardia Gastrointestinal: abdominal pain, nausea Immune: hypersensitivity reactions including skin rash, urticaria, fever, arthralgia, exfoliative dermatitis, erythema multiforme with histopathological findings of necrotizing vasculitis, and thrombocytopenic purpura Metabolism/Nutrition: anorexia, weight loss during prolonged therapy Nervous System: dizziness, drowsiness, dyskinesia, headache, rare reports of Tourette’s syndrome, toxic psychosis Vascular: blood pressure increased or decreased, cerebral arteritis and/or occlusion Although a definite causal relationship has not been established, the following have been reported in patients taking methylphenidate: Blood/Lymphatic: leukopenia and/or anemia Hepatobiliary: abnormal liver function, ranging from transaminase elevation to hepatic coma Psychiatric: transient depressed mood, aggressive behavior, libido changes Skin/Subcutaneous: scalp hair loss Urogenital: priapism Very rare reports of neuroleptic malignant syndrome (NMS) have been received, and, in most of these, patients were concurrently receiving therapies associated with NMS. In a single report, a 10-year-old boy who had been taking methylphenidate for approximately 18 months experienced an NMS-like event within 45 minutes of ingesting his first dose of venlafaxine. It is uncertain whether this case represented a drug-drug interaction, a response to either drug alone, or some other cause.

<table ID="_RefID5627C8484D074E98935E269EA26BF21B" width="100%"> <caption>Table 1. Treatment-Emergent Adverse Events <footnote ID="_RefID6AC81CA60A584C6EADC6D3D441006701">Events, regardless of causality, for which the incidence for patients treated with dexmethylphenidate hydrochloride extended-release capsules was at least 5% and twice the incidence among placebo-treated patients. Incidence has been rounded to the nearest whole number. </footnote> Occurring During Double-Blind Treatment&#x2013;Pediatric Patients </caption> <col width="43%"/> <col width="49%"/> <col width="9%"/> <tbody> <tr styleCode="Toprule"> <td align="center" styleCode="Botrule Toprule "> <paragraph/> </td> <td align="center" styleCode="Botrule Toprule "> <paragraph> <content styleCode="bold">Dexmethylphenidate Hydrochloride Extended-Release Capsules</content> </paragraph> <paragraph> <content styleCode="bold">N = 53</content> </paragraph> </td> <td align="center" styleCode="Botrule Toprule "> <paragraph> <content styleCode="bold">Placebo</content> </paragraph> <paragraph> <content styleCode="bold">N = 47</content> </paragraph> </td> </tr> <tr> <td styleCode="Toprule "> <paragraph> <content styleCode="bold">No. of Patients with AEs</content> </paragraph> </td> <td align="center" styleCode="Toprule "> <paragraph/> </td> <td align="center" styleCode="Toprule "> <paragraph/> </td> </tr> <tr> <td> <paragraph> Total </paragraph> </td> <td align="center"> <paragraph> 76% </paragraph> </td> <td align="center"> <paragraph> 57% </paragraph> </td> </tr> <tr> <td> <paragraph> <content styleCode="bold"> Primary System Organ Class/</content> </paragraph> <paragraph> <content styleCode="bold"> Adverse Event Preferred Term</content> </paragraph> </td> <td align="center"> <paragraph/> </td> <td align="center"> <paragraph/> </td> </tr> <tr> <td> <paragraph> <content styleCode="bold">Gastrointestinal Disorders</content> </paragraph> </td> <td align="center"> <paragraph> 38% </paragraph> </td> <td align="center"> <paragraph> 19% </paragraph> </td> </tr> <tr> <td> <paragraph> Dyspepsia </paragraph> </td> <td align="center"> <paragraph> 8% </paragraph> </td> <td align="center"> <paragraph> 4% </paragraph> </td> </tr> <tr> <td> <paragraph> <content styleCode="bold">Metabolism and Nutrition Disorders</content> </paragraph> </td> <td align="center"> <paragraph> 34% </paragraph> </td> <td align="center"> <paragraph> 11% </paragraph> </td> </tr> <tr> <td> <paragraph> Decreased Appetite </paragraph> </td> <td align="center"> <paragraph> 30% </paragraph> </td> <td align="center"> <paragraph> 9% </paragraph> </td> </tr> <tr> <td> <paragraph> <content styleCode="bold">Nervous System Disorders</content> </paragraph> </td> <td align="center"> <paragraph> 30% </paragraph> </td> <td align="center"> <paragraph> 13% </paragraph> </td> </tr> <tr> <td> <paragraph> Headache </paragraph> </td> <td align="center"> <paragraph> 25% </paragraph> </td> <td align="center"> <paragraph> 11% </paragraph> </td> </tr> <tr> <td> <paragraph> <content styleCode="bold">Psychiatric Disorders</content> </paragraph> </td> <td align="center"> <paragraph> 26% </paragraph> </td> <td align="center"> <paragraph> 15% </paragraph> </td> </tr> <tr styleCode="Botrule"> <td styleCode="Botrule "> <paragraph> Anxiety </paragraph> </td> <td align="center" styleCode="Botrule "> <paragraph> 6% </paragraph> </td> <td align="center" styleCode="Botrule "> <paragraph> 0% </paragraph> </td> </tr> </tbody> </table>

<table ID="_RefID2C44E6186F744E0D89C69B5DF5C751E7" width="100%"> <caption>Table 2. Dose-Related Adverse Events from a Fixed-dose Study of Double-Blind Treatment in Pediatric Patients by Organ-System and Preferred Term </caption> <col width="17%"/> <col width="25%"/> <col width="25%"/> <col width="25%"/> <col width="9%"/> <tbody> <tr styleCode="Toprule"> <td rowspan="3"> <paragraph> <content styleCode="bold">ADVERSE</content> </paragraph> <paragraph> <content styleCode="bold">EVENT</content> </paragraph> </td> <td align="center"> <paragraph> <content styleCode="bold">Dexmethylphenidate Hydrochloride Extended-Release Capsules</content> </paragraph> </td> <td align="center"> <paragraph> <content styleCode="bold">Dexmethylphenidate Hydrochloride Extended-Release Capsules</content> </paragraph> </td> <td align="center"> <paragraph> <content styleCode="bold">Dexmethylphenidate Hydrochloride Extended-Release Capsules</content> </paragraph> </td> <td align="center"> <paragraph> <content styleCode="bold">Placebo</content> </paragraph> </td> </tr> <tr> <td align="center"> <paragraph> <content styleCode="bold">10 mg/d</content> </paragraph> </td> <td align="center"> <paragraph> <content styleCode="bold">20 mg/d</content> </paragraph> </td> <td align="center"> <paragraph> <content styleCode="bold">30 mg/d</content> </paragraph> </td> <td/> </tr> <tr> <td align="center" styleCode="Botrule "> <paragraph> <content styleCode="bold">N = 64</content> </paragraph> </td> <td align="center" styleCode="Botrule "> <paragraph> <content styleCode="bold">N = 60</content> </paragraph> </td> <td align="center" styleCode="Botrule "> <paragraph> <content styleCode="bold">N = 58</content> </paragraph> </td> <td align="center" styleCode="Botrule "> <paragraph> <content styleCode="bold">N = 63</content> </paragraph> </td> </tr> <tr> <td styleCode="Toprule "> <paragraph> <content styleCode="bold">Gastrointestinal Disorders</content> </paragraph> </td> <td align="center" styleCode="Toprule "> <paragraph>22%</paragraph> </td> <td align="center" styleCode="Toprule "> <paragraph>23%</paragraph> </td> <td align="center" styleCode="Toprule "> <paragraph>29%</paragraph> </td> <td align="center" styleCode="Toprule "> <paragraph>24%</paragraph> </td> </tr> <tr> <td> <paragraph>Vomiting</paragraph> </td> <td align="center"> <paragraph> 2%</paragraph> </td> <td align="center"> <paragraph> 8%</paragraph> </td> <td align="center"> <paragraph> 9%</paragraph> </td> <td align="center"> <paragraph>0</paragraph> </td> </tr> <tr> <td> <paragraph> <content styleCode="bold">Metabolism and</content> </paragraph> <paragraph> <content styleCode="bold">Nutritional Disorders</content> </paragraph> </td> <td align="center"> <paragraph>16%</paragraph> </td> <td align="center"> <paragraph>17%</paragraph> </td> <td align="center"> <paragraph>22%</paragraph> </td> <td align="center"> <paragraph> 5%</paragraph> </td> </tr> <tr> <td> <paragraph>Anorexia</paragraph> </td> <td align="center"> <paragraph> 5%</paragraph> </td> <td align="center"> <paragraph> 5%</paragraph> </td> <td align="center"> <paragraph> 7%</paragraph> </td> <td align="center"> <paragraph>0</paragraph> </td> </tr> <tr> <td> <paragraph> <content styleCode="bold">Psychiatric Disorders</content> </paragraph> </td> <td align="center"> <paragraph>19%</paragraph> </td> <td align="center"> <paragraph>20%</paragraph> </td> <td align="center"> <paragraph>38%</paragraph> </td> <td align="center"> <paragraph> 8%</paragraph> </td> </tr> <tr> <td> <paragraph>Insomnia</paragraph> </td> <td align="center"> <paragraph> 5%</paragraph> </td> <td align="center"> <paragraph> 8%</paragraph> </td> <td align="center"> <paragraph>17%</paragraph> </td> <td align="center"> <paragraph> 3%</paragraph> </td> </tr> <tr> <td> <paragraph>Depression</paragraph> </td> <td align="center"> <paragraph>0</paragraph> </td> <td align="center"> <paragraph>0</paragraph> </td> <td align="center"> <paragraph> 3%</paragraph> </td> <td align="center"> <paragraph>0</paragraph> </td> </tr> <tr> <td> <paragraph>Mood Swings</paragraph> </td> <td align="center"> <paragraph>0</paragraph> </td> <td align="center"> <paragraph>0</paragraph> </td> <td align="center"> <paragraph> 3%</paragraph> </td> <td align="center"> <paragraph> 2%</paragraph> </td> </tr> <tr> <td> <paragraph> <content styleCode="bold">Other Adverse Events</content> </paragraph> </td> <td/> <td/> <td/> <td/> </tr> <tr> <td> <paragraph>Irritability</paragraph> </td> <td align="center"> <paragraph>0</paragraph> </td> <td align="center"> <paragraph> 2%</paragraph> </td> <td align="center"> <paragraph> 5%</paragraph> </td> <td align="center"> <paragraph>0</paragraph> </td> </tr> <tr> <td> <paragraph>Nasal Congestion</paragraph> </td> <td align="center"> <paragraph>0</paragraph> </td> <td align="center"> <paragraph>0</paragraph> </td> <td align="center"> <paragraph> 5%</paragraph> </td> <td align="center"> <paragraph>0</paragraph> </td> </tr> <tr styleCode="Botrule"> <td styleCode="Botrule "> <paragraph>Pruritus</paragraph> </td> <td align="center" styleCode="Botrule "> <paragraph>0</paragraph> </td> <td align="center" styleCode="Botrule "> <paragraph>0</paragraph> </td> <td align="center" styleCode="Botrule "> <paragraph> 3%</paragraph> </td> <td align="center" styleCode="Botrule "> <paragraph>0</paragraph> </td> </tr> </tbody> </table>

<table ID="_RefID8578413E1ABB452D8FE199779A150A2D" width="100%"> <caption>Table 3. Treatment-Emergent Adverse Events <footnote ID="_RefIDB07651D09D70417392117CDC223A5B76">Events, regardless of causality, for which the incidence was at least 5% in a dexmethylphenidate hydrochloride extended-release capsule group and which appeared to increase with randomized dose. Incidence has been rounded to the nearest whole number. </footnote> Occurring During Double-Blind Treatment&#x2013;Adults </caption> <col width="27%"/> <col width="21%"/> <col width="21%"/> <col width="21%"/> <col width="9%"/> <tbody> <tr styleCode="Toprule"> <td align="center" rowspan="2"> <paragraph/> </td> <td align="center"> <paragraph> <content styleCode="bold"> Dexmethylphenidate Hydrochloride Extended-Release Capsule, 20 mg</content> </paragraph> </td> <td align="center"> <paragraph> <content styleCode="bold"> Dexmethylphenidate Hydrochloride Extended-Release Capsule, 30 mg </content> </paragraph> </td> <td align="center"> <paragraph> <content styleCode="bold"> Dexmethylphenidate Hydrochloride Extended-Release Capsule, 40 mg </content> </paragraph> </td> <td align="center"> <paragraph> <content styleCode="bold">Placebo</content> </paragraph> </td> </tr> <tr> <td align="center" styleCode="Botrule "> <paragraph> <content styleCode="bold">N = 57</content> </paragraph> </td> <td align="center" styleCode="Botrule "> <paragraph> <content styleCode="bold">N = 54</content> </paragraph> </td> <td align="center" styleCode="Botrule "> <paragraph> <content styleCode="bold">N = 54</content> </paragraph> </td> <td align="center" styleCode="Botrule "> <paragraph> <content styleCode="bold">N = 53</content> </paragraph> </td> </tr> <tr> <td styleCode="Toprule "> <paragraph> <content styleCode="bold">No. of Patients with AEs</content> </paragraph> </td> <td align="center" styleCode="Toprule "> <paragraph/> </td> <td align="center" styleCode="Toprule "> <paragraph/> </td> <td align="center" styleCode="Toprule "> <paragraph/> </td> <td align="center" styleCode="Toprule "> <paragraph/> </td> </tr> <tr> <td> <paragraph> Total </paragraph> </td> <td align="center"> <paragraph>84%</paragraph> </td> <td align="center"> <paragraph> 94% </paragraph> </td> <td align="center"> <paragraph> 85% </paragraph> </td> <td align="center"> <paragraph> 68% </paragraph> </td> </tr> <tr> <td styleCode="Botrule "> <paragraph> <content styleCode="bold">Primary System Organ Class/ Adverse Event Preferred Term </content> </paragraph> </td> <td styleCode="Botrule "/> <td align="center" styleCode="Botrule "> <paragraph/> </td> <td align="center" styleCode="Botrule "> <paragraph/> </td> <td align="center" styleCode="Botrule "> <paragraph/> </td> </tr> <tr> <td styleCode="Toprule "> <paragraph> <content styleCode="bold">Gastrointestinal Disorders</content> </paragraph> </td> <td align="center" styleCode="Toprule "> <paragraph>28%</paragraph> </td> <td align="center" styleCode="Toprule "> <paragraph> 32% </paragraph> </td> <td align="center" styleCode="Toprule "> <paragraph> 44% </paragraph> </td> <td align="center" styleCode="Toprule "> <paragraph> 19% </paragraph> </td> </tr> <tr> <td> <paragraph> Dry Mouth </paragraph> </td> <td align="center"> <paragraph> 7%</paragraph> </td> <td align="center"> <paragraph> 20% </paragraph> </td> <td align="center"> <paragraph> 20% </paragraph> </td> <td align="center"> <paragraph> 4% </paragraph> </td> </tr> <tr> <td> <paragraph> Dyspepsia </paragraph> </td> <td align="center"> <paragraph> 5%</paragraph> </td> <td align="center"> <paragraph> 9% </paragraph> </td> <td align="center"> <paragraph> 9% </paragraph> </td> <td align="center"> <paragraph> 2% </paragraph> </td> </tr> <tr> <td> <paragraph> <content styleCode="bold">Nervous System Disorders</content> </paragraph> </td> <td align="center"> <paragraph>37%</paragraph> </td> <td align="center"> <paragraph> 39% </paragraph> </td> <td align="center"> <paragraph> 50% </paragraph> </td> <td> <paragraph> 28% </paragraph> </td> </tr> <tr> <td> <paragraph> Headache </paragraph> </td> <td align="center"> <paragraph>26%</paragraph> </td> <td align="center"> <paragraph> 30% </paragraph> </td> <td align="center"> <paragraph> 39% </paragraph> </td> <td align="center"> <paragraph> 19% </paragraph> </td> </tr> <tr> <td> <paragraph> <content styleCode="bold">Psychiatric Disorders</content> </paragraph> </td> <td align="center"> <paragraph>40%</paragraph> </td> <td align="center"> <paragraph> 43% </paragraph> </td> <td align="center"> <paragraph> 46% </paragraph> </td> <td align="center"> <paragraph> 30% </paragraph> </td> </tr> <tr> <td> <paragraph> Anxiety </paragraph> </td> <td align="center"> <paragraph> 5%</paragraph> </td> <td align="center"> <paragraph> 11% </paragraph> </td> <td align="center"> <paragraph> 11% </paragraph> </td> <td align="center"> <paragraph> 2% </paragraph> </td> </tr> <tr> <td> <paragraph> <content styleCode="bold">Respiratory, Thoracic and Mediastinal Disorders</content> </paragraph> </td> <td align="center"> <paragraph>16%</paragraph> </td> <td align="center"> <paragraph> 9% </paragraph> </td> <td align="center"> <paragraph> 15% </paragraph> </td> <td> <paragraph> 8% </paragraph> </td> </tr> <tr> <td styleCode="Botrule "> <paragraph> Pharyngolaryngeal Pain </paragraph> </td> <td align="center" styleCode="Botrule "> <paragraph> 4%</paragraph> </td> <td align="center" styleCode="Botrule "> <paragraph> 4% </paragraph> </td> <td align="center" styleCode="Botrule "> <paragraph> 7% </paragraph> </td> <td align="center" styleCode="Botrule "> <paragraph> 2% </paragraph> </td> </tr> </tbody> </table>