Dexmethylphenidate Hydrochloride Extended-Release

WARNING: ABUSE AND DEPENDENCE CNS stimulants, including Dexmethylphenidate Hydrochloride Extended-release Capsules, other methylphenidate-containing products, and amphetamines, have a high potential for abuse and dependence. Assess the risk of abuse prior to prescribing, and monitor for signs of abuse and dependence while on therapy [see Warning and Precautions (5.1) , Drug Abuse and Dependence (9.2 , 9.3) ] . WARNING: ABUSE AND DEPENDENCE See full prescribing information for complete boxed warning CNS stimulants, including Dexmethylphenidate Hydrochloride Extended-release Capsules, other methylphenidate-containing products, and amphetamines, have a high potential for abuse and dependence ( 5.1 , 9.2 , 9.3 ). Assess the risk of abuse prior to prescribing and monitor for signs of abuse and dependence while on therapy ( 5.1 , 9.2 ).

5 WARNINGS AND PRECAUTIONS Serious Cardiovascular Events: Sudden death has been reported in association with CNS stimulant treatment at usual doses in pediatric patients with structural cardiac abnormalities or other serious heart problems. In adults, sudden death, stroke, and myocardial infarction have been reported Avoid use in patients with known structural cardiac abnormalities, cardiomyopathy, serious heart rhythm arrhythmias, or coronary artery disease ( 5.2 ). Blood Pressure and Heart Rate Increases: Monitor blood pressure and pulse. Consider the benefits and risk in patients for whom an increase in blood pressure or heart rate would be problematic ( 5.3 ). Psychiatric Adverse Reactions: Use of stimulants may cause psychotic or manic symptoms in patients with no prior history, or exacerbation of symptoms in patients with preexisting psychiatric illness. Evaluate for existing psychotic or bipolar disorder prior to Dexmethylphenidate Hydrochloride Extended-release Capsules use ( 5.4 ). 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 ( 5.5 ). 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 ( 5.6 ). Long-Term Suppression of Growth: Monitor height and weight at appropriate intervals in pediatric patients ( 5.7 ). 5.1 Potential for Abuse and Dependence CNS stimulants, including Dexmethylphenidate Hydrochloride Extended-release Capsules, other methylphenidate-containing products, and amphetamines, have a high potential for abuse and dependence. Assess the risk of abuse prior to prescribing, and monitor for signs of abuse and dependence while on therapy [see Boxed Warning , Drug Abuse and Dependence ( 9.2 , 9.3 )] . 5.2 Serious Cardiovascular Reactions Sudden death, stroke and myocardial infarction have been reported in adults with CNS stimulant treatment at recommended doses. Sudden death has been reported in pediatric patients with structural cardiac abnormalities and other serious heart problems taking CNS stimulants at recommended doses for ADHD. Avoid use in patients with known serious structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, coronary artery disease, and other serious heart problems. Further evaluate patients who develop exertional chest pain, unexplained syncope, or arrhythmias during Dexmethylphenidate Hydrochloride Extended-release Capsules treatment. 5.3 Blood Pressure and Heart Rate Increases CNS stimulants cause an increase in blood pressure (mean increase approximately 2 to 4 mmHg) and heart rate (mean increase approximately 3 to 6 bpm). Individuals may have larger increases. Monitor all patients for hypertension and tachycardia. 5.4 Psychiatric Adverse Reactions Exacerbation of Preexisting Psychosis CNS stimulants may exacerbate symptoms of behavior disturbance and thought disorder in patients with a preexisting psychotic disorder. Induction of a Manic Episode in Patients with Bipolar Disorder CNS stimulants may induce a manic or mixed mood episode in patients. Prior to initiating treatment, screen patients for risk factors for developing manic episode (e.g., comorbid or history of depressive symptoms or a family history of suicide, bipolar disorder, or depression). New Psychotic or Manic Symptoms CNS stimulants, at recommended doses, may cause psychotic or manic symptoms (e.g., hallucinations, delusional thinking, or mania) in patients without a prior history of psychotic illness or mania. If such symptoms occur, consider discontinuing Dexmethylphenidate Hydrochloride Extended-release Capsules. In a pooled analysis of multiple short-term, placebo-controlled studies of CNS stimulants, psychotic or manic symptoms occurred in approximately 0.1% of CNS stimulant-treated patients, compared to 0 in placebo-treated patients. 5.5 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. 5.6 Peripheral Vasculopathy, Including Raynaud's Phenomenon CNS 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 post-marketing 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. 5.7 Long-Term Suppression of Growth CNS stimulants have been associated with weight loss and slowing of growth rate in pediatric patients. In a 7-week, double-blind, placebo-controlled study of dexmethylphenidate hydrochloride extended-release capsules, the mean weight gain was greater for pediatric patients (ages 6 to 17 years) receiving placebo (+0.4 kg) than for patients receiving dexmethylphenidate hydrochloride extended-release capsules (-0.5 kg). Careful follow-up of weight and height in pediatric patients 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 patients over 36 months (to the ages of 10 to 13 years), suggests that consistently medicated pediatric patients (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. Closely monitor growth (weight and height) in pediatric patients treated with CNS stimulants, including Dexmethylphenidate Hydrochloride Extended-release Capsules, and patients who are not growing or gaining height or weight as expected may need to have their treatment interrupted.

6 ADVERSE REACTIONS The following are discussed in more detail in other sections of the labeling: Abuse and Dependence [see Boxed Warning , Warnings and Precautions (5.1) , Drug Abuse and Dependence ( 9.2 , 9.3 )] Known hypersensitivity to methylphenidate or other ingredients of Dexmethylphenidate Hydrochloride Extended-release Capsules [see Contraindications (4) ] Hypertensive Crisis with Concomitant Use of Monoamine Oxidase Inhibitors [see Contraindications (4) , Drug Interactions (7.1) ] Serious Cardiovascular Reactions [see Warnings and Precautions (5.2) ] Blood Pressure and Heart Rate Increases [see Warnings and Precautions (5.3) ] Psychiatric Adverse Reactions [see Warnings and Precautions (5.4) ] Priapism [see Warnings and Precautions (5.5) ] Peripheral Vasculopathy, including Raynaud’s Phenomenon [see Warnings and Precautions (5.6) ] Long-Term Suppression of Growth [see Warnings and Precautions (5.7) ] The most common adverse reactions (greater than or equal to 5% and twice the rate of placebo): Pediatric patients 6 to 17 years: dyspepsia, decreased appetite, headache, and anxiety ( 6.1 ). Adults: dry mouth, dyspepsia, headache, pharyngolaryngeal pain, and anxiety ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Par Pharmaceutical at 1-800-828-9393 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. Clinical Trials Experience with Dexmethylphenidate Hydrochloride Extended-Release Capsules in Pediatric Patients with ADHD The safety data in this section is based on data from a 7-week controlled clinical study of dexmethylphenidate hydrochloride extended-release capsules in 100 (103 randomized) pediatric patients with ADHD ages 6 to 17 years (ages 6 to 12, n = 86; ages 13 to 17, n = 17). This study was a randomized, double-blind, placebo-controlled, parallel-group study to evaluate the time of onset, duration of efficacy, tolerability, safety of dexmethylphenidate hydrochloride extended-release capsules 5 mg to 30 mg/day who met DSM-IV criteria for ADHD [ see Clinical Studies (14.1) ] . Most Common Adverse Reactions (incidence of greater than or equal to 5% and at least twice placebo): dyspepsia, decreased appetite, headache and anxiety. Adverse Reactions Leading to Discontinuation : 50 of 684 (7.3%) pediatric patients treated with dexmethylphenidate immediate-release tablets experienced an adverse reaction 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). Table 1 enumerates adverse reactions for the placebo-controlled, parallel-group study in children and adolescents with ADHD at flexible dexmethylphenidate hydrochloride extended-release capsules doses of 5–30 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 was at least twice the incidence in placebo-treated patients. Table 1: Common Adverse Reactions in Pediatric Patients (6 to 17 years of age) with ADHD Abbreviation: attention deficit hyperactivity disorder. System Organ Class Adverse Reaction Dexmethylphenidate HCl ER Capsules N=53 Placebo N=47 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 reactions that occurred during a fixed-dose, double-blind, placebo-controlled trial in pediatric patients with ADHD taking dexmethylphenidate hydrochloride extended-release capsules up to 30 mg daily versus placebo. The table includes only those reactions that occurred in patients treated with dexmethylphenidate hydrochloride extended-release capsules for which the incidence was at least 5% and greater than the incidence among placebo-treated patients. Table 2: Dose-Related Adverse Reactions in Pediatric Patients (6 to 17 years of age) with ADHD Abbreviation: attention deficit hyperactivity disorder. System Organ Class Adverse Reaction Dexmethylphenidate HCl ER Capsules Dexmethylphenidate HCl ER Capsules Dexmethylphenidate HCl ER Capsules Placebo 10 mg/d N=64 20 mg/d N=60 30 mg/d 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 Reactions Irritability 0% 2% 5% 0% Nasal Congestion 0% 0% 5% 0% Pruritus 0% 0% 3% 0% Clinical Trials Experience With Dexmethylphenidate Hydrochloride Extended-Release Capsules in Adult Patients With ADHD The safety data in this section is based on data from a 5-week controlled clinical study of dexmethylphenidate hydrochloride extended-release capsules in 218 adult patients (221 randomized) with ADHD ages 18 to 60 years. In this study, 101 adult patients were treated for at least 6 months. This study was a randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy, safety, and tolerability of dexmethylphenidate hydrochloride extended-release capsules 20 mg, 30 mg, or 40 mg daily who met DSM-IV criteria for ADHD [ see Clinical Studies (14.2) ] . Most Common Adverse Reactions (incidence of greater than or equal to 5% and at least twice placebo): dry mouth, dyspepsia, headache, anxiety, and pharyngolaryngeal pain. Adverse Reactions Leading to Discontinuation : During the double-blind phase of the study, 10.7% of the dexmethylphenidate hydrochloride extended-release capsules - treated patients and 7.5% of the placebo-treated patients discontinued due to adverse reactions. Three patients (1.8%) in the dexmethylphenidate hydrochloride extended-release capsules discontinued due to insomnia and jittery, respectively and two patients (1.2%) in the dexmethylphenidate hydrochloride extended-release capsules discontinued due to anorexia and anxiety, respectively. Table 3 enumerates adverse reactions for the placebo-controlled, parallel-group study in adults with ADHD at fixed dexmethylphenidate hydrochloride extended-release capsules 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 capsules dose group and for which the incidences in patients treated with dexmethylphenidate hydrochloride extended-release capsules appeared to increase with dose. Table 3: Dose-Related Adverse Reactions in Adult Patients (18 to 60 years of age) with ADHD System Organ Class Adverse Reaction Dexmethylphenidate HCl ER Capsules 20 mg N=57 Dexmethylphenidate HCl ER Capsules 30 mg N=54 Dexmethylphenidate HCl ER Capsules 40 mg N=54 Placebo N=53 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 HCl ER Capsules 20 mg (N= 57) Dexmethylphenidate HCl ER Capsules 30 mg (N= 54) Dexmethylphenidate HCl ER Capsules 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 6.2 Post-Marketing Experience The following additional adverse reactions have been identified during post-approval use of dexmethylphenidate. 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 Musculoskeletal: rhabdomyolysis Immune System Disorders: hypersensitivity reactions, including angioedema and anaphylaxis Adverse Reactions Reported with all Ritalin (methylphenidate) and Dexmethylphenidate Hydrochloride Formulations The following adverse reactions associated with the use of all Ritalin (methylphenidate) and dexmethylphenidate hydrochloride formulations were identified in clinical trials, spontaneous reports, and literature. Because these reactions were reported voluntarily from a population of uncertain size, it is not always possible to estimate their frequency reliably or to establish a causal relationship to drug exposure. Infections and Infestations: nasopharyngitis Blood and the Lymphatic System Disorders: leukopenia, thrombocytopenia, anemia Immune System Disorders: hypersensitivity reactions, including angioedema and anaphylaxis Metabolism and Nutrition Disorders: decreased appetite, reduced weight gain, and suppression of growth during prolonged use in pediatric patients Psychiatric Disorders: insomnia, anxiety, restlessness, agitation, psychosis (sometimes with visual and tactile hallucinations), depressed mood Nervous System Disorders: headache, dizziness, tremor, dyskinesia including choreoathetoid movements, drowsiness, convulsions, cerebrovascular disorders (including vasculitis, cerebral hemorrhages and cerebrovascular accidents), serotonin syndrome in combination with serotonergic drugs Eye Disorders: blurred vision, difficulties in visual accommodation Cardiac Disorders: tachycardia, palpitations, increased blood pressure, arrhythmias, angina pectoris Respiratory, Thoracic and Mediastinal Disorders: cough Gastrointestinal Disorders: dry mouth, nausea, vomiting, abdominal pain, dyspepsia Hepatobiliary Disorders: abnormal liver function, ranging from transaminase elevation to severe hepatic injury Skin and Subcutaneous Tissue Disorders: hyperhidrosis, pruritus, urticaria, exfoliative dermatitis, scalp hair loss, erythema multiforme rash, thrombocytopenic purpura Musculoskeletal and Connective Tissue Disorders: arthralgia, muscle cramps, rhabdomyolysis Investigations: weight loss (adult ADHD patients) Additional Adverse Reactions Reported with Other Methylphenidate Products The list below shows adverse reactions not listed with Ritalin (methylphenidate) and dexmethylphenidate hydrochloride formulations [see Adverse Reactions (6.2) ] that have been reported with other methylphenidate products based on clinical trials data and postmarketing spontaneous reports. Blood and Lymphatic Disorders: pancytopenia Immune System Disorders: hypersensitivity reactions such as auricular swelling, bullous conditions, eruptions, exanthemas Psychiatric Disorders: affect lability, mania, disorientation, libido changes, Nervous System Disorders: migraine Eye Disorders: diplopia, mydriasis Cardiac Disorders: sudden cardiac death, myocardial infarction, bradycardia, extrasystole, supraventricular tachycardia, ventricular extrasystole Vascular Disorders: peripheral coldness, Raynaud's phenomenon Respiratory, Thoracic and Mediastinal Disorders: pharyngolaryngeal pain, dyspnea Gastrointestinal Disorders: diarrhea, constipation Skin and Subcutaneous Tissue Disorders: angioneurotic edema, erythema, fixed drug eruption Musculoskeletal, Connective Tissue and Bone Disorders: myalgia, muscle twitching Renal and Urinary Disorders: hematuria Reproductive System and Breast Disorders: gynecomastia General Disorders: fatigue, hyperpyrexia Urogenital Disorders: priapism

<table cellspacing="0" cellpadding="0" border="0" width="100%"><caption>Table 1: Common Adverse Reactions in Pediatric Patients (6 to 17 years of age) with ADHD</caption><tfoot><tr><td colspan="3">Abbreviation: attention deficit hyperactivity disorder.</td></tr></tfoot><tbody><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"><content styleCode="bold">System Organ Class</content> <content styleCode="bold">Adverse Reaction</content> </td><td styleCode="Rrule" valign="top"><content styleCode="bold">Dexmethylphenidate HCl ER Capsules N=53 </content> </td><td styleCode="Rrule" valign="top"><content styleCode="bold">Placebo</content> <content styleCode="bold">N=47</content> </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"><content styleCode="bold">Gastrointestinal Disorders</content> </td><td styleCode="Rrule" valign="top">38% </td><td styleCode="Rrule" valign="top">19% </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top">Dyspepsia </td><td styleCode="Rrule" valign="top">8% </td><td styleCode="Rrule" valign="top">4% </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"><content styleCode="bold">Metabolism and Nutrition Disorders</content> </td><td styleCode="Rrule" valign="top">34% </td><td styleCode="Rrule" valign="top">11% </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top">Decreased Appetite </td><td styleCode="Rrule" valign="top">30% </td><td styleCode="Rrule" valign="top">9% </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"><content styleCode="bold">Nervous System Disorders</content> </td><td styleCode="Rrule" valign="top">30% </td><td styleCode="Rrule" valign="top">13% </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top">Headache </td><td styleCode="Rrule" valign="top">25% </td><td styleCode="Rrule" valign="top">11% </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"><content styleCode="bold">Psychiatric Disorders</content> </td><td styleCode="Rrule" valign="top">26% </td><td styleCode="Rrule" valign="top">15% </td></tr><tr><td styleCode="Lrule Rrule" valign="top">Anxiety </td><td styleCode="Rrule" valign="top">6% </td><td styleCode="Rrule" valign="top">0% </td></tr></tbody></table>

<table cellspacing="0" cellpadding="0" border="0" width="100%"><caption>Table 2: Dose-Related Adverse Reactions in Pediatric Patients (6 to 17 years of age) with ADHD</caption><tfoot><tr><td colspan="5">Abbreviation: attention deficit hyperactivity disorder.</td></tr></tfoot><tbody><tr styleCode="Botrule"><td rowspan="2" styleCode="Lrule Rrule" valign="top"><content styleCode="bold">System Organ Class</content> <content styleCode="bold">Adverse Reaction</content> </td><td styleCode="Rrule" valign="top"><content styleCode="bold">Dexmethylphenidate HCl ER Capsules</content> </td><td styleCode="Rrule" valign="top"><content styleCode="bold">Dexmethylphenidate HCl ER Capsules</content> </td><td styleCode="Rrule" valign="top"><content styleCode="bold">Dexmethylphenidate HCl ER Capsules</content> </td><td styleCode="Rrule" valign="top"><content styleCode="bold">Placebo</content> </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"><content styleCode="bold">10 mg/d N=64 </content> </td><td styleCode="Rrule" valign="top"><content styleCode="bold">20 mg/d N=60 </content> </td><td styleCode="Rrule" valign="top"><content styleCode="bold">30 mg/d N=58 </content> </td><td styleCode="Rrule" valign="top"><content styleCode="bold">N=63</content> </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"><content styleCode="bold">Gastrointestinal Disorders</content> </td><td styleCode="Rrule" valign="top">22% </td><td styleCode="Rrule" valign="top">23% </td><td styleCode="Rrule" valign="top">29% </td><td styleCode="Rrule" valign="top">24% </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top">Vomiting </td><td styleCode="Rrule" valign="top">2% </td><td styleCode="Rrule" valign="top">8% </td><td styleCode="Rrule" valign="top">9% </td><td styleCode="Rrule" valign="top">0% </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"><content styleCode="bold">Metabolism and Nutritional Disorders </content> </td><td styleCode="Rrule" valign="top">16% </td><td styleCode="Rrule" valign="top">17% </td><td styleCode="Rrule" valign="top">22% </td><td styleCode="Rrule" valign="top">5% </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top">Anorexia </td><td styleCode="Rrule" valign="top">5% </td><td styleCode="Rrule" valign="top">5% </td><td styleCode="Rrule" valign="top">7% </td><td styleCode="Rrule" valign="top">0% </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"><content styleCode="bold">Psychiatric Disorders</content> </td><td styleCode="Rrule" valign="top">19% </td><td styleCode="Rrule" valign="top">20% </td><td styleCode="Rrule" valign="top">38% </td><td styleCode="Rrule" valign="top">8% </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top">Insomnia </td><td styleCode="Rrule" valign="top">5% </td><td styleCode="Rrule" valign="top">8% </td><td styleCode="Rrule" valign="top">17% </td><td styleCode="Rrule" valign="top">3% </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top">Depression </td><td styleCode="Rrule" valign="top">0% </td><td styleCode="Rrule" valign="top">0% </td><td styleCode="Rrule" valign="top">3% </td><td styleCode="Rrule" valign="top">0% </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top">Mood Swings </td><td styleCode="Rrule" valign="top">0% </td><td styleCode="Rrule" valign="top">0% </td><td styleCode="Rrule" valign="top">3% </td><td styleCode="Rrule" valign="top">2% </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"><content styleCode="bold">Other Adverse Reactions</content> </td><td styleCode="Rrule" valign="top"> </td><td styleCode="Rrule" valign="top"> </td><td styleCode="Rrule" valign="top"> </td><td styleCode="Rrule" valign="top"> </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top">Irritability </td><td styleCode="Rrule" valign="top">0% </td><td styleCode="Rrule" valign="top">2% </td><td styleCode="Rrule" valign="top">5% </td><td styleCode="Rrule" valign="top">0% </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top">Nasal Congestion </td><td styleCode="Rrule" valign="top">0% </td><td styleCode="Rrule" valign="top">0% </td><td styleCode="Rrule" valign="top">5% </td><td styleCode="Rrule" valign="top">0% </td></tr><tr><td styleCode="Lrule Rrule" valign="top">Pruritus </td><td styleCode="Rrule" valign="top">0% </td><td styleCode="Rrule" valign="top">0% </td><td styleCode="Rrule" valign="top">3% </td><td styleCode="Rrule" valign="top">0% </td></tr></tbody></table>

<table cellspacing="0" cellpadding="0" border="0" width="100%"><caption>Table 3: Dose-Related Adverse Reactions in Adult Patients (18 to 60 years of age) with ADHD</caption><tbody><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"><content styleCode="bold">System Organ Class</content> <content styleCode="bold">Adverse Reaction</content> </td><td align="center" styleCode="Rrule" valign="top"><content styleCode="bold">Dexmethylphenidate HCl ER Capsules 20 mg N=57 </content> </td><td align="center" styleCode="Rrule" valign="top"><content styleCode="bold">Dexmethylphenidate HCl ER Capsules 30 mg N=54 </content> </td><td align="center" styleCode="Rrule" valign="top"><content styleCode="bold">Dexmethylphenidate HCl ER Capsules 40 mg N=54 </content> </td><td align="center" styleCode="Rrule" valign="top"><content styleCode="bold">Placebo</content> <content styleCode="bold"> N=53 </content> </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"><content styleCode="bold">Gastrointestinal Disorders</content> </td><td align="center" styleCode="Rrule" valign="top">28% </td><td align="center" styleCode="Rrule" valign="top">32% </td><td align="center" styleCode="Rrule" valign="top">44% </td><td align="center" styleCode="Rrule" valign="top">19% </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top">Dry Mouth </td><td align="center" styleCode="Rrule" valign="top">7% </td><td align="center" styleCode="Rrule" valign="top">20% </td><td align="center" styleCode="Rrule" valign="top">20% </td><td align="center" styleCode="Rrule" valign="top">4% </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top">Dyspepsia </td><td align="center" styleCode="Rrule" valign="top">5% </td><td align="center" styleCode="Rrule" valign="top">9% </td><td align="center" styleCode="Rrule" valign="top">9% </td><td align="center" styleCode="Rrule" valign="top">2% </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"><content styleCode="bold">Nervous System Disorders</content> </td><td align="center" styleCode="Rrule" valign="top">37% </td><td align="center" styleCode="Rrule" valign="top">39% </td><td align="center" styleCode="Rrule" valign="top">50% </td><td align="center" styleCode="Rrule" valign="top">28% </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top">Headache </td><td align="center" styleCode="Rrule" valign="top">26% </td><td align="center" styleCode="Rrule" valign="top">30% </td><td align="center" styleCode="Rrule" valign="top">39% </td><td align="center" styleCode="Rrule" valign="top">19% </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"><content styleCode="bold">Psychiatric Disorders</content> </td><td align="center" styleCode="Rrule" valign="top">40% </td><td align="center" styleCode="Rrule" valign="top">43% </td><td align="center" styleCode="Rrule" valign="top">46% </td><td align="center" styleCode="Rrule" valign="top">30% </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top">Anxiety </td><td align="center" styleCode="Rrule" valign="top">5% </td><td align="center" styleCode="Rrule" valign="top">11% </td><td align="center" styleCode="Rrule" valign="top">11% </td><td align="center" styleCode="Rrule" valign="top">2% </td></tr><tr styleCode="Botrule"><td rowspan="2" styleCode="Lrule Rrule" valign="top"><content styleCode="bold">Respiratory, Thoracic and</content> <content styleCode="bold">Mediastinal Disorders</content> </td><td align="center" styleCode="Rrule" valign="top"> </td><td align="center" styleCode="Rrule" valign="top"> </td><td align="center" styleCode="Rrule" valign="top"> </td><td align="center" styleCode="Rrule" valign="top"> </td></tr><tr styleCode="Botrule"><td align="center" styleCode="Lrule Rrule" valign="top">16% </td><td align="center" styleCode="Rrule" valign="top">9% </td><td align="center" styleCode="Rrule" valign="top">15% </td><td align="center" styleCode="Rrule" valign="top">8% </td></tr><tr><td styleCode="Lrule Rrule" valign="top">Pharyngolaryngeal Pain </td><td align="center" styleCode="Rrule" valign="top">4% </td><td align="center" styleCode="Rrule" valign="top">4% </td><td align="center" styleCode="Rrule" valign="top">7% </td><td align="center" styleCode="Rrule" valign="top">2% </td></tr></tbody></table>