1 INDICATIONS AND USAGE Methylphenidate hydrochloride extended-release capsules (LA) is indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD), in pediatric patients 6 to 12 years of age [see Clinical Studies (14) ] .

Methylphenidate hydrochloride extended-release capsules (LA) is a central nervous system (CNS) stimulant indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in pediatric patients 6 to 12 years of age ( 1 ).

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 methylphenidate hydrochloride extended-release capsules (LA) [see Contraindications (4) ] Hypertensive crisis when used concomitantly with 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) ] Most common adverse reactions (greater than 5% during incidence) were headache, insomnia, upper abdominal pain, decreased appetite and anorexia ( 6 ).

To report SUSPECTED ADVERSE REACTIONS, contact Mayne Pharma at 1-844-825-8500 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1 Clinical Trial Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The clinical program for methylphenidate hydrochloride extended-release capsules (LA) consisted of 6 studies: 2 controlled clinical studies conducted in children with ADHD aged 6 to 12 years and 4 clinical pharmacology studies conducted in healthy adult volunteers.

These studies included a total of 256 subjects; 195 children with ADHD and 61 healthy adult volunteers.

The subjects received methylphenidate hydrochloride extended-release capsules (LA) in doses of 10 to 40 mg per day.

Safety of methylphenidate hydrochloride extended-release capsules (LA) was assessed by evaluating frequency and nature of adverse events, routine laboratory tests, vital signs, and body weight.

A placebo-controlled, double-blind, parallel-group study was conducted to evaluate the efficacy and safety of methylphenidate hydrochloride extended-release capsules (LA) in children with ADHD aged 6 to 12 years.

All subjects received methylphenidate hydrochloride extended-release capsules (LA) for up to 4 weeks, and had their dose optimally adjusted, prior to entering the double-blind phase of the trial.

In the 2-week double-blind treatment phase of this study, patients received either placebo or methylphenidate hydrochloride extended-release capsules (LA) at their individually-titrated dose (range, 10 to 40 mg).

Adverse reactions with an incidence greater than 5% during the initial 4-week single-blind methylphenidate hydrochloride extended-release capsules (LA) titration period of this study were headache, insomnia, upper abdominal pain, appetite decreased, and anorexia.

Adverse reactions with an incidence greater than 2% among methylphenidate hydrochloride extended-release capsules (LA) -treated subjects, during the 2-week double-blind phase of the clinical study, are shown in Table 2: Table 2: Adverse Reactions in Greater Than 2% Methylphenidate Hydrochloride Extended-Release Capsules (LA)-Treated Subjects in the 2-Week Double-Blind Phase Preferred Term Methylphenidate Hydrochloride Extended-Release Capsules (LA) N = 65 N (%) Placebo N = 71 N (%) Anorexia 2 (3.1) 0 (0.0) Insomnia 2 (3.1) 0 (0.0) Adverse Events Associated with Discontinuation of Treatment In the 2-week double-blind treatment phase of a placebo-controlled parallel-group study in children with ADHD, one methylphenidate hydrochloride extended-release capsules (LA)-treated subject (1/65, 1.5%) discontinued due to an adverse event (depressed mood).

In the single-blind titration period of this study, subjects received methylphenidate hydrochloride extended-release capsules (LA) for up to 4 weeks.

During this period a total of 6 subjects (6/161, 3.7%) discontinued due to adverse events.

The adverse events leading to discontinuation were anger (2 patients), hypomania, anxiety, depressed mood, fatigue, migraine, and lethargy.

6.2 Postmarketing Experience The following adverse reactions have been identified during the post approval use of methylphenidate products.

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.

Adverse Reactions Reported With Methylphenidate Hydrochloride Tablets, Methylphenidate Hydrochloride Extended-Release Tablets, and Methylphenidate Hydrochloride Extended- Release Capsules (LA) 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 children 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) Adverse Reactions Reported with Other Methylphenidate-Containing Products The list below shows adverse reactions not listed with methylphenidate hydrochloride tablets, methylphenidate hydrochloride extended-release tablets, or methylphenidate hydrochloride extended-release capsules (LA) formulations that have been reported with other methylphenidate-containing products.

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 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