Methylphenidate Hydrochloride

1 INDICATIONS AND USAGE Methylphenidate hydrochloride oral solution is indicated for the treatment of: Attention Deficit Hyperactivity Disorder (ADHD) in adults and pediatric patients 6 years of age and older Narcolepsy Methylphenidate hydrochloride is a central nervous system (CNS) stimulant indicated for the treatment of: Attention Deficit Hyperactivity Disorder (ADHD) in adults and pediatric patients 6 years of age and older (1 ) Narcolepsy ( 1 )

2 DOSAGE AND ADMINISTRATION Pediatric patients 6 years and older: Starting dose is 5 mg twice daily (before breakfast and lunch); increase the dose 5 mg to 10 mg weekly; daily dosage above 60 mg is not recommended. ( 2.2 ) Adults: Administer in divided doses 2 or 3 times daily, preferably 30 to 45 minutes before meals. Average dosage is 20 to 30 mg daily. Maximum recommended daily dosage is 60 mg. ( 2 ) 2.1 Pretreatment Screening Prior to treating patients with methylphenidate hydrochloride oral solution, assess for the presence of cardiac disease (i.e., perform a careful history, family history of sudden death or ventricular arrhythmia, and physical exam) [see Warnings and Precautions ( 5.2 )]. the family history and clinically evaluate patients for motor or verbal tics or Tourette's syndrome [see Warnings and Precautions ( 5.10 )]. 2.2 General Dosing Information Pediatric Patients 6 years of Age and Older The recommended starting dosage is 5 mg orally twice daily before breakfast and lunch (preferably 30 to 45 minutes before meals). Increase the dosage gradually, in increments of 5 mg to 10 mg weekly. Daily dosage above 60 mg is not recommended. Adults Administer orally in divided doses 2 or 3 times daily, preferably 30 to 45 minutes before meals. The maximum recommended daily dose is 60 mg. The average dosage is 20 to 30 mg daily. For adult patients who are unable to sleep if medication is taken late in the day, administer the last dose before 6 p.m. 2.3 Dosage Reduction and Discontinuation If paradoxical aggravation of symptoms or other adverse reactions occur, reduce dosage, or, if necessary, discontinue methylphenidate hydrochloride oral solution. If improvement is not observed after appropriate dosage adjustment over a one- month period, discontinue methylphenidate hydrochloride oral solution.

4 CONTRAINDICATIONS Methylphenidate hydrochloride oral solution is contraindicated in patients: with known hypersensitivity to methylphenidate or other components of methylphenidate hydrochloride oral solution. Hypersensitivity reactions such as angioedema and anaphylactic reactions have been reported in patients treated with methylphenidate [ see Adverse Reactions ( 6 )]. receiving concomitant treatment with monoamine oxidase inhibitors (MAOIs), or within 14 days following discontinuation of treatment with an MAOI, because of the risk of hypertensive crises [ see Drug Interactions ( 7 )]. Known hypersensitivity to methylphenidate or other components of methylphenidate hydrochloride oral solution( 4 ) Concurrent treatment with a monoamine oxidase inhibitor (MAOI), or use of an MAOI within the preceding 14 days ( 4 )

Not available.

6 ADVERSE REACTIONS The following adverse reactions are discussed in more detail in other sections of the labeling: Abuse, Misuse, and Addiction [ see Warnings and Precautions (5.1 ), Drug Abuse and Dependence ( 9.2 , 9.3 )] Known hypersensitivity to methylphenidate or other components of methylphenidate hydrochloride oral solution [ see Contraindications ( 4 )] Hypertensive crisis when used concomitantly with monoamine oxidase inhibitors [ see Contraindications ( 4 ), Drug Interactio ns ( 7 )] Risks to patient with serious cardiac disease [ see Warnings and Precautions ( 5.2 )] Increased blood pressure and heart rate [ 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 in pediatric patients [ see Warnings and Precautions ( 5.7 )] Acute angle closure glaucoma [see Warnings and Precautions ( 5.8 )] Increased intraocular pressure and glaucoma [see Warnings and Precautions ( 5.9 )] Motor and verbal tics, and worsening of Tourette's syndrome [see Warnings and Precautions ( 5.10 )] The following adverse reactions associated with the use of methylphenidate containing products were identified in clinical studies, postmarketing reports, or literature. Because some of these reactions were 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. Infections and infestations : nasopharyngitis Blood and the lymphatic system disorders : leukopenia, thrombocytopenia, anemia, pancytopenia Immune system disorders : hypersensitivity reactions, including angioedema and anaphylaxis, auricular swelling, bullous conditions, eruptions, exanthemas 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, affect lability, mania, disorientation, libido changes Nervous system disorders : headache, dizziness, tremor, dyskinesia including choreoatheetoid movements, drowsiness, convulsions, cerebral arteritis and/or occlusion, serotonin syndrome in combination with serotonergic drugs, migraine Eye disorders : blurred vision, difficulties in visual accommodation, diplopia, mydriasis Cardiac disorders: tachycardia, palpitations, increased blood pressure, arrhythmias, angina pectoris, sudden cardiac death, myocardial infarction, bradycardia, extrasystole Respiratory, thoracic and mediastinal disorders: cough, pharyngolaryngeal pain, dyspnea Gastrointestinal disorders: dry mouth, nausea, vomiting, abdominal pain, dyspepsia, diarrhea General disorders: fatigue, hyperpyrexia 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 angioneurotic edema, erythema, fixed drug eruption Musculoskeletal and connective tissue disorders : arthralgia, muscle cramps, rhabdomyolysis, myalgia, muscle twitching Renal and urinary disorders : hematuria Reproductive system and breast disorders : gynecomastia Urogenital disorders : priapism Vascular disorders : peripheral coldness, Raynaud's phenomenon Investigations : weight loss Common adverse reactions: tachycardia, palpitations, headache, insomnia, anxiety, hyperhidrosis, weight loss, decreased appetite, dry mouth, nausea, and abdominal pain. (6) To report SUSPECTED ADVERSE REACTIONS contact Lupin Pharmaceuticals, Inc. at 1-866-403-7592 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.