Dexmethylphenidate hydrochloride

1 INDICATIONS AND USAGE Dexmethylphenidate hydrochloride extended-release capsules are indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) [see Clinical Studies (14) ] . Limitations of Use The use of dexmethylphenidate hydrochloride extended-release capsules is not recommended in pediatric patients younger than 6 years of age because they had higher plasma exposure and a higher incidence of adverse reactions (e.g., weight loss) than patients 6 years and older at the same dosage [see Warnings and Precautions (5.7) , Use in Specific Populations (8.4) ]. Dexmethylphenidate hydrochloride extended-release capsules are a central nervous system (CNS) stimulant indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) ( 1 ). Limitations of Use The use of dexmethylphenidate hydrochloride extended-release capsules is not recommended in pediatric patients younger than 6 years of age because they had higher plasma exposure and a higher incidence of adverse reactions (e.g., weight loss) than patients 6 years and older at the same dosage (5.7 , 8.4) .

2 DOSAGE AND ADMINISTRATION Patients new to methylphenidate: Recommended starting dose is 5 mg once daily for pediatric patients and 10 mg once daily for adults with or without food in the morning ( 2.2 ). Patients currently on methylphenidate: Dexmethylphenidate hydrochloride extended-release dosage is half (1/2) the current total daily dosage of methylphenidate ( 2.2 ). Patients currently on Focalin (dexmethylphenidate) immediate-release tablets: Give the same daily dose of dexmethylphenidate hydrochloride extended-release capsules ( 2.2 ). Titrate weekly in increments of 5 mg in pediatric patients and 10 mg in adult patients ( 2.2 ). Maximum recommended daily dose: 30 mg in pediatric patients and 40 mg in adults ( 2.2 ). Capsules may be swallowed whole or opened and the entire contents sprinkled on applesauce ( 2.3 ). 2.1 Pretreatment Screening Prior to treating patients with dexmethylphenidate hydrochloride extended-release capsules, 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 before initiating dexmethylphenidate hydrochloride extended-release capsules [see Warnings and Precautions (5.10) ] . 2.2 Recommended Dosage Patients New to Methylphenidate The recommended starting dosage of dexmethylphenidate hydrochloride extended-release capsules for patients who are not currently taking dexmethylphenidate or racemic methylphenidate, or for patients who are on stimulants other than methylphenidate are: Pediatric patients: Start with 5 mg orally once daily in the morning with or without food. Adult patients: Start with 10 mg orally once daily in the morning with or without food. Patients Currently on Methylphenidate The recommended starting dose of dexmethylphenidate hydrochloride extended-release capsules for patients currently using methylphenidate is half (1/2) the total daily dose of racemic methylphenidate. Patients currently using Focalin (dexmethylphenidate) immediate-release tablets may be given the same daily dose of dexmethylphenidate hydrochloride extended-release capsules. Titration Schedule The dose may be titrated weekly in increments of 5 mg in pediatric patients and 10 mg in adult patients. The dose should be individualized according to the needs and response of the patient. Daily doses above 30 mg in pediatrics and 40 mg in adults have not been studied and are not recommended. 2.3 Administration Instructions Dexmethylphenidate hydrochloride extended-release capsule is administered orally and may be taken whole or the capsule may be opened and the entire contents sprinkled onto applesauce. If the patient is using the sprinkled administration method, the sprinkled applesauce should be consumed immediately; it should not be stored. Patients should take the applesauce with sprinkled beads in its entirety without chewing. The dose of a single capsule should not be divided. The contents of the entire capsule should be taken, and patients should not take anything less than one capsule per day. 2.4 Dosage Reduction and Discontinuation If paradoxical aggravation of symptoms or other adverse reactions occur, reduce the dosage, or if necessary, discontinue dexmethylphenidate hydrochloride extended-release capsules. If improvement is not observed after appropriate dosage adjustment over a one-month period, the drug should be discontinued.

5 WARNINGS AND PRECAUTIONS Risks to Patients with Serious Cardiac Disease: Avoid use in patients with known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmias, coronary artery disease, or other serious cardiac disease (5.2) . Increased Blood Pressure and Heart Rate: Monitor blood pressure and pulse (5.3) . Psychiatric Adverse Reactions: Prior to initiating dexmethylphenidate hydrochloride extended-release, screen patients for risk factors for developing a manic episode. If new psychotic or manic symptoms occur, consider discontinuing dexmethylphenidate hydrochloride extended-release (5.4) . Priapism: If abnormally sustained or frequent and painful erections occur, patients should seek immediate medical attention (5.5) . Peripheral Vasculopathy, including Raynaud’s Phenomenon: Careful observation for digital changes is necessary during dexmethylphenidate hydrochloride extended-release treatment. Further clinical evaluation (e.g., rheumatology referral) may be appropriate for patients who develop signs or symptoms of peripheral vasculopathy (5.6) . Long-Term Suppression of Growth in Pediatric Patients: Closely monitor growth (height and weight) in pediatric patients. Pediatric patients not growing or gaining height or weight as expected may need to have their treatment interrupted (5.7) . Acute Angle Closure Glaucoma: Dexmethylphenidate hydrochloride extended-release-treated patients considered at risk for acute angle closure glaucoma (e.g., patients with significant hyperopia) should be evaluated by an ophthalmologist (5.8) . Increased Intraocular Pressure (IOP) and Glaucoma: Prescribe dexmethylphenidate hydrochloride extended-release to patients with open-angle glaucoma or abnormally increased IOP only if the benefit of treatment is considered to outweigh the risk. Closely monitor patients with a history of increased IOP or open angle glaucoma (5.9) . Motor and Verbal Tics, and Worsening of Tourette’s Syndrome: Before initiating dexmethylphenidate hydrochloride extended-release, assess the family history and clinically evaluate patients for tics or Tourette’s syndrome. Regularly monitor patients for the emergence or worsening of tics or Tourette’s syndrome. Discontinue treatment if clinically appropriate (5.10) . 5.1 Abuse, Misuse, and Addiction Dexmethylphenidate hydrochloride extended-release has a high potential for abuse and misuse. The use of dexmethylphenidate hydrochloride extended-release exposes individuals to the risks of abuse and misuse, which can lead to the development of a substance use disorder, including addiction. Dexmethylphenidate hydrochloride extended-release can be diverted for non-medical use into illicit channels or distribution [see Drug Abuse and Dependence (9.2) ] . Misuse and abuse of CNS stimulants, including dexmethylphenidate hydrochloride extended-release, can result in overdose and death [see Overdosage (10) ] , and this risk is increased with higher doses or unapproved methods of administration, such as snorting or injection. Before prescribing dexmethylphenidate hydrochloride extended-release, assess each patient’s risk for abuse, misuse, and addiction. Educate patients and their families about these risks and proper disposal of any unused drug. Advise patients to store dexmethylphenidate hydrochloride extended-release in a safe place, preferably locked, and instruct patients to not give dexmethylphenidate hydrochloride extended-release to anyone else. Throughout dexmethylphenidate hydrochloride extended-release treatment, reassess each patient’s risk of abuse, misuse, and addiction and frequently monitor for signs and symptoms of abuse, misuse, and addiction. 5.2 Risks to Patients with Serious Cardiac Disease Sudden death has been reported in patients with structural cardiac abnormalities or other serious cardiac disease who were treated with CNS stimulants at the recommended ADHD dosage. Avoid dexmethylphenidate hydrochloride extended-release use in patients with…

4 CONTRAINDICATIONS Hypersensitivity to methylphenidate or other components of dexmethylphenidate hydrochloride extended-release capsules. Hypersensitivity reactions, such as angioedema and anaphylactic reactions have been reported in patients treated with methylphenidate [see Adverse Reactions (6.1) ]. 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 (7.1) ]. Known hypersensitivity to methylphenidate or other components of dexmethylphenidate hydrochloride extended-release capsules ( 4 ). Concurrent treatment with a monoamine oxidase inhibitor (MAOI), or use of an MAOI within the preceding 14 days ( 4 ).

7 DRUG INTERACTIONS Antihypertensive Drugs: Monitor blood pressure. Adjust dosage of antihypertensive drug as needed ( 7.1 ). 7.1 Clinically Important Drug Interactions with Dexmethylphenidate Hydrochloride Extended-Release Table 5 presents clinically important drug interactions with dexmethylphenidate hydrochloride extended-release. Table 5: Clinically Important Drug Interactions with Dexmethylphenidate Hydrochloride Extended-Release Monoamine Oxidase Inhibitors (MAOIs) Clinical Impact Concomitant use of MAOIs and CNS stimulants, including dexmethylphenidate hydrochloride extended-release, can cause hypertensive crisis. Potential outcomes include death, stroke, myocardial infarction, aortic dissection, ophthalmological complications, eclampsia, pulmonary edema, and renal failure [see Contraindications (4) ] . Intervention Concomitant use of dexmethylphenidate hydrochloride extended-release with MAOIs or within 14 days after discontinuing MAOI treatment is contraindicated. Antihypertensive Drugs Clinical Impact Dexmethylphenidate hydrochloride extended-release may decrease the effectiveness of drugs used to treat hypertension [see Warnings and Precautions (5.3) ] . Intervention Monitor blood pressure and adjust the dosage of the antihypertensive drug as needed. Halogenated Anesthetics Clinical Impact Concomitant use of halogenated anesthetics and dexmethylphenidate hydrochloride extended-release may increase the risk of sudden blood pressure and heart rate increase during surgery. Intervention Avoid use of dexmethylphenidate hydrochloride extended-release in patients being treated with anesthetics on the day of surgery. Risperidone Clinical Impact Combined use of methylphenidate with risperidone when there is a change, whether an increase or decrease, in dosage of either or both medications, may increase the risk of extrapyramidal symptoms (EPS) Intervention Monitor for signs of EPS

6 ADVERSE REACTIONS The following are discussed in more detail in other sections of the labeling: Abuse, Misuse, and Addiction [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) ] Risks to Patients 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 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 Amneal Pharmaceuticals at 1-877-835-5472 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. Adverse Reactions in Studies with Dexmethylphenidate Hydrochloride Extended-Release 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 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/day to 30 mg/day who met The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (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 Focalin (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 doses of 5 mg/day to 30 mg/day. The table includes only those events that occurred in 5% or more of patients treated with dexmethylphenidate hydrochloride extended-release and for which the incidence in patients treated with dexmethylphenidate hydrochloride extended-release 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 System organ class Adverse reaction Dexmethylphenidate Hydrochloride Extended-Release N=53 Placebo N=47 Gastrointestinal disorders 38% 19% Dyspepsia 8% 4% Metabolism …