Focalin

Indications and Usage ( 1 ) 09/2025 Warnings and Precautions ( 5.7 ) 09/2025

1 INDICATIONS AND USAGE Focalin XR is indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) [see Clinical Studies ( 14 )] . Limitations of Use The use of Focalin XR 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 )]. Focalin XR is a central nervous system (CNS) stimulant indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) ( 1 ). Limitations of Use The use of Focalin XR 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: Focalin XR 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 Focalin XR ( 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 Focalin XR, 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 Focalin XR [see Warnings and Precautions ( 5.10 )] . 2.2 Recommended Dosage Patients New to Methylphenidate The recommended starting dosage of Focalin XR 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 Focalin XR 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 Focalin XR. 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 Focalin XR 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 Focalin XR. If improvement is not observed after appropriate dosage adjustment over a one-month period, the drug should be discontinued.

3 DOSAGE FORMS AND STRENGTHS • 5 mg extended-release capsules – light blue opaque cap and body (imprinted with “NVR” on cap and “D5” on the body) • 10 mg extended-release capsules – light caramel opaque cap and body (imprinted with “NVR” on cap and “D10” on the body) • 15 mg extended-release capsules – green opaque cap and body (imprinted with “NVR” on cap and “D15” on the body) • 20 mg extended-release capsules – white opaque cap and body (imprinted with “NVR” on cap and “D20” on the body) • 25 mg extended-release capsules – light blue opaque cap and white opaque body (imprinted with “NVR” on cap and “D25” on the body) • 30 mg extended-release capsules – light caramel opaque cap and white opaque body (imprinted with “NVR” on cap and “D30” on the body) • 35 mg extended-release capsules – light blue opaque cap and light caramel opaque body (imprinted with “NVR” on cap and “D35” on the body) • 40 mg extended-release capsules – green opaque cap and white opaque body (imprinted with “NVR” on cap and “D40” on the body) Extended-release capsules: 5 mg, 10 mg, 15 mg, 20 mg, 25 mg, 30 mg, 35 mg, and 40 mg of dexmethylphenidate hydrochloride ( 3 ).

4 CONTRAINDICATIONS • Hypersensitivity to methylphenidate or other components of Focalin XR. 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 Focalin XR ( 4 ). • Concurrent treatment with a monoamine oxidase inhibitor (MAOI), or use of an MAOI within the preceding 14 days ( 4 ).

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 Focalin XR [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 Novartis Pharmaceuticals Corporation at 1-888-669-6682, 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 Focalin XR in Pediatric Patients with ADHD The safety data in this section is based on data from a 7-week controlled clinical study of Focalin XR 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 Focalin XR 5 mg 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 Focalin XR doses of 5–30 mg/day. The table includes only those events that occurred in 5% or more of patients treated with Focalin XR and for which the incidence in patients treated with Focalin XR 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: ADHD, attention deficit hyperactivity disorder. System organ class Adverse reaction Focalin XR 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 reacti …

7 DRUG INTERACTIONS • Antihypertensive Drugs: Monitor blood pressure. Adjust dosage of antihypertensive drug as needed ( 7.1 ). 7.1 Clinically Important Drug Interactions With Focalin XR Table 5 presents clinically important drug interactions with Focalin XR. Table 5: Clinically Important Drug Interactions With Focalin XR Monoamine Oxidase Inhibitors (MAOIs) Clinical Impact Concomitant use of MAOIs and CNS stimulants, including Focalin XR, 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 Focalin XR with MAOIs or within 14 days after discontinuing MAOI treatment is contraindicated. Antihypertensive Drugs Clinical impact Focalin XR 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 Focalin XR may increase the risk of sudden blood pressure and heart rate increase during surgery. Intervention Avoid use of Focalin XR 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

8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to ADHD medications, including Focalin XR, during pregnancy. Healthcare providers are encouraged to register patients by calling the National Pregnancy Registry for ADHD medications at 1-866-961-2388 or visiting https://womensmentalhealth.org/adhd-medications/ . Risk Summary Dexmethylphenidate is the d-threo enantiomer of racemic methylphenidate. Published studies and postmarketing reports on methylphenidate use during pregnancy have not identified a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. There may be risks to the fetus associated with the use of CNS stimulants during pregnancy (see Clinical Considerations) . Embryo-fetal development studies in rats showed delayed fetal skeletal ossification at doses up to 5 times the maximum recommended human dose (MRHD) of 20 mg/day given to adults based on plasma levels. A decrease in pup weight in males was observed in a pre- and post-natal development study with oral administration of methylphenidate to rats throughout pregnancy and lactation at doses 5 times the MRHD of 20 mg/day given to adults based on plasma levels (see Data) . The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Fetal/Neonatal Adverse Reactions CNS stimulants, such as Focalin XR, can cause vasoconstriction and thereby decrease placental perfusion. No fetal and/or neonatal adverse reactions have been reported with the use of therapeutic doses of methylphenidate during pregnancy; however, premature delivery and low birth weight infants have been reported in amphetamine-dependent mothers. Data Animal Data In embryo-fetal development studies conducted in rats and rabbits, dexmethylphenidate was administered orally at doses of up to 20 and 100 mg/kg/day, respectively, during the period of organogenesis. No evidence of malformations was found in either the rat or rabbit study; however, delayed fetal skeletal ossification was observed at the highest dose level in rats. When dexmethylphenidate was administered to rats throughout pregnancy and lactation at doses of up to 20 mg/kg/day, post-weaning body weight gain was decreased in male offspring at the highest dose, but no other effects on postnatal development were observed. At the highest doses tested, plasma levels [area under the curves (AUCs)] of dexmethylphenidate in pregnant rats and rabbits were approximately 5 and 1 times, respectively, those in adults dosed with 20 mg/day. Plasma levels in adults were comparatively similar to plasma levels in adolescents. Racemic methylphenidate has been shown to cause malformations (increased incidence of fetal spina bifida) in rabbits when given in doses of 200 mg/kg/day throughout organogenesis. 8.2 Lactation Risk Summary Dexmethylphenidate is the d-threo enantiomer of racemic methylphenidate. Limited published literature, based on milk sampling from seven mothers’ reports that methylphenidate is present in human milk, which resulted in infant doses of 0.16% to 0.7% of the maternal weight-adjusted dosage and a milk/plasma ratio ranging between 1.1 and 2.7. There are no reports of adverse effects on the breastfed infant and no effects on milk production. Long-term neurodevelopmental effects on infants from stimulant exposure are unknown. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Focalin XR and any potential adverse effects on the breastfed infant from Focalin XR or from the underlying maternal condi …

12.1 Mechanism of Action Dexmethylphenidate hydrochloride is a CNS stimulant. The mode of therapeutic action in ADHD is not known.

11 DESCRIPTION Focalin XR contains dexmethylphenidate hydrochloride, a CNS stimulant. Dexmethylphenidate hydrochloride is the d-threo enantiomer of racemic methylphenidate hydrochloride. Focalin XR is an extended-release formulation of dexmethylphenidate with a bi-modal release profile. Each bead-filled Focalin XR capsule contains half the dose as immediate-release beads and half as enteric-coated, delayed-release beads, thus providing an immediate release of dexmethylphenidate and a delayed release of dexmethylphenidate. Focalin XR is intended for oral administration and is available as 5 mg, 10 mg, 15 mg, 20 mg, 25 mg, 30 mg, 35 mg, and 40 mg extended-release capsules. Chemically, dexmethylphenidate hydrochloride is methyl α-phenyl-2-piperidineacetate hydrochloride, (R,R’)-(+)-. Its molecular formula is C 14 H 19 NO 2 •HCl. Its structural formula is: Note* = asymmetric carbon center Dexmethylphenidate hydrochloride is a white to off-white powder. Its solutions are acid to litmus. It is freely soluble in water and in methanol, soluble in alcohol, and slightly soluble in chloroform and in acetone. Its molecular weight is 269.77 g/mol. Inactive ingredients: ammonio methacrylate copolymer, gelatin, methacrylic acid copolymer, polyethylene glycol, sugar spheres, talc, titanium dioxide, and triethyl citrate. Each strength capsule also contains colorant ingredients in the capsule shell as follows: • 5 mg: E132 FD&C Blue No. 2 • 10 mg: FDA/E172 iron oxide yellow • 15 mg: FD&C Blue No. 2, FDA/E172 iron oxide yellow • 20 mg: contains no colorants • 25 mg: E132 FD&C Blue No. 2 • 30 mg: FDA/E172 iron oxide yellow • 35 mg: E132 FD&C Blue No. 2, FDA/E172 iron oxide yellow • 40 mg: E132 FD&C Blue No. 2, FDA/E172 iron oxide yellow Dexmethylphenidate hydrochloride structural formula.

10 OVERDOSAGE Clinical Effects of Overdose Overdose of CNS stimulants is characterized by the following sympathomimetic effects: • Cardiovascular effects including tachyarrhythmias, and hypertension or hypotension. Vasospasm, myocardial infarction, or aortic dissection may precipitate sudden cardiac death. Takotsubo cardiomyopathy may develop. • CNS effects including psychomotor agitation, confusion, and hallucinations. Serotonin syndrome, seizures, cerebral vascular accidents, and coma may occur. • Life-threatening hyperthermia (temperatures greater than 104°F) and rhabdomyolysis may develop. Overdose Management Consider the possibility of multiple drug ingestion. The pharmacokinetic profile of Focalin XR should be considered when treating patients with overdose. Because methylphenidate has a large volume of distribution and is rapidly metabolized, dialysis is not useful. Consider contacting the Poison Help line (1-800-222-1222) or a medical toxicologist for additional overdose management recommendations.

16 HOW SUPPLIED/STORAGE AND HANDLING Focalin XR (dexmethylphenidate hydrochloride) extended-release capsules are available as follows: 100 Count • 5 mg capsules (NDC 66758-235-01) light-blue, (imprinted “SDZ D5”) supplied in bottles of 100 • 10 mg capsules (NDC 66758-236-01) light caramel (imprinted “SDZ D10”) supplied in bottles of 100 • 15 mg capsules (NDC 66758-237-01) green (imprinted “SDZ D15”) supplied in bottles of 100 • 20 mg capsules (NDC 66758-238-01) white (imprinted “SDZ D20”) supplied in bottles of 100 • 25 mg capsules (NDC 66758-239-01) light-blue and white (imprinted “SDZ D25”) supplied in bottles of 100 • 30 mg capsules (NDC 66758-240-01) light caramel and white (imprinted “SDZ D30”) supplied in bottles of 100 • 35 mg capsules (NDC 66758-241-01) light-blue and light caramel (imprinted “SDZ D35”) supplied in bottles of 100 • 40 mg capsules (NDC 66758-242-01) green and white (imprinted “SDZ D40”) supplied in bottles of 100 30 Count • 5 mg capsules (NDC 66758-235-31) light-blue, (imprinted “SDZ D5”) supplied in bottles of 30 • 10 mg capsules (NDC 66758-236-31) light caramel (imprinted “SDZ D10”) supplied in bottles of 30 • 15 mg capsules (NDC 66758-237-31) green (imprinted “SDZ D15”) supplied in bottles of 30 • 20 mg capsules (NDC 66758-238-31) white (imprinted “SDZ D20”) supplied in bottles of 30 • 25 mg capsules (NDC 66758-239-31) light-blue and white (imprinted “SDZ D25”) supplied in bottles of 30 • 30 mg capsules (NDC 66758-240-31) light caramel and white (imprinted “SDZ D30”) supplied in bottles of 30 • 35 mg capsules (NDC 66758-241-31) light-blue and light caramel (imprinted “SDZ D35”) supplied in bottles of 30 • 40 mg capsules (NDC 66758-242-31) green and white (imprinted “SDZ D40”) supplied in bottles of 30 Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F and 86°F) [see USP Controlled Room Temperature]. Dispense in tight container (USP).