methylphenidate extended-release

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

1 INDICATIONS AND USAGE Methylphenidate extended-release orally disintegrating tablets is indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in pediatric patients 6 to 17 years of age [see Clinical Studies (14) ] . Limitations of Use The use of methylphenidate extended-release orally disintegrating tablets 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 (5.5) . Use in Specific Populations (8.4) ]. Methylphenidate extended-release orally disintegrating tablets is a central nervous system (CNS) stimulant indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in pediatric patients 6 to 17 years of age. ( 1 ) Limitations of Use The use of methylphenidate extended-release orally disintegrating tablets 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 Recommended starting dose for pediatric patients 6 to 17 years of age is 17.3 mg given orally once daily in the morning. Dosage may be increased weekly in increments of 8.6 mg to 17.3 mg per day. Daily dosage above 51.8 mg is not recommended. ( 2.2 ) Patients are advised to take methylphenidate extended-release orally disintegrating tablets consistently either with food or without food. ( 2.2 ) 2.1 Pretreatment Screening Prior to treating patients with methylphenidate extended-release orally disintegrating tablets, 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 methylphenidate extended-release orally disintegrating tablets [see Warnings and Precautions (5.9) ]. 2.2 General Administration Information Methylphenidate extended-release orally disintegrating tablets is given orally once daily in the morning. Advise patients to take methylphenidate extended-release orally disintegrating tablets consistently either with food or without food [see Clinical Pharmacology (12.3) ]. The recommended starting dose of methylphenidate extended-release orally disintegrating tablets for patients 6 to 17 years of age is 17.3 mg once daily in the morning. The dose may be titrated weekly in increments of 8.6 mg to 17.3 mg. Daily doses above 51.8 mg have not been studied and are not recommended. The dose should be individualized according to the needs and responses of the patient. 2.3 Dosage Reduction and Discontinuation If paradoxical aggravation of symptoms or other adverse reactions occur, reduce dosage, or, if necessary, discontinue methylphenidate extended-release orally disintegrating tablets. If improvement is not observed after appropriate dosage adjustment over a one-month period, discontinue methylphenidate extended-release orally disintegrating tablets. 2.4 Methylphenidate Extended-Release Orally Disintegrating Tablets Administration Instruct the patient or caregiver on the following administration instructions: Do not remove the tablet from the bottle until just prior to dosing. Take the tablet immediately after opening the bottle. Do not store the tablet for future use. Use dry hands when removing the tablet from bottle. As soon as the bottle is opened, remove the tablet and place on the patient’s tongue. Place the whole tablet on the tongue and allow it to disintegrate without chewing or crushing. The tablet will disintegrate in saliva so that it can be swallowed. No liquid is needed to take the tablet.

3 DOSAGE FORMS AND STRENGTHS 8.6 mg Extended-Release Orally Disintegrating Tablet: round, purple to light purple mottled (debossed “T1” on one side and plain on the other) 17.3 mg Extended-Release Orally Disintegrating Tablet: round, purple to light purple mottled (debossed “T2” on one side and plain on the other) 25.9 mg Extended-Release Orally Disintegrating Tablet: round, purple to light purple mottled (debossed “T3” on one side and plain on the other) Extended-release orally disintegrating tablets: 8.6 mg, 17.3 mg, 25.9 mg ( 3 )

4 CONTRAINDICATIONS Methylphenidate extended-release orally disintegrating tablets is contraindicated in patients with: Known hypersensitivity to methylphenidate or other components of methylphenidate extended-release orally disintegrating tablets. Hypersensitivity reactions such as angioedema and anaphylactic reactions have been reported in patients treated with methylphenidate products [see Adverse Reactions (6.2) ]. Concomitant treatment with monoamine oxidase inhibitors (MAOIs), and also within a minimum of 14 days following discontinuation of treatment with a monoamine oxidase inhibitor because of the risk of hypertensive crisis [see Drug Interactions (7.1) ]. Known hypersensitivity to methylphenidate or product components. ( 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: Known hypersensitivity to methylphenidate or other ingredients of methylphenidate extended-release orally disintegrating tablets [see Contraindications (4) ] Hypertensive crisis when used concomitantly with monoamine oxidase inhibitors [see Contraindications (4) and Drug Interactions (7.1) ] Abuse, Misuse, and Addiction [see Boxed Warning , Warnings and Precautions (5.1) , and Drug Abuse and Dependence ( 9.2 , 9.3 )] 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) ] Based on accumulated data from other methylphenidate products, the most common (>5% and twice the rate of placebo) adverse reactions are appetite decreased, insomnia, nausea, vomiting, dyspepsia, abdominal pain, weight decreased, anxiety, dizziness, irritability, affect lability, tachycardia, and blood pressure increased. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Neos Therapeutics, Inc. at 1-888-319-1789 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 Other Methylphenidate Products in Children, Adolescents, and Adults with ADHD Commonly reported (≥2% of the methylphenidate group and at least twice the rate of the placebo group) adverse reactions from placebo-controlled trials of methylphenidate products include: appetite decreased, weight decreased, nausea, abdominal pain, dyspepsia, dry mouth, vomiting, insomnia, anxiety, nervousness, restlessness, affect lability, agitation, irritability, dizziness, vertigo, tremor, blurred vision, blood pressure increased, heart rate increased, tachycardia, palpitations, hyperhidrosis, and pyrexia. Adverse Reactions in Studies with methylphenidate extended-release orally disintegrating tablets in Children with ADHD There is limited experience with methylphenidate extended-release orally disintegrating tablets in controlled trials. Based on this limited experience, the adverse reaction profile of methylphenidate extended-release orally disintegrating tablets appears similar to other methylphenidate extended release-products. 6.2 Postmarketing Experience The following adverse reactions have been identified during post approval use of methylphenidate products. Because these reactions are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency or establish a causal relationship to drug exposure. These adverse reactions are as follows: Blood and Lymphatic System Disorders: Pancytopenia, Thrombocytopenia, Thrombocytopenic purpura Cardiac Disorders: Angina pectoris, Bradycardia, Extrasystole, Supraventricular tachycardia, Ventricular extrasystole Eye Disorders: Diplopia, Increased intraocular pressure, Mydriasis, Visual impairment General Disorders: Chest pain, Chest discomfort, Hyperpyrexia Immune System Disorders: Hypersensitivity reactions such as Angioedema, Anaphylactic reactions, Auricular swelling, Bullous conditions, Exfoliative conditions, Urticarias, Pruritis NEC, Rashes, Erupti …

7 DRUG INTERACTIONS Antihypertensive Drugs: Monitor blood pressure. Adjust dosage of antihypertensive drug as needed. ( 7 ) 7.1 Clinically Important Interactions with Methylphenidate Extended-Release Orally Disintegrating Tablets Table 1: Drugs Having Clinically Important Interactions with Methylphenidate Monoamine Oxidase Inhibitors (MAOI) Clinical Impact Concomitant use of MAOIs and CNS stimulants 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 Do not administer methylphenidate extended-release orally disintegrating tablets concomitantly with MAOIs or within 14 days after discontinuing MAOI treatment. Gastric pH Modulators Clinical Impact May change the release profile and alter the pharmacodynamics of methylphenidate extended-release orally disintegrating tablets. Intervention Concomitant use of methylphenidate extended-release orally disintegrating tablets with a gastric pH modulator (i.e., a H2-blocker or a proton pump inhibitor) is not recommended. Antihypertensive Drugs Clinical Impact Methylphenidate extended-release orally disintegrating tablets may decrease the effectiveness of drug 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 methylphenidate extended-release orally disintegrating tablets may increase the risk of sudden blood pressure and heart rate increase during surgery. Intervention Avoid use of methylphenidate extended-release orally disintegrating tablets 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 methylphenidate extended-release orally disintegrating tablets during pregnancy. Healthcare providers are encouraged to register patients by calling the National Pregnancy Registry for Psychostimulants at 1-866-961-2388. Risk Summary Published studies and postmarketing reports on methylphenidate use during pregnancy are insufficient to inform a drug-associated risk of adverse pregnancy-related outcomes [see Data] . There are risks to the fetus associated with the use of central nervous system (CNS) stimulants during pregnancy [see Clinical Considerations] . No teratogenic effects were observed in embryo-fetal development studies with oral administration of methylphenidate to pregnant rats and rabbits during organogenesis at doses 4 and 18 times, respectively, the maximum recommended human dose (MRHD) of 51.8 mg (as base). However, spina bifida was observed in rabbits at a dose 60 times the MRHD [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 2-4% and 15-20%, respectively. Clinical Considerations Fetal/Neonatal adverse reactions CNS stimulants, such as methylphenidate extended-release orally disintegrating tablets, 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 Human Data A limited number of pregnancies have been reported in published observational studies and postmarketing reports describing methylphenidate use during pregnancy. Due to the small number of methylphenidate-exposed pregnancies with known outcomes, these data cannot definitely establish or exclude any drug-associated risk during pregnancy. Methodological limitations of these observational studies include small sample size, concomitant use of other medications, lack of detail regarding dose and duration of exposure to methylphenidate and non-generalizability of the enrolled populations. Animal Data In studies conducted in rats and rabbits, methylphenidate was administered orally at doses of up to 75 and 200 mg/kg/day, respectively, during the period of organogenesis. Teratogenic effects (increased incidence of fetal spina bifida) were observed in rabbits at the highest dose, which is approximately 60 times the maximum recommended human dose (MRHD) of 51.8 mg (as base) for adolescents on a mg/m2 basis. The no effect level for embryo-fetal development in rabbits was 60 mg/kg/day (18 times the MRHD for adolescent on a mg/m2 basis). There was no evidence of specific teratogenic activity in rats, although increased incidences of fetal skeletal variations were seen at the highest dose level (11 times the MRHD on a mg/m2 basis for adolescent), which was also maternally toxic. The no effect level for embryo-fetal development in rats was 25 mg/kg/day (4 times the MRHD on a mg/m2 basis for adolescent). 8.2 Lactation Risk Summary Limited published literature, based on breast milk sampling from five 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 considere …

12.1 Mechanism of Action Methylphenidate is a central nervous system (CNS) stimulant. The mode of therapeutic action in ADHD is not known.

11 DESCRIPTION Methylphenidate extended-release orally disintegrating tablets contains methylphenidate, a central nervous system (CNS) stimulant. Methylphenidate extended-release orally disintegrating tablets is an extended-release orally disintegrating tablet intended for once daily administration. Methylphenidate extended-release orally disintegrating tablets contains approximately 25% immediate-release and 75% extended-release methylphenidate. Methylphenidate is ionically-bound to the sulfonate of polystyrene sulfonate particles. Methylphenidate extended-release orally disintegrating tablets contains 8.6 mg, 17.3 mg or 25.9 mg of methylphenidate which is the same as the amount of methylphenidate (base equivalent) found, respectively, in 10 mg, 20 mg and 30 mg strength methylphenidate hydrochloride products. The chemical name of methylphenidate is methyl α-phenyl-2-piperidineacetate, and its structural formula is shown in Figure 1. Figure 1: Methylphenidate Structure Methylphenidate extended-release orally disintegrating tablets also contains the following inactive ingredients: Mannitol, Fructose, Microcrystalline Cellulose, Crospovidone, Methacrylic Acid, Polystyrene Sulfonate, Citric Acid, Colloidal Silicon Dioxide, Grape Flavor, Natural Masking Type Powder, Triethyl Citrate, Magnesium Stearate, Ethylcellulose, Sucralose, Lake Blend Purple, and Polyethylene Glycol 3350. Figure 1

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 methylphenidate extended-release orally disintegrating tablets 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 Methylphenidate extended-release orally disintegrating tablets are available in three strengths: 8.6 mg tablets, round, purple to light purple, mottled, and debossed “T1” on one side of the tablet; 17.3 mg tablets, round, purple to light purple, mottled, and debossed “T2” on one side of the tablet; 25.9 mg tablets, round, purple to light purple, mottled, and debossed “T3” on one side of the tablet. They are available as follows: NDC 62542-100-31 8.6 mg tablets: bottle containing 30 tablets each. NDC 62542-250-31 17.3 mg tablets: bottle containing 30 tablets each. NDC 62542-350-31 25.9 mg tablets: bottle containing 30 tablets each. Store methylphenidate extended-release orally disintegrating tablet bottles in a cool, dry place at 20°C to 25°C (68°F to 77°F); excursions permitted from 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature].