Methylphenidate Hydrochloride

Indications and Usage ( 1 ) 9/2025 Dosage and Administration ( 2.3 , 2.4 ) 2/2026 Warnings and Precautions: Long-Term Suppression of Growth in Pediatric Patients 9/2025 Warnings and Precautions: Removal Seizures and Hematologic Monitoring 2/2026

1 INDICATIONS AND USAGE Methylphenidate hydrochloride extended-release tablets are indicated for the treatment of attention deficit hyperactivity disorder (ADHD) in patients aged 6 to 65 years old. Limitations of Use The use of methylphenidate hydrochloride extended-release tablets are 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 ) and Use in Specific Populations ( 8.4 )]. Methylphenidate hydrochloride extended-release tablets are a CNS stimulant indicated for the treatment of attention deficit hyperactivity disorder (ADHD) in patients aged 6 to 65 years old. ( 1 ) Limitations of Use The use of methylphenidate hydrochloride extended-release tablets are 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 Prior to initiating methylphenidate hydrochloride extended-release tablets treatment assess for ( 2.1 ): the presence of cardiac disease for family history of tics or Tourette’ syndrome and clinically evaluate patients for motor or verbal tics or Tourette’s syndrome Administer once daily in the morning with or without food. Swallow whole with liquids; do not chew, divide, or crush. ( 2.2 ) Recommended dosage in pediatric patients 6 to 17 years of age new to methylphenidate: starting dosage is18 mg once daily. May be increased weekly in 18 mg increments. Maximum dosage for pediatric patients ( 2.3 ): 6 to 12 years: 54 mg once daily 13 to 17 years: 72 mg once daily Recommended dosage in adults (up to 65 years of age) new to methylphenidate: starting dosage is 18 mg or 36 mg once daily. May be increased weekly in 18 mg increments, up to 72 mg once daily. ( 2.3 ) Patients currently using immediate-release methylphenidate: starting methylphenidate hydrochloride extended-release tablets dosage is based on current dosage regimen. ( 2.4 ) 2.1 Pretreatment Screening Prior to treating patients with methylphenidate hydrochloride extended-release tablets, assess: For the presence of cardiac disease (e.g., perform a careful history, family history of sudden death or ventricular arrhythmia, and physical exam) [see Warnings and Precautions ( 5.2) ]. The family history for tics or Tourette’ syndrome and clinically evaluate patients for motor or verbal tics or Tourette’s syndrome [see Warnings and Precautions ( 5.11 )]. 2.2 Important Administration Instructions Administer methylphenidate hydrochloride extended-release tablets orally once daily in the morning with or without food. Swallow methylphenidate hydrochloride extended-release tablets whole with liquids. Do not split, crush, or chew the extended-release tablets because doing so will compromise the extended-release characteristics of methylphenidate hydrochloride extended-release tablets and may compromise the effectiveness or safety of methylphenidate hydrochloride extended-release tablets. 2.3 Recommended Methylphenidate Hydrochloride Extended-Release Tablets Dosage in Patients New to Methylphenidate See Table 1 for the recommended once-daily dosage of methylphenidate hydrochloride extended-release tablets in patients who were not taking a methylphenidate product. In patients who have not achieved an optimal response at a lower dosage, increase the methylphenidate hydrochloride extended-release tablets dosage in 18 mg increments at weekly intervals. However, if a slower titration is recommended for patients who have not achieved an optimal response taking 18 mg of methylphenidate hydrochloride extended-release tablets once daily, increase their daily dosage to 27 mg once per day. Table 1. Recommended Methylphenidate Hydrochloride Extended-Release Tablets Dosage in Patients New to Methylphenidate Patient Population Recommended Starting Dosage Dosage Range Pediatric patients 6 to 12 years of age 18 mg once daily 18 mg to 54 mg once daily Pediatric patients 13 to 17 years of age 18 mg once daily 18 mg to 72 mg once daily (not to exceed 2 mg/kg/day) Adults 18 to 65 years of age 18 or 36 mg once daily 18 mg to 72 mg once daily 2.4 Recommended Methylphenidate Hydrochloride Extended-Release Tablets Dosage in Patients Switching from Another Methylphenidate Product See Table 2 for the recommended starting dosage of methylphenidate hydrochloride extended-release tablets in patients switching from an immediate-release methylphenidate product administered twice daily or three times daily (total daily dosage of 10 to 60 mg/day). Table 2. Recommended Starting Dosage in Patients Switching from Another Methylphenidate Product Previous Immediate-release Methylphenidate Daily Dosage Recommended Methylphenidate Hydrochloride Extended-Release Tablets Starting Dosage 5 mg twice daily or three times daily 18 mg every morning 10 mg twice daily or three times daily 36 mg every morn …

3 DOSAGE FORMS AND STRENGTHS Methylphenidate hydrochloride extended-release tablets, USP are available in the following dosage strengths: 18 mg – Each yellow, film-coated, capsule shaped tablet imprinted with the Andrx logo and 725 on one side and plain on the other side contains 18 mg methylphenidate hydrochloride, USP. 27 mg – Each gray, film-coated, capsule shaped tablet imprinted with the Andrx logo and 734 on one side and plain on the other side contains 27 mg methylphenidate hydrochloride, USP. 36 mg – Each white, film-coated, capsule shaped tablet imprinted with the Andrx logo and 726 on one side and plain on the other side contains 36 mg methylphenidate hydrochloride, USP. 54 mg – Each red brown, film-coated, capsule shaped tablet imprinted with the Andrx logo and 727 on one side and plain on the other side contains 54 mg methylphenidate hydrochloride, USP. Extended-release tablets: 18 mg, 27 mg, 36 mg, and 54 mg ( 3 )

4 CONTRAINDICATIONS Methylphenidate hydrochloride extended-release tablets is contraindicated in patients: Known to be hypersensitive to methylphenidate or other components of methylphenidate hydrochloride extended-release tablets. Hypersensitivity reactions, such as angioedema and anaphylactic reactions, have been reported in patients treated with methylphenidate hydrochloride extended-release tablets. [see Adverse Reactions ( 6 )] . Receiving concomitant monoamine oxidase inhibitors (MAOIs), and within 14 days following discontinuation of treatment with a MAO inhibitor because of the risk of a hypertensive crisis [see Drug Interactions ( 7 )] . Known hypersensitivity to methylphenidate or other components of methylphenidate hydrochloride extended-release tablets ( 4 ) Receiving concomitant monoamine oxidase inhibitors and within 14 days following discontinuation of treatment with a MAO inhibitor ( 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) ] Hypersensitivity Reactions [see Contraindications ( 4 )] Monoamine Oxidase Inhibitors [see Contraindications ( 4 ), Drug Interactions ( 7 )] 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 )] Risks of Gastrointestinal Obstruction in Patients with Gastrointestinal Narrowing [see Warnings and Precautions ( 5.8 )] Acute Angle Closure Glaucoma [see Warnings and Precautions ( 5.9 )] Increased Intraocular Pressure and Glaucoma [see Warnings and Precautions ( 5.10 )] Motor and Verbal Tics, and Worsening of Tourette’s Syndrome [see Warnings and Precautions ( 5.11 )] The most common adverse reactions (≥5%) in double-blind clinical trials were: Pediatric patients 6 to 17 years: upper abdominal pain. ( 6.1 ) Adults up to 65 years of age: decreased appetite, headache, dry mouth, nausea, insomnia, anxiety, dizziness, weight decreased, irritability, tachycardia, and hyperhidrosis. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Teva at 1-888-838-2872 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 clinical trials of another drug and may not reflect the rates observed in clinical practice. The data below is based on a total of 3,906 patients in clinical studies who received methylphenidate hydrochloride extended-release tablets. Patients aged 6 up to 65 years old with ADHD were evaluated in 6 controlled clinical studies and 11 open-label clinical studies [see Table 3] . Table 3. Methylphenidate Hydrochloride Extended-Release Tablets-treated Patients in Double-Blind and Open-Label Clinical Studies Patient Population N Dosage Range Pediatric patients 6 to 12 years of age 2,216 18 to 54 mg once daily Adolescents 502 18 to 72 mg once daily Adults up to 65 years of age 1,188 18 to 108 mg once daily The most common adverse reactions (≥5%) in double-blind clinical trials were: Pediatric patients: upper abdominal pain [see Table 4] . Adults: decreased appetite, headache, dry mouth, nausea, insomnia, anxiety, dizziness, weight decreased, irritability, tachycardia, and hyperhidrosis [see Table 5] . The most common adverse reactions associated with methylphenidate hydrochloride extended-release tablets discontinuation (≥1%) from the pediatric and adult clinical trials were anxiety, irritability, insomnia, and increased blood pressure. Most Common Adverse Reactions in Double-Blind, Placebo-Controlled Clinical Trials: Adverse reactions in either the pediatric or adult double-blind adverse reactions tables may be relevant for both patient populations. Adverse Reactions in Pediatric Patients Aged 6 years and Older Table 4 displays adverse reactions reported in 2% or more of methylphenidate hydrochloride extended-release tablets -treated pediatric patients ages 6 and older with ADHD in 4 placebo-controlled, double-blind clinical trials. Table 4: Most Common Adverse Reactions 1 in Pediatric Patients 6 Years of Age and Older with ADHD in 4 Placebo-Controlled, Double-Blind Clinical Trials Methylphenidate Hydrochloride Extended-Release Tablets (n=321) Placebo (n=318) Upper abdominal pain 6% 4% Insomnia 2 3% 1% Nasopharyngitis 3% 2% Vomiting 3% 2% Pyrexia 2% 1% 1 Reported in ≥ 2% of Methylphenidate Hydrochloride Extended-Release …

7 DRUG INTERACTIONS Table 6 describes clinically significant drug interactions with methylphenidate hydrochloride extended-release tablets. Table 6: Clinically Significant Drug Interactions Monoamine Oxidase Inhibitors Prevention or Management Concomitant use of CNS stimulants, including methylphenidate hydrochloride extended-release tablets, with MAOIs or within 14 days after discontinuing an MAOI is contraindicated [ see Contraindications (4)]. Mechanism and Clinical Effect(s) Concomitant use of MAOIs and CNS stimulants, including methylphenidate hydrochloride extended-release tablets, can cause hypertensive crisis. Potential outcomes include death, stroke, myocardial infarction, aortic dissection, ophthalmological complications, eclampsia, pulmonary edema, and renal failure. Antihypertensive Drugs Prevention or Management Increase monitoring for blood pressure and adjust the dosage of the antihypertensive drug, as needed. Mechanism and Clinical Effect(s) Methylphenidate hydrochloride extended-release tablets may decrease effectiveness of drugs used to treat hypertension [see Warnings and Precautions 5.3]. Halogenated Anesthetics Prevention or Management Avoid use of methylphenidate hydrochloride extended-release tablets in patients being treated with anesthetics on the day of surgery. Mechanism and Clinical Effect(s) Concomitant use of halogenated anesthetics and methylphenidate hydrochloride extended-release tablets may increase the risk of sudden blood pressure and heart rate increase during surgery. Risperidone Prevention or Management Monitor for signs of extrapyramidal symptoms. Mechanism and Clinical Effect(s) The risk of risperidone-associated extrapyramidal symptoms may increase in patients taking concomitant methylphenidate hydrochloride extended-release tablets when there is a change in the methylphenidate hydrochloride extended-release tablets or risperidone dosage. Antihypertensive drugs: Monitor blood pressure. Adjust dosage of antihypertensive drug as needed. ( 7 ) See additional clinically significant drug interactions, in the DRUG INTERACTIONS section ( 7 ).

8 USE IN SPECIFIC POPULATIONS Caution should be exercised if administered to nursing mothers ( 8.3 ) Safety and efficacy has not been established in children less than six years old or elderly patients greater than 65 years of age ( 8.4 and 8.5 ) 8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to ADHD drugs, including methylphenidate hydrochloride extended-release tablets, during pregnancy. Healthcare providers are encouraged to advise patients to register by calling the National Pregnancy Registry for ADHD Medications at 1-866-961-2388 or visiting https://womensmentalhealth.org/adhd-medications/ . Risk Summary Published studies and post-marketing reports on methylphenidate use during pregnancy have inconsistent findings about a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. There are risks to the fetus associated with the use of central nervous system (CNS) stimulants during pregnancy ( see Clinical Considerations) . No effects on morphological development were observed in embryo-fetal development studies with oral administration of methylphenidate to pregnant rats and rabbits throughout organogenesis at doses up to 4 and 16 times, respectively, the maximum recommended human dose (MRHD) of 72 mg/day given to adults on a mg/m 2 basis. However, spina bifida was observed in rabbits at a dose 54 times the MRHD given to adults. A slight decrease in body weight was observed in pregnant rats at the highest dose of 30 mg/kg/day (4 times the MRHD given to adults). In a pre- and postnatal development study in which rats were treated with oral administration of methylphenidate throughout pregnancy and lactation, a decrease in pup body weight, alterations in sensory and neuromotor performance, and deficits in learning and memory were observed in both sexes at the highest dose (4 times the MRHD given to adults on a mg/m 2 basis) (see Data) . The background risk of major birth defects and miscarriage in those with ADHD is unknown. All pregnancies have a background risk of birth defects, 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 methylphenidate hydrochloride extended-release tablets, can cause vasoconstriction and thereby decrease placental perfusion. No fetal and/or neonatal adverse reactions have been reported with the use of a therapeutic dosage 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, methylphenidate was administered orally at doses up to 30 and 200 mg/kg/day, respectively, during the period of organogenesis. Malformations (increased incidence of fetal spina bifida) were observed in rabbits at the highest dose, which is approximately 54 times the maximum recommended human dose (MRHD) of 72 mg/day given to adults on a mg/m 2 basis. The no effect level for embryo-fetal development in rabbits was 60 mg/kg/day (16 times the MRHD given to adults on a mg/m 2 basis). There was no evidence of changes in morphological development in rats, although a reduction in maternal body weight was observed at the highest dose of 30 mg/kg/day (4 times the MRHD of 72 mg/day given to adults (on a mg/m 2 basis). The no effect level for maternal body weight in rats is 5 mg/day (equal to the MRHD for adults on a mg/m 2 basis); and the no effect level for embryo-fetal development is 30 mg/kg/day (4 times the MRHD for adults on a mg/m 2 basis). When methylphenidate was administered to rats throughout pregnancy and lactation at doses of up to 30 mg/kg/day, decreases in offspring body weight, alterat …

12.1 Mechanism of Action Methylphenidate is a central nervous system (CNS) stimulant. The mode of therapeutic action of methylphenidate in the treatment of ADHD is not known. Methylphenidate blocks the reuptake of norepinephrine and dopamine into the presynaptic neuron and increases the release of these monoamines into the extraneuronal space.

11 DESCRIPTION Methylphenidate hydrochloride extended-release tablets, USP are a central nervous system (CNS) stimulant. Methylphenidate hydrochloride extended-release tablets, USP are available in four strengths. Each extended-release tablet for oral administration contains 18 mg, 27 mg, 36 mg, or 54 mg of methylphenidate hydrochloride, USP. Chemically, methylphenidate hydrochloride, USP is d,l (racemic) methyl α-phenyl-2-piperidineacetate hydrochloride, its molecular formula is C 14 H 19 NO 2 •HCl, and its structural formula is: Methylphenidate hydrochloride, USP is a white, odorless crystalline 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. Methylphenidate hydrochloride extended-release tablets, USP also contain the following inert ingredients: colloidal silicon dioxide, fumaric acid, hypromellose 2208, hypromellose 2910, lactose monohydrate, magnesium stearate, methacrylic acid copolymer Type A, methacrylic acid copolymer Type B, talc, titanium dioxide, and triethyl citrate. The 18 mg strength also contains iron oxide red, iron oxide yellow, polyethylene glycol 3350, and polyvinyl alcohol. The 27 mg strength also contains FD&C Blue #2/Indigo Carmine Aluminum Lake, iron oxide black, iron oxide yellow, polyethylene glycol 3350, and polyvinyl alcohol. The 36 mg strength also contains triacetin. The 54 mg strength also contains iron oxide red, polyethylene glycol 3350, and polyvinyl alcohol. The imprinting ink contains ammonium hydroxide, iron oxide black, propylene glycol, and shellac. It is possible that methylphenidate hydrochloride extended-release tablets may be visible on abdominal x-rays under certain circumstances, especially when digital enhancing techniques are utilized. Meets USP Dissolution Test 11. Structural Formula

10 OVERDOSAGE 10.1 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. 10.2 Overdose Management Consider the possibility of multiple drug ingestion. The pharmacokinetic profile of methylphenidate hydrochloride extended-release 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/STORAGE AND HANDLING Methylphenidate hydrochloride extended-release tablets, USP are available as follows: 18 mg – Each yellow, film-coated, capsule shaped tablet imprinted with the Andrx logo and 725 on one side and plain on the other side contains 18 mg methylphenidate hydrochloride, USP. Tablets are supplied in bottles of 100 (NDC 62037-725-01). 27 mg – Each gray, film-coated, capsule shaped tablet imprinted with the Andrx logo and 734 on one side and plain on the other side contains 27 mg methylphenidate hydrochloride, USP. Tablets are supplied in bottles of 100 (NDC 62037-734-01). 36 mg – Each white, film-coated, capsule shaped tablet imprinted with the Andrx logo and 726 on one side and plain on the other side contains 36 mg methylphenidate hydrochloride, USP. Tablets are supplied in bottles of 100 (NDC 62037-726-01). 54 mg – Each red brown, film-coated, capsule shaped tablet imprinted with the Andrx logo and 727 on one side and plain on the other side contains 54 mg methylphenidate hydrochloride, USP. Tablets are supplied in bottles of 100 (NDC 62037-727-01). Storage and Handling Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [See USP Controlled Room Temperature]. Protect from humidity. Dispense in tight, light-resistant container as defined in USP, with a child-resistant closure (as required).