Methylphenidate Hydrochloride

Boxed Warning 10/2023 Indications and Usage ( 1 ) 10/2023 Dosage and Administration ( 2.1 , 2.6 ) 10/2023 Dosage and Administration, Maintenance/Extended Treatment ( 2.5 ) Removed 10/2023 Contraindications ( 4 ) 10/2023 Warnings and Precautions ( 5.1 , 5.2, 5.3 , 5.4 , 5.6 , 5.7 , 5.8 , 5.11 , 5.12 , 5.13 ) 10/2023 Warnings and Precautions ( 5.7 ) Removed 10/2023 Indications and Usage ( 1 ) 09/2025 Dosage and Administration ( 2.3 , 2.4 ) 02/2026 Warnings and Precautions: Long-Term Suppression of Growth in Pediatric Patients 09/2025 Warnings and Precautions: Removal Seizures and Hematologic Monitoring 02/2026

1 INDICATIONS AND USAGE Methylphenidate hydrochloride extended-release tablets are indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in children 6 years of age and older, adolescents, and adults up to the age of 65 [see Clinical Studies ( 14 )] . A diagnosis of Attention Deficit Hyperactivity Disorder (ADHD; DSM-IV) implies the presence of hyperactive-impulsive or inattentive symptoms that caused impairment and were present before age 7 years. The symptoms must cause clinically significant impairment, e.g., in social, academic, or occupational functioning, and be present in two or more settings, e.g., school (or work) and at home. The symptoms must not be better accounted for by another mental disorder. For the Inattentive Type, at least six of the following symptoms must have persisted for at least 6 months: lack of attention to details/careless mistakes; lack of sustained attention; poor listener; failure to follow through on tasks; poor organization; avoids tasks requiring sustained mental effort; loses things; easily distracted; forgetful. For the Hyperactive-Impulsive Type, at least six of the following symptoms must have persisted for at least 6 months: fidgeting/squirming; leaving seat; inappropriate running/climbing; difficulty with quiet activities; “on the go;” excessive talking; blurting answers; can’t wait turn; intrusive. The Combined Type requires both inattentive and hyperactive-impulsive criteria to be met. Methylphenidate hydrochloride extended-release Tablets is a CNS stimulant indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in children 6 years of age and older, adolescents, and adults up to the age of 65. ( 1 ) 1.1 Special Diagnostic Considerations Specific etiology of this syndrome is unknown, and there is no single diagnostic test. Adequate diagnosis requires the use of medical and special psychological, educational, and social resources. Learning may or may not be impaired. The diagnosis must be based upon a complete history and evaluation of the patient and not solely on the presence of the required number of DSM-IV characteristics. 1.2 Need for Comprehensive Treatment Program Methylphenidate hydrochloride extended-release tablets are indicated as an integral part of a total treatment program for ADHD that may include other measures (psychological, educational, social). Drug treatment may not be indicated for all patients with ADHD. Stimulants are not intended for use in patients who exhibit symptoms secondary to environmental factors and/or other primary psychiatric disorders, including psychosis. Appropriate educational placement is essential and psychosocial intervention is often helpful. When remedial measures alone are insufficient, the decision to prescribe stimulant medication will depend upon the physician's assessment of the chronicity and severity of the patient’s symptoms.

2 DOSAGE AND ADMINISTRATION Prior to initiating methylphenidate hydrochloride extended-release tablets treatment assess for (2.1): o the presence of cardiac disease o 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 hydrochloride extended-release tablets: starting dosage is18 mg once daily. May be increased weekly in 18 mg increments. Maximum dosage for pediatric patients (2.3): o 6 to 12 years: 54 mg once daily o 13 to 17 years: 72 mg once daily Recommended dosage in adults (up to 65 years of age) new to methylphenidate hydrochloride extended-release tablets: 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 1 …

3 DOSAGE FORMS AND STRENGTHS Methylphenidate hydrochloride extended-release tablets, USP are available in the following dosage strengths: Methylphenidate hydrochloride extended-release tablets USP, 18 mg are purple colored, capsule-shaped tablets imprinted with 'RDY 18' in black ink. Methylphenidate hydrochloride extended-release tablets USP, 27 mg are pink colored, capsule-shaped tablets imprinted with 'RDY 27' in black ink. Methylphenidate hydrochloride extended-release tablets USP, 36 mg are orange colored, capsule-shaped tablets imprinted with 'RDY 36' in black ink. Methylphenidate hydrochloride extended-release tablets USP, 54 mg are blue colored, capsule-shaped tablets imprinted with 'RDY 54' in black ink. Tablets: 18, 27, 36, and 54 mg ( 3 )

4 CONTRAINDICATIONS • Known hypersensitivity to the product ( 4.1 ) • Marked anxiety, tension, or agitation ( 4.2 ) • Glaucoma ( 4.3 ) • Tics or a family history or diagnosis of Tourette’s syndrome ( 4.4 ) • Do not use methylphenidate hydrochloride extended-release tablets in patients currently using or within 2 weeks of using an MAO inhibitor ( 4.5 ) 4.1 Hypersensitivity to Methylphenidate Hypersensitivity reactions, such as angioedema and anaphylactic reactions, have been observed in patients treated with methylphenidate hydrochloride extended-release tablets. Therefore, methylphenidate hydrochloride extended-release tablets are contraindicated in patients known to be hypersensitive to methylphenidate or other components of the product [see Adverse Reactions ( 6.6 )] . 4.2 Agitation Methylphenidate hydrochloride extended-release tablets are contraindicated in patients with marked anxiety, tension, and agitation, since the drug may aggravate these symptoms. 4.3 Glaucoma Methylphenidate hydrochloride extended-release tablets are contraindicated in patients with glaucoma. 4.4 Tics Methylphenidate hydrochloride extended-release tablets are contraindicated in patients with motor tics or with a family history or diagnosis of Tourette's syndrome [see Adverse Reactions ( 6.4 )]. 4.5 Monoamine Oxidase Inhibitors Methylphenidate hydrochloride extended-release tablets are contraindicated during treatment with monoamine oxidase (MAO) inhibitors, and also within a minimum of 14 days following discontinuation of a MAO inhibitor (hypertensive crises may result) [see Drug Interactions ( 7.1 )].

6 ADVERSE REACTIONS The following are discussed in more detail in other sections of the labeling: Abuse, Misuse, and Addiction [see Box Warning, Warnings and Precautions ( 5.1 ), and Drug Abuse and Dependence ( 9.2 , 9.3 )] Known hypersensitivity to methylphenidate or other ingredients [see Contraindications ( 4 )] Hypertensive crisis when used concomitantly with monoamine oxidase inhibitors [see Contraindications ( 4 ) and 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 )] Potential for Gastrointestinal Obstruction [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%) were: Pediatric patients 6 to 17 years: abdominal pain upper ( 6.1 ) Adults: decreased appetite, headache, dry mouth, nausea, insomnia, anxiety, dizziness, weight decreased, irritability, and hyperhidrosis ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Trigen Laboratories, LLC at 1-800-444-5164 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 clinical trials of another drug and may not reflect the rates observed in clinical practice. The safety of methylphenidate hydrochloride extended-release tablets for the treatment of ADHD is based on adequate and well-controlled studies of another formulation of methylphenidate hydrochloride extended-release tablets. Below is a display of adverse reactions from those adequate and well-controlled studies in ADHD. Adults and pediatric patients 6 to 17 years with ADHD were evaluated in six controlled clinical studies and eleven open-label clinical studies (see Table 3). Safety was assessed by collecting adverse reactions, vital signs, weights, and electrocardiograms (ECGs), and by performing physical examinations and laboratory analyses. A total of 3,906 patients participated in the clinical trials. Table 3: Exposure in Double-Blind and Open-Label Clinical Studies of Another Formulation of Methylphenidate Hydrochloride Extended-Release Tablets Patient Population N Dosage Range Pediatric patients 6 to 12 years 2216 18 mg to 54 mg once daily Pediatric patients 13 to 17 years 502 18 mg to 72 mg once daily Adults 1188 18 mg to 108 mg* once daily * 108 mg is 1.5 times the maximum recommended dosage of methylphenidate hydrochloride extended-release tablets. The most common adverse reactions in double-blind clinical trials (>5%) were: Pediatric patients 6 to 17 years: abdominal pain upper (see Table 4). Adults: decreased appetite, headache, dry mouth, nausea, insomnia, anxiety, dizziness, weight decreased, irritability, and hyperhidrosis (see Table 5). The most common adverse reactions associated with discontinuation (≥1%) from either pediatric or adult clinical trials were anxiety, irritability, insomnia, and blood pressure increased . Adverse reactions in either the pediatric or adult double-blind adverse reactions tables may be relevant for both patient populations. Pediatric Patients 6 to 17 Years Table 4 lists the adverse reactions reported in 1% or more of another formulation of methylphenidate hydrochloride extended-release tablet-treated pediatric patients (6 to 17 years) in four placebo-controlled, doub …

7 DRUG INTERACTIONS N/A Antihypertensive drugs: Monitor blood pressure. Adjust dosage of antihypertensive drug as needed (7) Halogenated anesthetics: Avoid use of Methylphenidate hydrochloride extended-release tablets on the day of surgery if halogenated anesthetics will be used (7) Risperidone: The combined use of methylphenidate with risperidone when there is a change in dose of either or both medications may increase the risk of extrapyramidal symptoms (EPS). Monitor for signs of EPS (7) . 7.1 Clinically Important Interactions with Methylphenidate hydrochloride extended-release tablets Table 1 presents clinically important drug interactions with Methylphenidate hydrochloride extended-release tablets. Table 1: Clinically Important Drug Interactions with Methylphenidate Hydrochloride Extended-Release Tablets Monoamine Oxidase Inhibitors (MAOI) Clinical Impact 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 [ see Contraindications (4) ] . Intervention Concomitant use of Methylphenidate hydrochloride extended-release tablets with MAOIs or within 14 days after discontinuing MAOI treatment is contraindicated. Examples selegiline, tranylcypromine, isocarboxazid, phenelzine, linezolid, methylene blue Antihypertensive Drugs Clinical Impact Methylphenidate hydrochloride extended-release tablets 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. Examples Potassium-sparing and thiazide diuretics, calcium channel blockers, angiotensin-converting-enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), beta blockers, centrally acting alpha-2 receptor agonists Halogenated Anesthetics Clinical Impact 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. Intervention Avoid use of Methylphenidate hydrochloride extended-release tablets in patients being treated with anesthetics on the day of surgery. Examples halothane, isoflurane, enflurane, desflurane, sevoflurane Risperidone The combined use of methylphenidate with risperidone when there is a change in dose of either or both medications may increase the risk of extrapyramidal symptoms (EPS). Monitor for signs of EPS.

8 USE IN SPECIFIC POPULATIONS Caution should be exercised if administered to nursing mothers ( 8.2 ) 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, altera …

12.1 Mechanism of Action Methylphenidate HCl is a central nervous system (CNS) stimulant. The mode of therapeutic action in Attention Deficit Hyperactivity Disorder (ADHD) is not known. Methylphenidate is thought to block the reuptake of norepinephrine and dopamine into the presynaptic neuron and increase the release of these monoamines into the extraneuronal space.

11 DESCRIPTION Methylphenidate hydrochloride extended-release tablet is a central nervous system (CNS) stimulant. Methylphenidate hydrochloride extended-release tablets are available in four strengths. Each extended-release tablet for once-a-day oral administration contains 18, 27, 36, or 54 mg of methylphenidate HCl USP and is designed to have a 12-hour duration of effect. Chemically, methylphenidate HCl is d,l (racemic) methyl α-phenyl-2-piperidineacetate hydrochloride. Its empirical formula is C 14 H 19 NO 2 •HCl. Its structural formula is: Methylphenidate HCl, USP is a white to off-white fine 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 also contains the following inert ingredients: butylated hydroxytoluene, cellulose acetate, colloidal silicon dioxide, FD&C Blue #1/Brilliant Blue FCF Aluminum Lake, FD&C Red #40/Allura Red AC Aluminum Lake, hypromellose, phosphoric acid, poloxamer, polyethylene oxide, povidone, sodium chloride, stearic acid, succinic acid. In addition 18 mg contains Opadry Purple (FD&C Blue #2/Indigo Carmine Aluminum Lake, FD&C Red #40/Allura Red AC Aluminum Lake, hypromellose 3 mPas, hypromellose 6 mPas, polyethylene glycol, polysorbate, titanium dioxide), 27 mg contains Opadry Pink (D&C Red #27/Phloxine Aluminum Lake, FD&C Blue #2/Indigo Carmine Aluminum Lake, hypromellose 3 mPas, hypromellose 6 mPas, polyethylene glycol, polysorbate, titanium dioxide), 36 mg contains Opadry Orange (FD&C Red #40/Allura Red AC Aluminum Lake, FD&C Yellow #6/Sunset Yellow FCF Aluminum Lake, hypromellose 3 mPas, hypromellose 6 mPas, polyethylene glycol, polysorbate, titanium dioxide), 54 mg contains Opadry Blue (FD&C Blue #2/Indigo Carmine Aluminum Lake, hypromellose 3 mPas, hypromellose 6 mPas, polyethylene glycol, polysorbate, titanium dioxide). Opacode Black contains black iron oxide, hypromellose 6 mPas, propylene glycol. "Meets USP Dissolution Test 12" 11.1 System Components and Performance Methylphenidate hydrochloride extended-release tablets uses osmotic pressure to deliver methylphenidate HCl at a controlled rate. The system, which resembles a conventional tablet in appearance, comprises an osmotically active trilayer core surrounded by a semipermeable membrane with an immediate-release drug overcoat. The trilayer core is composed of two drug layers containing the drug and excipients, and a push layer containing osmotically active components. There is a precision-laser drilled orifice on the drug-layer end of the tablet. In an aqueous environment, such as the gastrointestinal tract, the drug overcoat dissolves within one hour, providing an initial dose of methylphenidate. Water permeates through the membrane into the tablet core. As the osmotically active polymer excipients expand, methylphenidate is released through the orifice. The membrane controls the rate at which water enters the tablet core, which in turn controls drug delivery. Furthermore, the drug release rate from the system increases with time over a period of 6 to 7 hours due to the drug-concentration gradient incorporated into the two drug layers of methylphenidate hydrochloride extended-release tablets. The biologically inert components of the tablet remain intact during gastrointestinal transit and are eliminated in the stool as a tablet shell along with insoluble core components. 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. “FDA approved dissolution test specifications differ from USP”.

10 OVERDOSAGE Human Experience Signs and symptoms of acute overdosage, resulting principally from overstimulation of the central nervous system and from excessive sympathomimetic effects, may include the following: nausea, vomiting, diarrhea, restlessness, anxiety, agitation, tremors, hyperreflexia, muscle twitching, convulsions (which may be followed by coma), euphoria, confusion, hallucinations, delirium, sweating, flushing, headache, hyperpyrexia, tachycardia, palpitations, cardiac arrhythmias, hypertension, hypotension, tachypnea, mydriasis, dryness of mucous membranes, and rhabdomyolysis. Posterior reversible encephalopathy syndrome (PRES) symptoms including headache, altered mental status, hypertension, seizures, and visual disturbances including blindness have occurred in the setting of an amphetamine product overdose. Symptoms of PRES are usually reversible but may evolve into ischemic stroke or cerebral hemorrhage. Diagnosis of PRES should be confirmed by radiological procedure (e.g., MRI). Overdose Management Consult with a Certified Poison Control Center (1-800-222-1222) for the latest recommendations. 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. • Posterior reversible encephalopathy syndrome (PRES) symptoms including headache, altered mental status, hypertension, seizures, and visual disturbances including blindness have occurred in the setting of an amphetamine product overdose. Symptoms of PRES are usually reversible but may evolve into ischemic stroke or cerebral hemorrhage. Diagnosis of PRES should be confirmed by radiological procedure (e.g., MRI). 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. If an overdose occurs, 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: 10 mg: White to off white, round shaped, uncoated, tablets debossed with “FM4” on one side and plain on other side. Bottles of 100 tablets NDC 51407-527-01 20 mg: White to off white, round shaped, uncoated, tablets debossed with “FM5” on one side and plain on other side. Bottles of 100 tablets NDC 51407-528-01 NOTE : Methylphenidate hydrochloride extended-release tablets, USP are color-additive free. Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F) [See USP Controlled Room Temperature]. Protect from moisture. Dispense in a tight, light-resistant container as defined in the USP, with a child-resistant closure. Disposal Comply with local laws and regulations on drug disposal of CNS stimulants. Dispose of remaining, unused, or expired Methylphenidate hydrochloride extended-release tablets, USP by a medicine takeback program or by an authorized collector registered with the Drug Enforcement Administration. If no take-back program or authorized collector is available, mix Methylphenidate hydrochloride extended-release tablets, USP with an undesirable, nontoxic substance to make it less appealing to children and pets. Place the mixture in a container such as a sealed plastic bag and discard Methylphenidate hydrochloride extended-release tablets, USP in the household trash.