Methylphenidate
Capsule, Extended Release · Oral, Transdermal
Uses
Methylphenidate hydrochloride extended-release capsules are indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD), in pediatric patients 6 to 12 years of age [see Clinical Studies ( 14 )] . Limitations of Use The use of methylphenidate 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 )]. Methylphenidate hydrochloride extended-release capsules are a central nervous system (CNS) stimulant indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in pediatric patients 6 to 12 years of age ( 1 ). Limitations of Use The use of methylphenidate 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 ).
Dosage and administration
• Administer orally once daily in the morning ( 2.2 ).
• Capsules may be swallowed whole or opened and the entire contents sprinkled on applesauce ( 2.2 ).
• Should not be crushed, chewed, or divided ( 2.2 ).
• Patients new to methylphenidate: Start at 20 mg daily, titrating the dose weekly in 10-mg increments. Doses above 60 mg daily are not recommended ( 2.3 ).
• For patients currently using methylphenidate hydrochloride tablets: Dosage is based on current dose regimen ( 2.4 ).
• If switching from other methylphenidate products, discontinue treatment and titrate with methylphenidate hydrochloride extended release capsules ( 2.4 ). 2.1 Pretreatment Screening Prior to treating patients with methylphenidate 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 methylphenidate hydrochloride extended-release capsules [see Warnings and Precautions ( 5.10 )] . 2.2 General Dosing Information The recommended starting dose for methylphenidate hydrochloride extended-release capsules is 20 mg once daily. Increase dosage gradually, in increments of 10 mg weekly. Daily dosage above 60 mg is not recommended. When a lower initial dose is appropriate, patients may begin treatment with 10 mg. Administer methylphenidate hydrochloride extended-release capsules orally once daily in the morning. Methylphenidate hydrochloride extended-release capsules may be swallowed as whole capsules or may be administered by sprinkling the capsule contents on a small amount of applesauce (see specific instructions below). Methylphenidate hydrochloride extended-release capsules and/or their contents should not be crushed, chewed, or divided. The capsules may be carefully opened and the beads sprinkled over a spoonful of applesauce. The applesauce should not be warm because it could affect the modified release properties of this formulation. The mixture of drug and applesauce should be consumed immediately in its entirety. The drug and applesauce mixture should not be stored for future use. 2.3 Patients Currently Using Methylphenidate Hydrochloride Tablets The recommended dose of methylphenidate hydrochloride extended-release capsules for patients currently taking methylphenidate hydrochloride tablets twice daily is provided below in Table 1. Table 1: Recommended Dose Conversion from Methylphenidate Hydrochloride Tablets Previous Methylphenidate Hydrochloride Tablets’ Dose Recommended Methylphenidate Hydrochloride Extended-Release Capsules’ Dose 5 mg methylphenidate hydrochloride tablets twice daily 10 mg once daily 10 mg methylphenidate hydrochloride tablets twice daily 20 mg once daily 15 mg methylphenidate hydrochloride tablets twice daily 30 mg once daily 20 mg methylphenidate hydrochloride tablets twice daily 40 mg once daily 30 mg methylphenidate hydrochloride tablets twice daily 60 mg once daily 2.4 Switching from Other Methylphenidate Products If switching from other methylphenidate products, discontinue that treatment, and titrate with methylphenidate hydrochloride extended-release capsules using the titration schedule. Do not substitute for other methylphenidate products on a milligram-per-milligram basis, because different methylphenidate base compositions and differing pharmacokinetic profiles [see Description ( 11 ), Clinical Pharmacology ( 12.3 )] . Clinical judgment should be used when selecting the starting dose. Daily dosage above 60 mg is not recommended. 2.5 Dosage Reduction and Discontinuation If paradoxical worsening of symptoms or other adverse reactions occur, reduce the dosage, or, if necessary, discontinue methylphenidate hydrochloride extended-release capsules. If improvement is not observed after appropriate dosage adjustment over a one-month period, the drug should be discontinued.
Dosage forms and strengths
• 10 mg extended-release capsules white/light brown, (imprinted "SDZ R10")
• 20 mg extended-release capsules white, (imprinted "SDZ R20")
• 30 mg extended-release capsules yellow, (imprinted "SDZ R30")
• 40 mg extended-release capsules light brown, (imprinted "SDZ R40") Extended-release capsules: 10 mg, 20 mg, 30 mg, and 40 mg ( 3 ).
Contraindications
• Hypersensitivity to methylphenidate or other components of methylphenidate 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 product components ( 4 ).
• Concurrent treatment with a monoamine oxidase inhibitor (MAOI) or use of an MAOI within the preceding 14 days ( 4 ).
Warnings and precautions
• Risks to Patients with Serious Cardiac Disease: Avoid use in patients with known structural cardiac abnormalities, cardiomyopathy, serious cardiac rhythm 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 methylphenidate hydrochloride extended-release capsules, screen patients for risk factors for developing a manic episode. If new psychotic or manic symptoms occur, consider discontinuing methylphenidate hydrochloride extended-release capsules (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 treatment with methylphenidate hydrochloride extended-release capsules. 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 i n 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: Patients treated with methylphenidate hydrochloride extended-release capsules 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 methylphenidate hydrochloride extended-release capsules 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 abnormally increased IOP or open angle glaucoma ( 5.9 ).
• Motor and Verbal Tics, and Worsening of Tourette’s Syndrome : Before initiating methylphenidate hydrochloride extended-release capsules, 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 Methylphenidate hydrochloride extended-release capsules have a high potential for abuse and misuse. The use of methylphenidate hydrochloride extended-release capsules exposes individuals to the risks of abuse and misuse, which can lead to the development of a substance use disorder, including addiction. Methylphenidate hydrochloride extended-release capsules 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 methylphenidate hydrochloride extended-release capsules, 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 methylphenidate hydrochloride extended-release capsules, 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 methylphenidate hydrochloride extended-release capsules in a safe place, preferably locked, and instruct patients to not give methylphenidate hydrochloride extended-release capsules to anyone else. Throughout treatment with methylphenidate hydrochloride extended-release capsules, 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 are treated with CNS stimulants at the recommended ADHD dosage. Avoid use of methylphenidate hydrochloride extended-release capsules in patients with known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmia, coronary artery disease, or other serious cardiac disease. 5.3 Increased Blood Pressure and Heart Rate CNS stimulants cause an increase in blood pressure (mean increase approximately 2 to 4 mmHg) and heart rate (mean increase approximately 3 to 6 beats per minute). Some patients may have larger increases. Monitor all patients treated with methylphenidate hydrochloride extended-release capsules for hypertension and tachycardia. 5.4 Psychiatric Adverse Reactions Exacerbation of Preexisting Psychosis CNS stimulants may exacerbate symptoms of behavior disturbance and thought disorder in patients with a preexisting psychotic disorder. Induction of a Manic Episode in Patients with Bipolar Disorder CNS stimulants may induce a manic or mixed mood episode in patients. Prior to initiating treatment with methylphenidate hydrochloride extended-release capsules, screen patients for risk factors for developing a manic episode (e.g., comorbid or history of depressive symptoms or a family history of suicide, bipolar disorder, or depression). New Psychotic or Manic Symptoms CNS stimulants, at the recommended dosage, may cause psychotic or manic symptoms (e.g., hallucinations, delusional thinking, or mania) in patients without a prior history of psychotic illness or mania. In a pooled analysis of multiple short-term, placebo-controlled studies of CNS stimulants, psychotic or manic symptoms occurred in approximately 0.1% of CNS stimulant-treated patients, compared to 0% of placebo-treated patients. If such symptoms occur, consider discontinuing methylphenidate hydrochloride extended-release capsules.
Side effects
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 methylphenidate hydrochloride extended-release capsules [see Contraindications ( 4 )]
• Hypertensive crisis when used concomitantly with 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 )] Most common adverse reactions (greater than 5% during incidence) were headache, insomnia, upper abdominal pain, decreased appetite, and anorexia ( 6 ). To report SUSPECTED ADVERSE REACTIONS, contact Sandoz Inc., at 1-800-525-8747 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 practice. The clinical program for methylphenidate hydrochloride extended-release capsules consisted of 6 studies: 2 controlled clinical studies conducted in children with ADHD aged 6 to 12 years and 4 clinical pharmacology studies conducted in healthy adult volunteers. These studies included a total of 256 subjects; 195 children with ADHD and 61 healthy adult volunteers. The subjects received methylphenidate hydrochloride extended-release capsules in doses of 10 to 40 mg per day. Safety of methylphenidate hydrochloride extended-release capsules was assessed by evaluating frequency and nature of adverse events, routine laboratory tests, vital signs, and body weight. A placebo-controlled, double-blind, parallel-group study was conducted to evaluate the efficacy and safety of methylphenidate hydrochloride extended-release capsules in children with ADHD aged 6 to 12 years. All subjects received methylphenidate hydrochloride extended-release capsules for up to 4 weeks, and had their dose optimally adjusted, prior to entering the double-blind phase of the trial. In the 2-week double-blind treatment phase of this study, patients received either placebo or methylphenidate hydrochloride extended-release capsules at their individually-titrated dose (range, 10 mg to 40 mg). Adverse reactions with an incidence greater than 5% during the initial 4-week single-blind methylphenidate hydrochloride extended-release capsules titration period of this study were headache, insomnia, upper abdominal pain, appetite decreased, and anorexia. Adverse reactions with an incidence greater than 2% among methylphenidate hydrochloride extended-release capsules-treated subjects, during the 2-week double-blind phase of the clinical study, are shown in Table 2. Table 2: Adverse Reactions in Greater Than 2% Methylphenidate Hydrochloride Extended-Release Capsules-Treated Subjects in the 2-Week Double-Blind Phase Preferred Term Methylphenidate Hydrochloride Extended-Release Capsules N = 65 N (%) Placebo N = 71 N (%) Anorexia 2 (3.1) 0 (0.0) Insomnia 2 (3.1) 0 (0.0) Adverse Reactions Associated with Discontinuation of Treatment In the 2-week double-blind treatment phase of a placebo-controlled parallel-group study in children with ADHD, one methylphenidate hydrochloride extended-release capsules-treated subject (1/65, 1.5%) discontinued due to an adverse event (depressed mood). In the single-blind titration period of this study, subjects received methylphenidate hydrochloride extended-release capsules for up to 4 weeks. During this period a total of 6 subjects (6/161, 3.7%) discontinued due to adverse events. The adverse events leading to discontinuation were anger (2 patients), hypomania, anxiety, depressed mood, fatigue, migraine, and lethargy. 6.2 Postmarketing Experience The following adverse reactions have been identified during the post approval use of methylphenidate products. Because these reactions were reported voluntarily from a population of uncertain size, it is not always possible to estimate their frequency reliably or to establish a causal relationship to drug exposure.
Drug interactions
• Antihypertensive Drugs: Monitor blood pressure and heart. Adjust dosage of antihypertensive drug as needed ( 7.1 ). 7.1 Clinically Important Drug Interactions with Methylphenidate Hydrochloride Extended-Release Capsules Table 3 presents clinically important drug interactions with methylphenidate hydrochloride extended-release capsules. Table 3: Clinically Important Drug Interactions with Methylphenidate Hydrochloride Extended-Release Capsules Monoamine Oxidase Inhibitors (MAOI) Clinical impact Concomitant use of MAOIs and CNS stimulants, including methylphenidate hydrochloride extended-release capsules, 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 capsules with MAOIs or within 14 days after discontinuing MAOI treatment is contraindicated. Antihypertensive Drugs Clinical impact Methylphenidate hydrochloride extended-release capsules 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 methylphenidate hydrochloride extended-release capsules may increase the risk of sudden blood pressure and heart rate increase during surgery. Intervention Avoid use of methylphenidate hydrochloride extended-release capsules 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
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 methylphenidate hydrochloride extended-release capsules 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 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 use 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 during organogenesis at doses up to 10 and 15 times, respectively, the maximum recommended human dose (MRHD) of 60 mg/day given to adolescents on a mg/m 2 basis. However, spina bifida was observed in rabbits at a dose 52 times the MRHD given to adolescents. A decrease in pup body weight was observed in a pre- and post-natal development study with oral administration of methylphenidate to rats throughout pregnancy and lactation at doses 6 times the MRHD given to adolescents (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 methylphenidate hydrochloride extended-release capsules, 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, methylphenidate was administered orally at doses of up to 75 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 52 times the MRHD of 60 mg/day given to adolescents on a mg/m 2 basis. The no effect level for embryo-fetal development in rabbits was 60 mg/kg/day (15 times the MRHD given to adolescents on a mg/m 2 basis). There was no evidence of morphological development effects in rats, although increased incidences of fetal skeletal variations were seen at the highest dose level (10 times the MRHD of 60 mg/day given to adolescents on a mg/m 2 basis), which was also maternally toxic. The no effect level for embryo-fetal development in rats was 25 mg/kg/day (3 times the MRHD on a mg/m 2 basis). When methylphenidate was administered to rats throughout pregnancy and lactation at doses of up to 45 mg/kg/day, offspring body weight gain was decreased at the highest dose (6 times the MRHD of 60 mg/day given to adolescents on a mg/m 2 basis), but no other effects on postnatal development were observed. The no effect level for pre- and post-natal development in rats was 15 mg/kg/day (approximately 2 times the MRHD given to adolescents on a mg/m 2 basis). 8.2 Lactation Risk Summary 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 methylphenidate hydrochloride extended-release capsules and any potential adverse effects on the breastfed infant from methylphenidate hydrochloride extended-release capsules or from the underlying maternal condition. Clinical Considerations Monitor breastfeeding infants for adverse reactions, such as agitation, insomnia, anorexia, and reduced weight gain. 8.4 Pediatric Use The safety and effectiveness of methylphenidate hydrochloride extended-release capsules have not been established in pediatric patients below the age of 6 years. In studies evaluating extended-release methylphenidate products, patients 4 to <6 years of age had higher systemic methylphenidate exposures than those observed in older pediatric patients at the same dosage. Pediatric patients 4 to <6 years of age also had a higher incidence of adverse reactions, including weight loss. The safety and effectiveness of methylphenidate hydrochloride extended-release capsules for the treatment of ADHD have been established in pediatric patients aged 6 to 12 years. Long-Term Suppression of Growth Growth should be monitored during treatment with stimulants, including methylphenidate hydrochloride extended-release capsules. Pediatric patients who are not growing or gaining weight as expected may need to have their treatment interrupted [see Warnings and Precautions ( 5.7 )] . Juvenile Animal Toxicity Data Rats treated with methylphenidate early in the postnatal period through sexual maturation demonstrated a decrease in spontaneous locomotor activity in adulthood. A deficit in acquisition of a specific learning task was observed in females only.
Pregnancy
8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to ADHD medications, including methylphenidate hydrochloride extended-release capsules 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 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 use 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 during organogenesis at doses up to 10 and 15 times, respectively, the maximum recommended human dose (MRHD) of 60 mg/day given to adolescents on a mg/m 2 basis. However, spina bifida was observed in rabbits at a dose 52 times the MRHD given to adolescents. A decrease in pup body weight was observed in a pre- and post-natal development study with oral administration of methylphenidate to rats throughout pregnancy and lactation at doses 6 times the MRHD given to adolescents (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 methylphenidate hydrochloride extended-release capsules, 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, methylphenidate was administered orally at doses of up to 75 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 52 times the MRHD of 60 mg/day given to adolescents on a mg/m 2 basis. The no effect level for embryo-fetal development in rabbits was 60 mg/kg/day (15 times the MRHD given to adolescents on a mg/m 2 basis). There was no evidence of morphological development effects in rats, although increased incidences of fetal skeletal variations were seen at the highest dose level (10 times the MRHD of 60 mg/day given to adolescents on a mg/m 2 basis), which was also maternally toxic. The no effect level for embryo-fetal development in rats was 25 mg/kg/day (3 times the MRHD on a mg/m 2 basis). When methylphenidate was administered to rats throughout pregnancy and lactation at doses of up to 45 mg/kg/day, offspring body weight gain was decreased at the highest dose (6 times the MRHD of 60 mg/day given to adolescents on a mg/m 2 basis), but no other effects on postnatal development were observed. The no effect level for pre- and post-natal development in rats was 15 mg/kg/day (approximately 2 times the MRHD given to adolescents on a mg/m 2 basis).
Pediatric use
8.4 Pediatric Use The safety and effectiveness of methylphenidate hydrochloride extended-release capsules have not been established in pediatric patients below the age of 6 years. In studies evaluating extended-release methylphenidate products, patients 4 to <6 years of age had higher systemic methylphenidate exposures than those observed in older pediatric patients at the same dosage. Pediatric patients 4 to <6 years of age also had a higher incidence of adverse reactions, including weight loss. The safety and effectiveness of methylphenidate hydrochloride extended-release capsules for the treatment of ADHD have been established in pediatric patients aged 6 to 12 years. Long-Term Suppression of Growth Growth should be monitored during treatment with stimulants, including methylphenidate hydrochloride extended-release capsules. Pediatric patients who are not growing or gaining weight as expected may need to have their treatment interrupted [see Warnings and Precautions ( 5.7 )] . Juvenile Animal Toxicity Data Rats treated with methylphenidate early in the postnatal period through sexual maturation demonstrated a decrease in spontaneous locomotor activity in adulthood. A deficit in acquisition of a specific learning task was observed in females only. The doses at which these findings were observed are at least 4 times the MRHD of 60 mg/day given to children on a mg/m 2 basis. In a study conducted in young rats, methylphenidate was administered orally at doses of up to 100 mg/kg/day for 9 weeks, starting early in the postnatal period (postnatal Day 7) and continuing through sexual maturity (postnatal Week 10). When these animals were tested as adults (postnatal Weeks 13 to 14), decreased spontaneous locomotor activity was observed in males and females previously treated with 50 mg/kg/day (approximately 4 times the MRHD of 60 mg/day given to children on a mg/m 2 basis) or greater, and a deficit in the acquisition of a specific learning task was seen in females exposed to the highest dose (8 times the MRHD given to children on a mg/m 2 basis). The no effect level for juvenile neurobehavioral development in rats was 5 mg/kg/day (approximately 0.5 times the MRHD given to children on a mg/m 2 basis). The clinical significance of the long-term behavioral effects observed in rats is unknown.
Geriatric use
8.5 Geriatric Use Methylphenidate hydrochloride extended-release capsules have not been studied in the geriatric population.
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 hydrochloride extended-release capsules 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.
Description
Methylphenidate hydrochloride extended-release capsules are CNS stimulant. Methylphenidate hydrochloride extended-release capsules is an extended-release formulation of methylphenidate for oral administration with a bi-modal release profile. Each bead-filled methylphenidate hydrochloride extended-release capsule contains half the dose as immediate-release beads and half as enteric-coated beads, thus providing an immediate release of methylphenidate and a second delayed release of methylphenidate. The active substance in methylphenidate hydrochloride extended-release capsules is methyl α-phenyl-2-piperidineacetate hydrochloride, and its structural formula is Methylphenidate hydrochloride USP is a white, odorless, 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 g/mol. Inactive ingredients: ammonio methacrylate copolymer, black iron oxide (10 and 40 mg capsules only), gelatin, methacrylic acid copolymer, polyethylene glycol, red iron oxide (10 and 40 mg capsules only), sugar spheres, talc, titanium dioxide, triethyl citrate, and yellow iron oxide (10, 30, and 40 mg capsules only). Ritalin LA structural formula.
Mechanism of action
12.1 Mechanism of Action Methylphenidate hydrochloride is a CNS stimulant. The mode of therapeutic action in ADHD is not known.
How supplied
• 10 mg extended-release capsules (NDC 0781-2383-01) white/light brown, (imprinted “SDZ R10”) supplied in bottles of 100
• 20 mg extended-release capsules (NDC 0781-2384-01) white, (imprinted “SDZ R20”) supplied in bottles of 100
• 30 mg extended-release capsules (NDC 0781-2385-01) yellow, (imprinted “SDZ R30”) supplied in bottles of 100
• 40 mg extended-release capsules (NDC 0781-2386-01) light brown, (imprinted “SDZ R40”) supplied in bottles of 100 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).
Patient information
Advise the patient to read the FDA-approved patient labeling (Medication Guide). Abuse, Misuse, and Addiction Educate patients and their families about the risks of abuse, misuse, and addiction of methylphenidate hydrochloride extended-release capsules, which can lead to overdose and death, and proper disposal of any unused drug [see Warnings and Precautions ( 5.1 ), Drug Abuse and Dependence ( 9.2 ), Overdosage ( 10 )] . Advise patients to store methylphenidate hydrochloride extended-release capsules in a safe place, preferably locked, and instruct patients to not give methylphenidate hydrochloride extended-release capsules to anyone else. Risks to Patients with Serious Cardiac Disease Advise patients that there are potential risks to patients with serious cardiac disease, including sudden death, with use of methylphenidate hydrochloride extended-release capsules. Instruct patients to contact a healthcare provider immediately if they develop symptoms, such as exertional chest pain, unexplained syncope, or other symptoms suggestive of cardiac disease [see Warnings and Precautions ( 5.2 )]. Increased Blood Pressure and Heart Rate Instruct patients that methylphenidate hydrochloride extended-release capsules can cause elevations of their blood pressure and pulse rate [see Warnings and Precautions ( 5.3 )] . Psychiatric Adverse Reactions Advise patients that methylphenidate hydrochloride extended-release capsules, at recommended doses, can cause psychotic or manic symptoms, even in patients without prior history of psychotic symptoms or mania [see Warnings and Precautions ( 5.4 )] . Priapism Advise patients of the possibility of painful or prolonged penile erections (priapism). Instruct them to seek immediate medical attention in the event of priapism [see Warnings and Precautions ( 5.5 )] . Circulation Problems in Fingers and Toes [Peripheral Vasculopathy, Including Raynaud’s Phenomenon] Instruct patients beginning treatment with methylphenidate hydrochloride extended-release capsules about the risk of peripheral vasculopathy, including Raynaud’s phenomenon, and associated signs and symptoms: fingers or toes may feel numb, cool, painful, and/or may change color from pale, to blue, to red. Instruct patients to report to their physician any new numbness, pain, skin color change, or sensitivity to temperature in fingers or toes. Instruct patients to call their physician immediately with any signs of unexplained wounds appearing on fingers or toes while taking methylphenidate hydrochloride extended-release capsules. Further clinical evaluation (e.g., rheumatology referral) may be appropriate for certain patients [see Warnings and Precautions ( 5.6 )] . Long Term Suppression of Growth in Pediatric Patients Advise patients that methylphenidate hydrochloride extended-release capsules may cause slowing of growth and weight loss [see Warnings and Precautions ( 5.7 )] . Increased Intraocular Pressure (IOP) and Glaucoma Advise patients that IOP and glaucoma may occur during treatment with methylphenidate hydrochloride extended-release capsules [see Warnings and Precautions ( 5.9 )] . Motor and Verbal Tics and Worsening of Tourette’s Syndrome Advise patients that motor and verbal tics and worsening of Tourette’s Syndrome may occur during treatment with methylphenidate hydrochloride extended-release capsules. Instruct patients to notify their healthcare provider if emergence of new tics or worsening of tics or Tourette’s syndrome occurs [see Warnings and Precautions ( 5.10 )] . Alcohol Effect Advise patients to avoid alcohol while taking methylphenidate hydrochloride extended-release capsules. Consumption of alcohol while taking methylphenidate hydrochloride extended-release capsules may result in a more rapid release of the dose of methylphenidate [see Clinical Pharmacology ( 12.3 )] . Pregnancy Registry Advise patients that there is a pregnancy exposure registry that monitors pregnancy outcomes in patients exposed to methylphenidate hydrochloride extended-release capsules during pregnancy [see Use in Specific Populations ( 8.1 )] . Manufactured by Societal CDMO Gainesville, LLC Gainesville, GA 30504 for Sandoz Inc., Princeton, NJ 08540 6003693-01
Label text from the FDA structured product label by Sandoz Inc (revised Sep 23, 2025). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Methylphenidate Hydrochloride in 10 products
- Methylphenidate in 4 products
Methylphenidate NDC products (14)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 10702-163 | Methylphenidate Hydrochloride 5 mg/5mL Solution | KVK-Tech, Inc. | ANDA · DEA CII |
| 10702-164 | Methylphenidate Hydrochloride 10 mg/5mL Solution | KVK-Tech, Inc. | ANDA · DEA CII |
| 0378-8260 | Methylphenidate 1.1 mg/h Patch | Mylan Pharmaceuticals Inc. | ANDA · DEA CII |
| 0378-8261 | Methylphenidate 1.6 mg/h Patch | Mylan Pharmaceuticals Inc. | ANDA · DEA CII |
| 0378-8262 | Methylphenidate 2.2 mg/h Patch | Mylan Pharmaceuticals Inc. | ANDA · DEA CII |
| 0378-8263 | Methylphenidate 3.3 mg/h Patch | Mylan Pharmaceuticals Inc. | ANDA · DEA CII |
| 0781-2361 | Methylphenidate Hydrochloride 10 mg/1 Capsule, Extended Release | Sandoz Inc | NDA AUTHORIZED GENERIC · DEA CII |
| 0781-2362 | Methylphenidate Hydrochloride 20 mg/1 Capsule, Extended Release | Sandoz Inc | NDA AUTHORIZED GENERIC · DEA CII |
| 0781-2363 | Methylphenidate Hydrochloride 30 mg/1 Capsule, Extended Release | Sandoz Inc | NDA AUTHORIZED GENERIC · DEA CII |
| 0781-2364 | Methylphenidate Hydrochloride 40 mg/1 Capsule, Extended Release | Sandoz Inc | NDA AUTHORIZED GENERIC · DEA CII |
| 0781-2383 | Methylphenidate Hydrochloride 10 mg/1 Capsule, Extended Release | Sandoz Inc | NDA AUTHORIZED GENERIC · DEA CII |
| 0781-2384 | Methylphenidate Hydrochloride 20 mg/1 Capsule, Extended Release | Sandoz Inc | NDA AUTHORIZED GENERIC · DEA CII |
| 0781-2385 | Methylphenidate Hydrochloride 30 mg/1 Capsule, Extended Release | Sandoz Inc | NDA AUTHORIZED GENERIC · DEA CII |
| 0781-2386 | Methylphenidate Hydrochloride 40 mg/1 Capsule, Extended Release | Sandoz Inc | NDA AUTHORIZED GENERIC · DEA CII |
Frequently asked questions
What is Methylphenidate used for?
Methylphenidate hydrochloride extended-release capsules are indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD), in pediatric patients 6 to 12 years of age [see Clinical Studies ( 14 )] . Limitations of Use The use of methylphenidate hydrochloride extended-release capsules is not recommended in pediatric patients younger than 6 years of age because they had higher…
What are the side effects of Methylphenidate?
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 methylphenidate hydrochloride extended-release capsules [see Contraindications ( 4 )] • Hypertensive crisis when used… See the full label for the complete list.
Who makes Methylphenidate?
Methylphenidate is listed by 3 labelers in the FDA NDC directory, including KVK-Tech, Inc., Mylan Pharmaceuticals Inc., Sandoz Inc.