ABUSE SECTION.

9.2 Abuse. Ritalin has high potential for abuse and misuse which can lead to the development of substance use disorder, including addiction [see Warnings and Precautions (5.1)]. Ritalin can be diverted for non-medical use into illicit channels or distribution.Abuse is the intentional non-therapeutic use of drug, even once, to achieve desired psychological or physiological effect. Misuse is the intentional use, for therapeutic purposes, of drug by an individual in way other than prescribed by health care provider or for whom it was not prescribed. Drug addiction is cluster of behavioral, cognitive, and physiological phenomena that may include strong desire to take the drug, difficulties in controlling drug use (e.g., continuing drug use despite harmful consequences, giving higher priority to drug use than other activities and obligations), and possible tolerance or physical dependence.Misuse and abuse of methylphenidate hydrochloride may cause increased heart rate, respiratory rate, or blood pressure; sweating; dilated pupils; hyperactivity; restlessness; insomnia; decreased appetite; loss of coordination; tremors; flushed skin; vomiting; and/or abdominal pain. Anxiety, psychosis, hostility, aggression, and suicidal or homicidal ideation have also been observed with CNS stimulants abuse and/or misuse. Misuse and abuse of CNS stimulants, including Ritalin, 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.

ADVERSE REACTIONS SECTION.

6 ADVERSE REACTIONS. The following are discussed in more detail in other sections of the labeling:oAbuse, Misuse, and Addiction [see Boxed Warning, Warnings and Precautions (5.1), Drug Abuse and Dependence (9.2, 9.3)]oKnown hypersensitivity to methylphenidate or other ingredients of Ritalin [see Contraindications (4)]oHypertensive crisis with Concomitant Use of Monoamine Oxidase Inhibitors [see Contraindications (4), Drug Interactions (7.1)]oRisks to Patients with Serious Cardiac Disease [see Warnings and Precautions (5.2)]oIncreased Blood Pressure and Heart Rate [see Warnings and Precautions (5.3)]oPsychiatric Adverse Reactions [see Warnings and Precautions (5.4)]oPriapism [see Warnings and Precautions (5.5)]oPeripheral Vasculopathy, Including Raynauds Phenomenon [see Warnings and Precautions (5.6)] oLong-Term Suppression of Growth in Pediatric Patients [see Warnings and Precautions (5.7)]oAcute Angle Closure Glaucoma [see Warnings and Precautions (5.8)]oIncreased Intraocular Pressure and Glaucoma [see Warnings and Precautions (5.9)]oMotor and Verbal Tics, and Worsening of Tourettes Syndrome [see Warnings and Precautions (5.10)] The following adverse reactions associated with the use of Ritalin and other methylphenidate products were identified in clinical trials, spontaneous reports, and literature. Because these reactions were reported voluntarily from population of uncertain size, it is not always possible to estimate their frequency reliably or to establish causal relationship to drug exposure.Adverse Reactions Reported with RitalinInfections and Infestations: nasopharyngitisBlood and the Lymphatic System Disorders: leukopenia, thrombocytopenia, anemiaImmune System Disorders: hypersensitivity reactions, including angioedema, and anaphylaxisMetabolism and Nutrition Disorders: decreased appetite, reduced weight gain, and suppression of growth during prolonged use in pediatric patientsPsychiatric Disorders: insomnia, anxiety, restlessness, agitation, psychosis (sometimes with visual and tactile hallucinations), depressed mood, depressionNervous System Disorders: headache, dizziness, tremor, dyskinesia, including choreoatheetoid movements, drowsiness, convulsions, cerebrovascular disorders (including vasculitis, cerebral hemorrhages and cerebrovascular accidents), serotonin syndrome in combination with serotonergic drugsEye Disorders: blurred vision, difficulties in visual accommodationCardiac Disorders: tachycardia, palpitations, increased blood pressure, arrhythmias, angina pectorisRespiratory, Thoracic, and Mediastinal Disorders: coughGastrointestinal Disorders: dry mouth, nausea, vomiting, abdominal pain, dyspepsiaHepatobiliary Disorders: abnormal liver function, ranging from transaminase elevation to severe hepatic injurySkin and Subcutaneous Tissue Disorders: hyperhidrosis, pruritus, urticaria, exfoliative dermatitis, scalp hair loss, erythema multiforme rash, thrombocytopenic purpuraMusculoskeletal and Connective Tissue Disorders: arthralgia, muscle cramps, rhabdomyolysis, trismusInvestigations: weight loss (adult ADHD patients)Vascular Disorders: peripheral coldness, Raynauds phenomenonAdditional Adverse Reactions Reported with Other Methylphenidate-Containing ProductsThe list below shows adverse reactions not listed for Ritalin that have been reported with other methylphenidate-containing products.Blood and Lymphatic Disorders: pancytopeniaImmune System Disorders: hypersensitivity reactions, such as auricular swelling, bullous conditions, eruptions, exanthemasPsychiatric Disorders: affect lability, mania, disorientation, and libido changesNervous System Disorders: migraine, motor and verbal ticsEye Disorders: diplopia, increased intraocular pressure, mydriasisCardiac Disorders: sudden cardiac death, myocardial infarction, bradycardia, extrasystoleRespiratory, Thoracic, and Mediastinal Disorders: pharyngolaryngeal pain, dyspneaGastrointestinal Disorders: diarrhea, constipationSkin and Subcutaneous Tissue Disorders: angioneurotic edema, erythema, fixed drug eruptionMusculoskeletal, Connective Tissue, and Bone Disorders: myalgia, muscle twitchingRenal and Urinary Disorders: hematuriaReproductive System and Breast Disorders: gynecomastiaGeneral Disorders: fatigue, hyperpyrexiaUrogenital Disorders: priapism. oAbuse, Misuse, and Addiction [see Boxed Warning, Warnings and Precautions (5.1), Drug Abuse and Dependence (9.2, 9.3)]. oKnown hypersensitivity to methylphenidate or other ingredients of Ritalin [see Contraindications (4)]. oHypertensive crisis with Concomitant Use of Monoamine Oxidase Inhibitors [see Contraindications (4), Drug Interactions (7.1)]. oRisks to Patients with Serious Cardiac Disease [see Warnings and Precautions (5.2)]. oIncreased Blood Pressure and Heart Rate [see Warnings and Precautions (5.3)]. oPsychiatric Adverse Reactions [see Warnings and Precautions (5.4)]. oPriapism [see Warnings and Precautions (5.5)]. oPeripheral Vasculopathy, Including Raynauds Phenomenon [see Warnings and Precautions (5.6)] oLong-Term Suppression of Growth in Pediatric Patients [see Warnings and Precautions (5.7)]. oAcute Angle Closure Glaucoma [see Warnings and Precautions (5.8)]. oIncreased Intraocular Pressure and Glaucoma [see Warnings and Precautions (5.9)]. oMotor and Verbal Tics, and Worsening of Tourettes Syndrome [see Warnings and Precautions (5.10)] Common adverse reactions: tachycardia, palpitations, headache, insomnia, anxiety, hyperhidrosis, weight loss, decreased appetite, dry mouth, nausea, and abdominal pain (6). To report SUSPECTED ADVERSE REACTIONS, contact Novartis Pharmaceuticals Corporation at 1-888-669-6682 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.. Common adverse reactions: tachycardia, palpitations, headache, insomnia, anxiety, hyperhidrosis, weight loss, decreased appetite, dry mouth, nausea, and abdominal pain (6).

BOXED WARNING SECTION.

WARNING: ABUSE, MISUSE, AND ADDICTION. Ritalin has high potential for abuse and misuse, which can lead to the development of substance use disorder, including addiction. Misuse and abuse of CNS stimulants, including Ritalin, 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 Ritalin, assess each patients risk for abuse, misuse, and addiction. Educate patients and their families about these risks, proper storage of the drug, and proper disposal of any unused drug. Throughout Ritalin treatment, reassess each patients risk of abuse, misuse, and addiction and frequently monitor for signs and symptoms of abuse, misuse, and addiction [see Warnings and Precautions (5.1) and Drug Abuse and Dependence (9.2)]. WARNING: ABUSE, MISUSE, AND ADDICTIONSee full prescribing information for complete boxed warning.Ritalin has high potential for abuse and misuse, which can lead to the development of substance use disorder, including addiction. Misuse and abuse of CNS stimulants, including Ritalin, can result in overdose and death (5.1, 9.2, 10):o Before prescribing Ritalin, assess each patients risk for abuse, misuse, and addiction.o Educate patients and their families about these risks, proper storage of the drug, and proper disposal of any unused drug.o Throughout treatment, reassess each patients risk and frequently monitor for signs and symptoms of abuse, misuse, and addiction.

CARCINOGENESIS & MUTAGENESIS & IMPAIRMENT OF FERTILITY SECTION.

13.1 Carcinogenesis, Mutagenesis, and Impairment of Fertility. CarcinogenesisIn lifetime carcinogenicity study carried out in B6C3F1 mice, methylphenidate caused an increase in hepatocellular adenomas, and in males only, an increase in hepatoblastomas at daily dose of approximately 60 mg/kg/day. This dose is approximately times the MRHD of 60 mg/day given to children on mg/m2 basis. Hepatoblastoma is relatively rare rodent malignant tumor type. There was no increase in total malignant hepatic tumors. The mouse strain used is sensitive to the development of hepatic tumors and the significance of these results to humans is unknown.Methylphenidate did not cause any increase in tumors in lifetime carcinogenicity study carried out in F344 rats; the highest dose used was approximately 45 mg/kg/day, which is approximately times the MRHD (children) on mg/m2 basis.In 24-week carcinogenicity study in the transgenic mouse strain p53+/-, which is sensitive to genotoxic carcinogens, there was no evidence of carcinogenicity. Male and female mice were fed diets containing the same concentration of methylphenidate as in the lifetime carcinogenicity study; the high-dose groups were exposed to 60 to 74 mg/kg/day of methylphenidate.MutagenesisMethylphenidate was not mutagenic in the in vitro Ames reverse mutation assay, in the in vitro mouse lymphoma cell forward mutation assay, or in the in vitro chromosomal aberration assay using human lymphocytes. Sister chromatid exchanges and chromosome aberrations were increased, indicative of weak clastogenic response, in an in vitro assay in cultured Chinese Hamster Ovary cells. Methylphenidate was negative in vivo in males and females in the mouse bone marrow micronucleus assay.Impairment of FertilityNo human data on the effect of methylphenidate on fertility are available. Methylphenidate did not impair fertility in male or female mice that were fed diets containing the drug in an 18-week continuous breeding study. The study was conducted at doses up to 160 mg/kg/day, approximately 10times the MRHD of 60 mg/day given to adolescents on mg/m2 basis.

CLINICAL PHARMACOLOGY SECTION.

12 CLINICAL PHARMACOLOGY. 12.1 Mechanism of Action. Methylphenidate hydrochloride is CNS stimulant. The mode of therapeutic action in ADHD and narcolepsy is not known.. 12.2 Pharmacodynamics. Methylphenidate is racemic mixture comprised of the d- and l-threo enantiomers. The d-threo enantiomer is more pharmacologically active than the l-threo enantiomer. Methylphenidate blocks the reuptake of norepinephrine and dopamine into the presynaptic neuron and increases the release of these monoamines into the extraneuronal space.Cardiac ElectrophysiologyA formal QT study has not been conducted in patients taking Ritalin.The effect of dexmethylphenidate, the pharmacologically active d-enantiomer of Ritalin, on the QT interval was evaluated in double-blind, placebo- and open-label active (moxifloxacin)-controlled study following single doses of dexmethlyphenidate XR 40 mg (maximum recommended adult total daily dosage) in 75 healthy volunteers. Electrocardiograms were collected up to 12 hours postdose. Fredericas method for heart rate correction was employed to derive the corrected QT interval (QTcF). The maximum mean prolongation of QTcF intervals was less than ms, and the upper limit of the 90% confidence interval was below 10 ms for all time-matched comparisons versus placebo. This was below the threshold of clinical concern and there was no evident exposure response relationship.. 12.3 Pharmacokinetics. AbsorptionThe absolute bioavailability of methylphenidate is 22 +- % for the d-enantiomer and +- % for the l-enantiomer. Peakplasma concentrations of approximately 4.3 +- 2.3 ng/mL were reached on an average of hours after administration of 10mg tablet. The time to peak rate in children was 1.9 hours (0.3 to 4.4 hours) for Ritalin.Effect of FoodIngestion with food has no relevant effect on absorption of Ritalin.DistributionBinding to plasma proteins is low (10% to 33%). The volume of distribution was 2.65 +- 1.11 L/kg for d-methylphenidate and 1.80 +- 0.91 L/kg for l-methylphenidate.EliminationThe systemic clearance is 0.40 +- 0.12 L/h/kg for d-methylphenidate and 0.73 +- 0.28 L/h/kg for l-methylphenidate.MetabolismMethylphenidate is metabolized primarily by de-esterification to alpha-phenyl-piperidine acetic acid (ritalinic acid), which has little or no pharmacologic activity.ExcretionAfter oral administration, 78% to 97% of the dose is excreted in the urine and 1% to 3% in feces in the form of metabolites within 48 to 96 hours. Most of the dose is excreted in the urine as alpha-phenyl-2-piperidine acetic acid (60% to 86%). Studies in Specific PopulationsMale and Female PatientsNo gender differences in the pharmacokinetics of methylphenidate between healthy male and female adults are expected.Racial or Ethnic GroupsThere is insufficient experience with the use of Ritalin to detect ethnic variations in pharmacokinetics.Patients with Renal ImpairmentRitalin has not been studied in renally-impaired patients. Renal impairment is expected to have minimal effect on the pharmacokinetics of methylphenidate since less than 1% of radiolabeled dose is excreted in the urine as unchanged compound, and the major metabolite (ritalinic acid), has little or no pharmacologic activity.Patients with Hepatic ImpairmentRitalin has not been studied in patients with hepatic impairment. Hepatic impairment is expected to have minimal effect on the pharmacokinetics of methylphenidate since it is metabolized primarily to ritalinic acid by nonmicrosomal hydrolytic esterases that are widely distributed throughout the body.

CONTRAINDICATIONS SECTION.

4 CONTRAINDICATIONS. oHypersensitivity to methylphenidate or other components of Ritalin. Hypersensitivity reactions, such as angioedema and anaphylactic reactions, have been reported in patients treated with methylphenidate [see Adverse Reactions (6)].oConcomitant 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)]. oHypersensitivity to methylphenidate or other components of Ritalin. Hypersensitivity reactions, such as angioedema and anaphylactic reactions, have been reported in patients treated with methylphenidate [see Adverse Reactions (6)].. oConcomitant 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)]. oKnown hypersensitivity to methylphenidate or other product components of Ritalin (4).oConcurrent treatment with monoamine oxidase inhibitor (MAOI), or use of an MAOI within the preceding 14 days (4).. oKnown hypersensitivity to methylphenidate or other product components of Ritalin (4).. oConcurrent treatment with monoamine oxidase inhibitor (MAOI), or use of an MAOI within the preceding 14 days (4).

CONTROLLED SUBSTANCE SECTION.

9.1 Controlled Substance. Ritalin contains methylphenidate hydrochloride, Schedule II controlled substance.

DEPENDENCE SECTION.

9.3 Dependence. Physical DependenceRitalin may produce physical dependence. Physical dependence is state that develops as result of physiological adaptation in response to repeated drug use, manifested by withdrawal signs and symptoms after abrupt discontinuation or significant dose reduction of drug.Withdrawal signs and symptoms after abrupt discontinuation or dose reduction following prolonged use of CNS stimulants including Ritalin include dysphoric mood; depression; fatigue; vivid, unpleasant dreams; insomnia or hypersomnia; increased appetite; and psychomotor retardation or agitation.ToleranceRitalin may produce tolerance. Tolerance is physiological state characterized by reduced response to drug after repeated administration (i.e., higher dose of drug is required to produce the same effect that was once obtained at lower dose).

DESCRIPTION SECTION.

11 DESCRIPTION. Ritalin contains methylphenidate hydrochloride, CNS stimulant. It is available as tablets of mg, 10 mg, and 20 mg strengths for oral administration.Methylphenidate hydrochloride is methyl -phenyl-2-piperidineacetate hydrochloride, and its structural formula is: Methylphenidate hydrochloride USP is 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. Ritalin tablets contains the following inactive ingredients: D&C Yellow No. 10 (5-mg and 20-mg tablets), FD&C Green No. (10-mg tablets), lactose, magnesium stearate, polyethylene glycol, starch (5-mg and 10-mg tablets), sucrose, talc, and tragacanth (20-mg tablets).. Methylphenidate hydrochloride USP is 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. Methylphenidate hydrochloride structural formula.

DOSAGE & ADMINISTRATION SECTION.

2 DOSAGE AND ADMINISTRATION. oPediatric Patients Years and Older: Start with mg twice daily (before breakfast and lunch), titrating the dose weekly in 5- to 10-mg increments. Dosages above 60 mg/day are not recommended (2.2).oAdults: Average daily dosage is 20 mg to 30 mg, administered or times daily, preferably 30 to 45 minutes before meals. Maximum total daily dosage is 60 mg (2.2).. oPediatric Patients Years and Older: Start with mg twice daily (before breakfast and lunch), titrating the dose weekly in 5- to 10-mg increments.. Dosages above 60 mg/day are not recommended (2.2).. oAdults: Average daily dosage is 20 mg to 30 mg, administered or times daily, preferably 30 to 45 minutes before meals. Maximum total daily dosage is 60 mg (2.2).. 2.1 Pretreatment Screening. Prior to treating patients with Ritalin, assess:ofor the presence of cardiac disease (i.e., perform careful history, family history of sudden death or ventricular arrhythmia, and physical exam) [see Warnings and Precautions (5.2)].othe family history and clinically evaluate patients for motor or verbal tics or Tourettes syndrome before initiating Ritalin [see Warnings and Precautions (5.10)]. ofor the presence of cardiac disease (i.e., perform careful history, family history of sudden death or ventricular arrhythmia, and physical exam) [see Warnings and Precautions (5.2)].. othe family history and clinically evaluate patients for motor or verbal tics or Tourettes syndrome before initiating Ritalin [see Warnings and Precautions (5.10)]. 2.2 General Dosing Information. Pediatric Patients years and Older: Start with mg orally twice daily (before breakfast and lunch). Increase dosage gradually, in increments of 5-to 10-mg weekly. Daily dosage above 60 mg is not recommended.Adults: Average dosage is 20 to 30 mg daily. Administer orally in divided doses or times daily, preferably 30 to 45 minutes before meals. Maximum total daily dosage is 60 mg. Patients who are unable to sleep if medication is taken late in the day should take the last dose before p.m.. 2.3 Dosage Reduction and Discontinuation. If paradoxical worsening of symptoms or other adverse reactions occur, reduce the dosage, or, if necessary, discontinue Ritalin. If improvement is not observed after appropriate dosage adjustment over one-month period, the drug should be discontinued.

DOSAGE FORMS & STRENGTHS SECTION.

3 DOSAGE FORMS AND STRENGTHS. o5 mg, round, yellow, flat with CIBA monogram on one side and NDC on the reverse sideo10 mg, round, pale green, biconvex with CIBA monogram on one side and NDC and partial bisection on the reverse sideo20 mg, round, pale yellow, biconvex with CIBA monogram on one side and NDC 34 and partial bisection on the reverse side. o5 mg, round, yellow, flat with CIBA monogram on one side and NDC on the reverse side. o10 mg, round, pale green, biconvex with CIBA monogram on one side and NDC and partial bisection on the reverse side. o20 mg, round, pale yellow, biconvex with CIBA monogram on one side and NDC 34 and partial bisection on the reverse side. oTablets: mg, 10 mg, and 20 mg (3). oTablets: mg, 10 mg, and 20 mg (3).

DRUG ABUSE AND DEPENDENCE SECTION.

9 DRUG ABUSE AND DEPENDENCE. 9.1 Controlled Substance. Ritalin contains methylphenidate hydrochloride, Schedule II controlled substance.. 9.2 Abuse. Ritalin has high potential for abuse and misuse which can lead to the development of substance use disorder, including addiction [see Warnings and Precautions (5.1)]. Ritalin can be diverted for non-medical use into illicit channels or distribution.Abuse is the intentional non-therapeutic use of drug, even once, to achieve desired psychological or physiological effect. Misuse is the intentional use, for therapeutic purposes, of drug by an individual in way other than prescribed by health care provider or for whom it was not prescribed. Drug addiction is cluster of behavioral, cognitive, and physiological phenomena that may include strong desire to take the drug, difficulties in controlling drug use (e.g., continuing drug use despite harmful consequences, giving higher priority to drug use than other activities and obligations), and possible tolerance or physical dependence.Misuse and abuse of methylphenidate hydrochloride may cause increased heart rate, respiratory rate, or blood pressure; sweating; dilated pupils; hyperactivity; restlessness; insomnia; decreased appetite; loss of coordination; tremors; flushed skin; vomiting; and/or abdominal pain. Anxiety, psychosis, hostility, aggression, and suicidal or homicidal ideation have also been observed with CNS stimulants abuse and/or misuse. Misuse and abuse of CNS stimulants, including Ritalin, 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.. 9.3 Dependence. Physical DependenceRitalin may produce physical dependence. Physical dependence is state that develops as result of physiological adaptation in response to repeated drug use, manifested by withdrawal signs and symptoms after abrupt discontinuation or significant dose reduction of drug.Withdrawal signs and symptoms after abrupt discontinuation or dose reduction following prolonged use of CNS stimulants including Ritalin include dysphoric mood; depression; fatigue; vivid, unpleasant dreams; insomnia or hypersomnia; increased appetite; and psychomotor retardation or agitation.ToleranceRitalin may produce tolerance. Tolerance is physiological state characterized by reduced response to drug after repeated administration (i.e., higher dose of drug is required to produce the same effect that was once obtained at lower dose).

DRUG INTERACTIONS SECTION.

7 DRUG INTERACTIONS. oAntihypertensive Drugs: Monitor blood pressure. Adjust dosage of antihypertensive drug as needed (7.1).. oAntihypertensive Drugs: Monitor blood pressure. Adjust dosage of antihypertensive drug as needed (7.1).. 7.1 Clinically Important Drug Interactions with Ritalin. Table presents clinically important drug interactions with Ritalin.Table 1: Clinically Important Drug Interactions with RitalinMonoamine Oxidase Inhibitors (MAOI)Clinical ImpactConcomitant use of MAOIs and CNS stimulants, including Ritalin can cause hypertensive crisis. Potential outcomes include death, stroke, myocardial infarction, aortic dissection, ophthalmological complications, eclampsia, pulmonary edema, and renal failure [see Contraindications (4)].InterventionConcomitant use of Ritalin with MAOIs or within 14 days after discontinuing MAOI treatment is contraindicated.Antihypertensive DrugsClinical ImpactRitalin may decrease the effectiveness of drugs used to treat hypertension [see Warnings and Precautions (5.3)].InterventionMonitor blood pressure and adjust the dosage of the antihypertensive drug as needed.Halogenated AnestheticsClinical ImpactConcomitant use of halogenated anesthetics and Ritalin may increase the risk of sudden blood pressure and heart rate increase during surgery.InterventionAvoid use of Ritalin in patients being treated with anesthetics on the day of surgery.RisperidoneClinical ImpactCombined use of methylphenidate with risperidone when there is change, whether an increase or decrease, in dosage of either or both medications, may increase the risk of extrapyramidal symptoms (EPS)InterventionMonitor for signs of EPS.

GERIATRIC USE SECTION.

8.5 Geriatric Use. Ritalin has not been studied in the geriatric population.

HOW SUPPLIED SECTION.

16 HOW SUPPLIED/STORAGE AND HANDLING. o5 mg tablets (NDC 0078-0439-05) round, yellow, (imprinted CIBA 7) supplied in bottles of 100o10 mg tablets (NDC 0078-0440-05) round, pale green, scored, (imprinted CIBA 3) supplied in bottles of 100o20 mg tablets (NDC 0078-0441-05) round, pale yellow, scored, (imprinted CIBA 34) supplied in bottles of 100Store at 20C to 25C (68F to 77F); excursions permitted between 15C and 30C (59F and 86F) [see USP controlled room temperature].Protect from light.Dispense in tight, light-resistant container (USP).. o5 mg tablets (NDC 0078-0439-05) round, yellow, (imprinted CIBA 7) supplied in bottles of 100. o10 mg tablets (NDC 0078-0440-05) round, pale green, scored, (imprinted CIBA 3) supplied in bottles of 100. o20 mg tablets (NDC 0078-0441-05) round, pale yellow, scored, (imprinted CIBA 34) supplied in bottles of 100.

INDICATIONS & USAGE SECTION.

1 INDICATIONS AND USAGE. Ritalin is indicated for the treatment of:oAttention Deficit Hyperactivity Disorders (ADHD) in pediatric patients years and older and adultsoNarcolepsy. oAttention Deficit Hyperactivity Disorders (ADHD) in pediatric patients years and older and adults. oNarcolepsy. Ritalin is central nervous system (CNS) stimulant indicated for the treatment of Attention Deficit Hyperactivity Disorders (ADHD) and Narcolepsy (1).

INFORMATION FOR PATIENTS SECTION.

17 PATIENT COUNSELING INFORMATION. Advise the patient to read the FDA-approved patient labeling (Medication Guide).Abuse, Misuse, and AddictionEducate patients and their families about the risks of abuse, misuse, and addiction of Ritalin, 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 Ritalin in safe place, preferably locked, and instruct patients to not give Ritalin to anyone else.Risks to Patients with Serious Cardiac DiseaseAdvise patients that there are potential risks to patient with serious cardiac disease, including sudden death, with Ritalin use. Instruct patients to contact 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 RateInstruct patients that Ritalin can cause elevations of their blood pressure and pulse rate [see Warnings and Precautions (5.3)].Psychiatric Adverse ReactionsAdvise patients that Ritalin, 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)].PriapismAdvise 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 Raynauds Phenomenon]Instruct patients about the risk of peripheral vasculopathy, including Raynauds 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 Ritalin. 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 PatientsAdvise patients that Ritalin may cause slowing of growth and weight loss [see Warnings and Precautions (5.7)].Increased Intraocular Pressure (IOP) and GlaucomaAdvise patients that IOP and glaucoma may occur during treatment with Ritalin [see Warnings and Precautions (5.9)].Motor and Verbal Tics, and Worsening of Tourettes SyndromeAdvise patients that motor and verbal tics and worsening of Tourettes Syndrome may occur during treatment with Ritalin. Instruct patients to notify their healthcare provider if emergence of new tics or worsening of tics or Tourettes syndrome occurs [see Warnings and Precautions (5.10)]. Pregnancy RegistryAdvise patients that there is pregnancy exposure registry that monitors pregnancy outcomes in patients exposed to ADHD medications, including RITALIN, during pregnancy [see Use in Specific Populations (8.1)].Distributed by:Novartis Pharmaceuticals CorporationEast Hanover, New Jersey 07936.

LACTATION SECTION.

8.2 Lactation Risk SummaryLimited 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 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 mothers clinical need for Ritalin and any potential adverse effects on the breastfed infant from Ritalin or from the underlying maternal condition.Clinical ConsiderationsMonitor breastfeeding infants for adverse reactions, such as agitation, insomnia, anorexia, and reduced weight gain.

MECHANISM OF ACTION SECTION.

12.1 Mechanism of Action. Methylphenidate hydrochloride is CNS stimulant. The mode of therapeutic action in ADHD and narcolepsy is not known.

NONCLINICAL TOXICOLOGY SECTION.

13 NONCLINICAL TOXICOLOGY. 13.1 Carcinogenesis, Mutagenesis, and Impairment of Fertility. CarcinogenesisIn lifetime carcinogenicity study carried out in B6C3F1 mice, methylphenidate caused an increase in hepatocellular adenomas, and in males only, an increase in hepatoblastomas at daily dose of approximately 60 mg/kg/day. This dose is approximately times the MRHD of 60 mg/day given to children on mg/m2 basis. Hepatoblastoma is relatively rare rodent malignant tumor type. There was no increase in total malignant hepatic tumors. The mouse strain used is sensitive to the development of hepatic tumors and the significance of these results to humans is unknown.Methylphenidate did not cause any increase in tumors in lifetime carcinogenicity study carried out in F344 rats; the highest dose used was approximately 45 mg/kg/day, which is approximately times the MRHD (children) on mg/m2 basis.In 24-week carcinogenicity study in the transgenic mouse strain p53+/-, which is sensitive to genotoxic carcinogens, there was no evidence of carcinogenicity. Male and female mice were fed diets containing the same concentration of methylphenidate as in the lifetime carcinogenicity study; the high-dose groups were exposed to 60 to 74 mg/kg/day of methylphenidate.MutagenesisMethylphenidate was not mutagenic in the in vitro Ames reverse mutation assay, in the in vitro mouse lymphoma cell forward mutation assay, or in the in vitro chromosomal aberration assay using human lymphocytes. Sister chromatid exchanges and chromosome aberrations were increased, indicative of weak clastogenic response, in an in vitro assay in cultured Chinese Hamster Ovary cells. Methylphenidate was negative in vivo in males and females in the mouse bone marrow micronucleus assay.Impairment of FertilityNo human data on the effect of methylphenidate on fertility are available. Methylphenidate did not impair fertility in male or female mice that were fed diets containing the drug in an 18-week continuous breeding study. The study was conducted at doses up to 160 mg/kg/day, approximately 10times the MRHD of 60 mg/day given to adolescents on mg/m2 basis.

OVERDOSAGE SECTION.

10 OVERDOSAGE. Clinical Effects of OverdoseOverdose of CNS stimulants is characterized by the following sympathomimetic effects:oCardiovascular effects including tachyarrhythmias, and hypertension or hypotension. Vasospasm, myocardial infarction, or aortic dissection may precipitate sudden cardiac death. Takotsubo cardiomyopathy may develop.oCNS effects including psychomotor agitation, confusion, and hallucinations. Serotonin syndrome, seizures, cerebral vascular accidents, and coma may occur.oLife-threatening hyperthermia (temperatures greater than 104F) and rhabdomyolysis may develop.Overdose ManagementConsider the possibility of multiple drug ingestion. Because methylphenidate has large volume of distribution and is rapidly metabolized, dialysis is not useful. Consider contacting the Poison Help line (1-800-222-1222) or medical toxicologist for additional overdose management recommendations.. oCardiovascular effects including tachyarrhythmias, and hypertension or hypotension. Vasospasm, myocardial infarction, or aortic dissection may precipitate sudden cardiac death. Takotsubo cardiomyopathy may develop.. oCNS effects including psychomotor agitation, confusion, and hallucinations. Serotonin syndrome, seizures, cerebral vascular accidents, and coma may occur.. oLife-threatening hyperthermia (temperatures greater than 104F) and rhabdomyolysis may develop.

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL.

PRINCIPAL DISPLAY PANEL. NDC 0078-0439-05Ritalin(R) HCLmethylphenidate HCL USP5 mg100 tabletsRx onlyDispense with Medication Guideattached or provided separately.NOVARTIS. PRINCIPAL DISPLAY PANEL NDC 0078-0439-05 Ritalin(R) HCL methylphenidate HCL USP mg 100 tablets Rx only Dispense with Medication Guide attached or provided separately. NOVARTIS.

PEDIATRIC USE SECTION.

8.4 Pediatric Use. The safety and effectiveness of Ritalin for the treatment of ADHD have been established in pediatric patients aged to 17 years.The safety and effectiveness of Ritalin in pediatric patients less than aged years have not been established.The long-term efficacy of methylphenidate in pediatric patients has not been established.Long-Term Suppression of GrowthGrowth should be monitored during treatment with stimulants, including Ritalin. 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 DataRats treated with methylphenidate early in the postnatal period through sexual maturation demonstrated decrease in spontaneous locomotor activity in adulthood. deficit in acquisition of specific learning task was observed in females only. The doses at which these findings were observed are at least times the MRHD of 60 mg/day given to children on mg/m2 basis.In study conducted in young rats, methylphenidate was administered orally at doses of up to 100 mg/kg/day for 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 times the MRHD of 60 mg/day given to children on mg/m2 basis) or greater, and deficit in the acquisition of specific learning task was seen in females exposed to the highest dose (8 times the MRHD given to children on mg/m2 basis). The no effect level for juvenile neurobehavioral development in rats was mg/kg/day approximately 0.5 times the MRHD given to children on mg/m2 basis). The clinical significance of the long-term behavioral effects observed in rats is unknown.

PHARMACODYNAMICS SECTION.

12.2 Pharmacodynamics. Methylphenidate is racemic mixture comprised of the d- and l-threo enantiomers. The d-threo enantiomer is more pharmacologically active than the l-threo enantiomer. Methylphenidate blocks the reuptake of norepinephrine and dopamine into the presynaptic neuron and increases the release of these monoamines into the extraneuronal space.Cardiac ElectrophysiologyA formal QT study has not been conducted in patients taking Ritalin.The effect of dexmethylphenidate, the pharmacologically active d-enantiomer of Ritalin, on the QT interval was evaluated in double-blind, placebo- and open-label active (moxifloxacin)-controlled study following single doses of dexmethlyphenidate XR 40 mg (maximum recommended adult total daily dosage) in 75 healthy volunteers. Electrocardiograms were collected up to 12 hours postdose. Fredericas method for heart rate correction was employed to derive the corrected QT interval (QTcF). The maximum mean prolongation of QTcF intervals was less than ms, and the upper limit of the 90% confidence interval was below 10 ms for all time-matched comparisons versus placebo. This was below the threshold of clinical concern and there was no evident exposure response relationship.

PHARMACOKINETICS SECTION.

12.3 Pharmacokinetics. AbsorptionThe absolute bioavailability of methylphenidate is 22 +- % for the d-enantiomer and +- % for the l-enantiomer. Peakplasma concentrations of approximately 4.3 +- 2.3 ng/mL were reached on an average of hours after administration of 10mg tablet. The time to peak rate in children was 1.9 hours (0.3 to 4.4 hours) for Ritalin.Effect of FoodIngestion with food has no relevant effect on absorption of Ritalin.DistributionBinding to plasma proteins is low (10% to 33%). The volume of distribution was 2.65 +- 1.11 L/kg for d-methylphenidate and 1.80 +- 0.91 L/kg for l-methylphenidate.EliminationThe systemic clearance is 0.40 +- 0.12 L/h/kg for d-methylphenidate and 0.73 +- 0.28 L/h/kg for l-methylphenidate.MetabolismMethylphenidate is metabolized primarily by de-esterification to alpha-phenyl-piperidine acetic acid (ritalinic acid), which has little or no pharmacologic activity.ExcretionAfter oral administration, 78% to 97% of the dose is excreted in the urine and 1% to 3% in feces in the form of metabolites within 48 to 96 hours. Most of the dose is excreted in the urine as alpha-phenyl-2-piperidine acetic acid (60% to 86%). Studies in Specific PopulationsMale and Female PatientsNo gender differences in the pharmacokinetics of methylphenidate between healthy male and female adults are expected.Racial or Ethnic GroupsThere is insufficient experience with the use of Ritalin to detect ethnic variations in pharmacokinetics.Patients with Renal ImpairmentRitalin has not been studied in renally-impaired patients. Renal impairment is expected to have minimal effect on the pharmacokinetics of methylphenidate since less than 1% of radiolabeled dose is excreted in the urine as unchanged compound, and the major metabolite (ritalinic acid), has little or no pharmacologic activity.Patients with Hepatic ImpairmentRitalin has not been studied in patients with hepatic impairment. Hepatic impairment is expected to have minimal effect on the pharmacokinetics of methylphenidate since it is metabolized primarily to ritalinic acid by nonmicrosomal hydrolytic esterases that are widely distributed throughout the body.

PREGNANCY SECTION.

8.1 Pregnancy. Pregnancy Exposure RegistryThere is pregnancy exposure registry that monitors pregnancy outcomes in women exposed to ADHD medications, including Ritalin, 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 SummaryPublished studies and postmarketing reports on methylphenidate use during pregnancy have not identified 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 mg/m2 basis. However, spina bifida was observed in rabbits at dose 52 times the MRHD given to adolescents. decrease in pup body weight was observed in pre- and post-natal development study with oral administration of methylphenidate to rats throughout pregnancy and lactation at doses 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 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 ConsiderationsFetal/Neonatal Adverse ReactionsCNS stimulants, such as Ritalin, 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.DataAnimal DataIn 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 mg/m2 basis. The no effect level for embryo-fetal development in rabbits was 60 mg/kg/day (15times the MRHD given to adolescents on mg/m2 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 mg/m2 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 mg/m2 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 mg/m2 basis), but no other effects on postnatal development were observed. The no effect level for pre- and postnatal development in rats was 15 mg/kg/day (approximately times the MRHD given to adolescents on mg/m2 basis).

SPL MEDGUIDE SECTION.

MEDICATION GUIDERITALIN(R) (rit-ah-lin)(methylphenidate hydrochloride)tablets, for oral use, CIIWhat is the most important information should know about RITALINRITALIN may cause serious side effects, including:oAbuse, misuse, and addiction. RITALIN has high chance for abuse and misuse and may lead to substance use problems, including addiction. Misuse and abuse of RITALIN, other methylphenidate containing medicines, and amphetamine containing medicines, can lead to overdose and death. The risk of overdose and death is increased with higher doses of RITALIN or when it is used in ways that are not approved, such as snorting or injection.oYour healthcare provider should check you or your childs risk for abuse, misuse, and addiction before starting treatment with RITALIN and will monitor you or your child during treatment.oRITALIN may lead to physical dependence after prolonged use, even if taken as directed by your healthcare provider.oDo not give RITALIN to anyone else. See What is RITALIN for more information.oKeep RITALIN in safe place and properly dispose of any unused medicine. See How should store RITALIN for more information.oTell your healthcare provider if you or your child have ever abused or been dependent on alcohol, prescription medicines, or street drugs.oRisks for people with serious heart disease. Sudden death has happened in people who have heart defects or other serious heart disease. Your healthcare provider should check you or your child carefully for heart problems before starting RITALIN. Tell your healthcare provider if you or your child have any heart problems, heart disease, or heart defects. Call your healthcare provider or go to the nearest hospital emergency room right away if you or your child has any signs of heart problems, such as chest pain, shortness of breath, or fainting while taking RITALIN.oIncreased blood pressure and heart rate. Your healthcare provider should check you or your childs blood pressure and heart rate regularly during treatment with RITALIN.oMental (psychiatric) problems: All Patientsonew or worse behavior and thought problemso new or worse bipolar illnessonew psychotic symptoms (such as hearing voices, believing things that are not true, are suspicious) or new manic symptoms Tell your healthcare provider about any mental problems you or your child have, or about family history of suicide, bipolar illness, or depression. Call your healthcare provider right away if you or your child have any new or worsening mental symptoms or problems while taking RITALIN, especially seeing or hearing things that are not real, believing things that are not real, or are suspicious.What is RITALINoRITALIN is central nervous system (CNS) stimulant prescription medicine. It is used for the treatment of Attention Deficit Hyperactivity Disorder (ADHD). RITALIN may help increase attention and decrease impulsiveness and hyperactivity in patients with ADHD.oRITALIN should be used as part of total treatment program for ADHD that may include counseling or other therapies.oRITALIN is also used in the treatment of sleep disorder called narcolepsy.It is not known if RITALIN is safe and effective in children under years of age.RITALIN is federally controlled substance (CII) because it contains methylphenidate that can be target for people who abuse prescription medicines or street drugs. Keep RITALIN in safe place to protect it from theft. Never give your RITALIN to anyone else, because it may cause death or harm them. Selling or giving away RITALIN may harm others and is against the law.Who should not take RITALINRITALIN should not be taken if you or your child:oare allergic to methylphenidate hydrochloride, or any of the ingredients in RITALIN. See the end of this Medication Guide for complete list of ingredients in RITALIN.oare taking or have taken within the past 14 days an anti-depression medicine called monoamine oxidase inhibitor (MAOI).RITALIN may not be right for you or your child. Before starting RITALIN, tell your or your childs healthcare provider about all health conditions (or family history of), including:oheart problems, heart disease, heart defects, or high blood pressureomental problems, including psychosis, mania, bipolar illness, or depressionocirculation problems in fingers or toesohave eye problems, including increased pressure in your eye, glaucoma, or problems with your close-up vision (farsightedness)ohave or had repeated movements or sounds (tics) or Tourettes syndrome, or have family history of tics or Tourettes syndrome.oif you are pregnant or plan to become pregnant. It is not known if RITALIN will harm your unborn baby.oThere is pregnancy registry for females who are exposed to ADHD medications, including RITALIN, during pregnancy. The purpose of the registry is to collect information about the health of females exposed to RITALIN and their baby. If you or your child becomes pregnant during treatment with RITALIN, talk to your healthcare provider about registering with the National Pregnancy Registry of ADHD Medications at 1-866-961-2388 or visit online at https://womensmentalhealth.org/adhd-medications/.oif you are breastfeeding or plan to breastfeed. RITALIN passes into your breast milk. Talk to your healthcare provider about the best way to feed your baby during treatment with RITALIN.Tell your healthcare provider about all of the medicines that you or your child takes, including prescription and over-the-counter medicines, vitamins, and herbal supplements. RITALIN and some medicines may interact with each other and cause serious side effects. Sometimes the doses of other medicines will need to be adjusted while takingRITALIN.Your healthcare provider will decide whether RITALIN can be taken with other medicines.Especially tell your healthcare provider if you or your child takes:oanti-depression medicines, including MAOIsoblood pressure medicines (anti-hypertensive)Know the medicines that you or your child takes. Keep list of your medicines with you to show your healthcare provider and pharmacist.oYou should not take RITALIN on the day of your operation if certain type of anesthetic is used. This is because there is chance of sudden rise in blood pressure and heart rate during the operation.Do not start any new medicine while taking RITALIN without talking to your healthcare provider first.How should RITALIN be takenoTake RITALIN exactly as prescribed. Your healthcare provider may adjust the dose until it is right for you or your child.oRITALIN is usually taken to times day.oTake RITALIN 30 to 45 minutes before meal.oYour healthcare provider may do regular checks of the blood, heart, and blood pressure while taking RITALIN.Children should have their height and weight checked often while taking RITALIN. If you or your child take too much RITALIN, call your healthcare provider or Poison Help line at 1-800-222-1222 or go to the nearest hospital emergency room right away.What are the possible side effects of RITALINRITALIN may cause serious side effects, including:osee What is the most important information should know about RITALIN for information on reported heart and mental problems.opainful and prolonged erections (priapism) have occurred with methylphenidate. If you or your child develops priapism, seek medical help right away. Because of the potential for lasting damage, priapism should be evaluated by healthcare provider immediately.ocirculation problems in fingers and toes (peripheral vasculopathy, including Raynauds phenomenon):ofingers or toes may feel numb, cool, painfulofingers or toes may change color from pale, to blue, to redTell your healthcare provider if you or your child have, numbness, pain, skin color change, or sensitivity to temperature in the fingers or toes.Call your healthcare provider right away if you have or your child has any signs of unexplained wounds appearing on fingers or toes while taking RITALIN.oSlowing of growth (height and weight) in children. Children should have their height and weight checked often during treatment with RITALIN. RITALIN treatment may be stopped if your child is not growing or gaining weight.oEye problems (increased pressure in the eye and glaucoma). Call your healthcare provider right away if you or your child develop changes in your vision or eye pain, swelling, or redness.oNew or worsening tics or worsening Tourettes syndrome. Tell your healthcare provider if you or your child get any new or worsening tics or worsening Tourettes syndrome during treatment with RITALIN.Common side effects include:ofast heart beatoabnormal heartbeat (palpitations)oheadacheotrouble sleepingonervousnessosweating lotodecreased appetiteodry mouthonauseaostomach painCall your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. How should store RITALINoStore RITALIN in safe place and in tightly closed container at room temperature between 68F to 77F (20C to 25C).oProtect from light.oDispose of remaining, unused, or expired RITALIN by medicine take-back program at U.S. Drug Enforcement Administration (DEA) authorized collection site. If no take-back program or DEA authorized collector is available, mix RITALIN with an undesirable, nontoxic substance such as dirt, cat litter, or used coffee grounds to make it less appealing to children and pets. Place the mixture in container, such as sealed plastic bag and throw away RITALIN in the household trash. Visit www.fda.gov/drugdisposal for additional information on disposal of unused medicines.oKeep RITALIN and all medicines out of the reach of children.General information about the safe and effective use of RITALIN.Medicines are sometimes prescribed for purposes other than those listed in Medication Guide. You can ask your pharmacist or healthcare provider for information about RITALIN that is written for healthcare professionals. Do not use RITALIN for condition for which it was not prescribed. Do not give RITALIN to other people, even if they have the same symptoms that you have. It may harm them and it is against the law. What are the ingredients in RITALINActive ingredient: methylphenidate HCl Inactive ingredients: D&C Yellow No.10 (5-mg and 20-mg tablets), FD&C Green No.3 (10-mg tablets), lactose, magnesium stearate, polyethylene glycol, starch (5-mg and 10-mg tablets), sucrose, talc, and tragacanth (20-mg tablets) Distributed by:Novartis Pharmaceuticals CorporationEast Hanover, New Jersey 07936(C) NovartisFor more information and request for additional copies of the Medication Guide, call 1-888-669-6682. This Medication Guide has been approved by the U.S. Food and Drug Administration.Revised: 10/2023. oAbuse, misuse, and addiction. RITALIN has high chance for abuse and misuse and may lead to substance use problems, including addiction. Misuse and abuse of RITALIN, other methylphenidate containing medicines, and amphetamine containing medicines, can lead to overdose and death. The risk of overdose and death is increased with higher doses of RITALIN or when it is used in ways that are not approved, such as snorting or injection.. oYour healthcare provider should check you or your childs risk for abuse, misuse, and addiction before starting treatment with RITALIN and will monitor you or your child during treatment.. oRITALIN may lead to physical dependence after prolonged use, even if taken as directed by your healthcare provider.. oDo not give RITALIN to anyone else. See What is RITALIN for more information.. oKeep RITALIN in safe place and properly dispose of any unused medicine. See How should store RITALIN for more information.. oTell your healthcare provider if you or your child have ever abused or been dependent on alcohol, prescription medicines, or street drugs.. oRisks for people with serious heart disease. Sudden death has happened in people who have heart defects or other serious heart disease. Your healthcare provider should check you or your child carefully for heart problems before starting RITALIN.. Your healthcare provider should check you or your child carefully for heart problems before starting RITALIN.. Tell your healthcare provider if you or your child have any heart problems, heart disease, or heart defects.. Call your healthcare provider or go to the nearest hospital emergency room right away if you or your child has any signs of heart problems, such as chest pain, shortness of breath, or fainting while taking RITALIN.. oIncreased blood pressure and heart rate.. Your healthcare provider should check you or your childs blood pressure and heart rate regularly during treatment with RITALIN.. oMental (psychiatric) problems:. All Patients. onew or worse behavior and thought problems. new or worse bipolar illness. onew psychotic symptoms (such as hearing voices, believing things that are not true, are suspicious) or new manic symptoms. Tell your healthcare provider about any mental problems you or your child have, or about family history of suicide, bipolar illness, or depression.. Call your healthcare provider right away if you or your child have any new or worsening mental symptoms or problems while taking RITALIN, especially seeing or hearing things that are not real, believing things that are not real, or are suspicious.. oRITALIN is central nervous system (CNS) stimulant prescription medicine. It is used for the treatment of Attention Deficit Hyperactivity Disorder (ADHD). RITALIN may help increase attention and decrease impulsiveness and hyperactivity in patients with ADHD.. oRITALIN should be used as part of total treatment program for ADHD that may include counseling or other therapies.. oRITALIN is also used in the treatment of sleep disorder called narcolepsy.. oare allergic to methylphenidate hydrochloride, or any of the ingredients in RITALIN. See the end of this Medication Guide for complete list of ingredients in RITALIN.. oare taking or have taken within the past 14 days an anti-depression medicine called monoamine oxidase inhibitor (MAOI).. oheart problems, heart disease, heart defects, or high blood pressure. omental problems, including psychosis, mania, bipolar illness, or depression. ocirculation problems in fingers or toes. ohave eye problems, including increased pressure in your eye, glaucoma, or problems with your close-up vision (farsightedness). ohave or had repeated movements or sounds (tics) or Tourettes syndrome, or have family history of tics or Tourettes syndrome.. oif you are pregnant or plan to become pregnant. It is not known if RITALIN will harm your unborn baby.. oThere is pregnancy registry for females who are exposed to ADHD medications, including RITALIN, during pregnancy. The purpose of the registry is to collect information about the health of females exposed to RITALIN and their baby. If you or your child becomes pregnant during treatment with RITALIN, talk to your healthcare provider about registering with the National Pregnancy Registry of ADHD Medications at 1-866-961-2388 or visit online at https://womensmentalhealth.org/adhd-medications/.. oif you are breastfeeding or plan to breastfeed. RITALIN passes into your breast milk. Talk to your healthcare provider about the best way to feed your baby during treatment with RITALIN.. oanti-depression medicines, including MAOIs. oblood pressure medicines (anti-hypertensive). oYou should not take RITALIN on the day of your operation if certain type of anesthetic is used. This is because there is chance of sudden rise in blood pressure and heart rate during the operation.. oTake RITALIN exactly as prescribed. Your healthcare provider may adjust the dose until it is right for you or your child.. oRITALIN is usually taken to times day.. oTake RITALIN 30 to 45 minutes before meal.. oYour healthcare provider may do regular checks of the blood, heart, and blood pressure while taking RITALIN.. osee What is the most important information should know about RITALIN for information on reported heart and mental problems.. opainful and prolonged erections (priapism) have occurred with methylphenidate. If you or your child develops priapism, seek medical help right away. Because of the potential for lasting damage, priapism should be evaluated by healthcare provider immediately.. ocirculation problems in fingers and toes (peripheral vasculopathy, including Raynauds phenomenon):. ofingers or toes may feel numb, cool, painful. ofingers or toes may change color from pale, to blue, to red. oSlowing of growth (height and weight) in children. Children should have their height and weight checked often during treatment with RITALIN. RITALIN treatment may be stopped if your child is not growing or gaining weight.. oEye problems (increased pressure in the eye and glaucoma). Call your healthcare provider right away if you or your child develop changes in your vision or eye pain, swelling, or redness.. oNew or worsening tics or worsening Tourettes syndrome. Tell your healthcare provider if you or your child get any new or worsening tics or worsening Tourettes syndrome during treatment with RITALIN.. ofast heart beat. oabnormal heartbeat (palpitations). oheadache. otrouble sleeping. onervousness. osweating lot. odecreased appetite. odry mouth. onausea. ostomach pain. oStore RITALIN in safe place and in tightly closed container at room temperature between 68F to 77F (20C to 25C).. oProtect from light.. oDispose of remaining, unused, or expired RITALIN by medicine take-back program at U.S. Drug Enforcement Administration (DEA) authorized collection site. If no take-back program or DEA authorized collector is available, mix RITALIN with an undesirable, nontoxic substance such as dirt, cat litter, or used coffee grounds to make it less appealing to children and pets. Place the mixture in container, such as sealed plastic bag and throw away RITALIN in the household trash. Visit www.fda.gov/drugdisposal for additional information on disposal of unused medicines.. oKeep RITALIN and all medicines out of the reach of children.. What are the ingredients in RITALINActive ingredient: methylphenidate HCl Inactive ingredients: D&C Yellow No.10 (5-mg and 20-mg tablets), FD&C Green No.3 (10-mg tablets), lactose, magnesium stearate, polyethylene glycol, starch (5-mg and 10-mg tablets), sucrose, talc, and tragacanth (20-mg tablets) Distributed by:Novartis Pharmaceuticals CorporationEast Hanover, New Jersey 07936(C) NovartisFor more information and request for additional copies of the Medication Guide, call 1-888-669-6682. This Medication Guide has been approved by the U.S. Food and Drug Administration.Revised: 10/2023.

SPL UNCLASSIFIED SECTION.

2.1 Pretreatment Screening. Prior to treating patients with Ritalin, assess:ofor the presence of cardiac disease (i.e., perform careful history, family history of sudden death or ventricular arrhythmia, and physical exam) [see Warnings and Precautions (5.2)].othe family history and clinically evaluate patients for motor or verbal tics or Tourettes syndrome before initiating Ritalin [see Warnings and Precautions (5.10)]. ofor the presence of cardiac disease (i.e., perform careful history, family history of sudden death or ventricular arrhythmia, and physical exam) [see Warnings and Precautions (5.2)].. othe family history and clinically evaluate patients for motor or verbal tics or Tourettes syndrome before initiating Ritalin [see Warnings and Precautions (5.10)].

USE IN SPECIFIC POPULATIONS SECTION.

8 USE IN SPECIFIC POPULATIONS. 8.1 Pregnancy. Pregnancy Exposure RegistryThere is pregnancy exposure registry that monitors pregnancy outcomes in women exposed to ADHD medications, including Ritalin, 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 SummaryPublished studies and postmarketing reports on methylphenidate use during pregnancy have not identified 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 mg/m2 basis. However, spina bifida was observed in rabbits at dose 52 times the MRHD given to adolescents. decrease in pup body weight was observed in pre- and post-natal development study with oral administration of methylphenidate to rats throughout pregnancy and lactation at doses 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 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 ConsiderationsFetal/Neonatal Adverse ReactionsCNS stimulants, such as Ritalin, 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.DataAnimal DataIn 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 mg/m2 basis. The no effect level for embryo-fetal development in rabbits was 60 mg/kg/day (15times the MRHD given to adolescents on mg/m2 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 mg/m2 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 mg/m2 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 mg/m2 basis), but no other effects on postnatal development were observed. The no effect level for pre- and postnatal development in rats was 15 mg/kg/day (approximately times the MRHD given to adolescents on mg/m2 basis).. 8.2 Lactation Risk SummaryLimited 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 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 mothers clinical need for Ritalin and any potential adverse effects on the breastfed infant from Ritalin or from the underlying maternal condition.Clinical ConsiderationsMonitor breastfeeding infants for adverse reactions, such as agitation, insomnia, anorexia, and reduced weight gain.. 8.4 Pediatric Use. The safety and effectiveness of Ritalin for the treatment of ADHD have been established in pediatric patients aged to 17 years.The safety and effectiveness of Ritalin in pediatric patients less than aged years have not been established.The long-term efficacy of methylphenidate in pediatric patients has not been established.Long-Term Suppression of GrowthGrowth should be monitored during treatment with stimulants, including Ritalin. 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 DataRats treated with methylphenidate early in the postnatal period through sexual maturation demonstrated decrease in spontaneous locomotor activity in adulthood. deficit in acquisition of specific learning task was observed in females only. The doses at which these findings were observed are at least times the MRHD of 60 mg/day given to children on mg/m2 basis.In study conducted in young rats, methylphenidate was administered orally at doses of up to 100 mg/kg/day for 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 times the MRHD of 60 mg/day given to children on mg/m2 basis) or greater, and deficit in the acquisition of specific learning task was seen in females exposed to the highest dose (8 times the MRHD given to children on mg/m2 basis). The no effect level for juvenile neurobehavioral development in rats was mg/kg/day approximately 0.5 times the MRHD given to children on mg/m2 basis). The clinical significance of the long-term behavioral effects observed in rats is unknown.. 8.5 Geriatric Use. Ritalin has not been studied in the geriatric population.

WARNINGS AND PRECAUTIONS SECTION.

5 WARNINGS AND PRECAUTIONS. oRisks to Patients with Serious Cardiac Disease: Avoid use in patients with known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmias, coronary artery disease, or other serious cardiac disease (5.2).oIncreased Blood Pressure and Heart Rate: Monitor blood pressure and pulse (5.3).oPsychiatric Adverse Reactions: Prior to initiating Ritalin, screen patients for risk factors for developing manic episode. If new psychotic or manic symptoms occur, consider discontinuing Ritalin (5.4).oPriapism: If abnormally sustained or frequent and painful erections occur, patients should seek immediate medical attention (5.5).oPeripheral Vasculopathy, Including Raynauds Phenomenon: Careful observation for digital changes is necessary during Ritalin treatment. Further clinical evaluation (e.g., rheumatology referral) may be appropriate for patients who develop signs or symptoms of peripheral vasculopathy (5.6).oLong-Term Suppression of Growth in 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).oAcute Angle Closure Glaucoma: Ritalin -treated patients considered at risk for acute angle closure glaucoma (e.g., patients with significant hyperopia) should be evaluated by an ophthalmologist (5.8).oIncreased Intraocular Pressure (IOP) and Glaucoma: Prescribe Ritalin 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 history of increased IOP or open angle glaucoma (5.9).oMotor and Verbal Tics, and Worsening of Tourettes Syndrome: Before initiating Ritalin, assess the family history and clinically evaluate patients for tics or Tourettes syndrome. Regularly monitor patients for the emergence or worsening of tics or Tourettes syndrome. Discontinue treatment if clinically appropriate (5.10).. oRisks to Patients with Serious Cardiac Disease: Avoid use in patients with known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmias, coronary artery disease, or other serious cardiac disease (5.2).. oIncreased Blood Pressure and Heart Rate: Monitor blood pressure and pulse (5.3).. oPsychiatric Adverse Reactions: Prior to initiating Ritalin, screen patients for risk factors for developing manic episode. If new psychotic or manic symptoms occur, consider discontinuing Ritalin (5.4).. oPriapism: If abnormally sustained or frequent and painful erections occur, patients should seek immediate medical attention (5.5).. oPeripheral Vasculopathy, Including Raynauds Phenomenon: Careful observation for digital changes is necessary during Ritalin treatment. Further clinical evaluation (e.g., rheumatology referral) may be appropriate for patients who develop signs or symptoms of peripheral vasculopathy (5.6).. oLong-Term Suppression of Growth in 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).. oAcute Angle Closure Glaucoma: Ritalin -treated patients considered at risk for acute angle closure glaucoma (e.g., patients with significant hyperopia) should be evaluated by an ophthalmologist (5.8).. oIncreased Intraocular Pressure (IOP) and Glaucoma: Prescribe Ritalin 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 history of increased IOP or open angle glaucoma (5.9).. oMotor and Verbal Tics, and Worsening of Tourettes Syndrome: Before initiating Ritalin, assess the family history and clinically evaluate patients for tics or Tourettes syndrome. Regularly monitor patients for the emergence or worsening of tics or Tourettes syndrome. Discontinue treatment if clinically appropriate (5.10).. 5.1Abuse, Misuse, and Addiction Ritalin have high potential for abuse and misuse. The use of Ritalin exposes individuals to the risks of abuse and misuse, which can lead to the development of substance use disorder, including addiction. Ritalin 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 Ritalin, 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 Ritalin, assess each patients 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 Ritalin in safe place, preferably locked, and instruct patients to not give Ritalin to anyone else. Throughout Ritalin treatment, reassess each patients risk of abuse, misuse, and addiction and frequently monitor for signs and symptoms of abuse, misuse, and addiction.. 5.2Risks 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 Ritalin use in patients with known serious structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmia, coronary artery disease, or other serious cardiac disease.. 5.3Increased Blood Pressure and Heart Rate. CNS stimulants cause an increase in blood pressure (mean increase approximately to mmHg) and heart rate (mean increase approximately to beats per minute). Some patients may have larger increases. Monitor all Ritalin-treated patients for hypertension and tachycardia.. 5.4Psychiatric Adverse Reactions. Exacerbation of Pre-existing PsychosisCNS stimulants may exacerbate symptoms of behavior disturbance and thought disorder in patients with preexisting psychotic disorder. Induction of Manic Episode in Patients with Bipolar DisorderCNS stimulants may induce manic or mixed mood episode in patients. Prior to initiating Ritalin treatment, screen patients for risk factors for developing manic episode (e.g., comorbid or history of depressive symptoms or family history of suicide, bipolar disorder, or depression). New Psychotic or Manic SymptomsCNS stimulants, at the recommended dosage, may cause psychotic or manic symptoms (e.g., hallucinations, delusional thinking, or mania) in patients without prior history of psychotic illness or mania. In 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 Ritalin.. 5.5Priapism. Prolonged and painful erections, sometimes requiring surgical intervention, have been reported with methylphenidate use in both adult and pediatric male patients. Although priapism was not reported with methylphenidate initiation, it developed after some time on methylphenidate, often subsequent to an increase in dosage. Priapism also occurred during methylphenidate withdrawal (drug holidays or during discontinuation).Ritalin-treated patients who develop abnormally sustained or frequent and painful erections should seek immediate medical attention.. 5.6Peripheral Vasculopathy, Including Raynauds Phenomenon CNS stimulants, including Ritalin, used to treat ADHD are associated with peripheral vasculopathy, including Raynauds phenomenon. Signs and symptoms are usually intermittent and mild; however, sequelae have included digital ulceration and/or soft tissue breakdown. Effects of peripheral vasculopathy, including Raynauds phenomenon, were observed in postmarketing reports and at the therapeutic dosage of CNS stimulants in all age groups throughout the course of treatment. Signs and symptoms generally improved after dosage reduction or discontinuation of the CNS stimulant.Careful observation for digital changes is necessary during Ritalin treatment. Further clinical evaluation (e.g., rheumatology referral) may be appropriate for Ritalin-treated patients who develop signs or symptoms of peripheral vasculopathy.. 5.7Long-Term Suppression of Growth in Pediatric Patients. CNS stimulants have been associated with weight loss and slowing of growth rate in pediatric patients. Careful follow-up of weight and height in pediatric patients ages to 10 years who were randomized to either methylphenidate or non-medication treatment groups over 14 months, as well as in naturalistic subgroups of newly methylphenidate-treated and non-medication treated patients over 36 months (to the ages of 10 to 13 years), suggests that pediatric patients who received methylphenidate for days per week throughout the year had temporary slowing in growth rate (on average, total of about cm less growth in height and 2.7 kg less growth in weight over years), without evidence of growth rebound during this development period.Closely monitor growth (weight and height) in Ritalin-treated pediatric patients. Pediatric patients who are not growing or gaining height or weight as expected may need to have their treatment interrupted.. 5.8Acute Angle Closure Glaucoma There have been reports of angle closure glaucoma associated with methylphenidate treatment.Although the mechanism is not clear, Ritalin -treated patients considered at risk for acute angle closure glaucoma (e.g., patients with significant hyperopia) should be evaluated by an ophthalmologist.. 5.9Increased Intraocular Pressure and Glaucoma There have been reports of an elevation of intraocular pressure (IOP) associated with methylphenidate treatment [see Adverse Reactions (6)]. Prescribe Ritalin to patients with open-angle glaucoma or abnormally increased IOP only if the benefit of treatment is considered to outweigh the risk. Closely monitor Ritalin-treated patients with history of abnormally increased IOP or open angle glaucoma.. 5.10 Motor and Verbal Tics, and Worsening of Tourettes Syndrome CNS stimulants, including methylphenidate, have been associated with the onset or exacerbation of motor and verbal tics. Worsening of Tourettes syndrome has also been reported [see Adverse Reactions (6)]. Before initiating Ritalin, assess the family history and clinically evaluate patients for tics or Tourettes syndrome. Regularly monitor Ritalin-treated patients for the emergence or worsening of tics or Tourettes syndrome, and discontinue treatment if clinically appropriate.