ABUSE SECTION.

9.2 Abuse. Focalin 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)]. Focalin 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 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 Focalin, 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 Focalin [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)] 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 Focalin [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 most common adverse reactions (greater than or equal to 5% and twice the rate of placebo) in pediatric patients to 17 years were abdominal pain, fever, nausea, and anorexia (6.1).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.. 6.1 Clinical Trials Experience. Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.Adverse Reactions in Studies with Focalin in Pediatric Patients with ADHDThe safety data in this section is based on data related to Focalin exposure during the premarketing development program in total of 696 participants in clinical trials (684 patients, 12 healthy adult subjects). These participants received Focalin 5, 10, or 20 mg/day. The 684 ADHD patients (ages to 17 years) were evaluated in controlled clinical studies, clinical pharmacology studies, and open-label long-term safety studies. Most Common Adverse Reactions (incidence of greater than or equal to 5% and at least twice placebo): abdominal pain, fever, anorexia, and nauseaAdverse Reactions Leading to Discontinuation: Overall, 50 of 684 (7.3%) pediatric patients treated with Focalin experienced an adverse reaction that resulted in discontinuation. The most common reasons for discontinuation were twitching (described as motor or vocal tics), anorexia, insomnia, and tachycardia (approximately 1% each). Table enumerates adverse reactions for two, placebo-controlled, parallel group studies in pediatric patients with ADHD taking Focalin doses of 5, 10, and 20 mg/day. The table includes only those reactions that occurred in patients treated with Focalin for which the incidence was at least 5% and twice the incidence among placebo-treated patients. Table 1: Common Adverse Reactions in Pediatric Patients (6 to 17 years of age) With ADHDAbbreviation: ADHD, attention deficit hyperactivity disorder.System organ classAdverse reactionsFocalin(N 79)Placebo(N 82)Body as wholeAbdominal pain15% 6% Fever 5% 1% Digestive systemAnorexia6% 1% Nausea 9% 1% 6.2 Postmarketing Experience. The following additional adverse reactions have been identified during postapproval use of dexmethylphenidate. Because these reactions are reported voluntarily from population of uncertain size, it is not always possible to reliably estimate their frequency or establish causal relationship to drug exposure.Musculoskeletal: rhabdomyolysisImmune System Disorders: hypersensitivity reactions, such as angioedema, anaphylactic reactionsAdverse Reactions Reported with All Ritalin and Focalin FormulationsThe following adverse reactions associated with the use of all Ritalin and Focalin formulations 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.Infections 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 purpura Musculoskeletal and Connective Tissue Disorders: arthralgia, muscle cramps, rhabdomyolysis, trismusInvestigations: weight loss (adult ADHD patients)Vascular Disorders: peripheral coldness, Raynauds phenomenon Additional Adverse Reactions Reported with Other Methylphenidate-Containing ProductsThe list below shows adverse reactions not listed with Ritalin and Focalin formulations that have been reported with other methylphenidate products based on clinical trials data and post-marketing spontaneous reports.Blood and Lymphatic Disorders: pancytopeniaImmune System Disorders: hypersensitivity reactions, such as auricular swellingPsychiatric Disorders: affect lability, mania, disorientation, libido changesNervous System Disorders: migraine, motor and verbal tics Eye Disorders: diplopia, increased intraocular pressure, mydriasisCardiac Disorders: sudden cardiac death, myocardial infarction, bradycardia, extrasystole, supraventricular tachycardia, ventricular 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: fatigueUrogenital Disorders: priapism.

BOXED WARNING SECTION.

WARNING: ABUSE, MISUSE, AND ADDICTION. Focalin 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 Focalin, 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 Focalin, 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 Focalin 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.Focalin 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 Focalin, can result in overdose and death (5.1, 9.2, 10):oBefore prescribing Focalin, assess each patients risk for abuse, misuse, and addiction.oEducate patients and their families about these risks, proper storage of the drug, and proper disposal of any unused drug.oThroughout treatment, reassess each patients risk and frequently monitor for signs and symptoms of abuse, misuse, and addiction.. oBefore prescribing Focalin, assess each patients risk for abuse, misuse, and addiction.. oEducate patients and their families about these risks, proper storage of the drug, and proper disposal of any unused drug.. oThroughout 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. CarcinogenesisLifetime carcinogenicity studies have not been carried out with dexmethylphenidate. In lifetime carcinogenicity study carried out in B6C3F1 mice, racemic methylphenidate caused an increase in hepatocellular adenomas, and in males only, an increase in hepatoblastomas was seen at daily dose of approximately 60 mg/kg/day. This dose is approximately times the MRHD of 60 mg/day of racemic methylphenidate 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. Racemic 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) of 60 mg/day of racemic methylphenidate on mg/m2 basis.In 24-week carcinogenicity study with racemic methylphenidate 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 concentrations as in the lifetime carcinogenicity study; the high-dose group was exposed to 60-74 mg/kg/day of racemic methylphenidate.MutagenesisDexmethylphenidate 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 vivo mouse bone marrow micronucleus test. In an in vitro assay using cultured Chinese Hamster Ovary cells treated with racemic methylphenidate, sister chromatid exchanges and chromosome aberrations were increased, indicative of weak clastogenic response.Impairment of FertilityNo human data on the effect of methylphenidate on fertility are available. Fertility studies have not been conducted with dexmethylphenidate. Racemic 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 of up to 160 mg/kg/day, approximately 10 times the MRHD of 60 mg/day of racemic methylphenidate given adolescents on mg/m2 basis.

CLINICAL PHARMACOLOGY SECTION.

12 CLINICAL PHARMACOLOGY. 12.1 Mechanism of Action. Dexmethylphenidate hydrochloride is CNS stimulant. The mode of therapeutic action in ADHD is not known.. 12.2 Pharmacodynamics. PharmacodynamicsDexmethylphenidate is the more pharmacologically active d-enantiomer of racemic methylphenidate. Methylphenidate blocks the reuptake of norepinephrine and dopamine into the presynaptic neuron and increase the release of these monoamines into the extraneuronal space.Cardiac ElectrophysiologyA formal QT study has not been conducted in patients taking Focalin; however, large QT effect is not expected. At the recommended maximum total daily dosage of 40 mg, Focalin XR (dexmethylphenidate) extended-release capsule does not prolong the QTc interval to any clinically relevant extent.. 12.3 Pharmacokinetics. AbsorptionDexmethylphenidate hydrochloride is readily absorbed following oral administration of Focalin. In patients with ADHD, plasma dexmethylphenidate concentrations increase rapidly, reaching maximum in the fasted state at about to 1.5 hours postdose. No differences in the pharmacokinetics of Focalin were noted following single and repeated twice daily dosing, thus indicating no significant drug accumulation in children with ADHD.After single dose administration of Focalin to pediatric patients, dexmethylphenidate exposure (Cmax and AUC0-inf) showed dose-proportional increase in the range of 2.5 mg to 10 mg. Comparable plasma dexmethylphenidate levels were achieved following single dl-threo-methylphenidate HCl doses given as capsules in twice the total mg amount (equimolar with respect to Focalin).Approximately 90% of the dose is absorbed after oral administration of radiolabeled racemic methylphenidate. However, due to first pass metabolism the mean absolute bioavailability of dexmethylphenidate when administered in various formulations was 22% to 25%.Effect of FoodHigh fat breakfast did not significantly affect Cmax or AUC0-inf of dexmethylphenidate when two 10 mg Focalin tablets were administered, but delayed Tmax from 1.5 hours post dose to 2.9 hours post dose. DistributionThe plasma protein binding of dexmethylphenidate is not known; racemic methylphenidate is bound to plasma proteins by 12% to 15%, independent of concentration. Dexmethylphenidate shows volume of distribution of 2.65 +- 1.11 L/kg.EliminationPlasma dexmethylphenidate concentrations declined exponentially following oral administration of Focalin. Intravenous dexmethylphenidate was eliminated with mean clearance of 0.40 +- 0.12 L/hr/kg. The mean terminal elimination half-life of dexmethylphenidate was approximately 2.2 hours.MetabolismIn humans, dexmethylphenidate is metabolized primarily via de-esterification to d--phenyl-piperidine acetic acid (also known as d-ritalinic acid). This metabolite has little or no pharmacological activity. There is little or no in vivo interconversion to the l-threo-enantiomer.ExcretionAfter oral dosing of radiolabeled racemic methylphenidate in humans, about 90% of the radioactivity was recovered in urine. The main urinary metabolite of racemic dl-methylphenidate was dl-ritalinic acid, accountable for approximately 80% of the dose. Urinary excretion of parent compound accounted for 0.5% of an intravenous dose. Studies in Special PopulationsMale and Female PatientsPharmacokinetic parameters were similar for boys and girls (mean age 10 years).In single dose study conducted in adults, the mean dexmethylphenidate AUC0-inf values (adjusted for body weight) following single two 10 mg doses of Focalin were 25% to 35% higher in adult female volunteers (n 6) compared to male volunteers (n 9). Both Tmax and t1/2 were comparable for males and females.Racial or Ethnic GroupsThere is insufficient experience with the use of Focalin to detect ethnic variations in pharmacokinetics.Pediatric PatientsThe pharmacokinetics of dexmethylphenidate after Focalin administration have not been studied in children less than years of age. When single doses of Focalin were given to children between the ages of to 12 years and healthy adult volunteers, Cmax of dexmethylphenidate was similar, however, pediatric patients showed somewhat lower AUCs compared to the adults.Patients with Renal ImpairmentThere is no experience with the use of Focalin in patients with renal impairment. Since renal clearance is not an important route of methylphenidate clearance, renal impairment is expected to have little effect on the pharmacokinetics of Focalin.Patients with Hepatic ImpairmentThere is no experience with the use of Focalin in patients with hepatic impairment.Drug Interaction StudiesMethylphenidate is not metabolized by cytochrome P450 (CYP) isoenzymes to clinically relevant extent. Inducers or inhibitors of CYPs are not expected to have any relevant impact on methylphenidate pharmacokinetics. Conversely, the d- and l-enantiomers of methylphenidate did not relevantly inhibit CYP1A2, 2C8, 2C9, 2C19, 2D6, 2E1, or 3A. Clinically, methylphenidate coadministration did not increase plasma concentrations of the CYP2D6 substrate desipramine.

CLINICAL STUDIES SECTION.

14 CLINICAL STUDIES. The efficacy of Focalin for the treatment of ADHD was established in two double-blind, parallel-group, placebo-controlled trials in untreated or previously treated patients (ages to 17 years old) who met The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria for ADHD inattentive, hyperactive-impulsive, or combined inattentive/hyperactive-impulsive subtypes. The sample was predominantly younger (ages to 12 years); thus, the findings are most pertinent to this age group.In Study 1, patients were randomized to receive either Focalin (5, 10, or 20 mg/day total dose), racemic methylphenidate HCl (10, 20, or 40 mg/day total dose), or placebo in multicenter, 4-week, parallel group study in 132 pediatric patients. Patients received study medication twice daily separated by 3.5 to 5.5 hours interval. Treatment was initiated with the lowest dose, and doses could be doubled at weekly intervals, depending on clinical response and tolerability, up to the maximum dose. The primary outcome was change from baseline to week of the average score (an average of ratings during the week) of the teachers version of the Swanson, Nolan and Pelham (SNAP)-ADHD Rating Scale. This 18 text scale measures ADHD symptoms of inattention and hyperactivity/impulsivity, rated on scale of (Not at All) to (Very Much). Patients treated with Focalin showed statistically significant improvement in symptom scores from baseline over patients who received placebo (Table 3).Table 3: Summary of Efficacy Results from ADHD Acute-Phase Study in Pediatric Patients (6 17 years) (Study 1) Abbreviations: ADHD, attention deficit hyperactivity disorder; SD, standard deviation; SNAP; swanson, Nolan and Pelham; n, number of patients available at the assessment time point. aAverage of two ratings. bStatistically significantly different from placebo. Study numberTreatment groupPrimary efficacy measure: teacher SNAP-ADHD total Scorea Mean baseline score (SD)Mean change from baseline Week score (SD)Study 1Focalin 5-20 mg/dayb (n 44)1.4 (0.7) (n 42)- 0.7 (0.7) (n 42)Placebo (n 42)1.6 (0.7) (n 41)- 0.2 (0.7) (n 39)Study was multicenter, placebo-controlled, double-blind, 2-week treatment withdrawal study in 75 children (ages to 12 years) who were responders during 6-week, open-label initial treatment period. Children took study medication twice day separated by 3.5 to 5.5 hour interval. The primary outcome was proportion of treatment failures at the end of the 2-week withdrawal phase, where treatment failure was defined as rating of (much worse) or (very much worse) on the Investigator Clinical Global Impression Improvement (CGI-I). Patients continued on Focalin showed statistically significant lower rate of failure over patients who received placebo (Table 4).Table 4: Summary of Efficacy Results from ADHD Randomized Withdrawal Study in Pediatric Patients (6 17 years) (Study 2)Abbreviation: ADHD, attention deficit hyperactivity disorder. aOne patient did not have the value at Visit 10 and hence not included in this analysis. bStatistically significantly different from placebo. Study numberTreatment groupPrimary efficacy measure: proportion of treatment failurea Number of treatment failures Number of randomized patientsPercentageStudy 2Focalin 5-20 mg/dayb 6/3517.1% Placebo25/4062.5%.

CONTRAINDICATIONS SECTION.

4 CONTRAINDICATIONS. oHypersensitivity to methylphenidate or other components of Focalin. Hypersensitivity reactions, such as angioedema and anaphylactic reactions have been reported in patients treated with methylphenidate [see Adverse Reactions (6.1)].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 Focalin. Hypersensitivity reactions, such as angioedema and anaphylactic reactions have been reported in patients treated with methylphenidate [see Adverse Reactions (6.1)].. 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 components of Focalin (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 components of Focalin (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. Focalin contains dexmethylphenidate hydrochloride, Schedule II controlled substance.

DEPENDENCE SECTION.

9.3 Dependence. Physical DependenceFocalin 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 Focalin include dysphoric mood; depression; fatigue; vivid, unpleasant dreams; insomnia or hypersomnia; increased appetite; and psychomotor retardation or agitation.ToleranceFocalin 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. Focalin contains dexmethylphenidate hydrochloride, CNS stimulant. Dexmethylphenidate hydrochloride is the d-threo enantiomer of racemic methylphenidate hydrochloride. Focalin is available as 2.5 mg, mg, and 10 mg strength tablets for oral administration.Chemically, dexmethylphenidate hydrochloride is methyl -phenyl-2-piperidineacetate hydrochloride, (R,R)-(+)-. Its molecular formula is C14H19NO2oHCl. Its structural formula is:Note: asymmetric carbon centersDexmethylphenidate hydrochloride is white to off-white 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: FD&C Blue No.1 5516 aluminum lake (2.5 mg tablets), FD&C Yellow Lake 10 (5 mg tablets). The 10 mg tablets contain no dye. Lactose monohydrate, magnesium stearate, microcrystalline cellulose, pregelatinized starch, sodium starch glycolate.. Dexmethylphenidate hydrochloride structural formula.

DOSAGE & ADMINISTRATION SECTION.

2 DOSAGE AND ADMINISTRATION. oAdminister orally twice daily, hours apart with or without food (2).oFor patients new to methylphenidate: Recommend starting dose of mg once daily (2.5 mg twice daily) (2.2).oFor patients currently taking methylphenidate: Initiate Focalin therapy with half (1/2) the current total daily dose of methylphenidate (2.2).oTitrate weekly in increments of 2.5 to mg to maximum of 20 mg/day (10 mg twice daily) (2.2).. oAdminister orally twice daily, hours apart with or without food (2).. oFor patients new to methylphenidate: Recommend starting dose of mg once daily (2.5 mg twice daily) (2.2).. oFor patients currently taking methylphenidate: Initiate Focalin therapy with half (1/2) the current total daily dose of methylphenidate (2.2).. oTitrate weekly in increments of 2.5 to mg to maximum of 20 mg/day (10 mg twice daily) (2.2).. 2.1 Pretreatment Screening. Prior to treating patients with Focalin, 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 Focalin [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 Focalin [see Warnings and Precautions (5.10)].. 2.2 Recommended Dosage. Patients New to MethylphenidateThe recommended starting dose of Focalin for pediatric patients who are not currently taking racemic methylphenidate, or for patients who are on stimulants other than methylphenidate, is mg daily (2.5 mg twice daily) with or without food.Patients Currently on MethylphenidateThe recommended starting dose of Focalin for pediatric patients currently using methylphenidate is half (1/2) the total daily dose of racemic methylphenidate.Titration ScheduleThe dose may be titrated weekly in increments of 2.5 mg to mg to maximum of 20 mg daily (10 mg twice daily). The dose should be individualized according to the needs and response of the patient.. 2.3 Administration Instructions. Focalin is administered orally twice daily, at least hours apart.. 2.4 Dosage Reduction and Discontinuation. If paradoxical aggravation of symptoms or other adverse reactions occur, reduce the dosage, or if necessary, discontinue Focalin. 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. Focalin (dexmethylphenidate hydrochloride) tablets are D-shaped, embossed D on upper convex face and dosage strength on lower convex face in the following colors:o2.5 mg tablets blueo5 mg tablets yellowo10 mg tablets white. o2.5 mg tablets blue. o5 mg tablets yellow. o10 mg tablets white. Tablets: 2.5 mg, mg, and 10 mg (3).

DRUG ABUSE AND DEPENDENCE SECTION.

9 DRUG ABUSE AND DEPENDENCE. 9.1 Controlled Substance. Focalin contains dexmethylphenidate hydrochloride, Schedule II controlled substance.. 9.2 Abuse. Focalin 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)]. Focalin 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 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 Focalin, 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 DependenceFocalin 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 Focalin include dysphoric mood; depression; fatigue; vivid, unpleasant dreams; insomnia or hypersomnia; increased appetite; and psychomotor retardation or agitation.ToleranceFocalin 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 Focalin. Table presents clinically important drug interactions with Focalin.Table 2: Clinically Important Drug Interactions with FocalinMonoamine Oxidase Inhibitors (MAOIs)Clinical impactConcomitant use of MAOIs and CNS stimulants, including Focalin, 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 Focalin with MAOIs or within 14 days after discontinuing MAOI treatment is contraindicated.Antihypertensive DrugsClinical impactFocalin may decrease the effectiveness of drugs used to treat hypertension [see Warnings and Precautions (5.3)]. InterventionAdjust the dosage of the antihypertensive drug as needed. Halogenated AnestheticsClinical impactConcomitant use of halogenated anesthetics and Focalin may increase the risk of sudden blood pressure and heart rate increase during surgery.InterventionMonitor blood pressure and avoid use of Focalin 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. Focalin has not been studied in the geriatric population.

HOW SUPPLIED SECTION.

16 HOW SUPPLIED/STORAGE AND HANDLING. Focalin (dexmethylphenidate hydrochloride) tablets (D-shaped, embossed D on upper convex face and dosage strength on lower convex face) are available as follows:o2.5 mg tablets (NDC 0078-0380-05) blue, supplied in bottles of 100o5 mg tablets (NDC 0078-0381-05) yellow, supplied in bottles of 100o10 mg tablets (NDC 0078-0382-05) white, 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].Dispense in tight, light-resistant container (USP).. o2.5 mg tablets (NDC 0078-0380-05) blue, supplied in bottles of 100. o5 mg tablets (NDC 0078-0381-05) yellow, supplied in bottles of 100. o10 mg tablets (NDC 0078-0382-05) white, supplied in bottles of 100.

INDICATIONS & USAGE SECTION.

1 INDICATIONS AND USAGE. Focalin is indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) [see Clinical Studies (14)].. Focalin is central nervous system (CNS) stimulant indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) (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 Focalin, 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 Focalin in safe place, preferably locked, and instruct patients to not give Focalin to anyone else.Risks to Patients with Serious Cardiac DiseaseAdvise patients that there are potential risks to patients with serious cardiac disease, including sudden death, with Focalin 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 Focalin can cause elevations of their blood pressure and pulse rate [see Warnings and Precautions (5.3)].Psychiatric Adverse ReactionsAdvise patients that Focalin, 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 beginning treatment with Focalin 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 Focalin. 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 Focalin 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 Focalin [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 Focalin.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 Focalin, during pregnancy [see Use in Specific Populations (8.1)].Distributed by:Novartis Pharmaceuticals CorporationEast Hanover, New Jersey 07936.

LACTATION SECTION.

8.2 Lactation Risk SummaryDexmethylphenidate is the d-threo enantiomer of racemic methylphenidate. 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 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 Focalin and any potential adverse effects on the breastfed infant from Focalin 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. Dexmethylphenidate hydrochloride is CNS stimulant. The mode of therapeutic action in ADHD is not known.

NONCLINICAL TOXICOLOGY SECTION.

13 NONCLINICAL TOXICOLOGY. 13.1 Carcinogenesis, Mutagenesis, and Impairment of Fertility. CarcinogenesisLifetime carcinogenicity studies have not been carried out with dexmethylphenidate. In lifetime carcinogenicity study carried out in B6C3F1 mice, racemic methylphenidate caused an increase in hepatocellular adenomas, and in males only, an increase in hepatoblastomas was seen at daily dose of approximately 60 mg/kg/day. This dose is approximately times the MRHD of 60 mg/day of racemic methylphenidate 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. Racemic 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) of 60 mg/day of racemic methylphenidate on mg/m2 basis.In 24-week carcinogenicity study with racemic methylphenidate 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 concentrations as in the lifetime carcinogenicity study; the high-dose group was exposed to 60-74 mg/kg/day of racemic methylphenidate.MutagenesisDexmethylphenidate 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 vivo mouse bone marrow micronucleus test. In an in vitro assay using cultured Chinese Hamster Ovary cells treated with racemic methylphenidate, sister chromatid exchanges and chromosome aberrations were increased, indicative of weak clastogenic response.Impairment of FertilityNo human data on the effect of methylphenidate on fertility are available. Fertility studies have not been conducted with dexmethylphenidate. Racemic 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 of up to 160 mg/kg/day, approximately 10 times the MRHD of 60 mg/day of racemic methylphenidate given 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. NOVARTIS NDC 0078-0380-05Focalin(R) dexmethylphenidatehydrochloride2.5 mg100 TabletsRx onlyDispense with Medication Guideattached or provided separately.. PRINCIPAL DISPLAY PANEL NOVARTIS NDC 0078-0380-05 Focalin(R) dexmethylphenidate hydrochloride 2.5 mg 100 tablets Rx only Dispense with Medication Guide attached or provided separately.

PEDIATRIC USE SECTION.

8.4 Pediatric Use. The safety and effectiveness of Focalin have been established in pediatric patients aged to 17 years in two adequate and well-controlled clinical trials [see Clinical Studies (14)].The safety and effectiveness of Focalin in pediatric patients aged less than years have not been established.The long-term efficacy of Focalin in pediatric patients has not been established.Long-Term Suppression of GrowthGrowth should be monitored during treatment with stimulants, including Focalin. 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 racemic 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, racemic 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 of racemic methylphenidate 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. PharmacodynamicsDexmethylphenidate is the more pharmacologically active d-enantiomer of racemic methylphenidate. Methylphenidate blocks the reuptake of norepinephrine and dopamine into the presynaptic neuron and increase the release of these monoamines into the extraneuronal space.Cardiac ElectrophysiologyA formal QT study has not been conducted in patients taking Focalin; however, large QT effect is not expected. At the recommended maximum total daily dosage of 40 mg, Focalin XR (dexmethylphenidate) extended-release capsule does not prolong the QTc interval to any clinically relevant extent.

PHARMACOKINETICS SECTION.

12.3 Pharmacokinetics. AbsorptionDexmethylphenidate hydrochloride is readily absorbed following oral administration of Focalin. In patients with ADHD, plasma dexmethylphenidate concentrations increase rapidly, reaching maximum in the fasted state at about to 1.5 hours postdose. No differences in the pharmacokinetics of Focalin were noted following single and repeated twice daily dosing, thus indicating no significant drug accumulation in children with ADHD.After single dose administration of Focalin to pediatric patients, dexmethylphenidate exposure (Cmax and AUC0-inf) showed dose-proportional increase in the range of 2.5 mg to 10 mg. Comparable plasma dexmethylphenidate levels were achieved following single dl-threo-methylphenidate HCl doses given as capsules in twice the total mg amount (equimolar with respect to Focalin).Approximately 90% of the dose is absorbed after oral administration of radiolabeled racemic methylphenidate. However, due to first pass metabolism the mean absolute bioavailability of dexmethylphenidate when administered in various formulations was 22% to 25%.Effect of FoodHigh fat breakfast did not significantly affect Cmax or AUC0-inf of dexmethylphenidate when two 10 mg Focalin tablets were administered, but delayed Tmax from 1.5 hours post dose to 2.9 hours post dose. DistributionThe plasma protein binding of dexmethylphenidate is not known; racemic methylphenidate is bound to plasma proteins by 12% to 15%, independent of concentration. Dexmethylphenidate shows volume of distribution of 2.65 +- 1.11 L/kg.EliminationPlasma dexmethylphenidate concentrations declined exponentially following oral administration of Focalin. Intravenous dexmethylphenidate was eliminated with mean clearance of 0.40 +- 0.12 L/hr/kg. The mean terminal elimination half-life of dexmethylphenidate was approximately 2.2 hours.MetabolismIn humans, dexmethylphenidate is metabolized primarily via de-esterification to d--phenyl-piperidine acetic acid (also known as d-ritalinic acid). This metabolite has little or no pharmacological activity. There is little or no in vivo interconversion to the l-threo-enantiomer.ExcretionAfter oral dosing of radiolabeled racemic methylphenidate in humans, about 90% of the radioactivity was recovered in urine. The main urinary metabolite of racemic dl-methylphenidate was dl-ritalinic acid, accountable for approximately 80% of the dose. Urinary excretion of parent compound accounted for 0.5% of an intravenous dose. Studies in Special PopulationsMale and Female PatientsPharmacokinetic parameters were similar for boys and girls (mean age 10 years).In single dose study conducted in adults, the mean dexmethylphenidate AUC0-inf values (adjusted for body weight) following single two 10 mg doses of Focalin were 25% to 35% higher in adult female volunteers (n 6) compared to male volunteers (n 9). Both Tmax and t1/2 were comparable for males and females.Racial or Ethnic GroupsThere is insufficient experience with the use of Focalin to detect ethnic variations in pharmacokinetics.Pediatric PatientsThe pharmacokinetics of dexmethylphenidate after Focalin administration have not been studied in children less than years of age. When single doses of Focalin were given to children between the ages of to 12 years and healthy adult volunteers, Cmax of dexmethylphenidate was similar, however, pediatric patients showed somewhat lower AUCs compared to the adults.Patients with Renal ImpairmentThere is no experience with the use of Focalin in patients with renal impairment. Since renal clearance is not an important route of methylphenidate clearance, renal impairment is expected to have little effect on the pharmacokinetics of Focalin.Patients with Hepatic ImpairmentThere is no experience with the use of Focalin in patients with hepatic impairment.Drug Interaction StudiesMethylphenidate is not metabolized by cytochrome P450 (CYP) isoenzymes to clinically relevant extent. Inducers or inhibitors of CYPs are not expected to have any relevant impact on methylphenidate pharmacokinetics. Conversely, the d- and l-enantiomers of methylphenidate did not relevantly inhibit CYP1A2, 2C8, 2C9, 2C19, 2D6, 2E1, or 3A. Clinically, methylphenidate coadministration did not increase plasma concentrations of the CYP2D6 substrate desipramine.

PREGNANCY SECTION.

8.1 Pregnancy. Pregnancy Exposure RegistryThere is pregnancy exposure registry that monitors pregnancy outcomes in women exposed to ADHD medications, including Focalin, 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 SummaryDexmethylphenidate is the d-threo enantiomer of racemic methylphenidate. Published 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 during pregnancy (see Clinical Considerations). Embryo-fetal development studies in rats showed delayed fetal skeletal ossification at doses up to times the maximum recommended human dose (MRHD) of 20 mg/day given to adults based on plasma levels. decrease in pup weight in males 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 of 20 mg/day given to adults based on plasma levels. Plasma levels in adults were comparatively similar to plasma levels in 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 Focalin, 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, dexmethylphenidate was administered orally at doses of up to 20 and 100 mg/kg/day, respectively, during the period of organogenesis. No evidence of malformations was found in either the rat or rabbit study; however, delayed fetal skeletal ossification was observed at the highest dose level in rats. When dexmethylphenidate was administered to rats throughout pregnancy and lactation at doses of up to 20 mg/kg/day, post-weaning body weight gain was decreased in male offspring at the highest dose, but no other effects on postnatal development were observed. At the highest doses tested, plasma levels [area under the curves (AUCs)] of dexmethylphenidate in pregnant rats and rabbits were approximately and times, respectively, those in adults dosed with the MRHD of 20 mg/day.Racemic methylphenidate has been shown to cause malformations (increased incidence of fetal spina bifida) in rabbits when given in doses of 200 mg/kg/day throughout organogenesis.

RECENT MAJOR CHANGES SECTION.

Boxed Warning 10/2023Dosage and Administration (2.1, 2.2) 10/2023Warnings and Precautions (5.1, 5.2, 5.8, 5.9, 5.10) 10/2023.

SPL MEDGUIDE SECTION.

This Medication Guide has been approved by the U.S. Food and Drug Administration.Revised: 10/2023MEDICATION GUIDEFOCALIN(R) (foh-kuh-lin)(dexmethylphenidate hydrochloride) tablets for oral use, CIIWhat is the most important information should know about FOCALINFOCALIN may cause serious side effects, including:oAbuse, misuse, and addiction. FOCALIN has high chance for abuse and misuse and may lead to substance use problems, including addiction. Misuse and abuse of FOCALIN, 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 FOCALIN 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 FOCALIN and will monitor you or your child during treatment.oFOCALIN may lead to physical dependence after prolonged use, even if taken as directed by your healthcare provider.oDo not give FOCALIN to anyone else. See What is FOCALIN for more information.oKeep FOCALIN in safe place and properly dispose of any unused medicine. See How should store FOCALIN 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 FOCALIN. 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 FOCALIN.oIncreased blood pressure and heart rate. Your healthcare provider should check you or your childs blood pressure and heart rate regularly during treatment with FOCALIN.oMental (psychiatric) problems: All Patientsonew or worse behavior and thought problemsonew or worse bipolar illnessonew psychotic symptoms (such as hearing voices, believing things that are not true, are suspicious) or new manic symptomsTell 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 orproblems while taking FOCALIN, especially seeing or hearing things that are not real, believing things that are not real, or are suspicious.What is FOCALINoFOCALIN is central nervous system stimulant (CNS) prescription medicine. It is used for the treatment of Attention-Deficit Hyperactivity Disorder (ADHD). FOCALIN may help increase attention and decrease impulsiveness and hyperactivity in patients with ADHD.oFOCALIN should be used as part of total treatment program for ADHD that may include counseling or other therapies.FOCALIN is federally controlled substance (CII) because it contains dexmethylphenidate that can be target for people who abuse prescription medicines or street drugs. Keep FOCALIN in safe place to protect it from theft. Never give your FOCALIN to anyone else because it may cause death or harm them. Selling or giving away FOCALIN may harm others and is against the law.Who should not take FOCALINFOCALIN should not be taken if you or your child:oare allergic to methylphenidate hydrochloride, or any of the ingredients in FOCALIN. See the end of this Medication Guide for complete list of ingredients in FOCALIN.oare taking or have taken within the past 14 days an anti-depression medicine called monoamine oxidase inhibitor (MAOI).FOCALIN may not be right for you or your child. Before starting FOCALIN, 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 FOCALIN will harm your unborn baby.oThere is pregnancy registry for females who are exposed to ADHD medications, including FOCALIN during pregnancy. The purpose of the registry is to collect information about the health of females exposed to FOCALIN and their baby. If you or your child becomes pregnant during treatment with FOCALIN, 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. FOCALIN passes into your breast milk. Talk to your healthcare provider about the best way to feed the baby during treatment with FOCALIN.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. FOCALIN 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 taking FOCALIN.Your healthcare provider will decide whether FOCALIN can be taken with other medicines.Especially tell your healthcare provider if you or your child takes:oblood 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 FOCALIN 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 FOCALIN without talking to your healthcare provider first.How should FOCALIN be takenoTake FOCALIN exactly as prescribed. Your healthcare provider may adjust the dose until it is right for you or your child.oTake FOCALIN twice daily, at least hours apart.oFOCALIN may be taken with or without food.oYour healthcare provider may do regular checks of the blood, heart, and blood pressure while taking FOCALIN.oChildren should have their height and weight checked often while taking FOCALIN. FOCALIN treatment may be stopped if problem is found during these check-ups.If you or your child take too much FOCALIN, 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 FOCALINFOCALIN may cause serious side effects, including:osee What is the most important information should know about FOCALIN 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.oCall your healthcare provider right away if you have or your child has any signs of unexplained wounds appearing on fingers or toes while taking FOCALIN.oSlowing of growth (height and weight) in children. Children should have their height and weight checked often during treatment with FOCALIN. FOCALIN 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 FOCALIN.oCommon side effects include:oabdominal painofeveroanorexiaonausea Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. How should store FOCALINoStore FOCALIN 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 FOCALIN 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 FOCALIN 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 FOCALIN in the household trash. Visit www.fda.gov/drugdisposal for additional information on disposal of unused medicines.oKeep FOCALIN and all medicines out of the reach of children.General information about the safe and effective use of FOCALIN.Medicines are sometimes prescribed for purposes other than those listed in Medication Guide. You can ask your pharmacist or healthcare provider for information about FOCALIN that is written for healthcare professionals. Do not use FOCALIN for condition for which it was not prescribed. Do not give FOCALIN 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 FOCALINActive ingredient: dexmethylphenidate hydrochlorideInactive ingredients: FD&C Blue No.1 5516 aluminum lake (2.5 mg tablets), D&C Yellow Lake 10 (5 mg tablets); the 10 mg tablet contains no dye, lactose monohydrate, magnesium stearate, microcrystalline cellulose, pregelatinized starch, and sodium starch glycolate.Distributed by:Novartis Pharmaceuticals CorporationEast Hanover, New Jersey 07936(C) NovartisFor more information, call 1-888-669-6682.. oAbuse, misuse, and addiction. FOCALIN has high chance for abuse and misuse and may lead to substance use problems, including addiction. Misuse and abuse of FOCALIN, 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 FOCALIN 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 FOCALIN and will monitor you or your child during treatment.. oFOCALIN may lead to physical dependence after prolonged use, even if taken as directed by your healthcare provider.. oDo not give FOCALIN to anyone else. See What is FOCALIN for more information.. oKeep FOCALIN in safe place and properly dispose of any unused medicine. See How should store FOCALIN 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.. oIncreased blood pressure and heart rate. Your healthcare provider should check you or your childs blood pressure and heart rate regularly during treatment with FOCALIN.. oMental (psychiatric) problems:. All Patients. onew or worse behavior and thought problems. onew or worse bipolar illness. onew psychotic symptoms (such as hearing voices, believing things that are not true, are suspicious) or new manic symptoms. oFOCALIN is central nervous system stimulant (CNS) prescription medicine. It is used for the treatment of Attention-Deficit Hyperactivity Disorder (ADHD). FOCALIN may help increase attention and decrease impulsiveness and hyperactivity in patients with ADHD.. oFOCALIN should be used as part of total treatment program for ADHD that may include counseling or other therapies.. oare allergic to methylphenidate hydrochloride, or any of the ingredients in FOCALIN. See the end of this Medication Guide for complete list of ingredients in FOCALIN.. 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 FOCALIN will harm your unborn baby.. oThere is pregnancy registry for females who are exposed to ADHD medications, including FOCALIN during pregnancy. The purpose of the registry is to collect information about the health of females exposed to FOCALIN and their baby. If you or your child becomes pregnant during treatment with FOCALIN, 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. FOCALIN passes into your breast milk. Talk to your healthcare provider about the best way to feed the baby during treatment with FOCALIN.. oblood pressure medicines (anti-hypertensive). oYou should not take FOCALIN 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 FOCALIN exactly as prescribed. Your healthcare provider may adjust the dose until it is right for you or your child.. oTake FOCALIN twice daily, at least hours apart.. oFOCALIN may be taken with or without food.. oYour healthcare provider may do regular checks of the blood, heart, and blood pressure while taking FOCALIN.. oChildren should have their height and weight checked often while taking FOCALIN. FOCALIN treatment may be stopped if problem is found during these check-ups.. osee What is the most important information should know about FOCALIN 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. oCall your healthcare provider right away if you have or your child has any signs of unexplained wounds appearing on fingers or toes while taking FOCALIN.. oSlowing of growth (height and weight) in children. Children should have their height and weight checked often during treatment with FOCALIN. FOCALIN 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 FOCALIN.. oCommon side effects include:oabdominal painofeveroanorexiaonausea. oabdominal pain. ofever. oanorexia. onausea. oStore FOCALIN 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 FOCALIN 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 FOCALIN 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 FOCALIN in the household trash. Visit www.fda.gov/drugdisposal for additional information on disposal of unused medicines.. oKeep FOCALIN and all medicines out of the reach of children.

SPL UNCLASSIFIED SECTION.

2.1 Pretreatment Screening. Prior to treating patients with Focalin, 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 Focalin [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 Focalin [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 Focalin, 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 SummaryDexmethylphenidate is the d-threo enantiomer of racemic methylphenidate. Published 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 during pregnancy (see Clinical Considerations). Embryo-fetal development studies in rats showed delayed fetal skeletal ossification at doses up to times the maximum recommended human dose (MRHD) of 20 mg/day given to adults based on plasma levels. decrease in pup weight in males 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 of 20 mg/day given to adults based on plasma levels. Plasma levels in adults were comparatively similar to plasma levels in 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 Focalin, 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, dexmethylphenidate was administered orally at doses of up to 20 and 100 mg/kg/day, respectively, during the period of organogenesis. No evidence of malformations was found in either the rat or rabbit study; however, delayed fetal skeletal ossification was observed at the highest dose level in rats. When dexmethylphenidate was administered to rats throughout pregnancy and lactation at doses of up to 20 mg/kg/day, post-weaning body weight gain was decreased in male offspring at the highest dose, but no other effects on postnatal development were observed. At the highest doses tested, plasma levels [area under the curves (AUCs)] of dexmethylphenidate in pregnant rats and rabbits were approximately and times, respectively, those in adults dosed with the MRHD of 20 mg/day.Racemic methylphenidate has been shown to cause malformations (increased incidence of fetal spina bifida) in rabbits when given in doses of 200 mg/kg/day throughout organogenesis.. 8.2 Lactation Risk SummaryDexmethylphenidate is the d-threo enantiomer of racemic methylphenidate. 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 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 Focalin and any potential adverse effects on the breastfed infant from Focalin 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 Focalin have been established in pediatric patients aged to 17 years in two adequate and well-controlled clinical trials [see Clinical Studies (14)].The safety and effectiveness of Focalin in pediatric patients aged less than years have not been established.The long-term efficacy of Focalin in pediatric patients has not been established.Long-Term Suppression of GrowthGrowth should be monitored during treatment with stimulants, including Focalin. 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 racemic 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, racemic 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 of racemic methylphenidate 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. Focalin 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 Focalin, screen patients for risk factors for developing manic episode. If new psychotic or manic symptoms occur, consider discontinuing Focalin (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 Focalin 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: Focalin -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 Focalin 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 Focalin, 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 Focalin, screen patients for risk factors for developing manic episode. If new psychotic or manic symptoms occur, consider discontinuing Focalin (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 Focalin 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: Focalin -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 Focalin 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 Focalin, 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).. 5.1 Abuse, Misuse, and Addiction. Focalin has high potential for abuse and misuse. The use of Focalin exposes individuals to the risks of abuse and misuse, which can lead to the development of substance use disorder, including addiction. Focalin 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 Focalin, 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 Focalin, 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 Focalin in safe place, preferably locked, and instruct patients to not give Focalin to anyone else. Throughout Focalin treatment, reassess each patients 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 were treated with CNS stimulants at the recommended ADHD dosage.Avoid Focalin use 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 to mmHg) and heart rate (mean increase approximately to beats per minute). Some patients may have larger increases. Monitor all Focalin-treated patients for hypertension and tachycardia.. 5.4 Psychiatric Adverse Reactions. Exacerbation of Preexisting 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 Focalin 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 Focalin.. 5.5 Priapism. 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).Focalin-treated patients who develop abnormally sustained or frequent and painful erections should seek immediate medical attention.. 5.6 Peripheral Vasculopathy, Including Raynauds Phenomenon. CNS stimulants, including Focalin, 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 post-marketing reports and at the therapeutic dosages 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 Focalin treatment. Further clinical evaluation (e.g., rheumatology referral) may be appropriate for Focalin-treated patients who develop signs or symptoms of peripheral vasculopathy.. 5.7 Long-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 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 Focalin-treated pediatric patients. Pediatric patients who are not growing or gaining height or weight as expected may need to have their treatment interrupted.. 5.8 Acute Angle Closure Glaucoma There have been reports of angle closure glaucoma associated with methylphenidate treatment.Although the mechanism is not clear, Focalin-treated patients considered at risk for acute angle closure glaucoma (e.g.,patients with significant hyperopia) should be evaluated by an ophthalmologist.. 5.9 Increased Intraocular Pressure and Glaucoma There have been reports of an elevation of intraocular pressure (IOP) associated with methylphenidate treatment [see Adverse Reactions (6.2)]. Prescribe Focalin to patients with open-angle glaucoma or abnormally increased IOP only if the benefit of treatment is considered to outweigh the risk. Closely monitor Focalin-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 (6.2)].Before initiating Focalin, assess the family history and clinically evaluate patients for tics or Tourettes syndrome. Regularly monitor Focalin-treated patients for the emergence or worsening of tics or Tourettes syndrome, and discontinue treatment if clinically appropriate.