FDA label b3be8bf4-6989-4864-a22b-cc33e6dbb96b

WARNING: ABUSE AND DEPENDENCE CNSstimulants,including methylphenidate hydrochloride tablets, other methylphenidate-containing products, and amphetamines, have a highpotentialforabuseanddependence.Assesstherisk of abuse prior to prescribing, and monitor for signs of abuse and dependence while on therapy [see Warnings and Precautions ( 5.1 ), Drug Abuse and Dependence ( 9.2 , 9.3 )] . WARNING: ABUSE AND DEPENDENCE See full prescribing informationforcomplete boxed warning. CNS stimulants, including methylphenidate hydrochloride tablets, other methylphenidate-containing products, and amphetamines, have a high potential for abuse and dependence ( 5.1 , 9.2 , 9.3 ). Assess the risk of abuse prior to prescribing, and monitor for signs of abuse and dependence while on therapy( 5.1 , 9.2 ).

5 WARNINGS AND PRECAUTIONS Serious CardiovascularEvents :Sudden death has been reported in association with CNS-stimulant treatment at usual doses in pediatric patients with structural cardiac abnormalities or other serious heart problems.In adults, sudden death, stroke, and myocardialinfarction have been reported. Avoid use in patients with known structuralcardiacabnormalities,cardiomyopathy, serious heart rhythm arrhythmias, or coronary artery disease ( 5.2 ). Blood Pressure and Heart RateIncreases :Monitorblood pressure and pulse. Consider the benefits and risk in patients for whom an increase in blood pressure or heartrate would be problematic( 5.3 ). Psychiatric Adverse Reactions : Use of stimulantsmay cause psychotic or manicsymptoms in patients with no prior history or exacerbation of symptoms in patients with preexisting psychiatric illness. Evaluate for preexistingpsychotic or bipolar disorder prior to methylphenidate hydrochloride use( 5.4 ). Priapism :Cases of painful and prolonged penile erections, and priapism have been reported with methylphenidateproducts.Immediatemedical attention should be sought if signs or symptoms of prolonged penile erections or priapism areobserved( 5.5 ). Peripheral Vasculopathy, I ncluding Raynaud’s Phenomenon :Stimulants used to treat ADHD are associated with peripheralvasculopathy,includingRaynaud’sphenomenon.Carefulobservation for digital changes is necessaryduringtreatment with ADHD stimulants( 5.6 ). Long-Term Suppression of Growth : Monitor height and weight at appropriateintervals in pediatric patients ( 5.7 ). 5.1 Potential for Abuse and Dependence CNS stimulants,including methylphenidate hydrochloride tablets, other methylphenidate-containingproducts, and amphetamines, have a high potential for abuse and dependence. Assess the risk of abuse prior to prescribing, and monitor for signs of abuse and dependence while on therapy [seeBoxed Warning, Drug Abuse and Dependence (9.2, 9.3)]. 5.2 Serious Cardiovascular Reactions Sudden death, stroke, and myocardial infarction have been reported in adults with CNS stimulanttreatment at recommended doses. Sudden death has been reported in pediatric patients with structural cardiac abnormalities and other serious heart problems taking CNS stimulants at recommended doses for ADHD. Avoid use in patients with known serious structural cardiac abnormalities,cardiomyopathy, serious heart rhythm abnormalities,coronary artery disease, and other serious heart problems. Further evaluate patients who develop exertional chest pain, unexplained syncope, or arrhythmias during methylphenidate hydrochloride treatment. 5.3 Blood Pressure and Heart Rate Increases CNS stimulants cause an increase in blood pressure (mean increaseapproximately 2 to 4 mmHg) and heart rate (mean increase approximately 3 to 6 beats per minute). Individuals may have larger increases. Monitor all patients for hypertension and tachycardia. 5.4 Psychiatric Adverse Reactions Exacerbation of Preexisting Psychosis CNS stimulants may exacerbate symptoms of behavior disturbance and thought disorder in patients with a preexisting psychoticdisorder. Induction of a Manic Episode in Patients with Bipolar Disorder CNS stimulants may induce a manic or mixedmood episode in patients. Prior to initiating treatment, screen patients for risk factors for developing a manic episode (e.g., comorbid or history of depressive symptoms or a family history of suicide, bipolar disorder, or depression). New Psychotic or Manic Symptoms CNS stimulants, at recommended doses, may cause psychotic or manic symptoms (e.g., hallucinations, delusional thinking, or mania) in patients without a prior history of psychotic illness or mania. If such symptoms occur, consider discontinuing methylphenidate hydrochloride. In a pooled analysis of multipleshort-term, placebo-controlled studies of CNS stimulants,psychotic or manicsymptoms occurred in approximately 0.1% of CNSstimulant-treated patients, compared to 0 in placebo-treated patients. 5.5 Priapism Prolonged and painful erections, sometimes requiring surgical intervention, have been reported with methylphenidate products in both pediatric and adult patients. Priapism was not reported with drug initiation but developed after sometime on the drug, often subsequent to an increase in dose. Priapism has also appeared during a period of drug withdrawal (drug holidays or duringdiscontinuation).Patients who developabnormally sustained or frequent and painful erections should seek immediate medical attention. 5.6 Peripheral Vasculopathy, Including Raynaud’s Phenomenon CNS stimulants, including methylphenidate hydrochloride, used to treat ADHD are associated with peripheral vasculopathy, including Raynaud’s phenomenon. Signs and symptoms are usuallyintermittent and mild; however, very rare sequelae include digital ulceration and/or soft tissue breakdown. Effects of peripheral vasculopathy, including Raynaud’s phenomenon, were observed in postmarketing reports at different times and at therapeutic doses in all age groups throughoutthe course of treatment. Signs and symptomsgenerallyimprove after reduction in dose or discontinuation of drug. Careful observation for digital changes is necessary during treatment with ADHD stimulants. Further clinical evaluation (e.g., rheumatology referral) may be appropriate for certain patients. 5.7 Long-Term Suppression of Growth 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 7 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 consistently medicated pediatric patients (i.e., treatment for 7 days per week throughoutthe year) have a temporary slowing in growth rate (on average, a total of about 2 cm less growth in height and 2.7 kg less growth in weight over 3 years), without evidence of growth reboundduringthis period of development. Closely monitor growth (weight and height) in pediatric patients treated with CNS stimulants, including methylphenidate hydrochloride. Patients who are not growing or gainingheight or weight as expected may need to have their treatment interrupted.

6 ADVERSE REACTIONS The following are discussed in more detail in other sections of the labeling: Abuse and Dependence [see Boxed Warning, Warningsand Precautions ( 5.1 ), Drug Abuse and Dependence ( 9.2 , 9.3 ) ] Knownhypersensitivity to methylphenidate or other ingredients of methylphenidate hydrochloride tablets [see Contraindications( 4 )] Hypertensive crisis with Concomitant Use of Monoamine Oxidase Inhibitors [seeContraindications ( 4 ), Drug Interactions ( 7.1 )] Serious Cardiovascular Reactions [see Warningsand Precautions ( 5.2 )] Blood Pressure and Heart Rate Increases [see Warnings and Precautions ( 5.3 )] Psychiatric Adverse Reactions [seeWarningsandPrecautions( 5.4 )] Priapism [seeWarningsand Precautions ( 5.5 )] Peripheral Vasculopathy, IncludingRaynaud’sPhenomenon [seeWarningsand Precautions ( 5.6 )] Long-Term Suppression of Growth [see Warnings and Precautions ( 5.7 )] The following adverse reactions associated with the use of methylphenidate hydrochloride tablets, and othermethylphenidate products were identified in clinical trials,spontaneous reports, and literature. Because these reactions were reported voluntarily from a population of uncertain size, it is not always possible to estimate their frequency reliably or to establish a causal relationship to drug exposure. Adverse Reactions Reported With methylphenidate hydrochloride Infections andInfestations: nasopharyngitis Blood and the Lymphatic System Disorders : leukopenia, thrombocytopenia,anemia Immune System Disorders: hypersensitivity reactions, includingangioedema, and anaphylaxis Metabolism and Nutrition Disorders: decreased appetite, reduced weight gain, and suppression of growth during prolongeduse in pediatric patients Psychiatric Disorders: insomnia,anxiety, restlessness, agitation, psychosis(sometimes with visual and tactile hallucinations), depressed mood Nervous 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 drugs Eye Disorders: blurred vision, difficulties in visual accommodation Cardiac Disorders: tachycardia,palpitations, increased blood pressure, arrhythmias, angina pectoris Respiratory, Thoracic, and Mediastinal Disorders: cough Gastrointestinal Disorders: dry mouth, nausea, vomiting,abdominal pain, dyspepsia Hepatobiliary Disorders: abnormal liver function, ranging from transaminase elevation to severe hepatic injury Skin andSubcutaneousTissue Disorders: hyperhidrosis, pruritus, urticaria, exfoliative dermatitis, scalp hair loss, erythemamultiforme rash, thrombocytopenic purpura Musculoskeletal and Connective Tissue Disorders: arthralgia, muscle cramps, rhabdomyolysis Investigations: weight loss (adult ADHD patients) Additional Adverse Reactions Reported with Other Methylphenidate-ContainingProducts The list below shows adverse reactions not listed for methylphenidate hydrochloride tablets that have been reported with other methylphenidate-containingproducts. Blood and Lymphatic Disorders: pancytopenia Immune System Disorders: hypersensitivity reactions, such as auricular swelling, bullous conditions, eruptions, exanthemas Psychiatric Disorders: affect lability, mania,disorientation, and libido changes Nervous System Disorders: migraine Eye Disorders: diplopia, mydriasis Cardiac Disorders: sudden cardiac death, myocardial infarction, bradycardia, extrasystole Vascular Disorders: peripheral coldness, Raynaud'sphenomenon Respiratory, Thoracic, and Mediastinal Disorders: pharyngolaryngeal pain, dyspnea Gastrointestinal Disorders: diarrhea, constipation Skin andSubcutaneousTissue Disorders: angioneuroticedema,erythema, fixed drug eruption Musculoskeletal, Connective Tissue, and Bone Disorders: myalgia,muscle twitching Renal and Urinary Disorders: hematuria Reproductive System and Breast Disorders: gynecomastia General Disorders: fatigue, hyperpyrexia Urogenital Disorders : priapism Commonadverse reactions: tachycardia, palpitations, headache, insomnia, anxiety, hyperhidrosis, weight loss, decreased appetite, dry mouth, nausea, and abdominal pain ( 6 ). To report SUSPECTED ADVERSE REACTIONS, contact Ascend Laboratories, LLC at 1-877-ASC-RX01 (877-272-7901) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.