Methylphenidate hydrochloride extended-release tablets are indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in children 6 years of age and older, adolescents, and adults up to the age of 65 [see Clinical Studies ( 14 )] . A diagnosis of Attention Deficit Hyperactivity Disorder (ADHD; DSM-IV) implies the presence of hyperactive-impulsive or inattentive symptoms that caused impairment and were present before age 7 years.
The symptoms must cause clinically significant impairment, e.g., in social, academic, or occupational functioning, and be present in two or more settings, e.g., school (or work) and at home. The symptoms must not be better accounted for by another mental disorder. For the Inattentive Type, at least six of the following symptoms must have persisted for at least 6 months: lack of attention to details/careless mistakes; lack of sustained attention; poor listener; failure to follow through on tasks; poor organization; avoids tasks requiring sustained mental effort; loses things; easily distracted; forgetful.
For the Hyperactive-Impulsive Type, at least six of the following symptoms must have persisted for at least 6 months: fidgeting/squirming; leaving seat; inappropriate running/climbing; difficulty with quiet activities; “on the go;” excessive talking; blurting answers; can’t wait turn; intrusive. The Combined Type requires both inattentive and hyperactive-impulsive criteria to be met. Methylphenidate hydrochloride extended-release Tablets is a CNS stimulant indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in children 6 years of age and older, adolescents, and adults up to the age of 65.
( 1 )
1.1Special Diagnostic Considerations
Specific etiology of this syndrome is unknown, and there is no single diagnostic test. Adequate diagnosis requires the use of medical and special psychological, educational, and social resources. Learning may or may not be impaired. The diagnosis must be based upon a complete history and evaluation of the patient and not solely on the presence of the required number of DSM-IV characteristics.
1.2Need for Comprehensive Treatment Program
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Name two or more medicines and Osler runs an interaction check. A severe interaction is stated at the very top of the answer.
Methylphenidate hydrochloride extended-release tablets are indicated as an integral part of a total treatment program for ADHD that may include other measures (psychological, educational, social). Drug treatment may not be indicated for all patients with ADHD. Stimulants are not intended for use in patients who exhibit symptoms secondary to environmental factors and/or other primary psychiatric disorders, including psychosis.
Appropriate educational placement is essential and psychosocial intervention is often helpful. When remedial measures alone are insufficient, the decision to prescribe stimulant medication will depend upon the physician's assessment of the chronicity and severity of the patient’s symptoms.
Contraindications
Known hypersensitivity to the product ( 4.1 )
Marked anxiety, tension, or agitation ( 4.2 )
Glaucoma ( 4.3 )
Tics or a family history or diagnosis of Tourette’s syndrome ( 4.4 )
Do not use methylphenidate hydrochloride extended-release tablets in patients currently using or within 2 weeks of using an MAO inhibitor ( 4.5 )
4.1Hypersensitivity to Methylphenidate
Hypersensitivity reactions, such as angioedema and anaphylactic reactions, have been observed in patients treated with methylphenidate hydrochloride extended-release tablets. Therefore, methylphenidate hydrochloride extended-release tablets are contraindicated in patients known to be hypersensitive to methylphenidate or other components of the product [see Adverse Reactions ( 6.6 )] .
4.2Agitation
Methylphenidate hydrochloride extended-release tablets are contraindicated in patients with marked anxiety, tension, and agitation, since the drug may aggravate these symptoms.
4.3Glaucoma
Methylphenidate hydrochloride extended-release tablets are contraindicated in patients with glaucoma.
4.4Tics
Methylphenidate hydrochloride extended-release tablets are contraindicated in patients with motor tics or with a family history or diagnosis of Tourette's syndrome [see Adverse Reactions ( 6.4 )].
4.5Monoamine Oxidase Inhibitors
Methylphenidate hydrochloride extended-release tablets are contraindicated during treatment with monoamine oxidase (MAO) inhibitors, and also within a minimum of 14 days following discontinuation of a MAO inhibitor (hypertensive crises may result) [see Drug Interactions ( 7.1 )].
Warnings and precautions
Serious Cardiovascular Events: Sudden death has been reported in association with CNS stimulant treatment at usual doses in children and adolescents with structural cardiac abnormalities or other serious heart problems. Sudden death, stroke, and myocardial infarction have been reported in adults taking stimulant drugs at usual doses for ADHD. Stimulant products generally should not be used in patients with known structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, coronary artery disease, or other serious heart problems. ( 5.1 )
Increase in Blood Pressure: Monitor patients for changes in heart rate and blood pressure and use with caution in patients for whom an increase in blood pressure or heart rate would be problematic. ( 5.1 )
Psychiatric Adverse Events: Use of stimulants may cause treatment-emergent psychotic or manic symptoms in patients with no prior history, or exacerbation of symptoms in patients with preexisting psychiatric illness. Clinical evaluation for Bipolar Disorder is recommended prior to stimulant use. Monitor for aggressive behavior. ( 5.2 )
Seizures: Stimulants may lower the convulsive threshold.
Discontinue in the presence of seizures. ( 5.3 )
Priapism: cases of painful and prolonged penile erections and priapism have been reported with methylphenidate products. Immediate medical attention should be sought if signs or symptoms of painful or prolonged penile erections or priapism are observed. ( 5.4 )
Peripheral Vasculopathy, including Raynaud’s Phenomenon: Stimulants used to treat ADHD are associated with peripheral vasculopathy, including Raynaud’s phenomenon. Careful observation for digital changes is necessary during treatment with ADHD stimulants. ( 5.5 )
Visual Disturbance: difficulties with accommodation and blurring of vision have been reported with stimulant treatment. ( 5.7 )
Long-Term Suppression of Growth: monitor height and weight at appropriate intervals in pediatric patients. ( 5.6 )
Gastrointestinal obstruction with preexisting GI narrowing. ( 5.8 )
Hematologic monitoring: Periodic CBC, differential, and platelet counts are advised during prolonged therapy. ( 5.9 )
5.1 Serious Cardiovascular Events Sudden Death and Preexisting Structural Cardiac Abnormalities or Other Serious Heart Problems Children and Adolescents Sudden death has been reported in association with CNS stimulant treatment at usual doses in children and adolescents with structural cardiac abnormalities or other serious heart problems. Although some serious heart problems alone carry an increased risk of sudden death, stimulant products generally should not be used in children or adolescents with known serious structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, or other serious cardiac problems that may place them at increased vulnerability to the sympathomimetic effects of a stimulant drug.
Adults Sudden deaths, stroke, and myocardial infarction have been reported in adults taking stimulant drugs at usual doses for ADHD. Although the role of stimulants in these adult cases is also unknown, adults have a greater likelihood than children of having serious structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, coronary artery disease, or other serious cardiac problems. Adults with such abnormalities should also generally not be treated with stimulant drugs.
Hypertension and Other Cardiovascular Conditions Stimulant medications cause a modest increase in average blood pressure (about 2 to 4 mm Hg) and average heart rate (about 3 to 6 bpm) [see Adverse Reactions ( 6.5 )], and individuals may have larger increases. While the mean changes alone would not be expected to have short-term consequences, all patients should be monitored for larger changes in heart rate and blood pressure.
Caution is indicated in treating patients whose underlying medical conditions might be compromised by increases in blood pressure or heart rate, e.g., those with preexisting hypertension, heart failure, recent myocardial infarction, or ventricular arrhythmia. Assessing Cardiovascular Status in Patients Being Treated with Stimulant Medications Children, adolescents, or adults who are being considered for treatment with stimulant medications should have a careful history (including assessment for a family history of sudden death or ventricular arrhythmia) and physical exam to assess for the presence of cardiac disease, and should receive further cardiac evaluation if findings suggest such disease (e.g., electrocardiogram and echocardiogram).
Patients who develop symptoms such as exertional chest pain, unexplained syncope, or other symptoms suggestive of cardiac disease during stimulant treatment should undergo a prompt cardiac evaluation.
of stimulants may exacerbate symptoms of behavior disturbance and thought disorder in patients with a preexisting psychotic disorder. Bipolar Illness Particular care should be taken in using stimulants to treat ADHD in patients with comorbid bipolar disorder because of concern for possible induction of a mixed/manic episode in such patients. Prior to initiating treatment with a stimulant, patients with comorbid depressive symptoms should be adequately screened to determine if they are at risk for bipolar disorder; such screening should include a detailed psychiatric history, including a family history of suicide, bipolar disorder, and depression.
Emergence of New Psychotic or Manic Symptoms Treatment-emergent psychotic or manic symptoms, e.g., hallucinations, delusional thinking, or mania in patients without a prior history of psychotic illness or mania can be caused by stimulants at usual doses. If such symptoms occur, consideration should be given to a possible causal role of the stimulant, and discontinuation of treatment may be appropriate. In a pooled analysis of multiple short-term, placebo-controlled studies, such symptoms occurred in about 0.1% (4 patients with events out of 3,482 exposed to methylphenidate or amphetamine for several weeks at usual doses) of stimulant-treated patients compared to 0 in placebo-treated patients.
Aggression Aggressive behavior or hostility is often observed in patients with ADHD, and has been reported in clinical trials and the postmarketing experience of some medications indicated for the treatment of ADHD. Although there is no systematic evidence that stimulants cause aggressive behavior or hostility, patients beginning treatment for ADHD should be monitored for the appearance of or worsening of aggressive behavior or hostility.
5.3Seizures
There is some clinical evidence that stimulants may lower the convulsive threshold in patients with prior history of seizures, in patients with prior EEG abnormalities in absence of seizures, and, very rarely, in patients without a history of seizures and no prior EEG evidence of seizures. In the presence of seizures, the drug should be discontinued.
5.4Priapism Prolonged
and painful erections, sometimes requiring surgical intervention, have been reported with methylphenidate products, including methylphenidate hydrochloride extended-release tablets, in both pediatric and adult patients [see Adverse Reactions ( 6.6 )] . Priapism was not reported with drug initiation but developed after some time on the drug, often subsequent to an increase in dose. Priapism has also appeared during a period of drug withdrawal (drug holidays or during discontinuation).
Patients who develop abnormally sustained or frequent and painful erections should seek immediate medical attention.
5.5Peripheral
Vasculopathy, including Raynaud’s Phenomenon Stimulants, including methylphenidate hydrochloride, used to treat ADHD are associated with peripheral vasculopathy, including Raynaud’s phenomenon. Signs and symptoms are usually intermittent and mild; however, very rare sequelae i
Our copy of this section ends here. The full text is in the official label at the FDA. Open Drugs@FDA
Interactions
Do not use methylphenidate hydrochloride extended-release tablets in patients currently using or within 2 weeks of using an MAO inhibitor ( 7.1 )
Methylphenidate hydrochloride extended-release Tablets may increase blood pressure; use cautiously with vasopressors ( 7.2 )
Inhibition of metabolism of coumarin anticoagulants, anticonvulsants, and some antidepressants ( 7.3 )
7.1MAO Inhibitors
Methylphenidate hydrochloride extended-release tablets should not be used in patients being treated (currently or within the preceding 2 weeks) with MAO inhibitors [see Contraindications ( 4.5 )].
7.2Vasopressor Agents Because
of possible increases in blood pressure, methylphenidate hydrochloride extended-release tablets should be used cautiously with vasopressor agents [see Warnings and Precautions ( 5.1 )].
7.3Coumarin Anticoagulants, Antidepressants, and Selective Serotonin Reuptake Inhibitors
Human pharmacologic studies have shown that methylphenidate may inhibit the metabolism of coumarin anticoagulants, anticonvulsants (eg, phenobarbital, phenytoin, primidone), and some antidepressants (tricyclics and selective serotonin reuptake inhibitors). Downward dose adjustment of these drugs may be required when given concomitantly with methylphenidate. It may be necessary to adjust the dosage and monitor plasma drug concentrations (or, in the case of coumarin, coagulation times), when initiating or discontinuing concomitant methylphenidate.
7.4Risperidone
Combined use of methylphenidate with risperidone when there is a change, whether an increase or decrease, in dosage of either or both medications, may increase the risk of extrapyramidal symptoms (EPS). Monitor for signs of EPS.
Pregnancy and breastfeeding
8.1Pregnancy Pregnancy Category C
Methylphenidate has been shown to have teratogenic effects in rabbits when given in doses of 200 mg/kg/day, which is approximately 100 times and 40 times the maximum recommended human dose on a mg/kg and mg/m 2 basis, respectively. A reproduction study in rats revealed no evidence of harm to the fetus at oral doses up to 30 mg/kg/day, approximately 15-fold and 3-fold the maximum recommended human dose of methylphenidate hydrochloride Extended-Release Tablets on a mg/kg and mg/m 2 basis, respectively.
The approximate plasma exposure to methylphenidate plus its main metabolite PPAA in pregnant rats was 1 to 2 times that seen in trials in volunteers and patients with the maximum recommended dose of methylphenidate hydrochloride extended-release tablets based on the AUC. The safety of methylphenidate for use during human pregnancy has not been established.
Adverse reactions
The following are discussed in more detail in other sections of the labeling:
Drug Dependence [see Box Warning ]
Hypersensitivity to Methylphenidate [see Contraindications ( 4.1 )]
Agitation [see Contraindications ( 4.2 )]
Glaucoma [see Contraindications ( 4.3 )]
Tics [see Contraindications ( 4.4 )]
Monoamine Oxidase Inhibitors [see Contraindications ( 4.5 ) and Drug Interactions ( 7.1 )]
Serious Cardiovascular Events [see Warnings and Precautions ( 5.1 )]
Psychiatric Adverse Events [see Warnings and Precautions ( 5.2 )]
Seizures [see Warnings and Precautions ( 5.3 )]
Priapism [see Warnings and Precautions ( 5.4 )]
Long-Term Suppression of Growth [see Warnings and Precautions ( 5.6 )]
Visual Disturbance [see Warnings and Precautions ( 5.7 )]
Potential for Gastrointestinal Obstruction [see Warnings and Precautions ( 5.8 )]
Hematologic Monitoring [see Warnings and Precautions ( 5.9 )] The most common adverse reaction in double-blind clinical trials (>5%) in pediatric patients (children and adolescents) was abdominal pain upper. The most common adverse reactions in double-blind clinical trials (>5%) in adult patients were decreased appetite, headache, dry mouth, nausea, insomnia, anxiety, dizziness, weight decreased, irritability, and hyperhidrosis [see Adverse Reactions ( 6.1 )] . The most common adverse reactions associated with discontinuation (≥1%) from either pediatric or adult clinical trials were anxiety, irritability, insomnia, and blood pressure increased [see Adverse Reactions ( 6.3 )]. The development program for methylphenidate hydrochloride extended-release tablets included exposures in a total of 3,906 participants in clinical trials. Children, adolescents, and adults with ADHD were evaluated in 6 controlled clinical studies and 11 open-label clinical studies (see Table 3). Safety was assessed by collecting adverse events, vital signs, weights, and ECGs, and by performing physical examinations and laboratory analyses. Table 3. Methylphenidate Hydrochloride Extended-Release Tablets Exposure in Double-Blind and Open-Label Clinical Studies Patient Population N Dose Range Children 2216 18 to 54 mg once daily Adolescents 502 18 to 72 mg once daily Adults 1188 18 to 108 mg once daily Adverse events during exposure were obtained primarily by general inquiry and recorded by clinical investigators using their own terminology. Consequently, to provide a meaningful estimate of the proportion of individuals experiencing adverse events, events were grouped in standardized categories using MedDRA terminology. The stated frequencies of adverse events represent the proportion of individuals who experienced, at least once, a treatment-emergent adverse event of the type listed. An event was considered treatment-emergent if it occurred for the first time or worsened while receiving therapy following baseline evaluation. Throughout this section, adverse reactions are reported. Adverse reactions are adverse events that were considered to be reasonably associated with the use of methylphenidate hydrochloride extended-release tablets based on the comprehensive assessment of the available adverse event information. A causal association for methylphenidate hydrochloride extended-release tablets often cannot be reliably established in individual cases. Further, because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in clinical trials of another drug and may not reflect the rates observed in clinical practice. The majority of adverse reactions were mild to moderate in severity. The most common adverse reaction in double-blind clinical trials (>5%) in children and adolescents was abdominal pain upper. The most common adverse reactions in double-blind clinical trials (>5%) in adult patients were decreased appetite, headache, dry mouth, nausea, insomnia, anxiety, dizziness, weight decreased, irritability, and hyperhidrosis. ( 6.1 and 6.2 ) The most common adverse reactions associated with discontinuation (≥1%) from either pediatric or adult clinical trials were anxiety, irritability, insomnia, and blood pressure increased. ( 6.3 ) To report SUSPECTED ADVERSE REACTIONS, contact Dr. Reddy’s Laboratories, Inc. at 1-888-375-3784 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
6.1Commonly Observed Adverse Reactions in Double-Blind, Placebo-Controlled Clinical Trials
Adverse reactions in either the pediatric or adult double-blind adverse reactions tables may be relevant for both patient populations. Children and Adolescents Table 4 lists the adverse reactions reported in 1% or more of methylphenidate hydrochloride extended-release tablets-treated children and adolescent subjects in 4 placebo-controlled, double-blind clinical trials. Table 4. Adverse Reactions Reported by ≥1% of Methylphenidate Hydrochloride Extended-Release Tablets-Treated Children and Adolescent Subjects in 4 Placebo-Controlled, Double-Blind Clinical Trials of Methylphenidate Hydrochloride Extended-Release Tablets System/Organ Class Adverse Reaction Methylphenidate Hydrochloride (n=321) % Placebo (n=318) % Gastrointestinal Disorders Abdominal pain upper 6.2
3.8 Vomiting 2.8
1.6 General Disorders and Administration Site Conditions Pyrexia 2.2
0.9 Infections and Infestations Nasopharyngitis 2.8
0.3 Respiratory, Thoracic and Mediastinal Disorders Cough 1.9
0.9 Oropharyngeal pain 1.2 0.9 *Terms of Initial insomnia (methylphenidate hydrochloride=0.6%) and Insomnia (methylphenidate hydrochloride=2.2%) are combined into Insomnia. The majority of adverse reactions were mild to moderate in severity. Adults Table 5 lists the adverse reactions reported in 1% or more of methylphenidate hydrochloride extended-release tablets-treated adults in 2 placebo-controlled, double-blind clinical trials.
Table 5. Adverse Reactions Reported by ≥1% of Methylphenidate Hydrochloride Extended-Release Tablets-Treated Adult Subjects in 2 Placebo-Controlled, Double-Blind Clinical Trials* System/Organ Class Adverse Reaction Methylphenidate Hydrochloride (n=415) % Placebo (n=212) % Cardiac Disorders Tachycardia 4.8 0 Palpitations 3.1
0.9Ear and Labyrinth Disorders Vertigo 1.7 0 Eye Disorders
Vision blurred 1.7
0.5Gastrointestinal Disorders
Dry mouth 14.0
3.8 Nausea 12.8
3.3 Dyspepsia 2.2
0.9 Vomiting 1.7
0.5 Constipation 1.4
0.9 General Disorders and Administration Site Conditions Irritability 5.8
1.4Infections and Infestations
Upper respiratory tract infection 2.2
0.9Investigations
Weight decreased 6.5
3.3Metabolism and Nutrition Disorders
Decreased appetite 25.3
6.6Anorexia 1.7 0 Musculoskeletal and Connective Tissue Disorders
Muscle tightness 1.9 0 Nervous System Disorders Headache 22.2
15.6 Dizziness 6.7
5.2 Tremor 2.7
0.5Paresthesia 1.2 0 Sedation 1.2 0
Tension headache 1.2
0.5 Psychiatric Disorders Insomnia 12.3
6.1 Anxiety 8.2
2.4 Initial insomnia 4.3
2.8 Depressed mood 3.9
1.4 Nervousness 3.1
0.5 Restlessness 3.1 0 Agitation 2.2
0.5 Aggression 1.7
0.5 Bruxism 1.7
0.5 Depression 1.7
0.9 Libido decreased 1.7
0.5 Affect lability 1.4
0.9 Confusional state 1.2
0.5 Tension 1.2
0.5Respiratory, Thoracic and Mediastinal Disorders
Oropharyngeal pain 1.7
1.4Skin and Subcutaneous Tissue Disorders Hyperhidrosis 5.1
0.9 * Included doses up to 108 mg. The majority of ADRs were mild to moderate in severity .
This section includes adverse reactions reported by methylphenidate hydrochloride extended-release tablets-treated subjects in double-blind trials that do not meet the criteria specified for Table 4 or Table 5 and all adverse reactions reported by methylphenidate hydrochloride extended-release tablets-treated subjects who participated in open-label and postmarketing clinical tri
Our copy of this section ends here. The full text is in the official label at the FDA. Open Drugs@FDA
Composition
Active ingredients
METHYLPHENIDATE HYDROCHLORIDE 54MG
Strengths and forms
The FDA lists each strength of a product separately; these pages share one label.
Prognia shows this product information for reference and learning. It is not treatment advice and can lag behind the official text. Always check the current product information and local protocols before prescribing.
