INDICATIONS AND USAGE Attention Deficit Disorders, Narcolepsy Attention Deficit Disorders (previously known as Minimal Brain Dysfunction in Children).

Other terms being used to describe the behavioral syndrome below include: Hyperkinetic Child Syndrome, Minimal Brain Damage, Minimal Cerebral Dysfunction, Minor Cerebral Dysfunction.

Methylphenidate hydrochloride chewable tablets are indicated as an integral part of a total treatment program which typically includes other remedial measures (psychological, educational, social) for a stabilizing effect in children with a behavioral syndrome characterized by the following group of developmentally inappropriate symptoms: moderate-to-severe distractibility, short attention span, hyperactivity, emotional lability, and impulsivity.

The diagnosis of this syndrome should not be made with finality when these symptoms are only of comparatively recent origin.

Nonlocalizing (soft) neurological signs, learning disability, and abnormal EEG may or may not be present, and a diagnosis of central nervous system dysfunction may or may not be warranted.

Special Diagnostic Considerations Specific etiology of this syndrome is unknown, and there is no single diagnostic test.

Adequate diagnosis requires the use not only of medical but of special psychological, educational, and social resources.

Characteristics commonly reported include: chronic history of short attention span, distractibility, emotional lability, impulsivity, and moderate-to-severe hyperactivity; minor neurological signs and abnormal EEG.

Learning may or may not be impaired.

The diagnosis must be based upon a complete history and evaluation of the child and not solely on the presence of one or more of these characteristics.

Drug treatment is not indicated for all children with this syndrome.

Stimulants are not intended for use in the child who exhibits symptoms secondary to environmental factors and/or primary psychiatric disorders, including psychosis.

Appropriate educational placement is essential and psychosocial intervention is generally necessary.

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 child’s symptoms.

WARNINGS Abuse, Misuse, and Addiction Methylphenidate hydrochloride chewable tablets has a high potential for abuse and misuse.

The use of methylphenidate hydrochloride chewable tablets exposes individuals to the risks of abuse and misuse, which can lead to the development of a substance use disorder, including addiction.

Methylphenidate hydrochloride chewable tablets can be diverted for non-medical use into illicit channels or distribution (see DRUG ABUSE and DEPENDENCE).

Misuse and abuse of CNS stimulants, including methylphenidate hydrochloride chewable tablets can result in overdose and death (see OVERDOSAGE) , and this risk is increased with higher doses or unapproved methods of administration, such as snorting or injection.

Before prescribing methylphenidate hydrochloride chewable tablets, assess each patient’s risk for abuse, misuse, and addiction.

Educate patients and their families about these risks and proper disposal of any unused drug.

Advise patients to store methylphenidate in a safe place, preferably locked, and instruct patients to not give methylphenidate hydrochloride chewable tablets to anyone else.

Throughout methylphenidate hydrochloride chewable tablets treatment, reassess each patient’s risk of abuse, misuse, and addiction and frequently monitor for signs and symptoms of abuse, misuse, and addiction.

Risks to Patients with Serious Cardiac Disease Sudden death has been reported in patients with structural cardiac abnormalities or other serious cardiac disease who are treated with CNS stimulants at the recommended ADHD dosages.

Avoid methylphenidate hydrochloride chewable tablets use in patients with known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmia, coronary artery disease, or other serious cardiac disease.

Increased Blood Pressure and Heart Rate CNS stimulants cause an increase in blood pressure (mean increase about 2 to 4 mm Hg) and heart rate (mean increase about 3 to 6 bpm).

Monitor all patients for potential tachycardia and hypertension.

Psychiatric Adverse Reactions Exacerbations of Pre-Existing Psychosis – CNS stimulants may exacerbate symptoms of behavior disturbance and thought disorder in patients with a pre-existing psychotic disorder.

Induction of a Manic Episode in Patients with Bipolar Disease – CNS stimulants may induce a manic or mixed 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.

In a pooled analysis of multiple short-term, placebo-controlled studies of CNS stimulants, psychotic or manic symptoms occurred in approximately 0.1% of CNS stimulant-treated patients, compared with 0% of placebo-treated patients.

If such symptoms occur, consideration discontinuing methylphenidate hydrochloride chewable tablets.

Seizures 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.

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 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 discontinuation): Patients who develop abnormally sustained or frequent and painful erections should seek immediate medical attention.

Peripheral Vasculopathy, Including Raynaud’s Phenomenon Stimulants, including methylphenidate hydrochloride chewable tablets, 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 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 throughout the course of treatment.

Signs and symptoms generally improve 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.

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 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 pediatric patients over 36 months (to the ages of 10 to 13 years), suggests that pediatric patients who received methylphenidate for 7 days per week throughout the year had 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 rebound during this development period.

Closely monitor growth (weight and height) in methylphenidate hydrochloride chewable tablets-treated pediatric patients.

Pediatric patients who are not growing or gaining height or weight as expected may need to have their treatment interrupted (see PRECAUTIONS, PEDIATRIC USE).

Acute Angle Closure Glaucoma There have been reports of angle closure glaucoma associated with methylphenidate treatment.

Although the mechanism is not clear, methylphenidate hydrochloride chewable tablets-treated patients considered at risk for acute angle closure glaucoma (e.g., patients with significant hyperopia) should be evaluated by an ophthalmologist.

Increased Intraocular Pressure and Glaucoma There have been reports of an elevation of intraocular pressure (IOP) associated with methylphenidate treatment (see Adverse Reactions).

Prescribe methylphenidate hydrochloride chewable tablets to patients with open-angle glaucoma or abnormally increased IOP only if the benefit of treatment is considered to outweigh the risk.

Closely monitor methylphenidate hydrochloride chewable tablets-treated patients with a history of abnormally increased IOP or open angle glaucoma.

Motor and Verbal Tics, and Worsening of Tourette’s Syndrome CNS stimulants, including methylphenidate, have been associated with the onset or exacerbation of motor and verbal tics.

Worsening of Tourette’s syndrome has also been reported.

Assess the family history and clinically evaluate patients for tics or Tourette’s syndrome before initiating methylphenidate hydrochloride chewable tablets.

Regularly monitor patients for the emergence or worsening of tics or Tourette’s syndrome with methylphenidate hydrochloride chewable tablets, and discontinue treatment if clinically appropriate.

USE IN CHILDREN LESS THAN SIX YEARS OF AGE Methylphenidate hydrochloride chewable tablets should not be used in children under six years, since safety and efficacy in this age group have not been established.

ADVERSE REACTIONS Nervousness and insomnia are the most common adverse reactions but are usually controlled by reducing dosage and omitting the drug in the afternoon or evening.

Other reactions include hypersensitivity (including skin rash, urticaria, fever, arthralgia, exfoliative dermatitis, erythema multiforme with histopathological findings of necrotizing vasculitis, and thrombocytopenic purpura); anorexia; nausea; dizziness; palpitations; headache; dyskinesia; drowsiness; blood pressure and pulse changes, both up and down; tachycardia; angina; cardiac arrhythmia; abdominal pain; weight loss during prolonged therapy; libido changes; and rhabdomyolysis increased intraocular pressure and glaucoma, motor and verbal tics.

There have been rare reports of Tourette’s syndrome.

Toxic psychosis has been reported.

Although a definite causal relationship has not been established, the following have been reported in patients taking this drug: instances of abnormal liver function, ranging from transaminase elevation to severe hepatic injury; isolated cases of cerebral arteritis and/or occlusion; leukopenia and/or anemia; transient depressed mood; a few instances of scalp hair loss; serotonin syndrome in combination with serotonergic drugs.

Very rare reports of neuroleptic malignant syndrome (NMS) have been received, and, in most of these, patients were concurrently receiving therapies associated with NMS.

In a single report, a ten year old boy who had been taking methylphenidate for approximately 18 months experienced an NMS-like event within 45 minutes of ingesting his first dose of venlafaxine.

It is uncertain whether this case represented a drug-drug interaction, a response to either drug alone, or some other cause.

In children, loss of appetite, abdominal pain, weight loss during prolonged therapy, insomnia, and tachycardia may occur more frequently; however, any of the other adverse reactions listed above may also occur.