Ritalin LA®

(methylphenidate hydrochloride)
extended-release capsules
Rx only
Prescribing Information

WARNINGS

Serious Cardiovascular Events

Sudden Death and Pre-Existing 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 death, 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 2-4 mmHg) and
average heart rate (about 3-6 bpm), 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 pre-existing 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
Reference ID: 3303787
symptoms suggestive of cardiac disease during stimulant treatment should undergo a prompt cardiac
evaluation.
Psychiatric Adverse Events
Pre-Existing Psychosis
Administration of stimulants may exacerbate symptoms of behavior disturbance and thought disorder
in patients with a pre-existing 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 children and adolescents 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 children and adolescents with ADHD, and has
been reported in clinical trials and the postmarketing experience of some medications indicated for the
treatment of ADHD including methylphenidate. 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.

Long-Term Suppression of Growth

Careful follow-up of weight and height in children 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 children over 36 months (to
the ages of 10 to 13 years), suggests that consistently medicated children (i.e., treatment for 7 days per
week throughout the 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
rebound during this period of development. In the double-blind placebo-controlled study of Ritalin
LA® (methylphenidate hydrochloride) extended-release capsules, the mean weight gain was greater for
patients receiving placebo (+1.0 kg) than for patients receiving Ritalin LA (+0.1 kg). Published data
are inadequate to determine whether chronic use of amphetamines may cause a similar suppression of
growth, however, it is anticipated that they likely have this effect as well. Therefore, growth should be
monitored during treatment with stimulants, and patients who are not growing or gaining height or
weight as expected may need to have their treatment interrupted.
Reference ID: 3303787

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.
Visual Disturbance
Difficulties with accommodation and blurring of vision have been reported with stimulant treatment.
Use in Children Under Six Years of Age
Ritalin LA should not be used in children under six years of age, since safety and efficacy in this age
group have not been established.

Drug Dependence

Ritalin LA should be given cautiously to patients with a history of drug dependence or alcoholism.
Chronic abusive use can lead to marked tolerance and psychological dependence with varying degrees
of abnormal behavior. Frank psychotic episodes can occur, especially with parenteral abuse. Careful
supervision is required during withdrawal from abusive use, since severe depression may occur.
Withdrawal following chronic therapeutic use may unmask symptoms of the underlying disorder that
may require follow-up.

PRECAUTIONS

Hematologic Monitoring
Periodic CBC, differential, and platelet counts are advised during prolonged therapy.

Information for Patients

Prescribers or other health professionals should inform patients, their families, and their caregivers
about the benefits and risks associated with treatment with methylphenidate and should counsel them
in its appropriate use. A patient Medication Guide is available for Ritalin LA. The prescriber or health
professional should instruct patients, their families, and their caregivers to read the Medication Guide
and should assist them in understanding its contents. Patients should be given the opportunity to
discuss the contents of the Medication Guide and to obtain answers to any questions they may have.
The complete text of the Medication Guide is reprinted at the end of this document.
Patients should be advised to avoid alcohol while taking RITALIN LA. Consumption of alcohol while
taking RITALIN LA may result in a more rapid release of the dose of methylphenidate.

Adverse Events with Other Methylphenidate HCl Dosage Forms
Nervousness and insomnia are the most common adverse reactions reported with other
methylphenidate products.

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 below may also occur.

Other reactions include:

Cardiac:

• angina,
• arrhythmia,
• palpitations,
• pulse increased or decreased,
• tachycardia

Gastrointestinal:

• abdominal pain,
• nausea

Immune:

• hypersensitivity reactions including skin rash,
• urticaria, fever,
• arthralgia,
• exfoliative
  dermatitis,
• erythema multiforme with histopathological findings of necrotizing vasculitis,
• thrombocytopenic purpura

Metabolism/Nutrition:

• anorexia,
• weight loss during prolonged therapy

Nervous System:

• dizziness,
• drowsiness,
• dyskinesia,
• headache,
• rare reports of Tourette’s syndrome,
• toxic psychosis

Vascular:

• blood pressure increased or decreased; cerebrovascular vasculitis; cerebral occlusions;
  cerebral hemorrhages and cerebrovascular accidents

Blood/Lymphatic:

• leukopenia and/or anemia
  Hepatobiliary:
• abnormal liver function,
• ranging from transaminase elevation to hepatic coma

Psychiatric:

• transient depressed mood,
• aggressive behavior

Skin/Subcutaneous:

scalp hair loss 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.