The FDA ( Food and Drug Administration ) has made changes to the boxed warning, warning, warning and precautions sections of the prescribing information for Dexedrine ( Dextroamphetamine sulfate ), approved for the treatment of ( ADHD ) Attention-Deficit Hyperactivity Disorder and narcolepsy. The warnings describe reports of sudden death in association with CNS stimulant treatment at usual doses in children and adolescents with structural cardiac abnormalities or other serious heart problems.

In addition, the following language has been added to the Warnings section of the Dexedrine prescribing information:

WARNINGS

Serious Cardiovascular Events

Sudden death in patients with 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.

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 2-4 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 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.

Psychiatric adverse events

Preexisting psychosis

Administration 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 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. 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.

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.

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.

Source: GSK, 2006


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