Indicated for:

Attention Deficit Hyperactivity Disorder:

• Indicated for the treatment of attention deficit hyperactivity disorder (ADHD).

The safety and efficacy of ADDERALL XR in children under 6 years of age have not been studied).

ADDERALL XR has not been studied in the geriatric population.

The effectiveness of ADDERALL XR for long-term use, i.e., for more than 3 weeks in children and 4 weeks in adolescents and adults, has not been systematically evaluated in controlled trials. Therefore, the physician who elects to use ADDERALL XR for extended periods should periodically re-evaluate the long-term usefulness of the drug for the individual patient.

The maximum recommended dose for children 6-12 years of age is 30 mg/day; doses greater than 30 mg/day have not been studied in children.

In adult patients with severe renal impairment (GFR 15 to < 30 mL/min/1.73m²), the recommended dose is 15 mg once daily in the morning. In pediatric patients (6 to 17 years of age) with severe renal impairment, the recommended dose is 5 mg once daily. The maximum dose for children 6 to 12 years of age with severe renal impairment is 20 mg once daily. ADDERALL XR is not recommended in patients with end stage renal disease (ESRD) (GFR < 15 mL/min/1.73m²).

Amphetamines have a high potential for abuse. Administration of amphetamines for prolonged periods of time may lead to drug dependence and must be avoided. Particular attention should be paid to the possibility of subjects obtaining amphetamines for non-therapeutic use or distribution to others, and the drugs should be prescribed or dispensed sparingly. Misuse of amphetamines may cause sudden death and serious cardiovascular adverse reactions.

Drug treatment may not be indicated for all patients with this syndrome. Stimulants are not intended for use in the patient who exhibits 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 child’s symptoms.

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.

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.

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.

Administration of stimulants may exacerbate symptoms of behavior disturbance and thought disorder in patients with pre-existing psychotic disorder.

Particular care should be taken in using stimulants to treat ADHD patients with comorbid bipolar disorder because of concern for possible induction of mixed/manic episode in such patients.

Treatment-emergent psychotic or manic symptoms, e.g., hallucinations, delusional thinking, or mania in children and adolescents without 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.

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.

Monitor growth in children during treatment with stimulants. Patients who are not growing or gaining weight as expected may need to have their treatment interrupted.

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 the 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, ADDERALL XR should be discontinued.

Stimulants, including ADDERALL XR, used to treat ADHD are associated with peripheral vasculopathy, including Raynaud’s phenomenon.

Difficulties with accommodation and blurring of vision have been reported with stimulant treatment.

Amphetamines have been reported to exacerbate motor and phonic tics and Tourette’s syndrome.

ADDERALL XR administration is contraindicated in patients with the following conditions:

• Advanced arteriosclerosis
• Symptomatic cardiovascular disease
• Moderate to severe hypertension
• Hyperthyroidism
• Glaucoma
• Agitated states
• History of drug abuse
• Patients taking monoamine oxidase inhibitors (MAOIs), or within 14 days of stopping MAOIs (including MAOIs such as linezolid or intravenous methylene blue), because of an increased risk of hypertensive crisis

Serotonin syndrome, a potentially life-threatening reaction, may occur when amphetamines are used in combination with other drugs that affect the serotonergic neurotransmitter systems such as MAOIs, selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, and St. John’s Wort.

Amphetamines and amphetamine derivatives are known to be metabolized, to some degree, by cytochrome P450 2D6 (CYP2D6) and display minor inhibition of CYP2D6 metabolism. The potential for a pharmacokinetic interaction exists with the co administration of CYP2D6 inhibitors which may increase the risk with increased exposure to ADDERALL XR. In these situations, consider an alternative non serotonergic drug or an alternative drug that does not inhibit CYP2D6.

Concomitant use of MAOIs and CNS stimulants can cause hypertensive crisis. Potential outcomes include death, stroke, myocardial infarction, aortic dissection, ophthalmological complications, eclampsia, pulmonary edema, and renal failure.

The concomitant use of ADDERALL XR and serotonergic drugs (e.g., selective serotonin reuptake inhibitors (SSRI), serotonin norepinephrine reuptake inhibitors (SNRI), triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, St. John’s Wort) increases the risk of serotonin syndrome.

The concomitant use of ADDERALL XR and CYP2D6 inhibitors (e.g., paroxetine and fluoxetine also serotonergic drugs, quinidine, ritonavir) may increase the exposure of ADDERALL XR compared to the use of the drug alone and increase the risk of serotonin syndrome.

Co-administration of ADDERALL XR and gastrointestinal or urinary alkalinizing agents (e.g.,sodium bicarbonate, acetazolamide, some thiazides) should be avoided.

Gastrointestinal acidifying agents (e.g., guanethidine, reserpine, glutamic acid HCl, ascorbic acid), urinary acidifying agents (e.g., ammonium chloride, sodium acid phosphate, methenamine salts) lower blood levels and efficacy of amphetamines.

Co-administration of ADDERALL XR and tricyclic antidepressants may enhance the activity of tricyclic or sympathomimetic agents causing striking and sustained increases in the concentration of d-amphetamine in the brain; cardiovascular effects can be potentiated.

There are no adequate and well-controlled studies in pregnant women. There has been one report of severe congenital bony deformity, tracheoesophageal fistula, and anal atresia (vater association) in a baby born to a woman who took dextroamphetamine sulfate with lovastatin during the first trimester of pregnancy. Animal studies: fetal malformations and death.

Infants born to mothers dependent on amphetamines have an increased risk of premature delivery and low birth weight. Also, these infants may experience symptoms of withdrawal as demonstrated by dysphoria, including agitation, and significant lassitude.

Amphetamines are excreted in human milk. Mothers taking amphetamines should be advised to refrain from nursing.

GoToSource

• Use in patients under the age of 6. GoToSource

• Dosage greater than 30 mg per day in patients 6-12 years of age without renal impairment. GoToSource

• Cognition enhancement. GoToSource

• Weight loss. GoToSource

• Depression. GoToSource

• Use with SSRIS or SNRIS in the treatment of adult ADHD patients with generalized anxiety. GoToSource

• Fibromyalgia syndrome and chronic fatigue syndrome. GoToSource

• Obsessive compulsive disorder. GoToSource 

• Cocaine dependence. GoToSource 

• Cognitive impairment associated with multiple sclerosis. GoToSource

• Oppositional defiant disorder. GoToSource

Heart attacks. GoToSource

Takotsubo cardiomyopathy (sudden temporary weakening of heart muscle). GoToSource  

Cardiomyopathy with heart failure. GoToSource

Addiction. GoToSource

Growth suppression, anorexia, psychosis and exacerbation of tics and tourette syndrome. GoToSource

Acute, sustained chorea (movement disorder). GoToSource 

Elevated blood pressure, increased heart rate and sudden cardiac death. GoToSource

Hallucinations, delusions and anorexia. GoToSource

Peripheral vasculopathy including raynaud’s phenomenon (progressive circulation disorder caused by narrowing, blockage or spasms in a blood vessel). GoToSource

Seizures. GoToSource

Serotonin syndrome (life-threatening drug reaction). GoToSource

Bruxism (grinding of teeth). GoToSource

Priapism (frequent or prolonged erections). GoToSource

Anxiety, agitation, panic attacks, insomnia, irritability, hostility, impulsivity, akathisia (psychomotor restlessness), hypomania, mania and insomnia. GoToSource

Tremor, choreoathetosis, dystonia (feeling unwell or unhappy) dyskinesias (movement disorder), gait disturbance, ischemic infarction, intracerebral hemorrhage, depression and palpitations. GoToSource

Trichotillomania (hair pulling). GoToSource

Liver injury. GoToSource

Lawsuits filed for heart attacks, kidney failure, sudden death and addiction.