DEXEDRINE ER 30mg. Capsules.

BOXED WARNING

Dextroamphetamine is contraindicated in patients with moderate to severe hypertension, advanced arteriosclerosis, or symptomatic cardiac disease. The FDA recommends that, in general, stimulant medications not be used in patients with known serious cardiac structural abnormalities, a history of acute myocardial infarction, aortic stenosis, prosthetic heart valves, valvular heart disease, cardiomyopathy, ventricular dysfunction or heart failure, cardiac arrhythmias, coronary artery disease, or other serious cardiac problems. Stimulant medications may increase blood pressure or heart rate in some individuals, but more serious cardiac effects have also been associated with stimulant use. Sudden unexplained death (SUD) and myocardial infarction have occurred in adults receiving stimulants at standard dosages for attention-deficit hyperactivity-disorder (ADHD). Sudden death has also been associated with stimulant medications at usual doses in pediatrics with structural cardiac abnormalities or other serious heart problems. A large retrospective cohort study including over 1.2 million children and young adults 2—24 years of age did not find an increased risk of serious cardiovascular events in current users of drugs for the treatment of ADHD compared to nonusers (adjusted hazard ratio 0.75; 95% CI 0.31—1.85). Similar results were seen when current users of ADHD drugs were compared to former users and when current users with severe underlying cardiovascular disease were included in the analysis. The authors concluded that although the absolute magnitude of risk appears to be low, a modest increase in risk could not be ruled out. The American Heart Association (AHA) states that it is reasonable to consider the use of these medications in pediatric patients with congenital heart disease without current hemodynamic or arrhythmic concerns or congenital heart disease that is considered stable by the patient’s pediatric cardiologist, unless the cardiologist has specific concerns. However, these patients should be closely monitored and treatment discontinuation should be considered if the patient develops any of the following conditions: heart condition associated with sudden cardiac death (SCD), arrhythmia requiring cardiopulmonary resuscitation, direct current cardioversion/defibrillation or overdrive pacing, arrhythmia associated with SCD, any clinically significant arrhythmia that is not treated or controlled, QTc on electrocardiogram (ECG) > 0.46 sec, or heart rate or blood pressure > 2 SD above the mean for age. All patients being considered for treatment with stimulant medications should have a careful history taken, including assessment for a family history of sudden death or ventricular arrhythmias, and a physical exam to assess for the presence of cardiac disease. If cardiac disease is suspected, further cardiac evaluation including an ECG and echocardiogram is warranted. For pediatric patients, the AHA states that it is reasonable to obtain a baseline ECG as a part of the initial evaluation. If a child or adolescent has any significant findings on physical examination, ECG, or family history, consult a pediatric cardiologist before initiating the stimulant medication. Once the medication is started, a repeat ECG may be helpful if the original ECG was obtained before the child was 12 years old, if cardiac symptoms develop, or there is a change in family history.

DEA CLASS

Rx, schedule II

DESCRIPTION

Oral CNS stimulant; is the dextro-isomer of racemic amphetamine and twice as potent
Used for narcolepsy and as an adjunct in the treatment of attention-deficit disorder
Many states in the US restrict use as an anorectic agent

COMMON BRAND NAMES

Dexedrine, Dexedrine Spansule, DextroStat, Liquadd, ProCentra, Zenzedi

HOW SUPPLIED

Dexedrine Spansule/Dextroamphetamine/Dextroamphetamine Sulfate Oral Cap ER: 5mg, 10mg, 15mg
Dexedrine/Dextroamphetamine/Dextroamphetamine Sulfate/DextroStat/Zenzedi Oral Tab: 2.5mg, 5mg, 7.5mg, 10mg, 15mg, 20mg, 30mg
Dextroamphetamine/Dextroamphetamine Sulfate/Liquadd/ProCentra Oral Sol: 5mg, 5mL

DOSAGE & INDICATIONS

†Indicates off-label use

MAXIMUM DOSAGE

60 mg/day PO.

60 mg/day PO; individualize dosage based on response and tolerability.

60 mg/day PO.

6 years and older: 60 mg/day PO.
3 to 5 years: Maximum dosage information is not provided in the FDA-approved labeling; doses should not exceed 40 mg/day PO for immediate-release formulations. Do not use extended-release formulations.
Less than 3 years: Safety and efficacy have not been established.

Not indicated.

Not indicated.

DOSING CONSIDERATIONS

Specific guidelines for dosage adjustments in hepatic impairment are not available. Hepatic dysfunction has the potential to inhibit the elimination of amphetamines and result in prolonged exposure; use with caution and titrate dosages carefully.

Specific guidelines for dosage adjustments in renal impairment are not available. Renal dysfunction has the potential to inhibit the elimination of amphetamines and result in prolonged exposure; use with caution and titrate dosages carefully.

ADMINISTRATION

A MedGuide is available which informs patients about the cardiac and psychiatric risks associated with use, and should be provided by the authorized dispenser to each patient receiving a prescription.

STORAGE

Dexedrine:
– Store at controlled room temperature (between 68 and 77 degrees F)
Dexedrine Spansule:
– Store at controlled room temperature (between 68 and 77 degrees F)
DextroStat:
– Store at controlled room temperature (between 68 and 77 degrees F)
Liquadd :
– Store at controlled room temperature (between 68 and 77 degrees F)
ProCentra :
– Store at controlled room temperature (between 68 and 77 degrees F)
– Store in original container
Zenzedi:
– Store at controlled room temperature (between 68 and 77 degrees F)

CONTRAINDICATIONS / PRECAUTIONS

Dextroamphetamine is contraindicated for use in patients with known hypersensitivity or idiosyncrasy to the sympathomimetic amines or any component of these products.

Dextroamphetamine is contraindicated in patients with a history of substance abuse. Evaluate the child or adult patient for a history (or a family history of) abuse of prescription medicines or street drugs, or abuse or dependence on alcohol (alcoholism). Dextroamphetamine has a high potential for abuse. Administration of amphetamines for a prolonged period of time may lead to physical and psychological drug dependence. Misuse of amphetamines may cause sudden death and serious cardiovascular adverse events. The least amount reasonable should be prescribed or dispensed at one time in order to limit the potential for overuse or drug diversion. Symptoms of chronic intoxication include insomnia, irritability, change in personality, and psychotic symptoms that may be clinically indistinguishable from psychotic disorders.

Dextroamphetamine is contraindicated in patients in an agitated state. Stimulants such as dextroamphetamine should be used cautiously in those with bipolar disorder and/or mania due to the potential for manic episodes to occur. An assessment should be performed prior to initiation of therapy to determine the risk for bipolar disorder in patients presenting with symptoms of depression. Due to its toxic effects in overdose, dextroamphetamine should only be used in those with major depression or suicidal ideation when absolutely necessary. Aggression, hostility, and suicidal ideation or behaviors have been reported in both clinical trials and post-marketing experience with ADHD medications. Although causality has not been established and these behaviors may be inherent to ADHD, close monitoring is recommended. Patients and their caregivers should be advised to promptly report any changes in mood or behavior. If suicide-related events emerge during treatment, consideration should be given to dose reduction or drug discontinuation, especially if symptoms are severe, abrupt in onset, or were not part of the patient’s presenting symptoms. In psychotic individuals (e.g., schizophrenia), amphetamines may exacerbate behavioral disturbances, psychosis, or thought disorders.

Dextroamphetamine is contraindicated in patients with moderate to severe hypertension, advanced atherosclerosis, and symptomatic cardiovascular disease. Stimulant medications must be used very cautiously in patients with pre-existing hypertension, tachycardia, or other conditions in which a modest increase in blood pressure or heart rate could be detrimental. Stimulant medications cause a modest increase in average blood pressure (approximately 2—4 mmHg) and average heart rate (approximately 3—6 bpm); however, some individuals may have larger increases. Although these 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. Elevated blood pressure may require a dose reduction, discontinuation, and/or initiation of appropriate antihypertensive medication.

Dextroamphetamine is contraindicated in patients with moderate to severe hypertension, advanced arteriosclerosis, or symptomatic cardiac disease. The FDA recommends that, in general, stimulant medications not be used in patients with known serious cardiac structural abnormalities, a history of acute myocardial infarction, aortic stenosis, prosthetic heart valves, valvular heart disease, cardiomyopathy, ventricular dysfunction or heart failure, cardiac arrhythmias, coronary artery disease, or other serious cardiac problems. Stimulant medications may increase blood pressure or heart rate in some individuals, but more serious cardiac effects have also been associated with stimulant use. Sudden unexplained death (SUD) and myocardial infarction have occurred in adults receiving stimulants at standard dosages for attention-deficit hyperactivity-disorder (ADHD). Sudden death has also been associated with stimulant medications at usual doses in pediatrics with structural cardiac abnormalities or other serious heart problems. A large retrospective cohort study including over 1.2 million children and young adults 2—24 years of age did not find an increased risk of serious cardiovascular events in current users of drugs for the treatment of ADHD compared to nonusers (adjusted hazard ratio 0.75; 95% CI 0.31—1.85). Similar results were seen when current users of ADHD drugs were compared to former users and when current users with severe underlying cardiovascular disease were included in the analysis. The authors concluded that although the absolute magnitude of risk appears to be low, a modest increase in risk could not be ruled out. The American Heart Association (AHA) states that it is reasonable to consider the use of these medications in pediatric patients with congenital heart disease without current hemodynamic or arrhythmic concerns or congenital heart disease that is considered stable by the patient’s pediatric cardiologist, unless the cardiologist has specific concerns. However, these patients should be closely monitored and treatment discontinuation should be considered if the patient develops any of the following conditions: heart condition associated with sudden cardiac death (SCD), arrhythmia requiring cardiopulmonary resuscitation, direct current cardioversion/defibrillation or overdrive pacing, arrhythmia associated with SCD, any clinically significant arrhythmia that is not treated or controlled, QTc on electrocardiogram (ECG) > 0.46 sec, or heart rate or blood pressure > 2 SD above the mean for age. All patients being considered for treatment with stimulant medications should have a careful history taken, including assessment for a family history of sudden death or ventricular arrhythmias, and a physical exam to assess for the presence of cardiac disease. If cardiac disease is suspected, further cardiac evaluation including an ECG and echocardiogram is warranted. For pediatric patients, the AHA states that it is reasonable to obtain a baseline ECG as a part of the initial evaluation. If a child or adolescent has any significant findings on physical examination, ECG, or family history, consult a pediatric cardiologist before initiating the stimulant medication. Once the medication is started, a repeat ECG may be helpful if the original ECG was obtained before the child was 12 years old, if cardiac symptoms develop, or there is a change in family history.

Stroke has occurred in adults receiving stimulants at usual doses for ADHD ; therefore, patients with cerebrovascular disease should be closely monitored. Stimulant medications may increase blood pressure or heart rate in some individuals.

Dextroamphetamine is contraindicated in patients with glaucoma, due to the ability of sympathetic stimulation to block aqueous outflow and raise intraocular pressure. Occasionally, visual disturbance, such as change in visual accomodation or blurred vision, have been reported in individuals without ocular disease while they are taking dextroamphetamine. Patients should report any new visual disturbance as ophthalmic evaluation may be needed.

Dextroamphetamine is contraindicated for use in thyroid disease patients with hyperthyroidism, including thyrotoxicosis, as sympathomimetic stimulation may induce cardiac arrhythmias or other side effects.

Dextroamphetamine is classified as FDA pregnancy risk category C. There are no adequate and well controlled studies of dextroamphetamine use in pregnant women. Dextroamphetamine should only be used during pregnancy if the expected benefit to the mother clearly outweighs the potential fetal risk. Amphetamines have been shown to have both embryotoxic and teratogenic effects in some animals when administered at high doses. There is one case of a neonate born with a severe congenital bony deformity, tracheo-esophageal fistula, and anal atresia following maternal exposure to dextroamphetamine sulfate and lovastatin during the first trimester of pregnancy. However, most available data indicate that amphetamines are not teratogenic in humans. Among 671 mother-child pairs enrolled in the Collaborative Perinatal Project who had first trimester exposure to amphetamines and 1898 mother-child pairs with amphetamine exposures at any time during pregnancy, there was no evidence suggesting a relationship to large categories of major or minor malformations. Non-teratogenic effects are known to occur in human neonates who are born to mothers dependent on amphetamines. These have included increased incidences of premature births, low birth weights and length, lower occipitofrontal circumference, and physical withdrawal symptoms (e.g., abnormal sleep patterns, poor feeding, tremor, agitation, fatigue, and hypertonia). In one prospective comparison study, neonates exposed to cocaine, methamphetamine, or a combination of cocaine and narcotic in utero had a 35.1% incidence of cranial abnormalities (i.e., intraventricular hemorrhage, echodensities known to be associated with necrosis, and cavitary lesions) compared to a 5.3% incidence in normal infants as assessed by cranial ultrasonography. The authors speculated that the ultrasonographic abnormalities were probably related to the vasoconstrictive properties of the drugs. The effects of dextroamphetamine during labor and delivery are unknown.

According to the manufacturer, amphetamines are excreted into breast milk, and women who are taking amphetamines should refrain from breast-feeding. The effect of stimulant medication exposure via breast milk on the neurological development of the infant has not been well studied. Breast milk concentrations in one woman taking 20 mg daily of racemic amphetamine ranged from 55 to 138 ng/mL with milk to plasma ratios of 2.8 to 7.5. The infant was monitored for 24 months and no adverse effects from amphetamine exposure were noted. Similarly, there were no reports of neonatal insomnia or stimulation in 103 nursing infants whose mothers were taking various amounts of amphetamine. In one study of 4 women with attention deficit hyperactivity disorder receiving d-amphetamine (median dose 18 mg/day) while breast-feeding, the mean relative infant dose was 5.7% of the weight-adjusted maternal dose (range: 3.9 to 13.8%). Of the 3 infants in whom blood samples were obtained, plasma d-amphetamine levels were undetectable in one; d-amphetamine levels were approximately 6% and 14% of the corresponding maternal plasma concentrations in the remaining two infants. None of the four infants in the study showed any adverse effects. Methylphenidate may be considered an alternative to amphetamine agents in women who are breast-feeding an infant, although the medical use of stimulant medications has not been formally evaluated during lactation. The AAP previously considered amphetamines, when used as drugs of abuse, to be contraindicated in breast-feeding due to concerns of irritability and poor sleeping pattern in the infant. If breast-feeding cannot be avoided during administration of a stimulant, the nursing infant should be monitored for signs of central nervous system hyperactivity, including decreased appetite, insomnia, and irritability. If possible, long-term infant exposure to stimulants through breast milk should be avoided since the consequences of such exposure are unknown. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, health care providers are encouraged to report the adverse effect to the FDA.

Dextroamphetamine may precipitate motor or phonetic tics in those with Tourette’s syndrome. Some patients with Tourette’s syndrome may actually benefit from stimulant therapy; administer under close supervision and at the lowest effective dose.

The use of dextroamphetamine may cause dizziness, mask signs of fatigue or the need for rest, or impair the ability of a patient to participate in activities that require mental alertness. Patients should not perform such tasks, including driving or operating machinery, until they are aware of how this medication affects them.

Use dextroamphetamine with caution in patients with seizures or a history of a seizure disorder because the seizure threshold can be reduced, particularly during excess CNS stimulation (i.e., amphetamine overdosage). The effects of amphetamines on the seizure threshold, in normal therapeutic dosages, are less clear. Seizure threshold may be reduced in those with EEG abnormalities and rarely in patients without a seizure history or EEG abnormalities. If seizures occur, discontinuation of therapy is recommended.

The use of inhalational anesthetics during surgery may sensitize the myocardium to the effects of dextroamphetamine.

Amphetamines lower the seizure threshold. Because of a potential increased risk of seizures, amphetamines should not be used during intrathecal radiographic contrast administration. Dextroamphetamine should be discontinued 48 hours before the myelography and should not be resumed until at least 24 hours after the procedure.

Abrupt discontinuation of dextroamphetamine after chronic use is not recommended. Discontinuation may unmask severe mental depression or extreme fatigue, or precipitate withdrawal symptoms. Gradual withdrawal of therapy is recommended.

Dextroamphetamine may cause hypercortisolism, as amphetamines can cause a significant elevation in plasma corticosteroid concentrations. The elevation is greatest in the evening. Amphetamines may interfere with urinary steroid determinations; consider the possible effect of dextroamphetamine if determination of plasma corticosteroid concentrations is desired.

Dextroamphetamine should be used with caution in the geriatric patient for the treatment of attention deficit disorder (ADD/ADHD) or narcolepsy. Stimulant medications are used as the treatments of choice in the adult patient over 50 years of age with ADHD when behavioral and lifestyle modifications alone have failed to improve concerns associated with inattention, such as task focus and completion, or organization and time management. Medication should be titrated with low doses initially and with a slow increase. Debilitated or geriatric patients may be more susceptible to the CNS and sympathomimetic side effects of the amphetamines; use with caution in the older adult. Side effects of amphetamines or other stimulants are usually mild but may include mood or behavior changes, tremor, insomnia, increased blood pressure, headache, or gastroesophageal reflux or other GI complaints. Adults should have their blood pressure and heart rate checked at baseline and periodically during treatment. If treatment is considered necessary, periodically re-evaluate the long-term usefulness of the drug for the individual patient. According to the Beers Criteria, stimulants such as amphetamines are considered potentially inappropriate medications (PIMs) for use in geriatric patients with insomnia and should be avoided due to the potential for drug-induced CNS stimulant effects.

The elimination of amphetamine, including dextroamphetamine, is dependent on hepatic metabolism, urinary pH and urinary flow rates, as well as active secretion. Both hepatic disease and renal impairment have the potential to inhibit the elimination of amphetamines and result in prolonged exposures.

Children 3 years and older have been successfully treated for attention-deficit hyperactivity disorder (ADHD) with amphetamines. Safety and efficacy of dextroamphetamine have not been established in infants and children less than 3 years old. Sustained-release dextroamphetamine is not recommended for children less than 6 years of age. Amphetamines in general are not used for the management of obesity in children under 12 years of age. It should be noted that not all children with ADHD will require medication; non-drug measures are often instituted concurrently with drug therapy. Monitoring of the effectiveness of stimulant therapy by the health care prescriber, parents, and teachers is important; periodic reassessment of the need for medication is recommended. Appropriate stimulant therapy should not suppress normal emotions or intellectual ability; the occurrence of certain side effects may indicate a need for dosage reduction. In psychotic children, amphetamines may exacerbate behavioral disturbances, psychosis, or thought disorders. New onset psychotic or manic symptoms may develop in children and adolescents receiving therapeutic doses of stimulants. Discontinuation of therapy may be required. Although a direct causal relationship has not been established, aggressive behavior and hostility have been reported during use of some stimulants for ADHD in children. It is recommended to monitor for signs of aggression or worsening of pre-existing aggressive behavior when treatment is initiated. The potential for growth inhibition in pediatric patients should be monitored during stimulant therapy. Monitor height and weight parameters relative to age at treatment initiation and periodically thereafter (at minimum yearly). Patients who are not growing or gaining weight as expected may need to have their treatment interrupted. Data obtained on the effects of the stimulants on growth suppression in children 7—10 years of age suggested that regularly medicated children (7 days/week) had a temporary average slowing in growth of 2 cm in height and 2.7 kg in weight over 3 years. Data are inadequate to determine whether chronic use of stimulants causes long-term growth inhibition. Although data are limited, available studies do not indicate that stimulant use compromises the attainment of normal adult height and weight in most children. Sudden death has been reported in association with CNS stimulant treatment at usual doses in children with structural cardiac abnormalities or other serious heart problems (i.e., aortic stenosis, cardiomyopathy, congenital heart disease, prosthetic heart valves, valvular heart disease, ventricular dysfunction). Some case reports have involved concomitant medications, such as tricyclic antidepressants. A large retrospective cohort study including over 1.2 million children and young adults 2 to 24 years of age did not find an increased risk of serious cardiovascular events, including sudden cardiac death, myocardial infarction, or stroke in current users of drugs for the treatment of ADHD compared to nonusers (adjusted hazard ratio 0.75; 95% CI 0.31—1.85). The authors concluded that although the absolute magnitude of risk appears to be low, a modest increase in risk could not be ruled out. Although some structural cardiac abnormalities alone may carry an increased risk of sudden death, stimulant products generally should not be used in patients with known structural cardiac abnormalities or other serious heart conditions. Exceptions to this warning do exist, but careful screening and monitoring is recommended by the American Heart Association (see separate paragraph detailing cardiac contraindications and precautions).

Dextroamphetamine is contraindicated in patients who have received MAOI therapy within the past 14 days. MAOI antidepressants slow amphetamine metabolism, potentiating their effect on the release of norepinephrine and other monoamines from adrenergic nerve endings. This may precipitate hypertensive crisis, malignant hyperthermia, and a variety of toxic neurologic effects; these events can be fatal.

Stimulant medications are associated with peripheral vasculopathy, including Raynaud’s phenomenon. Worsening of peripheral vascular disease is possible. Effects on circulation have been observed with therapeutic doses at different times throughout therapy in all age groups. Signs and symptoms are usually intermittent and mild and generally improve after reduction in dose or discontinuation of drug. However, very rare sequelae include digital skin ulcer and/or soft tissue breakdown. Carefully monitor all patients for digital changes during treatment with stimulant medications, especially those with pre-existing circulation problems. Instruct patients to seek immediate medical attention if any new digital numbness, pain, skin discoloration, or temperature sensitivity occur, or if unexplained wounds appear on their fingers or toes. Further clinical evaluation (e.g., rheumatology referral) may be appropriate for certain patients.

Obesity treatment with dextroamphetamine should be initiated only in weight reduction programs for patients in whom alternative therapies, including repeated dietary reduction, exercise, or other medications have been ineffective. Eating disorders, such as anorexia nervosa or bulimia nervosa, should be ruled out prior to treatment with amphetamines. Patients with eating disorders may have physiologic complications, such as metabolic and electrolyte abnormalities, which increase their susceptibility to the adverse effects of stimulants. In addition, the abuse potential of stimulants in weight loss induction should be considered in patients with an eating disorder.