ADDERALL XR 25mg. Tablets.

DESCRIPTION

Central nervous system (CNS) stimulant
Used for attention-deficit hyperactivity disorder (ADHD) and narcolepsy
Patients with structural heart defects, cardiomyopathy, or heart-rhythm disturbances may be at risk for adverse cardiac events

COMMON BRAND NAMES

Adderall, Adderall XR, Mydayis

HOW SUPPLIED

Adderall XR/Amphetamine Aspartate, Amphetamine Sulfate, Dextroamphetamine Saccharate, Dextroamphetamine Sulfate/Amphetamine, Dextroamphetamine/Mydayis Oral Cap ER: 5mg, 10mg, 15mg, 20mg, 25mg, 30mg
Adderall/Amphetamine Aspartate, Amphetamine Sulfate, Dextroamphetamine Saccharate, Dextroamphetamine Sulfate/Amphetamine, Dextroamphetamine Oral Tab: 5mg, 7.5mg, 10mg, 12.5mg, 15mg, 20mg, 30mg

DOSAGE & INDICATIONS

MAXIMUM DOSAGE

60 mg/day PO for ADHD or narcolepsy for immediate-release tablets. For extended-release Adderall XR capsules, 20 mg/day PO is the recommended dose; in clinical trials for adult ADHD, 60 mg/day PO was the highest titration dose used. For extended-release Mydayis capsules, 50 mg/day PO for ADHD.

60 mg/day PO for ADHD or narcolepsy for immediate-release tablets. For extended-release capsules, geriatric patients have not been specifically evaluated.

40 mg/day PO for ADHD or 60 mg/day PO for narcolepsy using immediate-release tablets; some experts recommend an off-label maximum of 60 mg/day PO if weight is greater than 50 kg for the treatment of ADHD. In clinical trials of extended-release Adderall XR capsules, titration doses were allowed up to 40 mg/day PO for weight 75 kg or less and from 50 to 60 mg/day PO for weight more than 75 kg; however, there was no consistent evidence that doses above 20 mg/day PO conferred additional benefit. For extended-release Mydayis capsules, 25 mg/day PO for ADHD.

6 years and older: 40 mg/day PO for ADHD or 60 mg/day PO for narcolepsy using immediate-release tablets; some experts recommend an off-label maximum of 60 mg/day PO if weight is more than 50 kg for the treatment of ADHD. Maximum 30 mg/day PO for ADHD using extended-release Adderall XR capsules. For extended-release Mydayis capsules, safety and efficacy have not been established.
3 to 5 years: Maximum dosage information is not provided by FDA-approved labeling; doses should not exceed 40 mg/day PO for immediate-release tablets. Do not use extended-release capsules.
Less than 3 years: Safety and efficacy have not been established.

Not indicated.

DOSING CONSIDERATIONS

Specific guidelines for dosage adjustments in hepatic impairment are not available; the FDA-approved product labeling states that hepatic dysfunction has the potential to inhibit the elimination of amphetamine and result in prolonged exposures; use caution.

Immediate-release products:
Specific guidelines for dosage adjustments of immediate-release products in renal impairment in adults and pediatric patients are not available; the FDA-approved product labeling states that renal dysfunction has the potential to inhibit the elimination of amphetamine and result in prolonged exposures; use caution.

ADULT RENAL DOSE ADJUSTMENTS
Adult renal dose adjustments for extended-release capsules (Adderall XR)
eGFR 15 to 29 mL/minute/1.73 m2: 15 mg PO once daily in the morning.
eGFR less than 15 mL/minute/1.73 m2: Initiation of extended-release capsules (Adderall XR) is not recommended.

Adult renal dose adjustments for extended-release capsules (Mydayis)
eGFR 15 to 29 mL/minute/1.73 m2: Starting dose is is 12.5 mg PO once daily. Maximum dose is 25 mg PO once daily.
eGFR less than 15 mL/minute/1.73 m2: Initiation of extended-release capsules (Mydayis) is not recommended.

PEDIATRIC RENAL DOSE ADJUSTMENTS
Pediatric renal dose adjustments (6 to 17 years of age) for extended-release capsules (Adderall XR)
eGFR 15 to 29 mL/minute/1.73 m2: 5 mg PO once daily is the recommended dose. The maximum dose for children 6 to 12 years of age is 20 mg PO once daily.
eGFR less than 15 mL/minute/1.73 m2: Initiation of extended-release capsules (Adderall XR) is not recommended.

Pediatric renal dose adjustments (13 to 17 years of age) for extended-release capsules (Mydayis)
eGFR 15 to 29 mL/minute/1.73 m2: Starting and maximum dose is is 12.5 mg PO daily.
eGFR less than 15 mL/minute/1.73 m2: Initiation of extended-release capsules (Mydayis) is not recommended.

ADMINISTRATION

STORAGE

Adderall:
– Protect from moisture
– Store at controlled room temperature (between 68 and 77 degrees F)
Adderall XR:
– Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
Mydayis:
– Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F

CONTRAINDICATIONS / PRECAUTIONS

Amphetamine; dextroamphetamine mixed salts combinations are contraindicated for use in patients with known hypersensitivity to amphetamines or any component of these products.

Amphetamine; 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). Amphetamine; dextroamphetamine combinations have 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.

Amphetamine; dextroamphetamine combinations are contraindicated in patients in an agitated state. Stimulants such as amphetamine; dextroamphetamine should be used cautiously in those with bipolar disorder and/or mania due to the potential for manic episodes to occur in such patients. 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, amphetamine; 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.

Amphetamine; dextroamphetamine is contraindicated in patients with symptomatic cardiovascular disease, advanced atherosclerosis, and moderate to severe hypertension. However, patients with even mild hypertension or tachycardia should be closely monitored while taking amphetamines. Use stimulant medications with caution in patients for whom an elevation in blood pressure or heart rate may be clinically significant. Stimulant medications cause a modest increase in average blood pressure (approximately 2 to 4 mmHg) and average heart rate (approximately 3 to 6 bpm); however, some individuals may have larger increases. Elevated blood pressure may require a dose reduction, discontinuation, and/or initiation of appropriate antihypertensive medication. Periodic blood pressure and heart rate monitoring is recommended in all patients taking stimulant medications. Adolescents with ADHD were enrolled in a 4-week controlled comparative trial of Adderall XR vs. placebo; 7 of 64 (11%) placebo-treated patients and 7 of 100 (7%) patients receiving Adderall XR had elevations in systolic blood pressures > 15 mmHg. Dose-related blood pressure elevations have also been noted in single dose studies. All increases were transient, appeared maximal at 2 to 4 hours post dose and were not associated with symptoms.

Amphetamine; dextroamphetamine is contraindicated in patients with symptomatic cardiac disease, advanced arteriosclerosis, and moderate to severe hypertension. 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; 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 to 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 to 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) more than 0.46 sec, or heart rate or blood pressure more than 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 such as amphetamine; dextroamphetamine at usual doses for ADHD ; therefore, those with cerebrovascular disease should be closely monitored. Stimulant medications may increase blood pressure or heart rate in some individuals.

Children 3 years of age and older have been successfully treated for attention-deficit hyperactivity-disorder (ADHD) with amphetamines. It should be noted that not all children with ADHD will require medication; non-drug measures are often instituted concurrently with drug therapy. Amphetamines are not recommended for use in children and infants younger than 3 years of ageThe efficacy of stimulant therapy in children with ADHD is substantiated by a large body of evidence. However, do not use the Mydayis extended-release capsule formulation in children younger than 13 years of age, as safety and efficacy are not established, and a higher rate of adverse reactions was noted with this dosage form during clinical trials compared with adolescents. Safety and efficacy of Adderall XR (and generic equivalents) ha ve been established in pediatric patients 6 years and older. However, the efficacy of stimulant therapy in children with ADHD is substantiated by a large body of evidence. 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 in the child or adolescent; 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. Amphetamines are associated with a reduced appetite and weight loss. Over time weight will increase but not to the amount expected based on CDC normative values. 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. In one controlled trial in adolescents, the mean weight change from baseline within the initial 4 weeks of therapy was -1.1 pounds and -2.8 pounds, respectively, for patients receiving 10 mg and 20 mg Adderall XR. Higher doses were associated with greater weight loss within the initial 4 weeks of treatment. Data obtained on the effects of the stimulants on growth suppression in children 7 to 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. The long-term effects of stimulants on brain development and physical growth in children are unknown. 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 to 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.

Amphetamine; dextroamphetamine is contraindicated for use patients with hyperthyroidism, including thyrotoxicosis, since sympathomimetic stimulation may induce cardiac arrhythmias or other side effects.

Amphetamine; dextroamphetamine is contraindicated in patients with glaucoma. The sympathetic stimulation of amphetamines blocks aqueous outflow and raises intraocular pressure. Occasionally, visual disturbance, such as blurred vision and accommodation difficulties, have been reported in individuals without ocular disease while they are taking amphetamine; dextroamphetamine. Patients should report any new visual disturbance as ophthalmic evaluation may be needed.

Amphetamines are excreted in human breast milk by the lactating mother. Limited data from published literature have indicated a resulting infant dose of 2% to 13.8% of the maternal weight-adjusted dosage and a milk to plasma ratio ranging between 1.9 and 7.5. There are no reports of adverse effects on the breastfed infant. Long-term neurodevelopmental effects on infants are unknown. Large dosages of dextroamphetamine might interfere with milk production, especially in women whose lactation is not well established. Due to the potential for serious adverse reactions in nursing infants (cardiovascular reactions, blood pressure and heart rate increase, suppression of growth, and peripheral vasculopathy), breast-feeding is not recommended during the use of amphetamines. 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 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.

There are limited published literature and postmarketing reports on the use of amphetamine; dextroamphetamine during pregnancy; however, the data are insufficient to determine any drug-associated risks. Because stimulants cause vasoconstriction, they may decrease placental perfusion. Neonates born to stimulant-dependent mothers are at increased risk for premature delivery and low birth weight. In addition, neonates with in utero exposure to stimulants may experience withdrawal after delivery; monitor the newborn for symptoms of withdrawal such as feeding difficulty, irritability, agitation, and excessive drowsiness. Amphetamine; dextroamphetamine combinations should only be used during pregnancy if the expected benefit to the mother clearly outweighs the potential fetal risk. 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 1,898 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. 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 newborns as assessed by cranial ultrasonography. The authors speculated that the ultrasonographic abnormalities were probably related to the vasoconstrictive properties of the drugs.

Amphetamine; 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.

The use of amphetamine; 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 amphetamine; dextroamphetamine with caution in patients with 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 amphetamines and other sympathomimetic drugs.

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

Abrupt discontinuation of amphetamine; 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.

Amphetamine; dextroamphetamine has not been systematically studied in the geriatric population for use in 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.

Amphetamine; 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 amphetamine; dextroamphetamine if determination of plasma corticosteroid concentrations is desired.

Use amphetamine; dextroamphetamine with caution in patients with significant hepatic disease or renal impairment. The elimination of amphetamine; 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 amphetamine and result in prolonged exposures. Amphetamine; dextroamphetamine extended-release product dosages should be reduced in patients with an eGFR less than 30 mL/minute/1.73 m2, and use of these dosage forms in patients with renal failure (end-stage renal disease) is not recommended.

Amphetamine; dextroamphetamine is contraindicated in patients who have received MAOI therapy, including linezolid or intravenous methylene blue, 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, serotonin syndrome, and a variety of toxic neurologic effects; these events can be fatal. Increased risk for serotonin syndrome also may occur when amphetamines are co-administered with serotonergic agents (e.g., SSRIs, SNRIs, triptans, and others), and may also occur during overdosage situations. If serotonin syndrome occurs, discontinue amphetamine; dextroamphetamine and all other serotonergic agents, and initiate supportive treatment.

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.

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. The use of sympathomimetic drugs for weight loss has been associated with serious cardiovascular adverse events. Amphetamine; dextroamphetamine is not indicated or recommended for obesity treatment.