tained increases in the concentration of d-amphetamine in the brain; cardiovascular effects can be potentiated. monitor frequently and adjust or use alternative therapy based on clinical response. examples of tricyclic antidepressants include desipramine, protriptyline. cyp2d6 inhibitors the concomitant use of dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate and amphetamine sulfate tablets and cyp2d6 inhibitors may increase the exposure of dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate and amphetamine sulfate tablets compared to the use of the drug alone and increase the risk of serotonin syndrome. initiate with lower doses and monitor patients for signs and symptoms of serotonin syndrome particularly during dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate and amphetamine sulfate tablets initiation and after a dosage increase. if serotonin syndrome occurs, discontinue dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate and amphetamine sulfate tablets and the cyp2d6 inhibitor [see warnings, overdosage ]. examples of cyp2d6 inhibitors include paroxetine and fluoxetine (also serotonergic drugs), quinidine, ritonavir. serotonergic drugs the concomitant use of dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate and amphetamine sulfate tablets and serotonergic drugs increases the risk of serotonin syndrome. initiate with lower doses and monitor patients for signs and symptoms of serotonin syndrome, particularly during dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate and amphetamine sulfate tablets initiation or dosage increase. if serotonin syndrome occurs, discontinue dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate and amphetamine sulfate tablets and the concomitant serotonergic drug(s) [see warnings and precautions ]. examples of serotonergic drugs include selective serotonin reuptake inhibitors (ssri), serotonin norepinephrine reuptake inhibitors (snri), triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, st. john’s wort. mao inhibitors 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. do not administer dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate and amphetamine sulfate tablets concomitantly or within 14 days after discontinuing maoi [see contraindications and warnings ]. examples of maois include selegiline, tranylcypromine, isocarboxazid, phenelzine, linezolid, methylene blue. antihistamines amphetamines may counteract the sedative effect of antihistamines. antihypertensives amphetamines may antagonize the hypotensive effects of antihypertensives. chlorpromazine chlorpromazine blocks dopamine and norepinephrine receptors, thus inhibiting the central stimulant effects of amphetamines, and can be used to treat amphetamine poisoning. ethosuximide amphetamines may delay intestinal absorption of ethosuximide. haloperidol haloperidol blocks dopamine receptors, thus inhibiting the central stimulant effects of amphetamines. lithium carbonate the anorectic and stimulatory effects of amphetamines may be inhibited by lithium carbonate. meperidine amphetamines potentiate the analgesic effect of meperidine. methenamine therapy urinary excretion of amphetamines is increased, and efficacy is reduced, by acidifying agents used in methenamine therapy. norepinephrine amphetamines enhance the adrenergic effect of norepinephrine. phenobarbital amphetamines may delay intestinal absorption of phenobarbital; coadministration of phenobarbital may produce a synergistic anticonvulsant action. phenytoin amphetamines may delay intestinal absorption of phenytoin; coadministration of phenytoin may produce a synergistic anticonvulsant action. propoxyphene in cases of propoxyphene overdosage, amphetamine cns stimulation is potentiated and fatal convulsions can occur. proton pump inhibitors time to maximum concentration (tmax) of amphetamine is decreased compared to when administered alone. monitor patients for changes in clinical effect and adjust therapy based on clinical response. an example of a proton pump inhibitor is omeprazole. veratrum alkaloids amphetamines inhibit the hypotensive effect of veratrum alkaloids.

on; avoids tasks requiring sustained mental effort; loses things; easily distracted; forgetful. for the hyperactive-impulsive type, at least six of the following symptoms must have persisted for at least 6 months: fidgeting/squirming; leaving seat; inappropriate running/climbing; difficulty with quiet activities; “on the go;” excessive talking; blurting answers; can't wait turn; intrusive. the combined type requires both inattentive and hyperactive-impulsive criteria to be met. special diagnostic considerations specific etiology of this syndrome is unknown, and there is no single diagnostic test. adequate diagnosis requires the use not only of medical but of special psychological, educational, and social resources. learning may or may not be impaired. the diagnosis must be based upon a complete history and evaluation of the child and not solely on the presence of the required number of dsm-iv ® characteristics. need for comprehensive treatment program dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate and amphetamine sulfate tablets is indicated as an integral part of a total treatment program for adhd that may include other measures (psychological, educational, social) for patients with this syndrome. drug treatment may not be indicated for all children with this syndrome. stimulants are not intended for use in the child 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. long-term use the effectiveness of dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate and amphetamine sulfate tablets for long-term use has not been systematically evaluated in controlled trials. therefore, the physician who elects to use dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate and amphetamine sulfate tablets for extended periods should periodically re­evaluate the long-term usefulness of the drug for the individual patient.

ood 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 [see contraindications ]. hypertension and other cardiovascular conditions stimulant medications cause a modest increase in average blood pressure (about 2 to 4 mmhg) and average heart rate (about 3 to 6 bpm) [see adverse reactions ], 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 [see contraindications ]. 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 preexisting psychotic disorder. bipolar illness 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. 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 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 3482 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 will likely have this effect as well. therefore, growth should be monitored during treatment with stimulants, and patients who are not growing or gaining 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 seizure, 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. peripheral vasculopathy, including raynaud's phenomenon stimulants, including dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate and amphetamine sulfate tablets, used to treat adhd are associated with peripheral vasculopathy, including raynaud’s phenomenon. signs and symptoms are usually intermittent and mild; however, very rare sequelae include digital ulceration and/or soft tissue breakdown. effects of peripheral vasculopathy, including raynaud’s phenomenon, were observed in postmarketing reports at different times and at therapeutic doses in all age groups throughout the course of treatment. signs and symptoms generally improve after reduction in dose or discontinuation of drug. careful observation for digital changes is necessary during treatment with adhd stimulants. further clinical evaluation (e.g., rheumatology referral) may be appropriate for certain patients. serotonin syndrome 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 monoamine oxidase inhibitors (maois), selective serotonin reuptake inhibitors (ssris), serotonin norepinephrine reuptake inhibitors (snris), triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, and st. john’s wort [see drug interactions ]. amphetamines and amphetamine derivatives are known to be metabolized, to some degree, by cytochrome p450 2d6 (cyp2d6) and display minor inhibition of cyp2d6 metabolism [see clinical pharmacology ]. the potential for a pharmacokinetic interaction exists with the coadministration of cyp2d6 inhibitors which may increase the risk with increased exposure to dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate and amphetamine sulfate tablets. in these situations, consider an alternative non­serotonergic drug or an alternative drug that does not inhibit cyp2d6 [see drug interactions ]. serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, delirium, and coma), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). concomitant use of dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate and amphetamine sulfate tablets with maoi drugs is contraindicated [see contraindications ]. discontinue treatment with dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate and amphetamine sulfate tablets and any concomitant serotonergic agents immediately if the above symptoms occur, and initiate supportive symptomatic treatment. if concomitant use of dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate and amphetamine sulfate tablets with other serotonergic drugs or cyp2d6 inhibitors is clinically warranted, initiate dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate and amphetamine sulfate tablets with lower doses, monitor patients for the emergence of serotonin syndrome during drug initiation or titration, and inform patients of the increased risk for serotonin syndrome. visual disturbance difficulties with accommodation and blurring of vision have been reported with stimulant treatment.

recurrence of behavioral symptoms sufficient to require continued therapy. narcolepsy usual dose 5 mg to 60 mg per day in divided doses, depending on the individual patient response. narcolepsy seldom occurs in children under 12 years of age; however, when it does, dextroamphetamine sulfate may be used. the suggested initial dose for patients aged 6 to 12 is 5 mg daily; daily dose may be raised in increments of 5 mg at weekly intervals until optimal response is obtained. in patients 12 years of age and older, start with 10 mg daily; daily dosage may be raised in increments of 10 mg at weekly intervals until optimal response is obtained. if bothersome adverse reactions appear (e.g., insomnia or anorexia), dosage should be reduced. give first dose on awakening; additional doses (1 or 2) at intervals of 4 to 6 hours.

tained increases in the concentration of d-amphetamine in the brain; cardiovascular effects can be potentiated. monitor frequently and adjust or use alternative therapy based on clinical response. examples of tricyclic antidepressants include desipramine, protriptyline. cyp2d6 inhibitors the concomitant use of dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate and amphetamine sulfate tablets and cyp2d6 inhibitors may increase the exposure of dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate and amphetamine sulfate tablets compared to the use of the drug alone and increase the risk of serotonin syndrome. initiate with lower doses and monitor patients for signs and symptoms of serotonin syndrome particularly during dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate and amphetamine sulfate tablets initiation and after a dosage increase. if serotonin syndrome occurs, discontinue dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate and amphetamine sulfate tablets and the cyp2d6 inhibitor [see warnings, overdosage ]. examples of cyp2d6 inhibitors include paroxetine and fluoxetine (also serotonergic drugs), quinidine, ritonavir. serotonergic drugs the concomitant use of dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate and amphetamine sulfate tablets and serotonergic drugs increases the risk of serotonin syndrome. initiate with lower doses and monitor patients for signs and symptoms of serotonin syndrome, particularly during dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate and amphetamine sulfate tablets initiation or dosage increase. if serotonin syndrome occurs, discontinue dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate and amphetamine sulfate tablets and the concomitant serotonergic drug(s) [see warnings and precautions ]. examples of serotonergic drugs include selective serotonin reuptake inhibitors (ssri), serotonin norepinephrine reuptake inhibitors (snri), triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, st. john’s wort. mao inhibitors 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. do not administer dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate and amphetamine sulfate tablets concomitantly or within 14 days after discontinuing maoi [see contraindications and warnings ]. examples of maois include selegiline, tranylcypromine, isocarboxazid, phenelzine, linezolid, methylene blue. antihistamines amphetamines may counteract the sedative effect of antihistamines. antihypertensives amphetamines may antagonize the hypotensive effects of antihypertensives. chlorpromazine chlorpromazine blocks dopamine and norepinephrine receptors, thus inhibiting the central stimulant effects of amphetamines, and can be used to treat amphetamine poisoning. ethosuximide amphetamines may delay intestinal absorption of ethosuximide. haloperidol haloperidol blocks dopamine receptors, thus inhibiting the central stimulant effects of amphetamines. lithium carbonate the anorectic and stimulatory effects of amphetamines may be inhibited by lithium carbonate. meperidine amphetamines potentiate the analgesic effect of meperidine. methenamine therapy urinary excretion of amphetamines is increased, and efficacy is reduced, by acidifying agents used in methenamine therapy. norepinephrine amphetamines enhance the adrenergic effect of norepinephrine. phenobarbital amphetamines may delay intestinal absorption of phenobarbital; coadministration of phenobarbital may produce a synergistic anticonvulsant action. phenytoin amphetamines may delay intestinal absorption of phenytoin; coadministration of phenytoin may produce a synergistic anticonvulsant action. propoxyphene in cases of propoxyphene overdosage, amphetamine cns stimulation is potentiated and fatal convulsions can occur. proton pump inhibitors time to maximum concentration (tmax) of amphetamine is decreased compared to when administered alone. monitor patients for changes in clinical effect and adjust therapy based on clinical response. an example of a proton pump inhibitor is omeprazole. veratrum alkaloids amphetamines inhibit the hypotensive effect of veratrum alkaloids.

to amphetamine (d- or d,l-), at doses similar to those used clinically, can result in long-term neurochemical and behavioral alterations. reported behavioral effects include learning and memory deficits, altered locomotor activity, and changes in sexual function. there are no adequate and well-controlled studies in pregnant women. there has been one report of severe congenital bony deformity, tracheo-esophageal 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. amphetamines should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. nonteratogenic effects 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.

e t 1/2 of the l-isomer (9.77 to 11 hours vs.11.5 to 13.8 hours). the pk parameters (c max , auc 0-inf ) of d- and l-amphetamine increased approximately three-fold from 10 mg to 30 mg indicating dose-proportional pharmacokinetics. the effect of food on the bioavailability of dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate and amphetamine sulfate tablets has not been studied. metabolism and excretion amphetamine is reported to be oxidized at the 4 position of the benzene ring to form 4-­hydroxyamphetamine, or on the side chain α or β carbons to form alpha-hydroxy-amphetamine or norephedrine, respectively. norephedrine and 4-hydroxy-amphetamine are both active and each is subsequently oxidized to form 4-hydroxy-norephedrine. alpha-hydroxy-amphetamine undergoes deamination to form phenylacetone, which ultimately forms benzoic acid and its glucuronide and the glycine conjugate hippuric acid. although the enzymes involved in amphetamine metabolism have not been clearly defined, cyp2d6 is known to be involved with formation of 4-hydroxy-amphetamine. since cyp2d6 is genetically polymorphic, population variations in amphetamine metabolism are a possibility. amphetamine is known to inhibit monoamine oxidase, whereas the ability of amphetamine and its metabolites to inhibit various p450 isozymes and other enzymes has not been adequately elucidated. in vitro experiments with human microsomes indicate minor inhibition of cyp2d6 by amphetamine and minor inhibition of cyp1a2, 2d6, and 3a4 by one or more metabolites. however, due to the probability of auto-inhibition and the lack of information on the concentration of these metabolites relative to in vivo concentrations, no predications regarding the potential for amphetamine or its metabolites to inhibit the metabolism of other drugs by cyp isozymes in vivo can be made. with normal urine phs approximately half of an administered dose of amphetamine is recoverable in urine as derivatives of alpha-hydroxy-amphetamine and approximately another 30% to 40% of the dose is recoverable in urine as amphetamine itself. since amphetamine has a pka of 9.9, urinary recovery of amphetamine is highly dependent on ph and urine flow rates. alkaline urine phs result in less ionization and reduced renal elimination, and acidic phs and high flow rates result in increased renal elimination with clearances greater than glomerular filtration rates, indicating the involvement of active secretion. urinary recovery of amphetamine has been reported to range from 1% to 75%, depending on urinary ph, with the remaining fraction of the dose hepatically metabolized. consequently, both hepatic and renal dysfunction have the potential to inhibit the elimination of amphetamine and result in prolonged exposures. in addition, drugs that affect urinary ph are known to alter the elimination of amphetamine, and any decrease in amphetamine's metabolism that might occur due to drug interactions or genetic polymorphisms is more likely to be clinically significant when renal elimination is decreased [see precautions ].

se in the ames test, and negative responses in the in vitro sister chromatid exchange and chromosomal aberration assays. amphetamine, in the enantiomer ratio present in dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate and amphetamine sulfate tablets (immediate-release)(d- to l- ratio of 3:1), did not adversely affect fertility or early embryonic development in the rat at doses of up to 20 mg/kg/day (approximately 5 times the maximum recommended human dose of 30 mg/day on a mg/m 2 body surface area basis).

ablets ndc 64850-502-01 500 tablets ndc 64850-502-05 12.5 mg: a peach, oval biconvex tablet debossed with “e” over “503” separated by a full score on one side and four partial bisects on the other side debossed with 12 1/2. 30 tablets ndc 64850-503-30 100 tablets ndc 64850-503-01 500 tablets ndc 64850-503-05 15 mg: a peach, oval, flat-faced, beveled-edge tablet debossed with “e” over “504” separated by a full score on one side and two partial bisects and a full score on the other side debossed with 1 │ 5. 30 tablets ndc 64850-504-30 100 tablets ndc 64850-504-01 500 tablets ndc 64850-504-05 20 mg: a peach, oval, flat-faced, beveled-edge tablet with two partial bisects on one side debossed with “e” over “505” and two partial bisects and a full score on the other side debossed with 2 │ 0. 30 tablets ndc 64850-505-30 100 tablets ndc 64850-505-01 500 tablets ndc 64850-505-05 30 mg: a peach, oval, biconvex tablet with two partial bisects on one side debossed with “e” over “506” and two partial bisects and a full score on the other side debossed with 3 │ 0. 30 tablets ndc 64850-506-30 100 tablets ndc 64850-506-01 500 tablets ndc 64850-506-05 dispense in a tight, light-resistant container. store at 20° to 25°c (68° to 77°f) [see usp controlled room temperature]. distributed by: elite laboratories, inc. northvale, nj 07647 rev. 09/22 in0522

t the end of this document. circulation problems in fingers and toes [ peripheral vasculopathy, including raynaud's phenomenon] instruct patients beginning treatment with dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate and amphetamine sulfate tablets about the risk of peripheral vasculopathy, including raynaud’s phenomenon, and associated signs and symptoms: fingers or toes may feel numb, cool, painful, and/or may change color from pale, to blue, to red. instruct patients to report to their physician any new numbness, pain, skin color change, or sensitivity to temperature in fingers or toes. instruct patients to call their physician immediately with any signs of unexplained wounds appearing on fingers or toes while taking dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate and amphetamine sulfate tablets. further clinical evaluation (e.g., rheumatology referral) may be appropriate for certain patients.