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 sulfate extended-release capsules and cyp2d6 inhibitors may increase the exposure of dextroamphetamine sulfate extended-release capsules 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 sulfate extended-release capsules initiation and after a dosage increase. if serotonin syndrome occurs, discontinue dextroamphetamine sulfate extended-release capsules 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 sulfate extended-release capsules 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 sulfate extended-release capsules initiation or dosage increase. if serotonin syndrome occurs, discontinue dextroamphetamine sulfate extended-release capsules 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 sulfate extended-release capsules concomitantly or within 14 days after discontinuing maoi ( see contraindications and warnings ). examples of maois include selegiline, tranylcypromine, isocarboxazid, phenelzine, linezolid, methylene blue. proton pump inhibitors time to maximum concentration (t max ) 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. antihistamines amphetamines may counteract the sedative effect of antihistamines. antihypertensives amphetamines may antagonize the hypotensive effects of antihypertensives. chlorpromazine chlorpromazine blocks dopamine and norepinephrine reuptake, 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 and norepinephrine reuptake, thus inhibiting the central stimulant effects of amphetamines. lithium carbonate the 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; co-administration of phenobarbital may produce a synergistic anticonvulsant action. phenytoin amphetamines may delay intestinal absorption of phenytoin; co-administration of phenytoin may produce a synergistic anticonvulsant action. propoxyphene in cases of propoxyphene overdosage, amphetamine cns stimulation is potentiated and fatal convulsions can occur. veratrum alkaloids amphetamines inhibit the hypotensive effect of veratrum alkaloids. drug/laboratory test interactions amphetamines can cause a significant elevation in plasma corticosteroid levels. this increase is greatest in the evening. amphetamines may interfere with urinary steroid determinations. carcinogenesis/mutagenesis mutagenicity studies and long-term studies in animals to determine the carcinogenic potential of dextroamphetamine sulfate extended-release capsules have not been performed.

failure to follow through on tasks; poor organization; avoids tasks requiring sustained mental effort; loses things; easily distracted; forgetful. for the hyperactive-impulsive type, at least 6 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 of medical and 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 patient and not solely on the presences of the required number of dsm-iv characteristics. need for comprehensive treatment program dextroamphetamine sulfate extended-release capsules are 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 patients with this syndrome. stimulants are not intended for use in patients who exhibit 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 patient’s symptoms.

hildren 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 mmhg to 4 mmhg) and average heart rate (about 3 bpm to 6 bpm), and individuals may have larger increases. while the mean changes alone would not be expected to have short-term consequences, all patients should be monitored for larger changes in heart rate and blood pressure. caution is indicated in treating patients whose underlying medical conditions might be compromised by increases in blood pressure or heart rate, e.g., those with pre-existing 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 pre-existing psychosis administration of stimulants may exacerbate symptoms of behavior disturbance and thought disorder in patients with a pre-existing psychotic disorder. bipolar illness particular care should be taken in using stimulants to treat adhd in patients with comorbid bipolar disorder because of concern for possible induction of a mixed/manic episode in such patients. prior to initiating treatment with a stimulant, patients with comorbid depressive symptoms should be adequately screened to determine if they are at risk for bipolar disorder; such screening should include a detailed psychiatric history, including a family history of suicide, bipolar disorder, and depression. emergence of new psychotic or manic symptoms treatment emergent psychotic or manic symptoms, e.g., hallucinations, delusional thinking, or mania in children and adolescents without a prior history of psychotic illness or mania can be caused by stimulants at usual doses. if such symptoms occur, consideration should be given to a possible causal role of the stimulant, and discontinuation of treatment may be appropriate. in a pooled analysis of multiple short-term, placebo-controlled studies, such symptoms occurred in about 0.1% (4 patients with events out of 3,482 exposed to methylphenidate or amphetamine for several weeks at usual doses) of stimulant-treated patients compared to 0 in placebo-treated patients. aggression aggressive behavior or hostility is often observed in children and adolescents with adhd, and has been reported in clinical trials and the postmarketing experience of some medications indicated for the treatment of adhd. although there is no systematic evidence that stimulants cause aggressive behavior or hostility, patients beginning treatment for adhd should be monitored for the appearance of, or worsening of, aggressive behavior or hostility. long-term suppression of growth careful follow-up of weight and height in children ages 7 to 10 years who were randomized to either methylphenidate or non-medication treatment groups over 14 months, as well as in naturalistic subgroups of newly methylphenidate-treated and non-medication treated children older than 36 months (to the ages of 10 to 13 years), suggests that consistently medicated children (i.e., treatment for 7 days per week throughout the year) have a temporary slowing in growth rate (on average, a total of about 2 cm less growth in height and 2.7 kg less growth in weight over 3 years), without evidence of growth rebound during this period of development. published data are inadequate to determine whether chronic use of amphetamines may cause a similar suppression of growth, however, it is anticipated that they likely have this effect as well. therefore, growth should be monitored during treatment with stimulants, and patients who are not growing or gaining height or weight as expected may need to have their treatment interrupted. seizures there is some clinical evidence that stimulants may lower the convulsive threshold in patients with prior history of seizures, in patients with prior eeg abnormalities in absence of seizures, and, very rarely, in patients without a history of seizures and no prior eeg evidence of seizures. in the presence of seizures, the drug should be discontinued. peripheral vasculopathy, including raynaud’s phenomenon stimulants, including dextroamphetamine sulfate extended-release capsules, 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 co-administration of cyp2d6 inhibitors which may increase the risk with increased exposure to dextroamphetamine sulfate extended-release capsules. in these situations, consider an alternative non-serotonergic 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 sulfate extended-release capsules with maoi drugs is contraindicated ( see contraindications ). discontinue treatment with dextroamphetamine sulfate extended-release capsules and any concomitant serotonergic agents immediately if the above symptoms occur, and initiate supportive symptomatic treatment. if concomitant use of dextroamphetamine sulfate extended-release capsules with other serotonergic drugs or cyp2d6 inhibitors is clinically warranted, initiate dextroamphetamine sulfate extended-release capsules 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.

appropriate. attention deficit disorder with hyperactivity the dextroamphetamine sulfate extended-release capsule formulation is not recommended for pediatric patients younger than 6 years of age. in pediatric patients 6 years of age and older, start with 5 mg once or twice daily; daily dosage may be raised in increments of 5 mg at weekly intervals until optimal response is obtained. only in rare cases will it be necessary to exceed a total of 40 mg per day. dextroamphetamine sulfate extended-release capsules may be used for once-a-day dosage wherever appropriate. where possible, drug administration should be interrupted occasionally to determine if there is a recurrence of behavioral symptoms sufficient to require continued therapy.

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 sulfate extended-release capsules and cyp2d6 inhibitors may increase the exposure of dextroamphetamine sulfate extended-release capsules 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 sulfate extended-release capsules initiation and after a dosage increase. if serotonin syndrome occurs, discontinue dextroamphetamine sulfate extended-release capsules 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 sulfate extended-release capsules 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 sulfate extended-release capsules initiation or dosage increase. if serotonin syndrome occurs, discontinue dextroamphetamine sulfate extended-release capsules 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 sulfate extended-release capsules concomitantly or within 14 days after discontinuing maoi ( see contraindications and warnings ). examples of maois include selegiline, tranylcypromine, isocarboxazid, phenelzine, linezolid, methylene blue. proton pump inhibitors time to maximum concentration (t max ) 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. antihistamines amphetamines may counteract the sedative effect of antihistamines. antihypertensives amphetamines may antagonize the hypotensive effects of antihypertensives. chlorpromazine chlorpromazine blocks dopamine and norepinephrine reuptake, 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 and norepinephrine reuptake, thus inhibiting the central stimulant effects of amphetamines. lithium carbonate the 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; co-administration of phenobarbital may produce a synergistic anticonvulsant action. phenytoin amphetamines may delay intestinal absorption of phenytoin; co-administration of phenytoin may produce a synergistic anticonvulsant action. propoxyphene in cases of propoxyphene overdosage, amphetamine cns stimulation is potentiated and fatal convulsions can occur. veratrum alkaloids amphetamines inhibit the hypotensive effect of veratrum alkaloids. drug/laboratory test interactions amphetamines can cause a significant elevation in plasma corticosteroid levels. this increase is greatest in the evening. amphetamines may interfere with urinary steroid determinations. carcinogenesis/mutagenesis mutagenicity studies and long-term studies in animals to determine the carcinogenic potential of dextroamphetamine sulfate extended-release capsules have not been performed.

ry and low birth weight. also, these infants may experience symptoms of withdrawal as demonstrated by dysphoria, including agitation, and significant lassitude.

should be considered only in light of the complete history and evaluation of the child. the decision to prescribe amphetamines should depend on the physician’s assessment of the chronicity and severity of the child’s symptoms and their appropriateness for his or her age. prescription should not depend solely on the presence of one or more of the behavioral characteristics. when these symptoms are associated with acute stress reactions, treatment with amphetamines is usually not indicated.

ilability of the sustained-release capsule was similar compared to the immediate-release tablet. following administration of three 5 mg tablets, average maximal dextroamphetamine plasma concentrations (c max ) of 36.6 ng/ml were achieved at approximately 3 hours. following administration of one 15 mg sustained-release capsule, maximal dextroamphetamine plasma concentrations were obtained approximately 8 hours after dosing. the average c max was 23.5 ng/ml. the average plasma t 1/2 was similar for both the tablet and sustained-release capsule and was approximately 12 hours. in 12 healthy subjects, the rate and extent of dextroamphetamine absorption were similar following administration of the sustained-release capsule formulation in the fed (58 g to 75 g fat) and fasted state.

nckrodt. specgx llc webster groves, mo 63119 usa rev 02/2022 mallinckrodt™ pharmaceuticals an electronic copy of this medication guide can be obtained from www.mallinckrodt.com/medguide/l20d09.pdf or by calling 1-800-778-7898 for alternate delivery options. boxed m boxed m boxed m boxed m

ipheral vasculopathy, including raynaud’s phenomenon] instruct patients beginning treatment with dextroamphetamine sulfate extended-release capsules 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 sulfate extended-release capsules. further clinical evaluation (e.g., rheumatology referral) may be appropriate for certain patients.