Class: Amphetamines
VA Class: CN801
CAS Number: 51-63-8
Brands: Adderall, Dexedrine, DextroStat
- Abuse Potential
Amphetamines have a high potential for abuse.101 102 103
Administration of amphetamines for prolonged periods of time may lead to drug dependence.101 102 103 b
Particular attention should be paid to the possibility of individuals obtaining amphetamines for nontherapeutic use or distribution to others, and the drugs should be prescribed or dispensed sparingly.101 102 103
The possibility that family members may abuse the patient’s medication should be considered.e
Introduction
Dextrorotatory isomer of amphetamine; noncatechol, sympathomimetic amine with CNS-stimulating activity.102 b
Uses for Dextroamphetamine Sulfate
Attention Deficit Hyperactivity Disorder
Used as an adjunct to psychological, educational, social, and other remedial measures in the treatment of attention deficit hyperactivity disorder (ADHD) (hyperkinetic disorder, hyperkinetic syndrome of childhood, minimal brain dysfunction).101 102 103 b e
Can be used for ADHD in pediatric (children, adolescents) as well as adult patients.d e
Almost all studies comparing behavioral therapy versus stimulants alone have shown a much stronger therapeutic effect from stimulants than from behavioral therapy, and stimulants (e.g., amphetamines, methylphenidate) remain the drugs of choice for the management of ADHD.d e
Drug therapy is not indicated in all patients with ADHD, and such therapy should be considered only after a complete evaluation including medical history has been performed.b e
Use should depend on age, adequate diagnosis (based on medical, special psychological, educational, and social resources), and the clinician’s assessment of the severity and duration of symptoms and should not depend solely on one or more behavioral characteristics.103 b e
Not recommended for ADHD symptoms associated with acute stress reactions.b
Narcolepsy
Used as a stimulant to reduce daytime sleepiness in the management of narcolepsy.101 102 b
Amphetamines remain the mainstay of treatment for narcolepsy based on a long record of clinical experience.f
Tolerance to the clinical effects may develop with long-term therapy, particularly at high dosages.f
Exogenous Obesity
Has been used as an adjunct to caloric restriction and behavioral modification in the short-term treatment of exogenous obesity†.d However, because of the limited efficacy (short-lived) and risk of abuse, such use no longer is included in the FDA-approved labeling101 102 103 and is discouraged.d
The anorexigenic effect appears to be temporary, seldom lasting more than a few weeks, and tolerance may occur.d
Obesity usually is a chronic disease, and short-term or intermittent therapy with anorexigenic drugs is unlikely to maintain a long-term benefit.
Dextroamphetamine Sulfate Dosage and Administration
Administration
Oral Administration
When used as an anorexigenic, the dose is given 30–60 minutes before meals.d
Conventional Tablets (Adderall, Dexedrine, and Generic Equivalents)
Administer initial dose on awakening;101 102 b when administered in divided doses, additional doses are given at intervals of 4–6 hours.101 102 b Because of potential for insomnia, avoid administering in the late evening.101 102 b
Extended-release Capsules (Dexedrine Spansules and Generic Equivalents)
Administer initial dose on awakening.b Because of potential for insomnia, avoid administering in the late evening.102
Fixed-combination Extended-release Capsules (Adderall XR)
Administer on awakening.103 Because of potential for insomnia, avoid administering in the afternoon.103
Administer capsules with or without food;103 capsules may be swallowed intact or the entire contents of a capsule(s) may be sprinkled on a small amount of applesauce immediately prior to administration.103 Do not subdivide the capsule contents.103 Do not chew or crush the pellets contained in the capsules and do not store the sprinkle/food mixture for later use.103
Dosage
Dosages of dextroamphetamine sulfate alone and of total amphetamine base equivalence are the same.101 103 e f
Dextroamphetamine sulfate extended-release capsules or fixed-combination extended-release capsules containing various salts of dextroamphetamine and amphetamine can be substituted for their respective conventional short-acting preparations if less-frequent daily dosing is desirable.102 103 b
Dosage of fixed-combination preparations containing various salts of dextroamphetamine and amphetamine is expressed as total amphetamine base equivalence.101 103 b
Adjust dosage according to individual response and tolerance; the smallest dose required to produce the desired response should always be used.101 102 103 b
When possible, therapy should be interrupted occasionally to determine if there is a recurrence of behavioral symptoms sufficient to require continued treatment.101 102 103 b
Pediatric Patients
Attention Deficit Hyperactivity Disorder
Dosage titration usually requires 2–4 weeks.e
Conventional Tablets (Adderall, Dexedrine, and Generic Equivalents)
Oral
Dosing in pediatric patients may begin with once-daily administration in the early morning, adding a noon dose if the effect does not last throughout the school day.e Increasing the morning dose may extend its duration.e A third dose may be added at around 4 p.m. if necessary.e
Children 3–5 years of age: Initially, 2.5 mg daily; the daily dosage is increased in 2.5-mg increments at weekly intervals until the optimum response is attained.101 102 b e
Children ≥6 years of age: Initially, 5 mg once or twice daily; the daily dosage is increased in 5-mg increments at weekly intervals until the optimum response is attained.101 102 b e Total daily dosage rarely should exceed 40 mg.101 102 b e
Extended-release Capsules (Dexedrine Spansules and Generic Equivalents)
Oral
Total daily dosage of dextroamphetamine sulfate is the same for extended-release capsules (Dexedrine Spansules) and conventional tablets (Dexedrine).102
Although extended-release capsules usually are administered once daily,102 some patients may benefit from dividing the dosage into 2 doses daily.
Children 3–5 years of age: Dosage must be initiated and titrated with conventional tablets in this age group.102 Can substitute with once-daily dosing only when the total daily dose is divisible by 5 mg.102
Children ≥6 years of age: Initially, 5 or 10 mg once daily; the daily dosage is increased in 5-mg increments at weekly intervals until the optimum response is attained.102 b Total daily dosage rarely should exceed 40 mg.102 b
Fixed-combination Extended-release Capsules (Adderall XR)
Oral
Children 6–12 years of age: Initially, 10 mg once daily; daily dosage may be increased in 5- or 10-mg increments at weekly intervals to a maximum dosage of 30 mg daily.103 b Alternatively, initiate with 5 mg once daily when lower initial dosage is appropriate.103 b
Adolescents 13–17 years of age: Initially, 10 mg once daily.103 Increase to 20 mg once daily after 1 week if symptoms not adequately controlled.103 No evidence that dosages >20 mg daily provide any additional benefit.103
When switching from fixed-combination conventional tablets (Adderall) to fixed-combination extended-release capsules (Adderall XR), the total daily dosage may remain the same but may be given once daily.103 b
Narcolepsy
When intolerable adverse effects occur (e.g., insomnia, anorexia), dosage should be reduced.101 102 b
Conventional Tablets (Adderall, Dexedrine, and Generic Equivalents)
Oral
Children 6–12 years of age: Initially, 5 mg daily; daily dosage is increased in 5-mg increments at weekly intervals until the optimum response is attained.101 102 b
Children ≥12 years of age: Initially, 10 mg daily; daily dosage is increased in 10-mg increments at weekly intervals until the optimum response is attained.101 102 b
Maintenance: Usually, 5–60 mg daily, depending on patient age and response, given in divided doses.101 102 b
Extended-release Capsules (Dexedrine Spansules and Generic Equivalents)
Oral
Total daily dosage of dextroamphetamine sulfate is the same for extended-release capsules (Dexedrine Spansules) and conventional tablets (Dexedrine).102
Although extended-release capsules usually are administered once daily,102 some patients may benefit from dividing the dosage into 2 doses daily.
Children 6–12 years of age: Initially, 5 mg once daily; daily dosage is increased in 5-mg increments at weekly intervals until the optimum response is attained.102 b
Children ≥12 years of age: Initially, 10 mg once daily; daily dosage is increased in 10-mg increments at weekly intervals until the optimum response is attained.102 b
Maintenance: Usually, 5–60 mg once daily, depending on patient age and response, given in divided doses.102 b
Adults
Attention Deficit Hyperactivity Disorder
Conventional Tablets (Adderall, Dexedrine, and Generic Equivalents)
Dosage titration usually requires 2–4 weeks.e
Oral
Initially, 5 mg once or twice daily; the daily dosage is increased in 5- to 10-mg increments at weekly intervals until the optimum response is attained.101 102 b e Total daily dosage rarely should exceed 40 mg.101 102 b e
Extended-release Capsules (Dexedrine Spansules and Generic Equivalents)
Oral
Total daily dosage of dextroamphetamine sulfate is the same for extended-release capsules (Dexedrine Spansules) and conventional tablets (Dexedrine).102
Although extended-release capsules usually are administered once daily,102 some patients may benefit from dividing the dosage into 2 doses daily.
Initially, 5 or 10 mg once daily; the daily dosage is increased in 5-mg increments at weekly intervals until the optimum response is attained.102 b e Total daily dosage rarely should exceed 40 mg.102 b e
Fixed-combination Extended-release Capsules (Adderall XR)
Oral
20 mg once daily as initial therapy or when switching from other drugs.103 No evidence that dosages >20 mg daily provide any additional benefit.103
When switching from fixed-combination conventional tablets (Adderall) to fixed-combination extended-release capsules (Adderall XR), the total daily dosage may remain the same but may be given once daily.103 b
Narcolepsy
When intolerable adverse effects occur (e.g., insomnia, anorexia), dosage should be reduced.101 102 b
Conventional Tablets (Adderall, Dexedrine, and Generic Equivalents)
Oral
Initially, 10 mg daily; daily dosage is increased in 10-mg increments at weekly intervals until the optimum response is attained.101 102 b
Maintenance: Usually, 5–60 mg daily, depending on response, given in divided doses.101 102 b
Prescribing Limits
Pediatric Patients
Attention Deficit Hyperactivity Disorder
Excessive dosage can cause pediatric patients to become overfocused on the medication or to appear dull or overly restricted. Rarely, psychotic reactions, mood disturbances, or hallucinations can occur.
Conventional Tablets (Adderall, Dexedrine, and Generic Equivalents)
Oral
Dosage rarely should exceed a total daily dosage of 40 mg.101 b e Individual doses rarely should exceed 10 mg each in children <25 kg.e
Extended-release Capsules (Dexedrine Spansules and Generic Equivalents)
Oral
Dosage rarely should exceed a total daily dosage of 40 mg.102 b e Individual doses rarely should exceed 10 mg each in children <25 kg.e
Fixed-combination Extended-release Capsules (Adderall XR)
Oral
Children 6–12 years of age: Dosages >30 mg daily have not been studied systematically.103 b
Adolescents 13–17 years of age: Dosages up to 40 mg daily in individuals weighing ≤75 kg or 60 mg daily in those weighing >75 kg have been used in clinical studies; however, no evidence that dosages >20 mg daily provide any additional benefit.103
Long-term use (>3 weeks in children or >4 weeks in adolescents) has not been studied systematically.103 If used for long-term therapy, periodically reevaluate the usefulness of the drug.103
Adults
Attention Deficit Hyperactivity Disorder
Conventional Tablets (Adderall, Dexedrine, and Generic Equivalents)
Oral
Dosages up to 0.9 mg/kg daily but rarely exceeding 40 mg daily.101 102 b e Such higher doses may be more likely in adults than in school-aged children because of increased dosing frequency to cover a longer work day.e
Tolerance is more likely with relatively high dosages.e
Extended-release Capsules (Dexedrine Spansules and Generic Equivalents)
Oral
Dosages up to 0.9 mg/kg daily but rarely exceeding 40 mg daily.102 b e Such higher doses may be more likely in adults than in school-aged children because of increased dosing frequency to cover a longer work day.e
Tolerance is more likely with relatively high dosages.e
Fixed-combination Extended-release Capsules (Adderall XR)
Oral
Dosages up to 60 mg daily have been evaluated in clinical studies; however, no evidence that dosages >20 mg daily provide any additional benefit.103
Long-term use (>4 weeks) has not been studied systematically.103 If used for long-term therapy, periodically reevaluate the usefulness of the drug.103
Special Populations
Hepatic Impairment
No specific hepatic dosage recommendations.101 102 103
Renal Impairment
No specific renal dosage recommendations.101 102 103
Geriatric Patients
No specific geriatric dosage recommendations.101 103
Cautions for Dextroamphetamine Sulfate
Contraindications
Contraindicated in patients with hypersensitivity or idiosyncrasy to the sympathomimetic amines,101 102 103 d symptomatic cardiovascular disease,101 102 103 d hyperthyroidism,101 102 103 d moderate to severe hypertension,101 102 103 d glaucoma,101 102 103 d e or advanced arteriosclerosis;101 102 103 d within 14 days of MAO inhibitor therapy;101 102 103 d e and in agitated patients.101 102 103 d
Although amphetamines generally should not be used in patients with a history of drug abuse,101 102 103 d e some experts state that this is not an absolute contraindication, provided the patient can be monitored more carefully than would otherwise be indicated.e
Warnings/Precautions
Warnings
Sudden Death and Serious Cardiovascular Events
Sudden unexplained death, stroke, and MI reported in adults with ADHD receiving usual dosages of stimulants; sudden death also reported in children and adolescents with structural cardiac abnormalities or other serious cardiac conditions receiving usual dosages of the drugs.102 103 h
Epidemiologic data suggest a possible association between use of stimulants and sudden unexplained death in healthy children and adolescents.i j k FDA unable to conclude that these data affect evaluation of overall risk and benefit of stimulants used to treat ADHD in children and adolescents.i FDA is conducting an ongoing safety review of amphetamines and other stimulants to evaluate possible link between use of these agents and sudden death in children.i j k Pediatric patients with ADHD and their parents should avoid discontinuing the child’s use of such stimulants before consulting a clinician.i
Thoroughly review medical history (including evaluation for family history of sudden death or ventricular arrhythmia) and perform physical examination in all children, adolescents, and adults being considered for stimulant therapy; if initial findings suggest presence of cardiac disease, perform further cardiac evaluation (e.g., ECG, echocardiogram).102 103
In general, avoid use of CNS stimulants in patients with known serious structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, CAD, or other serious cardiac conditions.102 103 (See Contraindications under Cautions.)
Patients who develop exertional chest pain, unexplained syncope, or other manifestations suggestive of cardiac disease during stimulant therapy should undergo prompt cardiac evaluation.102 103
Effects on BP and Heart Rate
Possible modest increases in average BP (i.e., by about 2–4 mm Hg) and heart rate (i.e., by about 3–6 bpm); larger increases may occur.102 103 Modest increases not expected to have short-term sequelae; however, monitor all patients for larger changes in BP and heart rate.102 103
Caution advised in patients with underlying medical conditions that might be affected by increases in BP or heart rate (e.g., hypertension, heart failure, recent MI, ventricular arrhythmia).102 103
Exacerbation or Precipitation of Psychotic Symptoms
May exacerbate symptoms of behavior disturbance and thought disorder in patients with preexisting psychotic disorder.102 103
Psychotic symptoms (e.g., hallucinations, delusional thinking) may occur with usual dosages in children and adolescents without prior history of psychotic illness.102 103 If psychotic symptoms occur, consider causal relationship to stimulants, and discontinue therapy as appropriate.102 103
Precipitation of Manic Symptoms
May precipitate mixed or manic episodes in ADHD patients with comorbid bipolar disorder; use with caution in these patients.102 103 Prior to initiating therapy, carefully screen patients with ADHD and comorbid depressive symptoms to identify risk for bipolar disorder; screening should include a detailed psychiatric history (e.g., family history of suicide, bipolar disorder, or depression).102 103
Manic symptoms may occur with usual dosages in children and adolescents without prior history of mania.102 103 If manic symptoms occur, consider causal relationship to stimulants, and discontinue therapy as appropriate.102 103
Aggression
Aggressive behavior and hostility (frequently observed in children and adolescents with ADHD) reported in patients receiving drug therapy for ADHD.102 103 No systematic evidence that stimulants cause these adverse effects; however, monitor patients beginning treatment for ADHD for onset or worsening of aggressive behavior or hostility.102 103
Growth Suppression
Long-term (i.e., >14 months) administration expected to cause at least a temporary suppression of normal weight and/or height patterns in some children and adolescents.102 103 Dose-related weight loss reported in adolescents during first 4 weeks of therapy with fixed-combination extended-release capsules.103
Manufacturers recommend monitoring growth during treatment; patients not growing or gaining weight as expected may require temporary discontinuance of treatment.101 102 103 However, AAP states that studies of stimulants in children found little or no decrease in expected height, with any decrease in growth early in treatment being compensated for later on.
Seizures
Possible lowering of seizure threshold in patients with history of seizures, in those with prior EEG abnormalities but no history of seizures, and, very rarely, in those without history of seizures and with no prior evidence of EEG abnormalities.102 103 If seizures occur, discontinue therapy.102 103
Visual Effects
Visual disturbances (difficulty with accommodation, blurred vision) reported with stimulants.102 103
Sensitivity Reactions
Tartrazine Sensitivity
Some commercially available preparations of dextroamphetamine (e.g., DextroStat, Dexedrine tablets) contain the dye tartrazine (FD&C yellow No. 5), which may cause allergic reactions including bronchial asthma in susceptible individuals.102 b Incidence of tartrazine sensitivity is low, but it frequently occurs in patients who are sensitive to aspirin.b
General Precautions
Least amount of amphetamine feasible should be prescribed or dispensed at one time in order to minimize possible overdosage.101 102 103
Tics
Amphetamines reported to exacerbate motor and phonic tics and Tourette’s syndrome.101 102 103 However, a history of tics or their development during therapy is not an absolute contraindication to continued use.e Several controlled studies have not found stimulants to worsen or precipitate tics or Tourette’s syndrome.e Nevertheless, evaluate for presence of tics and Tourette’s syndrome in children and their families prior to initiating stimulant therapy.102 103 d
Specific Populations
Pregnancy
Category C.101 102 103 f
Risk of prematurity, low birth weight, and withdrawal symptoms (e.g., dysphoria, lassitude, agitation) in infants born to dependent women.101 102 103 f
Lactation
Distributed into milk.101 103 f Discontinue nursing or the drug.101 103
Pediatric Use
Not recommended for ADHD in children <3 years of age.101 102 103 e
Aggressive behavior, hostility, and psychotic (e.g., hallucinations, delusional thinking) or manic symptoms reported in children and adolescents receiving stimulants for management of ADHD.102 103 (See Warnings under Cautions.)
Sudden death reported in children and adolescents with structural cardiac abnormalities or other serious cardiac conditions receiving usual dosages of stimulants.102 103 Epidemiologic data also suggest a possible association between use of stimulants and sudden death in healthy children and adolescents.i j k (See Sudden Death and Serious Cardiovascular Events under Cautions.)
Long-term administration expected to cause at least a temporary suppression of normal weight and/or height patterns in some children and adolescents.102 103 (See Growth Suppression under Cautions.)
Hepatic Impairment
Possible inhibition of drug elimination, resulting in prolonged exposure.103
Renal Impairment
Possible inhibition of drug elimination, resulting in prolonged exposure.103
Common Adverse Effects
Most commonly abdominal pain (stomachache), loss of appetite, insomnia.103
Also, palpitations,101 102 103 tachycardia,101 102 103 elevation of BP,101 102 103 overstimulation,101 102 103 restlessness,101 102 103 dizziness,101 102 103 euphoria,101 102 103 dyskinesia,101 102 103 dysphoria,101 102 103 tremor,101 102 103 headache,101 102 103 dryness of mouth,101 102 103 taste aberration,101 103 diarrhea,101 102 103 constipation,101 102 103 abdominal bloating,101 103 impotence,101 102 103 changes in libido.101 102 103
Isolated reports of cardiomyopathy associated with chronic amphetamine use.101 102 103
Anorexia and weight loss may occur as undesirable effects when amphetamines are used for other than the anorectic effect.101 102 103
Interactions for Dextroamphetamine Sulfate
Inhibits MAO.103
Amphetamine or metabolites modestly inhibit CYP2D6, 1A2, and 3A4 in vitro.103 In vivo effects on metabolism of drugs metabolized by CYP isoenzymes not known.103
Specific Drugs and Laboratory Tests
Drug or Test
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Interaction
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Comments
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Acidifying agents, GI (ascorbic acid, glutamic acid hydrochloride, reserpine)
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Decreases absorption, serum concentrations, and efficacy of amphetamines101 102 103
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Acidifying agents, urinary (ammonium chloride, sodium acid phosphate)
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Increases urinary excretion and decreases serum concentrations and efficacy of amphetamines101 102 103
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Adrenergic blockers
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Potential inhibition of adrenergic blockade101 102 103
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Alkalinizing agents, GI (antacids, sodium bicarbonate)
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Increases absorption and serum concentrations and potentiates the effects of amphetamines101 102 103
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Avoid concomitant use103
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Alkalinizing agents, urinary (acetazolamide and some thiazides)
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Decreases urinary excretion and increases serum concentrations and potentiates the effects of amphetamines101 102 103
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Antidepressants, tricyclic (desipramine, protriptyline)
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Enhanced activity of tricyclic antidepressants; desipramine or protriptyline cause striking and sustained increases in the concentration of dextroamphetamine in the brain; cardiovascular effects can be potentiated101 102 103
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Antihistamines
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May counteract the sedative effects of antihistamines101 102 103
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Antihypertensives
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May antagonize the hypotensive effects of antihypertensives101 102 103
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Chlorpromazine
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Inhibits the central stimulant effects of amphetamines by blocking dopamine and norepinephrine receptors101 102 103
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Can be used to treat amphetamine poisoning101 102 d
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Ethosuximide
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Intestinal absorption may be delayed by amphetamines101 102 103
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Haloperidol
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Inhibits the central stimulant effects of amphetamines by blocking dopamine receptors101 102 103
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Lithium carbonate
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May inhibit the anorectic and stimulatory effects of amphetamine101 102 103
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MAO inhibitors
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Slow the metabolism of amphetamines, increasing their effect on the release of norepinephrine and other monoamines leading to headaches and other signs of hypertensive crisis101 102 103
Toxic neurologic effects, hypertensive crisis, and malignant hyperpyrexia can occur, sometimes with fatal results101 102 103
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Amphetamines contraindicated in patients currently or recently (within 14 days) receiving MAO inhibitor101 102 103
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Meperidine
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Amphetamines potentiate the analgesic effect of meperidine101 102 103
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Methenamine
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Acidifying agents used with methenamine increase urinary excretion and decrease efficacy of amphetamines101 102 103
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Norepinephrine
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Amphetamines enhance the adrenergic effects of norepinephrine101 102 103
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Phenobarbital
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Amphetamines may delay absorption of phenobarbital; concomitant use may produce a synergistic anticonvulsant action101 102 103
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Phenytoin
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Amphetamines may delay absorption of phenytoin; concomitant use may produce a synergistic anticonvulsant action101 102 103
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Propoxyphene
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In propoxyphene overdosage, amphetamine CNS stimulation is potentiated and fatal convulsions can occur101 102 103
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Sympathomimetic agents
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Enhanced activity of sympathomimetic agents102 103
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Test, plasma corticosteroids
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Can elevate plasma corticosteroid concentrations; this increase is greatest in the evening101 102 103
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Test, urinary steroids
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May interfere with urinary steroid determinations101 102 103
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Veratrum alkaloids
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Amphetamines inhibit the hypotensive effect of veratrum101 102 103
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Dextroamphetamine Sulfate Pharmacokinetics
Absorption
Bioavailability
Similar for dextroamphetamine sulfate extended-release capsules versus immediate-release tablets.102
Plasma concentration-time profiles for fixed combinations containing various salts of dextroamphetamine and amphetamine are similar for single 20-mg extended-release dose versus two 10-mg immediate-release doses given 4 hours apart.103
Peak plasma concentration and AUC of amphetamines decrease with increasing body weight in individuals receiving fixed-combination extended-release capsules (Adderall XR).103
Duration
Therapeutic effects persist for 4–24 hours.PDH
Food
Food does not affect the rate or extent of absorption of dextroamphetamine sulfate from the extended-release capsules (e.g., Dexedrine Spansules).102
Food does not affect the extent of absorption of the fixed-combination extended-release preparation (Adderall XR), but prolongs Tmax by 2.5 hours (for d-amphetamine) and 2.1 hours (for l-amphetamine).103 Opening the capsule and sprinkling the contents on applesauce results in comparable absorption to the intact capsule taken in the fasted state.103
Plasma Concentrations
Tmax, immediate-release dextroamphetamine sulfate: About 3 hours.101 102
Tmax, extended-release dextroamphetamine sulfate: About 8 hours.102
Tmax, immediate-release fixed combinations containing various salts of dextroamphetamine and amphetamine: About 3 hours.103
Tmax, extended-release fixed combinations containing various salts of dextroamphetamine and amphetamine: About 7 hours.103
Therapeutic plasma concentrations are 5–10 mcg/dL.PDH
Distribution
Extent
Distributed widely throughout body, with high levels in the brain.PDH
Apparently crosses the placenta since withdrawal manifestations have occurred in neonates.101 102 103 f
Distributed into milk in concentrations 3–7 times maternal blood concentrations.f
Volume of distribution increases with increasing body weight in individuals receiving fixed-combination extended-release capsules.103
Elimination
Metabolism
Metabolized to several active metabolites.103
Enzymes involved in metabolism not clearly defined; however, CYP2D6 is involved with formation of at least one metabolite.103 Because CYP2D6 is genetically polymorphic, potential variability in metabolism among patients exists.
