Brand names: Adderall XR, Dexedrine Spansules, Dyanavel XR, Mydayis, Procentra, Xelstrym, Zenzedi
Drug class: Amphetamines

Medically reviewed by Drugs.com on Oct 10, 2025. Written by ASHP.

Introduction

Dextrorotatory isomer of amphetamine; non-catecholamine, sympathomimetic amine with CNS-stimulating activity.

Uses for Dextroamphetamine

Attention Deficit Hyperactivity Disorder

Used orally (as dextroamphetamine sulfate conventional tablets [Zenzedi] and dextroamphetamine sulfate oral solution [ProCentra]) for the treatment of attention deficit hyperactivity disorder (ADHD) in pediatric patients 3–16 years of age.

Used orally (as dextroamphetamine sulfate sustained-release capsules [Dexedrine Spansule]) for the treatment of ADHD in pediatric patients 6–16 years of age.

Used transdermally (as dextroamphetamine transdermal system [Xelstrym]) for the treatment of ADHD in adults and pediatric patients ≥6 years of age.

Used orally (as amphetamine mixed salt biphasic extended-release capsules containing amphetamine aspartate monohydrate, amphetamine sulfate, dextroamphetamine saccharate, and dextroamphetamine sulfate [Adderall XR], and as extended-release oral suspension and extended-release tablets containing amphetamine, amphetamine aspartate, and dextroamphetamine sulfate [Dyanavel XR]) for the treatment of ADHD in adults and pediatric patients ≥6 years of age.

Used orally (as amphetamine mixed salt immediate-release conventional tablets containing amphetamine aspartate monohydrate, amphetamine sulfate, dextroamphetamine saccharate, and dextroamphetamine sulfate [Adderall]) for the treatment of ADHD in pediatric patients ≥3 years of age.

Used orally (as amphetamine mixed salt triphasic extended-release capsules containing amphetamine aspartate monohydrate, amphetamine sulfate, dextroamphetamine saccharate, and dextroamphetamine sulfate [Mydayis]) for the treatment of ADHD in adults and pediatric patients ≥13 years of age.

American Academy of Pediatrics (AAP) states that, for pediatric patients 6–12 years of age with ADHD, providers should prescribe FDA-approved medications for ADHD, in addition to parent training in behavior management (PTBM) and/or behavioral classroom interventions. Evidence is stated as particularly strong for stimulant medications (e.g., amphetamine, methylphenidate). For adolescents 12–18 years of age with ADHD, providers should prescribe FDA-approved medications with assent of the adolescent. Provider is also encouraged to prescribe behavioral and other evidence-based training interventions if available. Titrate doses of medications to achieve maximum benefit with tolerable side effects.

AAP also provides recommendations for pediatric patients with ADHD as young as 4 years of age. First-line treatments for pediatric patients 4–6 years of age are PTBM and behavioral classroom interventions. May consider methylphenidate if behavioral interventions do not provide significant improvement and there is moderate to severe continued disturbance in the child’s functioning; however, use of methylphenidate in this age group is considered off-label.

Treatment of ADHD in adults should follow a multimodal approach that includes psychoeducation, pharmacotherapy, cognitive behavior therapy, and coaching for ADHD. First-line pharmacotherapy agents include long-acting stimulants such as mixed amphetamine salts, methylphenidate, and lisdexamfetamine. Short-acting and intermediate-acting stimulants (including dextroamphetamine) are considered second-line and can also be adjunctive agents.

Narcolepsy

Used orally (as dextroamphetamine sulfate conventional tablets [Zenzedi], oral solution [ProCentra], sustained-release capsules [Dexedrine Spansule], and as amphetamine mixed salt immediate-release conventional tablets containing amphetamine aspartate monohydrate, amphetamine sulfate, dextroamphetamine saccharate, and dextroamphetamine sulfate [Adderall]) for the treatment of narcolepsy in adults and pediatric patients ≥6 years of age.

American Academy of Sleep Medicine (AASM) provides a strong recommendation for the use of several agents for the treatment of narcolepsy in adults, including modafinil, pitolisant, sodium oxybate, and solriamfetol. Conditional recommendation given for armodafinil, dextroamphetamine, and methylphenidate.

Autism Spectrum Disorder (ASD)

Has been used for the symptomatic treatment of inattention, impulsivity, and hyperactivity in pediatric patients with ASD^{† [off-label]}.

Guidelines from AAP suggest use of psychostimulants (e.g., methylphenidate, dexmethylphenidate, mixed amphetamine salts, lisdexamfetamine, dextroamphetamine) for symptoms of hyperactivity, impulsivity, inattention, and distractibility in pediatric patients with ASD if problems persist after behavioral interventions. Patients should start with a low dose, with increases as needed and tolerated. Stimulants may be most effective in children who do not have a comorbid intellectual disability.

Dextroamphetamine Dosage and Administration

General

Pretreatment Screening

• Perform a thorough medical history review (including evaluation for a family history of sudden death or ventricular arrhythmia) and physical examination to detect the presence of cardiac disease prior to initiating stimulant therapy.

• Prior to initiating stimulant therapy in patients with ADHD, obtain a detailed psychiatric history (e.g., current or prior depressive symptoms; family history of suicide, bipolar disorder, or depression) to determine if they are at risk for developing a manic episode.

• Prior to initiation of therapy, assess for family history of motor or verbal tics or Tourette’s syndrome, and clinically evaluate patients for such disorders.

• Evaluate patients for risk of abuse, misuse, and addiction prior to initiating therapy.

Patient Monitoring

• Routinely monitor for emergence or worsening of tics or Tourette’s syndrome.

• Closely monitor growth (weight and height) in pediatric patients receiving stimulant therapy.

• Throughout treatment, reassess each patient’s risk of abuse, misuse, and addiction. Frequently monitor for signs of abuse, misuse, and addiction during treatment.

• Monitor for hypertension and tachycardia.

Dispensing and Administration Precautions

• The Institute for Safe Medication Practices (ISMP) includes Adderall and Adderall XR on their List of Confused Drug Names, and recommends using special safeguards to ensure the accuracy of prescriptions for these drugs.

• The manufacturer states that medication errors, including substitution and dispensing errors, can occur with Mydayis and other amphetamine products, which can lead to potential overdosage. To avoid potential errors and overdosage, Mydayis should not be substituted with other amphetamine products on a milligram-per-milligram basis due to different amphetamine base compositions and differences in pharmacokinetics.

Administration

Administer orally or transdermally.

Oral Administration

Immediate-release Tablets and Oral Solution (Adderall, Procentra, Zenzedi)

Administer initial dose on awakening; when administered in divided doses, additional doses are given at intervals of 4–6 hours. Because of potential for insomnia, avoid administering in the late evening.

Sustained-release Capsules (Dexedrine Spansule)

Administer with or without food.

Extended-release Capsules (Adderall XR, Mydayis)

Administer on awakening. In the event of a missed dose, do not administer later in the day. Avoid administering in the afternoon because of the potential for insomnia.

Administer Adderall XR capsules with or without food, and Mydayis in a consistent manner relative to food intake. Capsules may be swallowed intact or the entire contents of the capsule may be sprinkled on a small amount of applesauce immediately prior to administration. Do not subdivide the capsule contents. Do not chew or crush the pellets contained in the capsules and do not store the sprinkle/food mixture for later use.

Extended-release Tablets and Oral Suspension (Dyanavel XR)

Administer once daily in the morning without regard to meals.

Tablets may be chewed or swallowed whole. Dosing increments of 2.5 mg can be attained by splitting functionally scored 5-mg tablet at the score line.

Insert bottle adapter firmly into bottle of suspension prior to use and do not remove after insertion. Shake the bottle well before each use. Use the oral dosing dispenser supplied by the pharmacist to administer each dose.

Transdermal Administration (Xelstrym)

Apply once daily in the morning 2 hours before effect is needed and remove 9 hours after application. Use only one transdermal system per 24-hour period.

Apply immediately after opening pouch and removing slip from above and below the system; do not use if the patch is cut or damaged. While avoiding touching the sticky side, peel away half of the clear plastic liner from the middle of the system, apply to the application site, and smooth down. Slowly peel the rest of the liner off while holding edge of the remaining protective liner, smoothing the system by pressing with the palm of the hand. Immediately wash hands with soap and water after applying and if the adhesive side is touched.

Apply system to clean (void of lotions, oils, or gels), intact, dry areas of the hip, upper arm, chest, upper back, or flank; avoid waistband or area where there are straps. Alternate application sites daily. Regularly check to ensure adhesion, and also check after using the bathroom, sleeping, bathing, swimming, showering, or undressing or changing clothes, or if sweating a lot. If the edges of the system lift, the system may be pressed firmly and smoothed down; do not use dressings, tape, or other common adhesives to ensure adhesiveness of the system. If a patch falls off during the intended period of use, it should be replaced with a new system applied at a different site; total wear time should not exceed 9 hours per day regardless of the number of transdermal systems used due to replacement.

Peel to remove. If any adhesive remains, an oil-based product or water and soap may be applied to the application site. Immediately wash hands after removal with soap and water.

After removal, fold used system in half so that the adhesive side adheres to itself and dispose of the system in an appropriate lidded container. Remove any unused systems that are no longer needed from their packaging, separate from the protective liner, fold so that the adhesive side adheres to itself, and then dispose of systems in an appropriate lidded container.

Dosage

Manufacturer states total daily dosage of immediate-release mixed amphetamine salts (Adderall) is bioequivalent to the same total daily dosage of mixed amphetamine salts extended-release capsules (Adderall XR) administered once daily.

Manufacturer states Mydayis should not be substituted with other amphetamine products on a milligram-per-milligram basis due to different amphetamine base compositions and pharmacokinetic profiles.

Manufacturer states Dyanavel XR extended-release oral suspension and Dyanavel XR extended-release oral tablets may be substituted on a milligram-per-milligram basis; however, other amphetamine products should not be substituted on a milligram-per-milligram basis.

Dosages of Dyanavel XR are expressed as the amount of amphetamine base, and dosages of Xelstrym are expressed as the amount of dextroamphetamine delivered over 9 hours; dosages of other dextroamphetamine products are expressed in terms of the total amount of the salt(s).

Adjust dosage according to individual response and tolerance; the smallest dose required to produce the desired response should always be used.

Pediatric Patients

Attention Deficit Hyperactivity Disorder

Immediate-release Preparations (Adderall, Procentra, Zenzedi)

Oral

Doses given at intervals of 4–6 hours.

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.

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. Total daily dosage rarely should exceed 40 mg.

Sustained-release Capsules (Dexedrine Spansule)

Oral

Total daily dosage of dextroamphetamine sulfate is the same for extended-release capsules (Dexedrine Spansule) and conventional tablets.

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. Total daily dosage rarely should exceed 40 mg.

Extended-release Capsules (Adderall XR, Mydayis)

Oral

Children 6–12 years of age (Adderall XR): 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. Alternatively, initiate with 5 mg once daily when lower initial dosage is appropriate.

Adolescents 13–17 years of age (Adderall XR): Initially, 10 mg once daily. Increase to 20 mg once daily after 1 week if symptoms not adequately controlled. No evidence that dosages >20 mg daily provide any additional benefit.

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.

Adolescents 13–17 years of age (Mydayis): 12.5 mg once daily as initial therapy or when switching from other medications. Increase to 25 mg once daily after 1 week if symptoms not adequately controlled.

Adderall XR: Duration of 10–12 hours.

Mydayis: Duration of 16 hours.

Extended-release Tablets and Oral Suspension (Dyanavel XR)

Oral

Children ≥6 years of age: Initially, 2.5 mg or 5 mg once daily; daily dosage may be increased by 2.5−10 mg increments at 4- to 7-day intervals to a maximum dosage of 20 mg once daily.

Dyanavel XR: Duration of 13 hours.

Transdermal System (Xelstrym)

Transdermal

Children ≥6 years of age: 4.5 mg per 9-hour period once daily as initial therapy or when switching from other medications; dosage may be increased in weekly increments of 4.5-mg to a maximum dosage of 18 mg per 9-hour period based on clinical response and tolerability.

Narcolepsy

Immediate-release Preparations (Adderall, Procentra, Zenzedi)

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.

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.

Maintenance: Usually, 5–60 mg daily, depending on patient age and response, given in divided doses.

Sustained-release Capsules (Dexedrine Spansule)

Oral

Total daily dosage of dextroamphetamine sulfate is the same for extended-release capsules (Dexedrine Spansule) and conventional tablets.

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.

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.

Maintenance: Usually, 5–60 mg once daily, depending on patient age and response, given in divided doses.

Adults

Attention Deficit Hyperactivity Disorder

Extended-release Capsules (Adderall XR, Mydayis)

Oral

Adderall XR: 20 mg once daily as initial therapy or when switching from other medications. No evidence that dosages >20 mg daily provide any additional benefit.

Mydayis: Initially, 12.5 mg once daily; an initial dose of 25 mg once daily may be considered for some patients. Daily dosage may be increased in 12.5-mg increments at weekly intervals to a maximum dosage of 50 mg once daily. Dosages >50 mg daily not shown to provide additional benefit.

Extended-release Tablets and Oral Suspension (Dyanavel XR)

Oral

Initially, 2.5 mg or 5 mg once daily; daily dosage may be increased by 2.5−10 mg increments at 4- to 7-day intervals to a maximum dosage of 20 mg once daily.

Dyanavel XR: Duration of 13 hours.

Transdermal System (Xelstrym)

Transdermal

9 mg per 9-hour period once daily as initial therapy or when switching from other medications; dosage may be titrated to a maximum dosage of 18 mg per 9-hour period based on clinical response and tolerability.

Narcolepsy

Immediate-release Preparations (Adderall, Procentra, Zenzedi)

Oral

Initially, 10 mg daily; daily dosage is increased in 10-mg increments at weekly intervals until the optimum response is attained.

Maintenance: Usually, 5–60 mg daily, depending on response, given in divided doses.

Sustained-release Capsules (Dexedrine Spansule)

Oral

Total daily dosage of dextroamphetamine sulfate is the same for extended-release capsules (Dexedrine Spansule) and conventional tablets.

Initially, 10 mg once daily; daily dosage is increased in 10-mg increments at weekly intervals until the optimum response is attained.

Maintenance: Usually, 5–60 mg once daily, depending on patient age and response, given in divided doses.

Special Populations

Hepatic Impairment

No specific hepatic dosage recommendations, although presence of hepatic impairment may reduce drug elimination and increase exposure.

Renal Impairment

Presence of renal impairment may reduce drug elimination and increase exposure.

Xelstrym: Do not exceed 13.5 mg per 9-hour period in patients with severe renal impairment. In patients with end-stage renal disease (ESRD), do not exceed 9 mg per 9-hour period. Dextroamphetamine not removed by dialysis.

Adderall XR: Reduce initial dosage in adults with severe renal impairment (GFR 15 to <30 mL/minute per 1.73 m²) to 15 mg once daily. Recommended initial dosage in children and adolescents 6–17 years of age with severe renal impairment is 5 mg once daily; maximum of 20 mg in children 6–12 years of age.

Mydayis: Reduce initial dosage in adults with severe renal impairment to 12.5 mg once daily; may further increase to maximum of 25 mg once daily. In adolescents 13–17 years of age with severe renal impairment, maximum recommended dosage is 12.5 mg daily if tolerated; do not escalate further.

Adderall XR and Mydayis not recommended in patients with ESRD (GFR <15 mL/minute per 1.73 m²).

Geriatric Patients

Not studied. In general, initiate at the lower end of the dosage range, reflecting the greater frequency of reduced hepatic, renal, or cardiac function and of concomitant diseases and medication therapy in geriatric patients.

Cautions for Dextroamphetamine

Contraindications

• Hypersensitivity to dextroamphetamine or other components of the formulation.

• Concomitant use of monoamine oxidase inhibitors (MAOIs), or within 14 days of discontinuing an MAOI (including linezolid and IV methylene blue), because of the increased risk of hypertensive crisis.

Warnings/Precautions

Warnings

Abuse, Misuse, and Addiction

Amphetamines expose patients to the risks of abuse and misuse, which can lead to the development of substance use disorder (including addiction). Misuse and abuse of CNS stimulants may result in overdose or death. Risk further increased with higher dosages or unapproved routes of administration (i.e., snorting, injection). Monitor patients for signs of abuse, misuse, and addiction during treatment. Tolerance can also occur. Advise patients and/or caregivers to not share amphetamines with others and to store the medication in a safe (preferably locked) location to prevent misuse and abuse.

Other Warnings/Precautions

Risks to Patients with Serious Cardiac Disease

Sudden death reported in patients with structural cardiac abnormalities or other serious cardiac conditions receiving usual dosages of stimulants for ADHD.

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., echocardiogram [ECG]).

In general, avoid use of CNS stimulants in patients with known serious structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, coronary artery disease, or other serious cardiac conditions.

Patients who develop exertional chest pain, unexplained syncope, or other manifestations suggestive of cardiac disease during stimulant therapy should undergo prompt cardiac evaluation.

Increased Blood Pressure 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. Monitor all patients for hypertension and tachycardia.

Psychiatric Adverse Effects

May exacerbate symptoms of behavior disturbance and thought disorder in patients with preexisting psychotic disorder.

Psychotic or manic symptoms (e.g., hallucinations, delusional thinking, mania) reported in patients without prior history of psychotic illness or mania receiving usual dosages of stimulants. If psychotic or manic symptoms occur, consider discontinuing therapy.

May precipitate mixed or manic episodes in ADHD patients with comorbid bipolar disorder; use with caution in these patients. 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).

Long-term Suppression of Growth in Pediatric Patients

Therapy with CNS stimulants associated with weight loss and a slowing of growth in children.

Closely monitoring growth (weight and height) during treatment; patients not growing or gaining weight as expected may require temporary discontinuance.

Peripheral Vasculopathy, including Raynaud's Phenomenon

Stimulants are associated with peripheral vascular disorders, including Raynaud’s phenomenon. Careful observation for digital changes warranted during stimulant therapy; further clinical evaluation (e.g., referral to rheumatologist) may be appropriate for certain patients who develop signs and symptoms of peripheral vasculopathy.

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. If seizures occur, discontinue therapy.

Serotonin Syndrome

Potentially fatal serotonin syndrome possible when amphetamines used with other medications that affect serotonergic neurotransmitters, such as MAOIs, SSRIs, SNRIs, triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, and St. John’s Wort (Hypericum perforatum).

Amphetamines metabolized to some extent by CYP2D6 and, to a minor extent, inhibit CYP2D6. In patients receiving concomitant CYP2D6 inhibitors, consider an alternate nonserotonergic medication or medication that does not inhibit CYP2D6.

Motor and Verbal Tics, and Worsening of Tourette's Syndrome

Amphetamines reported to exacerbate or cause onset of motor or verbal tics and worsening of Tourette’s syndrome.

Contact Sensitization

Possible contact sensitization (allergic contact dermatitis) with transdermal system. Discontinue if contact sensitization suspected.

Application Site Reactions

Local skin reactions (e.g., pain, pruritis, burning sensation, erythema, discomfort, edema, swelling) reported during wear time and immediately following removal of transdermal system. In order to minimize reactions, change application site each day.

Use of External Heat

Application of external heat increases rate and extent of absorption of amphetamines from transdermal system. Avoid exposing system to direct heat sources such as hair dryers, heating pads, electric blankets, and heated water beds.

Potential for Overdose Due to Medication Errors

Medication errors, including substitution and dispensing errors, can occur with Mydayis and other amphetamine products, which can cause overdosage. To avoid potential errors and overdosage, do not substitute Mydayis with other amphetamine products on a milligram-per-milligram basis because of different amphetamine base compositions and pharmacokinetic profiles.

Specific Populations

Pregnancy

National Pregnancy Registry for ADHD Medications available at 1-866-961-2388 and [Web].

Available data have not identified drug-associated risk of major birth defects and miscarriage.

Risk of prematurity and low birth weight observed in infants born to females receiving amphetamines. Monitor infants born to mothers receiving amphetamines during pregnancy for symptoms of withdrawal such as feeding difficulties, irritability, agitation, and excessive drowsiness.

Amphetamines can cause vasoconstriction, decreasing placental perfusion, and can stimulate uterine contractions, increasing the risk of preterm delivery.

Lactation

Distributed into milk at relative infant dose of 2–13.8% of maternal weight-adjusted dosage. Because of potential for serious adverse effects in breast-fed infants, breastfeeding not recommended in mothers receiving amphetamine therapy.

Pediatric Use

Not recommended for ADHD in children <3 years of age.

Safety and efficacy of conventional preparations of dextroamphetamine sulfate and mixed amphetamine salts for ADHD established in children ≥3 years of age.

Safety and efficacy of dextroamphetamine sustained-release capsules (Dexedrine Spansule) established in children ≥6 years of age.

Safety and efficacy of extended-release mixed amphetamine salts (Mydayis) established for ADHD in adolescents 13–17 years of age.

Safety and efficacy of extended-release mixed amphetamine salts (Adderall XR) established for ADHD in children ≥6 years of age.

Safety and efficacy of Dyanavel XR tablets and oral suspension established for ADHD in children and adolescents 6–17 years of age.

Safety and efficacy of Xelstrym transdermal system established for ADHD in children and adolescents 6–17 years of age.

Geriatric Use

No differences in response identified between geriatric patients and younger adults.

Hepatic Impairment

Possible inhibition of drug elimination, resulting in prolonged exposure.

Renal Impairment

Possible inhibition of drug elimination, resulting in prolonged exposure.

Common Adverse Effects

Conventional and sustained-release dextroamphetamine preparations: palpitations, tachycardia, blood pressure elevations, sudden death, myocardial infarction, reports of cardiomyopathy with chronic use, psychotic episodes (rare), overstimulation, restlessness, dizziness, insomnia, irritability, euphoria, dyskinesia, dysphoria, depression, tremor, headache, motor and verbal tics, exacerbation of Tourette’s syndrome, aggression, anger, logorrhea, dermatillomania, blurred vision, mydriasis, mouth dryness, unpleasant taste, diarrhea, constipation, intestinal ischemia, other gastrointestinal disturbances, anorexia, weight loss, urticaria, rash, angioedema, anaphylaxis, serious skin rashes (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis), impotence, libido changes, frequent or prolonged erections, alopecia, and rhabdomyolysis.

Mydayis(≥5% of patients and at least twice the rate of placebo in pediatric patients ≥13 years of age): decreased appetite, insomnia, nausea, irritability, and weight loss. In studies in adults, the most common adverse effects were insomnia, decreased appetite, dry mouth, weight loss, tachycardia, and anxiety.

Adderall XR (≥5% of patients and with an incidence higher than placebo in pediatric patients 6–12 years of age): loss of appetite, insomnia, abdominal pain, emotional lability, vomiting, nervousness, nausea, and fever. In pediatric patients 13–17 years of age, the most common adverse effects were loss of appetite, insomnia, abdominal pain, weight loss, and nervousness. In adults, the most common adverse effects were dry mouth, loss of appetite, insomnia, headache, weight loss, nausea, anxiety, agitation, dizziness, tachycardia, diarrhea, asthenia, and urinary tract infections.

Dextroamphetamine transdermal system: most common adverse reactions (≥2%) in pediatric patients 6–17 years of age were decreased appetite, headache, insomnia, tic, abdominal pain, vomiting, nausea, irritability, increased blood pressure, and increased heart rate. Most common adverse reactions (≥5%) in adults treated with lisdexamfetamine (Vyvanse) in clinical studies (which were used to support efficacy of dextroamphetamine transdermal system) were decreased appetite, insomnia, dry mouth, diarrhea, nausea, and anxiety.

Drug Interactions

Amphetamine or metabolites modestly inhibit CYP2D6, 1A2, and 3A4 in vitro. In vivo effects on metabolism of medications metabolized by CYP isoenzymes not known. Inhibits MAO.

Drugs Affecting Hepatic Microsomal Enzymes

CYP2D6 Inhibitors: Concomitant use of amphetamines with inhibitors of CYP2D6 may increase amphetamine exposure and the risk of serotonin syndrome.

Consider an alternative concomitant nonserotonergic medication or a medication that does not inhibit CYP2D6 in patients who are receiving CYP2D6 inhibitors.

Initiate patients receiving concomitant CYP2D6 inhibitors at lower amphetamine dosages and monitor for signs and symptoms of serotonin syndrome, especially during initiation and dosage increases. If serotonin syndrome occurs, discontinue dextroamphetamine therapy and the CYP2D6 inhibitor.

Drugs Metabolized by Hepatic Microsomal Enzymes

CYP1A2 Substrates: No dosage adjustment of CYP1A2 substrates (e.g., theophylline, duloxetine, melatonin) required when dextroamphetamine transdermal system (Xelstrym) is used concomitantly.

CYP2D6 Substrates: No dosage adjustment of CYP2D6 substrates (e.g., atomoxetine, desipramine, venlafaxine) required when dextroamphetamine transdermal system (Xelstrym) is used concomitantly.

CYP3A4 Substrates: No dosage adjustment of CYP3A4 substrates (e.g., midazolam, pimozide, simvastatin) required when dextroamphetamine transdermal system (Xelstrym) is used concomitantly.

CYP2C19 substrates: No dosage adjustment of CYP2C19 substrate (e.g., omeprazole, lansoprazole, clobazam) required when dextroamphetamine transdermal system (Xelstrym) is used concomitantly.

Specific Drugs and Laboratory Tests

Dextroamphetamine Pharmacokinetics

Absorption

Bioavailability

Similar for dextroamphetamine sulfate sustained-release capsules versus immediate-release tablets.

Plasma concentration-time profiles for fixed combinations containing various salts of dextroamphetamine and amphetamine are similar for single 20-mg extended-release dose (Adderall XR) versus two 10-mg immediate-release doses (Adderall) given 4 hours apart.

Peak plasma concentration and AUC of amphetamines decrease with increasing body weight in individuals receiving fixed-combination extended-release capsules (Adderall XR).

Plasma exposure similar for single 37.5 mg extended-release dose (Mydayis) versus 25 mg dose of Adderall XR followed by 12.5 mg immediate-release amphetamine 8 hours later.

Relative bioavailability of extended-release suspension (Dyanavel XR) is 106% for d-amphetamine and 111% for l-amphetamine compared with an equal dosage of Adderall , and is 94% for both d- and l-amphetamine compared to Adderall XR.

Relative bioavailability of an equivalent dose of extended-release tablets (Dyanavel XR) compared to extended-release suspension is 105% for d-amphetamine and 106% for l-amphetamine. Chewing or swallowing the extended-release tablets does not impact exposure or time to maximum concentration.

Although children eliminate amphetamine faster, for a given dose based on body weight, exposure is greater. After adjustment for body weight, amphetamine exposure is 30% less in children compared to adults.

Alcohol increases the rate of release in vitro from many extended-release preparations. Results are provided in Table 1 for specific extended-release formulations when available.

Duration

For duration of effect for various preparations, see Table 2.

Food

Food does not affect the rate or extent of absorption of dextroamphetamine sulfate from the sustained-release capsules (e.g., Dexedrine Spansules).

The effect of food on the extent of absorption of Adderall has not been evaluated.

Food does not affect the extent of absorption of the fixed-combination extended- release mixed amphetamine salts preparation (Adderall XR), but a high-fat meal prolongs time to maximum concentration by 2.5 hours (for d-amphetamine) and 2.7 hours (for l-amphetamine). Opening the capsule and sprinkling the contents on applesauce results in comparable absorption to the intact capsule taken in the fasted state.

Food does not affect the extent of absorption of Mydayis, but a high-fat meal prolongs time to maximum concentration by 5 hours (for d-amphetamine) and 4.5 hours (for l-amphetamine). Opening the capsule and sprinkling the contents on applesauce results in comparable absorption to the intact capsule taken in the fasted state.

Administration of the extended-release oral suspension (Dyanavel XR) with a high-fat meal prolongs time to peak plasma concentrations by 1 hour, increases maximum plasma concentrations by 2%, and decreases exposure by 5.7% (for d-amphetamine) and 7.4% (for l-amphetamine).

Administration of the extended-release tablets (Dyanavel XR) with a high-fat meal decreases maximum serum concentrations by 3% and decreases exposure by 4% (for d-amphetamine) and 7.3% (for l-amphetamine).

Plasma Concentrations

For timing of peak plasma concentrations, see Table 3.

No expected accumulation of Adderall XR at steady state when used in children.

Steady state achieved after 7−8 days of dosing with Mydayis; mean accumulation ratio of 1.6.

Application of a heating pad on Xelstrym shortens the median time to peak plasma concentrations by 2 hours and increases peak plasma concentrations and total exposure over 9 hours by 16% and 50%, respectively.

Application of Xelstrym to various recommended sites (e.g., hip, upper arm, chest, upper back, or flank) does not alter dextroamphetamine pharmacokinetics.

Distribution

Extent

Distributed into human milk.

Volume of distribution increases with increasing body weight in individuals receiving fixed-combination extended-release capsules (Adderall XR).

Elimination

Metabolism

Metabolized to several active metabolites.

Enzymes involved in metabolism not clearly defined; however, CYP2D6 is involved with formation of at least one metabolite. Because CYP2D6 is genetically polymorphic, potential variability in metabolism among patients exists.

Elimination Route

With normal urinary pH, excreted in urine as unchanged drug (approximately 30–40%) and metabolites (approximately 50%). Changes in urinary pH may alter excretion; urinary recovery of unchanged drug reported to range from 1–75%, depending on urinary pH.

Clearance increases with increasing body weight in individuals receiving fixed-combination extended-release capsules (Adderall XR). On a mg/kg basis, however, children have higher clearance than adolescents or adults.

Half-life

Elimination half-life increases with increasing body weight in individuals receiving fixed-combination extended-release capsules (Adderall XR).

For elimination half-lives of various dextroamphetamine and mixed amphetamine salt preparations, see Table 4.

Stability

Storage

Oral

Immediate-release Preparations

Store in tight, light-resistant containers at 20–25°C. (immediate-release dextroamphetamine sulfate tablets [e.g., Zenzedi] may be exposed to 15–30°C).

Sustained-release Capsules

Store in tight, light-resistant containers at 20–25°C.

Extended-release Capsules

Store at 20–25°C (excursions permitted between 15–30°C).

Extended-release Tablets and Oral Suspension

Store at 20–25°C (excursions permitted between 15–30°C).

Transdermal

Transdermal System

Store at 20–25°C protected from light (excursions permitted between 15–30°C). Keep sealed in the original pouch until use.

Dextroamphetamine Mechanism of Action

• Amphetamines are sympathomimetic amines with CNS stimulant activity.

• May block the reuptake of norepinephrine and dopamine into the presynaptic neuron and increase the release of these monoamines into the extraneural space.

• Peripheral actions of amphetamines include elevation of systolic and diastolic blood pressure, weak bronchodilation, and weak respiratory stimulation.

Advice to Patients

• Educate patients and their families on the risks of abuse, misuse, and addiction of amphetamines, which can lead to overdose and death, and inform them on proper disposal of unused medication. Advise patients to store amphetamines in a safe, preferably locked place, and to not give their medication to anyone else.

• Inform patients there are potential risks with amphetamine therapy in patients with serious heart disease, such as sudden death. Patients or caregivers should inform clinicians immediately if adverse cardiovascular effects (e.g., exertional chest pain, unexplained syncope, other symptoms suggestive of cardiac disease) occur during stimulant therapy.

• Inform patients that amphetamines can cause elevations in blood pressure and heart rate and they should be monitored for these effects.

• Inform patients that amphetamines, even at recommended doses, can cause psychotic or manic symptoms even in patients without a prior history of psychotic symptoms or mania.

• Inform patients and caregivers that growth should be monitored during amphetamine therapy in pediatric patients, and patients that are not growing or gaining weight as expected may require treatment interruption.

• Inform patients about the risk of peripheral vascular disorders, including Raynaud's phenomenon, and the associated signs and symptoms (e.g., feelings of numbness, coolness, or pain in fingers or toes; changes in color from pale to blue to red). Advise patients to report any new numbness, pain, skin color change, or sensitivity to temperature in fingers or toes to their clinician and to immediately contact their clinician if any signs of unexplained wounds appear on fingers or toes. Rheumatology referral may be appropriate for certain patients.

• Inform patients amphetamines can lower the seizure threshold. Advise patients to contact their healthcare provider immediately and to discontinue amphetamine therapy if a seizure occurs.

• Inform patients of the risk of serotonin syndrome with concomitant use of amphetamine and other drugs that affect serotonergic neurotransmitter systems such as monoamine oxidase inhibitors (MAOIs), linezolid, selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, and St. John’s Wort (Hypericum perforatum). Advise patients to contact their healthcare provider or report to the emergency department immediately if symptoms of serotonin syndrome occur.

• Inform patients that motor and verbal tics and worsening of Tourette’s syndrome can occur with amphetamine therapy. Patients should notify their healthcare provider if there are new, emerging, or worsening tics or symptoms of Tourette’s syndrome.

• Advise patients to avoid alcohol while taking certain formulations of extended-release amphetamine since alcohol can cause rapid release of the drug.

• Advise patients to avoid exposing the dextroamphetamine transdermal system to direct heat sources such as hair dryers, heating pads, electric blankets, and heated water beds while wearing it. Advise patients that in order to minimize skin irritation, discomfort, or pain with the patch, the application site should be changed each day.

• Advise patients to inform their clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary and herbal supplements, as well as any concomitant illnesses (e.g., cardiac/cardiovascular disease, thyroid disease, glaucoma, suicidal ideation or behaviors, mental/psychiatric disorder, seizures, hepatic or renal disease).

• Advise patients to inform their clinician if they are or plan to become pregnant or plan to breast-feed. Inform patients that there is a pregnancy registry for females exposed to amphetamines during pregnancy. Inform breastfeeding women that breastfeeding while taking amphetamines is not recommended.

• Advise patients of other important precautionary information.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

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