Amphetamine

Amphetamine is commercially available as amphetamine, amphetamine sulfate, and in mixed salt preparations containing either amphetamine aspartate, amphetamine sulfate, dextroamphetamine saccharate, and dextroamphetamine sulfate or amphetamine, amphetamine aspartate, and dextroamphetamine sulfate.1, 2, 3, 4, 5, 6

Amphetamine sulfate conventional tablets (e.g., Evekeo^®) and amphetamine mixed salt immediate-release conventional tablets containing amphetamine aspartate, amphetamine sulfate, dextroamphetamine saccharate, and dextroamphetamine sulfate (e.g., Adderall^®) are used for the treatment of attention deficit hyperactivity disorder (ADHD) in pediatric patients 3 years of age and older.1, 2 Amphetamine mixed salt triphasic extended-release capsules containing amphetamine aspartate, amphetamine sulfate, dextroamphetamine saccharate, and dextroamphetamine sulfate (e.g., Mydayis^®) are used for the treatment of ADHD in adults and pediatric patients 13 years of age and older.3 Amphetamine extended-release orally disintegrating tablets (e.g., Adzenys XR-ODT^®), amphetamine mixed salt biphasic extended-release capsules containing amphetamine aspartate, amphetamine sulfate, dextroamphetamine saccharate, and dextroamphetamine sulfate (e.g., Adderall XR^®), and extended-release oral suspension and extended-release tablets containing amphetamine, amphetamine aspartate, and dextroamphetamine sulfate (e.g., Dyanavel^® XR) are used for the treatment of ADHD in adults and pediatric patients 6 years of age and older.4, 5, 6

Amphetamine sulfate conventional tablets (e.g., Evekeo^®) are also used for the short-term treatment of exogenous obesity as an adjunct in a regimen for weight reduction based on caloric restriction in adults and pediatric patients 12 years of age and older who are refractory to alternative therapy (e.g., repeated diets, group programs, and other drugs).2

Attention Deficit Hyperactivity Disorder

Amphetamine sulfate conventional tablets (e.g., Evekeo^®) and amphetamine mixed salt immediate-release conventional tablets containing amphetamine aspartate, amphetamine sulfate, dextroamphetamine saccharate, and dextroamphetamine sulfate (e.g., Adderall^®) are used for the treatment of ADHD in pediatric patients 3 years of age and older.1, 2 Amphetamine mixed salt triphasic extended-release capsules containing amphetamine aspartate, amphetamine sulfate, dextroamphetamine saccharate, and dextroamphetamine sulfate (e.g., Mydayis^®) are used for the treatment of ADHD in adults and pediatric patients 13 years of age and older.3 Amphetamine extended-release orally disintegrating tablets (e.g., Adzenys XR-ODT^®), amphetamine mixed salt biphasic extended-release capsules containing amphetamine aspartate, amphetamine sulfate, dextroamphetamine saccharate, and dextroamphetamine sulfate (e.g., Adderall XR^®), and extended-release oral suspension and extended-release tablets containing amphetamine, amphetamine aspartate, and dextroamphetamine sulfate (e.g., Dyanavel^® XR) are used for the treatment of ADHD in adults and pediatric patients 6 years of age and older.4, 5, 6

Clinical Experience

Pediatric Patients

The efficacy and safety of amphetamine sulfate conventional tablets (e.g., Evekeo^®) for the treatment of ADHD were established in a multicenter, randomized, double-blind, placebo-controlled crossover laboratory classroom study in 107 pediatric patients 6-12 years of age.7 Pediatric patients with ADHD (inattentive, hyperactive/impulsive, or combined type) were randomized, after an initial 8 weeks of open-label dose optimization, to receive either amphetamine sulfate for 1 week followed by placebo for 1 week or placebo for 1 week followed by amphetamine sulfate for 1 week for the 2-week double-blind period.7 During the 8-week open-label period, patients would take amphetamine 5 mg twice daily; doses were titrated weekly in 5-mg increments until an optimal dose was achieved based on clinical response and tolerability.7 The main efficacy measure assessed was the Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP)-Combined score determined at 2 hours post-dose on 2 full-length laboratory classroom days (each 1 week apart).7 The SKAMP scale is a validated subjective laboratory classroom scale that contains 13 items on which subjects are rated on a 7-point scale for each.7 The mean age of patients in this study was 9.6 years; 60.8% were male and 59.8% were white.7 Amphetamine, compared to placebo, was found to substantially improve SKAMP-Combined scores at 2 hours post-dose.7 The onset of effect was found as soon as 45 minutes post-dose and extended through 10 hours.7

The efficacy and safety of the amphetamine extended-release oral suspension product (e.g., Dyanavel^® XR) for the treatment of ADHD were established in a multicenter, randomized, double-blind, placebo-controlled laboratory classroom study in 99 pediatric patients 6-12 years of age.6, 8 Pediatric patients with ADHD were randomized, after an initial 5 weeks of open-label dose optimization, to receive either the amphetamine extended-release oral suspension product or placebo orally once daily for 1 week.6, 8 During the 5-week open-label period, all patients were started on either 2.5 or 5 mg of amphetamine once daily in the morning.6, 8 The dosage was titrated every 4-7 days in increments of 2.5-10 mg until an optimal dosage was reached; the maximum daily dosage was 20 mg.6, 8 The main efficacy outcome was the change from pre-dose in the SKAMP-Combined score at 4 hours post-dose.6, 8 Patients who received the amphetamine extended-release oral suspension product had substantial improvements in the SKAMP-Combined score at 4 hours post-dose compared to patients who received placebo.5, 7 Substantial improvements in the SKAMP-Combined score were also seen at 1, 2, 6, 8, 10, 12, and 13 hours post-dose.5, 7

In 2016, a Cochrane review of 23 trials enrolling 2675 patients compared the efficacy of amphetamines (any oral form including amphetamine, dextroamphetamine, lisdexamfetamine, and mixed amphetamine salts, at any dosage) to placebo for the treatment of ADHD in children and adolescents 3-17 years of age.9 Within this meta-analysis, there were 12 studies that assessed mixed amphetamine salts and 2 studies that assessed amphetamine derivatives.9 The main efficacy outcome was change in core ADHD symptoms (i.e., inattention, hyperactivity, impulsivity).9 The Cochrane review found that amphetamines (any type) improve parent-rated, teacher-rated, clinician-rated, and investigator-rated ADHD symptoms.9 A subgroup analysis based on amphetamine type (dextroamphetamine, lisdexamfetamine, or mixed amphetamine salts) found that mixed amphetamine salts may improve parent-rated ADHD symptoms.9

Adults

The efficacy and safety of the extended-release amphetamine tablet product (e.g., Dyanavel^® XR) for the treatment of ADHD were assessed in a randomized, double-blind, placebo-controlled study in 130 adults up to 60 years of age.10 Patients with ADHD were randomized to receive either the amphetamine extended-release tablet product or placebo for 5 weeks.10 Patients randomized to receive the amphetamine product or matching placebo were initiated at a dosage of 5 mg orally once daily in the morning; the dosage was titrated in 5-mg increments each week to a final dosage of 20 mg for the remainder of the study period.10 The main efficacy outcome was the difference between the amphetamine product and placebo in the mean Permanent Product Measure of Performance Total (PERMP-T) across specific time points post-dose measured at the end of the 5-week period.10 The PERMP-T is a time-sensitive and skill-adjusted validated test consisting of simple math problems to be completed at multiple time points.10 This test helps to provide an objective measure of a subject's attention, productivity, and behavior in a simulated setting.10 The mean age of patients in this study was 32.4 years; 59.8% were male and 81.9% were white.10 At the end of week 5, patients who received the amphetamine extended-release tablet product had substantial improvements in the PERMP-T score averaged across all time points post-dose compared to patients who received placebo.10

In 2018, a Cochrane review of 19 trials enrolling 2521 patients compared the efficacy of amphetamines (dextroamphetamine, lisdexamfetamine, and mixed amphetamine salts) with placebo for the treatment of ADHD in adults.11 The main efficacy outcome was the severity of ADHD symptoms assessed by clinicians and patients.11 The mean age of patients in this meta-analysis was 35.3 years; 57.2% were Caucasian males and 78.8% had a combined type of ADHD.11 This Cochrane review found evidence suggesting that amphetamines are more efficacious than placebo in the reduction of the severity of clinician- and patient-assessed ADHD symptoms.11 A subgroup analysis based on amphetamine type (dextroamphetamine, lisdexamfetamine, or mixed amphetamine salts) found that mixed amphetamine salts, compared to placebo, may improve the severity of ADHD symptoms as assessed by clinicians, but not when assessed by participants.11

Clinical Perspective

The American Academy of Pediatrics (AAP) has developed guidelines for children and adolescents with ADHD.12 For pediatric patients 6-12 years of age with ADHD, FDA-labeled medications should be prescribed, in addition to parent training in behavior management (PTBM) and/or behavioral classroom interventions.12 For choice of medication, the evidence is particularly strong for stimulant drugs (e.g., amphetamines, methylphenidate).12 Evidence is sufficient but not as strong for atomoxetine, extended-release guanfacine, and extended-release clonidine.12 For adolescents 12-18 years of age with ADHD, FDA-labeled medications should be prescribed with the adolescent's assent.12 The provider is also encouraged to prescribe behavioral and other evidence-based training interventions if available.12 Dosages should be titrated to achieve maximum benefit with tolerable adverse effects.12

The AAP also provides recommendations for pediatric patients with ADHD as young as 4 years of age.12 The first lines of treatment for pediatric patients 4-6 years of age are PTBM and/or behavioral classroom interventions.12 AAP states that methylphenidate may be considered if these 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.12

International experts have published recommendations for the treatment of ADHD in adults.13, 14 Treatment of ADHD in adults should follow a multimodal approach that includes psychoeducation, pharmacotherapy, cognitive behavior therapy, and coaching for ADHD.13 First-line pharmacotherapy agents include long-acting stimulants such as mixed amphetamine salts, methylphenidate, and lisdexamfetamine.14 Short-acting and intermediate-acting stimulants are considered second-line and can also be adjunctive agents.14 Atomoxetine may also be used as a second-line or adjunctive agent.14

Narcolepsy

Guidelines from the American Academy of Sleep Medicine (AASM) provide a strong recommendation for the use of several agents for the treatment of narcolepsy in adults, including modafinil, pitolisant, sodium oxybate, and solriamfetol.15 A conditional recommendation is given for armodafinil, dextroamphetamine, and methylphenidate.15 These recommendations are derived from a systematic review and meta-analysis conducted by the AASM to assess the efficacy of interventions for the treatment of central disorders of hypersomnolence, including narcolepsy.16 The AASM guidelines note that the data support the use of individual medications rather than entire classes; however, enantiomers, racemic compounds, or prodrugs (e.g., armodafinil, amphetamine salts) might also be used for treatment.15

Exogenous Obesity

Amphetamine sulfate conventional tablets (e.g., Evekeo^®) are used for the short-term treatment of exogenous obesity as an adjunct in a regimen for weight reduction based on caloric restriction in adults and pediatric patients 12 years of age and older who are refractory to alternative therapy (e.g., repeated diets, group programs, and other drugs).2

The amphetamines were the first class of drugs approved for short-term pharmacologic treatment of obesity; however, most amphetamines have been withdrawn from the US market due to adverse events and the potential for addiction.18 In short-term placebo-controlled trials of amphetamine derivatives, patients who received active drugs demonstrated weight loss of approximately 0.5 pounds (0.23 kg) per week more than placebo.18 However, the amount of weight loss in clinical trials has varied, and the observed increase in weight loss may be attributed to non drug-related factors.2, 18

Guidelines from the American Gastroenterological Association (AGA) recommend the addition of pharmacologic agents in adults with obesity or overweight with weight-related complications who have had an inadequate response to lifestyle interventions.17 Selection of an appropriate drug or intervention should be based on the clinical profile and needs of the patient, including comorbidities, patient preferences, costs, and access.17 Given the chronic nature of weight management, long-term pharmacologic therapy is usually necessary in patients with obesity who have an inadequate response to lifestyle interventions alone.17 Amphetamine is indicated only for the short-term treatment of obesity.2

Autism Spectrum Disorder

Mixed amphetamine salts have been used for the symptomatic treatment of inattention, impulsivity, and hyperactivity in pediatric patients with autism spectrum disorder (ASD)†.19 The AAP has developed guidelines for children and adolescents with ASD.19 While there are not currently any medications that correct core social and communication symptoms in patients with ASD, there are medications that may be used to help manage behavioral and psychiatric symptoms.19 For symptoms of hyperactivity, impulsivity, inattention, and distractibility, the AAP suggests the use of psychostimulants (e.g., methylphenidate, dexmethylphenidate, mixed amphetamine salts, lisdexamfetamine, dextroamphetamine) after behavioral approaches are implemented if problems persist.19 Patients should be started on a low dosage of the stimulant, with dosage increases as needed and tolerated.19 Stimulants may be most effective in pediatric patients who do not have comorbid intellectual disability.19

Cocaine Use Disorder

Amphetamine and mixed amphetamine salts have been used in the treatment of cocaine use disorder†.20 According to guidelines from the American Society of Addiction Medicine (ASAM) and the American Academy of Addiction Psychiatry (AAAP), a long-acting amphetamine formulation can be considered to promote cocaine abstinence in patients with cocaine use disorder.20 For patients with co-occurring ADHD, a long-acting amphetamine formulation can be given additional consideration.20

Dosage and Administration ⬆ ⬇

General

Pretreatment Screening

Evaluate patients for cardiac disease (i.e., obtain careful medical history, perform physical examination, and screen for a family history of sudden death or ventricular arrhythmia).1, 2, 3, 4, 5, 6
Screen for a family history and clinically evaluate for motor or verbal tics or Tourette's syndrome prior to initiating therapy.1, 2, 3, 4, 5, 6
Because CNS stimulants, including amphetamines, have a high potential for abuse and dependence, assess the risks of abuse, misuse, and addiction prior to initiating therapy.1, 2, 3, 4, 5, 6
Screen for pre-existing psychotic or manic symptoms/illness and risk factors for developing a manic episode (comorbid or history of depressive symptoms or family history of suicide, bipolar disorder, or depression).1, 2, 3, 4, 5, 6

Patient Monitoring

Routinely monitor patients receiving amphetamine therapy for the emergence or worsening of tics or Tourette's syndrome, and reduce dosage or discontinue treatment if clinically needed.1, 2, 3, 4, 5, 6
Throughout treatment, reassess each patient's risk of abuse, misuse, and addiction.1, 2, 3, 4, 5, 6 Frequently monitor for signs of abuse, misuse, and addiction during treatment.1, 2, 3, 4, 5, 6
Monitor all patients for the development of hypertension and tachycardia.1, 2, 3, 4, 5, 6
Closely monitor growth (height and weight) in pediatric patients receiving stimulant therapy.1, 2, 3, 4, 5, 6
Monitor for the emergence or worsening of psychotic or manic symptoms/episodes.1, 2, 3, 4, 5, 6
Carefully observe for signs and symptoms of peripheral vasculopathy in fingers and toes during therapy.1, 2, 3, 4, 5, 6

Dispensing and Administration Precautions

Handling and Disposal

Amphetamine preparations should be disposed of by a medicine take-back program at a U.S. Drug Enforcement Administration (DEA) authorized collection site when they are no longer needed.1, 2 If there is no take-back program or authorized DEA collection site available, the drug can be mixed with an undesirable, nontoxic substance such as dirt, cat litter, or used coffee grounds and disposed of in a sealed plastic bag in the household trash.1, 2
The manufacturer states that medication errors, including substitution and dispensing errors, can occur with Mydayis^®, Adzenys XR-ODT^®, and other amphetamine products, which can lead to potential overdosage.3, 5 To avoid potential errors and overdosage, Mydayis^® and Adzenys XR-ODT^® should not be substituted with other amphetamine products on a milligram-per-milligram basis due to different amphetamine base compositions and differences in pharmacokinetics.3, 5
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.555

Administration

Amphetamine products are administered orally.1, 2, 3, 4, 5, 6

The following amphetamine formulations are commercially available in the United States: immediate-release amphetamine sulfate conventional tablets (e.g., Evekeo^®); immediate-release conventional tablets containing mixed amphetamine salts (amphetamine aspartate, amphetamine sulfate, dextroamphetamine saccharate, and dextroamphetamine sulfate; e.g., Adderall^®); triphasic extended-release capsules containing mixed amphetamine salts (amphetamine aspartate, amphetamine sulfate, dextroamphetamine saccharate, and dextroamphetamine sulfate; e.g., Mydayis^®); biphasic extended-release capsules containing mixed amphetamine salts (amphetamine aspartate, amphetamine sulfate, dextroamphetamine saccharate, and dextroamphetamine sulfate; e.g., Adderall XR^®); extended-release amphetamine orally disintegrating tablets (e.g., Adzenys XR-ODT^®); extended-release tablets containing amphetamine, amphetamine aspartate, and dextroamphetamine sulfate (e.g., Dyanavel^® XR); and extended-release oral suspension containing amphetamine, amphetamine aspartate, and dextroamphetamine sulfate (e.g., Dyanavel^® XR).1, 2, 3, 4, 5, 6

Immediate-release Tablets

Immediate-release conventional tablet preparations of amphetamine sulfate (Evekeo^®) and mixed amphetamine salts (Adderall^®) are administered 2 or 3 times daily in divided doses with the initial dose given upon awakening; additional doses (1 or 2) are given at intervals of 4-6 hours.1, 2

Because of the potential for insomnia, administration of immediate-release tablets should be avoided in the late evening.2

When used as an anorectic agent for the treatment of exogenous obesity, the manufacturer recommends administering Evekeo^® 30<60 minutes before meals.2

Store tablets at 20-25°C.1, 2

Extended-release Capsules

The commercially available extended-release capsules containing amphetamine sulfate and amphetamine aspartate in fixed combination with dextroamphetamine saccharate and dextroamphetamine sulfate (Adderall XR^®, Mydayis^®) may be swallowed intact with or without food; alternatively, the entire contents of the capsule may be sprinkled on a small amount (i.e., a spoonful) of applesauce immediately prior to administration.3, 4 The sprinkle/applesauce should be taken immediately and should not be stored.3, 4 Patients should take the sprinkled applesauce in its entirety without chewing.3, 4 Subdividing the contents of a capsule is not recommended.3, 4 The manufacturer states that Mydayis^® should be administered in a consistent manner relative to food intake.3

The daily dose of amphetamines (as extended-release capsules) should be given on awakening.3, 4 Since Mydayis^® can last for a duration of up to 16 hours and can cause difficulty sleeping, the manufacturer recommends taking the daily dose immediately upon awakening.3 In the event of a missed dose, doses should not be administered later in the day.3 Administration of extended-release capsules in the afternoon should be avoided because of the potential for insomnia.4

Store at 20-25°C; excursions are permitted between 15-30°C.3, 4

Extended-release Orally Disintegrating Tablets

Amphetamine extended-release orally disintegrating tablets (Adzenys XR-ODT^®) are administered once daily in the morning with or without food.5

The extended-release orally disintegrating tablets should be administered immediately following removal from the blister package.5 The tablet should be removed from the blister package with dry hands by peeling back the foil and not by pushing the tablet through the foil.5 The whole tablet should be placed on the patient's tongue and allowed to disintegrate in saliva without chewing or crushing.5 The tablet will disintegrate in saliva so that it can be swallowed.5

Store at 20-25°C; excursions are permitted between 15-30°C.5 Store blister packages in the rigid, plastic travel case after removal from the carton.5

Extended-release Tablets

Extended-release tablets containing amphetamine, amphetamine aspartate, and dextroamphetamine sulfate (Dyanavel^® XR) are administered once daily in the morning without regard to meals.6

The tablets may be chewed or swallowed whole.6 Dosing increments of 2.5 mg can be attained by dividing the functionally scored 5 mg extended-release tablet into equal halves at the score line.6

Store at 20-25°C; excursions are permitted between 15-30°C.6

Extended-release Oral Suspension

Extended-release oral suspension containing amphetamine, amphetamine aspartate, and dextroamphetamine sulfate (Dyanavel^® XR) is administered once daily in the morning without regard to meals.6

The bottle adapter should be firmly inserted into the bottle prior to use; do not remove after insertion.6 The bottle of suspension should be shaken well before each administration.6 The oral dosing dispenser supplied by the pharmacist should be used to administer the oral suspension.6

Store at 20-25°C; excursions are permitted from 15-30°C.6

Dosage

Immediate-release (Adderall^®) and extended-release formulations of mixed amphetamine salts (Adderall XR^®, Mydayis^®, Adzenys XR-ODT^®) contain d-amphetamine and l-amphetamine salts in a 3:1 ratio.1, 3, 4, 5 Evekeo^® contains a racemic mixture of d-amphetamine and l-amphetamine.2 Dyanavel^® XR extended-release tablets and oral suspension contain d-amphetamine and l-amphetamine in a 3.2:1 ratio.6

The manufacturer states that the 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.4

Manufacturers state that Mydayis^® and Adzenys XR-ODT^® should not be substituted with other amphetamine products on a milligram-per-milligram basis due to different amphetamine base compositions and pharmacokinetic profiles.3, 5

The manufacturer states that substitution of Dyanavel^® XR extended-release oral suspension for Dyanavel^® XR extended-release oral tablets may occur on a milligram-per-milligram basis; however, other amphetamine products should not be substituted on a milligram-per-milligram basis due to different amphetamine base compositions and pharmacokinetic profiles.6

Dosages of Adzenys XR-ODT^® and Dyanavel^® XR are expressed as the amount of amphetamine base,5, 6 whereas the dosages of other amphetamine products are expressed in terms of the total amount of amphetamine salts.1, 2, 3, 4

Dosage of amphetamines should be adjusted according to individual response, therapeutic needs, and tolerance; the smallest dosage required to produce the desired response should always be used.1, 2 When possible, therapy should be interrupted occasionally to determine if there is a recurrence of behavioral symptoms sufficient to require continued treatment.2

Adults

Attention Deficit Hyperactivity Disorder

Immediate-release Oral Preparations (Evekeo®, Adderall®) :

For the treatment of ADHD in adults, the initial dosage of immediate-release amphetamine sulfate (Evekeo^®) and mixed amphetamine salts (Adderall^®) is 5 mg once or twice daily; the daily dosage may be increased by 5 mg at weekly intervals until the optimum response is attained.1, 2 The duration of action of Evekeo^® and Adderall^® is approximately 4<6 hours.554 When immediate-release amphetamines are administered in divided doses throughout the day, the first dose is given upon awakening, with additional doses (1 or 2) given at intervals of 4-6 hours.1, 2 Total daily dosage rarely should exceed 40 mg.1, 2

Extended-Release Capsules (Adderall XR®, Mydayis®) :

In adults who are receiving drug therapy for ADHD for the first time or are being switched from therapy with another drug, the recommended dosage of extended-release capsules containing mixed amphetamine salts (Adderall XR^®) is 20 mg once daily.4 When switching from conventional tablets (Adderall^®) to extended-release capsules containing mixed amphetamine salts (Adderall XR^®), the total daily dosage of amphetamines may remain the same but should be given once daily.4

In adults 18-55 years of age, the recommended initial dosage of extended-release capsules containing mixed amphetamine salts (Mydayis^®) is 12.5 mg once daily in the morning upon awakening.3 An initial dosage of 25 mg once daily may be considered in some patients.3 The daily dosage may be increased in increments of 12.5 mg no sooner than weekly based on clinical response up to a maximum dosage of 50 mg once daily.3 Dosages above 50 mg daily have not demonstrated clinically meaningful benefit.3 Because the duration of action of Mydayis^® is estimated to be up to 16 hours, the drug should be administered immediately upon awakening to reduce the potential for insomnia.3

Extended-release Orally Disintegrating Tablets (Adzenys XR-ODT®) :

For the treatment of ADHD in adults, a dosage of 12.5 mg once daily in the morning is recommended.5 The duration of action of Adzenys XR-ODT^® is approximately 10<12 hours.554 Patients being switched from extended-release capsules containing mixed amphetamine salts (Adderall XR^®) at a dosage of 5 mg once daily can be switched to a dosage of 3.1 mg once every morning as the extended-release orally disintegrating tablet.5 Patients receiving extended-release capsules containing mixed amphetamine salts (Adderall XR^®) at a dosage of 10 mg once daily can be switched to a dosage of 6.3 mg once every morning as the extended-release orally disintegrating tablet.5 Patients receiving extended-release capsules containing mixed amphetamine salts (Adderall XR^®) at a dosage of 15 mg once daily can be switched to a dosage of 9.4 mg once every morning as the extended-release orally disintegrating tablet.5 Patients receiving extended-release capsules containing mixed amphetamine salts (Adderall XR^®) at a dosage of 20 mg once daily can be switched to a dosage of 12.5 mg once every morning as the extended-release orally disintegrating tablet.5 Patients receiving extended-release capsules containing mixed amphetamine salts (Adderall XR^®) at a dosage of 25 mg once daily can be switched to a dosage of 15.7 mg once every morning as the extended-release orally disintegrating tablet.5 Patients receiving extended-release capsules containing mixed amphetamine salts (Adderall XR^®) at a dosage of 30 mg once daily can be switched to a dosage of 18.8 mg once every morning as the extended-release orally disintegrating tablet.5

Extended-release Tablets and Oral Suspension (Dyanavel® XR) :

The initial dosage of extended-release amphetamine tablets and extended-release oral suspension is 2.5 or 5 mg once daily in the morning; the daily dosage may be increased by 2.5-10 mg per day every 4-7 days based on clinical response.6 The maximum recommended dosage is 20 mg once daily.6 The duration of action of Dyanavel^® XR is approximately 13 hours.13

Exogenous Obesity

For the treatment of exogenous obesity in adults, the usual dosage of immediate-release amphetamine sulfate tablets (Evekeo^®) is 5-10 mg administered 30-60 minutes before meals, up to a maximum of 30 mg daily.2

Narcolepsy

In the treatment of narcolepsy, the usual total dosage of immediate-release amphetamine salts (Adderall^®) is 5-60 mg daily, depending upon the patient's response, usually given in divided doses.1 The first dose should be given upon awakening, with additional doses (1 or 2) administered every 4-6 hours.1 In adults, the initial dosage is 10 mg daily; daily dosage is increased by 10 mg at weekly intervals until the optimum response is attained.1 When intolerable adverse effects (e.g., insomnia, anorexia) occur, dosage should be reduced.1

Pediatric Patients

Attention Deficit Hyperactivity Disorder

Immediate-release Tablets (Adderall®, Evekeo®) :

For the treatment of attention deficit hyperactivity disorder (ADHD) in children 3-5 years of age, the initial dosage of immediate-release amphetamine sulfate (Evekeo^®) and mixed amphetamine salts (Adderall^®) is 2.5 mg daily; the daily dosage may be increased by 2.5 mg at weekly intervals until the optimum response is attained.1, 2 In children ≥6 years of age, the initial dosage of amphetamine sulfate (Evekeo^®) and mixed amphetamine salts (Adderall^®) is 5 mg once or twice daily; the daily dosage may be increased by 5 mg at weekly intervals until the optimum response is attained.1, 2 The duration of action of Evekeo^® and Adderall^® is approximately 4<6 hours.554 When immediate-release amphetamines are administered in divided doses throughout the day, the first dose is given upon awakening, with additional doses (1 or 2) given at intervals of 4-6 hours.1, 2 Total daily dosage rarely should exceed 40 mg.1, 2

Extended-release Capsules (Adderall XR®, Mydayis®) :

In pediatric patients who are receiving drug therapy for ADHD for the first time or are being switched from therapy with another stimulant, amphetamine therapy may be initiated with extended-release capsules containing mixed amphetamine salts (Adderall XR^®).4 In children 6-12 years of age, the initial dosage of extended-release capsules containing mixed amphetamine salts (Adderall XR^®) is 10 mg once daily in the morning; daily dosage may be adjusted in increments of 5 or 10 mg at weekly intervals up to a maximum dosage of 30 mg daily.4 Treatment may be initiated with a dosage of 5 mg once daily when, in the opinion of the clinician, a lower initial dosage is appropriate.4 Dosages greater than 30 mg daily have not been studied in pediatric patients.4

In adolescents 13-17 years of age who are receiving drug therapy for ADHD for the first time or are being switched from therapy with another stimulant, the initial dosage of extended-release capsules containing mixed amphetamine salts (Adderall XR^®) is 10 mg once daily.4 Dosage may be increased to 20 mg once daily after 1 week if symptoms are not adequately controlled.4 The duration of action of Adderall XR^® is approximately 10-12 hours.554

In adolescents 13-17 years of age who are receiving drug therapy for ADHD for the first time or are being switched from therapy with another stimulant, amphetamine therapy may be initiated with extended-release capsules containing mixed amphetamine salts (Mydayis^®).3 In adolescents 13-17 years of age, the initial dosage of extended-release capsules containing mixed amphetamine salts (Mydayis^®) is 12.5 mg once daily immediately upon awakening; daily dosage may be increased in increments of 12.5 mg no sooner than weekly based on clinical response to a maximum dosage of 25 mg once daily.3 Dosages >25 mg once daily have not been evaluated in pediatric patients in clinical studies.3 Because the duration of action of Mydayis^® is estimated to be up to 16 hours, the drug should be administered immediately upon awakening to reduce the potential for insomnia.3

Extended-release Tablets and Oral Suspension (Dyanavel® XR) :

In children ≥6 years of age, the initial dosage of extended-release amphetamine tablets and extended-release oral suspension is 2.5 or 5 mg once daily in the morning; the daily dosage may be increased by 2.5-10 mg per day every 4-7 days based on clinical response.6 The maximum recommended dosage is 20 mg once daily.6 The duration of action of Dyanavel^® XR is approximately 13 hours.554

Extended-release Orally Disintegrating Tablets (Adzenys XR-ODT®) :

For the treatment of ADHD in pediatric patients ≥6 years of age, the initial dosage of extended-release orally disintegrating tablets is 6.3 mg once daily in the morning.5 The dosage may be increased in increments of 3.1 or 6.3 mg at weekly intervals based on clinical response.5 The maximum recommended dosage for pediatric patients 6-12 years of age is 18.8 mg once daily, and in adolescents 13-17 years of age, 12.5 mg once daily.5 The duration of action of Adzenys XR-ODT^® is approximately 10<12 hours.554

Patients being switched from extended-release capsules containing mixed amphetamine salts (Adderall XR^®) at a dosage of 5 mg once daily can be switched to a dosage of 3.1 mg once every morning as the extended-release orally disintegrating tablet.5 Patients receiving extended-release capsules containing mixed amphetamine salts (Adderall XR^®) at a dosage of 10 mg once daily can be switched to a dosage of 6.3 mg once every morning as the extended-release orally disintegrating tablet.5 Patients receiving extended-release capsules containing mixed amphetamine salts (Adderall XR^®) at a dosage of 15 mg once daily can be switched to a dosage of 9.4 mg once every morning as the extended-release orally disintegrating tablet.5 Patients receiving extended-release capsules containing mixed amphetamine salts (Adderall XR^®) at a dosage of 20 mg once daily can be switched to a dosage of 12.5 mg once every morning as the extended-release orally disintegrating tablet.5 Patients receiving extended-release capsules containing mixed amphetamine salts (Adderall XR^®) at a dosage of 25 mg once daily can be switched to a dosage of 15.7 mg once every morning as the extended-release orally disintegrating tablet.5 Patients receiving extended-release capsules containing mixed amphetamine salts (Adderall XR^®) at a dosage of 30 mg once daily can be switched to a dosage of 18.8 mg once every morning as the extended-release orally disintegrating tablet.5

Exogenous Obesity

For the treatment of exogenous obesity in pediatric patients ≥12 years of age, the usual dosage of immediate-release amphetamine sulfate tablets (Evekeo^®) is 5-10 mg administered 30-60 minutes before meals, up to a maximum of 30 mg daily.2

Narcolepsy

In the treatment of narcolepsy, the usual total dosage of immediate-release amphetamine salts (Adderall^®) is 5-60 mg daily, depending upon the patient's age and response, usually given in divided doses.1 The first dose should be given upon awakening, with additional doses (1 or 2) administered every 4-6 hours.1 In pediatric patients ≥12 years of age, the suggested initial dosage is 10 mg daily; daily dosage may be increased by 10 mg at weekly intervals until the optimum response is attained.1 Although narcolepsy seldom occurs in pediatric patients <12 years of age, such children also may receive dextroamphetamine alone.1 In patients 6-12 years of age, the recommended initial dosage is 5 mg daily; daily dosage may be increased by 5 mg at weekly intervals until optimum response is attained.1 If intolerable adverse effects (e.g., insomnia, anorexia) occur, dosage should be reduced.1 The first dose should be given upon awakening, with additional doses (1 or 2) administered every 4-6 hours.1

Special Populations

Hepatic Impairment

Manufacturers do not provide specific dosage recommendations, although the presence of hepatic impairment has the potential to reduce drug elimination and prolong exposure.1, 3, 4, 5, 6

Renal Impairment

Because of reduced clearance of amphetamines in severe renal impairment, the dosage of Mydayis^® and Adderall XR^® should be reduced.3, 4

In adults with severe renal impairment (glomerular filtration rate [GFR] 15 to <30 mL/minute per 1.73 m²), the recommended initial dosage of Mydayis^® is 12.5 mg once daily, which may be further increased to a maximum of 25 mg daily.3 In adolescents 13-17 years of age with severe renal impairment, the maximum recommended dosage of Mydayis^® is 12.5 mg daily if tolerated; the dosage should not be further escalated.3

The recommended initial dosage of Adderall XR^® in adults with severe renal impairment is 15 mg once daily in the morning.4 In pediatric patients 6-17 years of age with severe renal impairment, the recommended dosage of Adderall XR^® is 5 mg once daily.4 The maximum recommended dosage of Adderall XR^® in pediatric patients 6-12 years of age with severe renal impairment is 20 mg once daily.4

Mydayis^® and Adderall XR^® are not recommended in patients with end-stage renal disease (ESRD; GFR <15 mL/minute per 1.73 m²).3, 4

Geriatric Patients

Amphetamines have not been adequately studied in the geriatric patient population.1, 2, 4, 5, 6 Generally, dosage selection for geriatric patients should start at the lower end of the dosage range, reflecting the greater frequency of reduced hepatic, renal, or cardiac function and of concomitant diseases and drug therapy in geriatric patients.3

Cautions ⬆ ⬇

Contraindications

Hypersensitivity to amphetamines or other components of the formulation.1, 2, 3, 4, 5, 6
Concomitant use of monoamine oxidase (MAO) inhibitors, or within 14 days of discontinuing an MAO inhibitor (including linezolid and IV methylene blue), because of the increased risk of hypertensive crisis.1, 2, 3, 4, 5, 6

Warnings/Precautions

Warnings

Abuse, Misuse, and Addiction

A boxed warning is included in the prescribing information for amphetamines concerning the high potential for abuse and misuse.1, 2, 3, 4, 5, 6 The use of amphetamine exposes patients to the risks of abuse and misuse, which can lead to the development of substance use disorder (including addiction).1, 2, 3, 4, 5, 6 Misuse and abuse of CNS stimulants such as amphetamines can result in overdose or death.1, 2, 3, 4, 5, 6 This risk is further increased with higher dosages or unapproved routes of administration (i.e., snorting, injection).1, 2, 3, 4, 5, 6 Because CNS stimulants, including amphetamines, have a high potential for abuse and dependence, the risk of abuse, misuse, and addiction should be assessed prior to initiating amphetamines and reassessed throughout therapy.1, 2, 3, 4, 5, 6 Patients receiving stimulants should be also frequently monitored for signs of abuse, misuse, and addiction.1, 2, 3, 4, 5, 6

In addition, tolerance can develop during amphetamine therapy, which is characterized by a reduced response to the drug after repeated administration.1, 2, 3, 4, 5, 6 In patients who are physically dependent on CNS stimulants, abrupt cessation of therapy, rapid dosage reduction, or administration of an antagonist may result in a withdrawal syndrome characterized by dysphoric mood, fatigue, vivid and unpleasant dreams, insomnia or hypersomnia, increased appetite, and psychomotor retardation or agitation.1, 2, 3, 4, 5, 6

Patients and/or their caregivers should be advised that amphetamines can be abused and can result in dependence; they should be advised that amphetamines should not be shared with others and should be stored in a safe (preferably locked) location to prevent misuse and abuse.1, 2, 3, 4, 5, 6 Amphetamines should be disposed of by a medicine take-back program at a U.S. Drug Enforcement Administration (DEA) authorized collection site when no longer needed.1, 2, 3, 4, 5, 6 If there is no take-back program or authorized DEA collection site available, the drug can be mixed with an undesirable, nontoxic substance such as dirt, cat litter, or used coffee grounds and disposed of in a sealed plastic bag in the household trash.1, 2, 3, 4, 5, 6

Other Warnings/Precautions

Risks to Patients with Serious Cardiac Disease

Sudden death has been reported in patients with structural cardiac abnormalities or other serious cardiac disease receiving usual dosages of stimulants for the treatment of attention deficit hyperactivity disorder (ADHD).1, 2, 3, 4, 5, 6

Children, adolescents, and adults who are being considered for stimulant therapy should undergo 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.1, 2, 3, 4, 5, 6 In general, CNS stimulants should not be used in children, adolescents, or adults with known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmias, coronary artery disease, or other serious cardiac disease.1, 2, 3, 4, 5, 6

Patients or caregivers should inform clinicians immediately if adverse cardiovascular effects (e.g., exertional chest pain, dyspnea, unexplained syncope, other symptoms suggestive of cardiac disease) occur during stimulant therapy.1, 2, 3, 4, 5, 6

Increased Blood Pressure and Heart Rate

Stimulants, including amphetamines, can cause increases in average blood pressure by about 2-4 mm Hg and heart rate by about 3-6 beats/minute; larger increases may occur in some patients.1, 3, 5 All patients should be monitored for hypertension and tachycardia.1, 2, 3, 4, 5, 6

Psychiatric Adverse Effects

Psychotic or manic symptoms (e.g., hallucinations, delusional thinking, mania) have been reported in patients without a history of psychotic illness or mania who received usual dosages of stimulants.1, 2, 3, 4, 5, 6 In a pooled analysis of multiple short-term, placebo-controlled studies, such symptoms occurred in about 0.1% of patients receiving stimulants compared with 0% of those receiving placebo.1, 2, 3, 4, 5, 6 If psychotic or manic symptoms occur during stimulant therapy, discontinuance of therapy should be considered.1, 2, 3, 4, 5, 6

Stimulants have the potential to precipitate mixed or manic episodes in patients.1, 2, 3, 4, 5, 6 Prior to initiating therapy, patients should be screened for risk factors for developing a manic episode (e.g., current or prior depressive symptoms; family history of suicide, bipolar disorder, or depression).1, 2, 3, 4, 5, 6

Stimulants may exacerbate symptoms of behavior disturbance and thought disorder in patients with a preexisting psychotic disorder.1, 2, 3, 4, 5, 6

Long-term Suppression of Growth in Pediatric Patients

Therapy with CNS stimulants has been associated with weight loss and a slowing of growth in pediatric patients.1, 2, 3, 4, 5, 6

The manufacturers of stimulant preparations state that growth (weight and height) should be closely monitored during therapy, and pediatric patients who are not growing or gaining height or weight as expected may require temporary discontinuance of therapy.1, 2, 3, 4, 5, 6

Peripheral Vasculopathy, including Raynaud's Phenomenon

Because stimulants used to treat ADHD, including amphetamines, are associated with peripheral vascular disorders, including Raynaud's phenomenon, careful observation for digital changes is warranted during stimulant therapy, and further clinical evaluation (e.g., referral to a rheumatologist) may be appropriate for certain patients who develop signs or symptoms of peripheral vasculopathy.1, 2, 3, 4, 5, 6 Effects of peripheral vasculopathy, including Raynaud's phenomenon, were observed in postmarketing reports and at the therapeutic dosages of CNS stimulants in all age groups throughout the course of treatment.1, 2, 3, 4, 5, 6 Signs and symptoms are usually intermittent and mild; however, sequelae have included digital ulceration and/or soft tissue breakdown.1, 2, 3, 4, 5, 6 The manifestations generally improved after dosage reduction or discontinuance of the stimulant.1, 2, 3, 4, 5, 6

Seizures

Some evidence suggests that stimulants may lower the seizure threshold in patients with a history of seizures, in those with prior electroencephalography (EEG) abnormalities without seizures, and, very rarely, in patients without prior seizures and EEG abnormalities.1, 2, 3, 4 If seizures occur in a patient receiving amphetamines, the drug should be discontinued.1, 2, 3, 4

Serotonin Syndrome

Potentially fatal serotonin syndrome can occur when amphetamines are used in conjunction with other medications that affect serotonergic neurotransmitters, such as MAO inhibitors, selective serotonin-reuptake inhibitors (SSRIs), selective serotonin- and norepinephrine-reuptake inhibitors (SNRIs), triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, and St. John's wort ( Hypericum perforatum ).1, 2, 3, 4, 5, 6 Symptoms of serotonin syndrome can include mental status changes (e.g., agitation, hallucinations, delirium, 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 GI symptoms (e.g., nausea, vomiting, diarrhea).1, 2, 3, 4, 5, 6 Amphetamines and amphetamine derivatives are metabolized to some extent by cytochrome P-450 (CYP) isoenzyme 2D6, and to a minor extent, inhibit CYP2D6 metabolism.1, 2, 3, 4, 5, 6 Therefore, there is a potential pharmacokinetic interaction when amphetamines are used concomitantly with CYP2D6 inhibitors.1, 2, 3, 4, 5, 6 In patients receiving concomitant CYP2D6 inhibitors, an alternative non-serotonergic drug, or drug that does not also inhibit CYP2D6 should be considered.1, 2, 3, 4, 5, 6

Concomitant use of amphetamines and MAO inhibitors is contraindicated.1, 2, 3, 4, 5, 6 Concomitant use of amphetamines with other serotonergic medications or CYP2D6 inhibitors should only be considered if potential benefits justify the potential risks.4 If clinically feasible, consider initiating amphetamine therapy at a lower dosage and monitoring patients for the emergence of serotonin syndrome during therapy initiation or titration.1, 2, 3, 4, 5, 6 Patients should be informed of the risk of serotonin syndrome.1, 2, 3, 4, 5, 6 If symptoms of serotonin syndrome occur, amphetamines and any concomitant serotonergic agents should be immediately discontinued, and supportive care initiated.1, 2, 3, 4, 5, 6

Motor and Verbal Tics and Worsening of Tourette's Syndrome

Onset or exacerbation of motor or verbal tics and worsening of Tourette's syndrome have been reported with CNS stimulants, including amphetamines.1, 2, 3, 4, 5, 6

Prior to initiation of therapy, patients should be screened for a family history and clinically evaluated for motor or verbal tics or Tourette's syndrome.1, 2, 3, 4, 5, 6 Patients receiving amphetamines should be routinely monitored for the emergence or worsening of tics or Tourette's syndrome, and treatment discontinued if clinically needed.1, 2, 3, 4, 5, 6

Potential for Overdose Due to Medication Errors

The manufacturer states that medication errors, including substitution and dispensing errors, can occur with Mydayis^®, Adzenys XR-ODT^®, and other amphetamine products, which can lead to potential overdosage.3, 5 To avoid potential errors and overdosage, Mydayis^® and Adzenys XR-ODT^® should not be substituted with other amphetamine products on a milligram-per-milligram basis due to different amphetamine base compositions and differences in pharmacokinetics.3, 5

Specific Populations

Pregnancy

The National Pregnancy Registry for ADHD Medications monitors pregnancy outcomes in women exposed to ADHD medication during pregnancy.3, 4, 6 Clinicians are encouraged to register women who become pregnant while receiving amphetamines by calling 1-866-961-2388 or visiting [Web].3, 4, 6

Limited data from published studies and postmarketing reports are not sufficient to establish a drug-associated risk of major birth defects and miscarriage in women exposed to amphetamine during pregnancy.3, 4, 5, 6 Adverse pregnancy outcomes, including premature delivery and low birth weight, have been observed in infants of mothers dependent on amphetamines.3, 4, 5, 6

In embryofetal development studies in rats and rabbits, no effects on morphologic development were observed following oral administration of amphetamine during organogenesis at dosages up to 2 and 12 times, respectively, the maximum recommended human dosage.4 In a pre- and postnatal development study in rats, oral administration of amphetamine throughout pregnancy and lactation was associated with decreased pup survival and pup weight, which correlated with delayed development.4 Adverse effects on pup reproductive performance were also observed.4 Animal developmental studies have also reported long-term neurochemical and behavioral effects.4

Amphetamines can cause vasoconstriction and may decrease placental perfusion.3, 4, 5, 6 Additionally, amphetamines can stimulate uterine contractions, increasing the risk of preterm delivery.3, 4, 5, 6

Infants born to mothers receiving amphetamines during pregnancy are at increased risk of preterm delivery and low birth weight.3, 4, 5, 6 Infants born to mothers receiving amphetamines during pregnancy should be monitored for symptoms of withdrawal such as feeding difficulties, irritability, agitation, and excessive drowsiness.3, 4, 5, 6

Lactation

Based on limited case reports, amphetamine is present in human milk at a relative infant dose of 2-13.8% of the maternal weight-adjusted dosage and has a milk/plasma ratio between 1.9 and 7.5.4 There have been no reports of adverse effects from amphetamine exposure on the breast-fed infant.4 Long-term neurodevelopmental effects from amphetamine exposure through the breast milk are not known.4 There is the possibility that large dosages of amphetamine could interfere with milk production, particularly in mothers whose lactation has not been well established.4 Because of the potential for serious adverse effects in breast-fed infants, breastfeeding is not recommended during amphetamine therapy.4

Pediatric Use

Safety and efficacy of immediate-release amphetamine sulfate (Evekeo^®) and mixed amphetamine salts (Adderall^®) for ADHD have been established in pediatric patients ≥3 years of age.1, 2 Safety and efficacy of immediate-release amphetamine sulfate and mixed amphetamine salts for ADHD have not been established in pediatric patients <3 years of age.1, 2

Safety and efficacy of immediate-release amphetamine sulfate (Evekeo^®) have been established for the treatment of exogenous obesity in pediatric patients ≥12 years of age.2 Amphetamines are not recommended for use as anorectic agents in pediatric patients <12 years of age.2

Safety and efficacy of extended-release capsules containing mixed amphetamine salts (Mydayis^®) for ADHD have been established in pediatric patients 13-17 years of age.3 Safety and efficacy of extended-release capsules containing mixed amphetamine salts for ADHD have not been established in pediatric patients ≤12 years of age.3 Although extended-release capsules containing mixed amphetamine salts have been studied in pediatric patients 6-12 years of age in 2 clinical studies, a safe and effective dosage has not been established in patients ≤12 years of age.3

Safety and efficacy of extended-release capsules containing mixed amphetamine salts (Adderall XR^®) for ADHD have been established in pediatric patients ≥6 years of age.4 Safety and efficacy of extended-release capsules containing mixed amphetamine salts for ADHD have not been established in pediatric patients <6 years of age.4 Long-term effects of amphetamines are not well established in the pediatric patient population.4

Safety and efficacy of extended-release orally disintegrating tablets (Adzenys XR-ODT^®) have been established in pediatric patients 6-17 years of age based on 3 controlled clinical trials of up to 4 weeks in duration.5 Safety and efficacy of extended-release orally disintegrating tablets have not been established in pediatric patients <6 years of age.5

Safety and efficacy of extended-release oral tablets and suspension (Dyanavel^® XR) for ADHD have been established in pediatric patients 6-17 years of age.6 Safety and efficacy of extended-release oral tablets and suspension for ADHD have not been established in pediatric patients <6 years of age.6

Geriatric Use

The manufacturer of Mydayis^®states that clinical studies of amphetamine did not include a sufficient number of patients ≥65 years of age to assess differences in response compared to younger adults.3 Other reported clinical experience has not identified differences in response between geriatric patients and younger adults.3 Some other manufacturers state that their amphetamine formulations have not been studied in geriatric patients.1, 4

Hepatic Impairment

Pharmacokinetic studies have not been conducted to evaluate the effects of hepatic impairment on amphetamine exposure.6 Hepatic impairment has the potential to inhibit amphetamine elimination and prolong exposure.1, 3, 4, 5, 6

Renal Impairment

Pharmacokinetic studies have not been conducted to evaluate the effects of renal impairment on amphetamine exposure.6 Renal impairment has the potential to inhibit amphetamine elimination and prolong exposure.1, 3, 4, 5, 6

Common Adverse Effects

Adverse effects reported in patients receiving immediate-release amphetamine preparations (Adderall^®, Evekeo^®) include palpitations, tachycardia, blood pressure elevations, sudden death, myocardial infarction, isolated reports of cardiomyopathy with chronic use, psychotic episodes at recommended dosages (rare), overstimulation, restlessness, dizziness, insomnia, irritability, euphoria, dyskinesia, dysphoria, depression, tremor, headache, motor and verbal tics, Tourette's syndrome, aggression, anger, logorrhea, dermatillomania, blurred vision, mydriasis, dry mouth, unpleasant taste, diarrhea, constipation, intestinal ischemia, other GI 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.1, 2

Common adverse effects reported in ≥5% of patients and at least twice the rate of placebo in pediatric patients ≥13 years of age receiving extended-release capsules containing mixed amphetamine salts (Mydayis^®) include insomnia, decreased appetite, weight loss, irritability, and nausea; in studies in adults, the most common adverse effects were insomnia, decreased appetite, weight loss, dry mouth, increased heart rate, and anxiety.3

Common adverse effects reported in ≥5% of patients and with an incidence higher than placebo in pediatric patients 6-12 years of age receiving extended-release amphetamine capsules containing mixed amphetamine salts (Adderall XR^®) or extended-release orally disintegrating amphetamine tablets (Adzenys XR-ODT^®) include loss of appetite, insomnia, abdominal pain, emotional lability, vomiting, nervousness, nausea, and fever.4, 5 In pediatric patients 13-17 years of age, the most common adverse effects were loss of appetite, insomnia, abdominal pain, weight loss, and nervousness.4, 5 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.4, 5

The most common adverse effects reported in patients receiving amphetamine extended-release oral suspension or extended-release oral tablets (Dyanavel^® XR) include dry mouth, anorexia, weight loss, abdominal pain, nausea, insomnia, restlessness, emotional lability, dizziness, and tachycardia.6

Drug Interactions ⬆ ⬇

Amphetamines and amphetamine derivatives are metabolized to some extent by cytochrome P-450 (CYP) isoenzyme 2D6, and to a minor extent, inhibit CYP2D6 metabolism.1, 2, 3, 4, 5, 6 In vitro, metabolites of amphetamine have also been shown to minimally inhibit CYP1A2 and CYP3A4.1, 5, 6 The effects of amphetamine or its metabolites in vivo on drug metabolism by CYP enzymes are not known.5 Amphetamine also inhibits monoamine oxidase (MAO).1

CYP2D6 Inhibitors

Concomitant use of amphetamines with CYP2D6 inhibitors may increase amphetamine exposure and the risk of serotonin syndrome.1 Manufacturers suggest to consider selection of an alternative concomitant non-serotonergic drug or a drug that does not inhibit CYP2D6 in patients who are receiving CYP2D6 inhibitors.1, 2, 3, 4, 5, 6 One manufacturer states that amphetamines should only be used with CYP2D6 inhibitors if the potential benefits justify the potential risks.4

In patients concomitantly receiving CYP2D6 inhibitors, amphetamine therapy should be initiated at lower dosages and patients should be monitored for signs and symptoms of serotonin syndrome, especially when initiating amphetamine therapy and after dosage increases.1 If serotonin syndrome occurs, amphetamine therapy and the CYP2D6 inhibitor should both be discontinued.1

Acidifying Agents

Concomitant administration of acidifying agents lowers plasma levels and clinical efficacy of amphetamines.1, 3, 5 Examples of acidifying agents include GI acidifying agents (e.g., ascorbic acid, fruit juices) and urinary acidifying agents (e.g., ammonium chloride, sodium acid phosphate).1, 2 The dosage of amphetamines may therefore be increased during concomitant use based on clinical response.1

Concomitant administration of the urinary acidifying agent methenamine increases the urinary excretion of amphetamines, which reduces efficacy.1

Alkalinizing Agents

Concomitant administration of agents that increase GI (e.g., sodium bicarbonate) and urinary pH (e.g., acetazolamide, certain thiazides) can increase plasma levels of amphetamines, potentiating their activity.1, 2, 3 Alkaline urine pHs result in less ionization and reduced renal elimination of amphetamine.1, 2 Some manufacturers recommend complete avoidance of concomitant GI and/or urinary alkalinizing agents,1, 4, 5, 6 while others recommend exerting caution with concomitant use and adjusting the amphetamine dosage accordingly.3

Anticonvulsants

Intestinal absorption of ethosuximide, phenobarbital, or phenytoin may be delayed when used concomitantly with amphetamines.1 Synergistic anticonvulsant activity may also be observed with concomitant use of phenobarbital or phenytoin.1

Antihistamines

Concomitant use of amphetamines may counteract the sedative effects of antihistamines.1

Antihypertensive Agents

Concomitant use of amphetamines may antagonize the blood pressure-lowering effects of antihypertensive drugs and inhibit the effects of adrenergic blockers.1

Chlorpromazine

Concomitant use of chlorpromazine blocks dopamine and norepinephrine receptors, inhibiting the central stimulatory effects of amphetamines.1 Chlorpromazine can be used for the treatment of amphetamine poisoning.1

Haloperidol

Haloperidol, which blocks dopamine receptors, inhibits the central stimulatory effects of amphetamines.1

Lithium

Lithium may inhibit the anorectic and stimulatory effects of amphetamines.1

Meperidine

Concomitant use of meperidine and amphetamines may potentiate the analgesic effect of meperidine.1

Monoamine Oxidase Inhibitors

Amphetamine inhibits monoamine oxidase (MAO).1 Concomitant or recent use (within 14 days) of MAO inhibitors with CNS stimulants such as amphetamines can lead to hypertensive crisis, which can result in death, stroke, myocardial infarction, aortic dissection, ophthalmological complications, eclampsia, pulmonary edema, and renal failure.4 Concomitant use of amphetamines is contraindicated in patients taking MAO inhibitors, or within 14 days of discontinuing an MAO inhibitor (including linezolid and IV methylene blue).1, 4, 5, 6

Norepinephrine

Concomitant use of norepinephrine and amphetamines may increase the adrenergic effect of norepinephrine.1

Proton Pump Inhibitors

Time to peak plasma concentrations of amphetamine is decreased when the drug is used concomitantly with proton pump inhibitors (e.g., omeprazole).1 When proton pump inhibitors are used concomitantly with amphetamines, monitor patients for changes in clinical efficacy and adjust therapy as needed based on clinical response.1

Serotonergic Drugs

Potentially fatal serotonin syndrome can occur when amphetamines are used in conjunction with other serotonergic medications that affect serotonergic neurotransmitters, such as MAO inhibitors, selective serotonin-reuptake inhibitors (SSRIs), selective serotonin- and norepinephrine-reuptake inhibitors (SNRIs), triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, and St. John's wort ( Hypericum perforatum ).1, 2, 3, 4, 5, 6

Concomitant use of tricyclic antidepressants can also cause significant increases in d-amphetamine in the brain and can potentiate the cardiovascular effects of amphetamines.1, 2, 4 If a tricyclic antidepressant is used concomitantly, monitor patients frequently and adjust or use alternate drug therapy based on clinical response.1, 4

Concomitant use of amphetamines with other serotonergic medications should only be considered if potential benefits justify the potential risks.4 If clinically feasible, consider initiating amphetamine therapy at a reduced dosage and monitoring patients for the emergence of serotonin syndrome during therapy initiation or titration.1, 2, 4, 5, 6

Veratrum Alkaloids

Amphetamines inhibit the blood pressure-lowering effects of veratrum alkaloids.1

Other Information ⬆ ⬇

Description

Amphetamine is a non-catecholamine, sympathomimetic amine with CNS-stimulating activity.1, 2, 3, 4, 5, 6 The pharmacologic action of amphetamines in the treatment of ADHD has not been fully elucidated; however, its actions are thought to be related to the blockade of norepinephrine and dopamine reuptake into presynaptic neurons and the increased release of norepinephrine and dopamine into the extraneuronal space.1 Other than CNS stimulant activity, peripheral actions of amphetamine include elevation of systolic and diastolic blood pressure, weak bronchodilation, and respiratory stimulation.2 The l-amphetamine isomer exerts greater cardiovascular activity and less CNS excitatory effects compared to the d-amphetamine isomer.2 Racemic amphetamine is less effective as an appetite suppressant compared to dextroamphetamine.2

Amphetamines are commonly known as “anorectics” or “anorexigenics” in the treatment of obesity, although it is not known if their weight loss effects are primarily due to appetite suppression or other CNS or metabolic effects that may occur.2 The magnitude of weight loss with amphetamine therapy is a fraction of a pound each week, with the greatest weight loss usually occurring in the first weeks of treatment and declining thereafter.2

Commercially available amphetamine products include conventional tablets formulated for immediate release of the drug as well as extended-release capsules, tablets, oral suspension, and orally disintegrating tablets, which exert a longer duration of activity.1, 2, 4, 5, 6 Immediate-release formulations include amphetamine sulfate conventional tablets (Evekeo^®) and conventional tablets containing mixed amphetamine salts (amphetamine aspartate, amphetamine sulfate, dextroamphetamine saccharate, and dextroamphetamine sulfate; e.g., Adderall^®).1, 2 Two formulations of extended-release capsules containing mixed amphetamine salts are commercially available.3, 4 One formulation of extended-release capsules containing mixed amphetamine salts (Mydayis^®) contains 3 types of drug-releasing beads (1 immediate-release and 2 types of delayed-release beads),3 which allow for approximately one-third of the total drug to be delivered immediately, and the remaining two-thirds to be dissolved at pHs of 5.5 and 7.3, 554 The other formulation of extended-release capsules containing mixed amphetamine salts (Adderall XR^®) delivers the drug in equal amounts as an immediate release dose and as a sustained-release second dose.554 Extended-release amphetamine orally disintegrating tablets (Adzenys XR-ODT^®) deliver half of the total amphetamine dose immediately, and the remainder as a sustained-release second dose.554 Extended-release tablets and oral suspension (Dyanavel^® XR) contain amphetamine (complexed with sodium polystyrene sulfonate), amphetamine aspartate, and dextroamphetamine sulfate.6

While children eliminate amphetamine faster than adults, for a given dose of amphetamine, children have greater exposure to amphetamine based on an increased weight-based dosage compared to adults.4, 5 After adjustment for differences in body weight, amphetamine exposure is 30% less in children than adults.4, 5

Following oral administration of conventional tablets containing mixed amphetamine salts (Adderall^®), peak plasma concentrations of d-amphetamine and l-amphetamine were attained at 3 hours.1 The pharmacokinetics of d-amphetamine and l-amphetamine are dose-proportional over the oral dosing range of 10<30 mg.1 The effect of food on the pharmacokinetics of mixed amphetamine salts (Adderall^®) has not been evaluated.1 Effects persist for 4<6 hours after oral administration of immediate-release preparations of amphetamine; twice daily administration of Evekeo^® has a duration of activity of 10 hours.554

Following oral administration of extended-release capsules containing mixed amphetamine salts (Adderall XR^®), peak plasma concentrations are attained at 7 hours.4 The pharmacokinetics of Adderall XR^® are dose proportional over the oral dosing range of 20<60 mg in adults and adolescents that weigh >75 kg, over 10<40 mg in adolescents that weigh ≤75 kg, and over 5<30 mg in children 6<12 years of age.4 There is no expected accumulation of Adderall XR^® at steady state when used in children.4 Food does not affect the absorption of d- or l-amphetamine from Adderall XR^®, but administration with a high-fat meal prolongs the time to peak plasma concentrations by 2.5 hours for d-amphetamine from 5.2 hours to 7.7 hours, and 2.7 hours for l-amphetamine from 5.6 hours to 8.3 hours.4 There is comparable absorption to the intact capsule in the fasting state when the contents are opened and sprinkled onto applesauce.4 A single dose of extended-release capsules containing mixed amphetamine salts (Adderall XR^®) 20 mg provides comparable plasma concentrations of d-amphetamine and l-amphetamine to immediate-release mixed amphetamine salts (Adderall^®) 10 mg twice daily administered 4 hours apart.4 The duration of action of Adderall XR^® is approximately 10-12 hours.554

Following oral administration of extended-release capsules containing mixed amphetamine salts (Mydayis^®) in adults and pediatric patients, peak plasma concentrations occur at 8 hours for d- and l-amphetamine in adults, and at 7<10 hours in pediatric patients.3 The pharmacokinetics of Mydayis^® are linear and dose proportional over the oral dosing range of 12.5<50 mg; steady state is achieved after 7<8 days of standard dosing.3 Mydayis^® has a mean accumulation ratio of 1.6.3 A single 37.5-mg dose of Mydayis^® provides comparable plasma exposure to d- and l-amphetamine as a 25-mg dose of Adderall XR^® followed by a 12.5-mg dose of immediate-release amphetamine 8 hours later.3 Following oral administration of extended-release capsules containing mixed amphetamine salts (Mydayis^®) in the fasting state, peak plasma concentrations of d-amphetamine are attained at 7 hours, and l-amphetamine at 7.5 hours.3 When administered with a high-fat meal, absorption is not affected, but peak plasma concentrations of d- and l-amphetamine are delayed to 12 hours.3 There is comparable absorption to the intact capsule in the fasting state when the contents are opened and sprinkled onto applesauce.3 In vitro studies evaluating the effect of alcohol on the release of amphetamine indicated that there is increased release of Mydayis^® in the presence of 20% alcohol concentration, and more noticeably, at a 40% alcohol concentration.3 The duration of action of Mydayis^® is estimated to be up to 16 hours.3

Following administration of extended-release oral suspension (Dyanavel^® XR) in adults, the median time to peak plasma concentrations was 4 hours for d-amphetamine and l-amphetamine.6 After oral administration of extended-release tablets (Dyanavel^® XR) in adults, the median time to peak plasma concentrations was 5 hours for d-amphetamine and l-amphetamine.6 Under fasting conditions, chewing or swallowing the extended-release tablets does not significantly impact amphetamine exposure or time to peak plasma concentrations.6 In pediatric patients 6<12 years of age under fasting conditions, the median time to peak plasma concentrations was 3.9 hours for d-amphetamine and 4.5 hours for l-amphetamine.6 The relative bioavailability of extended-release suspension compared with an equal dosage of Adderall^® is 106% for d-amphetamine and 111% for l-amphetamine, and is 94% for both d- and l-amphetamine compared to Adderall XR^®.6 The relative bioavailability of an equivalent dosage of extended-release tablets compared to extended-release suspension is 105% for d-amphetamine and 106% for l-amphetamine.6 Administration of the extended-release suspension with a high fat meal delays the time to peak plasma concentrations by 1 hour, increases maximum plasma concentrations by 2%, and decreases exposure to d-amphetamine by 5.7% and l-amphetamine by 7.4%.6 Following oral administration of the extended-release tablets with a high fat meal, maximum plasma concentrations are decreased by 3%; total exposure to d-amphetamine is decreased by 4%, and l-amphetamine by 7.3%.6 The duration of action of the extended-release suspension and tablets is approximately 13 hours.554 In vitro studies evaluating the effect of alcohol on the extended-release oral suspension showed that in the presence of 40% alcohol concentration, there was dose dumping potential.6 When extended-release oral tablets were evaluated, there was no alcohol-induced dumping in the presence of 40% alcohol.6 Dose dumping was also not observed in the presence of 5%, 10%, or 20% alcohol for the extended-release suspension or tablets.6

Following oral administration of extended-release orally disintegrating tablets (Adzenys XR-ODT^®) in adults under fasting conditions, peak plasma concentrations occurred after 5 hours.5 When administered following a high-fat meal, the time to peak plasma concentrations was 7 hours.5 Although food prolongs the time to peak plasma concentrations, these changes are not considered clinically significant.5 A single 18.8-mg dose of extended-release orally disintegrating tablets provides comparable plasma concentrations of d- and l-amphetamine to a 30-mg dose of extended-release amphetamine mixed salts.5 In vitro studies evaluating the effect of alcohol on extended-release orally disintegrating tablets showed substantial release of amphetamine in the presence of 40% alcohol concentration, but not with 5%, 10%, or 20% concentrations.5

Although some of the enzymes involved in amphetamine metabolism have not been fully elucidated, cytochrome P-450 (CYP) isoenzyme 2D6 is known to be involved in the oxidation of 4-hydroxy-amphetamine.1 Because CYP2D6 is polymorphic, there is a potential for variability in metabolism amongst patients.1 Amphetamine reportedly undergoes oxidation to form several metabolites, which include 4-hydroxy-amphetamine, alpha-hydroxy-amphetamine, and norephedrine.1 Norephedrine and 4-hydroxy-amphetamine are active metabolites of amphetamine, which undergo subsequent oxidation to form 4-hydroxy-norephedrine.1 Alpha-hydroxy-amphetamine undergoes deamination to form phenylacetone, and ultimately, benzoic acid and its glucuronide and glycine conjugate hippuric acid.1

Following oral administration of immediate-release mixed amphetamine salts (Adderall^®), the mean elimination half-life of d-amphetamine ranges from 9.77<11 hours, and the mean elimination half-life of l-amphetamine ranges from 11.5<13.8 hours.1

Following oral administration of extended-release mixed amphetamine salts (Mydayis^®) in pediatric and adult patients, the mean elimination half-life of d-amphetamine ranges from 10<11 hours and l-amphetamine from 10<13 hours.3

The mean elimination half-life of Adderall XR^® is shorter for children than adults based on a mg/kg dosing weight.4 When adjusted for weight, amphetamine exposure is 30% less in children.4 The elimination half-life of d-amphetamine is 9 hours in children 6<12 years of age, 11 hours in adolescents 13<17 years of age, and 10 hours in adults.4 For the l-amphetamine isomer, the elimination half-life is 11 hours in children 6<12 years of age, 13<14 hours in adolescents, and 13 hours in adults.4

Following oral administration of extended-release oral suspension (Dyanavel^® XR), the mean elimination half-life of d-amphetamine is 12.4 hours and l-amphetamine, 15.1 hours.6 Following oral administration of extended-release tablets (Dyanavel^® XR), the mean elimination half-life of d-amphetamine is 13.5 hours and l-amphetamine, 17.3 hours.6 In pediatric patients 6<12 years of age, the mean elimination half-life of the extended-release oral suspension is 10.4 hours for d-amphetamine and 12.1 hours for l-amphetamine.6

Following oral administration of extended-release orally disintegrating tablets (Adzenys XR-ODT^®) in adults, the mean elimination half-life of d-amphetamine and l-amphetamine is 11 hours and 14 hours, respectively.5 In pediatric patients 6<12 years of age, the mean elimination half-life of d-amphetamine is 9<10 hours, and the mean elimination half-life of l-amphetamine is 10<11 hours.5

Amphetamine has a pKa of 9.9; therefore, urinary recovery of amphetamine is highly dependent on urine pH and flow rates.1 At normal urinary pHs, approximately 50% of an amphetamine dose is recovered in urine as derivatives of alpha-hydroxy-amphetamine, and another 30<40% in urine as unchanged amphetamine.1 Acidic urinary pH and high flow rates result in increased renal elimination that exceeds the clearance of glomerular filtration rates, while alkaline urinary pHs result in reduced ionization and renal elimination.1 The urinary recovery of amphetamine ranges from 1<75%, which depends on urinary pH; the remainder of the dose undergoes hepatic metabolism.1 Both renal and hepatic impairment can inhibit the elimination of amphetamine and prolong exposure.1

Advice to Patients

Advise patient or caregiver to read the FDA-approved patient labeling (medication guide).1, 3
Educate patients and their families on the risks of abuse, misuse, and addiction with amphetamines, which can lead to overdose and death, and inform them on proper disposal of unused drug.1, 3 Advise patients to store amphetamines in a safe, preferably locked, place, and to not give their medication to anyone else.1, 3
Inform patients that there are potential risks with amphetamine therapy in patients with serious heart disease, such as sudden death.3 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 therapy.1, 2, 5, 6
Inform patients or caregivers that amphetamines can cause elevations in blood pressure and heart rate and they should be monitored for these effects.3
Inform patients or caregivers of the potential for psychotic or manic symptoms, even in patients without a prior history of psychotic symptoms or mania, at recommended dosages.3
Inform patients and caregivers that amphetamines can potentially slow growth and cause weight loss in pediatric patients.4 Growth (height and weight) should be monitored often during amphetamine therapy in pediatric patients, and patients who are not growing or gaining weight as expected may require treatment interruption.4
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).3 Patients should be advised 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.3 Rheumatology referral may be appropriate for certain patients.3
Inform patients that amphetamines can lower the seizure threshold.3 Advise patients to contact their healthcare provider immediately and to discontinue amphetamine therapy if a seizure occurs.3
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 (MAO) inhibitors, linezolid, selective serotonin-reuptake inhibitors (SSRIs), selective serotonin- and norepinephrine-reuptake inhibitors (SNRIs), triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, and St. John's wort ( Hypericum perforatum ).3 Advise patients to contact their healthcare provider or report to the emergency department immediately if symptoms of serotonin syndrome occur.3
Inform patients that motor and verbal tics and worsening of Tourette's syndrome may occur during amphetamine therapy.3 Patients should notify their healthcare provider if emergence of new tics or worsening of tics or Tourette's syndrome occurs.3
Advise patients to avoid alcohol while taking certain formulations of extended-release amphetamine (including Mydayis^®, Adzenys XR-ODT^®, and Dyanavel^® XR) since alcohol can cause rapid release of the drug.3, 5, 6
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, suicidal ideation or behaviors, mental/psychiatric disorder, history of substance abuse, circulation problems in fingers and toes, motor and verbal tics or Tourette's syndrome, seizures, renal disease).3
Advise patients of the potential fetal effects from the use of amphetamines during pregnancy.3 Advise patients to inform their clinician if they are or plan to become pregnant or plan to breast-feed.3 Inform patients that there is a pregnancy registry for women exposed to amphetamines during pregnancy.3 Inform breastfeeding women that breastfeeding while taking amphetamines is not recommended.4
Advise patients of other important precautionary information.3

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.

Amphetamine sulfate preparations are subject to control under the Federal Controlled Substances Act of 1970 as schedule II (C-II) drugs.

Amphetamine (expressed as amphetamine base)

Routes	Dosage Forms	Strengths	Brand Names
Oral	Tablets, extended-release	5 mg total amphetamine (as 4 mg of amphetamine [in a 3.2 to 1 ratio of d to l-amphetamine complexed with sodium polystyrene sulfonate], and 1 mg of amphetamine [as 1 mg of amphetamine aspartate and 0.7 mg of dextroamphetamine sulfate])	Dyanavel^® XR (C-II)
		10 mg total amphetamine (as 8 mg of amphetamine [in a 3.2 to 1 ratio of d to l-amphetamine complexed with sodium polystyrene sulfonate], and 2 mg of amphetamine [as 2 mg of amphetamine aspartate and 1.4 mg of dextroamphetamine sulfate])	Dyanavel^® XR (C-II)
		15 mg total amphetamine (as 12 mg of amphetamine [in a 3.2 to 1 ratio of d to l-amphetamine complexed with sodium polystyrene sulfonate], and 3 mg of amphetamine [as 3 mg of amphetamine aspartate and 2 mg of dextroamphetamine sulfate])	Dyanavel^® XR (C-II)
		20 mg total amphetamine (as 16 mg of amphetamine [in a 3.2 to 1 ratio of d to l-amphetamine complexed with sodium polystyrene sulfonate], and 4 mg of amphetamine [as 4 mg of amphetamine aspartate and 2.7 mg of dextroamphetamine sulfate])	Dyanavel^® XR (C-II)
	Suspension, extended-release	Each 1 mL contains 2.5 mg total amphetamine (as 2 mg of amphetamine [in a 3.2 to 1 ratio of d to l-amphetamine complexed with sodium polystyrene sulfonate], and 0.5 mg of amphetamine [as 0.5 mg of amphetamine aspartate and 0.3 mg of dextroamphetamine sulfate])	Dyanavel^® XR (C-II)
	Orally disintegrating tablets, extended-release	3.1 mg (equivalent to 5 mg strength mixed salts of single-entity amphetamine)	Adzenys XR-ODT^® (C-II)
		6.3 mg (equivalent to 10 mg strength mixed salts of single-entity amphetamine)	Adzenys XR-ODT^® (C-II)
		9.4 mg (equivalent to 15 mg strength mixed salts of single-entity amphetamine)	Adzenys XR-ODT^® (C-II)
		12.5 mg (equivalent to 20 mg strength mixed salts of single-entity amphetamine)	Adzenys XR-ODT^® (C-II)
		15.7 mg (equivalent to 25 mg strength mixed salts of single-entity amphetamine)	Adzenys XR-ODT^® (C-II)
		18.8 mg (equivalent to 30 mg strength mixed salts of single-entity amphetamine)	Adzenys XR-ODT^® (C-II)

Amphetamine Sulfate

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Tablets	5 mg	Evekeo^® (C-II)
		10 mg	Evekeo^® (C-II)

Amphetamine Sulfate Combinations

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Capsules, extended-release	5 mg total amphetamine (as 1.25 mg, with amphetamine aspartate 1.25 mg, dextroamphetamine saccharate 1.25 mg, and dextroamphetamine sulfate 1.25 mg)	Adderall XR^® (C-II)	Takeda Pharmaceuticals
		10 mg total amphetamine (as 2.5 mg, with amphetamine aspartate 2.5 mg, dextroamphetamine saccharate 2.5 mg, and dextroamphetamine sulfate 2.5 mg)	Adderall XR^® (C-II)	Takeda Pharmaceuticals
		12.5 mg total amphetamine (as 3.125 mg with amphetamine aspartate 3.125 mg, dextroamphetamine saccharate 3.125 mg, and dextroamphetamine sulfate 3.125 mg)	Mydayis^® (C-II)
		15 mg total amphetamine (as 3.75 mg, with amphetamine aspartate 3.75 mg, dextroamphetamine saccharate 3.75 mg, and dextroamphetamine sulfate 3.75 mg)	Adderall XR^® (C-II)	Takeda Pharmaceuticals
		20 mg total amphetamine (as 5 mg, with amphetamine aspartate 5 mg, dextroamphetamine saccharate 5 mg, and dextroamphetamine sulfate 5 mg)	Adderall XR^® (C-II)	Takeda Pharmaceuticals
		25 mg total amphetamine (as 6.25 mg, with amphetamine aspartate 6.25 mg, dextroamphetamine saccharate 6.25 mg, and dextroamphetamine sulfate 6.25 mg)	Mydayis^® (C-II)
		25 mg total amphetamine (as 6.25 mg, with amphetamine aspartate 6.25 mg, dextroamphetamine saccharate 6.25 mg, and dextroamphetamine sulfate 6.25 mg)	Adderall XR^® (C-II)	Takeda Pharmaceuticals
		30 mg total amphetamine (as 7.5 mg, with amphetamine aspartate 7.5 mg, dextroamphetamine saccharate 7.5 mg, and dextroamphetamine sulfate 7.5 mg)	Adderall XR^® (C-II)	Takeda Pharmaceuticals
		37.5 mg total amphetamine (as 9.375 mg, with amphetamine aspartate 9.375 mg, dextroamphetamine saccharate 9.375 mg, and dextroamphetamine sulfate 9.375 mg)	Mydayis^® (C-II)	Takeda Pharmaceuticals
		50 mg total amphetamine (as 12.5 mg, with amphetamine aspartate 12.5 mg, dextroamphetamine saccharate 12.5 mg, and dextroamphetamine sulfate 12.5 mg)	Mydayis^® (C-II)	Takeda Pharmaceuticals
	Tablets	5 mg total amphetamine (as 1.25 mg, with amphetamine aspartate 1.25 mg, dextroamphetamine saccharate 1.25 mg, and dextroamphetamine sulfate 1.25 mg)*	Adderall^® (C-II; double-scored)	Teva Pharmaceuticals
			Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate, and Amphetamine Sulfate Tablets (C-II; double-scored)
		7.5 mg total amphetamine (as 1.875 mg, with amphetamine aspartate 1.875 mg, dextroamphetamine saccharate 1.875 mg, and dextroamphetamine sulfate 1.875 mg)*	Adderall^® (C-II; double-scored)	Teva Pharmaceuticals
			Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate, and Amphetamine Sulfate Tablets (C-II; double-scored)
		10 mg total amphetamine (as 2.5 mg, with amphetamine aspartate 2.5 mg, dextroamphetamine saccharate 2.5 mg, and dextroamphetamine sulfate 2.5 mg)*	Adderall^® (C-II; double-scored)	Teva Pharmaceuticals
			Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate, and Amphetamine Sulfate Tablets (C-II; double-scored)
		12.5 mg total amphetamine (as 3.125 mg, with amphetamine aspartate 3.125 mg, dextroamphetamine saccharate 3.125 mg, and dextroamphetamine sulfate 3.125 mg)*	Adderall^® (C-II; double-scored)	Teva Pharmaceuticals
			Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate, and Amphetamine Sulfate Tablets (C-II; double-scored)
		15 mg total amphetamine (as 3.75 mg, with amphetamine aspartate 3.75 mg, dextroamphetamine saccharate 3.75 mg, and dextroamphetamine sulfate 3.75 mg)*	Adderall^® (C-II; double-scored)	Teva Pharmaceuticals
			Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate, and Amphetamine Sulfate Tablets (C-II; double-scored)
		20 mg total amphetamine (as 5 mg, with amphetamine aspartate 5 mg, dextroamphetamine saccharate 5 mg, and dextroamphetamine sulfate 5 mg)*	Adderall^® (C-II; double-scored)	Teva Pharmaceuticals
			Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate, and Amphetamine Sulfate Tablets (C-II; double-scored)
		30 mg total amphetamine (as 7.5 mg, with amphetamine aspartate 7.5 mg, dextroamphetamine saccharate 7.5 mg, and dextroamphetamine sulfate 7.5 mg)*	Adderall^® (C-II; double-scored)	Teva Pharmaceuticals
			Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate, and Amphetamine Sulfate Tablets (C-II; double-scored)

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

section name header

Introduction ⬇

AHFS Class:

Generic Name(s):

Uses ⬆ ⬇

Dosage and Administration ⬆ ⬇

Handling and Disposal

Cautions ⬆ ⬇

Drug Interactions ⬆ ⬇

Other Information ⬆ ⬇

Preparations ⬆ ⬇

Amphetamine (expressed as amphetamine base)

Amphetamine Sulfate

Amphetamine Sulfate Combinations

Copyright ⬆ ⬇

References ⬆