Version July 2025
Dextroamphetamine/amphetamine has a high potential for abuse and misuse, which can lead to the development of a substance use disorder, including addiction. Misuse and abuse of CNS stimulants, including dextroamphetamine/amphetamine, can result in overdose and death, and this risk is increased with higher doses or unapproved methods of administration, such as snorting or injection.
Before prescribing dextroamphetamine/amphetamine, assess each patient's risk for abuse, misuse, and addiction. Educate patients and their families about these risks, proper storage of the drug, and proper disposal of any unused drug. Throughout dextroamphetamine/amphetamine treatment, reassess each patient's risk of abuse, misuse, and addiction and frequently monitor for signs and symptoms of abuse, misuse, and addiction.
Attention-deficit/hyperactivity disorder:
Immediate release: Oral: Initial: 5 mg once or twice daily; may increase daily dose based on response and tolerability in 5 to 10 mg increments at intervals ≥1 week up to a usual maximum of 40 mg/day in 1 to 2 divided doses (Ref). Note: Although doses >40 mg/day will rarely be necessary, doses as high as 60 mg/day with close monitoring may be necessary for optimal response in some patients (Ref).
Extended release: Oral: Initial: 10 to 20 mg once daily in the morning; may increase daily dose based on response and tolerability in 10 to 20 mg increments at intervals ≥1 week (Ref). Although doses >40 mg/day will rarely be necessary, doses up to 60 mg/day may be necessary for optimal response in some patients, but the frequency and severity of adverse effects are increased with higher doses (Ref).
Triple-bead extended release: Oral: Initial: 12.5 mg once daily in the morning; may increase daily dose based on response and tolerability in 12.5 mg increments at intervals ≥1 week (Ref). Maximum dose: 50 mg/day.
Cocaine use disorder (alternative agent) (off-label use):
Extended release: Oral: Initial: 10 to 20 mg once daily (as monotherapy or in combination with topiramate); may increase based on response and tolerability in increments of 10 mg every week up to a maximum of 60 mg/day (Ref).
Narcolepsy, daytime sleepiness (alternative agent): Oral: Initial: 10 mg once daily in the morning; may increase daily dose based on response and tolerability in increments of 10 mg every week until optimal response is obtained; usual dosage range: 20 to 60 mg/day in 1 to 3 divided doses (Ref). Some experts recommend initiating therapy with the IR formulation (FDA approved) and transitioning to extended release (off label) once the patient achieves a stable dose. Although the ER formulation is generally dosed once daily, some patients may require a second dose in the early afternoon (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Immediate release: There are no dosage adjustments provided in the manufacturer's labeling; use with caution; the potential exists for elimination of amphetamine to be inhibited resulting in prolonged exposure.
Hemodialysis: There are no specific dosage adjustments provided in the manufacturer's labeling; dextroamphetamine is not dialyzable (Ref).
Extended release: Adderall XR:
Mild to moderate impairment: There are no dosage adjustments provided in the manufacturer's labeling; use with caution; the potential exists for elimination of amphetamine to be inhibited resulting in prolonged exposure.
Severe impairment (GFR 15 to <30 mL/minute/1.73 m2): 15 mg once daily in the morning.
ESRD (GFR <15 mL/minute/1.73 m2): Use is not recommended; dextroamphetamine is not dialyzable.
Mydayis:
Mild or moderate impairment: There are no dosage adjustments provided in the manufacturer's labeling.
Severe impairment (GFR 15 to <30 mL/minute/1.73 m2): Maximum dose: 25 mg/day
ESRD (GFR <15 mL/minute/1.73 m2): Use is not recommended; dextroamphetamine is not dialyzable
There are no dosage adjustments provided in the manufacturer's labeling; use with caution.
Refer to adult dosing; use with caution and start at low end of dosage range.
(For additional information see "Dextroamphetamine and amphetamine: Pediatric drug information")
Dosage guidance:
Dosing: Use lowest effective individualized dose; administer first dose as soon as awake; avoid late evening doses.
Attention-deficit/hyperactivity disorder: Note: Extended-release products are not interchangeable on a mg-per-mg basis; use precaution to ensure appropriate product specific dosing.
Immediate-release tablets:
Children 3 to 5 years: Oral: Initial 2.5 mg once daily in the morning; increase daily dose by 2.5 mg at weekly intervals until optimal response is obtained; maximum daily dose: 40 mg/day administered in 1 to 2 divided doses per day; use intervals of 4 to 6 hours between doses. Note: Select patients may require daily dose to be given in 3 divided doses per day. Although FDA approved, current guidelines do not recommend dextroamphetamine/amphetamine use in children ≤5 years due to insufficient evidence (Ref).
Children ≥6 years and Adolescents: Oral: Initial: 5 mg once or twice daily; increase daily dose by 5 mg at weekly intervals until optimal response is obtained; usual maximum daily dose: 40 mg/day administered in 1 to 2 divided doses; use intervals of 4 to 6 hours between doses; some patients weighing >50 kg may require and tolerate doses up to 60 mg/day in divided doses with frequent monitoring (Ref). Note: Some patients may require daily dose to be administered as 3 divided doses per day.
Extended-release capsules:
Adderall XR:
Initial therapy:
Children 6 to 12 years: Oral: Initial: 5 to 10 mg once daily in the morning; increase daily dose by 5 mg or 10 mg at weekly intervals until optimal response is obtained; usual maximum daily dose: 30 mg/day; some patients weighing >50 kg may require and tolerate doses up to 60 mg/day (Ref)
Adolescents 13 to 17 years: Oral: Initial: 10 mg once daily in the morning; may increase to 20 mg daily after 1 week if symptoms are not controlled; usual maximum daily dose: 20 mg/day; some patients weighing >50 kg may require and tolerate doses up to 60 mg/day with frequent monitoring (Ref)
Converting Adderall to Adderall XR: Patients taking divided doses of immediate-release Adderall tablets may be switched to extended-release Adderall XR capsule using the same total daily dose (taken once daily); titrate dose at weekly intervals to achieve optimal response.
Mydayis: Note: Do not substitute Mydayis for other amphetamine products on a mg-per-mg basis because of different amphetamine base compositions and differing pharmacokinetic profiles.
Adolescents 13 to 17 years: Oral: Initial: 12.5 mg once daily in the morning; may increase by 12.5 mg increments at weekly intervals; maximum daily dose: 25 mg/day
Narcolepsy:
Children 6 to 12 years: Immediate-release tablets: Oral: Initial: 5 mg daily; increase daily dose by 5 mg at weekly intervals until optimal response is obtained; maximum daily dose: 60 mg/day given in 1 to 3 divided doses per day; use intervals of 4 to 6 hours between doses
Adolescents: Immediate-release tablets: Oral: Initial: 10 mg daily; increase daily dose by 10 mg at weekly intervals until optimal response is obtained; maximum daily dose: 60 mg/day given in 1 to 3 divided doses per day; use intervals of 4 to 6 hours between doses
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Immediate release: Children ≥3 years and Adolescents: There are no dosage adjustments provided in the manufacturer's labeling; use with caution; elimination may be decreased with renal impairment.
Extended release:
Adderall XR: Children ≥6 years and Adolescents ≤17 years:
GFR 15 to <30 mL/minute/1.73 m2: Initial dose: 5 mg once daily; maximum daily dose in children 6 to 12 years: 20 mg/day
GFR <15 mL/minute/1.73 m2: Use not recommended
Mydayis: Adolescents 13 to 17 years:
GFR 15 to <30 mL/minute/1.73 m2: Reduce maximum daily dose to 12.5 mg/day
GFR <15 mL/minute/1.73 m2: Use not recommended
Children ≥3 years and Adolescents: There are no dosage adjustments provided in the manufacturer's labeling; use with caution; elimination may be decreased with hepatic impairment.
Cardiovascular events including acute myocardial infarction (MI), stroke, sudden cardiac death (SCD), increased heart rate, and increased blood pressure have been reported in adult and pediatric patients (Ref). Amphetamine and dextroamphetamine salts, similar to other CNS stimulants, have been associated with sudden cardiac death in children and adolescents with preexisting structural cardiac abnormalities. Available data in patients without congenital heart disease are conflicting (Ref). A large retrospective cohort study showed an overall low incidence and risk of serious cardiovascular events in children and young adults (Ref); similarly, retrospective claims databases have not shown an increase in serious cardiovascular events (MI, sudden death, stroke) with stimulant use in young and middle-aged adults (Ref).
Mechanism : Dose-related; amphetamines increase the mean heart rate and systolic blood pressure by mediating noradrenergic and dopaminergic transmission (Ref). This increase in heart rate and blood pressure can ultimately lead to cardiovascular events such as arrhythmias and/or MI.
Onset: Varied; MI and SCD usually occur within hours (especially in cases of overdose), but arrhythmias usually occur with long-term use (Ref).
Risk factors:
• Higher doses (Ref)
• Prior structural heart disease (Ref)
• Family history of SCD or other cardiovascular diseases (eg, MI, cardiac arrhythmias) (Ref)
• Concurrent use of QTc prolonging medications may increase the risk of arrhythmias
• Strenuous exercise and dehydration (Ref)
Some studies have reported growth retardation in pediatric patients. Decreased height and weight changes have been described in children <12 years receiving long-term treatment (ie, ≥3 years) (Ref). Similarly, statistically significant reductions in total femoral, femoral neck, and lumbar bone mineral density (BMD) were observed in pediatric patients (age range: 8 to 17 years) actively treated with stimulants (including, but not limited to methylphenidate) when compared to matched unmedicated controls; also reported were significantly more subjects in the stimulant-treated group with BMD measurements in the osteopenic range compared to matched controls (38.3% vs 21.6%) (Ref). An association has been observed between cumulative stimulant exposure in childhood and decreased height velocity, decreased adult height, and increased weight in adulthood (Ref). In contrast, a longitudinal cohort-controlled trial reported no difference in peak height velocity and final adult height in subjects with attention-deficit/hyperactivity disorder and/or treated with stimulants (Ref).
Mechanism: Dose- and time-related; possibly due to effects on CNS growth factors and hepatic growth factors and direct cartilage effects. Weight loss may result from appetite suppression, reduced food intake, increased activity, and metabolic shifts (Ref).
Onset: Growth suppression in children: Delayed; appears to occur after months of active treatment (Ref).
Risk factors:
• Higher doses (Ref)
• Duration of treatment/cumulative exposure (Ref)
• Comorbid autism disorder (Ref)
New-onset psychosis or mania and exacerbation of psychotic or manic symptoms (eg, delusional thinking, auditory hallucination and visual hallucination, mania) may occur with neurostimulant use in all ages (Ref); symptoms resemble acute psychosis most commonly observed in schizophrenia (Ref). Amphetamine has also been associated with aggressive behavior or hostility in children; however, a causal relationship has not been established. A study of commercial insurance claims data from 221,846 patients (age: 13 to 25 years) prescribed amphetamines or methylphenidate reported a higher risk of psychosis with amphetamine products compared to methylphenidate (Ref). Studies in adults have suggested that the resolution of the psychotic episode may be incomplete without treatment and may take up to 6 months even if abstinence occurs (Ref).
Mechanism: Psychosis: Amphetamine stimulates the release of dopamine from presynaptic nerve endings and prevents its reuptake. This leads to an increased concentration of dopamine in the neuronal synapse, leading to glutamate dysregulation. Increased dopamine and glutamate dysregulation have been associated with the development of psychotic symptoms (Ref).
Onset: Varied; a study of commercial insurance claims data from 221,846 patients (age: 13 to 25 years) prescribed amphetamines or methylphenidate reported a mean time of 128 days (IQR: 48 to 333 days) from the time medication was dispensed to the first psychotic episode (Ref). In cases of overdose/intoxication, the onset of symptoms is usually acute and within hours.
Risk factors:
• Preexisting mood or psychotic disorders (Ref)
• Prior history of substance use/abuse (Ref)
• Family history of mood and psychotic disorders (eg, major depression, bipolar disorder, and schizophrenia) (Ref)
• Young age (children, adolescents, and young adults) (Ref)
• Concurrent use of corticosteroids (Ref)
Serotonin syndrome may occur when amphetamines are used in combination with drugs that affect the serotonergic neurotransmitter system in all ages. Early symptoms of serotonin syndrome include tachycardia, shivering, diarrhea, diaphoresis, muscle cramps, agitation, and increased body temperature; these symptoms are usually followed by hypertension, hyperthermia, hyperreflexia, delirium, tremors, and rigidity (Ref). Prompt treatment is needed to minimize risk of adverse outcome, including death (Ref). The incidence of serotonin syndrome from stimulants use is unknown, likely due to under reporting (Ref).
Mechanism: Amphetamines increase serotonin release and inhibit reuptake, which can lead to dangerously high extracellular concentration of serotonin especially when used in combination with other drugs that also increase serotonin concentrations (eg, CYP2D6 inhibitors, serotonin reuptake inhibitors, serotonin-norepinephrine uptake inhibitors) (Ref).
Onset: Rapid; symptoms usually begin within 24 hours of ingestion of the causative agent(s) (Ref).
Risk factors:
• Genetic polymorphism: Poor CYP2D6 metabolizers (Ref)
• Concurrent use of CYP2D6 inhibitors (Ref)
• Concurrent use of serotonergic agents (Ref)
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions are for the extended-release products in children, adolescents, and adults unless otherwise specified.
>10%:
Cardiovascular: Systolic hypertension (adolescents: 7% to 35%; transient) (table 1)
|
Drug (Dextroamphetamine and Amphetamine) |
Placebo |
Population |
Dose |
Dosage Form |
Number of Patients (Dextroamphetamine and Amphetamine) |
Number of Patients (Placebo) |
Comments |
|---|---|---|---|---|---|---|---|
|
35% |
N/A |
Adolescents |
20 mg |
Extended-release capsules |
23 |
N/A |
N/A |
|
12% |
N/A |
Adolescents |
10 mg |
Extended-release capsules |
17 |
N/A |
N/A |
|
7% |
11% |
Adolescents |
10 or 20 mg/day |
Extended-release capsules |
100 |
64 |
Isolated systolic blood pressure elevations ≥15 mmHg |
Gastrointestinal: Abdominal pain (children and adolescents: 11% to 14%), anorexia (22% to 36%), xerostomia (adolescents: 2% to 4%; adults: 23% to 35%)
Nervous system: Headache (adults: 26%), insomnia (8% to 31%)
1% to 10%:
Cardiovascular: Palpitations (adults: 2% to 4%), tachycardia (adults: 6%) (table 2)
|
Drug (Dextroamphetamine and Amphetamine) |
Placebo |
Population |
Dosage Form |
Number of Patients (Dextroamphetamine and Amphetamine) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|
|
6% |
3% |
Adults |
Extended-release capsules |
191 |
64 |
Dermatologic: Diaphoresis (adults: 2% to 4%), skin photosensitivity (adults: 2% to 4%)
Endocrine & metabolic: Decreased libido (adults: 2% to 4%), weight loss (4% to 10%)
Gastrointestinal: Bruxism (adults: 2%), constipation (adults: 2% to 4%), diarrhea (adults: 3% to 6%), dyspepsia (children and adolescents: 2% to 4%), nausea (2% to 8%), teeth clenching (adults: ≤4%), tooth infection (adults: ≤4%), upper abdominal pain (adolescents: 4%), vomiting (children and adolescents: 2% to 7%)
Genitourinary: Dysmenorrhea (adults: 2% to 4%), erectile dysfunction (adults: 2% to 4%), urinary tract infection (adults: 5%)
Infection: Infection (children and adults: 2% to 4%)
Nervous system: Agitation (adults: 2% to 8%), anxiety (adults: 7% to 8%), asthenia (≤6%), depression (adults: 3%), dizziness (2% to 7%), drowsiness (adolescents and adults: 2% to 4%), emotional lability (2% to 9%), fatigue (≤6%), irritability (adolescents: 6%), jitteriness (adults: 2%), nervousness (children and adolescents: 6%), speech disturbance (adults: 2% to 4%), twitching (adults: 2% to 4%)
Respiratory: Dyspnea (adults: 2% to 4%)
Miscellaneous: Accidental injury (children and adolescents: 2% to 4%), fever (children: 5%)
Frequency not defined: Nervous system: Drug abuse, drug dependence
Postmarketing:
Cardiovascular: Acute myocardial infarction (Ref), increased blood pressure (Ref), peripheral vascular disease (Ref), Raynaud phenomenon (Ref)
Dermatologic: Alopecia, dermatillomania, skin rash, Stevens-Johnson syndrome, toxic epidermal necrolysis (Ref), urticaria
Endocrine & metabolic: Change in libido, growth retardation (Ref), pituitary insufficiency (Ref)
Gastrointestinal: Ischemic bowel disease (intestinal), unpleasant taste
Genitourinary: Azoospermia (Ref), frequent erections, prolonged erection
Hypersensitivity: Anaphylaxis (Ref), angioedema
Nervous system: Aggressive behavior, auditory hallucination (Ref), dysphoria, euphoria, exacerbation of Gilles de la Tourette syndrome, formication, mania (Ref), outbursts of anger, overstimulation, paresthesia, psychosis (Ref), restlessness, talkativeness, tic disorder (including motor tics, vocal tics, and exacerbation of tics) (Ref), tremor, visual hallucination (Ref)
Neuromuscular & skeletal: Dyskinesia (Ref), rhabdomyolysis (Ref)
Ophthalmic: Blurred vision, mydriasis
Respiratory: Non-cardiogenic pulmonary edema (Ref), respiratory failure (Ref)
Hypersensitivity (eg, angioedema, anaphylaxis) to amphetamine or any component of the formulation; during or within 14 days following monoamine oxidase inhibitors (MAOIs) (including MAOIs such as linezolid or IV methylene blue).
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity or idiosyncrasy to sympathomimetic amines; arteriosclerosis (advanced); cardiovascular disease (symptomatic); hypertension (moderate to severe); hyperthyroidism; glaucoma; agitated states; drug abuse (history of); pheochromocytoma.
Concerns related to adverse effects:
• CNS effects: Amphetamines may impair the ability to engage in potentially hazardous activities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery, driving).
• Peripheral vasculopathy: Stimulants are associated with peripheral vasculopathy, including Raynaud phenomenon; signs/symptoms are usually mild and intermittent, and generally improve with dose reduction or discontinuation. Peripheral vasculopathy effects have been observed at different times, at therapeutic doses, and in all age groups. Digital ulceration and/or soft tissue breakdown have been observed; further evaluation (eg, rheumatology) may be necessary in patients developing signs and symptoms of peripheral vasculopathy.
• Visual disturbance: Difficulty in accommodation and blurred vision has been reported with the use of stimulants.
Disease-related concerns:
• Cardiovascular disorders: Avoid use in patients with known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmia, coronary artery disease, or other serious cardiac disease.
• Hepatic impairment: Use with caution in patients with hepatic impairment; elimination is reduced.
• Bipolar disorder: May precipitate a mixed or manic episode in patients with bipolar illness.
• Renal impairment: Use with caution in patients with renal impairment; elimination is reduced.
• Seizure disorder: Limited information exists regarding stimulant use in seizure disorder. Whereas patients with attention-deficit/hyperactivity disorder (ADHD) are at an increased risk for seizure activity compared to the general population, a retrospective study using drug claims data showed that the use of stimulant medications was associated with a lower risk (Cortese 2013; Wiggs 2018). Manufacturers of some stimulants recommend discontinuing therapy if seizures occur.
• Tourette syndrome/tics: Use with caution in patients with Tourette syndrome or other tic disorders. Stimulants may exacerbate tics (motor and phonic) and Tourette syndrome; however, evidence demonstrating increased tics is limited. Evaluate for tics and Tourette syndrome prior to therapy initiation (AAN [Pringsheim 2019]; NICE 2018).
Special populations:
• Older adult: Use caution in this age group due to CNS stimulant adverse effects.
• Pediatric: Pediatric patients 12 years of age and younger experienced high plasma exposure to Mydayis and more adverse reactions, including insomnia and decreased appetite, compared to patients 13 years of age and older.
Other warnings/precautions:
• ADHD treatment: Appropriate use: Recommended to be used as part of a comprehensive treatment program for attention-deficit disorders.
• Appropriate use: Mydayis: Medication errors, including substitution and dispensing errors, may occur, leading to possible overdosage. Do not substitute Mydayis for other amphetamine products on a mg-per-mg basis because of different amphetamine base compositions and differing pharmacokinetic profiles.
• Discontinuation of therapy: Abrupt discontinuation following high doses for prolonged periods results in extreme fatigue, mental depression, and sleep EEG changes; may also result in other symptoms of withdrawal.
Products contain equal amounts (by weight) of four salts: dextroamphetamine sulfate, amphetamine sulfate, dextroamphetamine saccharate, and amphetamine aspartate monohydrate. For example, a 10 mg capsule or tablet contains dextroamphetamine sulfate 2.5 mg, dextroamphetamine saccharate 2.5 mg, amphetamine aspartate monohydrate 2.5 mg, and amphetamine sulfate 2.5 mg.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule Extended Release 24 Hour, Oral:
Adderall XR: 20 mg, 30 mg, 25 mg
Adderall XR: 5 mg, 15 mg, 10 mg [contains fd&c blue #2 (indigotine,indigo carmine)]
Mydayis: 37.5 mg
Mydayis: 50 mg [contains fd&c blue #1 (brilliant blue)]
Mydayis: 25 mg, 12.5 mg [contains fd&c blue #2 (indigotine,indigo carmine)]
Generic: 10 mg, 12.5 mg, 15 mg, 20 mg, 25 mg, 30 mg, 37.5 mg, 5 mg, 50 mg
Tablet, Oral:
Adderall: 10 mg, 7.5 mg [scored; contains fd&c blue #1 (brill blue) aluminum lake, saccharin sodium]
Adderall: 15 mg, 12.5 mg, 30 mg, 20 mg [scored; contains fd&c yellow #6(sunset yellow)alumin lake, saccharin sodium]
Adderall: 5 mg [scored; contains saccharin sodium]
Generic: 10 mg, 12.5 mg, 15 mg, 20 mg, 30 mg, 5 mg, 7.5 mg
Yes
Capsule ER 24 Hour Therapy Pack (Adderall XR Oral)
5 mg (per each): $8.55
10 mg (per each): $8.55
15 mg (per each): $8.55
20 mg (per each): $8.55
25 mg (per each): $8.55
30 mg (per each): $8.55
Capsule ER 24 Hour Therapy Pack (Amphet-Dextroamphet 3-Bead ER Oral)
12.5 mg (per each): $11.71 - $12.88
25 mg (per each): $11.71 - $12.88
37.5 mg (per each): $11.71 - $12.88
50 mg (per each): $11.71 - $12.88
Capsule ER 24 Hour Therapy Pack (Amphetamine-Dextroamphet ER Oral)
5 mg (per each): $0.72 - $7.20
10 mg (per each): $0.72 - $7.20
15 mg (per each): $0.72 - $7.20
20 mg (per each): $0.72 - $7.20
25 mg (per each): $0.72 - $7.20
30 mg (per each): $0.72 - $7.20
Capsule ER 24 Hour Therapy Pack (Mydayis Oral)
12.5 mg (per each): $13.55
25 mg (per each): $13.55
37.5 mg (per each): $13.55
50 mg (per each): $13.55
Tablets (Adderall Oral)
5 mg (per each): $14.08
7.5 mg (per each): $14.08
10 mg (per each): $14.08
12.5 mg (per each): $14.08
15 mg (per each): $14.08
20 mg (per each): $14.08
30 mg (per each): $14.08
Tablets (Amphetamine-Dextroamphetamine Oral)
5 mg (per each): $0.17 - $2.06
7.5 mg (per each): $0.28 - $2.06
10 mg (per each): $0.19 - $2.06
12.5 mg (per each): $0.62 - $2.06
15 mg (per each): $0.23 - $2.06
20 mg (per each): $0.23 - $2.06
30 mg (per each): $0.32 - $2.06
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule Extended Release 24 Hour, Oral:
Adderall XR: 20 mg, 30 mg, 25 mg
Adderall XR: 5 mg, 10 mg, 15 mg [contains fd&c blue #2 (indigotine,indigo carmine)]
Generic: 10 mg, 15 mg, 20 mg, 25 mg, 30 mg, 5 mg
C-II
Oral: Administer with or without food. Administer Mydayis consistently either with food or without food.
Immediate release: Administer in 1 to 3 divided doses per day with intervals of 4 to 6 hours between doses. To avoid insomnia, late evening doses should be avoided.
Extended release: Administer upon awakening; to avoid insomnia, afternoon doses should be avoided. Capsule may be swallowed whole or it may be opened and the contents sprinkled on applesauce. Applesauce should be consumed immediately without chewing. Do not divide the contents of the capsule. Do not take less than one capsule per day; a single capsule should not be divided.
Oral:
Immediate-release tablet: Take on awakening; to avoid insomnia, last daily dose should be administered no less than 6 hours before retiring.
Extended-release capsule: Take on awakening. Avoid afternoon doses to prevent insomnia. Swallow capsule whole; do not chew or divide. May be administered with or without food; however, Mydayis should be taken in a consistent manner with regards to food. May open capsule and sprinkle contents on applesauce; consume applesauce/medication mixture immediately; do not store; do not chew sprinkled beads from capsule.
An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:
Adderall: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/011522s045lbl.pdf#page=15
Adderall XR: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/021303s038lbl.pdf#page=22
Mydayis: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/022063s005lbl.pdf#page=25
Attention-deficit/hyperactivity disorder: Treatment of attention-deficit/hyperactivity disorder (ADHD) as part of a total treatment program that typically includes other remedial measures (psychological, educational, social) for a stabilizing effect.
Narcolepsy, daytime sleepiness (immediate release only): Treatment of narcolepsy.
Cocaine use disorder
Adderall may be confused with Adderall XR, Inderal
Adderall XR may be confused with Adderall
Refer to individual components.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Acebrophylline: May increase stimulatory effects of CNS Stimulants. Risk X: Avoid
Ajmaline: May increase serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor
Alkalinizing Agents: May decrease excretion of Amphetamines. Management: Consider alternatives to using amphetamines and alkalinizing agents in combination. If these agents must be used together, patients should be monitored closely for excessive amphetamine effects. Risk D: Consider Therapy Modification
Amifampridine: Agents With Seizure Threshold Lowering Potential may increase neuroexcitatory and/or seizure-potentiating effects of Amifampridine. Risk C: Monitor
Amisulpride (Oral): Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Amisulpride (Oral). Specifically, the risk of seizures may be increased. Risk C: Monitor
Ammonium Chloride: May decrease serum concentration of Amphetamines. This effect is likely due to an enhanced excretion of amphetamines in the urine. Risk C: Monitor
Antihypertensive Agents: Amphetamines may decrease antihypertensive effects of Antihypertensive Agents. Risk C: Monitor
Antipsychotic Agents: May decrease stimulatory effects of Amphetamines. Antipsychotic Agents may increase adverse/toxic effects of Amphetamines. Risk C: Monitor
ARIPiprazole Lauroxil: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of ARIPiprazole Lauroxil. Specifically, the risk of seizures may be increased. Risk C: Monitor
ARIPiprazole: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of ARIPiprazole. Specifically, the risk of seizures may be increased. Risk C: Monitor
Artemether and Lumefantrine: May increase serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor
Asenapine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Asenapine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Atomoxetine: May increase hypertensive effects of Sympathomimetics. Atomoxetine may increase tachycardic effects of Sympathomimetics. Risk C: Monitor
Benperidol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Benperidol. Specifically, the risk of seizures may be increased. Risk C: Monitor
Blonanserin: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Blonanserin. Specifically, the risk of seizures may be increased. Risk C: Monitor
Bornaprine: Sympathomimetics may increase anticholinergic effects of Bornaprine. Risk C: Monitor
Brexpiprazole: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Brexpiprazole. Specifically, the risk of seizures may be increased. Risk C: Monitor
Bromperidol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Bromperidol. Specifically, the risk of seizures may be increased. Risk C: Monitor
BuPROPion: May increase neuroexcitatory and/or seizure-potentiating effects of Agents With Seizure Threshold Lowering Potential. Risk C: Monitor
Cannabinoid-Containing Products: May increase tachycardic effects of Sympathomimetics. Risk C: Monitor
Carbonic Anhydrase Inhibitors: May decrease excretion of Amphetamines. Risk C: Monitor
Cariprazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Cariprazine. Specifically, the risk of seizures may be increased. Risk C: Monitor
ChlorproMAZINE: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of ChlorproMAZINE. Specifically, the risk of seizures may be increased. Risk C: Monitor
Clothiapine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Clothiapine. Specifically, the risk of seizures may be increased. Risk C: Monitor
CloZAPine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of CloZAPine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Cocaine (Topical): May increase hypertensive effects of Sympathomimetics. Management: Consider alternatives to use of this combination when possible. Monitor closely for substantially increased blood pressure or heart rate and for any evidence of myocardial ischemia with concurrent use. Risk D: Consider Therapy Modification
CYP2D6 Inhibitors (Moderate): May increase serum concentration of Amphetamines. Management: Monitor for amphetamine toxicities (including serotonin syndrome) if used with a moderate CYP2D6 inhibitor. Initiate amphetamine therapy at lower doses, monitor frequently, and adjust doses as needed. Discontinue amphetamines if serotoinin syndrome occurs Risk C: Monitor
CYP2D6 Inhibitors (Strong): May increase serum concentration of Amphetamines. Management: Monitor for amphetamine toxicities (including serotonin syndrome) if used with a strong CYP2D6 inhibitor. Initiate amphetamine therapy at lower doses, monitor frequently, and adjust doses as needed. Discontinue amphetamines if serotoinin syndrome occurs. Risk C: Monitor
Dihydralazine: Sympathomimetics may decrease therapeutic effects of Dihydralazine. Risk C: Monitor
Doxofylline: Sympathomimetics may increase adverse/toxic effects of Doxofylline. Risk C: Monitor
DroPERidol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of DroPERidol. Specifically, the risk of seizures may be increased. Risk C: Monitor
Esketamine (Injection): May increase adverse/toxic effects of Sympathomimetics. Specifically, the risk for elevated heart rate, hypertension, and arrhythmias may be increased. Risk C: Monitor
Esketamine (Nasal): May increase hypertensive effects of CNS Stimulants. Risk C: Monitor
Fluorodopa F18: Coadministration of CNS Stimulants and Fluorodopa F18 may alter diagnostic results. Management: Discontinue medications used to treat Parkinson disease, including dopamine reuptake inhibitors and dopamine releasing agents, such as psychostimulants, 12 hours prior to fluorodopa F 18 administration if these medications can be safely withheld. Risk D: Consider Therapy Modification
Flupentixol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Flupentixol. Specifically, the risk of seizures may be increased. Risk C: Monitor
FluPHENAZine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of FluPHENAZine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Gastrointestinal Acidifying Agents: May decrease serum concentration of Amphetamines. Risk C: Monitor
Guanethidine: May increase hypertensive effects of Sympathomimetics. Guanethidine may increase arrhythmogenic effects of Sympathomimetics. Risk C: Monitor
Haloperidol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Haloperidol. Specifically, the risk of seizures may be increased. Risk C: Monitor
Iloperidone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Iloperidone. Specifically, the risk of seizures may be increased. Risk C: Monitor
Inhalational Anesthetics: Amphetamines may increase hypotensive effects of Inhalational Anesthetics. Risk C: Monitor
Inhibitors of the Proton Pump (PPIs and PCABs): May increase absorption of Amphetamines. Specifically, the amphetamine absorption rate may be increased in the first hours after dosing. Risk C: Monitor
Iobenguane Radiopharmaceutical Products: Amphetamines may decrease therapeutic effects of Iobenguane Radiopharmaceutical Products. Management: Discontinue all drugs that may inhibit or interfere with catecholamine transport or uptake for at least 5 biological half-lives before iobenguane administration. Do not administer these drugs until at least 7 days after each iobenguane dose. Risk X: Avoid
Iobenguane Radiopharmaceutical Products: CNS Stimulants may decrease therapeutic effects of Iobenguane Radiopharmaceutical Products. Management: Discontinue all drugs that may inhibit or interfere with catecholamine transport or uptake for at least 5 biological half-lives before iobenguane administration. Do not administer these drugs until at least 7 days after each iobenguane dose. Risk X: Avoid
Ioflupane I 123: Coadministration of Amphetamines and Ioflupane I 123 may alter diagnostic results. Risk C: Monitor
Iohexol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Iohexol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iohexol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic antiseizure drugs. Risk D: Consider Therapy Modification
Iomeprol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Iomeprol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iomeprol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic antiseizure drugs. Risk D: Consider Therapy Modification
Iopamidol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Iopamidol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iopamidol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic antiseizure drugs. Risk D: Consider Therapy Modification
Kratom: May increase adverse/toxic effects of Sympathomimetics. Risk X: Avoid
Landiolol: Sympathomimetics may decrease therapeutic effects of Landiolol. Risk C: Monitor
Levothyroxine: May increase therapeutic effects of Sympathomimetics. Sympathomimetics may increase therapeutic effects of Levothyroxine. Levothyroxine may increase adverse/toxic effects of Sympathomimetics. Specifically, the risk of coronary insufficiency may be increased in patients with coronary artery disease. Risk C: Monitor
Loxapine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Loxapine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Lumateperone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Lumateperone. Specifically, the risk of seizures may be increased. Risk C: Monitor
Lurasidone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Lurasidone. Specifically, the risk of seizures may be increased. Risk C: Monitor
Mavorixafor: May increase serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk X: Avoid
Methenamine: May decrease serum concentration of Amphetamines. This effect is likely due to an enhanced excretion of amphetamines in the urine. Risk C: Monitor
Methotrimeprazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Methotrimeprazine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Molindone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Molindone. Specifically, the risk of seizures may be increased. Risk C: Monitor
Monoamine Oxidase Inhibitors: May increase hypertensive effects of Amphetamines. While linezolid and tedizolid may interact via this mechanism, management recommendations differ from other monoamine oxidase inhibitors. Refer to monographs specific to those agents for details. Risk X: Avoid
Multivitamins/Fluoride (with ADE): May decrease serum concentration of Amphetamines. More specifically, the ascorbic acid (vitamin C) in many multivitamins may decrease amphetamine concentrations. Risk C: Monitor
Multivitamins/Minerals (with ADEK, Folate, Iron): May decrease serum concentration of Amphetamines. Risk C: Monitor
Multivitamins/Minerals (with AE, No Iron): May decrease serum concentration of Amphetamines. Specifically, vitamin C may impair absorption of amphetamines. Risk C: Monitor
OLANZapine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of OLANZapine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Opioid Agonists: Amphetamines may increase analgesic effects of Opioid Agonists. Risk C: Monitor
Paliperidone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Paliperidone. Specifically, the risk of seizures may be increased. Risk C: Monitor
Peginterferon Alfa-2b: May decrease serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Peginterferon Alfa-2b may increase serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor
Periciazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Periciazine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Perphenazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Perphenazine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Pimozide: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Pimozide. Specifically, the risk of seizures may be increased. Risk C: Monitor
Pipamperone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Pipamperone. Specifically, the risk of seizures may be increased. Risk X: Avoid
Polyethylene Glycol-Electrolyte Solution: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Polyethylene Glycol-Electrolyte Solution. Specifically, the risk of seizure may be increased. Risk C: Monitor
Prochlorperazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Prochlorperazine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Promazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Promazine. Specifically, the risk of seizures may be increased. Risk C: Monitor
QUEtiapine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of QUEtiapine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Quinolones: Amphetamines may increase cardiotoxic effects of Quinolones. Risk C: Monitor
RisperiDONE: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of RisperiDONE. Specifically, the risk of seizures may be increased. Risk C: Monitor
Selective Serotonin Reuptake Inhibitors (Strong CYP2D6 Inhibitors): Amphetamines may increase serotonergic effects of Selective Serotonin Reuptake Inhibitors (Strong CYP2D6 Inhibitors). This could result in serotonin syndrome. Selective Serotonin Reuptake Inhibitors (Strong CYP2D6 Inhibitors) may increase serum concentration of Amphetamines. Management: Monitor for amphetamine toxicities, including serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability). Initiate amphetamines at lower doses, monitor frequently, and adjust dose as needed. Risk C: Monitor
Serotonergic Agents (High Risk): Amphetamines may increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability). Initiate amphetamines at lower doses, monitor frequently, and adjust doses as needed. Risk C: Monitor
Sertindole: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Sertindole. Specifically, the risk of seizures may be increased. Risk C: Monitor
Sodium Phosphates: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Sodium Phosphates. Specifically, the risk of seizure or loss of consciousness may be increased in patients with significant sodium phosphate-induced fluid or electrolyte abnormalities. Risk C: Monitor
Solriamfetol: CNS Stimulants may increase hypertensive effects of Solriamfetol. CNS Stimulants may increase tachycardic effects of Solriamfetol. Risk C: Monitor
Solriamfetol: Sympathomimetics may increase hypertensive effects of Solriamfetol. Sympathomimetics may increase tachycardic effects of Solriamfetol. Risk C: Monitor
Sulpiride: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Sulpiride. Specifically, the risk of seizures may be increased. Risk C: Monitor
Tedizolid: May increase adverse/toxic effects of Sympathomimetics. Specifically, the risk for increased blood pressure and heart rate may be increased. Risk C: Monitor
Thioridazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Thioridazine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Thiothixene: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Thiothixene. Specifically, the risk of seizures may be increased. Risk C: Monitor
Tricyclic Antidepressants: May increase adverse/toxic effects of Amphetamines. Tricyclic Antidepressants may potentiate the cardiovascular effects of Amphetamines. Amphetamines may increase serotonergic effects of Tricyclic Antidepressants. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) and increased cardiovascular effects when these agents are combined. Risk C: Monitor
Trifluoperazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Trifluoperazine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Urinary Acidifying Agents: May decrease serum concentration of Amphetamines. Risk C: Monitor
Ziprasidone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Ziprasidone. Specifically, the risk of seizures may be increased. Risk C: Monitor
Zuclopenthixol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Zuclopenthixol. Specifically, the risk of seizures may be increased. Risk C: Monitor
Amphetamine serum levels may be reduced if taken with acidic food, juices, or vitamin C. Management: Monitor response when taken concurrently.
Azoospermia was described in a case report in a patient following the initiation of dextroamphetamine/amphetamine. A repeat semen analysis showed resolution 5 months after discontinuing (Abdalla 2021).
Outcome data following maternal use of dextroamphetamine/amphetamine during pregnancy are available (Cohen 2017; Huybrechts 2018; Rose 2021; Suarez 2024; Szpunar 2023). Placental perfusion may be decreased due to vasoconstriction caused by CNS stimulants. Use of amphetamines during pregnancy may lead to an increased risk of premature birth and low birth weight; newborns may experience symptoms of withdrawal. Monitor newborns for agitation, irritability, excessive drowsiness, or feeding difficulties.
Treatment for attention-deficit hyperactivity disorder (ADHD) typically involves behavioral therapies in combination with medication. Nonpharmacologic therapies are recommended as first-line treatment for pregnant patients with mild to moderate ADHD. The decision to use medication should be made as part of a shared decision-making process that considers the risk of untreated or undertreated moderate to severe ADHD; use of the lowest effective dose and minimum number of medications is recommended (Scoten 2024).
Refer to individual monographs for additional information.
Data collection to monitor pregnancy outcomes following exposure to dextroamphetamine/amphetamine is ongoing. Health care providers are encouraged to enroll patients exposed to dextroamphetamine/amphetamine during pregnancy in the National Pregnancy Registry for ADHD Medications (1-866-961-2388).
Dextroamphetamine and amphetamine are present in breast milk.
The manufacturer reports relative infant doses of 2% to 13.8% of the weight-adjusted maternal dose when evaluating the literature for both amphetamine and dextroamphetamine. In general, breastfeeding is considered acceptable when the relative infant dose of a medication is <10% (Anderson 2016; Ito 2000).
Outcome data following use of dextroamphetamine/amphetamine in breastfeeding patients are limited (Benassayag Kaduri 2024). Increased irritability, agitation, and crying have been reported in breastfeeding infants. As a class, amphetamines may also decrease milk supply (ACOG 2011). Effects on long-term neurodevelopment are not known.
Due to the potential for serious adverse reactions in the breastfed infant (including BP and heart rate increases, cardiovascular reactions, growth suppression, peripheral vasculopathy), breastfeeding is not recommended by the manufacturer. Nonpharmacologic therapies are recommended for breastfeeding patients with mild to moderate ADHD. The use of medications should be made as part of a shared decision-making process that considers the risk of untreated or undertreated moderate to severe ADHD; use of the lowest effective dose and minimum number of medications is recommended. Monitor infants exposed to ADHD medications via breast milk for adverse events, including feeding difficulties, irritability, and insomnia. Evaluate options (such as intermittent use, timing of feedings, or other alternatives) to achieve the lowest exposure to amphetamine derivatives in breast milk (Scoten 2024).
Breastfeeding is not recommended following maternal use of nonprescribed amphetamines (ACOG 2011; Scoten 2024).
Refer to individual monographs for additional information.
Cardiac evaluation (including medical or family history of sudden death or ventricular arrhythmia; ECG as indicated) should be completed at baseline and on any patient who develops exertional chest pain, unexplained syncope, and any symptom of cardiac disease during treatment with stimulants. Monitor BP and heart rate (baseline, following dose increases and periodically during treatment); growth rate (height and weight) and appetite in children; weight in adults; signs of peripheral vasculopathy (eg, digital changes); sleep and behavioral changes; assess family history and evaluate for tics or Tourette syndrome prior to initiation of therapy; assess for new signs or worsening of tics or Tourette syndrome during treatment. Assess for risk of abuse (including a history of ethanol or drug abuse) prior to prescribing and signs of misuse, abuse, or substance use disorder throughout treatment (NICE 2018).
Screen for bipolar disorder and risk factors for developing a manic episode prior to treatment; monitor for psychotic or manic symptoms (eg, delusional thinking, hallucinations, mania); monitor for development or worsening of aggressive behavior or hostility.
Amphetamines are noncatecholamine, sympathomimetic amines that promote release of catecholamines (primarily dopamine and norepinephrine) from their storage sites in the presynaptic nerve terminals. A less significant mechanism may include their ability to block the reuptake of catecholamines by competitive inhibition.
Note: The immediate-release tablets and ER capsules contain d-amphetamine and l-amphetamine salts in the ratio of 3:1.
Duration of action: Immediate-release tablet: 4 to 6 hours (Dopheide 2009); Adderall XR: 8 to 12 hours (Jain 2017); Mydayis: ≤16 hours
Absorption: Extended release: Food does not affect absorption, but prolongs Tmax of Adderall XR by 2 to 3 hours and Mydayis by 4 to 5 hours.
Half-life elimination:
Children 6 to 12 years: d-amphetamine: 9 hours; l-amphetamine: 11 hours
Adolescents 13 to 17 years: d-amphetamine: 11 hours; l-amphetamine: 13 to 14 hours
Adults: d-amphetamine: 10 hours; l-amphetamine: 13 hours
Metabolism: Hepatic oxidation via cytochrome P450 to 4-hydroxyamphetamine (active) norephedrine (active), and alpha-hydroxy-amphetamine with both active metabolites subsequently oxidized to 4-hydroxy-norephedrine. Cytochrome P450 2D6 is primarily responsible for the formation of 4-hydroxy-amphetamine.
Time to peak: Immediate release: 3 hours; Adderall XR: 7 hours; Mydayis: 7 to 10 hours (children and adolescents 6 to 17 years), 8 hours (adults)
Excretion: Urine (highly dependent on urinary pH); excreted as unchanged amphetamine (30% to 40%, may range from ~1% in alkaline urine to ~75% in acidic urine), and derivatives of alpha-hydroxyamphetamine (50%)
Pediatric: Children eliminated amphetamine faster than adults. The elimination half-life is approximately 1 hour shorter for d-amphetamine and 2 hours shorter for l-amphetamine in children than in adults. However, children had higher systemic exposure to amphetamine (Cmax and AUC) than adults for a given dose of ER capsules, which was attributed to the higher dose administered to children on a mg/kg basis compared with adults. Upon dose normalization on a mg/kg basis, children showed 30% less systemic exposure compared with adults. Patients 6 to 12 years of age experienced higher systemic exposure (72% to 79% higher Cmax and 83% higher AUC), compared with adults.
Weight: Weight is the primary determinant of apparent differences in the pharmacokinetics of d- and l-amphetamine across the age range. Systemic exposure measured by AUC∞ and Cmax decreased with increases in body weight, while apparent oral volume of distribution, apparent oral clearance, and elimination half-life increased with increases in body weight.
