Version July 2025
Lisdexamfetamine 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 lisdexamfetamine, 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 lisdexamfetamine, 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 lisdexamfetamine treatment, reassess each patient's risk of abuse, misuse, and addiction and frequently monitor for signs and symptoms of abuse, misuse, and addiction.
Dosage guidance:
Clinical considerations: Prior to treatment, assess for presence of cardiac disease and assess for risk of abuse.
Attention-deficit/hyperactivity disorder (ADHD): Oral: Initial: 30 mg once daily in the morning; may increase in increments of 10 mg or 20 mg at weekly intervals until optimal response is obtained; maximum: 70 mg/day. Note: Individualize dosage based on patient need and response to therapy. Administer at the lowest effective dose.
Binge eating disorder: Oral: Initial: 30 mg once daily in the morning; may titrate in increments of 20 mg at weekly intervals to target dose of 50 to 70 mg once daily (maximum: 70 mg/day); discontinue use if binge eating does not improve.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
GFR ≥30 mL/minute/1.73 m2: There are no dosage adjustments provided in the manufacturer's labeling.
GFR 15 to <30 mL/minute/1.73 m2: Maximum dose: 50 mg/day.
GFR <15 mL/minute/1.73 m2: Maximum dose: 30 mg/day.
ESRD requiring hemodialysis: Maximum dose: 30 mg/day; lisdexamfetamine and dextroamphetamine are not dialyzable.
There are no dosage adjustments provided in the manufacturer's labeling.
Refer to adult dosing; initiate dose at the low end of the dosing range.
(For additional information see "Lisdexamfetamine: Pediatric drug information")
Attention-deficit/hyperactivity disorder (ADHD): Children ≥6 years and Adolescents: Capsules, chewable tablets: Oral: Initial: 20 to 30 mg once daily in the morning; may increase in increments of 10 mg/day or 20 mg/day at 3- to 7-day intervals until optimal response is obtained; use lowest effective individualized dose; maximum daily dose: 70 mg/day (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Children ≥6 years and Adolescents: Capsules, chewable tablets: Oral:
GFR ≥30 mL/minute/1.73 m2: There are no dosage adjustments provided in the manufacturer's labeling.
GFR 15 to <30 mL/minute/1.73 m2: Maximum daily dose: 50 mg/day.
GFR <15 mL/minute/1.73 m2: Maximum daily dose: 30 mg/day.
ESRD requiring hemodialysis: Maximum daily dose: 30 mg/day; lisdexamfetamine and dextroamphetamine are not dialyzable.
There are no dosage adjustments provided in the manufacturer's labeling.
Cardiovascular events including myocardial infarctions (MI), stroke, sudden cardiac death (SCD), increased heart rate, and increased blood pressure have been reported with the use of CNS stimulants in adult and pediatric patients (Ref); syncope and severe cardiac arrythmia have been described with lisdexamfetamine in children and adolescents (Ref). CNS stimulants have also been associated with SCD 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). A study evaluating the cardiac effects of long-term treatment with lisdexamfetamine in adults did not find any clinically significant changes in cardiac structure or function (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 cardiac abnormalities (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)
Growth retardation, including weight loss and decreased rate of growth, has been reported in pediatric patients. Statistically significant decreases in weight, height, and BMI in children and adolescents (age range: 6 to 13 years) have been observed in short- and long-term studies (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 lisdexamfetamine) 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). The effect of lisdexamfetamine on weight in adults is variable and the long-term effects of treatment on growth into adulthood have yet to be determined (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: Varied; appears to occur within 4 weeks of initiating treatment (median 29 days; range: 1 to 677 days) (Ref).
Risk factors:
• Higher doses (Ref)
• Duration of treatment/cumulative exposure (Ref)
• Baseline height and/or weight above CDC norms upon initiation (Ref)
• Children and adolescents (Ref)
• No prior history of stimulant use (Ref)
New-onset psychosis or mania and exacerbation of psychotic or manic symptoms (eg, delusional thinking, hallucination) may occur with neurostimulant use in all ages (Ref). Aggressive behavior, hostility, and suicidal ideation have also been reported with lisdexamfetamine use in children and adolescents, however a causal relationship has not been established (Ref). 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 an amphetamine-associated 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. Reported adverse reactions are for children, adolescents, and adults unless otherwise indicated.
>10%:
Gastrointestinal: Decreased appetite (children and adolescents: 34% to 39%; adults 8% to 27%), upper abdominal pain (children: 12%; adults: 2%), xerostomia (children and adolescents: 4% to 5%; adults: 26% to 36%)
Nervous system: Insomnia (13% to 27%)
1% to 10%:
Cardiovascular: Increased blood pressure (adults: 3%) (table 1), increased heart rate (adults: 2% to 7%) (table 2), palpitations (adolescents and adults: 2%)
|
Drug (Lisdexamfetamine) |
Placebo |
Population |
Indication |
Number of Patients (Lisdexamfetamine) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|
|
3% |
0% |
Adults |
Attention deficit hyperactivity disorder |
358 |
62 |
|
Drug (Lisdexamfetamine) |
Placebo |
Population |
Indication |
Number of Patients (Lisdexamfetamine) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|
|
2% |
0% |
Adults |
Attention deficit hyperactivity disorder |
358 |
62 |
|
7% |
1% |
Adults |
Binge eating disorder |
373 |
372 |
Dermatologic: Hyperhidrosis (adults: 3% to 4%), pruritus (adults: 2%), skin rash (children: 3%)
Endocrine & metabolic: Decreased libido (adults: 1%), weight loss (children and adolescents: 9%; adults: 3% to 4%)
Gastrointestinal: Anorexia (2% to 5%), constipation (adults: 6%), diarrhea (adults: 4% to 7%), gastroenteritis (adults: 2%), nausea (6% to 7%), vomiting (children: 9%; adults: 2%)
Genitourinary: Erectile dysfunction (adults: 3%), urinary tract infection (adults: 2%)
Nervous system: Agitation (adults: 3%), anxiety (adults: 5% to 6%), dizziness (children: 5%), drowsiness (children: 2%), emotional lability (children: 3%), increased energy (adults: 2%), irritability (children: 10%), jitteriness (adults: 4% to 6%), nightmares (adults: 2%), paresthesia (adults: 2%), restlessness (adults: 2% to 3%), tic disorder (children: 2%), tremor (adolescents and adults: 2%)
Respiratory: Dyspnea (adults: 2%), oropharyngeal pain (adults: 2%)
Miscellaneous: Fever (children: 2%)
Frequency not defined: Nervous system: Drug abuse, drug dependence, talkativeness
Postmarketing:
Cardiovascular: Cardiac arrhythmia (Ref), cardiomyopathy, chest pain, peripheral vascular insufficiency, Raynaud disease (Ref), syncope (Ref)
Dermatologic: Alopecia (Ref), dermatillomania, Stevens-Johnson syndrome, urticaria
Endocrine & metabolic: Change in libido, growth retardation (Ref)
Gastrointestinal: Bruxism, dysgeusia, mesenteric ischemia
Genitourinary: Frequent erections (Ref), priapism (Ref)
Hepatic: Hepatitis (eosinophilic) (Ref)
Hypersensitivity: Anaphylaxis, angioedema
Nervous system: Aggressive behavior (Ref), depression (Ref), euphoria (Ref), headache (Ref), hostility (Ref), mania (Ref), outbursts of anger (Ref), paranoid ideation (including obsessive thoughts) (Ref), psychomotor agitation (Ref), seizure, suicidal ideation (Ref), tic disorder (including motor tics and vocal tics)
Neuromuscular & skeletal: Dyskinesia, rhabdomyolysis
Ophthalmic: Accommodation disturbance, angle-closure glaucoma (acute, bilateral) (Ref), blurred vision, diplopia, mydriasis
Miscellaneous: Crying (Ref)
Hypersensitivity to amphetamine products or any component of the formulation; concurrent use of monoamine oxidase (MAO) inhibitor (including linezolid or IV methylene blue), or within 14 days of the last MAO inhibitor dose.
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): Known hypersensitivity or idiosyncrasy to sympathomimetic amines; advanced arteriosclerosis; symptomatic cardiovascular disease; moderate-to-severe hypertension; hyperthyroidism; glaucoma; agitated states; history of drug abuse
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 which require mental alertness (eg, operating machinery or 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.
• Bipolar disorder: May precipitate a mixed or manic episode in patients with bipolar illness.
• Seizure disorder: Limited information exists regarding stimulant use in seizure disorder. Whereas patients with 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 (AACAP [Murphy 2013]; Pliszka 2007).
Special populations:
• Older adult: Use caution in this age group due to CNS stimulant adverse effects.
Other warnings/precautions:
• Abuse/misuse/diversion: Use with caution in patients with a history of ethanol or drug abuse. Prescriptions should be written for the smallest quantity consistent with good patient care to minimize possibility of overdose.
• ADHD treatment: Appropriate use: Recommended to be used as part of a comprehensive treatment program for attention deficit disorders.
• Weight loss: Appropriate use: Not indicated or recommended for weight loss; safety and efficacy not established for treatment of obesity.
• Discontinuation of therapy: Abrupt discontinuation following high doses or for prolonged periods may result in symptoms for withdrawal (eg, depression, extreme fatigue).
Prior to treatment with medications for attention-deficit/hyperactivity disorder (ADHD), the American Heart Association and the American Academy of Pediatrics recommend that all children and adolescents diagnosed with ADHD have a thorough cardiovascular assessment, including patient and family health histories, determination of all medications used (prescribed and over-the-counter), and a physical examination focused on cardiovascular disease risk factors. An ECG is not mandatory but is reasonable to consider prior to stimulant medication therapy. Prompt evaluation and appropriate referral and testing, if warranted, should occur if any cardiac symptoms present (Vetter 2008).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral, as dimesylate:
Vyvanse: 10 mg, 20 mg
Vyvanse: 30 mg [contains fd&c yellow #6 (sunset yellow)]
Vyvanse: 40 mg, 50 mg, 60 mg [contains fd&c blue #1 (brilliant blue)]
Vyvanse: 70 mg [contains fd&c blue #1 (brilliant blue), fd&c yellow #6 (sunset yellow)]
Generic: 10 mg, 20 mg, 30 mg, 40 mg, 50 mg, 60 mg, 70 mg
Tablet Chewable, Oral, as dimesylate:
Vyvanse: 10 mg, 20 mg, 30 mg, 40 mg, 50 mg, 60 mg
Generic: 10 mg, 20 mg, 30 mg, 40 mg, 50 mg, 60 mg
Yes
Capsules (Lisdexamfetamine Dimesylate Oral)
10 mg (per each): $6.60 - $14.74
20 mg (per each): $6.60 - $14.74
30 mg (per each): $6.60 - $14.74
40 mg (per each): $6.60 - $14.74
50 mg (per each): $6.60 - $14.74
60 mg (per each): $6.60 - $14.74
70 mg (per each): $6.60 - $14.74
Capsules (Vyvanse Oral)
10 mg (per each): $15.51
20 mg (per each): $15.51
30 mg (per each): $15.51
40 mg (per each): $15.51
50 mg (per each): $15.51
60 mg (per each): $15.51
70 mg (per each): $15.51
Chewable (Lisdexamfetamine Dimesylate Oral)
10 mg (per each): $13.85 - $14.74
20 mg (per each): $13.85 - $14.74
30 mg (per each): $13.85 - $14.74
40 mg (per each): $13.85 - $14.74
50 mg (per each): $13.85 - $14.74
60 mg (per each): $13.85 - $14.74
Chewable (Vyvanse Oral)
10 mg (per each): $15.51
20 mg (per each): $15.51
30 mg (per each): $15.51
40 mg (per each): $15.51
50 mg (per each): $15.51
60 mg (per each): $15.51
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, Oral, as dimesylate:
Vyvanse: 10 mg, 20 mg, 30 mg, 40 mg, 50 mg, 60 mg, 70 mg [contains fd&c blue #1 (brilliant blue), fd&c yellow #6 (sunset yellow)]
Generic: 10 mg, 20 mg, 30 mg, 40 mg, 50 mg, 60 mg, 70 mg
Tablet Chewable, Oral, as dimesylate:
Vyvanse: 10 mg, 20 mg, 30 mg, 40 mg, 50 mg, 60 mg
Generic: 10 mg, 20 mg, 30 mg, 40 mg, 50 mg, 60 mg
C-II
Administer in the morning without regard to meals; avoid afternoon doses because of potential for insomnia. Do not take less than one capsule or chewable tablet per day; a single dose should not be divided.
Capsules: Swallow capsule whole, do not chew. Capsule may be opened and the entire contents mixed with water, yogurt, or orange juice; stir until dispersed completely and consume the entire mixture immediately; do not store mixture. The active ingredient dissolves completely once dispersed; however, a film containing the inactive ingredients may remain in the glass or container once the mixture is consumed.
Chewable tablets: Chew thoroughly before swallowing.
Oral: Administer in the morning without regard to food; avoid afternoon doses to prevent insomnia. Do not take less than 1 chewable tablet or capsule daily; a single dose should not be divided.
Capsule: Swallow capsule whole, do not chew. Capsule may be opened and the entire contents dissolved in glass of water, yogurt, or orange juice; stir until dispersed completely and consume the resulting mixture immediately; do not store the mixture. The active ingredient dissolves completely once dispersed; however, a film containing the inactive ingredients may remain in the glass or container once the mixture is consumed.
Chewable tablets: Chew thoroughly before swallowing.
An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:
Vyvanse: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/021977s050,208510s007lbl.pdf#page=38
Attention-deficit/hyperactivity disorder: Treatment of attention-deficit/hyperactivity disorder (ADHD) in adults and pediatric patients ≥6 years of age.
Binge eating disorder: Treatment of moderate to severe binge eating disorder in adults.
Vyvanse may be confused with Glucovance, Visanne, ViVAXIM, Vytorin, Vivactil
Substrate of CYP2D6 (Major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential;
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
Sympathomimetics: May increase adverse/toxic effects of Sympathomimetics. 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
High-fat meal prolongs Tmax by ~1 hour. Management: Administer without regard to meals.
Outcome data following maternal use of lisdexamfetamine during pregnancy are limited (Bang Madsen 2023; Camacho 2023; 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).
Lisdexamfetamine is converted to dextroamphetamine; refer to the dextroamphetamine monograph for additional information.
Data collection to monitor pregnancy outcomes following exposure to lisdexamfetamine is ongoing. Health care providers are encouraged to enroll patients exposed to lisdexamfetamine during pregnancy in the National Pregnancy Registry for ADHD Medications (1-866-961-2388).
Lisdexamfetamine is converted to dextroamphetamine; dextroamphetamine is present in breast milk.
The manufacturer reports relative infant doses (RID) 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 RID of a medication is <10% (Anderson 2016; Ito 2000).
Outcome data following maternal use of lisdexamfetamine 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 attention-deficit/hyperactivity disorder (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 the dextroamphetamine monograph 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 blood pressure 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 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) or suicide-related behavior; monitor for development or worsening of aggressive behavior or hostility.
The exact mechanism of lisdexamfetamine in ADHD and binge eating disorder is not known. Lisdexamfetamine dimesylate is a prodrug that is converted to the active component dextroamphetamine (a noncatecholamine, sympathomimetic amine). Amphetamines are noncatecholamine, sympathomimetic amines that cause 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.
Duration of action: 8 to 14 hours (Jain 2017).
Absorption: Rapid.
Metabolism: Metabolized in the blood by hydrolytic activity of red blood cells to dextroamphetamine and l-lysine; lisdexamfetamine does not undergo CYP mediated metabolism; however, dextroamphetamine is metabolized to some degree by CYP2D6.
Half-life elimination: Lisdexamfetamine: <1 hour; Dextroamphetamine: 10 to 13 hours.
Time to peak:
Capsule: Tmax: Lisdexamfetamine: Children 6 to 12 years: 1 hour (fasting); Adults: ~1 hour; Dextroamphetamine: Children 6 to 12 years: 3.5 hours (fasting); Adults: 3.8 hours (fasting), 4.7 hours (after a high-fat meal).
Chewable tablet: Tmax: Lisdexamfetamine: 1 hour (fasting); Dextroamphetamine: 3.9 to 4.4 hours (fasting); 4.9 hours (after a high-fat meal).
Excretion: Urine (96%, 42% as amphetamine-related compounds, 2% as lisdexamfetamine, 25% hippuric acid); feces (minimal).
Altered kidney function: Mean dextroamphetamine clearance was reduced from 0.7 L/hour/kg to 0.4 L/hour/kg with severe renal impairment (GFR 15 to <30 mL/minute/1.73 m2) and to 0.3 L/hour/kg with ESRD.
