Brand name: Vyvanse
Drug class: Amphetamines
VA class: CN801
Chemical name: (2S)-2,6-diamino-N-[(1S)-1-methyl-2-phenylethly] hexanamide dimethanesulfonate
Molecular formula: C₁₅H₂₅N₃O • (CH₄O₃S)₂
CAS number: 608137-33-3

Medically reviewed by Drugs.com on May 18, 2023. Written by ASHP.

Introduction

Prodrug of dextroamphetamine; noncatechol, sympathomimetic amine with CNS-stimulating activity.

Uses for Lisdexamfetamine

Attention-Deficit/Hyperactivity Disorder

Used as adjunct to psychological, educational, social, and other remedial measures in the treatment of attention-deficit/hyperactivity disorder (ADHD) (hyperkinetic disorder, hyperkinetic syndrome of childhood, minimal brain dysfunction).

Safety and efficacy established in children ≥6 years of age, adolescents, and adults who met criteria for ADHD.

Almost all studies comparing behavioral therapy versus stimulants alone show a much stronger therapeutic effect from stimulants than from behavioral therapy, and stimulants (e.g., amphetamines, methylphenidate) remain the drugs of choice for the management of ADHD.

Drug therapy not indicated in all patients with ADHD; consider such therapy only after performing a complete evaluation including medical history.

Base use on age, adequate diagnosis (based on medical, special psychological, educational, social resources), and the clinician’s assessment of the severity, duration, and frequency of symptoms and not solely on one or more behavioral characteristics.

Binge-Eating Disorder

Used for treatment of moderate to severe binge-eating disorder in adults. Reduces mean number of binge days per week compared with placebo.

Do not use for weight loss; use of other sympathomimetic drugs for weight loss associated with serious adverse cardiovascular events. Efficacy and safety of lisdexamfetamine for treatment of obesity not established.

Related/similar drugs

Adderall, Vyvanse, methylphenidate, atomoxetine, Ritalin, Concerta

Lisdexamfetamine Dosage and Administration

General

• Assess patients for presence of cardiac disease prior to initiation of therapy. (See Sudden Death and Serious Cardiovascular Events under Cautions.)

• Assess potential for abuse of CNS stimulants prior to initiation of therapy. After prescribing amphetamine therapy, carefully maintain prescription records, and educate patients about abuse of stimulants; monitor for signs of abuse and overdose. Reevaluate need for continued therapy.

Administration

Oral Administration

Administer capsules or chewable tablets once daily in the morning without regard to meals. Because of potential for insomnia, avoid administering in the afternoon.

Swallow capsules whole.

Alternatively, capsule may be opened and entire contents mixed with water, orange juice, or yogurt until completely dispersed; administer resulting mixture immediately. Do not store mixture for use at later time.

Do not subdivide capsule contents; do not administer a dose less than the entire contents of one capsule or one chewable tablet.

Chew tablets thoroughly before swallowing.

Capsules can be substituted for chewable tablets on a mg-per-mg basis.

Dosage

Available as lisdexamfetamine dimesylate; dosage expressed in terms of the salt.

Pediatric Patients

Attention-Deficit/Hyperactivity Disorder

Oral

Children and adolescents ≥6 years of age: Initially, 30 mg once daily; dosage may be adjusted in 10- or 20-mg increments at weekly intervals.

If the initial 30-mg daily dosage is not tolerated, dosage may be decreased to 20 mg daily.

Adults

Attention-Deficit/Hyperactivity Disorder

Oral

Initially, 30 mg once daily; dosage may be adjusted in 10- or 20-mg increments at weekly intervals.

If the initial 30-mg daily dosage is not tolerated, dosage may be decreased to 20 mg daily.

Binge-Eating Disorder

Oral

Initially, 30 mg once daily; adjust dosage in 20-mg increments at weekly intervals to target dosage of 50–70 mg daily.

Discontinue drug if binge eating does not improve.

Prescribing Limits

Pediatric Patients

Attention-Deficit/Hyperactivity Disorder

Oral

Maximum 70 mg daily.

Adults

Attention-Deficit/Hyperactivity Disorder

Oral

Maximum 70 mg daily.

Binge-Eating Disorder

Oral

Maximum 70 mg daily.

Special Populations

Renal Impairment

Severe renal impairment (GFR 15 to <30 mL/minute per 1.73 m²): Maximum 50 mg daily.

End-stage renal disease (ESRD) (GFR <15 mL/minute per 1.73 m²): Maximum 30 mg daily.

Cautions for Lisdexamfetamine

Contraindications

• Known hypersensitivity to amphetamines or any ingredient in the formulation.

• Concurrent or recent (i.e., within 14 days) therapy with MAO inhibitors, including linezolid or IV methylene blue. (See Specific Drugs, Tests, and Foods under Interactions.)

Warnings/Precautions

Warnings

Abuse Potential

Potential for abuse and dependence. Assess risk of abuse prior to initiation of lisdexamfetamine and monitor patients for signs of abuse and dependence during therapy. (See Boxed Warning.)

Consider the possibility that family members may abuse the patient’s medication.

Other Warnings and Precautions

Sudden Death and Serious Cardiovascular Events

Sudden unexplained death, stroke, and MI reported in adults with ADHD receiving usual dosages of stimulants; sudden death also reported in children and adolescents with structural cardiac abnormalities or other serious cardiac conditions receiving usual dosages of the drugs. Postmarketing experience with lisdexamfetamine includes reports of cardiomyopathy, chest pain.

Although an initial epidemiologic study showed association between use of stimulants and sudden unexplained death in healthy children and adolescents, subsequent large epidemiologic studies in children and young adults or in adults 25–64 years of age found no association between ADHD drug use (stimulants, atomoxetine, pemoline [no longer commercially available in US]) and serious cardiovascular events (MI, stroke, sudden cardiac death), although small increases in cardiovascular risk could not be excluded.

Thoroughly review medical history (including evaluation for family history of sudden death or ventricular arrhythmia) and perform physical examination in all children, adolescents, and adults being considered for stimulant therapy; if initial findings suggest presence of cardiac disease, perform further cardiac evaluation (e.g., ECG, echocardiogram).

Avoid use of CNS stimulants in patients with known serious structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, CAD, or other serious cardiac conditions.

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

Effects on BP and Heart Rate

Possible modest increases in average BP (i.e., by about 2–4 mm Hg) and heart rate (i.e., by about 3–6 bpm); larger increases may occur. Monitor all patients for changes in BP and heart rate.

Exacerbation or Precipitation of Psychotic Symptoms

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

Psychotic symptoms (e.g., hallucinations, delusional thinking) may occur with usual dosages in children and adolescents without prior history of psychotic illness. If psychotic symptoms occur, consider causal relationship to stimulants, and discontinue therapy as appropriate.

Precipitation of Manic Symptoms

May precipitate mixed or manic episodes in patients with bipolar disorder. Prior to initiating therapy, carefully screen patients for risk factors for developing a manic episode; with screening, include a detailed psychiatric history (e.g., comorbid depressive symptoms or history of depressive symptoms; family history of suicide, bipolar disorder, or depression).

Manic symptoms may occur with usual dosages in children and adolescents without prior history of mania. If manic symptoms occur, consider causal relationship to stimulants, and discontinue therapy as appropriate.

Other Nervous System Effects

Amphetamines may impair the ability to engage in potentially hazardous activities (e.g., operating machinery or vehicles). Postmarketing experience includes reports of dyskinesia, tics, depression, dermatillomania, aggression, seizures.

Growth Suppression

Long-term (i.e., >12 months) administration expected to cause at least a temporary suppression of normal weight and/or height patterns in some children and adolescents. Dose-related weight loss reported in children and adolescents during 4 weeks of therapy with lisdexamfetamine.

Manufacturer recommends monitoring growth during treatment; patients not growing or gaining weight as expected may require temporary discontinuance of treatment. However, AAP states that studies of stimulants in children found little or no decrease in expected height, with any decrease in growth early in treatment being compensated for later on.

Peripheral Vascular Effects

Peripheral vascular disorders (e.g., Raynaud's phenomenon) reported in patients in all age groups receiving stimulants at therapeutic dosages and at various times throughout treatment course. Manifestations usually intermittent and mild, but ulceration of digits and/or breakdown of soft tissue occur rarely. Carefully observe patients for digital changes. (See Advice to Patients.)

Improvement generally observed following dosage reduction or drug discontinuance; some patients may require further evaluation (e.g., referral to rheumatologist).

Serotonin Syndrome

Potentially life-threatening serotonin syndrome may occur when amphetamines are used concomitantly with other drugs that affect serotonergic neurotransmission (e.g., MAO inhibitors, SSRIs, SNRIs, tricyclic antidepressants, 5-hydroxytryptamine [5-HT] type 1 receptor agonists [“triptans”], buspirone, fentanyl, lithium, tramadol, tryptophan, St. John's wort [Hypericum perforatum]). May also occur when lisdexamfetamine and CYP2D6 inhibitors are used concomitantly. (See Interactions.)

Symptoms may include mental status changes (e.g., agitation, hallucinations, delirium, coma), autonomic instability (e.g., tachycardia, labile BP, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular aberrations (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, GI symptoms (e.g., nausea, vomiting, diarrhea).

Concomitant use of lisdexamfetamine and MAO inhibitors is contraindicated. (See Contraindications under Cautions.)

If concomitant therapy with other serotonergic drugs or CYP2D6 inhibitors is clinically warranted, consider lower initial lisdexamfetamine dosage and monitor patient for emergence of serotonin syndrome, particularly during initiation of therapy and dosage increases. (See Advice to Patients.)

If symptoms of serotonin syndrome occur, discontinue lisdexamfetamine and any other concomitant serotonergic agents immediately and initiate supportive therapy.

Visual Effects

Visual disturbances reported with stimulants. Postmarketing experience includes reports of mydriasis, diplopia, difficulty with accommodation, blurred vision.

Hepatic Effects

Postmarketing experience includes reports of eosinophilic hepatitis.

GI Effects

Postmarketing experience includes reports of dysgeusia, bruxism, constipation.

Musculoskeletal Effects

Postmarketing experience includes reports of rhabdomyolysis.

Alopecia

Postmarketing experience includes reports of alopecia.

Endocrine Effects

Postmarketing experience includes reports of changes in libido, frequent or prolonged erections.

Specific Populations

Pregnancy

May cause fetal harm. Only limited data available in pregnant women. Amphetamines may stimulate uterine contractions in pregnant women increasing risk of premature delivery. Risk of prematurity and low birth weight in infants born to amphetamine-dependent women; monitor such infants for withdrawal symptoms (e.g., feeding difficulties, irritability, agitation, excessive drowsiness).

In animals, no effects on embryofetal morphology or survival when lisdexamfetamine administered throughout organogenesis. Prenatal and postnatal studies not conducted specifically with lisdexamfetamine. Administration of amphetamine to pregnant rats during gestation and lactation resulted in decreased pup survival and body weight correlating with developmental delays at clinically relevant dosages of amphetamine.

Lactation

Distributed into milk. No reports of adverse effects on nursing infants. Large dosages of dextroamphetamine may interfere with milk production, especially in women whose lactation is not well established. Because of potential for serious adverse effects to lisdexamfetamine in nursing infants, breast-feeding not recommended during therapy.

Pediatric Use

ADHD: Safety and efficacy not established in children <6 years of age.

Binge-eating disorder: Safety and efficacy not established in pediatric patients <18 years of age.

Psychotic (e.g., hallucinations, delusional thinking) or manic symptoms reported in children and adolescents receiving stimulants for management of ADHD. (See Warnings under Cautions.)

Sudden death reported in children and adolescents with structural cardiac abnormalities or other serious cardiac conditions receiving usual dosages of stimulants.

Long-term administration expected to cause at least a temporary suppression of normal weight and/or height patterns in some children and adolescents. (See Growth Suppression under Cautions.)

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether they respond differently than younger adults. Differences not identified with other reported clinical experience in responses between geriatric and younger adults.

Hepatic Impairment

Not specifically studied in hepatic impairment.

Renal Impairment

Reduced clearance and increased exposure of dextroamphetamine observed in patients with severe renal impairment or ESRD.

Dosage adjustment recommended in severe renal impairment or ESRD. (See Renal Impairment under Dosage and Administration.)

Dialysis does not substantially affect clearance of dextroamphetamine.

Common Adverse Effects

Children, adolescents, or adults with ADHD: Anorexia, anxiety, decreased appetite, decreased weight, diarrhea, dizziness, dry mouth, irritability, insomnia, nausea, upper abdominal pain, vomiting.

Adults with binge-eating disorder: Dry mouth, insomnia, decreased appetite, increased heart rate, constipation, jittery feeling, anxiety.

Drug Interactions

Amphetamines and their derivatives are metabolized by CYP2D6 and may show mild inhibition of CYP2D6 metabolism. The prodrug lisdexamfetamine not metabolized by CYP isoenzymes before its conversion to dextroamphetamine.

No clinically important interactions shown with lisdexamfetamine and substrates of CYP1A2, 2D6, or 3A; potential for minimal inhibition of CYP2C19. Dosage adjustment of concomitantly administered substrates of these isoenzymes not necessary.

Drugs Affecting Hepatic Microsomal Enzymes

CYP2D6 inhibitors: Potential pharmacokinetic interaction (increased exposure to dextroamphetamine); may increase risk of serotonin syndrome. Consider alternative therapy with a non-serotonergic drug or drug that does not inhibit CYP2D6.

Use concomitantly only when potential benefit justifies the potential risk. If clinically warranted, use lower dosages of lisdexamfetamine during initiation of therapy. Monitor patients for signs and symptoms of serotonin syndrome, especially when therapy is initiated or dosage increased.

If serotonin syndrome occurs, discontinue lisdexamfetamine, the CYP2D6 inhibitor, and any concomitantly administered serotonergic agents. (See Specific Drugs, Tests, and Foods under Interactions and also see Serotonin Syndrome under Cautions.)

Serotonergic Drugs

Potential pharmacologic interaction (potentially life-threatening serotonin syndrome) with serotonergic drugs.

Use concomitantly only when potential benefit justifies the potential risk. If clinically warranted, use lower dosages of lisdexamfetamine during initiation of therapy. Monitor patients for signs and symptoms of serotonin syndrome, especially when therapy is initiated or dosage increased.

If serotonin syndrome occurs, discontinue lisdexamfetamine and the concomitant serotonergic drug(s). (See Specific Drugs, Tests, and Foods under Interactions and also see Serotonin Syndrome under Cautions.)

Specific Drugs, Tests, and Foods

Lisdexamfetamine Pharmacokinetics

Absorption

Bioavailability

Lisdexamfetamine (a prodrug of dextroamphetamine) is rapidly absorbed from the GI tract. Peak plasma concentrations of lisdexamfetamine occur in approximately 1 hour; concentrations are low and transient; nonquantifiable by 8 hours after administration. Peak plasma concentrations of dextroamphetamine occur in approximately 3.5–3.7 hours.

Onset

Occurs within 2 hours after oral administration.

Duration

Approximately 10–12 hours.

Food

Food (high-fat meal or yogurt) delays time to peak plasma concentration of dextroamphetamine by about 1 hour, but administration with high-fat meal, yogurt, or orange juice does not affect magnitude of peak plasma concentration or AUC of dextroamphetamine.

Distribution

Extent

Amphetamines readily cross the blood-brain barrier and are distributed into most body tissues.

Amphetamines are distributed into milk in concentrations 3–7 times maternal blood concentrations.

Elimination

Metabolism

Lisdexamfetamine (a prodrug of dextroamphetamine) is converted to l-lysine and dextroamphetamine mainly via hydrolytic activity of RBCs, which have high capacity for this metabolism.

Lisdexamfetamine is not metabolized by CYP isoenzymes.

Elimination Route

Excreted principally in urine. Approximately 96% of a 70-mg radiolabeled oral dose of lisdexamfetamine was recovered in urine; parent drug accounted for about 2% of the recovered radioactivity.

Changes in urinary pH may alter excretion of amphetamines. (See Specific Drugs, Tests, and Foods under Interactions.)

Half-life

Lisdexamfetamine: <1 hour; dextroamphetamine: 9.4–13 hours.

Stability

Storage

Oral

Capsules, Chewable Tablets

Tight, light-resistant containers at 20–25°C (may be exposed to 15–30°C).

Actions

• Amphetamines are sympathomimetic amines with CNS stimulant activity.

• Lisdexamfetamine is a prodrug of dextroamphetamine; dextroamphetamine may block the reuptake of norepinephrine and dopamine into the presynaptic neuron and increase the release of these monoamines into the extraneural space.

• Pharmacologic actions of amphetamines are qualitatively similar to those of ephedrine and include CNS and respiratory stimulation and sympathomimetic activity including pressor response, bronchodilation, and contraction of the urinary bladder sphincter.

• Theories of dysfunction in ADHD focus on the prefrontal cortex, which controls many executive functions (e.g., planning, impulse control). Stimulants have putative effects on central dopamine and norepinephrine pathways that are crucial in frontal lobe function.

• Produces an anorexigenic effect, leading to loss of weight. No primary effect on appetite demonstrated in humans; postulated that anorexigenic effects are secondary to increased sympathetic activity resulting from release of norepinephrine and dopamine.

Advice to Patients

• Importance of providing patient or caregiver with a copy of the manufacturer’s patient information (medication guide); discuss and answer questions about its contents as needed. Importance of advising patient or caregiver to read and understand contents of medication guide before initiating therapy and each time the prescription is refilled.

• Importance of informing patients that lisdexamfetamine is a controlled substance possibly leading to abuse and dependence. Advise patients on proper storage and disposal of controlled substances.

• Importance of taking the drug in the morning to minimize insomnia.

• Risk of serious cardiovascular events (e.g., sudden death, MI, stroke, hypertension). Importance of patients immediately informing a clinician if they develop exertional chest pain, unexplained syncope, or other symptoms suggestive of cardiac disease.

• Risk of increased BP and heart rate; importance of advising patients to monitor BP and heart rate during therapy.

• Risk of psychiatric effects (e.g., psychosis, mania), even in patients without history of such effects.

• Risk of weight loss or delayed growth rate; importance of monitoring height and weight of pediatric patients during therapy.

• Appetite suppression may occur. Giving morning dose with a meal and providing high-caloric drink or snack late in the evening when stimulant effects have subsided may be helpful.

• Importance of instructing patients about the potential for amphetamines to impair their ability to perform potentially hazardous activities, such as driving or operating heavy machinery.

• Potential risk of peripheral vascular disorders (e.g., Raynaud's phenomenon) and associated signs and symptoms (e.g., numbness, coolness, pain, or changes in color [from pale to blue to red] in fingers or toes). Advise patients to report any new numbness, pain, skin color change, or sensitivity to temperature in fingers or toes and to immediately inform clinician if any signs of unexplained wounds appear on fingers or toes; further clinical evaluation may be appropriate.

• Potential risk of serotonin syndrome with concurrent use of lisdexamfetamine and other serotonergic agents (e.g., buspirone, fentanyl, lithium, SSRIs, SNRIs, tramadol, tricyclic antidepressants, 5-HT₁ receptor agonists [“triptans”], tryptophan, St. John’s wort [Hypericum perforatum]) or drugs that impair serotonin metabolism (e.g., MAO inhibitors). Importance of immediately contacting clinician if signs and/or symptoms of serotonin syndrome develop.

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, dietary supplements, and herbal products, as well as any concomitant illnesses/conditions (e.g., hypertension, cardiovascular disease, psychiatric disorders).

• Importance of women informing clinicians if they are or plan to become pregnant.

• Importance of advising women to avoid breast-feeding during therapy.

• Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

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

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

Subject to control under the Federal Controlled Substances Act of 1970 as a schedule II (C-II) drug.

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