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Lisdexamfetamine

Pronunciation

(lis dex am FET a meen)

Index Terms

  • Lisdexamfetamine Dimesylate
  • Lisdexamphetamine
  • NRP104

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule, Oral, as dimesylate:

Vyvanse: 10 mg [contains brilliant blue fcf (fd&c blue #1), fd&c yellow #6 (sunset yellow)]

Vyvanse: 20 mg, 30 mg, 40 mg, 50 mg, 60 mg, 70 mg [contains brilliant blue fcf (fd&c blue #1), fd&c red #40, fd&c yellow #10 (quinoline yellow)]

Brand Names: U.S.

  • Vyvanse

Pharmacologic Category

  • Central Nervous System Stimulant

Pharmacology

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.

Absorption

Rapid

Distribution

Dextroamphetamine: Vd: Adults: 3.5 to 4.6 L/kg; distributes into CNS; mean CSF concentrations are 80% of plasma

Metabolism

Metabolized in the blood by hydrolytic activity of red blood cells to dextroamphetamine and l-lysine; does not undergo CYP mediated metabolism

Excretion

Urine (96%, 42% as amphetamine-related compounds, 2% as lisdexamfetamine, 25% hippuric acid); feces (minimal)

Time to Peak

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)

Half-Life Elimination

Lisdexamfetamine: <1 hour; Dextroamphetamine: 10 to 13 hours

Special Populations: Renal Function Impairment

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.

Use: Labeled Indications

Attention-deficit/hyperactivity disorder: Treatment of attention-deficit/hyperactivity disorder (ADHD).

Binge eating disorder: Treatment of moderate to severe binge eating disorder in adults.

Contraindications

Hypersensitivity to amphetamine products or any component of the formulation; concurrent use of MAO inhibitor, or within 14 days of the last MAO inhibitor dose.

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

Dosing: Adult

Note: 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.

Dosing: Geriatric

Refer to adult dosing; initiate dose at the low end of the dosing range.

Dosing: Pediatric

Attention-deficit/hyperactivity disorder (ADHD): Note: Prior to treatment, assess for presence of cardiac disease and assess for risk of abuse. Individualize dosage based on patient need and response to therapy. Administer at the lowest effective dose.

Children ≥6 years and Adolescents: Oral: Refer to adult dosing.

Dosing: Renal Impairment

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.

Dosing: Hepatic Impairment

There are no dosage adjustments provided in the manufacturer’s labeling.

Administration

Administer in the morning without regard to meals; avoid afternoon doses because of potential for insomnia. 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. Do not take less than one capsule daily; a single capsule should not be divided.

Storage

Store at 20°C to 25°C (68°F to 77°F); excursions are permitted between 15°C and 30°C (59°F and 86°F). Protect from light.

Drug Interactions

Acebrophylline: May enhance the stimulatory effect of CNS Stimulants. Avoid combination

Alkalinizing Agents: May decrease the excretion of Amphetamines. Consider therapy modification

Ammonium Chloride: May decrease the serum concentration of Amphetamines. This effect is likely due to an enhanced excretion of amphetamines in the urine. Monitor therapy

Analgesics (Opioid): Amphetamines may enhance the analgesic effect of Analgesics (Opioid). Monitor therapy

Antacids: May decrease the excretion of Amphetamines. Monitor therapy

Antihistamines: Amphetamines may diminish the sedative effect of Antihistamines. Monitor therapy

Antihypertensive Agents: Amphetamines may diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy

Antipsychotic Agents: May diminish the stimulatory effect of Amphetamines. Monitor therapy

Ascorbic Acid: May decrease the serum concentration of Amphetamines. Monitor therapy

AtoMOXetine: May enhance the hypertensive effect of Sympathomimetics. AtoMOXetine may enhance the tachycardic effect of Sympathomimetics. Monitor therapy

Cannabinoid-Containing Products: May enhance the tachycardic effect of Sympathomimetics. Exceptions: Cannabidiol. Monitor therapy

Carbonic Anhydrase Inhibitors: May decrease the excretion of Amphetamines. Exceptions: Brinzolamide; Dorzolamide. Monitor therapy

Cocaine: May enhance the hypertensive effect 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. Consider therapy modification

Doxofylline: Sympathomimetics may enhance the adverse/toxic effect of Doxofylline. Monitor therapy

Ethosuximide: Amphetamines may diminish the therapeutic effect of Ethosuximide. Amphetamines may decrease the serum concentration of Ethosuximide. Monitor therapy

Gastrointestinal Acidifying Agents: May decrease the serum concentration of Amphetamines. Monitor therapy

Iobenguane I 123: Sympathomimetics may diminish the therapeutic effect of Iobenguane I 123. Avoid combination

Ioflupane I 123: Amphetamines may diminish the diagnostic effect of Ioflupane I 123. Monitor therapy

Linezolid: May enhance the hypertensive effect of Sympathomimetics. Management: Reduce initial doses of sympathomimetic agents, and closely monitor for enhanced pressor response, in patients receiving linezolid. Specific dose adjustment recommendations are not presently available. Consider therapy modification

Lithium: May diminish the stimulatory effect of Amphetamines. Monitor therapy

MAO Inhibitors: May enhance the hypertensive effect 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. Exceptions: Linezolid; Tedizolid. Avoid combination

Methenamine: May decrease the serum concentration of Amphetamines. This effect is likely due to an enhanced excretion of amphetamines in the urine. Monitor therapy

Multivitamins/Fluoride (with ADE): May decrease the serum concentration of Amphetamines. More specifically, the ascorbic acid (vitamin C) in many multivitamins may decrease amphetamine concentrations. Monitor therapy

Multivitamins/Minerals (with ADEK, Folate, Iron): May decrease the serum concentration of Amphetamines. Monitor therapy

Multivitamins/Minerals (with AE, No Iron): May decrease the serum concentration of Amphetamines. Specifically, vitamin C may impair absorption of amphetamines. Monitor therapy

PHENobarbital: Amphetamines may decrease the serum concentration of PHENobarbital. Monitor therapy

Phenytoin: Amphetamines may decrease the serum concentration of Phenytoin. Monitor therapy

Sympathomimetics: May enhance the adverse/toxic effect of other Sympathomimetics. Monitor therapy

Tedizolid: May enhance the hypertensive effect of Sympathomimetics. Tedizolid may enhance the tachycardic effect of Sympathomimetics. Monitor therapy

Tricyclic Antidepressants: May enhance the stimulatory effect of Amphetamines. Tricyclic Antidepressants may also potentiate the cardiovascular effects of Amphetamines. Monitor therapy

Urinary Acidifying Agents: May decrease the serum concentration of Amphetamines. Monitor therapy

Test Interactions

Amphetamines may elevate plasma corticosteroid levels; may interfere with urinary steroid determinations.

Adverse Reactions

>10%:

Central nervous system: Insomnia (13% to 27%)

Gastrointestinal: Decreased appetite (children and adolescents: 34% to 39%; adults: 8% to 27%), xerostomia (adults: 26% to 36%; children and adolescents: 4% to 5%), upper abdominal pain (children: 12%; adults: 2%)

1% to 10%:

Cardiovascular: Increased heart rate (adults: 2% to 7%), increased blood pressure (adults: 3%)

Central nervous system: Irritability (children: 10%), anxiety (adults: 5% to 6%), jitteriness (adults: 4% to 6%), dizziness (children: 5%), agitation (adults: 3%), emotional lability (children: 3%), restlessness (adults: 2% to 3%), drowsiness (children: 2%), increased energy (adults: 2%), nightmares (adults: 2%), paresthesia (adults: 2%), tics (children: 2%)

Dermatologic: Hyperhidrosis (adults: 3% to 4%), skin rash (children: 3%), pruritus (adults: 2%)

Endocrine & metabolic: Weight loss (children and adolescents: 9%; adults: 3% to 4%), decreased libido (adults: <2%)

Gastrointestinal: Vomiting (children: 9%; adults: 2%), diarrhea (adults: 7%), nausea (6% to 7%), constipation (adults: 6%), anorexia (adults: 5%), gastroenteritis (adults: 2%)

Genitourinary: Erectile dysfunction (adults: 3%)

Neuromuscular & skeletal: Tremor (adults: 2%)

Respiratory: Dyspnea (adults: 2%), oropharyngeal pain (2%)

Miscellaneous: Fever (children: 2%)

<1% (Limited to important or life-threatening): Accommodation disturbance, bruxism, cardiomyopathy, cerebrovascular accident, decreased linear skeletal growth rate, depression, dermatillomania, diplopia, exacerbation of tics, excoriation, frequent erections, hallucination, headache, hepatitis (eosinophilic), hypersensitivity, hypertension, incoherent speech, mania, mydriasis, myocardial infarction, overstimulation, peripheral vascular insufficiency, prolonged erection, psychotic reaction, Raynaud's phenomenon, seizure, Stevens-Johnson syndrome, suicidal tendencies, tachycardia

ALERT: U.S. Boxed Warning

Abuse and dependence:

CNS stimulants (amphetamines and methylphenidate-containing products), including lisdexamfetamine, have a high potential for abuse and dependence. Assess the risk of abuse prior to prescribing and monitor for signs of abuse and dependence while on therapy.

Warnings/Precautions

Concerns related to adverse effects:

• Cardiovascular events: Sudden death, stroke, and myocardial infarction have been reported in adults receiving the recommended doses of CNS stimulants. In children and adolescents with pre-existing structural cardiac abnormalities or other serious heart problems, sudden death has been reported while receiving the recommended doses of CNS stimulants for ADHD. These products should be avoided in patients with known serious structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, coronary artery disease (adults), or other serious cardiac problems that could increase the risk of sudden death. Patients should be carefully evaluated for these cardiac disorders prior to initiation of therapy. Patients who develop exertional chest pain, unexplained syncope, or arrhythmias during therapy should be evaluated promptly. CNS stimulants may increase heart rate (mean increase: 3 to 6 bpm) and blood pressure (mean increase: 2 to 4 mm Hg); monitor for adverse events related to tachycardia and hypertension.

• CNS effects: Amphetamines may impair the ability to engage in potentially hazardous activities.

• Hypersensitivity: Hypersensitivity, including anaphylaxis, Stevens-Johnson syndrome, angioedema, and urticaria have been observed.

• 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. Digital ulceration and/or soft tissue breakdown have been observed rarely; monitor for digital changes during therapy and seek further evaluation (eg, rheumatology) if necessary.

• Suicidal ideation/behavior: Suicidal ideation and/or behavior (including rare completed suicide) have been reported with ADHD drugs; monitor for signs of suicide-related behavior. Patients with suicidal thoughts/behavior should be evaluated immediately; alternative ADHD therapy may be necessary.

• Visual disturbance: Difficulty in accommodation and blurred vision has been reported with the use of stimulants.

Disease-related concerns:

• Abuse/misuse/diversion: [US Boxed Warning]: CNS stimulants (including lisdexamfetamine) have a high potential for abuse and dependence; assess for abuse potential prior to use and monitor for signs of abuse and dependence while on therapy. Use with caution in patients with history of ethanol or drug abuse. Prescriptions should be written for the smallest quantity consistent with good patient care to minimize possibility of overdose.

• Psychiatric disorders: Use with caution in patients with preexisting psychosis or bipolar disorder (may induce mixed/manic episode). May exacerbate symptoms of behavior and thought disorder in psychotic patients; new onset psychosis or mania may occur in children or adolescents with stimulant use. Patients should be screened for bipolar disorder and risk factors for developing mania prior to treatment; consider discontinuation if such symptoms (eg, delusional thinking, hallucinations, or mania) occur. May be associated with aggressive behavior or hostility (causal relationship not established); monitor for development or worsening of these behaviors.

• Tourette syndrome/tics: Use with caution in patients with Tourette syndrome; stimulants may exacerbate tics (motor and phonic) and Tourette syndrome. Evaluate for tics and Tourette syndrome prior to therapy initiation (Pliszka 2007).

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Elderly: Initiate dose at the low end of the dosing range.

• Pediatric: Appetite suppression may occur; particularly in children. Use of stimulants has been associated with weight loss and slowing of growth rate; monitor growth rate and weight during treatment. Treatment interruption may be necessary in patients who are not increasing in height or gaining weight as expected.

Other warnings/precautions:

• 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).

Monitoring Parameters

Cardiac evaluation should be completed on any patient who develops exertional chest pain, unexplained syncope, and any symptom of cardiac disease during treatment with stimulants. Thoroughly evaluate for cardiovascular risk and the presence of cardiac disease prior to initiating treatment. Monitor heart rate, blood pressure, and consider obtaining ECG prior to initiation (Vetter 2008). Monitor growth (height and weight) in children; CNS activity in all patients; signs of peripheral vasculopathy (eg, digital changes); behavioral changes. Assess for risk of abuse prior to prescribing and signs of misuse, abuse, or addiction throughout treatment.

Pregnancy Considerations

Lisdexamfetamine is converted to dextroamphetamine. The majority of human data is based on illicit amphetamine/methamphetamine exposure and not from therapeutic maternal use (Golub 2005). Use of amphetamines during pregnancy may lead to an increased risk of premature birth and low birth weight; newborns may experience symptoms of withdrawal. Behavioral problems may also occur later in childhood (LaGasse 2012).

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience anxiety, diarrhea, constipation, nausea, vomiting, dry mouth, lack of appetite, weight loss, insomnia, or abdominal pain. Have patient report immediately to prescriber signs of Stevens-Johnson syndrome/toxic epidermal necrolysis (red, swollen, blistered, or peeling skin [with or without fever]; red or irritated eyes; or sores in mouth, throat, nose, or eyes), severe headache, tachycardia, arrhythmia, decreased libido, sexual dysfunction, agitation, tremors, discoloration of hands or feet, burning or numbness of hands or feet, dark urine, muscle pain, muscle weakness, urinary retention, change in amount of urine passed, sores on fingers or toes, signs of severe cerebrovascular disease (change in strength on one side is greater than the other, trouble speaking or thinking, change in balance, or change in eyesight), angina, shortness of breath, severe dizziness, passing out, signs of depression (suicidal ideation, anxiety, emotional instability, illogical thinking), hallucinations, or behavioral changes (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

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