Lisdexamfetamine dimesylate is a prodrug of dextroamphetamine, a noncatecholamine, sympathomimetic amine with CNS-stimulating activity.1
Attention-Deficit/Hyperactivity Disorder
Lisdexamfetamine dimesylate is used for the treatment of attention deficit hyperactivity disorder (ADHD) in adults and pediatric patients 6 years of age and older.1
Safety and efficacy of lisdexamfetamine dimesylate for the treatment of ADHD in children and adolescents 6 years of age or older have been evaluated in 5 short-term studies (3 in children 6-12 years of age, 1 in adolescents 13-17 years of age, and 1 in children and adolescents 6-17 years of age) and 1 randomized withdrawal study.1 Safety and efficacy of lisdexamfetamine dimesylate in adults with ADHD were evaluated in 2 short-term studies and 1 randomized withdrawal study.1
In a short-term, randomized, double-blind, placebo-controlled parallel-group study in 290 pediatric patients 6-12 years of age with ADHD (hyperactive/impulsive or combined type), improvement in symptom scores, as measured using the ADHD Rating Scale version IV (ADHD-RS-IV), the revised Conners' Parent Rating Scale (CPRS-R), and the Clinical Global Impression of Improvement (CGI-I) scale, from baseline to study end (4 weeks) was substantially greater in children receiving lisdexamfetamine dimesylate titrated to a fixed, final dosage of 30, 50, or 70 mg daily than in those receiving placebo.1, 2 The ADHD-RS-IV is an 18-item scale that measures each of the core symptoms of ADHD with a total score range of 0-54 points, where 0 means no symptoms and 54 means the most severe symptoms.1, 2 The CPRS-R scale is parent-rated and is designed to assess symptoms of ADHD in the morning, afternoon, and evening.2 The CGI-I is an investigator-rated scale that assesses a patient's improvement of ADHD relative to baseline.2 Mean changes in symptom scores generally were similar for all 3 lisdexamfetamine dosage levels; however, changes in ADHD-RS-IV scores were numerically greater with the 70-mg dose than with the 30- and 50-mg doses.1, 2 Symptom control in patients receiving the drug was maintained throughout the day up to 6 p.m.1, 2
In addition, 2 short-term, double-blind, placebo-controlled, crossover studies were conducted in pediatric patients 6-12 years of age in an analog classroom environment using the Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) deportment score (a measure of deportment problems leading to classroom disruptions) as the primary measure of efficacy.1, 29, 50 Both studies utilized a 3- or 4-week open-label, dose-optimization period followed by randomization to 1 week each of double-blind treatment with dimesylate or placebo.1, 29, 50 One of the studies used an active comparator (extended-release mixed amphetamine salts [Adderall XR®] 10-30 mg daily) during dose-optimization and double-blind periods.1, 29 In both studies, patients had substantially greater improvement in SKAMP deportment scores on day 7 of each treatment period while receiving lisdexamfetamine compared with placebo.1, 29 This effect was observed at various intervals from 1.5-13 hours after dosing.1
In a randomized, double-blind, controlled study in children and adolescents 6-17 years of age with ADHD, improvement in the ADHD-RS-IV score from baseline to study end (7 weeks) was greater in patients receiving lisdexamfetamine dimesylate (given as a flexible dosage of 30-70 mg daily during the first 4 weeks and as a fixed dosage from weeks 5-7) than in those receiving placebo.1, 44
Safety and efficacy of lisdexamfetamine in adolescents and adults with ADHD were evaluated in 2 similarly designed, double-blind, randomized, placebo-controlled studies of 4 weeks' duration in 314 adolescents, 13-17 years of age, and 420 adults, 18-55 years of age, who met DSM-IV-TR criteria for ADHD.1, 47, 51 In these parallel-group studies, patients were randomized to receive 30, 50, or 70 mg of lisdexamfetamine dimesylate daily or placebo.1, 47, 51 All patients receiving lisdexamfetamine initially received 30 mg daily for the first week, with subsequent dosage titrations occurring in 20-mg increments at weekly intervals for those randomized to receive 50 or 70 mg of the drug daily.1 The primary measure of efficacy in both studies was the ADHD Rating Scale (ADHD-RS) score.1, 47, 51 At study end point (4 weeks), patients randomized to receive lisdexamfetamine demonstrated substantial improvements in ADHD symptoms compared with placebo recipients.1, 47, 51 Substantial improvements in ADHD symptoms were evident within the first week of treatment in all lisdexamfetamine groups.47, 51
In a crossover study in adults 18-55 years of age conducted in a simulated workplace environment, patients entered a 4-week, open-label, dose-optimization period with lisdexamfetamine dimesylate initiated at 30 mg and titrated up to a maximum of 70 mg daily followed by randomization to receive 1 week each of treatment with lisdexamfetamine or placebo.1, 46 The primary measure of efficacy was the Permanent Product Measure of Performance (PERMP) total score (a skill-adjusted math test that measures attention in ADHD) assessed on day 7 of each treatment period at various intervals from 2-14 hours after dosing.1, 46 Patients had substantially greater improvement in PERMP total scores after the treatment period with lisdexamfetamine compared with placebo.1, 46
Efficacy of lisdexamfetamine dimesylate for maintenance therapy for ADHD was evaluated in 2 placebo-controlled, randomized withdrawal studies; 1 was in children and adolescents 6-17 years of age with ADHD and the other was in adults 18-55 years of age with ADHD.1, 45 In the pediatric study, patients who had demonstrated a clinical response to lisdexamfetamine during a 26-week, open-label, dose-optimization period were randomized to continue their lisdexamfetamine dosage or receive placebo during the 6-week, double-blind study period.1, 45 In the adult study, patients who received at least 6 months of lisdexamfetamine therapy and maintained treatment response during a 3-week, open-label treatment period were randomized to continue their lisdexamfetamine dosage or receive placebo during the 6-week, double-blind study period.1, 52 Treatment failure was defined as at least a 50% increase in ADHD-RS total score and at least a 2-point increase as measured using the Clinical Global Impression of Severity (CGI-S) scale; in both studies, substantially fewer patients receiving lisdexamfetamine (15.8 and 9% of pediatric and adult patients, respectively) experienced treatment failure than those receiving placebo (67.5 and 75% of pediatric and adult patients, respectively).1, 45, 52
In 2016, a Cochrane review of 23 trials enrolling 2675 patients compared the efficacy of amphetamines (any oral form including amphetamine, dextroamphetamine, lisdexamfetamine, and mixed amphetamine salts, at any dosage) to placebo for the treatment of ADHD in children and adolescents 3-17 years of age.53 Within this meta-analysis, there were 6 studies that assessed lisdexamfetamine.53 The main efficacy outcome was change in core ADHD symptoms (i.e., inattention, hyperactivity, impulsivity).53 The Cochrane review found that amphetamines (any type) improved parent-, teacher-, clinician-, and investigator-rated ADHD symptoms.53 A subgroup analysis based on amphetamine type (dextroamphetamine, lisdexamfetamine, mixed amphetamine salts) found that lisdexamfetamine did not substantially improve parent-rated ADHD symptoms when compared to placebo.53
In 2018, a Cochrane review of 19 trials enrolling 2521 patients compared the efficacy of amphetamines (dextroamphetamine, lisdexamfetamine, and mixed amphetamine salts) with placebo for the treatment of ADHD in adults.54 The main efficacy outcome was the severity of ADHD symptoms assessed by clinicians and patients.54 The mean age of patients in this meta-analysis was 35.3 years of a 57.2% were male and 78.8% had a combined type of ADHD.54 This Cochrane review found evidence suggesting that amphetamines are more efficacious than placebo in the reduction of the severity of clinician- and patient-assessed ADHD symptoms.54 A subgroup analysis based on amphetamine type (dextroamphetamine, lisdexamfetamine, mixed amphetamine salts) found that lisdexamfetamine, compared to placebo, may improve the severity of ADHD symptoms as assessed by clinicians and patients.54
The American Academy of Pediatrics (AAP) has developed guidelines for children and adolescents with ADHD.55 For pediatric patients 6-12 years of age with ADHD, the provider should prescribe FDA-approved medications for ADHD, in addition to parent training in behavior management (PTBM) and/or behavioral classroom interventions.55 For the choice of medication, evidence is stated as particularly strong for stimulant medications (e.g., amphetamines, methylphenidate).55 Evidence is stated as sufficient but not as strong for atomoxetine, extended-release guanfacine, and extended-release clonidine.55 For adolescents 12-18 years of age with ADHD, the provider should prescribe FDA-approved medications with the assent of the adolescent.55 The provider is also encouraged to prescribe behavioral and other evidence-based training interventions if available.55 Doses of medications should be titrated to achieve maximum benefit with tolerable side effects.55
International experts have published recommendations for the treatment of ADHD in adults.56, 57 Treatment of ADHD in adults should follow a multimodal approach that includes psychoeducation, pharmacotherapy, cognitive behavior therapy, and coaching.56 First-line pharmacotherapy agents include long-acting stimulants such as mixed amphetamine salts, methylphenidate, and lisdexamfetamine.57 Short-acting and intermediate-acting stimulants are considered second-line and can also be adjunctive agents.57 Atomoxetine may also be used as a second-line or adjunctive agent.57
Lisdexamfetamine dimesylate is used for the treatment of moderate to severe binge-eating disorder (BED) in adults.1
Lisdexamfetamine dimesylate is not indicated for weight loss.1 Use of other sympathomimetic drugs for weight loss has been associated with serious cardiovascular adverse events.1 The safety and effectiveness of lisdexamfetamine for the treatment of obesity have not been established.1
The efficacy of lisdexamfetamine dimesylate for the treatment of BED has been established in 2 randomized, double-blind, placebo-controlled studies of 12-weeks' duration in adults 18-55 years of age with moderate to severe BED (DSM-IV criteria).1, 40 Moderate to severe disorder was defined as having at least 3 binge days per week for 2 consecutive weeks prior to baseline and a baseline CGI-S score of 4 or greater.1, 40 Patients were randomized to receive placebo or lisdexamfetamine; lisdexamfetamine dimesylate was initiated at 30 mg daily and increased to 50 mg daily after 1 week, with increases to 70 mg daily as tolerated and clinically indicated.1, 40 In both studies, lisdexamfetamine was substantially more effective than placebo in reducing the mean number of binge days per week from baseline to week 12.1, 40 From a mean of 4.6-4.82 binge days per week at baseline, lisdexamfetamine-treated patients experienced an average of 1.35-1.66 fewer binge days per week by week 12 than those receiving placebo.1, 40
The efficacy of lisdexamfetamine dimesylate for the treatment of BED was also assessed in a randomized, double-blind, placebo-controlled study that consisted of a 3-week, forced-dose, titration period followed by an 8-week, dose maintenance period.1, 58 Adults with at least moderate to severe BED were randomized to receive 30, 50, or 70 mg of lisdexamfetamine dimesylate daily or placebo.58 Patients who received lisdexamfetamine were initiated at the 30 mg daily dosage and titrated weekly in increments of 20 mg daily to the assigned dosage during the 3-week titration period.58 The dosage was then maintained for the duration of the 8-week dose maintenance period.58 The primary endpoint was the mean change in binge-eating behaviors, measured as days per week, from baseline to week 11.58 Patients who received lisdexamfetamine dimesylate 50 or 70 mg daily, but not 30 mg daily, had substantial improvements in the primary endpoint compared to patients who received placebo.1, 58
The efficacy of lisdexamfetamine dimesylate for the treatment of BED was also assessed in a randomized, double-blind, placebo-controlled withdrawal study in adults 18-55 years of age with moderate to severe BED.1, 59 Patients who responded to lisdexamfetamine dimesylate during a 12-week, open-label, treatment phase were randomized to continue lisdexamfetamine or switch to placebo for up to 26 weeks.1, 59 The primary endpoint of this study was time to relapse, defined as ≥2 binge-eating days per week for 2 consecutive weeks and ≥2-point CGI-S score increases from randomized withdrawal baseline.59 Patients who were randomized to continue to receive lisdexamfetamine had substantially lower relapse rates at the end of the study period compared with patients who were randomized to treatment with placebo.1, 59 The relapse rate for patients who received lisdexamfetamine was 3.7% versus 32.1% for patients who received placebo.59
Guidelines from the American Psychiatric Association (APA) recommend that patients with BED be treated with eating disorder-focused cognitive-behavioral therapy (CBT) or interpersonal therapy, in either a group or an individual format.60 For adults who have not responded to psychotherapy alone or who prefer medication, the APA suggests treatment with either an antidepressant medication or lisdexamfetamine.60
Lisdexamfetamine has been used for the symptomatic treatment of inattention, impulsivity, and hyperactivity in pediatric patients with autism spectrum disorder (ASD)†.61
The AAP has developed guidelines for children and adolescents with ASD.61 While there are not currently any medications that correct core social and communication symptoms in patients with ASD, there are medications that may be used to help manage behavioral and psychiatric symptoms.61 For symptoms of hyperactivity, impulsivity, inattention, and distractibility, the AAP suggests the use of psychostimulants (e.g., methylphenidate, dexmethylphenidate, mixed amphetamine salts, lisdexamfetamine, dextroamphetamine) after behavioral approaches are implemented if problems persist.61
Dispensing and Administration Precautions
Administer lisdexamfetamine dimesylate capsules or chewable tablets once daily in the morning without regard to meals.1 Because of potential for insomnia, avoid administering in the afternoon.1
Capsules may be swallowed whole or may be opened and the entire contents mixed with water, orange juice, or yogurt until completely dispersed; the resulting mixture should be administered immediately and not stored for use at a later time.1
Do not subdivide capsule contents; do not administer a dose less than the entire contents of one capsule or one chewable tablet.1
Chewable tablets should be chewed thoroughly before swallowing.1
Lisdexamfetamine capsules can be substituted for chewable tablets on a mg-per-mg basis.1
Store capsules and chewable tablets in tight, light resistant containers at 20-25°C (excursions permitted between 15-30°C).1
Available as lisdexamfetamine dimesylate; dosage expressed in terms of the salt.1
Attention-Deficit/Hyperactivity Disorder
The recommended initial dosage of lisdexamfetamine in pediatric patients ≥6 years of age with ADHD is 30 mg once daily.1 Dosage may be adjusted in 10- or 20-mg increments at weekly intervals up to a maximum dosage of 70 mg daily.1
Attention-Deficit/Hyperactivity Disorder
The recommended initial dosage of lisdexamfetamine in adults with ADHD is 30 mg once daily.1 Dosage may be adjusted in 10- or 20-mg increments at weekly intervals up to a maximum dosage of 70 mg daily.1
The recommended initial dosage of lisdexamfetamine in adults with moderate to severe binge-eating disorder (BED) is 30 mg once daily.1 Dosage should be adjusted in 20-mg increments at weekly intervals to a target dosage of 50-70 mg once daily.1 The maximum recommended dosage is 70 mg once daily.1
Lisdexamfetamine therapy should be discontinued if binge eating does not improve.1
The manufacturer makes no specific dosage recommendations for patients with hepatic impairment.1
In patients with severe renal impairment (glomerular filtration rate [GFR] 15 to <30 mL/minute per 1.73 m2), the maximum dosage of lisdexamfetamine dimesylate is 50 mg daily.1 In patients with end-stage renal disease (GFR <15 mL/minute per 1.73 m2), the maximum recommended dosage is 30 mg daily.1
The manufacturer does not provide specific dosage recommendations in geriatric patients; however, dosage in geriatric patients should generally start at the lower end of the dosing range, reflecting the greater incidence of reduced hepatic, renal, or cardiac function, and of concomitant diseases and drug therapies.1
A boxed warning is included in the prescribing information for lisdexamfetamine concerning the high potential for abuse and misuse.1 The use of lisdexamfetamine exposes patients to the risks of abuse and misuse, which can lead to the development of substance use disorder (including addiction).1 Misuse and abuse of CNS stimulants such as lisdexamfetamine can result in overdose or death.1 This risk is further increased with higher dosages or unapproved routes of administration (i.e., snorting, injection).1 The potential for abuse, misuse, and addiction should be assessed prior to initiation of CNS stimulant therapy, and patients should be monitored for signs of abuse, misuse, and addiction frequently during therapy.1
In addition, tolerance can develop during CNS stimulant therapy, which is characterized by a reduced response to the drug after repeated administration.1 In patients who are physically dependent on CNS stimulants, abrupt cessation of therapy, rapid dosage reduction, or administration of an antagonist may result in a withdrawal syndrome characterized by dysphoric mood, depression, fatigue, vivid and unpleasant dreams, insomnia or hypersomnia, increased appetite, and psychomotor retardation or agitation.1
Patients and/or their caregivers should be advised that lisdexamfetamine can be abused and can result in dependence; they should be advised that lisdexamfetamine should not be shared with others and should be stored in a safe (preferably locked) location to prevent misuse and abuse.1 Lisdexamfetamine should be disposed of by a medicine take-back program at a U.S. Drug Enforcement Administration (DEA) authorized collection site when it is no longer needed.1 If there is no take-back program or authorized DEA collection site available, the drug can be mixed with an undesirable, nontoxic substance such as dirt, cat litter, or used coffee grounds and disposed of in a sealed plastic bag in the household trash.1
Other Warnings and Precautions
Risks to Patients with Serious Cardiac Disease
Sudden unexplained death has been reported in patients with structural cardiac abnormalities or other serious cardiac disease receiving usual dosages of stimulants for attention deficit hyperactivity disorder (ADHD).1
A thorough medical history review (including evaluation for family history of sudden death or ventricular arrhythmia) and physical examination should be performed in all children, adolescents, and adults being considered for stimulant therapy, including lisdexamfetamine.1 Use of CNS stimulants should be avoided in patients with known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmias, coronary artery disease, or other serious cardiac disease.1
Patients who develop exertional chest pain, unexplained syncope, arrhythmias, or other manifestations suggestive of cardiac disease during stimulant therapy should inform clinicians immediately.1
Increased Blood Pressure and Heart Rate
Stimulants can cause modest increases in average blood pressure (i.e., by about 2-4 mm Hg) and heart rate (i.e., by about 3-6 beats/minute); larger increases may occur.1 All patients should be monitored for potential hypertension and tachycardia.1
Stimulants may exacerbate symptoms of behavior disturbance and thought disorder in patients with preexisting psychotic disorder.1
Stimulants may precipitate mixed or manic episodes in patients with bipolar disorder.1 Prior to initiating therapy, patients should be screened for risk factors for developing a manic episode; screening should include a detailed psychiatric history (e.g., comorbid depressive symptoms or history of depressive symptoms; family history of suicide, bipolar disorder, or depression).1
Psychotic or manic symptoms (e.g., hallucinations, delusional thinking) may occur with usual dosages in children and adolescents without a history of psychotic illness or mania.1 In a pooled analysis of multiple short-term, placebo-controlled studies, such symptoms occurred in about 0.1% of patients receiving stimulants compared with 0% of those receiving placebo.1 If psychotic or manic symptoms occur, consider causal relationship to stimulants, and discontinue therapy as appropriate.1
Long-term Suppression of Growth in Pediatric Patients
Administration of stimulants in children with ADHD has been associated with growth suppression (height and weight).1 Dose-related weight loss has been reported in children and adolescents during 4 weeks of therapy with lisdexamfetamine.1
The manufacturer recommends closely monitoring growth during treatment; patients not growing or gaining weight as expected may require temporary discontinuance of treatment.1
Peripheral Vasculopathy, Including Raynaud's Phenomenon
Stimulants, including lisdexamfetamine, are associated with peripheral vascular disorders, such as Raynaud's phenomenon.1 Manifestations usually are intermittent and mild, but ulceration of the digits and/or breakdown of soft tissue may occur rarely.1 Peripheral vascular disorders, including Raynaud's phenomenon, have been reported during postmarketing experience in patients in all age groups receiving stimulants at therapeutic dosages and at various times throughout the treatment course.1 Manifestations generally improve following dosage reduction or drug discontinuance.1 Careful observation for digital changes is warranted during therapy with stimulants, and further clinical evaluation (e.g., referral to a rheumatologist) may be appropriate for patients with signs or symptoms of peripheral vasculopathy.1
Potentially life-threatening serotonin syndrome may occur when amphetamines are used concomitantly with other drugs that affect serotonergic neurotransmission, including monoamine oxidase (MAO) inhibitors, selective serotonin-reuptake inhibitors (SSRIs), selective serotonin- and norepinephrine-reuptake inhibitors (SNRIs), tricyclic antidepressants, 5-hydroxytryptamine (5-HT) type 1 receptor agonists (“triptans”), buspirone, fentanyl, lithium, tramadol, tryptophan, and St. John's wort (Hypericum perforatum) .1 Symptoms of serotonin syndrome may include mental status changes (e.g., agitation, hallucinations, delirium, coma), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular aberrations (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and/or GI symptoms (e.g., nausea, vomiting, diarrhea).1
Serotonin syndrome also may occur when lisdexamfetamine and inhibitors of cytochrome P-450 (CYP) isoenzyme 2D6 are used concomitantly.1 The potential for a pharmacokinetic interaction exists, since such concomitant administration may increase the exposure of dextroamphetamine, the active metabolite of lisdexamfetamine, and thereby increase the risk of serotonin syndrome.1 In such clinical situations, alternative therapy should be considered with a non-serotonergic drug or a drug that does not inhibit CYP2D6.1
Concomitant use of lisdexamfetamine and MAO inhibitors is contraindicated.1 If symptoms of serotonin syndrome occur, therapy with lisdexamfetamine and any other concomitant serotonergic agents should be discontinued immediately and supportive therapy initiated.1
Initiation of lisdexamfetamine therapy at lower dosages should be considered, if clinically warranted.1 Patients should be monitored for the emergence of serotonin syndrome during initiation of therapy or when dosage is increased.1
Motor and Verbal Tics and Worsening of Tourette's Syndrome
Onset or exacerbation of motor or verbal tics and worsening of Tourette's syndrome have been reported with CNS stimulants.1
Prior to initiation of therapy, patients should be screened for a family history and clinically evaluated for motor or verbal tics or Tourette's syndrome.1 Patients receiving lisdexamfetamine should be routinely monitored for the emergence or worsening of tics or Tourette's syndrome, and treatment discontinued if clinically needed.1
The National Pregnancy Registry for ADHD Medications monitors outcomes in women exposed to ADHD medications during pregnancy.1 Clinicians are encouraged to register women who become pregnant while receiving lisdexamfetamine by calling 866-961-2388 or visiting [Web].1
Data are limited regarding use of lisdexamfetamine dimesylate in pregnant women.1 Amphetamines may decrease placental perfusion through vasoconstriction, and may stimulate uterine contractions in pregnant women, increasing the risk of premature delivery.1 Infants born to amphetamine-dependent women have increased risk of prematurity and low birth weight; such infants should be monitored for withdrawal symptoms (e.g., feeding difficulties, irritability, agitation, excessive drowsiness).1
In animals, lisdexamfetamine dimesylate had no effects on embryofetal morphology or survival when administered orally to rats and rabbits throughout the period of organogenesis.1 Prenatal and postnatal studies were not conducted specifically with lisdexamfetamine dimesylate.1 However, administration of amphetamine to pregnant rats during gestation and lactation resulted in decreased pup survival and body weight that correlated with developmental delays at clinically relevant dosages of amphetamine.1
Amphetamine is distributed into human milk based on limited case reports.1 There are no reports of adverse effects on breast-feeding infants; long-term neurodevelopmental effects from amphetamine exposure are not known.1 Large dosages of dextroamphetamine may interfere with milk production, especially in women whose lactation is not well established.1 Because of the potential for serious adverse reactions to lisdexamfetamine in breast-feeding infants (e.g., blood pressure and heart rate increases, growth suppression, peripheral vasculopathy), the manufacturer does not recommend breast-feeding during therapy.1
Safety and efficacy of lisdexamfetamine for the management of ADHD have not been established in children <6 years of age.1
Safety and efficacy of lisdexamfetamine for binge-eating disorder have not been established in pediatric patients <18 years of age.1
Psychotic (e.g., hallucinations, delusional thinking) or manic symptoms have been reported in children and adolescents receiving stimulants for management of ADHD.1
Long-term administration is expected to cause at least a temporary suppression of normal weight and/or height patterns in some children and adolescents.1
Clinical studies of lisdexamfetamine dimesylate did not include sufficient numbers of patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.1 While other reported clinical experience has not revealed differences in response between geriatric and younger adults, dosage selection in geriatric patients should generally start at the lower end of the dosage range, reflecting the greater frequency of decreased hepatic, renal, and/or cardiac function and of concomitant disease and drug therapy in such patients.1
Lisdexamfetamine has not been specifically studied in hepatic impairment.1
Reduced clearance has been observed in patients with severe renal impairment (glomerular filtration rate [GFR] 15 to <30 mL/minute per 1.73 m2) or end-stage renal disease (GFR <15 mL/minute per 1.73 m2) compared with individuals with normal renal function.1 Dosage of lisdexamfetamine dimesylate should not exceed 50 mg daily in patients with severe renal impairment or 30 mg daily in patients with end-stage renal disease.1 Lisdexamfetamine is not removed by dialysis.1
Adverse effects occurring in ≥5% of children, adolescents, or adults receiving lisdexamfetamine for ADHD and at a frequency at least twice that reported with placebo include anorexia, anxiety, decreased appetite, decreased weight, diarrhea, dizziness, dry mouth, irritability, insomnia, nausea, upper abdominal pain, and vomiting.1
Adverse effects occurring in ≥5% of adults receiving lisdexamfetamine for binge-eating disorder and at a frequency at least twice that reported with placebo include dry mouth, insomnia, decreased appetite, increased heart rate, constipation, jittery feeling, and anxiety.1
Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes
The prodrug lisdexamfetamine dimesylate is not metabolized by cytochrome-P450 (CYP) isoenzymes before its conversion to dextroamphetamine; therefore, pharmacokinetic interactions are unlikely with drugs that inhibit or induce CYP isoenzymes.1 The manufacturer states that lisdexamfetamine is unlikely to affect the pharmacokinetics of drugs metabolized by CYP isoenzymes 1A2 (e.g., duloxetine, melatonin, theophylline), 2D6 (e.g., atomoxetine, desipramine, venlafaxine), 2C19 (e.g., clobazam, lansoprazole, omeprazole), or 3A4 (e.g., midazolam, pimozide, simvastatin).1
A pharmacokinetic interaction (increased exposure of dextroamphetamine) may occur when lisdexamfetamine is used concomitantly with inhibitors of CYP2D6 and may increase the risk of serotonin syndrome.1 Initiate lisdexamfetamine at lower dosages when used concomitantly with inhibitors of CYP2D6.1 Monitor for the emergence of serotonin syndrome during initiation and dosage titration of lisdexamfetamine.1 If serotonin syndrome occurs, discontinue the CYP2D6 inhibitor and lisdexamfetamine.1
Increased urinary excretion and decreased serum concentrations and efficacy of amphetamines may occur with concomitant use of urinary acidifying agents (e.g., ascorbic acid).1 Lisdexamfetamine dosage should be increased based on clinical response during such concomitant therapy.1
Decreased urinary excretion and increased serum concentrations of amphetamines resulting in potentiation of action may occur with concomitant use of alkalinizing agents (e.g., sodium bicarbonate).1 Concomitant use of lisdexamfetamine with urinary alkalinizing agents should be avoided.1
No clinically important pharmacokinetic interactions were observed when guanfacine and lisdexamfetamine were used concomitantly.1 Dosage adjustment of either drug is not necessary.1
Concomitant use of monoamine oxidase (MAO) inhibitors and CNS stimulants can result in potentially life-threatening hypertensive crisis.1 Amphetamines are contraindicated in patients who are currently receiving or have recently (within 14 days) received an MAO inhibitor.1
Concomitant use of omeprazole and lisdexamfetamine is not expected to have a clinically important effect on the pharmacokinetics of omeprazole.1 Dosage adjustment of either drug is not necessary.1
A pharmacologic interaction (potentially life-threatening serotonin syndrome) may occur with drugs affecting serotonergic neurotransmission, including 5-hydroxytryptamine type 1 (5-HT1) receptor agonists (“triptans”), buspirone, fentanyl, lithium, selective serotonin-reuptake inhibitors (SSRIs), selective serotonin- and norepinephrine-reuptake inhibitors (SNRIs), tramadol, tricyclic antidepressants, tryptophan, and St. John's wort ( Hypericum perforatum ).1
Concomitant use of tricyclic antidepressants (e.g., desipramine, protriptyline) can also cause significant increases in d-amphetamine in the brain and can potentiate the cardiovascular effects of amphetamines.1 If a tricyclic antidepressant is used concomitantly, monitor patients frequently and adjust or use alternate drug therapy based on clinical response.1
Lower dosages of lisdexamfetamine should be used during initiation of such concomitant therapy, and patients should be monitored for signs and symptoms of serotonin syndrome, especially when therapy is initiated or dosage is increased.1 If serotonin syndrome occurs, both lisdexamfetamine and the serotonergic drug should be discontinued, and supportive care should be initiated.1
No clinically important pharmacokinetic interactions were observed when venlafaxine and lisdexamfetamine were used concomitantly.1 Dosage adjustment of either drug is not necessary.1
Lisdexamfetamine, a prodrug of dextroamphetamine, is a CNS stimulant.1 Lisdexamfetamine is inactive until hydrolyzed in vivo to l-lysine and dextroamphetamine, which is responsible for the drug's activity.1 The exact mechanism of therapeutic action in attention deficit hyperactivity disorder (ADHD) and binge-eating disorder is not known.1 Amphetamines block the reuptake of norepinephrine and dopamine into the presynaptic neuron and increase the release of the monoamines into the extraneuronal space.1
Following single-dose administration of lisdexamfetamine, the pharmacokinetics of dextroamphetamine are linear over the oral dosage range of 30-70 mg in children 6-12 years of age and over the oral dosage range of 50-250 mg in adults.1 Following single-dose administration of a lisdexamfetamine capsule, peak plasma concentrations of lisdexamfetamine occur in approximately 1 hour; concentrations are low and transient, and become nonquantifiable by 8 hours after administration.1 Peak plasma concentrations of dextroamphetamine occur in approximately 3.5 hours.1 Following administration of the chewable tablets, peak plasma concentrations of lisdexamfetamine occur at about 1 hour and dextroamphetamine at 4.4 hours.1 Lisdexamfetamine and dextroamphetamine do not accumulate at steady state in adults.1 Administration of capsules with food (high-fat meal or yogurt) delays time to peak plasma concentrations of dextroamphetamine by about 1 hour; however, administration with a high-fat meal, yogurt, or orange juice does not affect the AUC or magnitude of the peak plasma concentration of dextroamphetamine.1 Peak plasma concentrations and AUC of lisdexamfetamine are reduced by about 15% when the chewable tablets are administered versus the capsules; however, exposure to dextroamphetamine is similar between products.1 Food (high-fat meal) decreases the magnitude of peak plasma concentrations and AUC of dextroamphetamine by about 5-7% and delays the time to peak concentrations by about 1 hour.1 Lisdexamfetamine is not metabolized by CYP isoenzymes.1 Lisdexamfetamine is converted to l-lysine and dextroamphetamine by hydrolytic activity of erythrocytes, which have a high capacity for metabolism of lisdexamfetamine.1 Lisdexamfetamine is excreted principally in urine.1 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.1 Changes in urinary pH may alter excretion of amphetamines.1 The elimination half-life of lisdexamfetamine is less than 1 hour in patients ≥6 years of age, and is approximately 8.6-9.5 hours in pediatric patients 6-12 years of age and 10-11.3 hours in adults for dextroamphetamine.1
Additional Information
The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.
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.1
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Oral | Capsules | 10 mg | Vyvanse® (C-II) | Takeda Pharmaceuticals |
20 mg | Vyvanse® (C-II) | Takeda Pharmaceuticals | ||
30 mg | Vyvanse® (C-II) | Takeda Pharmaceuticals | ||
40 mg | Vyvanse® (C-II) | Takeda Pharmaceuticals | ||
50 mg | Vyvanse® (C-II) | Takeda Pharmaceuticals | ||
60 mg | Vyvanse® (C-II) | Takeda Pharmaceuticals | ||
70 mg | Vyvanse® (C-II) | Takeda Pharmaceuticals | ||
Tablets, chewable | 10 mg | Vyvanse® (C-II) | Takeda Pharmaceuticals | |
20 mg | Vyvanse® (C-II) | Takeda Pharmaceuticals | ||
30 mg | Vyvanse® (C-II) | Takeda Pharmaceuticals | ||
40 mg | Vyvanse® (C-II) | Takeda Pharmaceuticals | ||
50 mg | Vyvanse® (C-II) | Takeda Pharmaceuticals | ||
60 mg | Vyvanse® (C-II) | Takeda Pharmaceuticals |
1. Takeda Pharmaceuticals America, Inc. Vyvanse® (lisdexamfetamine dimesylate) capsules prescribing information. Lexington, MA; 2023 Oct.
2. Biederman J, Krishnan S, Zhang Y et al. Efficacy and tolerability of lisdexamfetamine dimesylate (NRP-104) in children with attention-deficit/hyperactivity disorder: a phase III, multicenter, randomized, double-blind, forced-dose, parallel-group study. Clin Ther . 2007; 29:450-63. [PubMed 17577466]
29. Biederman J, Boellner SW, Childress A et al. Lisdexamfetamine dimesylate and mixed amphetamine salts extended-release in children with ADHD: a double-blind, placebo-controlled, crossover analog classroom study. Biol Psychiatry . 2007; 62:970-6. [PubMed 17631866]
40. McElroy SL, Hudson J, Ferreira-Cornwell MC et al. Lisdexamfetamine Dimesylate for Adults with Moderate to Severe Binge Eating Disorder: Results of Two Pivotal Phase 3 Randomized Controlled Trials. Neuropsychopharmacology . 2016; 41:1251-60. [PubMed 26346638]
44. Coghill D, Banaschewski T, Lecendreux M et al. European, randomized, phase 3 study of lisdexamfetamine dimesylate in children and adolescents with attention-deficit/hyperactivity disorder. Eur Neuropsychopharmacol . 2013; 23:1208-18. [PubMed 23332456]
45. Coghill DR, Banaschewski T, Lecendreux M et al. Maintenance of efficacy of lisdexamfetamine dimesylate in children and adolescents with attention-deficit/hyperactivity disorder: randomized-withdrawal study design. J Am Acad Child Adolesc Psychiatry . 2014; 53:647-657.e1. [PubMed 24839883]
46. Wigal T, Brams M, Gasior M et al. Randomized, double-blind, placebo-controlled, crossover study of the efficacy and safety of lisdexamfetamine dimesylate in adults with attention-deficit/hyperactivity disorder: novel findings using a simulated adult workplace environment design. Behav Brain Funct . 2010; 6:34. [PubMed 20576091]
47. Findling RL, Childress AC, Cutler AJ et al. Efficacy and safety of lisdexamfetamine dimesylate in adolescents with attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry . 2011; 50:395-405. [PubMed 21421179]
50. Wigal SB, Kollins SH, Childress AC, Squires L; for the 311 Study Group. A 13-hour laboratory school study of lisdexamfetamine dimesylate in school-aged children with attention-deficit/hyperactivity disorder. Child Adolesc Psychiatry Ment Health. 2009;3(1):17.
51. Adler LA, Goodman DW, Kollins SH, et al. Double-blind, placebo-controlled study of the efficacy and safety of lisdexamfetamine dimesylate in adults with attention-deficit/hyperactivity disorder. J Clin Psychiatry. 2008;69(9):1364-1373.
52. Brams M, Weisler R, Findling RL, et al. Maintenance of efficacy of lisdexamfetamine dimesylate in adults with attention-deficit/hyperactivity disorder: randomized withdrawal design. J Clin Psychiatry. 2012;73(7):977-983.
53. Punja S, Shamseer L, Hartling L, et al. Amphetamines for attention deficit hyperactivity disorder (ADHD) in children and adolescents. Cochrane Database Syst Rev. 2016;2(2):CD009996.
54. Castells X, Blanco-Silvente L, Cunill R. Amphetamines for attention deficit hyperactivity disorder (ADHD) in adults. Cochrane Database Syst Rev. 2018;8(8):CD007813.
55. Wolraich ML, Hagan JF Jr, Allan C et al. Clinical Practice Guideline for the Diagnosis, Evaluation, and Treatment of Attention-Deficit/Hyperactivity Disorder in Children and Adolescents. Pediatrics. 2019; 144(4):e20192528.
56. Kooij JJS, Bijlenga D, Salerno L et al. Updated European Consensus Statement on diagnosis and treatment of adult ADHD. Eur Psychiatry. 2019; 56:14-34.
57. CADDRA - Canadian ADHD Resource Alliance. Canadian ADHD Practice Guidelines, 4.1 Edition, 2020.
58. McElroy SL, Hudson JI, Mitchell JE, et al. Efficacy and safety of lisdexamfetamine for treatment of adults with moderate to severe binge-eating disorder: a randomized clinical trial. JAMA Psychiatry. 2015;72(3):235-246.
59. Hudson JI, McElroy SL, Ferreira-Cornwell MC, Radewonuk J, Gasior M. Efficacy of Lisdexamfetamine in Adults With Moderate to Severe Binge-Eating Disorder: A Randomized Clinical Trial. JAMA Psychiatry. 2017;74(9):903-910.
60. Crone C, Fochtmann LJ, Attia E, et al. The American Psychiatric Association Practice Guideline for the Treatment of Patients With Eating Disorders. Am J Psychiatry. 2023;180(2):167-171.
61. Hyman SL, Levy SE, Myers SM; COUNCIL ON CHILDREN WITH DISABILITIES, SECTION ON DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS. Identification, Evaluation, and Management of Children With Autism Spectrum Disorder. Pediatrics. 2020;145(1):e20193447.