lisdexamfetamine-dimesylate and Tachycardia

To review the pharmacology, pharmacokinetics, efficacy, and safety of the prodrug lisdexamfetamine for the treatment of attention-deficit/hyperactivity disorder (ADHD) in children and adults and describe its potential place in therapy.. Primary literature published between January 1, 1990, and August 1, 2008, was selected from PubMed using the search key words lisdexamfetamine, Vyvanse, and NRP104. References of selected publications were also reviewed. Posters and abstracts of research presented at national meetings were reviewed when available. The product labeling for Vyvanse was also used.. Preference was given to published, randomized, and controlled research describing the pharmacokinetics, efficacy, and safety of lisdexamfetamine. Noncontrolled studies, postmarketing reports, and poster presentations were considered secondly. All published studies were included.. Lisdexamfetamine is a prodrug of dextroamphetamine covalently bound to l-lysine, which is activated during first-pass metabolism. The unique pharmacokinetic profile owing to lisdexamfetamine's prodrug design and rate-limited enzymatic biotransformation allows for once-daily dosing with a duration of activity of approximately 12 hours. Lisdexamfetamine has been proven to reduce the symptoms of ADHD both in children aged 6-12 years and adults aged 18-55 years, decreasing ADHD rating scale scores by approximately 27 and 19 points, respectively. Adverse effects with an incidence greater than 10% during preclinical trials included appetite suppression, insomnia, and headache. Lisdexamfetamine's unique pharmacokinetic properties may provide additional safety with regard to reducing abuse potential. As with other central nervous system (CNS) stimulants, concerns regarding sudden cardiac death and adverse effects on growth also apply to lisdexamfetamine.. Lisdexamfetamine provides another amphetamine-based CNS stimulant option for treatment of children and adults with ADHD. However, its use may be limited by a lack of significant differentiation when compared with currently used stimulants and a lack of evidence to support its use in adolescents.

Topics: Animals; Attention Deficit Disorder with Hyperactivity; Dextroamphetamine; Humans; Lisdexamfetamine Dimesylate; Randomized Controlled Trials as Topic; Sleep Initiation and Maintenance Disorders; Tachycardia

To evaluate the safety profile, based on cardiovascular measurements, of lisdexamfetamine dimesylate (LDX) in children with and without prior exposure to stimulant medication in the treatment of attention-deficit/hyperactivity disorder (ADHD).. This single-blind, modified laboratory school study used open-label dose optimization of children aged 6 to 12 years. Lisdexamfetamine dimesylate, initiated at 30 mg, was dose titrated in 20-mg weekly increments to a possible 70 mg over 4 to 5 weeks. Safety outcomes presented in this study were assessed using vital signs (blood pressure and pulse) and electrocardiograms, conducted at baseline and following LDX treatment. Analyses were performed across all subjects, as well as post hoc based on prior treatment status. In addition, hematologic and blood biochemistry analyses were conducted at baseline but not following treatment.. Twenty-eight subjects enrolled in the study, with 27 safety protocol completers (n = 14 prior stimulant exposure; n = 13 stimulant naïve). In total, 2 subjects in the stimulant-naïve group experienced changes from baseline vital sign measurements outside the normal range: 1 with tachycardia and 1 with blood pressure ≥ 95th percentile of the normal age range. One other subject in the stimulant-naïve group experienced prolonged QTc in response to LDX, which resolved at follow-up. Pretreatment laboratory work revealed no differences on any parameters when reviewed by exposure subgroup.. While LDX reduced the core symptoms of ADHD to a similar degree in treatment-naïve and previously treated groups of children with ADHD, more cardiovascular effects were measured in stimulant-naïve children than in children who had previously been exposed to stimulant treatment. Future controlled studies with larger samples should address the impact of prior stimulant exposure on other ADHD treatments.

Topics: Attention Deficit Disorder with Hyperactivity; Blood Pressure; Central Nervous System Stimulants; Child; Dextroamphetamine; Dose-Response Relationship, Drug; Electrocardiography; Female; Humans; Lisdexamfetamine Dimesylate; Male; Single-Blind Method; Systole; Tachycardia

Topics: Adolescent; Adult; Attention Deficit Disorder with Hyperactivity; Blood Pressure; Central Nervous System Stimulants; Dextroamphetamine; Double-Blind Method; Dyspnea; Female; Headache; Humans; Irritable Mood; Lisdexamfetamine Dimesylate; Male; Middle Aged; Sleep Initiation and Maintenance Disorders; Tachycardia; Treatment Outcome; Young Adult

The relative bioavailability of oral lisdexamfetamine dimesylate, a prodrug of d-amphetamine, and active d-amphetamine was assessed in an open-label, single-dose, 3-treatment, 3-period, randomized, crossover study in 18 healthy adult volunteers. Following a fast of at least 10 hours, subjects were administered an intact capsule of 70 mg lisdexamfetamine, a solution containing the capsule contents, or an intact capsule with a high-fat meal. Standard meals started 4 hours following lisdexamfetamine administration. Blood samples were taken predose (0 hours) and 0.5 to 72 hours postdose, and the concentrations of d-amphetamine and lisdexamfetamine were measured. AUC and C(max) for d-amphetamine were similar when lisdexamfetamine 70 mg was administered to healthy adults in the fed or fasted state. The AUC of intact lisdexamfetamine was similar when the latter was taken without food or in solution, but C(max) was lower when lisdexamfetamine was administered with food. The t(max) of d-amphetamine and intact lisdexamfetamine was similar when taken in solution or in the fasted state but was about 1 hour longer when taken with food. Adverse events were typical for amphetamine products. These findings indicate that food does not have a significant effect on d-amphetamine or lisdexamfetamine bioavailability in healthy adults and that lisdexamfetamine was well tolerated.

Topics: Administration, Oral; Adult; Area Under Curve; Biological Availability; Blood Pressure; Capsules; Cross-Over Studies; Dextroamphetamine; Eating; Fasting; Female; Flushing; Food-Drug Interactions; Half-Life; Headache; Humans; Hyperkinesis; Lisdexamfetamine Dimesylate; Lysine; Male; Metabolic Clearance Rate; Molecular Structure; Tachycardia

Stimulant medications are approved to treat attention deficit hyperactivity disorder (ADHD) in children over the age of 6 years. Fatal ingestion of stimulants by children has been reported, although most ingestions do not result in severe toxicity. Lisdexamfetamine dimesylate, a once daily long-acting stimulant, is a prodrug requiring conversion to its active form, dextroamphetamine, in the bloodstream. Based on its unique pharmacokinetics, peak levels of d-amphetamine are delayed. We describe a case of accidental ingestion of lisdexamfetamine dimesylate in an infant.. A previously healthy 10-month-old infant was admitted to the hospital with a 5-h history of tachycardia, hypertension, dyskinesia, and altered mental status of unknown etiology. Confirmatory urine testing, from a specimen collected approximately 16 h after the onset of symptoms, revealed an urine amphetamine concentration of 22,312 ng/mL (positive cutoff 200 ng/mL). The serum amphetamine concentration, from a specimen collected approximately 37 h after the onset of symptoms, was 68 ng/mL (positive cutoff 20 ng/mL). Urine and serum were both negative for methamphetamine, methylenedioxyamphetamine (MDA), methylenedioxymethamphetamine (MDMA, Ecstasy), and methylenedioxyethamphetamine (MDEA). During the hospitalization, it was discovered that the infant had access to lisdexamfetamine dimesylate prior to the onset of symptoms.. Amphetamine ingestions in young children are uncommon but do occur. Clinicians should be aware of signs and symptoms of amphetamine toxicity and consider ingestion when a pediatric patient presents with symptoms of a sympathetic toxidrome even when ingestion is denied.

Topics: Accidents, Home; Acetaminophen; Adrenergic Uptake Inhibitors; Analgesics, Non-Narcotic; Central Nervous System Stimulants; Chromatography, Liquid; Dioxoles; Dyskinesia, Drug-Induced; Female; Humans; Hypertension; Infant; Lisdexamfetamine Dimesylate; Metabolome; Sympathomimetics; Tachycardia; Tandem Mass Spectrometry