lisdexamfetamine-dimesylate and Drug-Overdose

Topics: Adult; Amphetamine-Related Disorders; Attention Deficit Disorder with Hyperactivity; Blood Platelets; Drug Overdose; Fever; Humans; Lisdexamfetamine Dimesylate; Male; Thrombocytopenia; Valproic Acid

Lisdexamfetamine is a pro-drug stimulant that requires the enzymatic hydrolysis of lysine from dexamphetamine for pharmacologic effects. There is limited information comparing non-therapeutic lisdexamfetamine and dextroamphetamine exposures.. The objective was to compare lisdexamfetamine exposures with dextroamphetamine/amphetamine extended release and dextroamphetamine/amphetamine immediate release.. A retrospective observational case series of single-substance exposures to lisdexamfetamine, dextroamphetamine/amphetamine extended release, or dextroamphetamine/amphetamine immediate release reported to the National Poison Data System from 2007 to 2012 was performed. Data were analyzed for demographics, reason, clinical effects, management site, and outcomes.. There were 23,553 exposures: lisdexamfetamine (7,113), dextroamphetamine/amphetamine extended release (6,245), and dextroamphetamine/amphetamine immediate release (10,195). The most frequent clinical effects observed for lisdexamfetamine, dextroamphetamine/amphetamine extended release, and dextroamphetamine/amphetamine immediate release were agitation (19.8%, 21.7%, and 25.1%, respectively) and tachycardia (19.2%, 22.8%, and 23.9%, respectively). The reason was most often exploratory (93.4%) in children < 6 years and therapeutic error (65.6%) in children aged 6-12 years. In adolescents and adults most common reasons were suicide attempts (28.4%) followed by abuse (19.5%) and therapeutic errors (18.8%). Overall, 61.6% of cases were managed in a health care facility, with the majority treated in the emergency department only. The majority of cases (76.0%) experienced no or minor effects. More serious outcomes (moderate/major/death) occurred in 21.2% of lisdexamfetamine, 24.7% of dextroamphetamine/amphetamine extended release, and 25.5% of dextroamphetamine/amphetamine immediate release. There were 4 deaths (1 dextroamphetamine/amphetamine extended release and 3 dextroamphetamine/amphetamine immediate release). In patients aged 6 years and more, abuse/misuse was more frequently reported for dextroamphetamine/amphetamine immediate release (32.5%) and dextroamphetamine/amphetamine extended release (23.0%) than that for lisdexamfetamine (13.5%). The odds of abuse/misuse was 2.3 (95% confidence interval [CI]: 2.0-2.4) times higher for dextroamphetamine/amphetamine immediate release than that for lisdexamfetamine and dextroamphetamine/amphetamine extended release combined; the odds of dextroamphetamine/amphetamine extended release abuse/misuse was 1.9 (95% CI: 1.7-2.2) times higher than lisdexamfetamine. In 2011, the number of lisdexamfetamine abuse/misuse cases exceeded dextroamphetamine/amphetamine extended release by approximately 26% and plateaued in 2012, but was significantly lower (∼75%) than dextroamphetamine/amphetamine immediate release.. Toxic effects were similar for all three drugs. Although the majority of cases were treated at health care facilities, the majority of patients experienced no effects or minor toxicity. Serious outcomes occurred in approximately 21% of lisdexamfetamine and 25% of dextroamphetamine/amphetamine extended release and dextroamphetamine/amphetamine immediate release. Lisdexamfetamine may have less abuse potential, especially compared with the immediate-release dextroamphetamine/amphetamine formulation.

Topics: Adolescent; Adult; Amphetamine-Related Disorders; Central Nervous System Stimulants; Chi-Square Distribution; Child; Delayed-Action Preparations; Dextroamphetamine; Drug Overdose; Humans; Linear Models; Lisdexamfetamine Dimesylate; Medication Errors; Odds Ratio; Poison Control Centers; Poisoning; Retrospective Studies; Risk Factors; Suicide, Attempted; United States; Young Adult

A 6-year-old girl displayed symptoms of serotonin syndrome after accidental ingestion of Vyvanse (lisdexamfetamine dimesylate). Dexmedetomidine was administered because of persistent neuromuscular hyperactivity and severe agitation despite initial therapy with benzodiazepines. Some children show a paradoxical reaction to benzodiazepines, and dexmedetomidine has a possible role in the treatment of serotonin syndrome.

Topics: Adrenergic alpha-2 Receptor Agonists; Anti-Anxiety Agents; Central Nervous System Stimulants; Child; Dexmedetomidine; Dextroamphetamine; Drug Overdose; Female; Humans; Lisdexamfetamine Dimesylate; Lorazepam; Midazolam; Serotonin Syndrome