| Human Toxicity Excerpts | /HUMAN EXPOSURE STUDIES/ Lisdexamfetamine is a pro-drug stimulant that requires the enzymatic hydrolysis of lysine from dextroamphetamine for pharmacologic effects. There is limited information comparing non-therapeutic lisdexamfetamine and dextroamphetamine exposures. OBJECTIVE: The objective was to compare lisdexamfetamine exposures with dextroamphetamine/amphetamine extended release and dextroamphetamine/amphetamine immediate release. METHODS: 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. RESULTS: 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 combinedthe 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. CONCLUSIONS: 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./SIGNS AND SYMPTOMS/ Manifestations of acute overdosage with amphetamines include restlessness, tremor, hyperreflexia, rhabdomyolysis, rapid respiration, hyperpyrexia, confusion, assaultiveness, hallucinations, panic states. Fatigue and depression usually follow the central stimulation. Cardiovascular effects include arrhythmias, hypertension or hypotension and circulatory collapse. Gastrointestinal symptoms include nausea, vomiting, diarrhea and abdominal cramps. Fatal poisoning is usually proceeded by convulsions and coma. /Amphetamines//SIGNS AND SYMPTOMS/ Manifestations of chronic intoxication with amphetamines include severe dermatoses, marked insomnia, irritability, hyperactivity and personality changes. The most severe manifestation of chronic intoxication is psychosis, often clinically indistinguishable from schizophrenia. This is rare with oral amphetamines. /Amphetamines//SIGNS AND SYMPTOMS/ Infants born to mothers dependent on amphetamines have an increased risk of premature delivery and low birth weight. Also, these infants may experience symptoms of withdrawal as demonstrated by dysphoria, including agitation, and significant lassitude. /Amphetamines/For more Human Toxicity Excerpts (Complete) data for DEXTROAMPHETAMINE (17 total), please visit the HSDB record page. |
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