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Pediatric Guanfacine Exposures Reported to the National Poison Data System, 2000–2016

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Pediatric Guanfacine Exposures Reported to the National Poison Data System, 2000–2016 Clinical Toxicology ISSN: 1556-3650 (Print) 1556-9519 (Online) Journal homepage: https://www.tandfonline.com/loi/ictx20 Pediatric guanfacine exposures reported to the National Poison Data System, 2000–2016 Emily Jaynes Winograd, Dawn Sollee, Jay L. Schauben, Thomas Kunisaki, Carmen Smotherman & Shiva Gautam To cite this article: Emily Jaynes Winograd, Dawn Sollee, Jay L. Schauben, Thomas Kunisaki, Carmen Smotherman & Shiva Gautam (2019): Pediatric guanfacine exposures reported to the National Poison Data System, 2000–2016, Clinical Toxicology, DOI: 10.1080/15563650.2019.1605076 To link to this article: https://doi.org/10.1080/15563650.2019.1605076 Published online: 22 Apr 2019. Submit your article to this journal Article views: 19 View Crossmark data Full Terms & Conditions of access and use can be found at https://www.tandfonline.com/action/journalInformation?journalCode=ictx20 CLINICAL TOXICOLOGY https://doi.org/10.1080/15563650.2019.1605076 POISON CENTRE RESEARCH Pediatric guanfacine exposures reported to the National Poison Data System, 2000–2016 Emily Jaynes Winograda, Dawn Solleea, Jay L. Schaubena, Thomas Kunisakia, Carmen Smothermanb and Shiva Gautamb aFlorida/USVI Poison Information Center – Jacksonville, UF Health – Jacksonville/University of Florida Health Science Center, Jacksonville, FL, USA; bCenter for Health Equity and Quality Research, UF Health – Jacksonville, Jacksonville, FL, USA ABSTRACT ARTICLE HISTORY Introduction: The purpose of this study was to characterize the frequency, reasons for exposure, clin- Received 10 December 2018 ical manifestations, treatments, duration of effects, and medical outcomes of pediatric guanfacine Revised 12 March 2019 exposures reported to the National Poison Data System (NPDS) from 2000 to 2016. Accepted 25 March 2019 Methods: Data extracted from poison control center call records for pediatric (0–5 years, 6–12 years, Published online 19 April 2019 – and 13 19 years), single-substance guanfacine ingestions reported to NPDS between 2000 and 2016 KEYWORDS was retrospectively analyzed. Guanfacine; toxicity; Results: A total of 10927 cases were identified for analysis. Pediatric single-substance guanfacine pediatric; poison exposures reported to NPDS increased significantly during the study period, with a marked increase center data among 6–12-year-olds. The most commonly documented clinical effects across age groups were drow- siness (n ¼ 4262, 39%), bradycardia (n ¼ 1696, 15.5%), and hypotension (n ¼ 1127, 10.3%). The duration of effect for most cases was >8 hours but 24 hours (n ¼ 2395, 44.2%). The median documented quantity of guanfacine ingested was 0.11 mg/kg (range: 0.004–7.8 mg/kg). The difference between mg/kg ingested in no effect and minor effect groups compared to moderate and major effect groups was statistically significant in all three age groups. Conclusions: Pediatric guanfacine exposures reported to U.S. poison centers have increased signifi- cantly in the last fifteen years. The most common clinical findings secondary to guanfacine exposure were bradycardia, hypotension, and CNS depression. There was a statistically significant difference between the mg/kg of guanfacine ingested in the groups experiencing no effect or mild effect com- pared to moderate or major effects. However, the maximum ingested dose reported among 0–5-year- olds in the no effect group was 2.72 mg/kg, while the minimum dose eliciting a major effect in both 0–5 and 6–12-year-olds was 0.05 mg/kg. The overall incidence of major effects was very low, with the vast majority of patients experiencing minor symptoms or less. Based on this data, we agree with cur- rent recommendations that any symptomatic pediatric patient exposed to guanfacine should be observed in a health care facility for at least 24 hours. Introduction or an alternative to these agents [3]. The mechanism of Guanfacine is a centrally acting a -adrenergic receptor action of guanfacine in ADHD is unknown [4]. The standard 2 – agonist similar to clonidine used in the treatment of atten- dose of guanfacine for the treatment of ADHD is 2 7 mg/day tion-deficit/hyperactivity disorder (ADHD). Like clonidine, depending on patient age, weight, and product formula- guanfacine was initially marketed as an antihypertensive tion [4]. Adverse effects of guanfacine are secondary to the drug’s agent as stimulation of presynaptic a2-adrenergic receptors in the central nervous system results in decreased sympa- sympatholytic effects and include somnolence, bradycardia, thetic tone. Decreased sympathetic tone leads to a reduction and hypotension. Toxic manifestations seen in unintentional in peripheral vascular resistance and a decrease in guanfacine exposures and overdose are largely an extension blood pressure. of these adverse effects, including significant central nervous In 2009, the Food and Drug Administration (FDA) system depression, and delayed and prolonged hypotension approved the use of guanfacine for ADHD in pediatric [5]. Death has not been reported secondary to guanfa- patients 6 years of age and older under the brand name cine ingestion. IntunivVR [1]. However, off-label use of guanfacine for this The epidemiology and toxicity of pediatric guanfacine indication began in 1995 [2]. While stimulant medications exposures has not been fully analyzed since 2002 [6]. like methylphenidate and amphetamines remain first-line McGrath and colleagues conducted a retrospective review of treatments for ADHD, guanfacine can be used as an adjunct 870 guanfacine exposures in patients <19 years of age CONTACT Emily Jaynes Winograd [email protected] Florida/USVI Poison Information Center – Jacksonville, UF Health – Jacksonville/University of Florida Health Science Center, 655 West 8th Street, Box C-23, Jacksonville, FL 32209, USA ß 2019 Informa UK Limited, trading as Taylor & Francis Group 2 E. J. WINOGRAD ET AL. reported to the American Association of Poison Control eight minutes, providing near real-time information on Centers (AAPCC) Toxic Exposure Surveillance System from national poisoning conditions. Case data available through 1993–1999. They found that the number of reported guanfa- NPDS includes patient demographic information, exposure cine exposures increased eightfold over the study period. details (e.g., substance, dose, route), clinical effects, therapies The majority of exposed children experienced no symptoms, provided, duration of effect, and medical outcome. while 14.8% of children experienced moderate or major NPDS was retrospectively queried for cases of guanfacine effects (defined as symptoms more pronounced, more pro- (including brand name products IntunivVR and TenexVR ) inges- longed, or more systemic than minor symptoms, usually tion in patients 19 years of age reported between January requiring some form of treatment; and signs and symptoms 1, 2000 and December 31, 2016. Fifty relevant NPDS prod- that were life threatening or resulted in significant residual uct-specific codes were utilized for the query as the generic disability or disfigurement). The most commonly observed code for this category (077773, antihypertensives excluding symptoms were drowsiness/lethargy, bradycardia, and hypo- diuretics) was too broad. The age range was selected based tension. The average exposure dose was not reported [6]. on the NPDS definition of pediatric, which includes all Wang and colleagues conducted a similar analysis of unin- patients 19 years of age [13]. The following NPDS tentional exposures to central a2-adrenergic receptor ago- “exposure reason” options were included: Unintentional – nists clonidine, guanfacine, and tizanidine in children 12 General, Therapeutic Error,orUnknown; Intentional – years of age reported to the National Poison Data System Suspected Suicide, Misuse,orAbuse; and Unknown Reason. (NPDS) from 2000–2011 [7]. Drowsiness and bradycardia Calls reported as “information calls”, non-human exposures, were the most commonly observed clinical effects following multi-substance exposure cases involving guanfacine, or any central a2-adrenergic receptor agonist exposure in their routes other than “ingestion”, were excluded. Likewise, cases study, while severe outcomes like coma and respiratory were excluded if patient age or medical outcome were not depression were infrequent. documented, if the case was not followed to a known med- Based on the available evidence, the POISINDEXVR mono- ical outcome, if clinical effects were deemed unrelated to the graph for guanfacine states that there is no indication for exposure, or if it was confirmed that no exposure had home management of guanfacine exposure in young chil- occurred. Missing patient weight or dose ingested data were dren. All pediatric patients with a history of guanfacine not reasons for exclusion. ingestion should be referred to a health care facility for Data were analyzed based on three age groups: 0–5 years, evaluation and observation [5]. It is recommended that leth- 6–12 years, and 13–19 years. We evaluated data for patient argic patients be monitored for 24 hours due to the potential weight in kilograms, gender, reason for ingestion, quantity of for delayed hypotension [1]. Conversely, Lexi-ToxTM states guanfacine ingested in milligrams and mg/kg, clinical effects, that only symptomatic patients require emergency depart- therapies provided, duration of effect, medical outcome, and ment evaluation, though the guanfacine monograph does year of ingestion based on these age groups. not provide separate disposition guidance based on patient Clinical
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