Lamotrigine is a new generation antiepileptic which blocks sodium channels and can cause significant toxicity in overdose. A case of a three-year-old child who suffered a seizure and required endotracheal intubation after accidental lamotrigine ingestion is presented. The lamotrigine concentration measured 23.2 mcg/mL which is the highest reported after accidental pediatric exposure. A review of the literature regarding pediatric lamotrigine poisoning is also included

Beauchamp, Gillian A., MD

Cannon, Robert D., DO

Cook, Matthew D, DO

Griswold, Ashley, DO

Katz, Kenneth D, MD

Tully, Briana

Lehigh Valley Health Network: LVHN Scholarly Works

Lehigh Valley Health Network LVHN Scholarly Works Department of Emergency Medicine Lamotrigine ODT-Induced Seizure in a 3-Year-Old Child after Accidental Ingestion Ashley Griswold DO Lehigh Valley Health Network, Ashley.Griswold@lvhn.org Briana Tully Lehigh Valley Health Network, briana.tully@lvhn.org Kenneth D. Katz MD Lehigh Valley Health Network, kenneth_d.katz@lvhn.org Gillian A. Beauchamp MD Lehigh Valley Health Network, gillian.beauchamp@lvhn.org Matthew D. Cook DO Lehigh Valley Health Network, Matthew_D.Cook@lvhn.org See next page for additional authors Follow this and additional works at: https://scholarlyworks.lvhn.org/emergency-medicine  Part of the Emergency Medicine Commons, and the Pediatrics Commons Published In/Presented At Griswold, A. Tully, B. Katz, K. Beauchamp, G. Cook, M. Cannon, R. (2019). Lamotrigine ODT-Induced Seizure in a 3-Year-Old Child after Accidental Ingestion. Case Reports in Emergency Medicine. doi.org/10.1155/2019/2675931. This Article is brought to you for free and open access by LVHN Scholarly Works. It has been accepted for inclusion in LVHN Scholarly Works by an authorized administrator. For more information, please contact LibraryServices@lvhn.org. Authors Ashley Griswold DO, Briana Tully, Kenneth D. Katz MD, Gillian A. Beauchamp MD, Matthew D. Cook DO, and Robert D. Cannon DO This article is available at LVHN Scholarly Works: https://scholarlyworks.lvhn.org/emergency-medicine/542 Case ReportLamotrigine ODT-Induced Seizure in a 3-Year-Old Child afterAccidental IngestionAshley Griswold ,1 Briana Tully,2 Kenneth Katz ,2 Gillian Beauchamp,2Matthew Cook,2 and Robert Cannon21Department of Pediatrics, Lehigh Valley Health Network/University of South Florida Morsani College of Medicine,Cedar Crest Boulevard & I-78, Allentown, PA 18103, USA2Department of Emergency and Hospital Medicine, Lehigh Valley Health Network/University of South Florida Morsani College ofMedicine, Cedar Crest Boulevard & I-78, Allentown, PA 18103, USACorrespondence should be addressed to Kenneth Katz; kenneth d.katz@lvhn.orgReceived 5 September 2018; Accepted 23 December 2018; Published 13 January 2019Academic Editor: Vasileios PapadopoulosCopyright © 2019 AshleyGriswold et al.This is an open access article distributed under theCreativeCommons Attribution License,which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Lamotrigine is a new generation antiepileptic which blocks sodium channels and can cause significant toxicity in overdose. Acase of a three-year-old child who suffered a seizure and required endotracheal intubation after accidental lamotrigine ingestion ispresented.The lamotrigine concentrationmeasured 23.2mcg/mLwhich is the highest reported after accidental pediatric exposure.A review of the literature regarding pediatric lamotrigine poisoning is also included.1. IntroductionLamotrigine was developed in 1994 and is prescribed for bothpartial and generalized seizures as well as bipolar disorder.The drug inhibits seizure activity primarily through voltage-gated sodium channel blockade. It also acts presynaptically asan inhibitor of glutamate and aspartate. In the postsynapticsetting, it diminishes excitability by inhibiting sodium con-ductance andmay also reduce high-voltage activated calciumcurrents [1–3]. Unlike other anticonvulsants, lamotrigine haslittle or no effect on serotonergic, dopaminergic, or adrener-gic receptors [2, 4]. Reported adverse effects with therapeuticuse include nausea, vomiting, diplopia, dizziness, ataxia,tremor, and urinary tract infections. Most effects are mildto moderate in intensity and do not lead to discontinuation[1, 2]. More serious adverse events are dermatologic, suchas Stevens-Johnson Syndrome, which appears to be morecommon in children than adults [2].2. Case PresentationA three-year-old, 14.5 kg boy, without medical history andprescribed no medications, presented to the emergencydepartment (ED) within an hour of ingesting between sevenand sixteen oral disintegrating 25 mg lamotrigine tablets andone to six 0.5 mg clonazepam tablets from his brother’s pillorganizer.Emergency Medical Services arrived at the home within20 minutes of ingestion and found the patient minimallyresponsive and arousable only to painful stimuli with poorrespiratory effort. Bag-valve-mask ventilation was provided.An intraosseous (IO) linewas established, and the patient wastransported to the ED.In the ED, the child had a Glasgow Coma Scale of3 and minimal independent respiratory effort. Vital signsincluded heart rate of 100 beats per minute, pulse oximetry100% (100% oxygen via bag-valve mask), temperature 35.7∘C(96.2∘F), and blood pressure 92/43 mmHg. The child thendeveloped a tonic-clonic seizure which was treated with 1mg IO lorazepam. The patient was endotracheally intubatedfor airway protection and admitted to the pediatric inten-sive care unit (PICU) for further monitoring and care. Anelectrocardiogram (QRS interval of 86ms), complete bloodcount, serum chemistries, serum acetaminophen, salicylateand ethanol concentrations were all unremarkable.Serum lamotrigine concentrations measured 23.2mcg/mL and 18.5 mcg/mL approximately three and 24 hoursHindawiCase Reports in Emergency MedicineVolume 2019, Article ID 2675931, 3 pageshttps://doi.org/10.1155/2019/26759312 Case Reports in Emergency MedicineTable 1: Case reports of pediatric seizures following lamotrigine ingestion.Reference Age, sex Dose, formula Presentation Drugconcentration Management OutcomePresentcase3-year-oldmaleUp to 27.6mg/kg in ODTtabletsAcute: 1 seizure <1 minutein duration within 1 hourwith myoclonic activity,dysconjugate gaze, coma23.2 mcg/mL(3-4-hour level) &18.5 mcg/mL(24-hour level)Lorazepam,intubationDischarged wellafter 72 hoursGrosso(2016)3.2-year-oldmale1600 mg total(wt not given)200 mg tabletsAcute: tonic-clonic statusepilepticus uponpresentation. After 30 minpostictal pattern28.4 mg/L after 10hours of fluidsRectal diazepam x2, IVPmidazolam, thencont infusionDischarged atapprox 72 hrs.Hyperphagia stillpresent atdischargeMoore(2013)1-year-oldfemaleUnknownquantityAcute: initially agitated andcrying with intermittentmyoclonus of herextremities18 mg/L at 8 h and11.8 mg/L at 19 h LorazepamDischarged wellafter 19 hoursClose(2010)2-year-oldmaleUp to 43 mg/kgtabletAcute: 2 seizures of5-second duration within 3hours with ataxia,drowsiness, nystagmus,hyperreflexia vomitingNot available Diazepam Discharged wellafter 12 hoursThundiyil(2007)19-month-oldmaleUnknownamount of achewable tabletAcute: 2 seizures of<10-second duration in 1hour with irritability,vomiting, sinus tachycardia20.3 mg/L (1-hourlevel) Activated charcoalDischarged wellafter 24 hoursWillis(2007)12-day-oldmale Not availableAcute: repeated poisoning(including in the hospital);2 seizures (9 days apart),with arm movements,irritability, poorinteraction, poor feeding35 mg/L (2 daysafter the secondseizure)Lorazepam,phenytoin,paraldehyde19-day admissionwith seizures atdays 4 and 13,discharged well tochild protectionLofton(2004)3-year-oldfemale Not availableAcute: multiple seizureswith vomiting Not available Not available Not availableBriassoulis(1998)2-year-oldmale 62 mg/kg tabletAcute: 2 seizures (15- and5-minute duration) within90 minutes with muscleweakness andincoordination, ataxia,tremor, hypertonia3.8 mg/L (2-hourlevel)Midazolam, gastriclavage, activatedcharcoalDischarged wellafter 48 hoursModified from the following: Close BR, Banks CJ: Seizures secondary to lamotrigine toxicity in a two-year-old. Ann Pharmacother 2010;44:1112-5.after ingestion, respectively. Serum liquid chromatography-mass spectrometry detected the following: acetaminophen,lamotrigine, 7-aminoclonazepam, midazolam, alpha-hydroxymidazolam, and lorazepam. This result is consistentwith both ingestion of lamotrigine and clonazepam, as wellas iatrogenic administration of lorazepam, midazolam, andacetaminophen.While in the PICU, the child demonstrated mild hyper-kinesia and periods of agitation. He was extubated onhospital day (HD) one, and these symptoms resolved over thesubsequent 36 hours. Ultimately, the patient was dischargedin normal condition on HD five.3. DiscussionLamotrigine poisoning in children is very rare. Sevenidentified cases of patients describe seizures, as well ashyperkinesia and ataxia following ingestion [3, 5–10]. Thesecase reports of acute lamotrigine poisoning in pediatricpatients were identified through literature review (Table 1).Case reports of lamotrigine intoxication in children wereidentified by searching PubMed using the following searchterms: lamotrigine, lamictal, overdose, poisoning, pediatric,seizure, and adverse reactions. Case reports describing adultpatients with adverse reactions as well as adverse reactionsresulting from therapeutic dosing or chronic ingestion wereexcluded. Three cases of pediatric lamotrigine poisoningwhich included serum concentrations were identified. Thehighest documented serum concentration was measured ina 12-day-old boy who was being repeatedly poisoned while inthe hospital and not after a single, accidental ingestion as inthe case described in this report [5].Lamotrigine is rapidly absorbed in the stomach witha bioavailability of approximately 98%. The drug is 50%Case Reports in Emergency Medicine 3plasma protein-bound, undergoes hepatic metabolism viaglucuronidation, and is mainly eliminated by the kidneyswith an elimination half-life of approximately 29 hours [1,11]. Oral disintegrating tablets and regular immediate releaseoral tablets are bioequivalent [11]. Typically, the maximumlamotrigine dosage for maintenance in the pediatric agegroup is a maximum of one to five mg/kg/day divided intoone or two doses. The largest potential dose consumed in ourcase was five times the maximummaintenance dosage for hisage group [7].Lamotrigine poisoning can cause seizures, behavioraldisturbances, and cardiotoxicity. Seizures generally occurbetween 20 minutes and three hours after ingestion andhave been described as myoclonic, tonic- clonic, and statusepilepticus (Table 1). Hyperkinetic armmotion, dysconjugategaze, and ataxic gait were evident on physical examinationin this case. Severe ataxia and dysmetria have been reportedand attributed to inhibition of GABA release [12]. Oculogyriccrisis may occur from alteration of dopaminergic tone [12].Neurologic effects generally resolve over 12 to 48 hours.While there have been no reported cases of cardiotoxicityin the pediatric population, this is a known risk of lam-otrigine intoxication causing ventricular dysrhythmias inadults.Treatment of lamotrigine poisoning comprises airwaysupport and the use of titrated benzodiazepines, barbitu-rates, or propofol to ameliorate seizure and motor activity[13]. Administration of intravenous sodium bicarbonate isindicated for prolonged QRS interval or ventricular dys-rhythmias. Intralipid emulsion administration with clinicalimprovement was reported in a case of a patient sufferingfrom combined lamotrigine and bupropion toxicity [14].Measurement of serum lamotrigine concentrations may beused to confirm exposure but may not be readily available;therefore, empiric treatment as outlined above is recom-mended.Pediatric lamotrigine poisoning can cause severe toxicity,including abnormal motor activity, seizures, and possiblecardiac dysrhythmias. The mainstay of treatment is empiricand supportive with attention to the airway and control ofseizures.DisclosureThe abstract titled “Lamotrigine ODT-Induced Seizure in a3-Year-Old Child after Accidental Ingestion: A Case Report”was presented at the American College of Medical Toxicol-ogy’s 2018 Annual Scientific Meeting.Conflicts of InterestThe authors declare that there are no conflicts of interestregarding the publication of this article.AcknowledgmentsTheauthors would like to thank Lauren Crowley, B.A., for herassistance in editing and formatting this case report.References[1] H. Stefan and T. J. Feuerstein, “Novel anticonvulsant drugs,”Pharmacology &erapeutics, vol. 113, no. 1, pp. 165–183, 2007.[2] J. A.Messenheimer, L. Giorgi, andM. E. Risner, “The tolerabilityof lamotrigine in children,” Drug Safety, vol. 22, no. 4, pp. 303–312, 2000.[3] A. L. Lofton andW. Klein-Schwartz, “Evaluation of lamotriginetoxicity reported to poison centers,”Annals of Pharmacotherapy,vol. 38, no. 11, pp. 1811–1815, 2004.[4] A. W. C. Yuen, “Lamotrigine: A Review of Antiepileptic Effi-cacy,” Epilepsia, vol. 35, pp. S33–S36, 1994.[5] T. Willis, H. Roper, and L. Rabb, “Lamotrigine poisoningpresenting as seizures: A case of deliberate poisoning,” ChildAbuse & Neglect, vol. 31, no. 1, pp. 85–88, 2007.[6] J. G. Thundiyil, I. B. Anderson, P. J. Stewart, and K. R. Olson,“Lamotrigine-induced seizures in a child: Case report andliterature review,”Clinical Toxicology, vol. 45, no. 2, pp. 169–172,2007.[7] B. R. Close and C. J. Banks, “Seizures secondary to lamotriginetoxicity in a two-year-old,” Annals of Pharmacotherapy, vol. 44,no. 6, pp. 1112–1115, 2010.[8] G. Briassoulis, P. Kalabalikis, M. Tamiolaki, and T. Hatzis,“Lamotrigine childhood overdose,” Pediatric Neurology, vol. 19,no. 3, pp. 239–242, 1998.[9] M. Daana, Y. Nevo, A. Tenenbaum, I. Taustein, and I. Berger,“Lamotrigine overdose in a child,” Journal of Child Neurology,vol. 22, no. 5, pp. 642–644, 2007.[10] P. W. Moore, J. W. Donovan, K. K. Burkhart, and D. Haggerty,“A case series of patients with lamotrigine toxicity at one centerfrom 2003 to 2012,” Clinical Toxicology, vol. 51, no. 7, pp. 545–549, 2013.[11] Package insert I, “Lamotrigine - lamotrigine chewabledispersible tablet, highlights of prescribing information,” 2017,https://www.gsksource.com/pharma/content/dam/GlaxoSmith-Kline/US/en/Prescribing Information/Lamictal/pdf/LAMICTAL-PI-MG.PDF.[12] S. Grosso, S. Ferranti, C. Gaggiano, E. Grande, B. Loi, and R. DiBartolo, “Massive lamotrigine poisoning. A case report,” Brain& Development, vol. 39, no. 4, pp. 349–351, 2017.[13] H.-Y. Chen, T. E. Albertson, and K. R. Olson, “Treatment ofdrug-induced seizures,” British Journal of Clinical Pharmacol-ogy, vol. 81, no. 3, pp. 412–419, 2016.[14] J. D. Presley and P. A. Chyka, “Intravenous lipid emulsion toreverse acute drug toxicity in pediatric patients,” Annals ofPharmacotherapy, vol. 47, no. 5, pp. 735–743, 2013.

Lamotrigine ODT-Induced Seizure in a 3-Year-Old Child after Accidental Ingestion

Abstract

Similar works

Full text

Available Versions

Lehigh Valley Health Network: LVHN Scholarly Works