{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T12:22:34Z","timestamp":1756902154815,"version":"3.44.0"},"reference-count":14,"publisher":"The Pediatric Pharmacy Association","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017]]},"abstract":"<jats:sec>\n          <jats:title>OBJECTIVE<\/jats:title>\n          <jats:p>Pediatric patients often require larger doses of antiepileptic drug (AED) than adults in order to attain therapeutic serum concentrations and\/or achieve seizure control. Safety and efficacy data are often extrapolated from adult literature; hence, optimal dosage may only be determined anecdotally or based on expert opinion. With limited pediatric dosing guidelines, milligrams per day that are based on weight may exceed the maximum adult dose. The primary objective of this study is to evaluate the safety of exceeding maximum doses as specified by the US Food and Drug Administration or manufacturers of commonly used AEDs in pediatric patients.<\/jats:p>\n        <\/jats:sec>\n        <jats:sec>\n          <jats:title>METHODS<\/jats:title>\n          <jats:p>This study is a single-center, retrospective analysis of all pediatric patients seen in the outpatient clinic between October 2010 and October 2014 who were prescribed a dose that exceeds the maximum approved dose of oxcarbazepine, zonisamide, topiramate, levetiracetam, lamotrigine, or clobazam. Baseline demographics (ie, sex, age, race\/ethnicity, weight, height, diagnosis), serum drug concentrations, and appropriate laboratory tests were collected. Side effects were reviewed.<\/jats:p>\n        <\/jats:sec>\n        <jats:sec>\n          <jats:title>RESULTS<\/jats:title>\n          <jats:p>During the 4-year study period, 41,137 prescriptions were included. A total of 2% of prescriptions exceeded the maximum dose of 1 of the included AEDs. The most common AED prescribed above the maximum dose was levetiracetam (53%), whereas lamotrigine was the least common (6%). The largest doses prescribed exceeded the maximum by 3-fold (i.e., levetiracetam dose of 9000 mg\/day).<\/jats:p>\n        <\/jats:sec>\n        <jats:sec>\n          <jats:title>CONCLUSION<\/jats:title>\n          <jats:p>It appears safe to use doses exceeding the maximum approved dose of the evaluated AEDs in pediatric patients, with appropriate counseling and monitoring for adverse effects.<\/jats:p>\n        <\/jats:sec>","DOI":"10.5863\/1551-6776-22.4.256","type":"journal-article","created":{"date-parts":[[2017,9,12]],"date-time":"2017-09-12T17:06:41Z","timestamp":1505236001000},"page":"256-260","source":"Crossref","is-referenced-by-count":0,"title":["Evaluation of Safety in Exceeding Maximum Adult Doses of Commonly Used Second-Generation Antiepileptic Drugs in Pediatric Patients"],"prefix":"10.5863","volume":"22","author":[{"given":"Mindl M.","family":"Messinger","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sunita N.","family":"Misra","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gary D.","family":"Clark","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shannon M.","family":"DiCarlo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"3883","reference":[{"issue":"5","key":"i1551-6776-22-4-256-b1","series-title":"N Engl J Med","first-page":"314","article-title":"Early identification of refractory epilepsy","volume":"342","year":"2000","unstructured":"Kwan\n              P\n            , BrodieMJ.\n          Early identification of refractory epilepsy. N Engl J Med. 2000;342(5):314\u2013319."},{"issue":"8","key":"i1551-6776-22-4-256-b2","series-title":"Clin Pharmacokinet","first-page":"627","article-title":"Clinical pharmacokinetics of new-generation antiepileptic drugs at the extremes of age: an update","volume":"52","year":"2013","unstructured":"Italiano\n              D\n            , PeruccaE.\n          Clinical pharmacokinetics of new-generation antiepileptic drugs at the extremes of age: an update. Clin Pharmacokinet. 2013;52(8):627\u2013645."},{"key":"i1551-6776-22-4-256-b3","series-title":"Epilepsy Behav","first-page":"101","article-title":"The Pediatric Epilepsy Side Effects Questionnaire: establishing clinically meaningful change","volume":"45","year":"2015","unstructured":"Junger\n              KW\n            , MoritaD, ModiAC.\n          The Pediatric Epilepsy Side Effects Questionnaire: establishing clinically meaningful change. Epilepsy Behav. 2015;45:101\u2013104."},{"issue":"suppl 8","key":"i1551-6776-22-4-256-b4","series-title":"Epilepsia","first-page":"63","article-title":"Rational polytherapy","volume":"50","year":"2009","unstructured":"French\n              JA\n            , FaughtE.\n          Rational polytherapy. Epilepsia. 2009;50(suppl 8):63\u201368."},{"issue":"5","key":"i1551-6776-22-4-256-b5","series-title":"Epilepsy Curr","first-page":"260","article-title":"Seeking the rational (or at least avoiding the irrational)","volume":"15","year":"2015","unstructured":"Gidal\n              BE.\n            \n          \n          Seeking the rational (or at least avoiding the irrational). Epilepsy Curr. 2015;15(5):260\u2013262."},{"key":"i1551-6776-22-4-256-b6","series-title":"J Cent Nerv Syst Dis","first-page":"51","article-title":"The safety and tolerability of newer antiepileptic drugs in children and adolescents","volume":"4","year":"2012","unstructured":"Kayani\n              S\n            , SirsiD.\n          The safety and tolerability of newer antiepileptic drugs in children and adolescents. J Cent Nerv Syst Dis. 2012;4:51\u201363."},{"issue":"1","key":"i1551-6776-22-4-256-b7","series-title":"Epilepsy Res","first-page":"101","article-title":"Efficacy and tolerability of high oral doses of levetiracetam in children with epilepsy","volume":"91","year":"2010","unstructured":"Obeid\n              M\n            , PongAW.\n          Efficacy and tolerability of high oral doses of levetiracetam in children with epilepsy. Epilepsy Res. 2010;91(1):101\u2013105."},{"issue":"3","key":"i1551-6776-22-4-256-b8","series-title":"Epilepsy Behav","first-page":"557","article-title":"Pyridoxine supplementation for the treatment of levetiracetam-induced behavior side effects in children: preliminary results","volume":"13","year":"2008","unstructured":"Major\n              P\n            , GreenbergE, KhanA, ThieleEA.\n          Pyridoxine supplementation for the treatment of levetiracetam-induced behavior side effects in children: preliminary results. Epilepsy Behav. 2008;13(3):557\u2013559."},{"issue":"2","key":"i1551-6776-22-4-256-b9","series-title":"J Child Adolesc Psychopharmacol","first-page":"209","article-title":"Behavioral effects of levetiracetam mitigated by pyridoxine","volume":"19","year":"2009","unstructured":"Davis\n              GP\n            , McCarthyJT, MagillDB, CoffeyB.\n          Behavioral effects of levetiracetam mitigated by pyridoxine. J Child Adolesc Psychopharmacol. 2009;19(2):209\u2013211."},{"issue":"12","key":"i1551-6776-22-4-256-b10","series-title":"Neurology","first-page":"2237","article-title":"Adjunctive therapy with oxcarbazepine in children with partial seizures: the Oxcarbazepine Pediatric Study Group","volume":"54","year":"2000","unstructured":"Glauser\n              TA\n            , NigroM, SachdeoR, \n          et al. Adjunctive therapy with oxcarbazepine in children with partial seizures: the Oxcarbazepine Pediatric Study Group. Neurology. 2000;54(12):2237\u20132244."},{"issue":"1","key":"i1551-6776-22-4-256-b11","series-title":"Pediatr Neurol","first-page":"60","article-title":"Clobazam: effect on frequency of seizures and safety profile in different subgroups of children with epilepsy","volume":"51","year":"2014","unstructured":"Klehm\n              J\n            , Thome-SouzaS, Sanchez FernandezI, \n          et al. Clobazam: effect on frequency of seizures and safety profile in different subgroups of children with epilepsy. Pediatr Neurol. 2014;51(1):60\u201366."},{"issue":"3","key":"i1551-6776-22-4-256-b12","series-title":"Clin Neuropharmacol","first-page":"121","article-title":"Could adult European pharmacoresistant epilepsy patients be treated with higher doses of zonisamide?","volume":"39","year":"2016","unstructured":"Miro\n              J\n            , JarabaS, JuvanyR, \n          et al. Could adult European pharmacoresistant epilepsy patients be treated with higher doses of zonisamide?Clin Neuropharmacol. 2016;39(3):121\u2013124."},{"issue":"6","key":"i1551-6776-22-4-256-b13","series-title":"Br J Clin Pharmacol","first-page":"958","article-title":"Metabolic disturbances and renal stone promotion on treatment with topiramate: a systematic review","volume":"77","year":"2014","unstructured":"Dell'Orto\n              VG\n            , BelottiEA, Goeggel-SimonettiB, \n          et al. Metabolic disturbances and renal stone promotion on treatment with topiramate: a systematic review. Br J Clin Pharmacol. 2014;77(6):958\u2013964."},{"issue":"5","key":"i1551-6776-22-4-256-b14","series-title":"Pharmacogenet Genomics","first-page":"297","article-title":"Metabolic acidosis with topiramate and zonisamide: an assessment of its severity and predictors","volume":"21","year":"2011","unstructured":"Mirza\n              NS\n            , AlfirevicA, JorgensenA, \n          et al. Metabolic acidosis with topiramate and zonisamide: an assessment of its severity and predictors. Pharmacogenet Genomics. 2011;21(5):297\u2013302."}],"container-title":["The Journal of Pediatric Pharmacology and Therapeutics"],"original-title":[],"link":[{"URL":"https:\/\/jppt.kglmeridian.com\/view\/journals\/jppt\/22\/4\/article-p256.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/meridian.allenpress.com\/jppt\/article-pdf\/22\/4\/256\/1787725\/1551-6776-22_4_256.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/jppt.kglmeridian.com\/downloadpdf\/journals\/jppt\/22\/4\/article-p256.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/jppt.kglmeridian.com\/downloadpdf\/journals\/jppt\/22\/4\/article-p256.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,16]],"date-time":"2025-05-16T00:45:53Z","timestamp":1747356353000},"score":1,"resource":{"primary":{"URL":"https:\/\/jppt.kglmeridian.com\/view\/journals\/jppt\/22\/4\/article-p256.xml"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017]]},"references-count":14,"journal-issue":{"issue":"4"},"URL":"https:\/\/doi.org\/10.5863\/1551-6776-22.4.256","relation":{},"ISSN":["1551-6776"],"issn-type":[{"type":"print","value":"1551-6776"}],"subject":[],"published":{"date-parts":[[2017]]}}}