Neurotoxicity following addition of intravenous valproate to lamotrigine therapy

Burneo, Jorge G.; Limdi, Nita A.; Kuzniecky, Ruben; Knowlton, Robert C.; Méndez, M. Ballesta; Lawn, Nicholas; Faught, Edward; Welty, Timothy E.; Prasad, Ashoka Jahnavi

doi:10.1212/01.wnl.0000065915.68602.91

Cited by 11 publications

(3 citation statements)

References 5 publications

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“…The patient recovered completely within 48 h of discontinuation of valproate. Reversible symptoms of encephalopathy, including confusion or lethargy, were observed in three adult patients with absence SE treated with intravenous valproate and who were on maintenance therapy with lamotrigine [78]. In these patients, the authors related the symptoms to elevated serum levels of lamotrigine due to the well characterized pharmacokinetic interaction between valproate and lamotrigine, whereby valproate inhibits hepatic glucuronidation of lamotrigine.…”

Section: Resultsmentioning

confidence: 99%

Efficacy and Safety of Intravenous Valproate for Status Epilepticus: A Systematic Review

et al. 2014

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IntroductionThe effectiveness of valproate (VPA) in the treatment of focal and generalized epilepsies is well established. The drug has a wide spectrum of action, good tolerability, and has been available as an injectable formulation since 1993. Despite the lack of class A evidence, it has been used extensively in various forms of status epilepticus (SE).AimOur aim was to present a systematic review of data from randomized and non-randomized controlled trials to evaluate the efficacy and safety of intravenous VPA for the treatment of SE.MethodsData sources included MEDLINE, back tracing of references in pertinent studies, and contact with the manufacturer of VPA (Sanofi-Aventis).ResultsOverall, the search strategy yielded 433 results (425 MEDLINE, seven congress abstracts, one unpublished study); after excluding duplicate publications and case reports, 30 studies were identified (the earliest was published in 1993, the most recent in 2012); ten were controlled (six randomized controlled trials, four non-randomized controlled studies), and 20 uncontrolled trials (eight prospective observational studies, 12 retrospective case series). The cumulative literature describes the experiences of 860 patients with various forms of SE treated with intravenous VPA. The overall response rate to abrogate SE was 70.9 % (601/848; 95 % confidence interval [CI] 67.8–73.9). Response rates to intravenous VPA were better in children than in adults and did not differ between the SE types. The most commonly reported effective doses were between 15 and 45 mg/kg in bolus (6 mg/kg/min) followed by 1–3 mg/kg/h infusion. Safety studies of intravenous VPA administration in patients with SE showed a low incidence of adverse events overall (<10 %), mainly dizziness, thrombocytopenia, and mild hypotension, which was independent of infusion rates. Of note, good cardiovascular and respiratory tolerability was observed in these studies, even at high doses and fast infusion rates (up to 30 mg/kg at 10 mg/kg/min), despite multiple morbidities or other antiepileptic drugs. The most serious concern relates to the possibility of acute encephalopathy, sometimes related to hepatic abnormalities or hyperammonemia.ConclusionsThe published experience is consistent with VPA being a safe and effective therapeutic option for patients with established SE who have previously failed conventional first-line treatment with benzodiazepines, but high-quality randomized controlled trials are needed to inform clinicians on its comparative effectiveness in SE.

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Section: Resultsmentioning

confidence: 99%

Efficacy and Safety of Intravenous Valproate for Status Epilepticus: A Systematic Review

et al. 2014

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“…So wurde über eine 45-jährige Frau mit nichtkonvulsivem Status epilepticus bei bekannter generalisierter Epilepsie berichtet, die unter 1000 mg VPAiv pro Tag nach erfolgloser Gabe von Lorazepam am zweiten Tag eine Somnolenz und EEG-Verlangsamung mit Laktatanstieg und Hirnödem entwickelte, was nach Absetzen von VPA innerhalb von 24 Stunden reversibel war ( [113]; Inzidenz 2/72 Patienten = 3 %). Bei 3 erwachsenen Patienten wurden reversible Zeichen einer zentralen Neurotoxizität mit Verwirrtheit und Lethargie in Zusammenhang mit VPAiv (zusätzlich zu Lamotrigin) bei Absenzenstatus beobachtet [114]. Die Neurotoxizität wurde auf die durch die VPA-Zugabe erhöhten Serumkonzentrationen von Lamotrigin zurückgeführt; nach Absetzen von Lamotrigin (2 Patienten) beziehungsweise Lamotrigin und VPA (1 Patient) bildeten sich die Beschwerden innerhalb von 1 ± 2 Tagen vollständig zurück.…”

Section: Sicherheit Und Verträglichkeit Von Vpaivunclassified

Derzeitiger Stellenwert intravenöser Valproinsäure in der Therapie des generalisierten tonisch-klonischen Status epilepticus

Bergmann¹,

Despland²,

König³

et al. 2005

Akt Neurol

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“…Moreover, a few reports suggest, that patients are more vulnerable when VPA is added to premedication with topiramate, phenytoin, phenobarbital, lamotirigin or lorazepam [1]. Neurotoxicity was reported in three patients on lamotrigin after adding IV VPA for treatment of frequent absences seizures [4].…”

mentioning

confidence: 99%

Acute encephalopathy after intravenous administration of valproate in non‐convulsive status epilepticus

Embacher

Karner

Wanschitz

et al. 2006

Euro J of Neurology

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Neurotoxicity following addition of intravenous valproate to lamotrigine therapy

Cited by 11 publications

References 5 publications

Efficacy and Safety of Intravenous Valproate for Status Epilepticus: A Systematic Review

Efficacy and Safety of Intravenous Valproate for Status Epilepticus: A Systematic Review

Derzeitiger Stellenwert intravenöser Valproinsäure in der Therapie des generalisierten tonisch-klonischen Status epilepticus

Acute encephalopathy after intravenous administration of valproate in non‐convulsive status epilepticus

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