Intravenous topiramate for seizure emergencies - First in human case report.

Topiramate (TPM) is widely used in focal and generalized epilepsies. It is commercially available as tablets and sprinkles capsules for oral treatment. Previous studies comparing intravenous (IV) to oral TPM in healthy adults showed more rapid pharmacodynamic effects in cases of IV administration. Despite promising findings, no clinical application in humans followed. We present a case of a pregnant woman with idiopathic generalized epilepsy who experienced a generalized tonic-clonic seizure in the third trimenon due to low TPM levels attributed to pregnancy followed by repeated prolonged absences. We applied a new meglumine-based solution (1%) of TPM (10 mg/ml) in two IV infusions of 200 mg each under EEG monitoring over a total duration of 1 hour. The infusion was well tolerated and led to a rapid increase in plasma TPM levels. A clinical as well as electroencephalographic improvement was documented within the first hours. To the best available knowledge, this is the first reported case where IV TPM was used therapeutically for seizure treatment in humans. It is also the first time that the new meglumine-based solution was used in a human with epilepsy. The advantages of IV route delivery and the solution's quick preparation, high tolerability, and low toxicity make it ideal for use in many clinical settings and high-care patients. IV TPM seems to be a reasonable adjunctive option for adults with seizures, previously stabilized on oral TPM, who need rapid plasma concentration boosting. Although our experience was successful in using injectable TPM in seizure emergencies, randomized controlled clinical trials are required to make recommendations for the use of IV TPM on patients with epilepsy. This paper was presented at the 8th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures held in September 2022 in Salzburg, Austria.
Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: L.A. does not report any conflict of interest. P.B.V. does not report any conflict of interest. F.R. does not report any conflict of interest. C.O.S. does not report any conflict of interest. W.L. is cofounder and CSO of PrevEp Inc. (Bethesda, MD), which is developing the meglumine-based solution of TPM. G.K. does not report any conflict of interest. E.T. has received personal fees from Arvelle Therapeutics, Inc., Argenx, Bial, Biogen, Biocodex, Böhringer Ingelheim, Eisai, Epilog, Everpharma, GlaxoSmithKline, GW Pharma, Jazz Pharmaceuticals, LivaNova PLC, Marinus Pharmaceuticals, Inc., Medtronic, NewBridge Pharmaceuticals, Novartis, Sandoz, Sanofi, Sunovion Pharmaceuticals, Inc., Takeda, UCB Pharma, and Xenon; grants from Austrian Science Fund (FWF), Bayer, Biogen, Eisai, European Union, GlaxoSmithKline, Novartis, Österreichische Nationalbank, Red Bull, and UCB Pharma; He is CEO of NeuroConsult GmbH.; and has been a trial investigator for Eisai, GlaxoSmithKline, Marinus, Pfizer, and UCB Pharma.
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