Clinical effects and toxicokinetic evaluation following massive topiramate ingestion

Michael J Lynch; Anthony F Pizon; Mohamed G Siam; Matthew D Krasowski

doi:10.1007/s13181-010-0065-y

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Clinical effects and toxicokinetic evaluation following massive topiramate ingestion

Journal article

Open access

Peer reviewed

Clinical effects and toxicokinetic evaluation following massive topiramate ingestion

Michael J Lynch, Anthony F Pizon, Mohamed G Siam and Matthew D Krasowski

Journal of medical toxicology, Vol.6(2), pp.135-138

06/2010

DOI: 10.1007/s13181-010-0065-y

PMCID: PMC2916051

PMID: 20376593

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Abstract

Topiramate is used to treat a variety of neurologic and psychiatric diseases due to its benign safety profile. Data regarding the toxicity and toxicokinetics of topiramate in acute overdose are limited. A case of massive, acute ingestion resulting in the highest reported topiramate level is presented, including toxicokinetic evaluation. A 37-year-old woman presented with coma unresponsive to naloxone following topiramate ingestion. She had normal vital signs without respiratory depression. She was intubated for airway protection, given 3.5 mg lorazepam IV for facial and neck muscle twitching, and transferred to our facility. No additional sedation was required for 18 h on the ventilator. Following mental status improvement, the patient was extubated. Confusion, dysarthria, and imbalance resolved over the next 2 days. Nonanion gap metabolic acidosis persisted for 3 days. Peak serum topiramate level was 356.6 microg/ml (reference range, 5-20 microg/ml). Massive topiramate ingestion led to prolonged coma with normal vital signs and nonanion gap metabolic acidosis. Coma of this severity has not been previously reported. Serum half-life, which has not been studied after overdose, was 16 h. Despite the large ingestion and significant presenting symptoms, the patient recovered fully with supportive intensive care alone. Massive acute topiramate ingestion may lead to nonanion gap metabolic acidosis and prolonged coma which resolves with intensive supportive care. Toxicokinetic data following large, suicidal ingestion of topiramate were similar to previously published pharmacokinetic information.

Anticonvulsants - pharmacokinetics

Fructose - pharmacokinetics

Gas Chromatography-Mass Spectrometry

Drug Overdose

Anticonvulsants - poisoning

Humans

Blood Gas Analysis

Anticonvulsants - therapeutic use

Acidosis - chemically induced

Hypnotics and Sedatives - therapeutic use

Bipolar Disorder - drug therapy

Respiration, Artificial

Fructose - therapeutic use

Bipolar Disorder - psychology

Lorazepam - therapeutic use

Fructose - analogs & derivatives

Adult

Critical Care

Female

Fructose - poisoning

Coma - chemically induced

Details

Title: Subtitle: Clinical effects and toxicokinetic evaluation following massive topiramate ingestion
Creators: Michael J Lynch - Division of Medical Toxicology, Department of Emergency Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, USA. lyncmj@upmc.edu
Anthony F Pizon
Mohamed G Siam
Matthew D Krasowski
Resource Type: Journal article
Publication Details: Journal of medical toxicology, Vol.6(2), pp.135-138
Publisher: United States
DOI: 10.1007/s13181-010-0065-y
PMID: 20376593
PMCID: PMC2916051
ISSN: 1556-9039
eISSN: 1937-6995
Grant note: K08 GM074238 / NIGMS NIH HHS K08 GM074238-04 / NIGMS NIH HHS K08 GM074238-03 / NIGMS NIH HHS K08-GM074238 / NIGMS NIH HHS
Language: English
Date published: 06/2010
Academic Unit: Pathology
Record Identifier: 9984046924602771

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