Topiramate Overdose: Clinical and Laboratory Features

Fakhoury, Toufic; Murray, Lindsay; Seger, Donna; McLean, Michael; Abou‐Khalil, Bassel

doi:10.1006/ebeh.2002.0339

Cited by 44 publications

(32 citation statements)

References 17 publications

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“…However, anticonvulsant effects were seen in animals treated with topiramate for more than 6 hours prior to pharmacological induction of seizures with kainate (7). The occurrence of secondarily generalized seizures in our patient after the relatively small dose of topiramate (31.25 mg/kg) in comparison to doses described by Fakhoury et al (5), suggests that acute poisoning may be more severe in those patients who were not previously treated with topiramate.…”

Section: To the Editorcontrasting

confidence: 44%

“…It also has been used in the treatment of cluster headache, essential tremor, binge eating disorder, acute mania, Tourette's syndrome, neuropathic pain, bipolar disorder, alcohol dependence, and to facilitate weight loss in obese patients (1)(2)(3)(4). The exact mechanism of topiramate action is unknown, although inhibition of voltage-sensitive sodium and calcium channels, potentialization of gamma-aminobutyric acid (GABA) mediated chloride currents, and selective blockade of kainate-activated glutamate receptors are considered (1,3,4,5). Topiramate also weakly inhibits carbonic anhydrase, specifically the activity of CA II and IV isoforms found in the kidney and brain (5).…”

Section: To the Editormentioning

confidence: 99%

“…The exact mechanism of topiramate action is unknown, although inhibition of voltage-sensitive sodium and calcium channels, potentialization of gamma-aminobutyric acid (GABA) mediated chloride currents, and selective blockade of kainate-activated glutamate receptors are considered (1,3,4,5). Topiramate also weakly inhibits carbonic anhydrase, specifically the activity of CA II and IV isoforms found in the kidney and brain (5). The medical literature on acute topiramate toxicity is limited and contains only six published cases (1)(2)(3)(4)(5)(6).…”

Section: To the Editormentioning

confidence: 99%

“…Topiramate also weakly inhibits carbonic anhydrase, specifically the activity of CA II and IV isoforms found in the kidney and brain (5). The medical literature on acute topiramate toxicity is limited and contains only six published cases (1)(2)(3)(4)(5)(6). According to the best of our knowledge, there is only one article (5) describing status epilepticus in two patients massively intoxicated with topiramate (400 mg/kg and 487 mg/ kg).…”

Section: To the Editormentioning

confidence: 99%

See 3 more Smart Citations

Letter To The Editor: “Seizures induced by topiramate overdose”

Anand

Chodorowski

Wiśniewski

2007

Clinical Toxicology

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Section: To the Editorcontrasting

confidence: 44%

Section: To the Editormentioning

confidence: 99%

Section: To the Editormentioning

confidence: 99%

Section: To the Editormentioning

confidence: 99%

See 2 more Smart Citations

Letter To The Editor: “Seizures induced by topiramate overdose”

Anand

Chodorowski

Wiśniewski

2007

Clinical Toxicology

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“…Fakhoury et al 8 re p o rt e d two patients who attempted suicide by taking a topiramate overdose. Their metabolic acidosis re t u rn e d to normal after 5-6 days.…”

Section: Discussionmentioning

confidence: 99%

Topiramate and severe metabolic acidosis: case report

Burmeister

Pereira

Hartke

et al. 2005

Arq. Neuro-Psiquiatr.

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-Topiramate infrequently induces anion gap metabolic acidosis through carbonic anhydrase inhibition on the distal tubule of the nephron -a type 2 renal tubular acidosis. We report on a 40 years old woman previously healthy that developed significant asymptomatic metabolic acidosis during topiramate therapy at a dosage of 100mg/day for three months. Stopping medication was followed by normalization of the acid-base status within five weeks. This infrequent side effect appears unpredictable and should be given careful attention.KEY WORDS: topiramate, metabolic acidosis, carbonic anhydrase inhibitor.Acidose metabólica grave por topiramato: relato de caso RESUMO -Topiramato pode produzir raramente uma acidose metabólica através da inibição da anidrase carbônica no túbulo distal do néfron -acidose tubular renal do tipo 2. Relatamos o caso de mulher de 40 anos previamente saudável que desenvolveu quadro de acidose metabólica assintomática grave, sem outra etiologia identificável, durante uso de topiramato na dose de 100mg/dia por três meses. Este efeito colateral, embora infrequente, parece ser imprevisível e requer atenção cuidadosa.PALAVRAS-CHAVE: topiramato, acidose metabólica, inibidor da anidrase carbônica.Topiramate was approved by the FDA (US -F o o d and Drug Administration) in 1996 for clinical use as an anticonvulsant drug. Since then, other clinical i ndications have been studied, such as the tre a tment of bipolar disord e r, or neuropathic pain syndro m e s re l i e f 1 , 2 , and migraine and cluster headache 3 -5 . As a consequence, it is likely that clinical use will tend t o expand progressively. Initially, significant adverse reactions to topiramate were related to the central nervous system (somnolence, nervousness, psychomotor slowing, memory problems, fatigue), or w e re gastrointestinal (nausea), ocular (diplopia, nystagmus) and neuromuscular (tre m o r, pare s t h e s i a ) . N e v e rtheless, since 1996, when it was approved by FDA, at least twelve reports were made relating metabolic acidosis to the use of topiramate, both in adults and in childre n 6 -1 7. Finally, in December 20 03, FDA released a note about the risk of metabolic acidosis caused by topiramate usage 1 8. Severe m etabolic acidosis can occur in patients under topiramate treatment, even when the daily dosage is low. The absence of relevant clinical symptoms re n d e r s it more difficult to recognize.We present a case of severe asymptomatic metabolic acidosis due to topiramate in an adult woman. CASEA 46-year old previously healthy white woman came to our hospital with a complaint of intense chest pain for at least 5 days with tenderness on the site of the pain i n d icating traumatic origin. There were no other symptoms, and physical examination plus X-ray and laboratory evaluation excluded pleural or pulmonary disease. Later, a radiograph of the ribs, a chest CT scan and a radionuc l e a r bone scan showed a small traumatic lesion in the area of the pain. At the hospital entrance, her arterial blood gas analysis...

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Carbonic Anhydrases: Off Targets, Add‐On Activities, or Emerging Novel Targets?

Supuran

2012

Polypharmacology in Drug Discovery

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Topiramate Overdose: Clinical and Laboratory Features

Cited by 44 publications

References 17 publications

Letter To The Editor: “Seizures induced by topiramate overdose”

Letter To The Editor: “Seizures induced by topiramate overdose”

Topiramate and severe metabolic acidosis: case report

Carbonic Anhydrases: Off Targets, Add‐On Activities, or Emerging Novel Targets?

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