Topiramate and severe metabolic acidosis: case report

Abstract

-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...

Topiramate, a concealed cause of severe metabolic acidosis

“…Less commonly a variety of gastrointestinal symptoms have also been described [6]. Several reports describe toxicity at varying doses of ingestion when used for migraine and epilepsy (Table 2) [4,5,[7][8][9][10][11][12][13][14][15][16][17][18][19][20]. Based on a retrospective review of 567 cases of topiramate toxicity (during 2000-2001), the American Association of Poison Control revealed that: 39% were adults, mild mental status changes were common, and severe respiratory depression or persistent NAGMA were infrequent yet other reports confirm their occurrence [5,[10][11][12].…”

Severe Non-Anion Gap Metabolic Acidosis Induced by Topiramate: A Case Report

“…The first three actions account for its intended neurological effects, whereas the fourth action induces a Type 2 renal tubule acidosis (RTA). The distal tubule of the nephron is unable to reclaim filtered bicarbonate, allowing increased urinary excretion, resulting in lowered serum bicarbonate levels (5,6,8,9).…”

Renal Tubular Acidosis Following Topiramate

“…Burmeister et al [1] reported a case of a 46-year-old patient who was prescribed topiramate for vertigo and developed metabolic acidosis with a pH of 7.31 and serum bicarbonates of 8.9. Similarly, Ozer and Altunkaya [2] reported a case of a 58-year-old patient on topiramate for refractory temporal lobe epilepsy who developed metabolic acidosis with a pH of 7.29 and serum bicarbonates of 20 mM.…”