Predisposition to metabolic acidosis induced by topiramate

Abstract

RATIONALE: Metabolic acidosis induced by topiramate is a well documented but infrequent adverse event. The objective was to demonstrate the lowering of carbon dioxide serum levels, which is usually asymptomatic but may facilitate the occurrence of metabolic acidosis in patients using topiramate. METHODS: We evaluated, prospectively, the carbon dioxide serum levels of 18 patients seen at the epilepsy clinic of our university hospital, before and 3 months after introducing topiramate. RESULTS: Five patients were female and 13 were male, age ranging from 2 to 16 years old (mean=9.3). Carbon dioxide mean serum levels were 25 and 21.2 mmol/L (normal = 22 to 30), before and 3 months after introducing topiramate, respectively. Dose ranged from 2.08 to 11.76 mg/kg/day (mean=6.7mg/kg/day). Adverse events were anorexia, nausea and somnolence. CONCLUSION: We conclude that the lowering of carbon dioxide serum levels induced by topiramate is mostly asymptomatic, but may facilitate the occurrence of metabolic acidosis. Since patients in use of topiramate have refractory epilepsy, they may need epilepsy surgery, and must be carefully monitored for the risk of metabolic acidosis during surgery.

Mixed acid-base disorder secondary to topiramate use in traumatic brain injury

“…[2] With widespread use of topiramte (TPM), there have been case reports of metabolic acidosis secondary to renal acidification defects. [3456] The mechanism involves the inhibition of the enzyme carbonic anhydrase (CA) impairing both the normal proximal reabsorption of filtered HCO 3 − and distal excretion of hydrogen ion. [2] Topiramate-induced renal tubular acidosis can make patients acutely ill and chronically and lead to nephrolithiasis and osteoporosis.…”

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

“…Topiramate is a relatively new neuromodulator that received Food and Drug Administration approval in 1999 for seizure and migraine prophylaxis; the manufacturer issued an alert in 2003 after cases of hyperchloremic metabolic acidosis were reported in children (5,6). The drug has four recognized actions: 1) sodium channel blocker, 2) potentiates gamma-aminobutyric acid, 3) glutamate antagonist, and 4) inhibits isoenzymes of carbonic anhydrase (6)(7)(8). The first three actions account for its intended neurological effects, whereas the fourth action induces a Type 2 renal tubule acidosis (RTA).…”

Hyperchloremic, normal anion-gap, metabolic acidosis due to topiramate

“…[13][14][15][16][17][18] An investigational study has linked topiramate's inhibition of carbonate dehydratase to its ability to cause hyperchloremic, normal anion-gap, metabolic acidosis secondary to decreases in serum bicarbonate. 19 The significance of this mechanism is not completely understood with regard to its contribution to the drug's therapeutic indication. Experimental studies have associated serum bicarbonate ionic current effects with GABA and N-methyl-D-aspartate receptors, which ultimately affect the hippocampus, the origin of known forms of epilepsy.…”