Metabolic acidosis topiramate

Topiramate Difficulties concentrating Metabolic acidosis Kidney stones... 

Metabolic acidosis Hyperchloremic, nonanion gap, metabolic acidosis is associated with topiramate treatment. This metabolic acidosis is caused by renal bicarbonate loss because of the inhibitory effect of topiramate on carbonic anhydrase. Generally, topiramate-induced metabolic acidosis occurs early in treatment, although cases can occur at any time during treatment. Bicarbonate decrements usually are mild to moderate rarely, patients can experience severe decrements to values below 10 mEq/L. Conditions or therapies that predispose to acidosis may be additive to the bicarbonate lowering effects of topiramate. If metabolic acidosis develops and persists, consider reducing the dose or discontinuing topiramate. 

Since topiramate can be associated with metabolic acidosis in both children and adults the incidence and magnitude of the effect of topiramate on serum bicarbonate concentrations in an adult population have been evaluated in a retrospective cohort study in 54 patients (40 women), of whom 26 had low serum bicarbonate concentrations while taking topiramate (mean concentration 18.8 mmol/1, range 13-21) (1131). However, this was not associated with any clinically significant problems. 

Topiramate lowers serum bicarbonate by inhibiting carbonic anhydrase. In 20 of 29 children there was a greater than 10% fall in serum bicarbonate after starting topiramate (mean absolute reduction 4.7 mmol/1), but none had significant sjmptoms of metabohc acidosis, except possibly for anorexia in one (44). In another report, mild to moderate metabolic acidosis (bicarbonate concentrations, 16-21 mmol/1) developed in three topiramate-treated patients aged 25-51 years the condition was not considered clinically significant, but it led to diagnostic tests to exclude other causes (45). 

Mental changes and metabolic acidosis can occur with topiramate, through inhibition of carbonic anhydrase. 

A 20-year-old man taking topiramate, valproate, and phenytoin had acute mental changes with hyperchloremic metabolic acidosis (46). He had been receiving a modest dose of topiramate for 9 months. His mental status returned to normal within 48 hours of withdrawal. 

Two children developed symptomatic metabolic acidosis while taking topiramate (47). 

An 11-year-old boy with refractory partial epilepsy who had been taking topiramate 300 mg/day for 13 months developed hyperventilation. He had a hyperchloremic metabolic acidosis with partial respiratory compensation. The hyperventilation and acidosis resolved after the administration of sodium bicarbonate and reduction of the dose of topiramate. 

Ko CH, Kong CK. Topiramate-induced metabolic acidosis report of two cases. Dev Med Child Neurol 2001 43(10) 701. ... 

A young woman developed a symptomatic non-anion gap metabolic acidosis, with dyspnea and confusion, believed to have been caused by topiramate [295 ]. She was given intravenous fluids and sodium bicarbonate and was later intubated. After topiramate withdrawal, she recovered completely over 72 hours. 

In a 37-year-old woman who took a massive topiramate ingestion there was prolonged coma, with normal vital signs and a non-anion gap metabolic acidosis [300 ]. 

Shiber JR. Severe non-anion gap metabolic acidosis induced by topiramate a case report J Emerg Med 2010 38(4) 494-6. 

Drug overdose Of 16 796 toxic exposures to antiepileptic drugs (phenytoin, valproic acid, and carbamazepine) in the USA in 2006, 12 resulted in death, as reported by the US Toxic Surveillance System [67 ]. Some specific problems determined by overdose of some old and new antiepileptic drugs have been briefly reviewed. For example, topiramate can cause a significant metabolic acidosis, lamotrigine Stevens-Johnson syndrome, oxcarbazepine hyponatremia, and levetiracetam psychosis. Possible adoption of guidelines for critical care management of overdose are discussed. 

Add-base balance In some patients topiramate can cause metabolic acidosis, whose susceptibility factors, underlying mechanisms, and clinical effects have been reviewed [318 ]. Topiramate impairs both the normal reabsorption of filtered HCO by the proximal renal tubule and the excretion of by the distal renal tubule. This combination of defects is termed mixed renal tubular acidosis. The mechanism involves inhibition of carbonic anhydrase. This mechanism can make patients acutely ill, and chronically can lead to nephrolithiasis, osteoporosis, and in children growth retardation. The usefulness of monitoring HCO concentrations has not been proven and is not routine. Hence, there is no proven method for predicting or preventing the effect of topiramate on acid-base balance. However, patients with a history of renal calculi or known mixed renal tubular acidosis should not receive topiramate. 

Another case of topiramate-induced metabolic acidosis has been discussed [319 ]. 

Drug overdose Seven cases of acute topiramate toxicity observed in two clinical units of poison centers have been described [333" ]. The doses of topiramate were 11-218 mg/kg. Somnolence was characteristic and vertigo, agitation, and mydriasis were less common. There was a metabolic acidosis in four cases. One patient who had not previously taken topiramate and who had taken 31 mg/kg had three secondarily generalized tonic-clonic seizures. All recovered without sequelae and were discharged after 4-8 days. 

Mathews KD, Stark JE. Hyperchloremic, normal anion-gap, metabolic acidosis due to topiramate. Am J Health Syst Pharm 2008 65(15) 1430-4. 

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