Topiramate and metabolic acidosis in pediatric epilepsy

Purpose: Topiramate (TPM) has been widely used as an adjunctive therapy for treating epilepsy. TPM is reported to have multiple mechanisms of action, including inhibition of carbonic anhydrase, which may result in metabolic a cidosis from decreased serum bicarbonate (HCO3-). Methods: Clinical data from 30 children who received TPM as adjunctive ther apy for medically refractory epilepsy were reviewed at Children's Hospital, Boston. Serum HCO3-levels were assessed before, during, and after disconti nuing TPM (n = 9). When multiple data were available, mean values were used for analysis. Results: Of the 30 patients, 21 had a >10% decrease in HCO3- levels. The me an decrease in HCO3- among the 21 patients was 4.7 mEq/L, and maximum was 1 0 mEq/L. No clinical symptoms occurred, and HCO3- supplement was not needed , except for one patient who developed tachypnea from worsened acidosis aft er prolonged status epilepticus during a suspected viral illness. Among the 21 patients, TPM was discontinued in seven children because of a lack of e fficacy, and in two because of anorexia. After discontinuing TPM, the serum HCO3- returned to the previous level before starting TPM in all nine. Conclusions: Decreased HCO3- levels occurred in the majority of patients re viewed, usually only to a small to moderate extent, but by 8 and 10 mEq/L i n two cases. In patients at risk for acidosis, the decrease in HCO3- may ca use significant consequences, such as severe acidosis or renal calculi. Mon itoring HCO3- levels before and during TPM therapy may be indicated, especi ally with conditions that predispose to acidosis.