Topiramate and metabolic acidosis in infants and toddlers

Topiramate (TPM) inhibits carbonic anhydrase, with metabolic acidosis as a possible side effect, although this has been reported in only two adult cases. We investigated the acid-base metabolism in infants and toddlers treated with TPM.

Nine infants and toddlers aged 5 months to 2.3 years (median, 6 months) were treated with TPM at maximal doses of 8.2-26 mg/kg/day (median, 11 mg/kg/day). The maximal TPM dose was achieved after 8-35 days (median, 17 days). TPM was given in addition to other antiepileptic drugs (AEDs) in five cases and as a sole AED in four patients with refractory epilepsy resistant to multiple AEDs. The diagnoses were infantile spasms (n = 5), epilepsia partialis continua (n = 1), infantile epileptic encephalopathy (n = 1), and Lennox-Gastaut syndrome (n = 2).

The blood gases were normal before treatment with TPM in all nine children. Metabolic acidosis developed in eight children after 8-26 days (median, 14 days) of TPM treatment with a minimum of serum bicarbonate between 15 to 18 mM (median, 17 mM), a minimal base excess between -6.2 and -11.2 mM (median, -7.9 mM), and pH between 7.22 and 7.40 (median, 7.35). Four of nine children showed clinical signs of hyperventilation and received oral sodium bicarbonate (1-2 mmol/kg), while TPM was still effective.

Because metabolic acidosis developed in eight of the nine infants and toddlers taking TPM, we would suggest that the acid-base metabolism be monitored in young children who receive TPM.