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RESEARCH PRODUCT

Topiramate and Metabolic Acidosis in Infants and Toddlers

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Summary:  Purpose: 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. Methods: 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). Results: 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. Conclusions: 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.