Topiramate and metabolic acidosis in infants and toddlers.
OBJECTIVE
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.
Philippi
Heike
H
Department of Pediatrics, Johannes Gutenberg-University, Mainz, Germany. philippi@kinder.klinik.uni-mainz.de
Boor
Rainer
R
Reitter
Bernd
B
D000136:Acid-Base Equilibrium / Q000187:drug effects; D000138:Acidosis / Q000139:chemically induced* / Q000378:metabolism; D000367:Age Factors; D000927:Anticonvulsants / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D001639:Bicarbonates / Q000097:blood; D001784:Blood Gas Analysis; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004827:Epilepsy / Q000188:drug therapy* / Q000378:metabolism; D005500:Follow-Up Studies; D005632:Fructose / Q000009:adverse effects* / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D007223:Infant; D000077236:Topiramate; D016896:Treatment Outcome
D000927:Anticonvulsants; D001639:Bicarbonates; D000077236:Topiramate; D005632:Fructose