Topiramate and metabolic acidosis in pediatric epilepsy.
OBJECTIVE
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 acidosis from decreased serum bicarbonate (HCO3-).


METHODS
Clinical data from 30 children who received TPM as adjunctive therapy for medically refractory epilepsy were reviewed at Children's Hospital, Boston. Serum HCO3- levels were assessed before, during, and after discontinuing 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 mean decrease in HCO3- among the 21 patients was 4.7 mEq/L, and maximum was 10 mEq/L. No clinical symptoms occurred, and HCO3- supplement was not needed, except for one patient who developed tachypnea from worsened acidosis after prolonged status epilepticus during a suspected viral illness. Among the 21 patients, TPM was discontinued in seven children because of a lack of efficacy, 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 reviewed, usually only to a small to moderate extent, but by 8 and 10 mEq/L in two cases. In patients at risk for acidosis, the decrease in HCO3- may cause significant consequences, such as severe acidosis or renal calculi. Monitoring HCO3- levels before and during TPM therapy may be indicated, especially with conditions that predispose to acidosis.
Takeoka
M
M
Department of Neurology, Children's Hospital, and Harvard Medical School, Boston, Massachusetts, USA. maxtakeoka@aol.com
Holmes
G L
GL
Thiele
E
E
Bourgeois
B F
BF
Helmers
S L
SL
Duffy
F H
FH
Riviello
J J
JJ
D000138:Acidosis / Q000097:blood / Q000139:chemically induced* / Q000453:epidemiology; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000927:Anticonvulsants / Q000009:adverse effects* / Q000097:blood / Q000627:therapeutic use; D001639:Bicarbonates / Q000097:blood; D002257:Carbonic Anhydrase Inhibitors / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004827:Epilepsy / Q000097:blood / Q000188:drug therapy*; D005632:Fructose / Q000009:adverse effects* / Q000031:analogs & derivatives / Q000097:blood / Q000627:therapeutic use; D006801:Humans; D007223:Infant; D000077236:Topiramate
D000927:Anticonvulsants; D001639:Bicarbonates; D002257:Carbonic Anhydrase Inhibitors; D000077236:Topiramate; D005632:Fructose