Metabolic acidosis with topiramate and zonisamide: an assessment of its severity and predictors

Objective Carbonic anhydrase (CA) inhibitors topiramate and zonisamide can induce metabolic acidosis in some patients. Our aims were to assess the prevalence and severity of this acidosis and to determine its predictors. Methods For 70 patients established on treatment with topiramate (n = 55) or zonisamide (n = 14) or both (n = 1), we measured electrolytes, and genotyped single nucleotide polymorphisms (SNPs) in the main renal CA isoenzymes (II, IV and XII). Results Twenty-six percent of patients had a metabolic acidosis (serum bicarbonate < 20 mmol/l). The mean serum bicarbonate of patients taking topiramate was significantly lower than those taking zonisamide (P = 0.002). We found no association between serum bicarbonate and the dose of drug or the duration of treatment. Serum bicarbonate levels were associated with the CA type XII SNPs rs2306719 (P = 0.006 by one-way analysis of variance) and rs4984241 (P = 0.015), but this association was not strong enough to survive correction for multiple testing. Conclusion The development of acidosis with topiramate and zonisamide is not determined by drug dose or by treatment duration, but may be influenced by polymorphisms in the gene for CA type XII. The aforementioned SNPs lie 9.8 kb apart in intron 1 of the CA type XII gene, and deserve further study in a larger cohort of patients. Pharmacogenetics and Genomics 21:297-302 (C) 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.