To the Editor: Although Drs LaRoche and Helmers1 discussed many of the important safety issues for new antiepileptic drugs in their Scientific Review article, additional safety issues have arisen with topiramate and zonisamide since their initial approval. Some of these safety issues may be related to the ability of these drugs to inhibit the enzyme carbonic anhydrase.
For topiramate, a warning describing a syndrome of acute myopia with secondary angle-closure glaucoma associated with treatment was added to the product labeling in 2001.2 It is important to note that although this adverse event is uncommon, prompt discontinuation of topiramate is imperative and appears to reverse the process. In 2003, a further warning was added for oligohydrosis, which is characterized by deficient formation and secretion of sweat that can lead to life-threatening fevers and heat stroke. This adverse effect may be more significant in children than in adults treated with topiramate3 and may be especially problematic in summer and in warm climates. A warning for metabolic acidosis was also added in 2003: topiramate use is associated with a hyperchloremic, non–anion gap metabolic acidosis and decreased serum bicarbonate levels. Some manifestations of chronic, untreated metabolic acidosis include bone loss and increased risk of fractures. Chronic metabolic acidosis can lead to growth retardation in children. The product labeling recommends baseline and periodic serum bicarbonate measurements during topiramate treatment. If metabolic acidosis develops and persists, then a dose reduction or discontinuation of topiramate should be considered.
Regarding zonisamide, the authors stated that "in the pediatric population there have been rare reports of high fever secondary to hyperhidrosis." We point out that similar to the situation with topiramate, the high fevers are secondary to oligohydrosis, not hyperhidrosis.4 Pediatric age appears to be a risk factor for zonisamide-induced oligohydrosis.4 Patients should be warned about the potential for oligohydrosis, particularly during summer and in warm climates.
Additionally, literature reports have linked zonisamide to metabolic acidosis,5 which may be related to inhibition of carbonic anhydrase.
Updates on drug-specific safety information can be obtained at http://www.fda.gov/medwatch.
Disclaimer: This letter expresses the views of the authors and does not necessarily represent those of the US Food and Drug Administration.
Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature
Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal
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