Elevated Sweat Chloride Level in Children Without Cystic Fibrosis Receiving Topiramate or Zonisamide (original) (raw)
"Background: Topiramate and zonisamide are used as anticonvulsant medications in children, and Topiramate is also used for migraine prophylaxis. There are reports of topiramate and zonisamide causing oligohydrosis as a side-effect (Clin Neuropharmacol 2008; 31: 339-346, Pediatr Neurol 2003; 28: 184-189), but their effect on sweat chloride levels has not been studied systematically (Indian Pediatr 2008; 45: 238-240). Hypothesis: Topiramate and zonisamide not only reduce sweat production, but they can also cause elevation of sweat electrolytes. Methods: Eighteen patients who were receiving topiramate or zonisamide therapy for at least 6 months were enrolled either from Neurology outpatient clinic or Epilepsy Monitoring Unit, and were only included in the study if they had no signs or symptoms and a negative family history of cystic fibrosis. Patients underwent pilocarpine iontopheresis and sweat collection via Macroduct system (Wescor Inc., Logan, UT) as per Clinical and Laboratory Standards Institute (CLSI) and Cystic Fibrosis Foundation (CFF) guidelines. The samples were analyzed the same day using a chloridometer and the mean sweat chloride values were compared to published normative data (J Pediatr 2008; 153: 758-63) by Student’s t-test. Results: Of the 18 pts (age range 3-22 years, mean age 9.94 years, sex ratio M:F = 0.44) that were enrolled for this study, 14 adequate samples (>15 µL volume) could be obtained from left arm, and 13 from right arm. There were 14 patients on topiramate and 4 were receiving zonisamide. The mean sweat chloride level was 41.77 ± 18.71 mEq/L from the left arm and 46.475 ± 19.29 mEq/L from the right arm for patients receiving topiramate. For patients on Zonisamide therapy, the mean sweat chloride level was 29.83 ± 10.00 mEq/L from the left arm, and 36.5 ± 3.54 mEq/L from the right arm. Sweat chloride values and volumes did not correlate with dose of either anticonvulsant (p=0.5). Overall 7/14 (50%) patients on topiramate or zonisamide had either a borderline (> 40 mEq/L but < 60 mEq/L) or elevated (> 60 mEq/L) sweat chloride test result. Comparing these results to the standard reference values for sweat chloride in the normal population, the mean sweat chloride level of patients on topiramate was noted to be significantly higher (p<0.001) for both arms. There was no significant difference in the mean values for sweat chloride between the topiramate and zonisamide groups for both sides (p>0.05). The insufficient sweat collection rate was 3/18 (17%) for both arms, and another 3/18 had insufficient sweat collected from one of the arms. This rate is much higher than the goal of <5% inadequate sweat collection rate that is established by CFF for accredited sweat testing laboratories, and suggests that drug-induced oligohydrosis is operative in this patient population. Conclusions: Topiramate and zonisamide can not only cause oligohydrosis, but they can also elevate sweat chloride levels in patients with no clinical features of cystic fibrosis. Further studies to explore whether this is due to interaction with CFTR or via a different mechanism, are underway."
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