Zonisamide and renal calculi in patients with epilepsy: how big an issue?
OBJECTIVE
To determine the prevalence of renal calculi in patients treated with zonisamide during randomized, controlled and open-label clinical trials, and from post-marketing surveillance data.


METHODS
Reports of renal calculi from four placebo-controlled double-blind trials of zonisamide, their long-term open-label treatment extension phases, and the US/European zonisamide clinical trial programme were reviewed. One double-blind study and its extension included routine ultrasound screening to identify asymptomatic calculi. Post-marketing surveillance data were also investigated, as was concomitant treatment with topiramate.


RESULTS
No symptomatic renal calculi were reported during four randomized double-blind, placebo-controlled trials involving 848 subjects (including 498 zonisamide recipients) treated for up to 3 months. In long-term extension studies with treatment for up to 24 months, symptomatic renal calculi were reported in 9/626 (1.4%) patients. Pooled safety data from all US/European clinical trials identified 15/1296 (1.2%) patients with symptomatic renal calculi during treatment for up to 8.7 years. Post-marketing surveillance revealed nine cases from 59 667 patient-years of exposure in the USA, and 14 from 709 294 patient-years of exposure in Japan; only one case occurred during concomitant topiramate and zonisamide treatment. No imbalance in electrolyte levels was found from 35 patients receiving such co-treatment in clinical trials.


CONCLUSIONS
The available data suggest that the risk of developing renal calculi during zonisamide treatment is low. Data are insufficient to determine whether concomitant treatment with topiramate increases the risk of renal stones.
Wroe
Stephen
S
National Hospital for Neurology & Neurosurgery, Queen Square, London, UK. S.wroe@prion.ucl.ac.uk <wroe@prion.ucl.ac.uk>
D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D004311:Double-Blind Method; D004827:Epilepsy / Q000188:drug therapy*; D005260:Female; D005632:Fructose / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use; D006801:Humans; D007555:Isoxazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007669:Kidney Calculi / Q000139:chemically induced* / Q000000981:diagnostic imaging; D008297:Male; D008875:Middle Aged; D010919:Placebos; D011358:Product Surveillance, Postmarketing; D000077236:Topiramate; D014463:Ultrasonography; D000078305:Zonisamide
D000927:Anticonvulsants; D007555:Isoxazoles; D010919:Placebos; D000077236:Topiramate; D005632:Fructose; D000078305:Zonisamide