Rationale & Objective: Driven by expanding indications, topiramate and zonisamide utilization has increased over time. This trend may be associated with greater occurrence of kidney stones given the effects of these medications on urine chemistries. We sought to examine the relationship between topiramate and zonisamide use and kidney stone risk.
Study Design: Retrospective cohort study.
Setting & Participants: Individuals in Optum's de-identified Clinformatics® Data Mart Database (CDM) and Medicare enrollees with at least one prescription filled for topiramate or zonisamide between January 1, 2011 and September 30, 2019, and age- and sex-matched controls.
Exposure: New topiramate or zonisamide use.
Outcome: Symptomatic stone event defined as an emergency department visit, hospitalization, or surgery for kidney stones.
Analytical Approach: Cox proportional hazards regression.
Results: Among 1,122,301 study participants, 187,032 filled a prescription for topiramate or zonisamide at some point during the study period. The unadjusted cumulative incidence of symptomatic stone events between three months and three years after the first filled prescription were 2.9% and 2.0% among users of topiramate or zonisamide versus 1.2% and 1.3% among nonusers in the CDM and Medicare cohorts, respectively (P<0.001 for each comparison). After controlling for covariates, users had a significantly higher hazard than nonusers of experiencing a symptomatic stone event (CDM cohort: hazard ratio [HR], 1.58 [95% confidence interval {CI}, 1.49 to 1.68]; Medicare cohort: HR, 1.22 [95% CI, 1.11 to 1.34]). There was a stronger association with stone risk among younger adults receiving either topiramate or zonisamide and the hazard of a symptomatic stone event increased with higher topiramate doses.
Limitations: Potential bias in unmeasured differences between users of topiramate or zonisamide and nonusers. Participants may have been diagnosed with kidney stone disease prior to the study period.
Conclusions: Use of Topiramate or zonisamide was associated with an increased hazard of symptomatic stone events. These finding inform the consideration of risks and benefits of these medications.
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