2244 TOPIRAMATE RESULTS IN A RAPID AND PROGRESSIVE DECLINE IN URINARY CITRATE OVER 60 DAYS: A PROSPECTIVE STUDY

Abstract

INTRODUCTION AND OBJECTIVES: Topiramate is commonly prescribed for migraine headaches and, recently, weight loss. It exerts a well-known hypocitraturic effect. We characterized the time course to hypocitraturia, a risk factor for calcium lithiasis. METHODS: Under IRB approval, headache clinic providers offered participation to adult patients starting topiramate; a titrated dosage regimen reaching 100-200 mg/d within 1 month was prescribed. Patients withheld initiation until a baseline 24-h urine collection could be done. After starting topiramate, patients provided 24-h urine collections at 30 and 60 d for comparison. RESULTS: Twelve patients (M:F, 0.71; 38 y) were recruited from 9/2011-4/2012 and contributed complete 24-h urine collections, confirmed by 24-h urinary creatinine excretion. At baseline, 83% (n 10) were normocitraturic (urinary citrate 581 274 mg/d); 2 patients were mildly hypocitraturic (250 39 mg/d). At 30 d, mean urinary citrate excretion decreased nearly 300 mg and averaged 279 121 mg/d; it continued to decrease through 60 d (218 82 mg/d), at which time, 83% (6 of 7 patients with 24-h urine analyses) were hypocitraturic (196 64 mg/d for 6 with hypocitraturia). Paired t-tests confirmed differences in urinary citrate between baseline and 30-d and between baseline and 60-d (p 0.01 and 0.002, respectively) but not between 30 and 60 d, though the 22% decline in mean urinary citrate excretion from 30 to 60 d is nonetheless clincally relevant. Urine pH increased from 6.1 at baseline to 6.6 and 6.5 at 30and 60-d, respectively (p 0.04 for each comparison), increasing brushite supersaturation of urine. No patients reported stone events in the 6-12 month evaluation period. Of 8 hypocitraturic patients offered potassium citrate therapy (30 mEq/d), 4 agreed to initiate it. In the 1 patient from this group who has thus far completed a follow-up 24-h urine collection, urinary citrate excretion increased 102 mg/d within 2 weeks. CONCLUSIONS: Hypocitraturia from topiramate is rapid and progressive. This should be taken into account when starting therapy, particularly in patients with a history of urolithiasis or with identifiable lithogenic risk factors. Potassium citrate should be considered as adjunctive therapy in select individuals, and urinary citrate excretion should be monitored to ensure therapeutic effect.