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Alkali replacement raises urinary citrate excretion in patients with topiramate‐induced hypocitraturia
Author(s) -
Allan Jhagroo R.,
Wertheim Margaret L.,
Penniston Kristina L.
Publication year - 2016
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/bcp.12751
Subject(s) - topiramate , urine , excretion , urology , urinary system , medicine , kidney stones , chemistry , psychiatry , epilepsy
Aims The aims of this study were to assess (1) the magnitude and temporality of decreased urinary citrate excretion in patients just starting topiramate and (2) the effect of alkali replacement on topiramate‐induced hypocitraturia. Methods Study 1 was a prospective, non‐intervention study in which patients starting topiramate for headache remediation provided pre‐ and post‐topiramate 24 h urine collections for measurement of urine citrate. Study 2 was a clinical comparative effectiveness study in which patients reporting to our stone clinic for kidney stones and who were treated with topiramate were prescribed alkali therapy. Pre‐ and post‐alkali 24 h urinary citrate excretion was compared. Results Data for 12 and 22 patients (studies 1 and 2 respectively) were evaluated. After starting topiramate, urinary citrate excretion dropped significantly by 30 days ( P = 0.016) and 62% of patients had hypocitraturia (citrate <320 mg day –1 ). At 60 days, urine citrate was even lower than at baseline ( P = 0.0032) and 86% of patients had developed hypocitraturia. After starting alkali, urine citrate increased in stone‐forming patients on topiramate (198 ± 120 to 408 ± 274 mg day –1 ; P = 0.042 for difference). 85% of patients were hypocitraturic on topiramate alone vs . 40% after adding alkali. The increase in urinary citrate was greater in patients provided ≥90 mEq potassium citrate. Conclusions Our study is the first to provide clinical evidence that alkali therapy can raise urinary citrate excretion in patients who form kidney stones while being treated with topiramate. Clinicians should consider alkali therapy for reducing the kidney stone risk of patients benefitting from topiramate treatment for migraine headaches or other conditions.