Nephrolithiasis topiramate

Drugs that inhibit carbonic anhydrase (acetazolamide, topiramate, and zonisamide) are associated with a small risk (up to 1.5%) of nephrolithiasis. Increased excretion of V-acetyl-beta-glucosaminidase, a marker of renal tubular integrity, has been reported with valproate and carbamazepine, but it is probably not clinically significant (SEDA-18, 60). 

By inhibiting carbonic anhydrase, topiramate reduces the urinary excretion of citrate and increases urinary pH, leading to higher calcium phosphate saturation and a risk of nephrolithiasis. During 1074 patient-years of topiramate exposure in 1183 patients, 18 (1.5%) had 21 episodes of renal calcuh, suggesting an incidence of nephrohthiasis comparable to that reported for acetazol-amide (SEDA-20, 66). 

The most common side-effects of topiramate are paresthesia (27%), headache (21%), fatigue (20%), dizziness (14%), somnolence (1 3%), anorexia (11%), and weight loss (11 %). Less common side-effects, but with important clinical implications, are depression (7%), difficulty with concentration (7%), and confusion (5%). " As with other anhydrase inhibitors, topiramate has been associated with kidney-stone formation, and the incidence of nephrolithiasis is estimated to be 2-4 times higher than that expected in a similar untreated population. Many of the central nervous system effects of topiramate, including cognitive complaints, can be managed by gradual introduction and dose escalation. ... 

Wasserstein AG, Rak I, Reife RA. Nephrolithiasis during treatment with topiramate. Epilepsia 1995 36(Suppl 3) S153. 

Add-base balance In some patients topiramate can cause metabolic acidosis, whose susceptibility factors, underlying mechanisms, and clinical effects have been reviewed [318 ]. Topiramate impairs both the normal reabsorption of filtered HCO by the proximal renal tubule and the excretion of by the distal renal tubule. This combination of defects is termed mixed renal tubular acidosis. The mechanism involves inhibition of carbonic anhydrase. This mechanism can make patients acutely ill, and chronically can lead to nephrolithiasis, osteoporosis, and in children growth retardation. The usefulness of monitoring HCO concentrations has not been proven and is not routine. Hence, there is no proven method for predicting or preventing the effect of topiramate on acid-base balance. However, patients with a history of renal calculi or known mixed renal tubular acidosis should not receive topiramate. 

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