When topiramate is given as monotherapy, approximately 85% of an administered dose is excreted in the urine as unchanged drug. In combination therapy, the proportion of topiramate cleared by the kidney decreases because of hepatic enzyme induction. The clearance of topiramate is decreased by 42% in patients with moderate renal impairment (creatinine clearance 30–69 mL/min/1.73m2) and by 54% in subjects with severe impairment (creatinine clearance less than 30mL/min/1.73m2).70 A reduction in the dosing rate for topiramate is recommended for patients with moderate or severe renal impairment.
Topiramate is water soluble and weakly protein bound. Significant amounts of topiramate are cleared during hemodialysis.70 Its plasma concentration may fall below the minimum needed to maintain antiepileptic effect.70 Thus, a supplemental dose of topiramate may be required before dialysis.
Unfortunately, there are no guidelines for determining the size of the supplemental dose. Because the volume of distribution for topiramate has not been determined, the equation shown in Correction for drug loss during hemodialysis cannot be used to compute a loading dose.
The elimination half-life of topiramate is 21 hours in healthy subjects, and the clearance of topiramate is decreased by 50% in severe renal impairment.70 These figures suggest that the elimination half-life of topiramate is 36 hours in patients with severe renal insufficiency. Thus, a supplemental dose equal to the dose administered over 36 hours would supply one-half of the drug needed to produce a peak plasma concentration.
Reviewed and revised February 2004 by Steven C. Schachter, MD, epilepsy.com Editorial Board.
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