Sevelamer Hydrochloride (Renagel®), a Nonabsorbed Phosphate-Binding Polymer, Does Not Interfere with Digoxin or Warfarin Pharmacokinetics

Authors


GelTex Pharmaceuticals, Inc., 153 Second Avenue, Waltham, MA 02451.

Abstract

Sevelamer hydrochloride (Renagel®) is a nonabsorbed phosphate-binding polymer marketed for the treatment of hyperphosphatemia in adult patients receiving hemodialysis. Sevelamer also exhibits bile acid-binding properties resulting in LDL cholesterol lowering. Potential drug interactions between digoxin and warfarin and sevelamer were studied. These two drugs were chosen because they are known to bind to the bile acid-binding polymers, cholestyramine and colestipol. Studies were single dose, crossover, with or without six 2.4 g doses of sevelamer. Plasma concentrations were determined using validated analytical methods. The pharmacokinetic profiles of digoxin and warfarin were not altered by the simultaneous and continued administration of sevelamer. Values for the ratio of ∞ln[AUC(0-∞)], ln[AUC(0-t)], and ln[Cmax] with and without sevelamer were close to 100%, and the 90% confidence intervals for these ratios were within the 80% to 125% range. It was concluded that sevelamer does not interfere with the absorption or excretion of digoxin or warfarin.

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