An In-Depth Pharmacological and Clinical Review of Sevelamer (DB00658): From Phosphate Binding to Pleiotropic Effects

Executive Summary

1.1 Overview

Sevelamer is a non-absorbable, calcium- and metal-free polymeric phosphate binder developed for the management of hyperphosphatemia, a common and serious complication of chronic kidney disease (CKD).[1] Its primary clinical application is in patients with advanced CKD, particularly those undergoing hemodialysis or peritoneal dialysis, where impaired renal phosphate excretion leads to dangerously elevated serum phosphorus levels.[2] Sevelamer functions locally within the gastrointestinal (GI) tract by binding to dietary phosphate, thereby preventing its systemic absorption and helping to control serum phosphorus concentrations.[5]

1.2 Key Formulations and Mechanism

The drug is commercially available in two principal salt forms: sevelamer hydrochloride, marketed as Renagel®, and sevelamer carbonate, marketed as Renvela®.[1] The carbonate formulation was subsequently developed to address a key clinical limitation of the original hydrochloride salt—the potential for its chloride load to contribute to or exacerbate metabolic acidosis, a prevalent issue in the CKD population.[8] The fundamental mechanism of action is identical for both forms and relies on the drug's polymeric structure. Within the gut, the numerous amine groups on the polymer become protonated, acquiring a positive charge that allows them to form strong ionic and hydrogen bonds with negatively charged phosphate ions from ingested food.[1] This chelation process creates a large, insoluble complex that is excreted in the feces, effectively removing phosphate from the body before it can be absorbed.[1]

1.3 The Pleiotropic Profile