Sodium Zirconium Cyclosilicate (ZS-9): A Novel Agent for the Treatment of Hyperkalemia

Kristin E Linder, Michelle A Krawczynski, Dayne Laskey
Pharmacotherapy 2016, 36 (8): 923-33
Hyperkalemia is a potentially life-threatening electrolyte abnormality that may be caused by select medications, underlying organ dysfunction, or alterations in potassium homeostasis. Treatment for this condition has remained largely unchanged since the release of sodium polystyrene sulfonate (SPS) in 1958. Despite its widespread use, the safety and efficacy of SPS remains controversial. Two novel potassium-binding resins have emerged in recent years. Patiromer was the first of these to receive U.S. Food and Drug Administration approval for the treatment of hyperkalemia in October 2015. A second potassium-binding resin, a zirconium cyclosilicate currently known as ZS-9, may provide yet another alternative to the archetypal treatment with SPS. ZS-9 is an orally administered nonabsorbed inorganic compound that selectively binds potassium ions in vivo. Two phase III multicenter, randomized, placebo-controlled, double-blind trials have evaluated ZS-9 for the treatment of acute hyperkalemia. In this review, we discuss the pharmacology, clinical efficacy, safety, and potential place in therapy of ZS-9 for the enhanced elimination of potassium in the setting of hyperkalemia.


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