Sodium Zirconium Cyclosilicate: A Review in Hyperkalaemia

Abstract

Sodium zirconium cyclosilicate (Lokelma™) [hereafter referred to as SZC] is a non-absorbed, non-polymer zirconium silicate compound that preferentially exchanges hydrogen and sodium for potassium and ammonium ions in the gastrointestinal tract (GIT), thereby increasing faecal potassium excretion and lowering serum potassium levels. It is available as a powder for oral suspension (in water) and is approved in the EU and the USA for the treatment of hyperkalaemia in adults. In two multinational, phase III studies in adults with hyperkalaemia, SZC 10 g three times daily lowered serum potassium levels to within the normal range (3.5–5.0 mmol/L) during the first 48 h of treatment, and SZC 5 and 10 g once daily maintained normokalaemia over ≤ 28 days’ therapy. These beneficial effects were consistent across all patient subgroups (e.g. chronic kidney disease, diabetes, heart failure, concomitant use of RAAS inhibitor therapy), and appeared to be maintained over the longer term (≤ 12 months). SZC was generally well tolerated in adults with hyperkalaemia. Its tolerability profile was generally similar to that seen with placebo over ≤ 28 day, and its safety profile appeared to remain consistent over the longer term (≤ 12 months). Moreover, the incidence of hypokalemia was low. Current evidence indicates that SZC is a promising therapy for the management of hyperkalaemia in adults.

Potassium Binders for Hyperkalemia in Chronic Kidney Disease—Diet, Renin-Angiotensin-Aldosterone System Inhibitor Therapy, and Hemodialysis

“…83,84 Sodium zirconium cyclosilicate was generally well tolerated in phase 2 and phase 3 trials, with an incidence of gastrointestinal adverse events similar to that of placebo, and a dose-related increase in the incidence of mild to moderate edema in patients during maintenance dosing resolved spontaneously or with diuretic therapy (edema was more common in patients treated with SZC 15 gdthe highest dose of SZC in clinical trials). 33,56,85 Hypokalemia that resolved with dose reductions or discontinuation of SZC was also reported in clinical trials. 35 Ongoing trials are also investigating the effect of SZC in optimizing RAAS inhibitor therapy and in rapid reduction and normalization of serum K þ in an emergency setting.…”

“…In a study of approximately 4500 patients initiating therapy with SPS, only 49.8% continued treatment for more than 7 days and less than 10% continued for more than 60 days. 32 Recently, 2 new K þ -binding drugs were approved by the US Food and Drug Administration (FDA) for the treatment of hyperkalemia: sodium zirconium cyclosilicate (SZC; formerly ZS-9), a nonpolymer compound that exchanges K þ for sodium and hydrogen ions in the gastrointestinal tract, 33 and patiromer, a polymer that exchanges K þ for calcium ions in the gastrointestinal tract 34…”

New Treatment Options for Hyperkalemia in Patients with Chronic Kidney Disease

“…In phase 2 and 3 trials, the incidence of gastrointestinal adverse events (nausea, constipation, vomiting or diarrhea) was similar between the treated group and the placebo group [78]. However, as was the case for patiromer, SZC should also not be used in patients with severe constipation, bowel obstructions or impaction, including abnormal postoperative bowel motility disorders [79].…”

Hyperkalemia in heart failure: current treatment and new therapeutic perspectives

“…SZC is a non-absorbable polymer consisting of a threedimensional crystal lattice capable of selectivity trapping K + ions by exchanging them with sodium and hydrogen at the level of the colon and small intestine (Hoy, 2018;Stavros et al, 2014). Hy-drogen ions are more exchangeable, while sodium remains in part linked to the structure, thus avoiding dangerous hypernatremia.…”