Mechanism of Action of Lokelma (Sodium Zirconium Cyclosilicate)
Lokelma reduces serum potassium by selectively binding potassium ions throughout the entire gastrointestinal tract in exchange for hydrogen and sodium ions, thereby increasing fecal potassium excretion. 1, 2
Ion Exchange Mechanism
Lokelma is a non-absorbed zirconium silicate compound that functions as a selective cation exchanger, preferentially capturing potassium (K+) and ammonium ions while releasing hydrogen (H+) and sodium (Na+) ions in the GI tract. 3
The drug works throughout both the small and large intestines, which distinguishes it from older potassium binders like sodium polystyrene sulfonate that act primarily in the colon. 2 This broader site of action may explain its rapid onset and effectiveness across a larger intestinal surface area. 2
Each 5-gram dose contains 400 mg of sodium that is theoretically available for absorption as potassium is bound and sodium is released. 1
Clinical Pharmacodynamics
The onset of action is remarkably rapid, with median time to potassium normalization of 2.2 hours when using the initial dosing regimen of 10g three times daily. 4
At 48 hours, 98% of patients achieve normokalemia (serum potassium 3.5-5.0 mEq/L) with the initial treatment phase. 4
The potassium-lowering effect is dose-dependent: at 48 hours, mean serum potassium reductions are approximately 0.5 mmol/L with 5g three times daily and 0.7 mmol/L with 10g three times daily. 5
Additional Metabolic Effects
- Lokelma causes a dose-dependent increase in serum bicarbonate concentrations due to the exchange of hydrogen ions for potassium. 1 This produces increases of 1.1 mmol/L with 5g daily, 2.3 mmol/L with 10g daily, and 2.6 mmol/L with 15g daily. 1 This effect may provide additional benefit for patients with metabolic acidosis, which is common in chronic kidney disease. 1
Independence from Renal Function
- The mechanism of action is completely independent of kidney function since the drug works entirely within the GI tract and is not systemically absorbed. 6 This makes it effective regardless of residual renal function or dialysis status, with no dose adjustment required based on eGFR. 6
Clinical Context from Guidelines
The 2022 AHA/ACC/HFSA Heart Failure Guidelines acknowledge that sodium zirconium cyclosilicate lowers potassium levels and enables continuation of RAAS inhibitor therapy in patients with heart failure, though the guidelines note that the effectiveness for improving long-term outcomes remains uncertain. 7
The Mayo Clinic recommends 10g three times daily for initial treatment, which reduces serum potassium by approximately 1.1 mEq/L during the 48-hour treatment period, followed by maintenance dosing of 5-15g once daily. 1