From the Guidelines
Lokelma (sodium zirconium cyclosilicate) works by selectively capturing potassium ions in the gastrointestinal tract in exchange for hydrogen and sodium ions, which are then eliminated through the feces, making it an effective treatment for hyperkalemia. The mechanism of action of Lokelma involves the exchange of potassium ions for hydrogen and sodium ions in the small and large intestines, resulting in the elimination of potassium ions through fecal excretion 1. This selective binding of potassium ions makes Lokelma a highly effective treatment for hyperkalemia, with a rapid onset of action, often beginning to lower potassium levels within 1 hour of administration 1.
Some key characteristics of Lokelma include:
- Highly selective binding of potassium ions, with minimal binding of other ions such as calcium and magnesium
- Rapid onset of action, with significant reductions in serum potassium levels observed within 1 hour of administration
- Effective in both acute and chronic hyperkalemia management, with a recommended initial dose of 10g three times daily for up to 48 hours, followed by a maintenance dose of 5-10g once daily
- Common side effects include edema and hypokalemia, which can be mitigated with regular monitoring of potassium levels and adjustment of the dose as needed
The efficacy and safety of Lokelma have been established in several clinical trials, including a study of emergency department patients with serum potassium concentrations of 5.8 mEq/L or higher, which showed significant reductions in mean serum potassium levels within 2 hours of administration 1. Additionally, a 12-month study of patients with end-stage renal disease and persistent hyperkalemia demonstrated the effectiveness of Lokelma in maintaining normal predialysis serum potassium levels 1.
Overall, Lokelma is a valuable treatment option for hyperkalemia, offering a rapid and effective way to lower potassium levels and reduce the risk of complications associated with hyperkalemia. Its mechanism of action, involving the selective binding of potassium ions in the gastrointestinal tract, makes it an attractive alternative to other treatments, and its efficacy and safety have been well established in clinical trials 1.
From the FDA Drug Label
LOKELMA (sodium zirconium cyclosilicate) is a non-absorbed zirconium silicate that preferentially captures potassium in exchange for hydrogen and sodium. In vitro, LOKELMA has a high affinity for potassium ions, even in the presence of other cations such as calcium and magnesium LOKELMA increases fecal potassium excretion through binding of potassium in the lumen of the gastrointestinal tract. Binding of potassium reduces the concentration of free potassium in the gastrointestinal lumen, thereby lowering serum potassium levels.
The mechanism of action (MoA) of Lokelma (sodium zirconium cyclosilicate) is as a potassium binder that preferentially exchanges potassium for hydrogen and sodium. It works by increasing fecal potassium excretion through binding of potassium in the gastrointestinal tract, which reduces the concentration of free potassium and thereby lowers serum potassium levels 2.
From the Research
Mechanism of Action of Lokelma (Sodium Zirconium Cyclosilicate)
- Lokelma (sodium zirconium cyclosilicate) 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) 3.
- This exchange increases faecal potassium excretion and lowers serum potassium levels 3.
- The potassium lowering action of sodium zirconium cyclosilicate is predictable and rapid, leading to significant reduction of serum potassium within 1 hour of administration by irreversibly eliminating excess potassium rather than acting via intracellular translocation 4.
- Sodium zirconium cyclosilicate has a unique mechanism of action consisting of thermodynamically favorable sequestration of potassium ions, enabling rapid trapping and removal of excess potassium 4.
Key Features of Sodium Zirconium Cyclosilicate
- 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 3.
- Sodium zirconium cyclosilicate was generally well tolerated in adults with hyperkalaemia, with a tolerability profile similar to that seen with placebo over ≤ 28 days, and its safety profile appeared to remain consistent over the longer term (≤ 12 months) 3.
- The incidence of hypokalemia was low 3.