What is the mechanism of action of Lokelma (sodium zirconium cyclosilicate)?

From the Guidelines

Lokelma (sodium zirconium cyclosilicate) works by selectively capturing potassium ions in the gastrointestinal tract through a process of ion exchange, making it an effective treatment for hyperkalemia.

Mechanism of Action

Lokelma's mechanism of action involves the exchange of sodium ions for potassium ions in the gastrointestinal tract, particularly in the colon where potassium concentration is highest 1. This exchange occurs because potassium has a higher binding affinity for the zirconium cyclosilicate structure than sodium does. Once potassium is bound to Lokelma, it becomes non-absorbable and is eliminated from the body through feces, effectively reducing serum potassium levels.

Key Characteristics

Some key characteristics of Lokelma include:

• Highly selective for potassium ions, with minimal binding to other ions such as calcium and magnesium 1
• Onset of action within 1 hour of administration 1
• Does not enter systemic circulation, making it generally well-tolerated 1
• Typically dosed at 10g three times daily for initial treatment, followed by maintenance dosing of 5-10g once daily, adjusted based on serum potassium monitoring 1

Safety and Efficacy

Lokelma has been shown to be effective in reducing serum potassium levels in patients with hyperkalemia, with significant reductions in serum potassium levels observed within 1 hour of administration 1. The medication has also been found to be generally well-tolerated, with common side effects including edema and hypokalemia if overused 1. Overall, Lokelma is a safe and effective treatment option for patients with hyperkalemia, with a mechanism of action that makes it an attractive alternative to other potassium-binding agents.

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 of Lokelma is to preferentially capture potassium in exchange for hydrogen and sodium, increasing fecal potassium excretion and reducing serum potassium levels 2.

• The drug works by binding to potassium in the gastrointestinal tract, reducing the concentration of free potassium and thereby lowering serum potassium levels.
• Lokelma has a high affinity for potassium ions, even in the presence of other cations such as calcium and magnesium.
• The key mechanism is the exchange of potassium for hydrogen and sodium, which leads to increased fecal potassium excretion and decreased serum potassium levels 2.

From the Research

Lokelma Mechanism

• Lokelma, also known as sodium zirconium cyclosilicate (SZC), is a non-absorbed, non-polymer zirconium silicate compound that works by exchanging hydrogen and sodium for potassium and ammonium ions in the gastrointestinal tract (GIT) 3.
• This mechanism increases faecal potassium excretion and lowers serum potassium levels, making it an effective treatment for hyperkalaemia in adults 3, 4.
• SZC has been shown to be generally well tolerated in adults with hyperkalaemia, with a tolerability profile similar to that of placebo over 28 days, and a safety profile that remains consistent over the longer term (≤ 12 months) 3.
• The incidence of hypokalemia with SZC is low, making it a promising therapy for the management of hyperkalaemia in adults 3.

Key Features of Lokelma

• Preferentially exchanges hydrogen and sodium for potassium and ammonium ions in the GIT 3.
• Increases faecal potassium excretion and lowers serum potassium levels 3, 4.
• Available as a powder for oral suspension (in water) and approved in the EU and the USA for the treatment of hyperkalaemia in adults 3.
• Can be used to initiate, maintain, or titrate renin-angiotensin-aldosterone system inhibitors in patients with hyperkalaemia 4, 5.

Comparison with Other Treatments

• SZC has been compared to patiromer, another oral potassium binder, in the management of acute hyperkalemia, with no significant difference in effectiveness between the two medications 6.
• SZC has also been compared to sodium polystyrene sulfonate (SPS), with SZC showing improved efficacy and safety profiles 4.