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

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From the Guidelines

Lokelma (sodium zirconium cyclosilicate) works by binding potassium ions in exchange for hydrogen and sodium ions in the gastrointestinal tract, specifically in the small and large intestines, leading to the elimination of potassium through fecal excretion. This mechanism of action is highly selective for potassium ions, with the added ability to bind ammonium ions as well 1. The onset of action for Lokelma is relatively quick, starting to lower potassium levels within 1 hour of administration 1.

Key Characteristics of Lokelma

  • High selectivity for potassium ions: Lokelma is highly selective for potassium ions, which reduces the risk of binding to other essential ions like calcium and magnesium 1.
  • Rapid onset of action: With an onset of action of 1 hour, Lokelma can quickly help manage hyperkalemia 1.
  • Site of action: The medication acts in both the small and large intestines, providing a broader range of action compared to some other potassium-binding agents 1.
  • Dosing: The initial dosing for correction of hyperkalemia is 10g three times daily, which can be adjusted for maintenance therapy 1.

Clinical Considerations

The use of Lokelma is particularly beneficial in patients with hyperkalemia due to its selective mechanism of action and relatively fast onset of action. Common side effects include gastrointestinal disorders such as constipation, diarrhea, nausea, and vomiting, as well as mild to moderate edema 1. It's essential for patients to have their potassium levels monitored regularly while on this medication to avoid hypokalemia. Lokelma's profile makes it a valuable option for managing hyperkalemia, especially in patients with chronic kidney disease or those on medications known to increase potassium levels.

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 captures potassium in exchange for hydrogen and sodium
  • Increases fecal potassium excretion through binding of potassium in the gastrointestinal tract
  • Reduces the concentration of free potassium in the gastrointestinal lumen, thereby lowering 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, 4, 5.
  • The potassium-lowering action of sodium zirconium cyclosilicate is predictable and rapid, leading to significant reduction of serum potassium within 1 hour of administration 4.
  • Sodium zirconium cyclosilicate achieves a rapid correction of serum potassium levels (within 2 days) and maintains normokalemia in the long term (up to 1 year) 5.

Key Features of Sodium Zirconium Cyclosilicate

  • It is a nonabsorbable, inorganic crystal that selectively binds potassium and ammonium in exchange of Na+ and H+ in the whole gastrointestinal tract 5.
  • Its potassium-lowering efficacy is maintained irrespective of the use of renin-angiotensin-aldosterone system inhibitors (RAASIs) 3, 5.
  • Sodium zirconium cyclosilicate has a good safety profile, with common adverse reactions including gastrointestinal events and a dose-dependent risk of edema 3, 5.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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