What is the mechanism of action of Lokelma (sodium zirconium cyclosilicate) and what counseling should be provided to patients regarding dosing, administration, dietary potassium and sodium restrictions, drug interactions, monitoring, and potential adverse effects?

Lokelma (Sodium Zirconium Cyclosilicate): Mechanism of Action and Patient Counseling

Mechanism of Action

Lokelma is a selective, non-absorbed inorganic crystal that binds potassium in exchange for hydrogen and sodium ions throughout the entire gastrointestinal tract (both small and large intestines), increasing fecal potassium excretion and lowering serum potassium levels. 1, 2, 3

• Unlike older potassium binders that work primarily in the colon, Lokelma acts along a larger surface area of the GI tract, which contributes to its rapid onset of action 1
• The selective binding mechanism preferentially captures potassium and ammonium ions while releasing sodium and hydrogen ions 2, 3

Dosing and Administration

Initial (Correction) Phase:

• Start with 10 g three times daily for 48 hours to achieve rapid potassium reduction 4, 5, 6
• Expected potassium reduction is approximately 1.1 mEq/L over the 48-hour treatment period 4
• Onset of action begins at 1-2 hours, with median time to normalization of 2.2 hours 4, 6
• 84% of patients achieve normokalemia within 24 hours 6

Maintenance Phase:

• After achieving normokalemia, reduce to 5-15 g once daily based on potassium levels 4, 6
• Mix powder in water and administer as oral suspension 2

Critical Limitation:

• Lokelma is NOT recommended for life-threatening hyperkalemia due to its delayed onset compared to emergency treatments 4
• For life-threatening hyperkalemia (K+ >6.5 mEq/L with ECG changes), use insulin/glucose, beta-agonists, or dialysis first 4

Drug Interactions and Timing

Lokelma can bind other medications throughout the GI tract, reducing their absorption 4

• Separate administration of other oral medications by at least 2 hours before or after Lokelma 4
• This is particularly important for medications with narrow therapeutic windows
• The drug interaction potential is lower than with sodium polystyrene sulfonate due to Lokelma's selective binding mechanism 3

Dietary Counseling

Sodium Content:

• Each 10 g dose contains 1200 mg of sodium during the correction phase (three times daily = 3600 mg/day) 4
• Maintenance doses contain 400-1200 mg sodium daily depending on dose (5-15 g) 4, 5
• Counsel patients with heart failure or hypertension about this significant sodium load 4, 5

Potassium Restrictions:

• Continue dietary potassium restriction as appropriate for underlying kidney disease 7
• Lokelma facilitates continuation of RAAS inhibitors, which provide cardiovascular and renal protection, rather than requiring their discontinuation 7, 4

Monitoring Requirements

Serum Potassium:

• Check potassium levels after 1 week during initiation 4
• Recheck after any dose adjustments 4
• Regular monitoring is essential to avoid hypokalemia, which occurred in 10-11% of patients on 10-15 g daily doses 6

Peripheral Edema:

• Monitor for edema, especially with maintenance doses ≥10 g daily 4, 5
• Edema incidence is dose-dependent: 2% with 5 g, 6% with 10 g, and 14% with 15 g daily 4, 5

Serum Bicarbonate:

• Lokelma causes dose-dependent increases in serum bicarbonate (1.1-2.6 mmol/L), which may benefit patients with metabolic acidosis 5

Adverse Effects

Most Common:

• Gastrointestinal symptoms: constipation, diarrhea, and nausea 4, 5
• These are generally mild and do not require discontinuation 1

Dose-Dependent:

• Edema (see monitoring section above) 4, 5
• Hypokalemia with higher doses 6

Safety Profile:

• Unlike sodium polystyrene sulfonate, Lokelma has not been associated with intestinal necrosis in clinical trials 1
• Generally well tolerated with safety profile similar to placebo in trials up to 28 days, maintained over 12 months 2, 6

Special Populations and Clinical Context

RAAS Inhibitor Therapy:

• Lokelma enables optimization and continuation of RAAS inhibitors in patients with heart failure and CKD who develop hyperkalemia 4, 7
• Potassium-lowering efficacy is maintained regardless of concomitant RAAS inhibitor use 3
• This is clinically important as discontinuing RAAS inhibitors leads to adverse cardiorenal outcomes 7

Chronic Kidney Disease:

• Efficacy is consistent across CKD stages, diabetes, and heart failure subgroups 2
• Newer potassium binders like Lokelma are preferred over sodium polystyrene sulfonate due to superior efficacy, safety, and palatability 7, 1