When should Lokelma (sodium zirconium cyclosilicate) be given to a patient with hyperkalemia?

When to Give Lokelma (Sodium Zirconium Cyclosilicate)

Lokelma should be initiated for chronic hyperkalemia (K+ >5.0 mEq/L) in patients requiring ongoing RAAS inhibitor therapy, or for acute non-life-threatening hyperkalemia (K+ 5.1-6.5 mEq/L) when rapid correction within 1-2 hours is needed. 1

FDA-Approved Indications and Limitations

• Lokelma is FDA-approved for treatment of hyperkalemia in adults, but should NOT be used as emergency treatment for life-threatening hyperkalemia due to delayed onset of action. 1
• The drug works by selectively exchanging sodium and hydrogen for potassium in the gastrointestinal tract, with onset of action within 1 hour and significant reductions in serum potassium within 2 hours. 2, 3

Specific Clinical Scenarios for Initiation

Chronic Hyperkalemia Management

• Initiate Lokelma when K+ >5.0 mEq/L in patients on RAAS inhibitors (ACE inhibitors, ARBs, mineralocorticoid receptor antagonists) to enable continuation of these life-saving medications. 4
• The European Society of Cardiology recommends starting potassium-lowering agents like Lokelma when K+ rises above 5.0 mEq/L in patients receiving maximum-tolerated RAAS inhibitor doses, allowing maintenance of cardioprotective therapy. 4, 5
• For patients with K+ 5.0-6.5 mEq/L on RAAS inhibitors, initiate Lokelma while maintaining RAAS inhibitor therapy unless an alternative treatable cause is identified. 5, 6

Acute Non-Life-Threatening Hyperkalemia

• For acute hyperkalemia (K+ 5.1-6.5 mEq/L) without ECG changes, Lokelma 10g three times daily for 48 hours provides rapid correction within 1-2 hours. 1, 7
• Sodium zirconium cyclosilicate reduces serum potassium within 1 hour of a single 10g dose and is effective for both acute and chronic management. 4, 5
• In emergency department patients with K+ ≥5.8 mEq/L, SZC 10g (3 doses in 10 hours) reduced mean serum K+ by 0.72 mEq/L within 2 hours. 4

Patients on Chronic Hemodialysis

• For hemodialysis patients with persistent predialysis hyperkalemia, start Lokelma 5g once daily on non-dialysis days, or 10g once daily if K+ >6.5 mEq/L. 1
• The DIALIZE study demonstrated that once-daily SZC on non-dialysis days effectively maintained normal predialysis serum K+ levels over 8 weeks in ESRD patients. 4
• Target predialysis potassium of 4.0-5.5 mEq/L to minimize mortality risk in advanced CKD, with monitoring after one week of initiation or dose adjustment. 5, 1

Dosing Algorithm

Initial Treatment Phase (First 48 Hours)

• Standard dose: 10g three times daily for up to 48 hours, administered as oral suspension in water. 1
• Separate administration from other oral medications by at least 2 hours before or after Lokelma to avoid binding interactions. 1
• In phase 3 trials, 10g three times daily reduced mean serum K+ by 1.1 mEq/L within 48 hours. 4, 7

Maintenance Treatment Phase

• After initial correction, transition to 10g once daily and monitor serum potassium to adjust dose. 1
• Up-titrate in 5g increments at intervals of 1 week or longer based on serum potassium levels, with maintenance dose range of 5g every other day to 15g daily. 1
• Decrease dose or discontinue if serum potassium falls below desired target range. 1

Advantages Over Alternative Potassium Binders

• Lokelma has faster onset (1 hour) compared to patiromer (7 hours), making it preferable for more urgent outpatient scenarios. 4, 5
• Both patiromer and SZC are superior to sodium polystyrene sulfonate (Kayexalate), which has limited efficacy data and serious gastrointestinal adverse effects including bowel necrosis. 4, 5
• In acute hyperkalemia, SZC is the drug of choice due to more rapid reduction of serum potassium, whereas patiromer may be preferred for chronic hyperkalemia due to SZC's association with edema. 8

Monitoring Requirements

• Check serum potassium within 1 week of starting Lokelma, then reassess at 1-2 weeks, 3 months, and every 6 months thereafter. 5
• For hemodialysis patients, assess serum potassium after one week during initiation and after dose adjustments, monitoring predialysis values after the long interdialytic interval. 1
• Individualize monitoring frequency based on eGFR, heart failure, diabetes, or history of hyperkalemia. 5

Critical Safety Considerations

Contraindications and Warnings

• Avoid Lokelma in patients with severe constipation, bowel obstruction, or impaction, as it has not been studied in these conditions and may worsen gastrointestinal status. 1
• Each 5g dose contains approximately 400mg sodium, requiring monitoring for edema, particularly in patients who should restrict sodium intake or are prone to fluid overload. 1
• Edema was more commonly seen in patients treated with 15g once daily and is dose-dependent. 4, 1, 8

Hypokalemia Risk

• Monitor closely for hypokalemia, which may be even more dangerous than hyperkalemia, particularly in hemodialysis patients. 5, 1
• Discontinue or decrease Lokelma if serum potassium falls below desired target range or if clinically significant hypokalemia develops. 1

When NOT to Use Lokelma

• Do not use for life-threatening hyperkalemia (K+ >6.5 mEq/L with ECG changes) requiring immediate treatment—use IV calcium, insulin/glucose, and albuterol instead. 1
• For severe hyperkalemia with ECG changes (peaked T waves, widened QRS, prolonged PR interval), immediate membrane stabilization with calcium gluconate is required, followed by intracellular shift agents. 5
• Hemodialysis remains the most effective method for severe hyperkalemia, especially in patients with renal failure unresponsive to medical management. 4, 5

Special Population Considerations

Patients with CKD

• Patients with advanced CKD (stage 4-5) tolerate higher potassium levels (3.3-5.5 mEq/L) due to compensatory mechanisms, but maintaining target K+ 4.0-5.0 mEq/L minimizes mortality risk. 4, 5
• Lokelma enables aggressive maintenance of RAAS inhibitors in proteinuric CKD, as these drugs slow CKD progression and provide mortality benefit. 5

Patients with Heart Failure

• The 2022 AHA/ACC/HFSA guidelines note that while patiromer and SZC lower potassium levels, their effectiveness in improving clinical outcomes by facilitating continuation of RAASi therapy remains uncertain. 4
• However, their use is reasonable given the lack of alternatives and the mortality risk associated with both hyperkalemia and RAAS inhibitor discontinuation. 4, 5

Common Pitfalls to Avoid

• Never delay acute treatment of severe hyperkalemia waiting for Lokelma to work—it is not an emergency therapy. 1
• Do not permanently discontinue RAAS inhibitors for hyperkalemia—instead, use Lokelma to enable continuation of these life-saving medications. 4, 5
• Remember to separate Lokelma administration from other oral medications by at least 2 hours to prevent binding interactions. 1
• Monitor for edema, especially in heart failure patients or those on 15g daily doses, as each 5g contains approximately 400mg sodium. 1, 8