When do we start Lokelma (sodium zirconium cyclosilicate) in patients with hyperkalemia?

When to Start Lokelma (Sodium Zirconium Cyclosilicate)

Start Lokelma in patients with chronic hyperkalemia (K+ >5.0 mEq/L) despite optimized diuretic therapy and correction of metabolic acidosis, particularly when continuation of RAAS inhibitor therapy is clinically necessary for cardiovascular or renal protection. 1

Clinical Indications for Initiating Lokelma

Primary Indication: Chronic Hyperkalemia Management

• Initiate Lokelma when serum potassium is persistently >5.0 mEq/L in patients who have failed conservative measures including diuretic optimization and metabolic acidosis correction 1
• The European Society of Cardiology recommends starting potassium-lowering therapy when K+ increases to >5.0 mEq/L in patients on maximum-tolerated guideline-recommended RAAS inhibitor doses 1
• Lokelma is particularly indicated when RAAS inhibitor therapy (ACE inhibitors, ARBs, mineralocorticoid antagonists) must be maintained for cardiovascular disease, heart failure, or proteinuric chronic kidney disease 2, 3, 4

Specific Clinical Scenarios

For Outpatients with Moderate Hyperkalemia (K+ 5.5-6.5 mEq/L):

• Start Lokelma to enable continuation of RAAS inhibitors rather than discontinuing these life-saving medications 2, 3
• The European Heart Journal recommends initiating potassium-lowering therapy while maintaining RAAS inhibitor doses in this range 3, 4

For Patients with Severe Hyperkalemia (K+ >6.5 mEq/L):

• Lokelma may be started as soon as K+ is >5.0 mEq/L after initial emergency stabilization, but should NOT be used as emergency treatment for life-threatening hyperkalemia due to delayed onset of action 5
• Initial stabilization with calcium, insulin/glucose, or urgent dialysis must be prioritized first 2

For Patients on Chronic Hemodialysis:

• Start Lokelma at 5 g once daily on non-dialysis days for predialysis potassium management 5
• Consider 10 g once daily on non-dialysis days if serum potassium is >6.5 mEq/L 5

Dosing Algorithm

Initial Treatment Phase (First 48 Hours)

• Standard dose: 10 g three times daily for up to 48 hours to rapidly normalize potassium 5
• Median time to normalization is 2.2 hours, with 84% achieving normokalaemia by 24 hours and 98% by 48 hours 6
• Mean potassium reduction is approximately 1.1 mEq/L over 48 hours 2

Maintenance Phase (After 48 Hours)

• Recommended maintenance dose: 10 g once daily 5
• Adjust dose at 1-week intervals in 5 g increments based on serum potassium levels 5
• Maintenance dose range: 5 g every other day to 15 g daily 5
• Monitor serum potassium within 1 week of starting therapy and after dose adjustments 2

Key Advantages Supporting Early Initiation

Fastest Onset Among Potassium Binders:

• Lokelma has onset of action at 1-2 hours, superior to patiromer (7 hours) when rapid reduction is needed 2
• The American College of Cardiology recommends Lokelma as first-line when faster onset is needed 2

Enables RAAS Inhibitor Optimization:

• Discontinuation or dose reduction of RAAS inhibitors leads to adverse cardiorenal outcomes 1
• Both the Journal of the American College of Cardiology and Mayo Clinic Proceedings emphasize that Lokelma allows higher proportions of patients to maintain or increase RAAS inhibitor doses 2
• In heart failure patients, maintaining guideline-directed medical therapy with RAAS inhibitors improves mortality and morbidity 2

Efficacy Across CKD Stages:

• SZC corrects hyperkalemia and maintains normokalaemia in outpatients regardless of CKD stage 7
• 82% of patients with eGFR <30 mL/min/1.73 m² achieved normokalaemia within 24 hours, with sustained control at Day 365 7

Critical Timing Considerations

When NOT to Use Lokelma:

• Do not use as emergency treatment for life-threatening hyperkalemia with ECG changes (peaked T waves, widened QRS, prolonged PR interval) due to delayed onset of action 5
• Avoid in patients with severe constipation, bowel obstruction, or impaction, as it has not been studied in these conditions 5

Optimal Timing for Initiation:

• Start Lokelma before discontinuing or reducing RAAS inhibitors in patients with K+ 5.0-6.5 mEq/L 3, 4
• For K+ >6.5 mEq/L, temporarily reduce RAAS inhibitors and start Lokelma when K+ decreases to >5.0 mEq/L 3, 4

Monitoring Protocol

Initial Phase:

• Check potassium within 1 week of starting therapy 2, 5
• Assess for edema, particularly at higher doses (14% incidence at 15 g daily) 2, 5

Maintenance Phase:

• Regular potassium monitoring is essential to avoid overcorrection and hypokalemia 2
• Individualize monitoring frequency based on CKD stage, heart failure, diabetes, and history of hyperkalemia 3
• Reassess potassium 7-10 days after dose changes 3

Common Pitfalls to Avoid

• Do not delay Lokelma initiation in favor of discontinuing beneficial RAAS inhibitor therapy in patients with cardiovascular disease or proteinuric CKD 3, 4
• Do not use Lokelma alone for acute life-threatening hyperkalemia—it requires 1-2 hours for onset and is not appropriate for emergency stabilization 2, 5
• Monitor for hypokalemia during maintenance therapy, particularly in hemodialysis patients 5
• Be aware of sodium content: each 10 g dose contains 1200 mg sodium during correction phase and 400-1200 mg daily during maintenance 2
• Separate from other oral medications by at least 2 hours before or after Lokelma administration 5