What is the recommended dosing for Lokelma (sodium zirconium cyclosilicate) for hyperkalemia in patients with Chronic Kidney Disease (CKD)?

Lokelma Dosing for Hyperkalemia in CKD

For initial treatment of hyperkalemia in CKD patients, start Lokelma 10 g three times daily for up to 48 hours, then transition to 10 g once daily for maintenance, with dose adjustments between 5 g every other day to 15 g daily based on serum potassium monitoring. 1

Initial Treatment Phase (Correction Phase)

• Administer 10 g three times daily for up to 48 hours to rapidly reduce serum potassium levels 1
• This regimen produces a mean serum potassium reduction of 1.1 mEq/L (from approximately 5.6 to 4.5 mEq/L) 2
• Onset of action begins within 1 hour of the first dose, making it faster than patiromer (7 hours) but not suitable for life-threatening hyperkalemia requiring emergency treatment 2, 1
• During the correction phase, 82-100% of patients achieve normokalaemia (3.5-5.0 mmol/L) within 24-72 hours, regardless of CKD stage 3

Maintenance Treatment Phase

• Start with 10 g once daily after the initial 48-hour correction phase 1
• Monitor serum potassium and adjust dose at intervals of 1 week or longer in increments of 5 g 1
• The maintenance dose range is 5 g every other day to 15 g daily, titrated to maintain potassium in the desired target range 1
• In clinical trials, 90% of patients maintained normokalaemia on 10 g daily dosing over 28 days, with sustained efficacy up to 12 months 2, 3

Special Considerations for Dialysis Patients

• For patients on chronic hemodialysis, administer Lokelma only on non-dialysis days 1
• Start with 5 g once daily on non-dialysis days for most patients 1
• Consider 10 g once daily on non-dialysis days if serum potassium is greater than 6.5 mEq/L 1
• Monitor pre-dialysis potassium after the long inter-dialytic interval and adjust dose accordingly (range: 5-15 g once daily on non-dialysis days) 1

Dose-Response Relationship

The efficacy of Lokelma is clearly dose-dependent based on phase 3 trial data 4:

• 1.25 g: 0.11% exponential rate of change in serum K+ at 48 hours
• 2.5 g: 0.16% rate of change
• 5 g: 0.21% rate of change
• 10 g: 0.30% rate of change (most effective studied dose)
• All doses ≥2.5 g showed P<.001 versus placebo 4

Monitoring Protocol

• Check serum potassium within 2-4 weeks after initiation or dose adjustment 4
• Decrease the dose or discontinue if serum potassium falls below the desired target range 1
• The reversible decrease in eGFR on initiation is generally not an indication to discontinue therapy 4
• Monitor for edema, particularly in patients who should restrict sodium intake, as each 5 g dose contains approximately 400 mg of sodium 1, 2

Critical Clinical Context: Maintaining RAAS Inhibitors

• Do not discontinue RAAS inhibitors (ACE inhibitors, ARBs) when managing hyperkalemia with Lokelma 2
• Hyperkalemia associated with RAAS inhibitors can often be managed by reducing serum potassium levels rather than decreasing or stopping RAAS inhibitors 4
• The newer potassium binders like Lokelma specifically enable optimization of cardioprotective RAAS inhibitor therapy in CKD patients 2, 5
• Continue ACE inhibitors or ARBs even when eGFR falls below 30 ml/min per 1.73 m² unless there is symptomatic hypotension or uncontrolled hyperkalemia despite medical treatment 4

Efficacy Across CKD Stages

• Lokelma demonstrates consistent efficacy regardless of CKD stage, with similar rates of achieving normokalaemia in patients with eGFR <30 versus ≥30 mL/min/1.73 m² 3
• During the correction phase, 82% of patients in both eGFR subgroups achieved normokalaemia within 24 hours 3
• At Day 365 of maintenance therapy, 82% of patients with eGFR <30 and 90% with eGFR ≥30 maintained normokalaemia 3

Safety Profile and Common Pitfalls

• Edema is the most common adverse effect, occurring in approximately 6% of patients on 10 g daily versus 14% on 15 g daily 2
• The incidence of hypokalemia is low compared to older potassium binders 6
• Avoid use in patients with severe constipation, bowel obstruction, or impaction, as Lokelma has not been studied in these conditions 1
• Administer other oral medications at least 2 hours before or 2 hours after Lokelma to avoid potential binding interactions 1

Advantages Over Older Potassium Binders

• Lokelma is more selective for potassium than sodium polystyrene sulfonate (SPS), which has been associated with serious gastrointestinal adverse events including colonic necrosis and a 33% mortality rate 4
• Unlike SPS, Lokelma does not cause hypocalcemia or hypomagnesemia due to its selective binding properties 4, 6
• Lokelma works in both the small and large intestines, contributing to its faster onset compared to patiromer 2