What is the recommended dosing regimen of Lokelma (sodium zirconium cyclosilicate) sachets for an adult patient with hyperkalemia?

Lokelma (Sodium Zirconium Cyclosilicate) Dosing for Hyperkalemia

For initial treatment of hyperkalemia, administer Lokelma 10 g three times daily for up to 48 hours, followed by a maintenance dose of 10 g once daily, with adjustments based on serum potassium levels. 1

Initial Treatment Phase (Acute Correction)

Administer 10 g of Lokelma three times daily for up to 48 hours to rapidly reduce serum potassium levels in adults with hyperkalemia 1. This dosing regimen achieves normokalaemia (serum potassium 3.5-5.0 mmol/L) in the majority of patients within 24-48 hours 2, 3.

• Onset of action begins within 1 hour of the first dose, making Lokelma suitable for non-emergent hyperkalemia management 4, 5
• The mean serum potassium reduction is approximately 1.1-1.3 mmol/L within 48 hours with the 10 g three-times-daily regimen 4, 5, 6
• In the HARMONIZE trial, 92.9% of patients achieved normokalaemia within 48 hours using this initial dosing 3
• Lokelma works in both the small and large intestines by preferentially exchanging hydrogen and sodium for potassium ions 5, 7

Reconstitution and Administration

Empty the entire contents of the packet(s) into a drinking glass containing approximately 3 tablespoons of water, stir well, and drink immediately 1. If powder remains, add more water, stir, and drink until no powder remains to ensure the entire dose is taken 1.

Administer other oral medications at least 2 hours before or 2 hours after Lokelma to avoid potential drug interactions 1.

Maintenance Treatment Phase

After the initial 48-hour correction phase, transition to 10 g once daily for continued hyperkalemia management 1. This maintenance dose effectively sustains normokalaemia over extended periods 2, 3.

• Monitor serum potassium levels and adjust the Lokelma dose at intervals of 1 week or longer, in increments of 5 g 1
• The recommended maintenance dose range is 5 g every other day to 15 g daily, depending on serum potassium response 1
• In clinical trials, 5 g and 10 g once-daily doses maintained normokalaemia over 28 days, with the 10 g dose providing superior potassium control 4, 3, 6
• Decrease the dose or discontinue Lokelma if serum potassium falls below the desired target range 1

Long-Term Efficacy

Lokelma maintains its efficacy and safety profile over extended treatment periods 2:

• Efficacy and safety have been documented for up to 12 months of continuous therapy 4, 2
• In the long-term study, 82-90% of patients maintained normokalaemia at Day 365, regardless of chronic kidney disease stage 2
• 88% of patients maintained mean serum potassium ≤5.1 mmol/L throughout an 11-12 month study period 5

Special Population: Chronic Hemodialysis Patients

For patients on chronic hemodialysis, administer Lokelma only on non-dialysis days 1:

• Starting dose: 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 serum potassium after the long inter-dialytic interval and adjust dose accordingly 1
• Maintenance dose range: 5 g to 15 g once daily on non-dialysis days 1
• Assess serum potassium one week after initiation or dose adjustment 1

Dose-Response Relationship

The efficacy of Lokelma is clearly dose-dependent 5:

• 1.25 g dose: 0.11% exponential rate of change in serum K⁺ at 48 hours 5
• 2.5 g dose: 0.16% rate of change 5
• 5 g dose: 0.21% rate of change 5
• 10 g dose: 0.30% rate of change (most effective studied dose) 5, 6

All doses ≥2.5 g showed statistically significant reductions versus placebo (P<0.001) 5.

Monitoring Protocol

• Check serum potassium within 2-4 weeks after initiation or dose adjustment 5
• Decrease the dose or discontinue if serum potassium falls below the desired target range 5, 1
• Monitor for edema, particularly in patients who should restrict sodium intake or are prone to fluid overload, as each 5 g dose contains approximately 400 mg of sodium 5, 1
• The most common adverse effects are mild to moderate edema (occurring in approximately 6% of patients on 10 g daily, compared to 14% on 15 g daily) and hypokalemia 4, 5

Important Limitations and Precautions

Lokelma should not be used as an emergency treatment for life-threatening hyperkalemia due to its delayed onset of action (approximately 1 hour), which is insufficient for acute, life-threatening situations requiring immediate intervention 1.

• Avoid use in patients with severe constipation, bowel obstruction, or impaction, as Lokelma has not been studied in these conditions and may be ineffective or worsen gastrointestinal symptoms 1
• Lokelma has not been associated with serious adverse events in randomized trials, unlike older potassium binders such as sodium polystyrene sulfonate 4
• The incidence of hypokalemia is low with appropriate monitoring and dose adjustment 7

Advantages Over Other Potassium Binders

• Faster onset of action (1 hour) compared to patiromer (7 hours) 5
• More selective for potassium than sodium polystyrene sulfonate (SPS), reducing the risk of serious gastrointestinal adverse events 5
• Does not cause hypocalcemia or hypomagnesemia due to selective binding properties, unlike SPS 5
• Sustained increases in serum bicarbonate have been observed, which may provide added benefit for patients with metabolic acidosis 4, 8