LOKELMA (Sodium Zirconium Cyclosilicate) Treatment Protocol for Hyperkalemia
Lokelma is a highly selective potassium binder that works throughout both small and large intestines to rapidly reduce serum potassium levels in patients with hyperkalemia, with onset of action beginning within 1 hour of administration. 1, 2
Mechanism of Action
- Lokelma is a non-absorbed, non-polymer zirconium silicate compound that preferentially exchanges hydrogen and sodium for potassium ions in the gastrointestinal tract 2
- Unlike other potassium binders that work primarily in the colon, Lokelma acts throughout the entire GI tract, which contributes to its faster onset of action 1, 2
- Lokelma is highly selective for potassium compared to other binders like sodium polystyrene sulfonate (SPS) 2, 3
Dosing Protocol
Initial Treatment Phase
- Recommended starting dose: 10 g administered three times daily for up to 48 hours 4
- In clinical trials, this dosing regimen consistently demonstrated a mean reduction of 1.1 mEq/L in serum potassium within 48 hours 5, 2
- Median time to normalization is approximately 2.2 hours, with 84% of patients achieving normokalemia by 24 hours and 98% by 48 hours 6
- Onset of action begins within 1 hour, particularly in patients with severe hyperkalemia (≥6.0 mEq/L) 2, 7
Maintenance Phase
- Recommended maintenance dose: 10 g once daily 4
- Dose can be adjusted at one-week intervals as needed (by 5 g daily) to maintain desired serum potassium target range 4
- Available maintenance doses: 5 g, 10 g, and 15 g once daily 2
- Clinical trials showed that these maintenance doses effectively maintained normal potassium levels (3.5-5.0 mEq/L) for up to 28 days 5, 2
- Long-term studies have demonstrated efficacy and safety for up to 12 months 8, 9
Special Populations: Patients on Chronic Hemodialysis
- Recommended starting dose for patients on chronic hemodialysis: 5 g once daily on non-dialysis days 4
- Monitor closely for hypokalemia in this population 4
Administration Instructions
- Lokelma should be mixed with approximately 3 tablespoons of water and stirred well 4
- The powder does not dissolve and the mixture will appear as a suspension 4
- Other oral medications should be administered at least 2 hours before or 2 hours after Lokelma to avoid potential drug interactions 4
Efficacy
- In the HARMONIZE trial, Lokelma reduced mean serum potassium from 5.6 mEq/L at baseline to 4.5 mEq/L at 48 hours 6
- During maintenance therapy, the proportion of patients maintaining normal potassium levels was significantly higher with all Lokelma doses compared to placebo (80%, 90%, and 94% for the 5-g, 10-g, and 15-g groups vs. 46% with placebo) 6
- Long-term studies show that 88.3% of patients maintained mean serum K+ ≤5.1 mmol/L for up to 11 months 9
Safety Profile and Adverse Effects
- Most common adverse effects: 5, 2, 6
- Mild to moderate edema (dose-dependent, more common with 15 g dose)
- Hypokalemia (particularly with higher doses)
- Unlike sodium polystyrene sulfonate (SPS), Lokelma has not been associated with intestinal necrosis 1
- Lokelma has radio-opaque properties and may give the appearance typical of an imaging agent during abdominal X-ray procedures 4
Important Monitoring Recommendations
- Regular monitoring of serum potassium is essential to avoid hypokalemia and guide dose adjustments 3
- More frequent monitoring is recommended during the initial treatment phase and after dose adjustments 3
- Monitor for signs of edema, particularly with higher maintenance doses 5, 6
Limitations of Use
- Lokelma should not be used as an emergency treatment for life-threatening hyperkalemia because of its delayed onset of action (although faster than other oral potassium binders) 4
- In emergency situations, traditional rapid-acting measures (insulin/glucose, calcium, albuterol) should be used first 5
Clinical Pearls
- Lokelma offers advantages over other potassium binders including faster onset of action (1 hour vs. 7 hours for patiromer) and better selectivity for potassium 2, 3
- The medication works well in patients with various comorbidities including chronic kidney disease, heart failure, and diabetes 10, 8
- When used in the emergency department in combination with insulin and glucose, Lokelma may provide incremental benefit in treating hyperkalemia 7