What is Lokelma (sodium zirconium cyclosilicate) used for in adults with hyperkalemia?

What is Lokelma?

Lokelma (sodium zirconium cyclosilicate) is a selective potassium binder approved for the treatment of hyperkalemia in adults, but it should not be used as emergency treatment for life-threatening hyperkalemia due to its delayed onset of action. 1

Mechanism of Action

Lokelma is a non-absorbed, inorganic zirconium silicate compound that works throughout the entire gastrointestinal tract—both small and large intestines—selectively exchanging hydrogen and sodium ions for potassium and ammonium ions, thereby increasing fecal potassium excretion and lowering serum potassium levels. 2, 3, 4 This distinguishes it from older potassium binders like sodium polystyrene sulfonate that work primarily in the colon. 2

Clinical Efficacy

Acute Correction Phase

• Initial dosing: 10 g three times daily for up to 48 hours achieves normalization of serum potassium (3.5-5.0 mEq/L) in 84% of patients within 24 hours and 98% within 48 hours. 5
• Onset of action: Begins at 1-2 hours, with median time to normalization of 2.2 hours. 6, 5
• Mean potassium reduction: Approximately 1.1 mEq/L decrease over 48 hours. 6

Maintenance Phase

• Maintenance dosing: 5-15 g once daily (typically starting at 10 g daily) maintains normokalaemia for up to 28 days and beyond. 1, 5
• Long-term efficacy: Sustained potassium control has been demonstrated for up to 12 months across all patient subgroups, including those with chronic kidney disease, diabetes, heart failure, and those on RAAS inhibitor therapy. 3, 7
• In the HARMONIZE trial, 80-94% of patients maintained mean potassium <5.1 mEq/L during days 8-29 depending on dose (5 g, 10 g, or 15 g daily), compared to only 46% with placebo. 5

Dosing Recommendations

Standard Patients

• Initial treatment: 10 g three times daily for up to 48 hours 1
• Maintenance: 10 g once daily, adjustable from 5 g every other day to 15 g daily based on serum potassium monitoring 1

Chronic Hemodialysis Patients

• Administer only on non-dialysis days 1
• Starting dose: 5 g once daily on non-dialysis days (or 10 g if serum potassium >6.5 mEq/L) 1
• Maintenance range: 5-15 g once daily on non-dialysis days 1

Administration

• Empty packet contents into approximately 3 tablespoons of water, stir well, and drink immediately 1
• Other oral medications should be administered at least 2 hours before or 2 hours after Lokelma to avoid binding interactions in the GI tract 6, 1

Safety Profile and Adverse Effects

Common Adverse Effects

• Gastrointestinal symptoms: Constipation, diarrhea, and nausea are most common 6
• Edema: Dose-dependent incidence of 2% with 5 g, 6% with 10 g, and 14% with 15 g daily 6, 5
• Hypokalemia: Occurred in 10-11% of patients receiving 10-15 g daily in clinical trials, but was rare with 5 g daily 5

Sodium Content

• Each 5 g dose contains approximately 400 mg of sodium 1
• During the correction phase (10 g three times daily), patients receive 1200 mg sodium per dose 6
• During maintenance, sodium intake ranges from 400-1200 mg daily depending on dose 6

Serious Adverse Events

• Unlike sodium polystyrene sulfonate (SPS/Kayexalate), which has been associated with intestinal necrosis, Lokelma has not shown this specific risk in randomized trials 2
• No serious gastrointestinal adverse events have been reported in clinical trials 2

Contraindications and Precautions

• Avoid 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 status 1
• Not for emergency treatment of life-threatening hyperkalemia—use insulin/glucose, beta-agonists, or dialysis first 6, 1

Clinical Context and Guidelines

Role in RAAS Inhibitor Optimization

• The Mayo Clinic and European Heart Journal guidelines recognize that newer potassium binders like Lokelma may facilitate optimization of RAAS inhibitor therapy in patients with cardiovascular disease and chronic kidney disease who develop hyperkalemia. 8
• This is clinically important because hyperkalemia is a major reason for discontinuation or dose reduction of life-saving RAAS inhibitors in patients with heart failure and CKD. 8

Comparison to Alternatives

• Superior to Kayexalate: Clinical data for Lokelma is well-documented compared to limited evidence for sodium polystyrene sulfonate, with superior efficacy and safety profiles. 6
• Faster than Patiromer: Lokelma has onset at 1-2 hours versus approximately 7 hours for patiromer. 9
• More palatable: Better tolerability facilitates adherence compared to older agents. 6

Monitoring Requirements

• Regular serum potassium monitoring is essential to avoid hypokalemia and guide dose adjustments 9
• Monitor for peripheral edema given dose-dependent risk 6, 9
• Assess serum potassium after one week during initiation and after dose adjustments 1

Key Clinical Pitfalls

• Do not use for acute life-threatening hyperkalemia (e.g., with ECG changes or serum potassium >6.5 mEq/L requiring immediate intervention)—the 1-2 hour onset is too slow 6, 1
• Remember medication separation: Administer other oral medications at least 2 hours before or after Lokelma to prevent binding interactions 6, 1
• Watch for edema in high-risk patients: The sodium content and dose-dependent edema risk requires careful monitoring, especially in patients with heart failure 6, 1
• Avoid in severe GI motility disorders: Effectiveness is uncertain and may worsen constipation or obstruction 1