In which adult patients is Lokelma (sodium zirconium cyclosilicate) indicated for treatment of hyperkalemia?

Lokelma Indications

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

Primary Indication

• Lokelma is FDA-approved for the treatment of hyperkalemia in adults, defined as serum potassium >5.0–5.5 mEq/L. 1, 2
• The medication is specifically designed for both acute correction (potassium ≥5.8 mEq/L) and chronic maintenance of normokalemia. 2, 3

Critical Limitation

• Lokelma is NOT indicated for life-threatening hyperkalemia requiring emergency treatment because its onset of action begins at 1-2 hours, which is too slow for cardiac emergencies. 2, 1
• For life-threatening hyperkalemia with ECG changes, insulin/glucose, beta-agonists, calcium, or dialysis must be used first. 2

Specific Clinical Scenarios Where Lokelma Is Indicated

Enabling RAAS Inhibitor Continuation

• The most important indication for Lokelma is enabling continuation of life-saving RAAS inhibitors (ACE inhibitors, ARBs, mineralocorticoid antagonists) in patients with cardiovascular disease, heart failure, or chronic kidney disease who develop hyperkalemia. 2, 4
• The European Heart Journal and Mayo Clinic guidelines recognize that newer potassium binders like Lokelma facilitate optimization of RAAS inhibitor therapy in patients with cardiovascular disease and CKD who develop hyperkalemia. 2
• Discontinuation of RAAS inhibitors is associated with adverse cardiorenal outcomes, making Lokelma's role in maintaining these medications clinically critical. 2

Chronic Kidney Disease (All Stages)

• Lokelma is indicated for patients with CKD stages 1-5, including those on dialysis, with efficacy demonstrated across all stages of kidney disease. 3, 5
• In patients with advanced CKD (stages 4-5), 82% achieved normokalaemia within 24 hours during the correction phase, and 82% maintained normokalaemia at Day 365. 5
• For patients on chronic hemodialysis, Lokelma is administered only on non-dialysis days, starting at 5 g once daily (or 10 g if potassium >6.5 mEq/L). 1

Heart Failure Patients

• Lokelma is indicated for heart failure patients requiring RAAS inhibitors who develop hyperkalemia, allowing maintenance of these cardioprotective medications. 2, 4
• The use of Lokelma helps maintain normokalaemia in patients with heart failure, permitting continuation of life-saving RAAS inhibitors. 2

Diabetes with Hyperkalemia

• Lokelma is indicated for diabetic patients with hyperkalemia, particularly those on RAAS inhibitors for nephroprotection. 3, 6
• The beneficial effects of Lokelma are consistent across diabetic patient subgroups. 3

Recurrent or Chronic Hyperkalemia

• Lokelma is indicated for long-term management of chronic hyperkalemia, with safety and efficacy demonstrated for up to 12 months. 3, 5
• For patients with recurrent hyperkalemia despite dietary restriction and diuretic therapy, Lokelma provides sustained potassium control. 2, 4

Specific Potassium Thresholds for Initiation

Mild to Moderate Hyperkalemia (5.0-6.5 mEq/L)

• For patients on RAAS inhibitors with potassium 5.0-6.5 mEq/L, initiate Lokelma while maintaining RAAS inhibitor therapy unless an alternative treatable cause is identified. 4
• The European Society of Cardiology recommends initiating an approved potassium-lowering agent like Lokelma in this range to enable continuation of cardioprotective medications. 4

Severe Hyperkalemia (>6.5 mEq/L)

• When potassium >6.5 mEq/L, temporarily discontinue or reduce RAAS inhibitors, then initiate Lokelma once potassium <5.5 mEq/L to prevent recurrence and allow eventual resumption of RAAS therapy. 4
• After acute stabilization with emergency measures (calcium, insulin, dialysis), Lokelma can be started for ongoing management. 2, 4

Dosing Algorithm by Clinical Scenario

Initial Treatment (Correction Phase)

• For initial treatment of hyperkalemia, administer Lokelma 10 g three times daily for up to 48 hours. 1
• This achieves normokalaemia (3.5-5.0 mEq/L) in 82-100% of patients within 24-72 hours. 3, 5

Maintenance Treatment

• For continued treatment, the recommended dose is 10 g once daily, with adjustments based on serum potassium levels. 1
• The maintenance dose range is 5 g every other day to 15 g daily, titrated at 1-week intervals in 5 g increments. 1

Hemodialysis Patients

• Start with 5 g once daily on non-dialysis days (or 10 g if potassium >6.5 mEq/L), targeting pre-dialysis potassium of 4.0-5.5 mEq/L. 1, 2

Comparative Advantages Supporting Its Use

Superior to Sodium Polystyrene Sulfonate (Kayexalate)

• Lokelma is preferred over Kayexalate due to superior efficacy, better safety profile (no intestinal necrosis), and improved patient tolerability. 2
• Kayexalate is linked to serious gastrointestinal complications (intestinal ischemia, colonic necrosis) with a 33% mortality rate, whereas Lokelma has no such risk. 2
• Lokelma's efficacy is supported by multiple robust clinical trials, while Kayexalate has only one small 7-day trial. 2

Rapid Onset Compared to Patiromer

• Lokelma has a 1-hour onset of action versus 7 hours for patiromer, making it more suitable for urgent outpatient scenarios. 2, 4
• Both agents are effective for chronic management, but Lokelma's faster action provides flexibility. 2

Monitoring Requirements

• Check serum potassium within 1 week after initiating Lokelma or after dose adjustments to avoid hypokalemia and guide titration. 2
• Monitor for peripheral edema due to dose-dependent sodium content (400-1200 mg sodium per dose). 2, 1
• Regular monitoring is essential in high-risk patients with CKD, heart failure, or diabetes. 2, 4

Important Caveats

Sodium Content and Edema Risk

• Each 5 g dose contains approximately 400 mg sodium, with edema incidence increasing dose-dependently: 2% with 5 g, 6% with 10 g, and 14% with 15 g daily. 2, 1
• Monitor for fluid retention, particularly in heart failure patients. 2

Drug Interactions

• Administer other oral medications at least 2 hours before or after Lokelma to avoid reduced absorption, as Lokelma can bind medications throughout the GI tract. 2, 1

Gastrointestinal Considerations

• Avoid Lokelma in patients with severe constipation, bowel obstruction, or impaction, as it has not been studied in these conditions and may worsen gastrointestinal symptoms. 1
• Common adverse effects include constipation, diarrhea, and nausea. 2

Dietary Considerations

• Patients should continue a potassium-restricted diet while receiving Lokelma, allowing safe management of serum potassium levels. 2
• However, Lokelma may allow for less restrictive dietary potassium limitations compared to no treatment. 2