When is Lokelma (sodium zirconium cyclosilicate) indicated for hyperkalaemia in patients who can take oral medication, have no gastrointestinal obstruction, and may have chronic kidney disease, heart failure, or be on RAAS inhibitors?

When to Give Lokelma (Sodium Zirconium Cyclosilicate)

Lokelma is indicated for the treatment of chronic hyperkalemia in adults who can take oral medication and have no gastrointestinal obstruction, but it should NOT be used as emergency treatment for life-threatening hyperkalemia due to its delayed onset of action. 1

Primary Indications for Initiating Lokelma

Chronic Hyperkalemia Requiring Potassium Binder Therapy

Start Lokelma when serum potassium is ≥5.0 mEq/L in patients on RAAS inhibitors (ACE inhibitors, ARBs, mineralocorticoid receptor antagonists) who require continuation of these life-saving medications. 2, 3

• For patients with potassium 5.0–6.5 mEq/L on RAAS inhibitors: initiate Lokelma while maintaining RAAS inhibitor therapy unless an alternative treatable cause is identified 2
• For patients with potassium >6.5 mEq/L: temporarily discontinue or reduce RAAS inhibitor, then initiate Lokelma once potassium drops to <5.5 mEq/L to enable safe resumption of RAAS therapy 2

Specific Clinical Scenarios

Heart Failure Patients: Lokelma enables continuation of guideline-directed medical therapy with RAAS inhibitors, which provide mortality benefit 4, 3

Chronic Kidney Disease: Lokelma allows aggressive maintenance of RAAS inhibitors in proteinuric CKD, as these medications slow disease progression 4, 2

Hemodialysis Patients: Start with 5 g once daily on non-dialysis days to maintain predialysis potassium 4.0–5.0 mEq/L 2

Dosing Algorithm

Acute Correction Phase (First 48 Hours)

• Standard dose: 10 g three times daily with meals for 48 hours 4, 1
• This achieves mean potassium reduction of approximately 1.1 mEq/L over 48 hours 4
• Median time to normalization is 2.2 hours, with 84% achieving normokalemia by 24 hours 5

Maintenance Phase (After 48 Hours)

• Maintenance dosing: 5–15 g once daily, titrated based on potassium levels 4, 2
• Check potassium within 1 week of starting therapy and after any dose adjustments 4, 2

When NOT to Use Lokelma

Do NOT use Lokelma for life-threatening hyperkalemia with ECG changes (peaked T waves, widened QRS, prolonged PR interval). 4, 1

• Lokelma has onset of action at 1–2 hours, which is too slow for emergency management 4
• For life-threatening hyperkalemia, use insulin/glucose, beta-agonists, calcium gluconate, or dialysis first 4
• Lokelma can be initiated after acute stabilization to prevent recurrence 2

Contraindications:

• Gastrointestinal obstruction 1
• Inability to take oral medication 1

Advantages Over Alternative Potassium Binders

Lokelma is preferred over sodium polystyrene sulfonate (Kayexalate) due to superior efficacy and safety profile. 4, 3

• Kayexalate is associated with intestinal ischemia, colonic necrosis, and doubling of risk for serious GI adverse events with ~33% mortality 4
• Kayexalate causes hypocalcemia and hypomagnesemia due to non-selective cation binding, while Lokelma is highly selective for potassium 4
• Lokelma has robust clinical trial evidence, whereas Kayexalate has only one small 7-day trial 4

Lokelma vs. Patiromer:

• Lokelma has faster onset (1–2 hours) compared to patiromer (7 hours) 4, 3
• Choose Lokelma when more rapid potassium reduction is needed 3
• Both are acceptable for chronic management 3

Safety Monitoring

Monitor for dose-dependent edema: 2% at 5 g, 6% at 10 g, 14% at 15 g daily 4

• Each 10 g dose contains 1200 mg sodium during correction phase, 400–1200 mg sodium daily during maintenance 4
• Monitor for peripheral edema, especially in heart failure patients 4

Common adverse effects: constipation, diarrhea, nausea 4

Drug interactions: Lokelma can bind other medications throughout the GI tract, reducing their absorption 4

Hypokalemia risk: Regular potassium monitoring is essential to avoid overcorrection 4, 3

Clinical Pitfalls to Avoid

• Never delay emergency treatment (calcium, insulin, dialysis) while waiting to start Lokelma in patients with severe hyperkalemia and ECG changes 4, 2
• Do not discontinue RAAS inhibitors permanently in patients with cardiovascular disease or proteinuric CKD—use Lokelma to enable continuation of these life-saving medications 4, 2
• Remember that dietary potassium restriction alone is insufficient—patients with chronic hyperkalemia on RAAS inhibitors require pharmacologic potassium binding 4, 2
• Monitor potassium closely to prevent hypokalemia, which may be more dangerous than mild hyperkalemia 2