What medications can be used to reduce hyperkalemia in outpatients?

Outpatient Medications for Hyperkalemia Management

For outpatient management of hyperkalemia, sodium zirconium cyclosilicate (Lokelma) is the preferred first-line agent, dosed at 10g three times daily for up to 48 hours, followed by 10g once daily for maintenance, with patiromer (Veltassa) as an alternative option. 1, 2

First-Line Agent: Sodium Zirconium Cyclosilicate (Lokelma)

Initial Treatment Phase

• Start with 10g three times daily for up to 48 hours to achieve rapid potassium reduction 2
• Onset of action begins within 1 hour, with median time to normalization of 2.2 hours 1, 3
• Expect a mean reduction of 1.1 mEq/L within 48 hours (from 5.6 to 4.5 mEq/L) 1, 3
• 84% of patients achieve normokalemia by 24 hours, and 98% by 48 hours 4

Maintenance Phase

• Transition to 10g once daily after achieving normokalemia 2
• Maintenance dose range: 5g every other day to 15g daily, adjusted based on serum potassium monitoring 2
• 90% of patients maintain normokalemia on 10g daily dosing over 28 days 3
• Monitor potassium weekly during initiation and after dose adjustments 2

Advantages Over Other Agents

• Fastest onset (1 hour vs. 7 hours for patiromer) 1, 3
• Works in both small and large intestines, contributing to rapid action 3
• More selective for potassium than sodium polystyrene sulfonate 1
• No serious adverse events in randomized trials 1

Common Side Effects

• Edema is the most common adverse effect (dose-dependent: 6% at 10g daily, 14% at 15g daily) 1, 3
• Each 5g dose contains approximately 400mg sodium—monitor patients prone to fluid overload 3, 2
• Hypokalemia (10-11% at higher doses) 4

Drug Interactions

• Administer other oral medications at least 2 hours before or after Lokelma 2

Second-Line Agent: Patiromer (Veltassa)

Dosing

• Starting dose: 8.4g once daily (can be given as 4.2g twice daily) 1
• Dose range: 4.2g to 16.8g daily, adjusted based on potassium levels 1
• Onset of action: approximately 7 hours 1

Key Considerations

• Separate from other oral medications by 3 or more hours due to nonselective binding 1
• Exchanges calcium for potassium—monitor for hypercalcemia (rare but reported) 1
• Common adverse effects: gastrointestinal symptoms (constipation, diarrhea, nausea), hypomagnesemia 1
• Indicated for patients ≥12 years old 5

Third-Line Agent: Sodium Polystyrene Sulfonate (SPS/Kayexalate)

Limited Role in Outpatient Management

• Not recommended for routine chronic use due to safety concerns 1
• Associated with serious gastrointestinal adverse events including colonic necrosis 1
• Doubling in risk of hospitalization for serious GI complications 1
• Reported overall mortality rate of 33% in some studies 1
• Nonselective binding may cause hypocalcemia and hypomagnesemia 1

If Used (Last Resort)

• Dose: 30g once daily 1
• Mean potassium reduction: 1.04 mEq/L over 7 days 1
• Should not be used as emergency treatment due to delayed onset 6

Critical Clinical Considerations

Do NOT Discontinue RAAS Inhibitors

• Maintain cardioprotective medications (ACE inhibitors, ARBs, MRAs) while managing hyperkalemia with potassium binders 1, 3
• Newer potassium binders enable optimization of RAAS inhibitor therapy 1
• Hyperkalemia should not be a reason to stop life-saving cardiovascular medications 1

Monitoring Strategy

• Check potassium levels 1 week after initiation or dose adjustment 2
• Adjust doses in 5g increments at intervals of 1 week or longer 2
• Monitor for hypokalemia—discontinue if potassium falls below target range 2

Special Populations

• Hemodialysis patients: Start with 5g once daily on non-dialysis days only (10g if K+ >6.5 mEq/L) 2
• Monitor pre-dialysis potassium after the long interdialytic interval 2

Contraindications and Precautions

• Avoid Lokelma in severe constipation, bowel obstruction, or impaction 2
• Not for emergency treatment of life-threatening hyperkalemia (all agents have delayed onset) 2, 5, 6