What are the recommendations for using new potassium-binding agents, such as patiromer (Veltassa) or sodium zirconium cyclosilicate (Lokelma), in the management of hyperkalemia?

Recommendations for New Potassium-Binding Agents in Hyperkalemia Management

The newer potassium-binding agents, patiromer (Veltassa) and sodium zirconium cyclosilicate (SZC, Lokelma), are recommended for managing hyperkalemia in patients with chronic kidney disease, heart failure, or those on renin-angiotensin-aldosterone system inhibitors (RAASi) when traditional measures are insufficient. 1

Mechanism and Characteristics of New Potassium Binders

• Both patiromer and SZC are non-absorbed compounds that bind potassium in the gastrointestinal tract to facilitate fecal excretion 2
• SZC exchanges hydrogen and sodium for potassium in both small and large intestines, while patiromer exchanges calcium for potassium primarily in the colon 2
• SZC has a faster onset of action (1 hour) compared to patiromer (7 hours), making it more suitable for urgent but non-emergency hyperkalemia 2, 1
• Both agents are more selective and palatable than older potassium binders like sodium polystyrene sulfonate (SPS) 2

Indications and Dosing

• Patiromer is indicated for hyperkalemia treatment in adults and pediatric patients ≥12 years old with a recommended starting dose of 8.4g once daily for adults (4g for pediatric patients), titrated weekly as needed 3
• SZC is indicated for hyperkalemia in adults with a recommended starting dose of 10g three times daily for up to 48 hours for initial correction, followed by 10g once daily for maintenance 4
• For patients on hemodialysis, SZC starting dose is 5g once daily on non-dialysis days 4
• Neither agent should be used as emergency treatment for life-threatening hyperkalemia due to their delayed onset of action 3, 4

Clinical Efficacy

• SZC can reduce serum potassium by 0.72 mEq/L within 2 hours in emergency department patients with severe hyperkalemia (≥5.8 mEq/L) 2
• In chronic hyperkalemia, once-daily SZC (5-10g) effectively maintains normokalemia over 14-28 days 2
• The DIALIZE study demonstrated that SZC effectively maintains normal predialysis potassium levels in ESRD patients with persistent hyperkalemia 2
• Patiromer has demonstrated efficacy in maintaining normokalemia for up to 12 months in clinical trials 1

Safety Considerations

• Most common adverse effects of SZC include hypokalemia and dose-dependent edema 2
• Patiromer's most common adverse effects include constipation, hypomagnesemia, diarrhea, nausea, abdominal discomfort, and flatulence 3
• Patiromer may cause hypercalcemia due to its calcium exchange mechanism, though cases are rare 2
• SZC contains 400mg of sodium per 5g dose, which may be a concern in sodium-sensitive patients 2
• Drug interactions: Other oral medications should be administered at least 3 hours before or after patiromer 3 and at least 2 hours before or after SZC 4

Algorithm for Selection of Potassium Binders

1. For acute, non-emergency hyperkalemia requiring rapid correction:

   • Choose SZC due to faster onset of action (within 1 hour) 1
   • Initial dose: 10g three times daily for up to 48 hours 4

2. For chronic hyperkalemia management:

   • Patient factors to consider:
     • Edema risk: Prefer patiromer in patients with heart failure or edema concerns (SZC contains sodium) 2, 1
     • Metabolic acidosis: Consider SZC which provides sustained increases in serum bicarbonate 2
     • Calcium concerns: Avoid patiromer in patients with hypercalcemia risk 2
     • Magnesium status: Monitor magnesium with patiromer due to risk of hypomagnesemia 3

3. For patients on RAASi therapy:

   • Both agents allow continuation or optimization of RAASi therapy in patients who would otherwise require dose reduction or discontinuation 2, 1
   • European Society of Cardiology recommends starting potassium-lowering therapy if potassium increases to >5.0 mEq/L in patients on RAASi 2

Monitoring Recommendations

• Check serum potassium within 1 week of starting or dose escalation 2
• Monitor for hypokalemia, especially with higher doses 2
• With patiromer, monitor serum magnesium periodically 3
• With SZC, monitor for edema, especially in patients with heart failure or volume overload 4

Pitfalls and Caveats

• Neither agent should be used for emergency treatment of life-threatening hyperkalemia 3, 4
• Drug-drug interactions are a concern; administer other oral medications at appropriate intervals from potassium binders 3, 4
• Cost considerations may influence clinical use, as these newer agents are more expensive than traditional options 2
• Rebound hyperkalemia can occur if treatment is abruptly discontinued 2