Can Lokelma (sodium zirconium cyclosilicate) and Kayexalate (sodium polystyrene sulfonate) be used for Hyperkalemia in dialysis patients?

Hyperkalemia Management in Dialysis Patients: Lokelma and Kayexalate

Lokelma (sodium zirconium cyclosilicate) can be used for hyperkalemia in dialysis patients and is supported by FDA approval and clinical trial evidence specifically in this population, while Kayexalate (sodium polystyrene sulfonate) has limited evidence and safety concerns. 1

Evidence for Lokelma in Dialysis Patients

The FDA has specifically approved Lokelma for dialysis patients based on a dedicated clinical trial (Study 4, NCT03303521) in 196 chronic hemodialysis patients with persistent pre-dialysis hyperkalemia. 1

Efficacy in Dialysis Population

• In the hemodialysis trial, 41% of patients on Lokelma maintained pre-dialysis serum potassium between 4.0-5.0 mEq/L on at least 3 out of 4 dialysis treatments after the long inter-dialytic interval, compared to only 1% on placebo (p<0.001) 1
• The mean baseline potassium in this dialysis study was 5.8 mEq/L, demonstrating effectiveness in the typical hyperkalemic dialysis patient 1
• Lokelma was dosed at 5 g once daily on non-dialysis days, with weekly adjustments in 5 g increments up to 15 g once daily based on pre-dialysis potassium levels 1

Dosing Algorithm for Dialysis Patients

For dialysis patients, start Lokelma at 5 g once daily on non-dialysis days, then adjust weekly in 5 g increments (up to maximum 15 g daily) based on pre-dialysis potassium measurements after the long inter-dialytic interval, targeting 4.0-5.0 mEq/L. 1

Critical Safety Considerations in Dialysis

• Dialysis patients experiencing acute illness (decreased oral intake, diarrhea) must contact their healthcare provider immediately, as Lokelma dose may need adjustment 1
• Each 10 g dose contains 400-1200 mg sodium during maintenance, which requires monitoring for fluid retention in dialysis patients 2
• Edema risk increases dose-dependently: 2% with 5 g, 6% with 10 g, and 14% with 15 g daily 2
• Monitor for hypokalemia, as this is the most common adverse effect alongside dose-dependent edema 3, 2

Kayexalate: Limited Evidence and Safety Concerns

Kayexalate has extremely limited clinical evidence for efficacy, with only two small clinical trials demonstrating potassium reduction in chronic hyperkalemia, and carries significant safety concerns including risk of intestinal necrosis. 4, 5

Why Kayexalate is Problematic

• Unlike Lokelma, which has not been associated with serious gastrointestinal adverse events in randomized trials, Kayexalate (sodium polystyrene sulfonate) has been associated with intestinal necrosis 3
• The Mayo Clinic Proceedings guidelines note that clinical data for Kayexalate remains limited compared to the well-documented efficacy of newer potassium binders 4
• The National Institute for Health and Care Excellence recommends newer agents (Lokelma and patiromer) over Kayexalate due to superior efficacy and safety profiles 6

Comparative Advantages of Lokelma

• Lokelma works throughout both small and large intestines, potentially affecting a larger surface area than Kayexalate which works primarily in the colon 3
• Lokelma has a rapid onset of action beginning at 1-2 hours, with mean potassium reduction of approximately 1.1 mEq/L over 48 hours 6, 2
• The newer agent is more palatable than Kayexalate, facilitating adherence and potentially leading to improved outcomes 4

Important Limitations and Caveats

Lokelma should NOT be used as emergency treatment for life-threatening hyperkalemia due to its delayed onset of action; use insulin/glucose, beta-agonists, or dialysis first for acute emergencies. 2, 1

Drug Interactions

• Lokelma can bind other medications throughout the GI tract, reducing their absorption 2
• Separate other oral medications by at least 2 hours before or after Lokelma administration 1

Monitoring Requirements

• Regular serum potassium monitoring is essential to avoid hypokalemia and guide dose adjustments 6
• Monitor for peripheral edema, particularly at higher doses 6, 2
• In dialysis patients, adjust monitoring frequency based on clinical status and any acute illness 1

Clinical Decision Algorithm

1. For chronic hyperkalemia in dialysis patients: Use Lokelma 5 g once daily on non-dialysis days as first-line potassium binder 1
2. Adjust dose weekly in 5 g increments based on pre-dialysis potassium after long inter-dialytic interval 1
3. Target pre-dialysis potassium of 4.0-5.0 mEq/L 1
4. Monitor for edema and hypokalemia, adjusting dose accordingly 6, 2
5. Avoid Kayexalate given limited evidence and safety concerns, unless Lokelma is unavailable 4, 3, 6