What is the appropriate use and dosage of Kayexalate (sodium polystyrene sulfonate) for treating hyperkalemia?

Appropriate Use and Dosage of Kayexalate for Hyperkalemia

Kayexalate (sodium polystyrene sulfonate) should be avoided for chronic hyperkalemia management due to its association with severe gastrointestinal side effects including fatal intestinal necrosis, and newer potassium binders should be used instead. 1

Indications and Limitations

• Kayexalate is indicated for the treatment of non-emergency hyperkalemia (K+ >5.0 mEq/L) 2
• Should NOT be used for emergency treatment of life-threatening hyperkalemia due to its delayed and variable onset of action (hours to days) 1, 2
• Has never undergone rigorous testing in placebo-controlled clinical trials to prove efficacy and safety for acute or chronic hyperkalemia 1

Dosage and Administration

• Oral administration: 15-60g daily, given as 15g (four level teaspoons) 1-4 times daily 2
• Rectal administration: 30-50g every 6 hours 2
• Must be administered at least 3 hours before or after other oral medications (6 hours in patients with gastroparesis) 2
• For oral suspension: mix each dose with 3-4 mL of water or syrup per gram of resin 2
• For rectal administration: administer as warm emulsion in 100 mL of aqueous vehicle and flush with 50-100 mL of fluid 2

Mechanism of Action and Efficacy

• Functions as a cation-exchange resin that binds K+ ions in exchange for sodium ions in the distal colon 1
• Is nonselective for K+, with affinity for calcium and magnesium ions as well 1
• In clinical studies, demonstrated a mean decrease in serum K+ of 1.25 mEq/L compared to 0.21 mEq/L with placebo over 7 days 1
• Increases sodium content significantly (up to 324% in some preparations) while providing only modest decreases in potassium 3

Safety Concerns and Contraindications

• Contraindicated in patients with hypersensitivity to polystyrene sulfonate resins, obstructive bowel disease, or neonates with reduced gut motility 2
• Associated with serious adverse events including 1:
  • Intestinal necrosis and fatal GI injury 4, 5, 6
  • Colonic necrosis (especially when combined with sorbitol) 4, 5
  • Doubling in risk of hospitalization for serious gastrointestinal adverse events 1
  • Overall mortality rate of 33% in some studies 1
• Can cause electrolyte disturbances including hypomagnesemia, hypokalemia, hypocalcemia, and systemic alkalosis 1

Current Recommendations

• As recommended by several regulatory agencies, chronic use of SPS alone or in conjunction with sorbitol should be avoided 1
• For patients with cardiovascular disease on RAAS inhibitors who develop hyperkalemia:
  • For K+ levels >5.0-<6.5 mEq/L: newer K+-lowering agents are preferred 1
  • For K+ levels >6.5 mEq/L: discontinue/reduce RAASi and initiate a K+-lowering agent 1
• Newer potassium binders (patiromer or sodium zirconium cyclosilicate) are recommended as safer alternatives for chronic hyperkalemia management 1, 6

Special Considerations

• Use with caution in patients who cannot tolerate sodium load (heart failure, severe hypertension, marked edema) as Kayexalate contains 1500 mg of sodium per 15g dose 1
• Avoid use in patients at risk for developing constipation or impaction, including those with history of impaction, chronic constipation, inflammatory bowel disease, or previous bowel resection 2
• Monitor for signs of intestinal necrosis, which may occur even with low-dose, short-term therapy 6
• Discontinue use immediately in patients who develop constipation 2

Monitoring

• Close monitoring of serum K+ levels is essential during treatment 1
• Monitor for electrolyte imbalances, particularly hypomagnesemia and hypocalcemia 1
• Assess for gastrointestinal symptoms that may indicate adverse effects 1, 5