What is the appropriate dosing regimen of sodium polystyrene sulfonate (Kayexalate) for an adult with hyperkalemia?

Kayexalate (Sodium Polystyrene Sulfonate) Dosing for Hyperkalemia

Critical Limitation: Not for Emergency Use

Kayexalate should NOT be used as emergency treatment for life-threatening hyperkalemia due to its delayed onset of action (several hours to days). 1 For acute severe hyperkalemia with ECG changes or potassium >6.5 mEq/L, use faster-acting treatments first: IV calcium gluconate, insulin/glucose, and albuterol. 2

Standard Dosing Regimens

Oral Administration

• Standard adult dose: 15-60 g daily, typically given as 15 g (four level teaspoons) one to four times daily 1
• Suspend each dose in 3-4 mL of liquid per gram of resin (water or syrup preferred) 1
• Administer with patient in upright position 1
• Must be given at least 3 hours before or after other oral medications (6 hours in gastroparesis) 1

Rectal Administration

• Average adult dose: 30-50 g every 6 hours as retention enema 1
• Administer as warm emulsion in 100 mL aqueous vehicle, flush with 50-100 mL fluid 1
• Retain as long as possible, follow with cleansing enema using up to 2 liters of non-sodium containing solution 1

Expected Efficacy

The potassium-lowering effect is modest and dose-dependent:

• 15 g oral dose: reduces potassium by approximately 0.39-0.51 mEq/L 3, 4
• 30 g oral dose: reduces potassium by approximately 0.58-0.93 mEq/L 5, 3, 4
• 60 g oral dose: reduces potassium by approximately 0.91 mEq/L 3
• 30 g rectal dose: reduces potassium by only 0.22 mEq/L 3

Time to effect: Potassium reduction typically occurs 14-16 hours post-administration 6

Serious Safety Concerns

Gastrointestinal Toxicity

Kayexalate carries significant risk of intestinal necrosis, bowel perforation, ischemic colitis, and gastrointestinal bleeding—some cases fatal. 1 The risk doubles for serious GI adverse events, with an overall mortality rate of 33% reported. 7

Absolute Contraindications

• Hypersensitivity to polystyrene sulfonate resins 1
• Obstructive bowel disease 1
• Neonates with reduced gut motility 1
• Never use concomitantly with sorbitol (increases necrosis risk) 1

High-Risk Populations to Avoid

• Patients without recent bowel movement post-surgery 1
• History of constipation, impaction, or inflammatory bowel disease 1
• Ischemic colitis or vascular intestinal atherosclerosis 1
• Previous bowel resection or obstruction 1

Critical Monitoring Requirements

Electrolyte Monitoring

• Monitor serum potassium during therapy—severe hypokalemia may occur 1
• Monitor calcium and magnesium (resin is not selective; small amounts of other cations are also lost) 1
• Check for hypernatremia: each 15 g dose contains 1,500 mg (60 mEq) sodium 1

Sodium Content Warning

Each 15 g dose contains 100 mg (4.3 mmol) sodium per gram of powder. 8 Monitor patients sensitive to sodium intake (heart failure, hypertension, edema) for fluid overload and adjust other sodium sources. 1

Preferred Alternative in Specific Populations

In children with severe hypertension and hyperkalemia, non-sodium-containing potassium binders (calcium polystyrene sulfonate) should be used where available. 8, 7 Calcium polystyrene sulfonate has a more favorable safety profile than sodium polystyrene sulfonate, especially for long-term use. 2

Modern Clinical Context

Newer FDA-approved potassium binders (patiromer and sodium zirconium cyclosilicate) are now preferred for long-term hyperkalemia management due to superior safety profiles. 7 Sodium polystyrene sulfonate should be avoided for chronic management due to severe GI adverse effects including bowel necrosis. 7

Practical Dosing Algorithm

For mild hyperkalemia (5.0-5.9 mEq/L) without ECG changes:

• Start with 30 g oral dose if GI tract functional and no contraindications 3
• Recheck potassium 14-24 hours post-dose 6, 5
• 60 g oral dose may be used for more aggressive reduction (expect ~0.9 mEq/L decrease) 3

For moderate hyperkalemia (6.0-6.5 mEq/L):

• Use faster-acting agents first (insulin/glucose, albuterol), then consider Kayexalate as adjunct 2
• 30-60 g oral dose if patient stable without ECG changes 3

Rectal administration is significantly less effective and should be reserved for patients unable to take oral medication. 3