What is the recommended dosage of Keyexalate (sodium polystyrene sulfonate) for an outpatient with hyperkalemia?

Kayexalate (Sodium Polystyrene Sulfonate) Outpatient Dosing for Hyperkalemia

Standard Outpatient Dosing

For outpatient management of chronic hyperkalemia, the typical dose of Kayexalate is 15 grams orally once to four times daily, with an average total daily dose ranging from 15-60 grams. 1

• Each 15-gram dose (approximately four level teaspoons) should be suspended in 45-60 mL of water or syrup (3-4 mL liquid per gram of resin) 1
• Administer with the patient in an upright position to reduce aspiration risk 1
• The suspension must be prepared fresh and used within 24 hours 1
• Do not heat the resin as this alters its exchange properties 1

Critical Limitations for Outpatient Use

Kayexalate should NOT be used as emergency treatment for life-threatening hyperkalemia due to its delayed onset of action (several hours to days). 2, 3, 1

• For acute severe hyperkalemia (K+ >6.5 mEq/L) or ECG changes, use rapid-acting treatments first: IV calcium gluconate, insulin/glucose, and nebulized albuterol 2, 3
• The practical exchange ratio is approximately 1 mEq potassium per 1 gram of resin 2
• In clinical trials, 30 grams daily reduced serum potassium by 1.04 mEq/L more than placebo over 7 days in patients with mild hyperkalemia 2, 4

Medication Separation Requirements

Administer Kayexalate at least 3 hours before or 3 hours after other oral medications. 1

• Patients with gastroparesis require a 6-hour separation from other medications 1
• This separation prevents binding of other medications by the resin 1

Sodium Content Warning

Each 15-gram dose contains 1,500 mg (60 mEq) of sodium, which may be problematic in patients with hypertension, heart failure, or fluid overload. 2, 1

• Monitor patients sensitive to sodium intake for signs of fluid overload 1
• Where available, consider non-sodium-containing potassium binders (calcium polystyrene sulfonate) for patients with severe hypertension 2

Absolute Contraindications for Outpatient Use

Do not prescribe Kayexalate to outpatients with the following conditions: 2, 1

• Obstructive bowel disease 1
• Patients who have not had a bowel movement post-surgery 2
• History of constipation or impaction 2
• Inflammatory bowel disease 2
• Ischemic colitis or vascular intestinal atherosclerosis 2
• Previous bowel resection or obstruction 2

Serious Safety Concerns

Serious gastrointestinal adverse events, including intestinal necrosis (with 33% mortality rate), bleeding, and perforation have been reported, particularly when used with sorbitol. 2, 5

• Concomitant administration with sorbitol is NOT recommended 2, 1
• Colon is the most commonly affected site (76.3% of cases) 5
• The average time to developing GI adverse events is approximately 20 days 5
• Discontinue immediately if constipation develops 1

Required Monitoring

Monitor serum potassium, calcium, and magnesium during therapy, as Kayexalate is not totally selective for potassium. 2, 1

• Check electrolytes within 3-7 days after starting treatment 2
• Monitor for signs of hypokalemia, hypocalcemia, and hypomagnesemia 1
• Watch for sodium overload and gastrointestinal toxicity 2

Preferred Alternative Agents

Newer potassium binders (patiromer or sodium zirconium cyclosilicate) are superior to Kayexalate and should be prioritized when available. 2, 3, 6

• Patiromer has an onset of action of approximately 7 hours 2
• Sodium zirconium cyclosilicate (Lokelma) has an onset of approximately 1 hour 2
• These agents offer more predictable onset, better tolerability, and superior safety profiles compared to Kayexalate 2, 3, 6

Clinical Context for Appropriate Use

Kayexalate use should be limited to situations where newer agents are unavailable, and only in patients with normal bowel function and mild-to-moderate chronic hyperkalemia. 2, 7

• Low-dose daily Kayexalate (15-30 grams) can be effective for secondary prevention of hyperkalemia in CKD outpatients on RAAS inhibitors 7
• The intensity and duration of therapy depend on severity and resistance of hyperkalemia 1
• Consider this agent only after optimizing diuretic therapy and correcting metabolic acidosis 2