What is the role of Kayexalate (sodium polystyrene sulfonate) in managing hyperkalemia?

From the Guidelines

Kayexalate (sodium polystyrene sulfonate) should not be used as a first-line treatment for hyperkalemia due to its slow onset of action, potential for serious gastrointestinal adverse effects, and the availability of newer, safer potassium binders like patiromer and sodium zirconium cyclosilicate. The use of Kayexalate is associated with risks of intestinal ischemia and colonic necrosis, a doubling in the risk of hospitalization for serious gastrointestinal adverse events, and a reported overall mortality rate of 33% 1. Its nonselective binding properties may also lead to hypocalcemia and hypomagnesemia, and because orally administered Kayexalate potentially binds to other oral medications, their administration should be carefully managed 1. Newer potassium binders like patiromer and sodium zirconium cyclosilicate have been shown to be effective and safe in clinical trials, and are now approved for use in the United States and the European Union 1. The National Institute for Health and Care Excellence has recently provided recommendations regarding the use of these newer agents for the treatment of acute life-threatening hyperkalemia, stating that they may be considered for use in conjunction with standard care 1. In patients with hyperkalemia, an evaluation should be made of the patient’s diet, use of supplements, salt substitutes, and nutraceuticals that contain potassium, as well as of concomitant medications that may contribute to hyperkalemia 1. In general, renin-angiotensin-aldosterone system inhibitor therapy should be started at a low dosage and titrated to the maximum tolerated evidence-based doses shown to reduce the risk of cardiovascular and renal events in clinical trials 1. If potassium levels raise above 5.0 mEq/L, potassium-lowering measures should be initiated, and treatment with a potassium-lowering agent may be initiated as soon as potassium levels exceed 5 mEq/L 1. Given the potential risks and limitations of Kayexalate, it is recommended to use newer potassium binders like patiromer and sodium zirconium cyclosilicate as first-line treatment for hyperkalemia, reserving Kayexalate for second-line or adjunctive therapy in specific cases where its use is deemed necessary.

From the FDA Drug Label

Sodium polystyrene sulfonate is indicated for the treatment of hyperkalemia. Limitation of Use: Sodium Polystyrene Sulfonate should not be used as an emergency treatment for life-threatening hyperkalemia because of its delayed onset of action [see Clinical Pharmacology ( 12.2)].

The role of Kayexalate (sodium polystyrene sulfonate) in managing hyperkalemia is to treat the condition by binding to potassium in the gut and removing it from the body. However, it should not be used as an emergency treatment for life-threatening hyperkalemia due to its delayed onset of action 2. The recommended dosage varies depending on the severity of hyperkalemia, with oral doses ranging from 15 g to 60 g per day, and rectal doses ranging from 30 g to 50 g every six hours 2. Key considerations for its use include:

• Administering the medication at least 3 hours before or after other oral medications
• Avoiding use in patients with obstructive bowel disease, hypersensitivity to polystyrene sulfonate resins, or reduced gut motility in neonates
• Monitoring for signs of intestinal necrosis and other gastrointestinal adverse events 2.

From the Research

Role of Kayexalate in Managing Hyperkalemia

• Kayexalate, also known as sodium polystyrene sulfonate, is a cation exchange resin that has been used for over 50 years to treat hyperkalemia 3.
• It is not effective as an acute therapy, but it may be useful when given more chronically 3.
• Kayexalate works by binding potassium in the gastrointestinal tract and facilitating its excretion through the feces 4.
• However, its use is associated with gastrointestinal side effects and safety concerns, such as rare GI damage 4, 5.

Comparison with Other Treatments

• Newer agents, such as patiromer and sodium zirconium cyclosilicate, have been shown to be effective and well-tolerated for the treatment of hyperkalemia 4, 6.
• These agents have improved upon the traditional standard of Kayexalate, with fewer adverse effects and more rapid reduction of serum potassium levels 4, 7, 6.
• A retrospective chart review found that sodium zirconium cyclosilicate and Kayexalate had similar rates of normokalemia achievement when used in combination with IV insulin for acute hyperkalemia 7.

Safety and Efficacy

• Kayexalate has been associated with electrolyte abnormalities and gastrointestinal side effects, including constipation and diarrhea 4, 5.
• Patiromer and sodium zirconium cyclosilicate have been shown to be safe and effective for the treatment of hyperkalemia, with fewer adverse effects than Kayexalate 4, 6.
• However, sodium zirconium cyclosilicate has been associated with an increased risk of edema, particularly in patients with chronic kidney disease or heart failure 6.