Ottawa, Ontario—A study has raised continued concerns about the gastrointestinal (GI) safety of sodium polystyrene sulfonate, which is commonly prescribed for the treatment of hyperkalemia.

In 2009, case reports of intestinal injury after administration of sodium polystyrene sulfonate with sorbitol resulted in an FDA warning and discontinuation of combined 70% sorbitol–sodium polystyrene sulfonate formulations.

A study published in JAMA Internal Medicine sought to assess the risk of hospitalization for adverse GI events associated with sodium polystyrene sulfonate use in patients of advanced age.

University of Ottawa–led researchers conducted the population-based, retrospective matched cohort study of eligible adults older than age 66 years who received sodium polystyrene sulfonate from April 1, 2003, to September 30, 2015, in Ontario, Canada.

Defined as the primary outcome was a composite of adverse GI events—hospitalization or emergency department visit with intestinal ischemia/thrombosis, GI ulceration/perforation, or resection/ostomy within 30 days of initial sodium polystyrene sulfonate prescription.

From more than 1.8 million eligible adults, 27,704 patients were dispensed sodium polystyrene sulfonate; participants had a mean age of 78.5 years and were mostly male—54.7%. For the study, 20,020 sodium polystyrene sulfonate users were matched to an equal number of nonusers.

Results indicate that sodium polystyrene sulfonate use versus nonuse was associated with a higher risk of an adverse GI event over the following 30 days (37 events [0.2%]; incidence rate, 22.97 per 1,000 person-years vs. 18 events [0.1%]; incidence rate, 11.01 per 1,000 person-years) (hazard ratio, 1.94; 95% CI, 1.10-3.41).

Researchers point out that the findings remained consistent in additional analyses, including the subpopulation with baseline laboratory values (hazard ratio, 2.91; 95% CI, 1.38-6.12). Intestinal ischemia/thrombosis was the most common type of GI injury, they said.

“The use of sodium polystyrene sulfonate is associated with a higher risk of hospitalization for serious adverse GI events,” study authors conclude. “These findings require confirmation and suggest caution with the ongoing use of sodium polystyrene sulfonate.”

In an accompanying editorial, commentators from the University of California, San Francisco and the San Francisco Veterans Affairs Medical Center suggest the research could be practice-changing. “So what should clinicians do?” they ask. “Given the evidence, sodium polystyrene sulfonate should not be used to reduce serum potassium levels. There are a number of other approaches to treating elevated serum potassium levels, including dietary restriction of potassium, potassium-wasting diuretics, and lower doses or discontinuation of medications that increase serum potassium. Given the lack of evidence of GI adverse events related to patiromer, it may be tempting to choose this drug rather than sodium polystyrene sulfonate. However, studies of patiromer have been small and short-term (3 days to 8 weeks), and the drug has not been widely used in practice. It is possible that this drug may also cause significant adverse events.”

The editorial concludes that “evidence for positive outcomes with cation-exchange resins is weak, and accumulating evidence suggests that sodium polystyrene sulfonate increases risk for serious GI adverse events such as intestinal necrosis. Despite this, sodium polystyrene sulfonate is still commonly used to treat moderate hyperkalemia when no treatment or alternative treatments should be preferred. Newer cation-exchange agents are entering clinical use, but data describing their success in reducing hyperkalemia are limited, and there is very little data regarding long-term safety.”

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