Sodium polystyrene sulfonate (SPS) has been commonly prescribed to treat hyperkalemia since its approval in 1959. Now new evidence published online ahead of print in JAMA Internal Medicine links outpatient use of the cation-exchange resin with serious adverse gastrointestinal (GI) events, corroborating previous case reports of intestinal injury.

Of 1,853,866 adults older than 66 years in Ontario, Canada, 27,704 received SPS during the period 2003 to 2015, Manish M. Sood, MD, of The Ottawa Hospital, and colleagues reported. The investigators matched SPS users (median age 78 years) to nonusers using high-dimensional propensity scores, accounting for age, sex, diabetes, congestive heart failure, acute kidney injury, chronic dialysis, and hyperkalemia history. Compared with nonuse, SPS use was associated with a 1.9-fold higher risk of hospitalization or emergency department visit within 30 days of initial prescription. The composite GI end point encompassed intestinal ischemia or thrombosis, GI ulceration or perforation, or resection or ostomy. There were 37 events (0.2%) among SPS users and 18 events (0.1%) among nonusers at an incidence rate of 23 vs 11.0 per 1000 person-years, respectively.

In a subset of patients matched by estimated glomerular filtration rate and serum potassium, SPS users still had a 2.9-fold higher risk for the composite end point. The study found no significant difference in adverse GI events by comorbidities, reduced kidney function, history of hyperkalemia, or use of renin-angiotensin-aldosterone system blockade.

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SPS recipients had a 4.5-, 1.8-, and 1.3-fold higher risk of intestinal ischemia or thrombosis, GI ulceration or perforation, or resection or ostomy, respectively.

In 2009, the FDA warned of the risk of intestinal necrosis with administration of sorbitol along with SPS and recommended avoiding this combination. But study analyses showed adverse GI effects occurred with SPS even after the 2009 warning.

“These findings require confirmation and suggest that clinicians should exercise caution in prescribing sodium polystyrene sulfonate,” Dr Sood and his colleagues stated. SPS is sold under the brand names Kayexalate and Kionex or as a generic. The team had no information on the dose or route of SPS administration, which are study limitations.

Monica Parks, MD, and Deborah Grady, MD, MPH, of the University of California, San Francisco, agreed with the caution in an accompanying editorial: “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.”

The editorialists hesitated to recommend new hyperkalemia drugs. “Newer cation-exchange agents are entering clinical use,” they noted, “but data describing their success in reducing hyperkalemia are limited, and there is very little data regarding long-term safety.”

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Noel JA, Bota SE, Petrcich W, et al. Risk of hospitalization for serious adverse gastrointestinal events associated with sodium polystyrene sulfonate use in patients of advanced age. JAMA Intern Med. (Published online June 10, 2019.) doi:10.1001/jamainternmed.2019.0631

Parks M and Grady D. Sodium polystyrene sulfonate for hyperkalemia. JAMA Intern Med. (Published online June 10, 2019.) doi:10.1001/jamainternmed.2019.1291