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Concerns About GI Events Continue With Sodium Polystyrene Sulfonate

by Brenda Mooney

September 22, 2019

About 9,000 Veterans Were Prescribed Drug for Hyperkalemia

OTTAWA, ONTARIO—Continuing concerns are being raised about the gastrointestinal safety of sodium polystyrene sulfonate, which is commonly prescribed for the treatment of hyperkalemia.

The issue is of special concern at the VA, where patients tend to be older with more comorbidities. A recent report suggested that about 8,000 VA patients were being treated with sodium polystyrene sulfonate.

Risk of Hospitalization for Serious Adverse Gastrointestinal Events Associated With Sodium Polystyrene Sulfonate Use in Patients of Advanced Age
30-Day Probability of Gastrointestinal (GI) Injury Requiring Hospitalization or Emergency Department Visit Associated With Sodium Polystyrene Sulfonate Use Compared With NonuseResults presented are for the matched analysis of sodium polystyrene sulfonate users to nonusers on the logit of the high-dimensional propensity score (±0.2 of the standard deviation) and the following: age, sex, diabetes, congestive heart failure, prior acute kidney injury, chronic dialysis, history of hyperkalemia, previous nephrologist visit, medication use (β-blocker or renin-angiotensin-aldosterone system blockade), and index date (within 1 year). Additional adjustment was for place of residence.

A study published in JAMA Internal Medicine recently sought to assess the risk of hospitalization for adverse GI events associated with sodium polystyrene sulfonate use in patients of advanced age. “The use of sodium polystyrene sulfonate is associated with a higher risk of hospitalization for serious adverse GI events,” study authors from the University of Ottawa concluded. “These findings require confirmation and suggest caution with the ongoing use of sodium polystyrene sulfonate.”1

Commentators from the San Francisco VAMC and the University of California San Francisco explained why the findings are so important for pharmacists and other health professionals.2

“In addition to very weak evidence for positive outcomes, there is mounting evidence of harm caused by this drug,” wrote the San Francisco VAMC’s Deborah Grady, MD, MPH, who also is the deputy editor of JAMA Internal Medicine, and her colleague at UCSF Monica Parks, MD.

Grady and Parks noted the following history:

  • As early as the 1980s, cases of intestinal necrosis associated with sodium polystyrene sulfonate in sorbitol, the typical method of administration, were reported;
  • In 2009, the FDA warned of the risk of intestinal necrosis with administration of sodium polystyrene sulfonate in sorbitol and recommended avoiding the combination of these medications in postoperative patients and those with intestinal obstruction or chronic bowel disease, including constipation.
  • In a literature review published in 2010, intestinal necrosis was described only as a complication of the combination of sodium polystyrene sulfonate and sorbitol; in particular, 70% sorbitol and sodium polystyrene sulfonate preparations without sorbitol were reported to be safe.

The editorialists pointed out that the mechanism of action leading to intestinal necrosis was assumed to be related to hyperosmotic load from sorbitol leading to adenosine triphosphate–dependent sodium-potassium pump dysfunction, alteration of cellular membrane transport systems, and reduced intestinal blood flow. Comorbidities such as intestinal obstruction, diabetes or vascular disease were thought to heighten the risk.

“More recently, however, case reports of intestinal necrosis following sodium polystyrene sulfonate administration without sorbitol have also emerged,” the commentary stated. “A systematic review of 48 cases of intestinal necrosis after drug administration found 17 cases among patients not taking sorbitol, suggesting that sodium polystyrene sulfonate alone could also cause this complication.”

The recent population-based, retrospective matched cohort study focused on eligible adults older than age 66 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 and were mostly, 54.7%, male. For the study, 20,020 sodium polystyrene sulfonate users were matched to an equal number of nonusers.

 

Adverse GI Events

Results indicated that sodium polystyrene sulfonate use vs. 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 1000 person-years vs 18 events [0.1%]; incidence rate, 11.01 per 1000 person-years) (hazard ratio, 1.94; 95% CI, 1.10-3.41).

Researchers explained 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.

“So what should clinicians do?” the editorial asks. “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 se rum potassium.”

A newer cation-exchange resin, patiromer, has recently been approved for lowering serum potassium levels in patients with chronic hyperkalemia. Patiromer is a polymer-based agent that binds potassium in the colon in exchange for calcium. Patiromer, marketed as Veltassa, is not available as a generic drug and costs about $1,000 per month compared with about $10 per month for sodium polystyrene sulfonate, according to the article.

The commentary did not suggest that was the best alternative to sodium polystyrene sulfonate at this point, however, stating, “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 (three days to eight weeks), and the drug has not been widely used in practice. It is possible that this drug may also cause significant adverse events.”

A presentation at the recent American Nephrology Nurses Association Meeting, involving researchers form the Stratton VAMC in Albany, NY, and the Salt Lake City  VAMC, suggested use of patiromer remains limited with VA patients.3

The retrospective cohort study sought to describe treatment patterns in veterans with hyperkalemia—either with sodium polystyrene sulfonate or with patiromer, the novel sodium-free, non-absorbed potassium (K+) binder. To do that, researchers collected data from the VA Corporate Data Warehouse from Jan. 1, 2016 until Dec. 31, 2017.

Included were patients with evidence of hyperkalemia, defined as K+ ≥5.1 mEq/L, and heart failure, diabetes mellitus, or CKD prior to index. Follow-up lasted until discontinuation, death or six months post index.

The study team measured utilization parameters including initial dose, Rx fills, days supplied/fill, proportion of days covered, and percentage of patients with a proportion of days covered greater than 80%.

Results indicated that 193 patients with hyperkalemia were treated with patiromer at index vs. 8,942 treated with sodium polystyrene sulfonate. The study determined that, in the patiromer group, median age was 69 years, 24% were African American, 96% had CKD, and 37% had heart failure. In the SPS group, median age was 70 years, 22% were African American, 68% had CKD, and 27% had heart failure. The initial doses were 8.4 g patiromer and 15 g sodium polystyrene sulfonate.

Researchers calculated that the median number of prescription fills were two in the patiromer group and one in the SPS group. At the same time, median days supplied/prescription fill was 30 in the patiromer group and three in the SPS group, while median PDC was 41% in the patiromer group and 2% in the SPS group. The PDC ≥80% was 16% in the patiromer group and 1% in the SPS group.

 

“This descriptive analysis among US veterans showed contrasting utilization patterns for patients exposed to patiromer and SPS for the treatment of hyperkalemia,” the researchers explained. “The days supplied/prescription, the number of prescription fills, and the higher PDC suggest a more chronic treatment pattern for patiromer and an episodic pattern for SPS. Given the limited number of patiromer users in this database, these findings warrant further study.”

  1. Noel JA, Bota SE, Petrcich W, Garg AX, et. Al. Risk of Hospitalization for Serious Adverse Gastrointestinal Events Associated With Sodium Polystyrene Sulfonate Use in Patients of Advanced Age. JAMA Intern Med. 2019 Jun 10. doi: 10.1001/jamainternmed.2019.0631. [Epub ahead of print] PubMed PMID: 31180477; PubMed Central PMCID: PMC6563537.
  2. Parks M, Grady D. Sodium Polystyrene Sulfonate for Hyperkalemia. JAMA Intern Med. 2019;179(8):1023-1024. doi:10.1001/jamainternmed.2019.1291
  3. Gosmanova EO, Kovesdy CP, Woods SD, et al. Disparities in real-world utilization patterns of potassium binders in US veterans with hyperkalemia. Abstract of a presentation at the 2019 American Nephrology Nurses Association National Symposium, April 14-17, 2019, Dallas Texas.


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