Ion-Exchange Resins for the Treatment of Hyperkalemia: Are They Safe and Effective? is the title of a Clinical Commentary in this month’s Journal of the American Society of Nephrology. Kayexalate is the brand name of the commonly prescribed cation exchange resin sodium polystyrene sulfonate (SPS) used to treat hyperkalemia (high blood potassium).
The drug was first marketed in 1958 four years before the FDA required that makers of new drugs show that they were safe and efficacious. Since then it has been widely used and generally considered safe and efficacious. I have given it or watched it be given to thousands of patients and have never observed a complication attributed to its use. But recently the benign impression of the resin held by most physicians has been challenged.
Studies demonstrating the effectiveness of SPS in humans have not been as robust as would now be required were this drug under FDA review today. While it does seem to be effective in reducing potassium levels in hyperkalemic patients, it appears to take several days to do the job.
Soon after it was released doctors recognized that it could cause severe constipation and even life threatening intestinal impaction. Accordingly it was given with the over the counter osmotic laxative sorbitol. For decades everything seemed fine, “but by 2005, the FDA had received 35 adverse event reports of serious bowel injuries associated with both oral and rectal of the mixture (SPS and 70% sorbitol), many of them fatal.” [Quotation from above article, parenthesis added by me.] On the basis of animal work sorbitol was considered the culprit. The FDA soon recommended that the sorbitol concentration be reduced to 33% though 70% sorbitol is still marketed as an over the counter laxative.
Yet reports of bowel injury, some fatal following use of SPS and 33% sorbitol have been reported. The authors of this commentary conclude : “Clinicians must weigh uncontrolled studies showing benefit against uncontrolled studies showing harm. It would be wise to exhaust other alternative for managing hyperkalemia before turning to these largely unproven and potentially harmful therapies.
It’s hard to know what to make of these observations. Much of what doctors do is based on shaky evidence. While my experience with SPS is greater than most doctors, it’s small considering how many doses of the drug are administered yearly – 5 million. Prudence demands that we cast a jaundiced eye on SPS though controlled studies examining the safety and effectiveness of the preparation will likely never be done.