Don't give Kayexalate within 3 hours of other drugs, says FDA
The FDA is warning physicians not to provide other enterally-absorbed drugs within 3 hours before or after giving sodium polystyrene sulfonate (Kayexalate, Concordia Pharmaceuticals) for hyperkalemia. In testing performed 59 years after its launch, it was discovered that Kayexalate can bind to many prescription drugs, potentially rendering them ineffective. For patients with gastroparesis or ileus, FDA advises waiting 6 hours after giving Kayexalate, before giving other enterally absorbed medications. The FDA updated the package insert for sodium polystyrene sulfonate in July 2017 to reflect these new dosing recommendations. Sodium polystyrene sulfonate has been around since the 1950s. The drug lowers potassium levels in patients with hyperkalemia by binding to potassium in the colon. It was previously known that Kayexalate could bind to lithium or levothyroxine (Synthroid), but extensive studies of its binding effects on other medications had not been performed. Ironically, it was the release of a “me-too” brand-name potassium binder named patiromer (Veltassa, Relypsa) that led to the realization of Kayexalate’s binding effects. Patiromer was discovered during testing to bind numerous drugs, leading to the FDA insisting its package insert advise physicians not to give oral medications for 6 hours before or after patiromer. After patiromer’s approval, FDA required Concordia Pharmaceuticals to study sodium polystyrene sulfonate’s binding effects on other oral drugs. FDA’s initial advice to physicians was to separate Kayexalate dosing by at least 6 hours from oral drugs. Later in 2016, the interval was reduced to 3 hours for both patiromer and Kayexalate. In in vitro experiments, Kayexalate bound significantly to six oral drugs tested (warfarin, metoprolol, amlodipine, amoxicillin, furosemide, and phenytoin). "The study found significant binding to sodium polystyrene sulfonate occurred with all of these medicines," the FDA said in its safety announcement. It’s interesting that in over 50 years since Kayexalate’s first availability in 1958, this potential for adverse effects went unnoticed. FDA did not report on any known adverse events resulting from proximal administration of Kayexalate and other enterally absorbed medications.
Reference: FDA Drug Safety Communication: FDA recommends separating dosing of potassium-lowering drug sodium polystyrene sulfonate (Kayexalate) from all other oral drugs