Pharmacists Can Help Manage Therapies for Hyperkalemia

Hyperkalemia, an electrolyte abnormality characterized by elevated potassium levels, presents a significant challenge in clinical practice. While it affects only 2% to 3% of the general population, its prevalence dramatically increases to about 10% in hospitalized patients, according to Ralph J. Riello III, PharmD, BCPS, an assistant professor adjunct of nephrology at Yale School of Medicine. This condition is particularly common in individuals with chronic kidney disease (CKD) and comorbid heart failure (HF) or those on medications like renin-angiotensin system antagonists, potassium-sparing diuretics, mineralocorticoid receptor antagonists, and even nonsteroidal anti-inflammatory drugs (NSAIDs). In these high-risk groups, the annual risk of hyperkalemia can approach 10% to 20%.

Hyperkalemia, chronic kidney disease, and hypertension often don’t manifest until the diseases become chronically uncontrolled, according to Ralph J. Riello III, PharmD, BCPS. | Image Credit: jarun011 - stock.adobe.com

“I see so many parallels in and actually risk factors for hyperkalemia, chronic kidney disease, or even hypertension. [They] are silent diseases where they’re mostly asymptomatic until very severe manifestations of chronically uncontrolled [disease],” Riello said in Drug Topics’ Pharmacist View.

Clinical signs, such as characteristic electrocardiogram changes or physical symptoms like paresthesia, numbness, or muscle weakness, typically manifest only when potassium levels exceed 5.5 or 6 mEq/L. This lack of immediate symptomatic impact means it is often not front of mind for patients or physicians.

Physicians may also fear uptitrating therapies due to hyperkalemia risk, potentially leading to suboptimal treatment and avoidable hospitalizations. For patients, the burden involves navigating conflicting dietary advice and constant worry about potassium intake.

“Patients may misinterpret dietary counseling as this new credence on life [and] to worry about absolutely everything that they’re eating,” Riello said. “Sometimes those messages can be conflicting, too, with a primary care [physician] trying to treat hypertension, [and] a recommended diet is the DASH [Dietary Approaches to Stop Hypertension] diet, but of course that increases your potassium.”

Pharmacists play a crucial role in acute management, from proactive monitoring and anticipating problems to treatment selection and adverse event management. For chronic hyperkalemia, which can affect up to 20% of CKD or HF patients and 50% of those with end-stage renal disease, management has evolved significantly. Historically, sodium polystyrene sulfate (SPS) was used, but it was never ideal, according to Riello.

Approved based on minimal evidence from small trials in the 1960s, SPS has considerable safety concerns, including gastrointestinal perforation, especially with sorbitol-containing formulations, and unpredictable efficacy.

“The mainstay is potassium binders, and historically, that’s been managed by sodium polystyrene sulfate or SPS,” Riello said. “But owing to vastly superior efficacy, safety, and more rapid uptake of binding potassium, and then subsequent elimination, is the novel K [potassium] binder.”

The introduction of novel potassium binders, sodium zirconium cyclosilicate (SZC) and patiromer, has fundamentally transformed the treatment landscape. These newer agents offer superior efficacy and safety, as well as more rapid action.

Patiromer is a calcium-based ion exchange resin that works gradually, with peak effects between 24 and 48 hours. It requires spacing from other medications due to potential drug interactions, and SZC contains a sodium load—400 mg per 5 g—that can be a concern for volume-overloaded HF patients, but it acts rapidly, typically within 1 to 2 hours, making it a preferred choice for acute, emergent hyperkalemia.

Pharmacists are vital in selecting the appropriate novel binder, considering individual patient factors, formulary availability, and insurance coverage.

“The pharmacist is often the one helping wade through which agent might be appropriate where we are in the treatment algorithm,” Riello said. “You know what’s coming next, and maybe even selecting nuance between some of the agents, where a patient may have some characteristic factors that may make me want to lean one way or the other. Given the 2 choices between at least the 2 novel K binders.”

Another area where pharmacists are essential is transitions of care. Transitions of care, especially from inpatient to outpatient settings, are vulnerable periods where medication errors and missed follow-ups can occur.

“Transitions of care is an incredibly vulnerable period for our admitted inpatients or outpatients who are in the emergency department going to be admitted any phase of care,” Riello said. “Change is an opportunity to introduce a poor handoff or a medication-related error, and it’s important that, especially as the pharmacist, we’re thinking about all the ways with which things can potentially go wrong before they happen.”

Pharmacists are uniquely positioned to bridge these gaps by ensuring that prior authorizations for new therapies are completed and providing comprehensive patient counseling on medications, diet, and OTC products like NSAIDs that can exacerbate hyperkalemia.

Pharmacists can use predictive analytics and artificial intelligence to identify patients at high risk based on potassium trends and trajectories. They can also address health system fragmentation and implement standardized protocols and electronic health record nudges to ensure guideline-based care.

“Everything practicing health care in today’s day and age is going to be a lot more complicated moving forward as we begin to sort of incorporate technology into a lot of these problems,” he said. “Learning how to use those appropriately and how they can help support us as clinicians to make a big impact on our patients.”

With their detailed knowledge of medications and patient counseling skills, pharmacists are crucial in addressing these challenges, ensuring patients receive optimal, guideline-directed care while managing the risks of hyperkalemia across the entire continuum of care.

“I think you should individualize those treatment decisions,” Riello said. “Look for unique and innovative ways to get patients on guideline-directed medical therapy, because the benefit of those agents is just far too strong to not at least try to get your patients on all 4 of those pillars, and if that requires us to add a novel K binder to prevent that risk of hyperkalemia, so be it.”