Using Potassium Binders to Simplify Hyperkalemia Management

Using Potassium Binders to Simplify Hyperkalemia Management
Hyperkalemia, or high serum potassium, can be defined differently depending on which reference or healthcare professional you consult. The upper limit of normal varies across guidelines and publications; serum potassium concentrations of 5.0, 5.5, or 6.0 mEq/L are commonly used as cutoffs, creating a gray zone around diagnosis. For example, a patient with a serum potassium of 5.6 mEq/L has mild hyperkalemia in the eyes of a nephrologist based on the Kidney Disease: Improving Global Outcomes Consensus Conference. However, that patient has moderate hyperkalemia from the perspective of a heart failure team following guidance from Journal of the American College of Cardiology’s State of the Art Review.

To further complicate the picture, a single serum potassium value does not provide enough information to classify hyperkalemia as a transient, acute event or a sustained, recurrent, chronic event. An appropriate assessment and understanding of the underlying causes can help healthcare professionals get out of the gray zone when it comes to hyperkalemia management.   

Determining Which Patients Are at High Risk for Chronic Hyperkalemia
It’s important to recognize that comorbidities, such as diabetes, heart failure, and CKD, increase risk for hyperkalemia and adverse clinical outcomes, including mortality. There’s also a catch-22 in terms of the guideline-directed medical therapies used to treat these comorbidities. Although renin–angiotensin–aldosterone system (RAAS) inhibitors (eg, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, angiotensin receptor-neprilysin inhibitors, and aldosterone antagonists) have been shown in clinical trials to improve morbidity and mortality, they may precipitate drug-induced hyperkalemia. As a result, these drugs are often underprescribed in patients with a history of hyperkalemia or mild hyperkalemia (5.0-5.5 mEq/L) at baseline. In addition, chronic hyperkalemia is a common electrolyte abnormality: The reported prevalence from cohort studies was 54% in patients with predialysis CKD and 39% in patients with heart failure in Denmark. As such, our strategies to treat these patients must take the potential for hyperkalemia into account.

Clinical Pathway for Chronic Hyperkalemia Management
Multidisciplinary management of chronic hyperkalemia is recommended and should include physicians, nurses, nutritionists, and pharmacists. In general, salt substitutes should be avoided. Whereas counseling regarding dietary potassium intake is a reasonable place to start, there is limited evidence to suggest that potassium restriction will achieve the desired effect in most patients. Adherence to a low-potassium diet can be difficult—and there are many healthy, potassium-rich foods with beneficial effects including decreased blood pressure and decreased risk of stroke—therefore, consistency is key.

Pharmacists should review for medication-related etiologies for hyperkalemia (such as nonsteroidal anti-inflammatory drugs, herbal supplements, and the medications mentioned above). Although loop diuretics are useful adjunct agents, I use them with caution, particularly in patients with CKD or heart failure. Adverse events associated with diuretic therapy may include volume depletion, worsening kidney function, hypokalemia, and syncope.

The Role of Potassium Binders
Recurrent hyperkalemia warrants consideration of a potassium binder. Although sodium polystyrene sulfonate (SPS) has been around for decades, it was approved before the era of evidence-based medicine, which means that there are no clinical trial data on onset of effect or time to normalization of potassium levels. There are also serious safety concerns with the use of this agent. Even though the FDA issued a warning in 2009 to avoid sorbitol-containing SPS due to risk for colonic necrosis and other serious gastrointestinal adverse events, there are case reports of fatal gastrointestinal injury even with sorbitol-free SPS.

In my practice I do not use SPS, as there are 2 newer potassium binders with robust safety and efficacy data. Of most importance, these drugs have been studied in various patients, including those with diabetes, CKD, heart failure and on concurrent RAAS inhibitor therapy. Both patiromer and sodium zirconium cyclosilicate work within hours of first dose and have data to support long-term use and normokalemia for ≤1 year. They are dosed once daily as maintenance therapy and supplied as powders for suspension: Patiromer can be mixed with water or other beverages or soft foods whereas sodium zirconium cyclosilicate should be mixed with water. Administration of other drugs should be separated by 2 hours when using sodium zirconium cyclosilicate or 3 hours when using patiromer.

In our practice, we encourage patients to take their potassium binder before bed to mitigate drug–drug interactions and create a routine to improve adherence. It is important to educate patients that rebound hyperkalemia may occur within 3-6 days when these drugs are stopped abruptly when counseling them about adherence.

Can Novel Potassium Binders Be Used for Acute Hyperkalemia?
Sodium zirconium cyclosilicate and patiromer are not approved and should not be used in acute, life-threatening hyperkalemia. However, a recent study using electronic health record data examined patiromer use for non–life-threatening hyperkalemia in more than 800 patients in an institution setting (emergency department, inpatient unit, or intensive care unit). A single dose of patiromer was associated with a rapid and significant decrease in serum potassium, and 82% of patients required no additional doses. These findings suggest that patiromer monotherapy may be useful intermittently for acute, non–life-threatening hyperkalemia, although further research is needed.

Clinical Pearls
Balancing the risks of hyperkalemia and the benefits RAAS inhibitors creates a complex clinical challenge. However, novel potassium binders can and should be used to enable RAAS inhibition, especially for patients with heart failure. Evidence to support this comes from the DIAMOND trial, which demonstrated that 85% of patients were able to receive the optimized level of RAAS inhibitors with the use of patiromer.

Regarding pediatric patients, there are real-world data on patiromer in infants and the ongoing PEDZ-K study will provide insight on sodium zirconium cyclosilicate in children under 18 years of age.

Insurance coverage or institutional formularies may dictate which potassium binder we prescribe. Some insurance plans require prior authorization. Manufacturers of these compounds often have funds to assist patients with their copay, if needed.

There are a few clinical scenarios where one binder may be preferred over the other. For instance, sodium zirconium cyclosilicate exchanges potassium for sodium; therefore, dose-dependent edema is an adverse drug event for which we must assess in our patients with heart failure. On the other hand, patiromer exchanges potassium for calcium but can also remove magnesium, so monitoring for hypomagnesemia is warranted. Although there are real-world data on patiromer use in dialysis-dependent end-stage kidney disease, the DIALIZE trial specifically examined the effects of sodium zirconium cyclosilicate on predialysis potassium levels to establish a dosing regimen on nondialysis days, only.

Patient acceptance may also guide choice: As noted above, patiromer may be suspended in a various liquids or soft foods (including yogurt) for administration, whereas sodium zirconium cyclosilicate must be suspended in water, according to the prescribing information for this drug. For those patients who cannot tolerate sodium zirconium cyclosilicate as a water suspension, patiromer might be the better choice.

These strategies can be used by pharmacists to promote adoption and implementation of guideline-directed medical therapy and potassium binders into routine clinical practice to improve outcomes for their patients.

Your Thoughts?
Do you have any experience using potassium binders for your patients with hyperkalemia? Start the conversation by adding your comments to the box.