Sodium zirconium cyclosilicate (SZC) (Lokelma) is a non-absorbed, non-polymer inorganic powder with a uniform micropore structure that preferentially captures potassium in exchange for hydrogen and sodium cations. It is indicated for the treatment of hyperkalemia in adult patients. The recommended starting dose for patients whose serum potassium level is > 5.0 mmol/L (correction phase) is 10 g administered three times a day as an oral suspension (in water) for up to two days. For continued maintenance treatment, a dose of 5 g daily is recommended, with possible titration up to 10 g once daily or down to 5 g once every other day, as needed. No more than 10 g daily should be used for maintenance therapy. The sponsor submitted a price for SZC of $12.50 per 5 g and $25.00 per 10 g sachet. At the recommended dose of 10 g three times a day during the correction phase, SZC costs $75 daily. The average annual cost of SZC for maintenance treatment ranges from $2,283 to $9,131 per patient ($6.25 to $25 daily). The sponsor submitted a cost-utility analysis comparing SZC with best supportive care (BSC), which included the intermittent use of sodium polystyrene sulfonate (SPS) or calcium polystyrene sulfonate (CPS) for the correction of serum potassium levels as well as lifestyle interventions for the maintenance of serum potassium levels. The sponsor considered two distinct populations in its economic evaluation: 1) adult patients with hyperkalemia who require corrective treatment; and, 2) adult patients requiring maintenance treatment who have chronic kidney disease (CKD), an estimated glomerular filtration rate (eGFR) of < 30 mL/min/1.73m, a history of at least two hyperkalemia events, and who are required to be suboptimally managed on renin-angiotensin-aldosterone system inhibitor (RAASi) therapies. The primary analysis reflected a population of adult patients with hyperkalemia and an underlying condition of advanced CKD and/or heart failure (HF), with scenario analyses focusing on a CKD-only and an HF-only population. The sponsor’s base-case model was conducted from the perspective of the Canadian publicly funded health care payer over a lifetime horizon (up to a maximum age of 100 years). Future costs and benefits were discounted at 1.5% per annum. In the model, patients transition between HF and CKD states. They may also experience worsening of kidney function, transition to end-stage renal disease, and initiate renal replacement therapy (RRT). Patients were assumed to experience a hyperkalemia event when their serum potassium levels exceeded a defined threshold (5.5 mmol/L). Major adverse cardiac events (MACEs), hospitalization, changes in RAASi use, and mortality were dependent on serum potassium levels. The sponsor assumed that patients who started treatment on SZC would move on to BSC if they discontinued their initial treatment. Reinitiation was allowed after the first 28-day period and prior to RRT initiation. Both CKD and HF progression were based on the literature, and a mixed-effects regression model based on clinical trial data was used to inform treatment-specific serum potassium profiles. Utility values were obtained from the literature. The sponsor reported that SZC was associated with both more costs (increases of $663 for acute correction and $28,719 for maintenance) and quality-adjusted life-years (QALYs) than BSC (0.008 more QALYs for acute correction and 0.343 more QALYs for maintenance). The resulting incremental cost-effectiveness ratios (ICERs) were $82,067 per QALY for acute correction and $83,693 per QALY for maintenance.