Becker's Hospital Review

STUDY 3 DESIGN: LOKELMA was evaluated for long-term efficacy in 751 patients with hyperkalemia in an open-label, single-arm, 12-month, phase 3 study. Following the initial-phase treatment of LOKELMA 10 g tid, patients who achieved normokalemia within 72 hours (n=746; 99%) entered the maintenance phase. For maintenance treatment, the initial dose of LOKELMA was 5 g qd and was adjusted to a minimum of 5 g qod up to a maximum of 15 g qd, based on i-STAT K + was 5 g qd and was adjusted to a minimum of 5 g qod up to a maximum of 15 g qd, based on i-STAT K + was 5 g qd and was adjusted to a minimum of 5 g qod up to a maximum of 15 g qd, based on i-STAT K level. The primary endpoints included the percentage of patients who achieved normokalemia (K + normokalemia (K + normokalemia (K = 3.5 - 5.0 mEq/L), based on serum K + based on serum K + based on serum K levels, during the initial phase and the percentage of patients who maintained mean serum K + levels, during the initial phase and the percentage of patients who maintained mean serum K + levels, during the initial phase and the percentage of patients who maintained mean serum K ≤5.1 mEq/L during Months 3-12 of the maintenance phase. 1,5 89% of patients continued RAAS inhibitor use while taking LOKELMA. 5 *Patients were counted more than once if they required more than 1 RAAS inhibitor adjustment, so the total percentage across all 4 categories may exceed 100%. 5 LOKELMA is a registered trademark of the AstraZeneca group of companies. ©2023 AstraZeneca. All rights reserved. US-73859 3/23 You are encouraged to report the negative side effects of prescription drugs to the FDA. Visit www.FDA.gov/medwatch or call 1-800-FDA-1088. Abbreviations: HK=hyperkalemia; K + HK=hyperkalemia; K + HK=hyperkalemia; K = potassium; qd=once daily; qod=every other day; RAASi=renin-angiotensin-aldosterone system inhibitor; tid=3 times a day References: 1. LOKELMA ® (sodium zirconium cyclosilicate) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2022. 2. Kidney Disease: Improving Global Outcomes (KDIGO) Diabetes Work Group. KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease. Kidney Int. 2022;102(5S):S1-S127. doi:10.1016/j.kint.2022.06.008 3. Kidney Disease: Improving Global Outcomes (KDIGO) Blood Pressure Work Group. KDIGO 2021 clinical practice guideline for the management of blood pressure in chronic kidney disease. Kidney Int. 2021;99(3S):S1-S87. doi:101016/j.kint.2020.11.003 4. Heidenreich PA, Bozkurt B, Aguilar D, et al. 2022 AHA/ACC/HFSA guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association joint committee on clinical practice guidelines. J Am Coll Cardiol. 2022;79(17):e263-e421. doi:10.1016/j.jacc.2021.12.012 5. Spinowitz BS, Fishbane S, Pergola PE, et al. Sodium zirconium cyclosilicate among individuals with hyperkalemia: a 12-month phase 3 study. Clin J Am Soc Nephrol. 2019;14(6):798-809. doi:10.2215/CJN.12651018 IMPORTANT SAFETY INFORMATION FOR LOKELMA INDICATION AND LIMITATION OF USE LOKELMA is indicated for the treatment of hyperkalemia in adults. LOKELMA should not be used as an emergency treatment for life-threatening hyperkalemia because of its delayed onset of action. WARNINGS AND PRECAUTIONS: ▶ Gastrointestinal Adverse Events in Patients with Motility Disorders: Avoid LOKELMA in patients with severe constipation, bowel obstruction or impaction, including abnormal post-operative bowel motility disorders. LOKELMA has not been studied in patients with these conditions and it may be ineffective and may worsen gastrointestinal conditions ▶ Edema: Each 5-g dose of LOKELMA contains approximately 400 mg of sodium, but the extent of absorption by the patient is unknown. In clinical trials of LOKELMA in patients who were not on dialysis, edema was observed and was generally mild to moderate in severity and was more commonly seen in patients treated with 15 g once daily. Monitor for signs of edema, particularly in patients who should restrict their sodium intake or are prone to fluid overload (eg, heart failure or renal disease). Advise patients to adjust dietary sodium, if appropriate. Increase the dose of diuretics as needed In a clinical trial of LOKELMA in patients on chronic hemodialysis in which most patients were treated with doses of 5 g to 10 g once daily on non-dialysis days, there was no difference in the mean change from baseline in interdialytic weight gain (a measure of fluid retention) between the LOKELMA and placebo groups ▶ Hypokalemia in Patients on Hemodialysis: Patients on hemodialysis may be prone to acute illness that can increase the risk of hypokalemia on LOKELMA (eg, illnesses associated with decreased oral intake, diarrhea). Consider adjusting LOKELMA dose based on potassium levels in these settings ▶ Diagnostic Tests: LOKELMA has radio-opaque properties and, therefore, may give the appearance typical of an imaging agent during abdominal X-ray procedures ADVERSE REACTIONS: The most common adverse reaction in non-dialysis patients with LOKELMA was mild to moderate edema. In placebo-controlled trials up to 28 days, edema was reported in 4.4%, 5.9%, 16.1% of non-dialysis patients treated with 5 g, 10 g, and 15 g of LOKELMA once daily, respectively vs 2.4% of non-dialysis patients receiving placebo. DRUG INTERACTIONS: LOKELMA can transiently increase gastric pH. In general, oral medications with pH-dependent solubility should be administered at least 2 hours before or 2 hours after LOKELMA. Spacing is not needed if it has been determined the concomitant medication does not exhibit pH-dependent solubility. Please read the full Important Safety Information on this spread and adjacent Brief Summary of full Prescribing Information. continued RAASi therapy while taking LOKELMA long term. 5 In the 483 patients on RAASi therapy at baseline, during the maintenance phase of Study 3, a 12-month, open-label study evaluating LOKELMA in patients with hyperkalemia: 74% of patients had no change in RAASi dose; 13% of patients had an increase in RAASi dose*; 14% of patients had a decrease in RAASi dose*; 11% of patients discontinued RAASi In a prespecified exploratory analysis of Study 3 5 9 of 10 patients N e a r l y In patients WITH hyperkalemia not on dialysis, LOKELMA is prescribed to treat HK. 1 Managing HK can enable guideline-recommended RAASi treatment 2-4

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