HK=hyperkalemia; K+=potassium.
References:1. Data on File, US-86037. AZPLP. 2. LOKELMA® (sodium zirconium cyclosilicate) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024. 3. Kosiborod M, Rasmussen HS, Lavin P, et al. Effect of sodium zirconium cyclosilicate on potassium lowering for 28 days among outpatients with hyperkalemia: the HARMONIZE randomized clinical trial. JAMA. 2014;312(21):2223-2233.
References: 1. Dunn JD, Benton WW, Orozco-Torrentera E, Adamson RT. The burden of hyperkalemia in patients with cardiovascular and renal disease. Am J Manag Care. 2015;21(15):S307-S315. 2. Data on File, REF-34835. AZPLP. 3. Collins AJ, Pitt B, Reaven N, et al. Association of serum potassium with all-cause mortality in patients with and without heart failure, chronic kidney disease, and/or diabetes. Am J Nephrol. 2017;46(3):213-221. 4. Collins AJ, Pitt B, Reaven N, et al. Association of serum potassium with all-cause mortality in patients with and without heart failure, chronic kidney disease, and/or diabetes. Am J Nephrol. 2017;46(3 Suppl):S1-S13. 5. LOKELMA® (sodium zirconium cyclosilicate) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2022. 6. Betts KA, Woolley JM, Mu F, Xiang C, Tang W, Wu EQ. The cost of hyperkalemia in the United States. Kidney Int Rep. 2018;3(2):385-393. 7. Cupisti A, Kovesdy CP, D'Alessandro C, et al. Dietary approach to recurrent or chronic hyperkalaemia in patients with decreased kidney function. Nutrients. 2018;10(261):1-159. 8. Ikizler TA, Burrowes JD, Byham-Gray LD, et al. KDOQI Nutrition in CKD Guideline Work Group. KDOQI clinical practice guideline for nutrition in CKD: 2020 update. Am J Kidney Dis. 2020;76(3)(suppl 1):S1-S107. 9. Palmer BF, Carrero JJ, Clegg DJ, et al. Clinical management of hyperkalemia. Mayo Clin Proc. 2021;96(3):744-762. 10. Downer MK, Gea A, Stampfer M, et al. Predictors of short- and long-term adherence with a Mediterranean-type diet intervention: the PREDIMED randomized trial. Int J Behav Nutr Phys Act. 2016;13:67. 11. Epstein M, Reaven NL, Funk SE, McGaughey KJ, Oestreicher N, Knispel J. Evaluation of the treatment gap between clinical guidelines and the utilization of renin-angiotensin-aldosterone system inhibitors. Am J Manag Care. 2015;21(11 suppl):S212-S220. 12. Kidney Disease: Improving Global Outcomes (KDIGO) Diabetes Work Group. KDIGO 2020 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease. Kidney Int. 2020;98(4S):S1-S115. 13. Kidney Disease: Improving Global Outcomes. KDIGO 2021 Clinical Practice Guideline for the Management of Blood Pressure in Chronic Kidney Disease. Kidney Int. 2021;99(3S):S1-S87. 14. Hollander-Rodriguez JC, Calvert JF Jr. Hyperkalemia. Am Fam Physician. 2006;73(2):283-290. 15. Weisberg LS. Management of severe hyperkalemia. Crit Care Med. 2008;36(12):3246-3251. 16. Parham WA, Mehdirad AA, Biermann KM, Fredman CS. Hyperkalemia revisited. Tex Heart Inst J. 2006;33(1):40-47. 17. Palmer BF. Regulation of potassium homeostasis. Clin J Am Soc Nephrol. 2015;10:1050-1060. 18. Mushiyakh Y, Dangaria H, Qavi S, Ali N, Pannone J, Tompkins D. Treatment and pathogenesis of acute hyperkalemia. J Community Hosp Intern Med. 19. Rafique Z, Peaco*ck F, Armstead T, et al. Hyperkalemia management in the emergency department: An expert panel consensus. JACEP Open. 2021;2:e12572.
Ca2+=calcium; GI=gastrointestinal; K+=potassium; Mg2+=magnesium; MOA=mechanism of action; qod=every other day; SPS=sodium polystyrene sulfonate.
References: 1. LOKELMA® (sodium zirconium cyclosilicate) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024. 2. Stavros F, Yang A, Leon A, Nuttall M, Rasmussen HS. Characterization of structure and function of ZS-9, a K+ selective ion trap. PLoS One. 2014;9(12):e114686. 3. Sodium Polystyrene Sulfonate Suspension [package insert]. Farmville, North Carolina: CMP Pharma Inc; 2021. 4. Veltassa® (patiromer) [prescribing information]. Redwood City, CA: Relypsa, Inc; 2023. 5. Pitt B, Bakris GL. New potassium binders for the treatment of hyperkalemia: current data and opportunities for the future. Hypertension. 2015;66(4):731-738. 6. Palmer BF. Potassium binders for hyperkalemia in chronic kidney disease–diet, renin-angiotensin-aldosterone system inhibitor therapy, and hemodialysis. Mayo Clin Proc. 2020;95(2):339-354. 7. Clegg DJ, Cody M, Palmer BF. Challenges in treating cardiovascular disease: restricting sodium and managing hyperkalemia. Mayo Clin Proc. 2017;92(8):1248-1260. 8. Lien YH. Patiromer: Can less be better than more? Am J Med. 2018;131(5):459-460. 9. Beccari MV, Meaney CJ. Clinical utility of patiromer, sodium zirconium cyclosilicate, and sodium polystyrene sulfonate for the treatment of hyperkalemia: an evidence-based review. Core Evid. 2017;12:11-24. 10.Kayexalate® (sodium polystyrene sulfonate) [prescribing information]. St. Michael, Barbados: Concordia Pharmaceuticals Inc; 2017. 11. Li L, Harrison SD, Cope MJ, et al. Mechanism of action and pharmacology of patiromer, a nonabsorbed cross-linked polymer that lowers serum potassium concentration in patients with hyperkalemia. J Cardiovasc Pharmacol Ther. 2016;21(5):456-465.
K+=potassium; LIDI=long interdialytic interval; qd=once daily; qod=every other day; SIDI=short interdialytic interval; tid=three times daily.
References: 1. LOKELMA® (sodium zirconium cyclosilicate) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024. 2. Packham DK, Rasmussen HS, Lavin PT, et al. Sodium zirconium cyclosilicate in hyperkalemia [article and supplementary material]. N Engl J Med. 2015;372(3):222-231. 3. Kosiborod M, Rasmussen HS, Lavin P, et al. Effect of sodium zirconium cyclosilicate on potassium lowering for 28 days among outpatients with hyperkalemia: the HARMONIZE randomized clinical trial. JAMA. 2014;312(21):2223-2233. 4. Roger SD, Spinowitz BS, Lerma EV, et al. Efficacy and safety of sodium zirconium cyclosilicate for treatment of hyperkalemia: an 11-month open-label extension of HARMONIZE. Am J Nephrol. 2019;50(6):473-480. 5. Data on File, US-73614, AZPLP. 6. Fishbane S, Ford M, f*ckagawa M, et al. A phase 3b, randomized, double-blind, placebo-controlled study of sodium zirconium cyclosilicate for reducing the incidence of predialysis hyperkalemia. J Am Soc Nephrol. 2019;30(9):1723-1733.
K+=potassium.
References: 1. Data on File, US-79654. AZPLP. 2. Formulary Data are provided by Fingertip Formulary® and are current as of [7/17/2023].
CKD=chronic kidney disease; DM=diabetes mellitus; GI=gastrointestinal; HF=heart failure; HTN=hypertension; K+= potassium; qd=once daily; SAEs=serious adverse events.References: 1. LOKELMA® (sodium zirconium cyclosilicate) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024. 2. 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. 3. U.S. Food & Drug Administration. Drug Approval Package: LOKELMA (sodium zirconium cyclosilicate) Medical Review(s). AccessedSeptember 19, 2023. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/207078Orig1s000MedR.pdf 4. Fishbane S, Ford M, f*ckagawa M, et al. A phase 3b, randomized, double-blind, placebo-controlled study of sodium zirconium cyclosilicate for reducing the incidence of predialysis hyperkalemia. J Am Soc Nephrol. 2019;30(9):1723-1733.
K+=potassium; LIDI=long interdialytic interval; qod=every other day; RAASi=renin-angiotensin-aldosterone system inhibitor; tbsp=tablespoon.
References: 1. LOKELMA® (sodium zirconium cyclosilicate) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024. 2. Kosiborod M, Rasmussen HS, Lavin P, et al. Effect of sodium zirconium cyclosilicate on potassium lowering for 28 days among outpatients with hyperkalemia: the HARMONIZE randomized clinical trial. JAMA. 2014;312(21):2223-2233. 3. Packham DK, Rasmussen HS, Lavin PT, et al. Sodium zirconium cyclosilicate in hyperkalemia [article and supplementary material]. N Engl J Med. 2015;372(3):222-231. 4. Spinowitz BS, Fishbane S, Pergola PE, et al; ZS-005 Study Investigators. Sodium zirconium cyclosilicate among individuals with hyperkalemia: a 12-month phase 3 study. Clin J Am Soc Nephrol. 2019;14(6):798-809. 5. Roger SD, Spinowitz BS, Lerma EV, et al. Efficacy and safety of sodium zirconium cyclosilicate for treatment of hyperkalemia: an 11-month open-label extension of HARMONIZE. Am J Nephrol. 2019;50(6):473-480.
References: 1. Spinowitz BS, Fishbane S, Pergola PE, et al; ZS-005 Study Investigators. Sodium zirconium cyclosilicate among individuals with hyperkalemia: a 12-month phase 3 study. Clin J Am Soc Nephrol. 2019;14(6):798-809. 2. Packham DK, Rasmussen HS, Lavin PT, et al. Sodium zirconium cyclosilicate in hyperkalemia [article and supplementary material]. N Engl J Med. 2015;372(3):222-231. 3. Kosiborod M, Rasmussen HS, Lavin P, et al. Effect of sodium zirconium cyclosilicate on potassium lowering for 28 days among outpatients with hyperkalemia: the HARMONIZE randomized clinical trial. JAMA. 2014;312(21):2223-2233. 4. Roger SD, Spinowitz BS, Lerma EV, et al. Efficacy and safety of sodium zirconium cyclosilicate for treatment of hyperkalemia: an 11-month open-label extension of HARMONIZE. Am J Nephrol. 2019;50(6):473-480. 5. LOKELMA® (sodium zirconium cyclosilicate) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2022. 6. Data on file, US-53732, AZPLP.
References: 1. Dunn JD, Benton WW, Orozco-Torrentera E, Adamson RT. The burden of hyperkalemia in patients with cardiovascular and renal disease. Am J Manag Care.2015;21(15 Suppl):s307-s315. 2. Data on File, REF-34835. AZPLP. 3. Collins AJ, Pitt B, Reaven N, et al. Association of serum potassium with all-cause mortality in patients with and without heart failure, chronic kidney disease, and/or diabetes. Am J Nephrol.2017;46(3):213-221. doi:10.1159/0004798024. Collins AJ, Pitt B, Reaven N, et al. Association of serum potassium with all-cause mortality in patients with and without heart failure, chronic kidney disease, and/or diabetes. Am J Nephrol. 2017;46(3 Suppl):S1-S13. 5. LOKELMA® (sodium zirconium cyclosilicate) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2022. 6.Betts KA, Woolley JM, Mu F, Xiang C, Tang W, Wu EQ. The cost of hyperkalemia in the United States. Kidney Int Rep. 2018;3(2):385-393 2017;46(3):213-221. doi:10.1016/j.ekir.2017.11.0037. Epstein M, Reaven NL, Funk SE, McGaughey KJ, Oestreicher N, Knispel J. Evaluation of the treatment gap between clinical guidelines and the utilization of renin-angiotensin-aldosterone system inhibitors. Am J Manag Care. 2015;21(11 suppl):S212-S220. 8.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:10.10 S220. 816/j.kint.2022.06.0089. Kidney Disease: Improving Global Outcomes (KDIGO) Diabetes Work Group. KDIGO 2020 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease. Kidney Int. 2020;98(4S):S1-S115. doi:10.1016/j.kint.2020.06.019 10. Kidney Disease: Improving Global Outcomes. KDIGO 2021 Clinical Practice Guideline for the Management of Blood Pressure in Chronic Kidney Disease. Kidney Int. 2021;99(3S):S1-S87. doi:10.1016/j.kint.2020.11.003 11. Hollander-Rodriguez JC, Calvert JF Jr. Hyperkalemia. Am Fam Physician. 2006;73(2):283-290. 12. Weisberg LS. Management of severe hyperkalemia. Crit Care Med. 2008;36(12):3246-3251. doi:10.1097/CCM.0b013e31818f222b 13. Parham WA, Mehdirad AA, Biermann KM, Fredman CS. Hyperkalemia revisited. Tex Heart Inst J. 2006;33(1):40-47. 14. Palmer BF. Regulation of potassium homeostasis. Clin J Am Soc Nephrol. 2015;10(6):1050-1060. doi:102215/CJN.08580813 15. Mushiyakh Y, Dangaria H, Qavi S, Ali N, Pannone J, Tompkins D. Treatment and pathogenesis of acute hyperkalemia. J Community Hosp Intern Med Perspect. 2012;1(14):10.3402/jchimp.v1i4.732. doi:10.3402/jchimp.vi4.7372 16. Rafique Z, Peaco*ck F, Armstead T, et al. Hyperkalemia management in the emergency department: An expert panel consensus.J Am Coll Emerg Physicians Open. 2021;2(5):e12572. doi:10.1002/emp2.12572
CKD=chronic kidney disease; DM=diabetes mellitus; HF=heart failure; HTN=hypertension; K+=potassium; MOA=mechanism of action; RAASi=renin-angiotensin-aldosterone system inhibitor.References: 1. Epstein M, Reaven NL, Funk SE, et al. Evaluation of the treatment gap between clinical guidelines and the utilization of renin-angiotensin-aldosterone system inhibitors. Am J Manag Care. 2015;21:S212-S220. 2. Kidney Disease: Improving Global Outcomes (KDIGO) Diabetes Work Group. KDIGO 2020 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease. Kidney Int. 2020;98(4S):S1-S115. 3. Kidney Disease: Improving Global Outcomes. KDIGO 2021 Clinical Practice Guideline for the Management of Blood Pressure in Chronic Kidney Disease. Kidney Int. 2021;99(3S):S1-S87. 4.Data on File, US-53732, AZPLP.
ACEi=angiotensin-converting enzyme inhibitor; ARB=angiotensin II receptor blocker; BP=blood pressure; CKD=chronic kidney disease; ED=emergency department; HbA1c=glycated hemoglobin; HF=heart failure; HK=hyperkalemia; K+=potassium; MRA=mineralocorticoid receptor antagonist; RAASi=renin-angiotensin-aldosterone system inhibitor; SGLT2i=sodium-glucose cotransporter 2 inhibitor; SPS=sodium polystyrene sulfonate. References: 1. Data on File, US-86037, AZPLP. 2. Data on File, US-77519, AZPLP.
ACEi=angiotensin-converting enzyme inhibitor; ARB=angiotensin II receptor blocker; ARNI=angiotensin receptor-neprilysin inhibitor; HK=hyperkalemia; K+= potassium; MRA=mineralocorticoid receptor antagonist; qod=every other day; qd=once daily; RAASi=renin-angiotensin-aldosterone system; RWE=real-world evidence; tid=three times daily; US=United States.References: 1. LOKELMA® (sodium zirconium cyclosilicate) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024. 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. 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. 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. Circulation. 2022;145(18):e895-e1032. 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. 6. Agiro A, Amin A, Cook EE, et al. Real-world modifications of renin-angiotensin-aldosterone system inhibitors in patients with hyperkalemia initiating sodium zirconium cyclosilicate therapy: the OPTIMIZE I study. Adv Ther. 2023;40(6):2886–2901. 7. Data on File, REF-212117, AZPLP.
ACC=American College of Cardiology;ACEi=angiotensin-converting enzyme inhibitor; AHA=American Heart Association; ARB=angiotensin II receptor blocker; ARNI=angiotensin receptor-neprilysin inhibitor; CI=confidence interval; CKD=chronic kidney disease; CV=cardiovascular; DM=diabetes mellitus; ECG=electrocardiogram; ED=emergency department; eGFR=estimated glomerular filtration rate; EHR=electronic health records; ESKD=end-stage kidney disease; GI=gastrointestinal; HD=hemodialysis; HF=heart failure;HFSA=Heart Failure Society of America; HK=hyperkalemia; HR=hazard ratio; HTN=hypertension; ICD=International Classification of Diseases; IDN=integrated delivery network; K+= potassium; KDIGO=Kidney Disease: Improving Global Outcomes; MI=myocardial infarction; MNT=medical nutrition therapy; MRA=mineralocorticoid receptor antagonist; NA+=sodium; RAASi=renin-angiotensin-aldosterone system inhibitor; RCTs=randomized controlled trials; RWE=real world evidence; SD=standard deviation; SPS=sodium polystyrene sulfonate. References: 1. Collins AJ, Pitt B, Reaven N, et al. Association of serum potassium with all-cause mortality in patients with and without heart failure, chronic kidney disease, and/or diabetes. Am J Nephrol. 2017;46(3):213-221. 2. LOKELMA® (sodium zirconium cyclosilicate) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024. 3. Collins AJ, Pitt B, Reaven N, et al. Association of serum potassium with all-cause mortality in patients with and without heart failure, chronic kidney disease, and/or diabetes. Am J Nephrol. 2017;46(3 Suppl):S1-S13. 4.Epstein M, Reaven NL, Funk SE, et al. Evaluation of the treatment gap between clinical guidelines and the utilization of renin-angiotensin-aldosterone system inhibitors.Am J Manag Care. 2015;21(11 Suppl):S212-S220. 5.Kidney Disease: Improving Global Outcomes (KDIGO) Diabetes Work Group. KDIGO 2020 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease. Kidney Int. 2020;98(4S):S1-S115. 6.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. 7. Rowan CG, Agiro A, Chan A, et al. Recurrence of hyperkalemia following dietary counseling: REVOLUTIONIZE I real-world evidence study. Presented at: National Kidney Foundation (NFK) Spring Clinical Meetings 2023; April 11-15, 2023. Poster 296. 8.Data on File, REF-178557, AZPLP. 9.An J, Zhou H, Ni L, et al. Discontinuation of renin-angiotensin-aldosterone system inhibitors secondary to hyperkalemia translates into higher cardiorenal outcomes. Am J Nephrol. 2023;54(7-8):258-267. 10.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. 11. Data on File, REF-197797, AZPLP. 12. Data on File, REF-196652, AZPLP. 13. Heidenreich P, 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 Guideline. J Am Coll Cardiol. 2022;79(17):e263-e421. 14. Hollander-Rodriguez JC and Calvert JF Jr. Hyperkalemia. Am Fam Physician. 2006;73(2):283-290. 15. Weisberg LS. Management of severe hyperkalemia. Crit Care Med. 2008;36(12):3246-3251. 16. Parham WA, Mehdirad AA, Biermann KM, et al. Hyperkalemia revisited. Tex Heart Inst J. 2006;33(1):40-47. 17. Dunn JD, Benton WW, Orozco-Torrentera E, et al. The burden of hyperkalemia in patients with cardiovascular and renal disease. Am J Manag Care. 2015;21(15 Suppl):s307-s315. 18. Palmer BF. Regulation of potassium homeostasis. Clin J Am Soc Nephrol. 2015;10:1050-1060. 19. Mushiyakh Y, Dangaria H, Qavi S, et al. Treatment and pathogenesis of acute hyperkalemia. J Community Hosp Intern Med Perspect. 2012;1(4):7372.20. Rafique Z, Peaco*ck F, Armstead T, et al. Hyperkalemia management in the emergency department: An expert panel consensus. J Am Coll Emerg Physicians Open. 2021;2(5):e12572.
ACEi=angiotensin-converting enzyme inhibitor; ARB=angiotensin II receptor blocker; ARNI=angiotensin receptor-neprilysin inhibitor; ATLAS=Advanced Mapping Tactics for Learning Analysis; CKD=chronic kidney disease; eLAAD= electronic longitudinal access and adjudication data; GDMT=guideline-directed medical therapy; HF=heart failure; HK=hyperkalemia; K+=potassium; MRA=mineralocorticoid receptor antagonist; RAASi=renin-angiotensin-aldosterone system inhibitor; US=United States. References: 1.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. 2.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. 3.Heidenreich P, 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 Guideline. J Am Coll Cardiol. 2022;79(17):e263-e421.
