Skip to main content
Log in

Sodium zirconium cyclosilicate in hyperkalaemia: a profile of its use

  • Adis Drug Q&A
  • Published:
Drugs & Therapy Perspectives Aims and scope Submit manuscript

Abstract

Sodium zirconium cyclosilicate (SZC) [Lokelma] is a useful oral option for the treatment of hyperkalaemia in adults. As a non-absorbed, non-polymer compound, SZC lowers serum potassium levels by binding potassium in the gastrointestinal (GI) tract and promoting faecal potassium excretion. SZC is effective in restoring and maintaining normokalaemia and is generally well tolerated; most adverse events reported in phase 3 clinical trials were manageable without treatment interruption. SZC appears to be effective and generally well tolerated regardless of common factors associated with hyperkalaemia, including concomitant renin-angiotensin-aldosterone system inhibitor (RAASi) therapy, chronic kidney disease, diabetes and heart failure. Recent data suggest that SZC is also effective and similarly well tolerated in patients with end-stage kidney disease receiving haemodialysis, who typically have persistent predialysis hyperkalaemia. Real-world data and additional long-term data will be valuable in more definitively establishing the position of SZC in the treatment of hyperkalaemia.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Wooten JM, Kupferman FE, Kupferman JC. A brief review of the pharmacology of hyperkalemia: causes and treatment. South Med J. 2019;112(4):228–33.

    Article  CAS  Google Scholar 

  2. Llubani R, Vukadinovic D, Werner C, et al. Hyperkalaemia in heart failure: pathophysiology, implications and therapeutic perspectives. Curr Heart Fail Rep. 2018;15(6):390–7.

    Article  CAS  Google Scholar 

  3. Lakkis JI, Weir MR. Hyperkalemia in the hypertensive patient. Curr Cardiol Rep. 2018;20(2):12.

    Article  Google Scholar 

  4. Alfonzo A, Spar J, MacTier R, et al. Clinical practice guidelines: treatment of acute hyperkalaemia in adults. Bristol: UK Renal Association; 2014.

    Google Scholar 

  5. Weir MR, Rolfe M. Potassium homeostasis and renin-angiotensin-aldosterone system inhibitors. Clin J Am Soc Nephrol. 2010;5(3):531–48.

    Article  CAS  Google Scholar 

  6. Ben Salem C, Badreddine A, Fathallah N, et al. Drug-induced hyperkalemia. Drug Saf. 2014;37(9):677–92.

    Article  CAS  Google Scholar 

  7. Gumz ML, Rabinowitz L, Wingo CS. An integrated view of potassium homeostasis. N Engl J Med. 2015;373(1):60–72.

    Article  CAS  Google Scholar 

  8. Tamargo J, Caballero R, Delpón E. New therapeutic approaches for the treatment of hyperkalemia in patients treated with renin-angiotensin-aldosterone system inhibitors. Cardiovasc Drugs Ther. 2018;32(1):99–119.

    Article  CAS  Google Scholar 

  9. Kovesdy CP, Appel LJ, Grams ME, et al. Potassium homeostasis in health and disease: a scientific workshop cosponsored by the National Kidney Foundation and the American Society of Hypertension. Am J Kidney Dis. 2017;70(6):844–58.

    Article  CAS  Google Scholar 

  10. Dhondup T, Qian Q. Acid–base and electrolyte disorders in patients with and without chronic kidney disease: an update. Kidney Dis (Basel). 2017;3(4):136–48.

    Article  Google Scholar 

  11. Seferovic PM, Ponikowski P, Anker SD, et al. Clinical practice update on heart failure 2019: pharmacotherapy, procedures, devices and patient management. An expert consensus meeting report of the Heart Failure Association of the European Society of Cardiology. Eur J Heart Fail. 2019;21(10):1169–86.

    Article  Google Scholar 

  12. Butler J, Khan MS, Anker SD. Novel potassium binders as enabling therapy in heart failure. Eur J Heart Fail. 2019;21(5):550–2.

    Article  Google Scholar 

  13. Palmer BF, Clegg DJ. Achieving the benefits of a high-potassium, paleolithic diet, without the toxicity. Mayo Clin Proc. 2016;91(4):496–508.

    Article  Google Scholar 

  14. Yusuf AA, Hu Y, Singh B, et al. Serum potassium levels and mortality in hemodialysis patients: a retrospective cohort study. Am J Nephrol. 2016;44(3):179–86.

    Article  CAS  Google Scholar 

  15. Kovesdy CP, Regidor DL, Mehrotra R, et al. Serum and dialysate potassium concentrations and survival in hemodialysis patients. Clin J Am Soc Nephrol. 2007;2(5):999–1007.

    Article  CAS  Google Scholar 

  16. Lokelma™ (sodium zirconium cyclosilicate) for oral suspension: EU summary of product characteristics. Södertälje: AstraZeneca AB; 2019.

  17. Lokelma™ (sodium zirconium cyclosilicate) for oral suspension: US prescribing information. Wilmington (DE): AstraZeneca; 2018.

  18. Lokelma™ (sodium zirconium cyclosilicate powder for oral suspension): Canadian product monograph. Mississauga (ON): AstraZeneca Canada Inc.; 2019.

  19. Stavros F, Yang A, Leon A, et al. Characterization of structure and function of ZS-9, a K+ selective ion trap. PLoS One. 2014;9(12):e114686.

    Article  Google Scholar 

  20. 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):2223–33.

    Article  Google Scholar 

  21. Zannad F, Rasmussen HS, Lavin PT, et al. Effect of sodium zirconium cyclosilicate (ZS-9) on aldosterone from the phase 3 randomized, double-blind, placebo-controlled HARMONIZE study [abstract no. P1592]. Eur J Heart Fail. 2015;17(Suppl 1):342.

    Google Scholar 

  22. Ash SR, Singh B, Lavin PT, et al. A phase 2 study on the treatment of hyperkalemia in patients with chronic kidney disease suggests that the selective potassium trap, ZS-9, is safe and efficient. Kidney Int. 2015;88(2):404–11.

    Article  CAS  Google Scholar 

  23. Packham DK, Rasmussen HS, Lavin PT, et al. Sodium zirconium cyclosilicate in hyperkalemia. N Engl J Med. 2015;372(3):222–31.

    Article  Google Scholar 

  24. Anker SD, Kosiborod M, Zannad F, et al. Maintenance of serum potassium with sodium zirconium cyclosilicate (ZS-9) in heart failure patients: results from a phase 3 randomized, double-blind, placebo-controlled trial. Eur J Heart Fail. 2015;17(10):1050–6.

    Article  CAS  Google Scholar 

  25. Kosiborod M, McCullough PA, Rasmussen H, et al. Acute efficacy of sodium zirconium cyclosilicate (ZS-9) in patients on mineralocorticoid-receptor antagonists: analysis from two phase 3 studies [abstract no. 13555]. Circulation. 2015;132(Suppl 3):A13555.

    Google Scholar 

  26. Fishbane S, Ford M, Fukagawa 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):1723–33.

    Article  Google Scholar 

  27. Blair HA. Patiromer: a review in hyperkalaemia. Clin Drug Investig. 2018;38(8):785–94.

    Article  CAS  Google Scholar 

  28. 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):473–80.

    Article  CAS  Google Scholar 

  29. 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.

    Article  Google Scholar 

  30. Sodium zirconium cyclosilicate. EU assessment report. London: European Medicines Agency; 2018.

    Google Scholar 

  31. Data on file, AstraZeneca, 2019.

  32. McCullough P, Pergola P, Fishbane S, et al. Efficacy and safety of sodium zirconium cyclosilicate to treat hyperkalemia among patients taking renin-angiotensin-aldosterone system inhibitors in a 12-month open-label, phase 3 study: a post hoc subgroup analysis [abstract no. 16610]. Circulation. 2017;136(Suppl 1):A16610.

    Google Scholar 

  33. Fishbane S, Roger S, Packham D, et al. Sodium zirconium cyclosilicate for hyperkalaemia in patients with diabetes mellitus: retrospective analysis of a 12 month open label, phase 3 study [abstract no. SP421]. Nephrol Dial Transplant. 2018;33(Suppl 1):i489–90.

    Article  Google Scholar 

  34. Roger S, Lavin P, Lemma E, et al. Safety and efficacy of sodium zirconium cyclosilicate for long-term treatment of hyperkalaemia in patients with chronic kidney disease: results from an open-label, phase 3 study [abstract no. FP071]. Nephrol Dial Transplant. 2018;33(Suppl 1):i72.

    Article  Google Scholar 

  35. Veltassa (patiromer) powder for oral suspension: EU summary of product characteristics. Paris: Vifor Fresenius Medical Care Renal Pharma France; 2019.

  36. Long B, Warix JR, Koyfman A. Controversies in management of hyperkalemia. J Emerg Med. 2018;55(2):192–205.

    Article  Google Scholar 

  37. Hoy SM. Sodium zirconium cyclosilicate: a review in hyperkalaemia. Drugs. 2018;78(15):1605–13.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The article was updated from Drugs 2018;78(15):1605–13 [37] by writers/editors of Adis International Ltd./Springer Nature and was reviewed by: B. Geavlete, Department of Urology, Saint John Emergency Clinical Hospital, Bucharest, Romania; J. Jose, School of Pharmacy, University of Nizwa, Nizwa, Oman; R. B. Shah, Department of Pharmacology, GMERS Medical College and Hospital, Gandhinagar, Gujarat, India; S. Hiremath, Division of Nephrology, Ottawa Hospital Research Institute, Ottawa, ON, Canada. During the peer review process, AstraZeneca, the marketing-authorization holder of sodium zirconium cyclosilicate, was also offered an opportunity to provide a scientific accuracy review of their data. Changes resulting from comments received were made on the basis of scientific and editorial merit.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Julia Paik.

Ethics declarations

Funding

The preparation of this review was not supported by any external funding.

Conflict of interest

J. Paik is an employee of Adis International Ltd./Springer Nature, is responsible for the article content and declares no conflicts of interest.

Additional information

Enhanced material

for this Adis Drug Q&A can be found at https://doi.org/10.6084/m9.figshare.11594193.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Paik, J. Sodium zirconium cyclosilicate in hyperkalaemia: a profile of its use. Drugs Ther Perspect 36, 89–96 (2020). https://doi.org/10.1007/s40267-020-00706-0

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40267-020-00706-0

Navigation