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Sodium Zirconium Cyclosilicate: A Review in Hyperkalaemia

  • Sheridan M. Hoy
Adis Drug Evaluation
  • 47 Downloads

Abstract

Sodium zirconium cyclosilicate (Lokelma™) [hereafter referred to as SZC] is a non-absorbed, non-polymer zirconium silicate compound that preferentially exchanges hydrogen and sodium for potassium and ammonium ions in the gastrointestinal tract (GIT), thereby increasing faecal potassium excretion and lowering serum potassium levels. It is available as a powder for oral suspension (in water) and is approved in the EU and the USA for the treatment of hyperkalaemia in adults. In two multinational, phase III studies in adults with hyperkalaemia, SZC 10 g three times daily lowered serum potassium levels to within the normal range (3.5–5.0 mmol/L) during the first 48 h of treatment, and SZC 5 and 10 g once daily maintained normokalaemia over ≤ 28 days’ therapy. These beneficial effects were consistent across all patient subgroups (e.g. chronic kidney disease, diabetes, heart failure, concomitant use of RAAS inhibitor therapy), and appeared to be maintained over the longer term (≤ 12 months). SZC was generally well tolerated in adults with hyperkalaemia. Its tolerability profile was generally similar to that seen with placebo over ≤ 28 day, and its safety profile appeared to remain consistent over the longer term (≤ 12 months). Moreover, the incidence of hypokalemia was low. Current evidence indicates that SZC is a promising therapy for the management of hyperkalaemia in adults.

Notes

Acknowledgements

During the peer review process, the manufacturer of sodium zirconium cyclosilicate was also offered an opportunity to review this article. Changes resulting from comments received were made on the basis of scientific and editorial merit.

Compliance with Ethical Standards

Funding

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

Conflict of interest

Sheridan Hoy is a salaried employee of Adis/Springer, is responsible for the article content and declares no relevant conflicts of interest.

References

  1. 1.
    Gumz ML, Rabinowitz L, Wingo CS. An integrated view of potassium homeostasis. N Engl J Med. 2015;373(1):60–72.CrossRefPubMedCentralGoogle Scholar
  2. 2.
    Tamargo J, Caballero R, Delpón E. New therapeutic approaches for the treatment of hyperkalaemia in patients treated with renin-angiotensin-aldosterone system inhibitors. Cardiovasc Drugs Ther. 2018;32(1):99–119.CrossRefPubMedCentralGoogle Scholar
  3. 3.
    Dixon BS. Zirconium cyclosilicate for treatment of hyperkalaemia. JAMA. 2014;312(21):2217–8.CrossRefPubMedCentralGoogle Scholar
  4. 4.
    UK Renal Association. Clinical practice guidelines: treatment of acute hyperkalaemia in adults. 2014. http://www.renal.org. Accessed 3 Aug 2018.
  5. 5.
    Georgianos PI, Agarwal R. Revisiting RAAS blockade in CKD with newer potassium-binding drugs. Kidney Int. 2018;93(2):325–34.CrossRefPubMedCentralGoogle Scholar
  6. 6.
    Long B, Warix JR, Koyfman A. Controversies in management of hyperkalaemia. J Emerg Med. 2018;55(2):192–205.CrossRefPubMedCentralGoogle Scholar
  7. 7.
    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.CrossRefPubMedCentralGoogle Scholar
  8. 8.
    AstraZeneca. Lokelma (sodium zirconium cyclosilicate) for oral suspension: EU summary of product characteristics. 2018. http://www.ema.europa.eu/ema/. Accessed 3 Aug 2018.
  9. 9.
    AstraZeneca. Lokelma™ (sodium zirconium cyclosilicate) for oral suspension: US prescribing information. 2018. http://www.fda.gov/. Accessed 3 Aug 2018.
  10. 10.
    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.CrossRefPubMedCentralGoogle Scholar
  11. 11.
    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.):342.Google Scholar
  12. 12.
    European Medicines Agency. Sodium zirconium cyclosilicate: EU assessment report. 2018. http://www.ema.europa.eu/ema/. Accessed 3 Aug 2018.
  13. 13.
    Ash SR, Singh B, Lavin PT, et al. A phase 2 study on the treatment of hyperkalaemia 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.CrossRefPubMedCentralGoogle Scholar
  14. 14.
    Packham DK, Rasmussen HS, Lavin PT, et al. Sodium zirconium cyclosilicate in hyperkalaemia. N Engl J Med. 2015;372(3):222–31.CrossRefPubMedCentralGoogle Scholar
  15. 15.
    Kosiborod M, Rasmussen HS, Lavin P, et al. Effect of sodium zirconium cyclosilicate on potassium lowering for 28 days among outpatients with hyperkalaemia: the HARMONIZE randomized clinical trial. JAMA. 2014;312(21):2223–33.CrossRefPubMedCentralGoogle Scholar
  16. 16.
    Data on file, AstraZeneca, 2018.Google Scholar
  17. 17.
    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.CrossRefPubMedCentralGoogle Scholar
  18. 18.
    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. Circulation 2015;132(Suppl 3).Google Scholar
  19. 19.
    US National Institutes of Health. ClinicalTrials.gov identifier NCT02107092. 2016. http://clinicaltrials.gov/. Accessed 3 Aug 2018.
  20. 20.
    Fishbane S, Adler S, Singh B, et al. Maintained efficacy and safety of sodium zirconium cyclosilicate for hyperkalaemia: 12-month, open-label, phase 3 study [abstract no. TH-PO1112]. J Am Soc Nephrol. 2017;28(Suppl):390.Google Scholar
  21. 21.
    Spinowitz BS, Pergola PE, Lerma EV, et al. Initial response rates for sodium zirconium cyclosilicate treatment of hyperkalaemia [abstract no. 281]. Am J Kidney Dis. 2018;71(4):585–6.Google Scholar
  22. 22.
    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.CrossRefGoogle Scholar
  23. 23.
    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.CrossRefGoogle Scholar
  24. 24.
    McCullough P, Pergola P, Fishbane S, et al. Efficacy and safety of sodium zirconium cyclosilicate to treat hyperkalaemia 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
  25. 25.
    Packham D, Roger S, Pergola P, et al. Acute efficacy of sodium zirconium cyclosilicate for hyperkalaemia in outpatients with potassium ≥ 6.0 mEq/L: post-hoc subgroup analysis of a phase 3 trial [abstract no. TH-PO1113]. J Am Soc Nephrol. 2017;28(Suppl):390.Google Scholar
  26. 26.
    US National Institutes of Health. ClinicalTrials.gov identifier NCT02163499. 2018. http://clinicaltrials.gov/. Accessed 3 Aug 2018.
  27. 27.
    US FDA Center for Drug Evaluation and Research. Medical review(s). 2017. http://www.fda.gov/. Accessed 3 Aug 2018.
  28. 28.
    Vifor France. Veltassa (patiromer): EU summary of product characteristics. 2017. http://www.ema.europa.eu. Accessed 3 Aug 2018.

Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  1. 1.SpringerAucklandNew Zealand

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