For US Healthcare Professionals
IMPORTANT SAFETY INFORMATION FOR LOKELMA® (sodium zirconium cyclosilicate)
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.
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.
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IMPORTANT SAFETY INFORMATION FOR LOKELMA® (sodium zirconium cyclosilicate)
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IMPORTANT SAFETY INFORMATION FOR LOKELMA® (sodium zirconium cyclosilicate)
Ca2+=calcium; GI=gastrointestinal; HK=hyperkalemia; K+=potassium; Mg2+=magnesium; 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. SPS® Suspension [prescribing information]. Farmville, NC: CMP Pharma, Inc; 2021. 4. 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.
ACEi=angiotensin-converting enzyme inhibitor; ARB=angiotensin II receptor blocker; ARNI=angiotensin receptor-neprilysin inhibitor; CI=confidence interval; CKD=chronic kidney disease; CV=cardiovascular; ED=emergency department; eGFR=estimated glomerular filtration rate; ESKD=end-stage kidney disease; HD=hemodialysis; HF=heart failure; HFrEF=heart failure with reduced ejection fraction; HK=hyperkalemia; HR=hazard ratio; ICD=International Classification of Diseases; K+=potassium; MRA=mineralocorticoid receptor antagonist; RAASi=renin‐angiotensin‐aldosterone system inhibitor; US=United States.
References: 1. Rastogi A, Pollack CV Jr, Lesén E, et al. Association between reduced RAASi therapy and progression to ESKD in hyperkalemic CKD patients. Presented at: American Society of Nephrology (ASN) Kidney Week 2023; November 2-5, 2023; Philadelphia, PA. Poster TH-PO1028. 2. Kanda E, Rastogi A, Murohara T, et al. Clinical impact of suboptimal RAASi therapy following an episode of hyperkalemia. BMC Nephrol. 2023;24(1):18. 3. Data on File, REF-196652. AZPLP. 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):213-221. 5. 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.
ACEi=angiotensin-converting enzyme inhibitor; ARB=angiotensin II receptor blocker; ARNI=angiotensin receptor-neprilysin inhibitor; ATLAS=Advanced Mapping Tactics for Learning Analysis; eLAAD=electronic longitudinal access and adjudication data; GDMT=guideline-directed medical therapy; HK=hyperkalemia; K+=potassium; MRA=mineralocorticoid receptor antagonist; RAASi=renin-angiotensin-aldosterone system inhibitor; US=United States.
ACEi=angiotensin-converting enzyme inhibitor; ARB=angiotensin II receptor blocker; K+=potassium; MRA=mineralocorticoid receptor antagonist; qd=once daily; qod=every other day; RAASi=renin-angiotensin-aldosterone system inhibitor; tid=three times a day.
References: 1. LOKELMA® (sodium zirconium cyclosilicate) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024. 2. Data on File, US-108426. AZPLP. 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. SPS® Suspension [prescribing information]. Farmville, NC: CMP Pharma, Inc; 2021. 5. Veltassa® (patiromer) [package insert]. Redwood City, CA: Vifor Pharma, Inc; 2023. 6. 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. 7. 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. 8. Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2024 clinical practice guideline for evaluation and management of chronic kidney disease. Kidney Int. 2024;105(4S):S117-S314. 9. 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. 10. 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.
K+=potassium; LIDI=long interdialytic interval; qd=once daily; SIDI=short interdialytic interval.
References: 1. LOKELMA® (sodium zirconium cyclosilicate) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024. 2. Data on File, US-108426. AZPLP. 3. 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):1723-1733.
CKD=chronic kidney disease; DM=diabetes mellitus; HF=heart failure; HTN=hypertension; qd=once daily.
References: 1. LOKELMA® (sodium zirconium cyclosilicate) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024. 2. Data on File, US-108426. AZPLP. 3. 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. 4. U.S. Food & Drug Administration. Drug Approval Package: LOKELMA (sodium zirconium cyclosilicate) Medical Review(s). Accessed January 28, 2026. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/207078Orig1s000MedR.pdf
GI=gastrointestinal; K+=potassium; SAEs=serious adverse events.
References: 1. LOKELMA® (sodium zirconium cyclosilicate) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024. 2. Data on File, US-108426. AZPLP. 3. 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):1723-1733.
K+=potassium; qd=once daily; tid=three times a day.
References: 1. LOKELMA® (sodium zirconium cyclosilicate) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024. 2. Data on File, US-108426. AZPLP. 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. 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. 5. 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. 6. 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.
K+=potassium; LIDI=long interdialytic interval.
References: 1. LOKELMA® (sodium zirconium cyclosilicate) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024. 2. Data on File, US-108426. AZPLP. 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.
EGWP=Employer Group Waiver Plans; FEHBP=Federal Employees Health Benefits Program; HCP=healthcare professional; K+=potassium; MA=Medicare Advantage; PACE=Program of All-Inclusive Care for the Elderly; PBM=Pharmacy Benefit Manager; PCP=primary care physician; PDP=prescription drug plan; SN=special needs.
References: 1. Data on File, US-108426. AZPLP. 2. Formulary Data are provided by Fingertip Formulary® and are current as of 3/13/2025.
Reference: 1. Data on File, US-108426. AZPLP.
Reference: 1. Data on File, US-108426. AZPLP.
CI=confidence interval; CKD=chronic kidney disease; CV=cardiovascular; DM=diabetes mellitus; EHR=electronic health records; ESKD=end-stage kidney disease; HF=heart failure; HK=hyperkalemia; HTN=hypertension; K+=potassium; MACE=major adverse cardiovascular event; MACE+=major adverse cardiovascular event plus hospitalization for unstable angina; MNT=medical nutrition therapy; MRA=mineralocorticoid receptor antagonist; RAASi=renin‐angiotensin‐aldosterone system inhibitor; RWE=real-world evidence; SD=standard deviation; US=United States.
References: 1. Bakris G, Agiro A, Greatsinger A, et al. REVOLUTIONIZE III: consequences of recurrent hyperkalemia on healthcare resource utilization and medical cost. Presented at: American Society of Nephrology (ASN) Kidney Week 2023; November 1-5, 2023; Philadelphia, PA. Poster TH-PO355. 2. Bakris G, Agiro A, Greatsinger A, et al. Recurrent hyperkalemia is associated with higher rates of cardiovascular outcomes and all-cause mortality in patients with CKD: The REVOLUTIONIZE III study. Presented at: Heart Association (AHA) Scientific Sessions 2023; November 11-13, 2023; Philadelphia, PA. Poster 12768. 3. Data on File, REF-197797. AZPLP. 4. Rowan CG, Agiro A, Chan KA, et al. Hyperkalemia recurrence following medical nutrition therapy in patients with Stage 3-4 chronic kidney disease: The REVOLUTIONIZE I Real-World Study. Adv Ther. 2024;41(6):2381-2398. 5. Trevisan M, de Deco P, Xu H, et al. Incidence, predictors and clinical management of hyperkalaemia in new users of mineralocorticoid receptor antagonists. Eur J Heart Fail. 2018;20(8):1217-1226.
CI=confidence interval; CKD=chronic kidney disease; ED=emergency department; ESKD=end-stage kidney disease; HD=hemodialysis; HK=hyperkalemia; IRR=inter-rater reliability; K+=potassium; SD=standard deviation; US=United States.
References: 1. Data on File, REF-217791. AZPLP. 2. Data on File, US-108426. AZPLP. 3. Data on File, US-63248. AZPLP.
