HYPERKALEMIA RISK
As an HCP, managing high potassium can be challenging for you and your patients
In an RWE STUDY of patients from the EHR databases of multiple IDNs*
Serum K+ ≥5.0 was associated with an increased risk of all-cause mortality in patients with hyperkalemia, regardless of comorbidity profile1*
Serum K+ ≥5.0 was associated with an increased risk of all-cause mortality in patients with high potassium, regardless of comorbidity profile1*
LOKELMA® (sodium zirconium cyclosilicate) is not indicated to reduce the risk of death.2
Population-weighted adjusted predicted probability of mortality was 5.3% over an average 18-month follow-up for patients with CKD Stages 3-5 and mild hyperkalemia (5.0–<5.5 mEq/L).3
*
Retrospective study of 911,698 patients from multiple integrated health delivery networks (Humedica). Control group included 338,297 individuals without known HF, CKD, diabetes, cardiovascular disease, or hypertension. Patient data came from private insurers, Medicare and Medicaid users, and uninsured individuals.1
Modifying RAASi therapy (eg, ACEi/ARB/MRA) may pose a risk to your patients with hyperkalemia4
ZORA real-world evidence HF subgroup (n=9086): analysis of US patients with HF and/or Stage 3 or 4 CKD and high potassium:
Risk of HF-related hospitalizations or ED visits associated with RAASi* modification due to high potassium4
43
%increased risk with RAASi discontinuation
Adjusted† HR 1.43 (95% CI: 1.25–1.65; n=1966; 392 events)
40
%increased risk with RAASi down-titration
Adjusted† HR 1.40 (95% CI: 1.11–1.78; n=430; 84 events)
compared with patients who maintained their RAASi dose (n=3049; 421 events)
Regardless of modification approach to guideline-directed RAASi following high potassium, patients with HF may be at greater risk for HF hospitalizations or ED visits4
LOKELMA® (sodium zirconium cyclosilicate) is not indicated to reduce the risk of death or HF-related hospitalization.2
ZORA was an observational analysis of Optum’s de-identified market clarity data between July 2019 and September 2021 in 15,488 adult patients with CKD stage 3-4 and/or HF with an index high potassium episode (based on ICD codes) and ≥1 filled RAASi prescription within 6 months before index high potassium. Primary outcome evaluated the risk of ED visits or hospitalizations for HF or progression to ESKD (initiation of HD or a diagnosis of ESKD or stage 5 CKD) in patients who discontinued or down-titrated RAASi compared to those who maintained RAASi following index high potassium episode. Data represent a subgroup of 9086 patients with HF (diagnosis code) evaluated following index high potassium event.4,5
KEY LIMITATIONS: Information on race, certain risk factors, other comorbidities, and severity markers for CKD and HF were not available. The primary outcome did not account for mortality as a competing risk. A higher proportion of patients who discontinued or down-titrated RAASi therapy had severe index HK episode (potassium ≥6.0 mEq/L) and higher use of MRA at baseline. Patients who were hospitalized and died within 90 days were excluded, leading to an underestimation of the risk of outcomes.4
* RAASi included ACEi, ARB, ARNI, and MRA. RAASi discontinuation was defined as no fill of a new prescription within 90 days after index. RAASi down-titration was defined as >25% reduction in dose of any previously prescribed RAASi.4,5
† Adjusted for age, sex, history of HK, diabetes, CKD including stage, and baseline use of RAASi.4
Could high potassium be a driving force behind compromising guideline-directed MRA therapy?6,7
Observational study of Stockholm-based patients who were initiated on an MRA6,7:
In patients who initiated MRA and developed HK‡ (n=1761)6
47
%of patients discontinued§ MRA (n=827)
74
%were not reintroduced to MRA therapy during the subsequent year
In patients with HF who initiated MRA and developed HK‡ (n=1235)7
47
%of patients discontinued§ MRA
Study Design: Observational, descriptive study utilizing Stockholm CREAtinine Measurements (SCREAM) project data to assess the 1-year incidence and clinical predictors of HK as well as the clinical management of HK by quantifying drug prescription changes after an episode of HK in 13,726 adults not on dialysis that initiated MRA therapy (no previous dispensation recorded of spironolactone and eplerenone) and had an index HK event between January 2007 to December 2010. A comparison cohort of new users of beta blockers was propensity score matched 1:1 to new MRA users to assess difference of incidence of HK. The MRA treatment lengths and dosages were ascertained by pharmacy dispensations. Majority (99%) of patients were dispensed spironolactone and the remaining (<1%) eplerenone, and most common comorbidities included HF (46%) and HTN (64%), among others. In both populations, overall and in patients with HF, following HK, MRA was reduced in 5% of each respective population, with the remainder continuing the same dose.6
KEY LIMITATIONS: Residual confounding may exist due to unmeasured variables such as: body mass index, blood pressure or smoking habits, ejection fraction in heart failure patients, and information on dietary interventions to control K+ intake. MRA use was based on MRA purchases and there was no confirmation on actual amount of medication taken. Causality cannot be inferred.6
‡
First-detected HK episode (K+ >5.0 mEq/L), following initiation of MRA therapy.6
§
Absence of subsequent MRA purchase or MRA purchase occurring >30 days from the estimated pill supply.6
Have you considered the risks of RAASi modification for managing high potassium in your patients?
Learn how LOKELMA can help treat high potassium
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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.
PLEASE READ FULL PRESCRIBING INFORMATION for LOKELMA.
You may report side effects related to AstraZeneca products.
K+=potassium; RAASi=renin‐angiotensin‐aldosterone system inhibitor.
References: 1. LOKELMA® (sodium zirconium cyclosilicate) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024. 2. 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. 3. 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 Herat Association joint committee on clinical practice guidelines. J Am Coll Cardiol. 2022;79(17):e263-e241. 4. 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.
ACEi=angiotensin-converting enzyme inhibitor; ARB=angiotensin II receptor blocker; ARNI=angiotensin receptor-neprilysin inhibitor; CI=confidence interval; CKD=chronic kidney disease; CV=cardiovascular; DM=diabetes mellitus; ED=emergency department; eGFR=estimated glomerular filtration rate; EHR=electronic health records; ESKD=end-stage kidney disease; HD=hemodialysis; HF=heart failure; HK=hyperkalemia; HR=hazard ratio; HTN=hypertension; ICD=International Classification of Diseases; IDN=integrated delivery network; K+=potassium; MNT=medical nutrition therapy; MRA=mineralocorticoid receptor antagonist; RAASi=renin‐angiotensin‐aldosterone system inhibitor; RWE=real-world evidence; US=United States.
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. 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. 5. 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. 6. Data on File, REF-197797. AZPLP. 7. 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. 8. Rastogi A, Pollack CV Jr, Lesen 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. 9. 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. 10. Data on File, REF-196652, AZPLP. 11. Trevisan M, de Deco P, Xu H, et al. Incidence, predictors and clinical management of hyperkalemia in new users of mineralocorticoid receptor antagonists. Eur J of Heart Fail. 2018;20(8):1217-1226. 12. Supplement to: Trevisan M, de Deco P, Xu H, et al. Incidence, predictors and clinical management of hyperkalemia in new users of mineralocorticoid receptor antagonists. Eur J of Heart Fail. 2018;20(8):1217-1226.
ACEi=angiotensin-converting enzyme inhibitor; ARB=angiotensin II receptor blocker; ARNI=angiotensin receptor-neprilysin inhibitor; CI=confidence interval; CKD=chronic kidney disease; CV=cardiovascular; DM=diabetes mellitus; ED=emergency department; eGFR=estimated glomerular filtration rate; EHR=electronic health records; ESKD=end-stage kidney disease; HD=hemodialysis; HF=heart failure; HK=hyperkalemia; HR=hazard ratio; HTN=hypertension; ICD=International Classification of Diseases; IDN=integrated delivery network; K+=potassium; MNT=medical nutrition therapy; MRA=mineralocorticoid receptor antagonist; RAASi=renin‐angiotensin‐aldosterone system inhibitor; RWE=real-world evidence; US=United States.
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. 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. 5. 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. 6. Data on File, REF-197797. AZPLP. 7. 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. 8. Rastogi A, Pollack CV Jr, Lesen 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. 9. 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.
ACEi=angiotensin-converting enzyme inhibitor; ARB=angiotensin II receptor blocker; ARNI=angiotensin receptor-neprilysin inhibitor; CI=confidence interval; CKD=chronic kidney disease; CV=cardiovascular; DM=diabetes mellitus; ED=emergency department; eGFR=estimated glomerular filtration rate; EHR=electronic health records; ESKD=end-stage kidney disease; HD=hemodialysis; HF=heart failure; HK=hyperkalemia; HR=hazard ratio; HTN=hypertension; ICD=International Classification of Diseases; IDN=integrated delivery network; K+=potassium; MNT=medical nutrition therapy; MRA=mineralocorticoid receptor antagonist; RAASi=renin‐angiotensin‐aldosterone system inhibitor; RWE=real-world evidence; US=United States.
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. 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. 5. 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. 6. Data on File, REF-197797. AZPLP. 7. 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. 8. Rastogi A, Pollack CV Jr, Lesen 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. 9. 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.
ACEi=angiotensin-converting enzyme inhibitor; ARB=angiotensin II receptor blocker; ARNI=angiotensin receptor-neprilysin inhibitor; CI=confidence interval; CKD=chronic kidney disease; CV=cardiovascular; DM=diabetes mellitus; ED=emergency department; eGFR=estimated glomerular filtration rate; EHR=electronic health records; ESKD=end-stage kidney disease; HD=hemodialysis; HF=heart failure; HR=hazard ratio; HTN=hypertension; ICD=International Classification of Diseases; IDN=integrated delivery network; K+=potassium; MNT=medical nutrition therapy; MRA=mineralocorticoid receptor antagonist; RAASi=renin‐angiotensin‐aldosterone system inhibitor; RWE=real-world evidence; US=United States.
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. Data on File, REF-196652, AZPLP. 5. 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. 6. Trevisan M, de Deco P, Xu H, et al. Incidence, predictors and clinical management of hyperkalemia in new users of mineralocorticoid receptor antagonists. Eur J of Heart Fail. 2018;20(8):1217-1226. 7. Supplement to: Trevisan M, de Deco P, Xu H, et al. Incidence, predictors and clinical management of hyperkalemia in new users of mineralocorticoid receptor antagonists. Eur J of Heart Fail. 2018;20(8):1217-1226.
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. SPS® Suspension [prescribing information]. 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. 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.
ACEi=angiotensin-converting enzyme inhibitor; ARB=angiotensin II receptor blocker; CKD=chronic kidney disease; HF=heart failure; HK=hyperkalemia; K+=potassium; MRA=mineralocorticoid receptor antagonist; RAASi=renin‐angiotensin‐aldosterone system inhibitor.
Reference: 1. Data on File, US-63248, AZPLP.
ACEi=angiotensin-converting enzyme inhibitor; ARB=angiotensin II receptor blocker; CKD=chronic kidney disease; HK=hyperkalemia; K+=potassium; RAASi=renin‐angiotensin‐aldosterone system inhibitor.
Reference: 1. Data on File, US-86969, AZPLP.
ACEi=angiotensin-converting enzyme inhibitor; ARB=angiotensin II receptor blocker; CKD=chronic kidney disease; HK=hyperkalemia; K+=potassium; RAASi=renin‐angiotensin‐aldosterone system inhibitor.
Reference: 1. Data on File, US-63248, AZPLP.
ACEi=angiotensin-converting enzyme inhibitor; ARB=angiotensin II receptor blocker; CKD=chronic kidney disease; HF=heart failure; K+=potassium; MRA=mineralocorticoid receptor antagonist; RAASi=renin‐angiotensin‐aldosterone system inhibitor.
Reference: 1. Data on File, US-77519, AZPLP.
CI=confidence interval; CKD-chronic kidney disease; ED=emergency department; ESKD=end-stage kidney disease; FDA=Food and Drug Administration; HK=hyperkalemia; IRR=incidence rate ratio; K+=potassium; LIDI=long interdialytic interval; qd=once daily; qod=every other day; SIDI=short interdialytic interval; tid=three times daily; US=United States.
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. SPS® Suspension [prescribing information]. Farmville, NC: CMP Pharma, Inc; 2021. 5. Veltassa® (patiromer) [package insert]. Redwood City, CA: Vifor Pharma, Inc; 2023. 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. 7. Data on File, REF-217791, AZPLP. 8. Data on File, REF-237731, AZPLP. 9. Data on File, US-63248, AZPLP. 10. 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.
CI=confidence interval; CKD-chronic kidney disease; ED=emergency department; ESKD=end-stage kidney disease; FDA=Food and Drug Administration; HK=hyperkalemia; IRR=incidence rate ratio; K+=potassium; LIDI=long interdialytic interval; qd=once daily; qod=every other day; SIDI=short interdialytic interval; tid=three times daily; US=United States.
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. SPS® Suspension [prescribing information]. Farmville, NC: CMP Pharma, Inc; 2021. 5. Veltassa® (patiromer) [package insert]. Redwood City, CA: Vifor Pharma, Inc; 2023. 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. 7. Data on File, REF-217791, AZPLP. 8. Data on File, REF-237731, AZPLP. 9. Data on File, US-63248, AZPLP. 10. 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.
CI=confidence interval; CKD-chronic kidney disease; ED=emergency department; ESKD=end-stage kidney disease; FDA=Food and Drug Administration; HK=hyperkalemia; IRR=incidence rate ratio; K+=potassium; LIDI=long interdialytic interval; qd=once daily; qod=every other day; SIDI=short interdialytic interval; tid=three times daily; US=United States.
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. SPS® Suspension [prescribing information]. Farmville, NC: CMP Pharma, Inc; 2021. 5. Veltassa® (patiromer) [package insert]. Redwood City, CA: Vifor Pharma, Inc; 2023. 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. 7. Data on File, REF-217791, AZPLP. 8. Data on File, REF-237731, AZPLP. 9. Data on File, US-63248, AZPLP. 10. 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.
FDA=Food and Drug Administration; 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. 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. 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. 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. Data on File, US-77519, AZPLP. 6. 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.
ACEi=angiotensin-converting enzyme inhibitor; ARB=angiotensin II receptor blocker; ARNI=angiotensin receptor-neprilysin inhibitor; HK=hyperkalemia; K+=potassium; MRA=mineralocorticoid receptor antagonist; qd=once daily; qod=every other day; RAASi=renin-angiotensin-aldosterone system; tid=three times daily.
References: 1. LOKELMA® (sodium zirconium cyclosilicate) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024. 2. Kidney Disease: Improving Global Outcomes (KDIGO) KD Work Group. KDIGO 2024 clinical practice guideline for evaluation and management of chronic kidney disease. Kidney Int. 2024;105(4S):S117-S314. 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 Guidelines. J Am Coll Cardiol. 2022;79(17):e263-e421. 4. 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.
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). Accessed September 12, 2024. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/207078Orig1s000MedR.pdf 4. Data on File, REF-262719. AZPLP. 5. 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; LIDI=long interdialytic interval; qod=every other day; 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.
K+=potassium.
References: 1. Data on File, US-63248, AZPLP. 2. Formulary Data are provided by Fingertip Formulary® and are current as of 3/13/2025.
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.
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.
PLEASE READ FULL PRESCRIBING INFORMATION for LOKELMA.
You may report side effects related to AstraZeneca products.
K+=potassium; RAASi=renin‐angiotensin‐aldosterone system inhibitor.
References: 1. LOKELMA® (sodium zirconium cyclosilicate) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024. 2. 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. 3. 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 Herat Association joint committee on clinical practice guidelines. J Am Coll Cardiol. 2022;79(17):e263-e241. 4. 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.
ACEi=angiotensin-converting enzyme inhibitor; ARB=angiotensin II receptor blocker; ARNI=angiotensin receptor-neprilysin inhibitor; CI=confidence interval; CKD=chronic kidney disease; CV=cardiovascular; DM=diabetes mellitus; ED=emergency department; eGFR=estimated glomerular filtration rate; EHR=electronic health records; ESKD=end-stage kidney disease; HD=hemodialysis; HF=heart failure; HK=hyperkalemia; HR=hazard ratio; HTN=hypertension; ICD=International Classification of Diseases; IDN=integrated delivery network; K+=potassium; MNT=medical nutrition therapy; MRA=mineralocorticoid receptor antagonist; RAASi=renin‐angiotensin‐aldosterone system inhibitor; RWE=real-world evidence; US=United States.
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. 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. 5. 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. 6. Data on File, REF-197797. AZPLP. 7. 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. 8. Rastogi A, Pollack CV Jr, Lesen 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. 9. 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. 10. Data on File, REF-196652, AZPLP. 11. Trevisan M, de Deco P, Xu H, et al. Incidence, predictors and clinical management of hyperkalemia in new users of mineralocorticoid receptor antagonists. Eur J of Heart Fail. 2018;20(8):1217-1226. 12. Supplement to: Trevisan M, de Deco P, Xu H, et al. Incidence, predictors and clinical management of hyperkalemia in new users of mineralocorticoid receptor antagonists. Eur J of Heart Fail. 2018;20(8):1217-1226.
ACEi=angiotensin-converting enzyme inhibitor; ARB=angiotensin II receptor blocker; ARNI=angiotensin receptor-neprilysin inhibitor; CI=confidence interval; CKD=chronic kidney disease; CV=cardiovascular; DM=diabetes mellitus; ED=emergency department; eGFR=estimated glomerular filtration rate; EHR=electronic health records; ESKD=end-stage kidney disease; HD=hemodialysis; HF=heart failure; HK=hyperkalemia; HR=hazard ratio; HTN=hypertension; ICD=International Classification of Diseases; IDN=integrated delivery network; K+=potassium; MNT=medical nutrition therapy; MRA=mineralocorticoid receptor antagonist; RAASi=renin‐angiotensin‐aldosterone system inhibitor; RWE=real-world evidence; US=United States.
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. 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. 5. 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. 6. Data on File, REF-197797. AZPLP. 7. 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. 8. Rastogi A, Pollack CV Jr, Lesen 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. 9. 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.
ACEi=angiotensin-converting enzyme inhibitor; ARB=angiotensin II receptor blocker; ARNI=angiotensin receptor-neprilysin inhibitor; CI=confidence interval; CKD=chronic kidney disease; CV=cardiovascular; DM=diabetes mellitus; ED=emergency department; eGFR=estimated glomerular filtration rate; EHR=electronic health records; ESKD=end-stage kidney disease; HD=hemodialysis; HF=heart failure; HK=hyperkalemia; HR=hazard ratio; HTN=hypertension; ICD=International Classification of Diseases; IDN=integrated delivery network; K+=potassium; MNT=medical nutrition therapy; MRA=mineralocorticoid receptor antagonist; RAASi=renin‐angiotensin‐aldosterone system inhibitor; RWE=real-world evidence; US=United States.
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. 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. 5. 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. 6. Data on File, REF-197797. AZPLP. 7. 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. 8. Rastogi A, Pollack CV Jr, Lesen 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. 9. 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.
ACEi=angiotensin-converting enzyme inhibitor; ARB=angiotensin II receptor blocker; ARNI=angiotensin receptor-neprilysin inhibitor; CI=confidence interval; CKD=chronic kidney disease; CV=cardiovascular; DM=diabetes mellitus; ED=emergency department; eGFR=estimated glomerular filtration rate; EHR=electronic health records; ESKD=end-stage kidney disease; HD=hemodialysis; HF=heart failure; HR=hazard ratio; HTN=hypertension; ICD=International Classification of Diseases; IDN=integrated delivery network; K+=potassium; MNT=medical nutrition therapy; MRA=mineralocorticoid receptor antagonist; RAASi=renin‐angiotensin‐aldosterone system inhibitor; RWE=real-world evidence; US=United States.
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. Data on File, REF-196652, AZPLP. 5. 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. 6. Trevisan M, de Deco P, Xu H, et al. Incidence, predictors and clinical management of hyperkalemia in new users of mineralocorticoid receptor antagonists. Eur J of Heart Fail. 2018;20(8):1217-1226. 7. Supplement to: Trevisan M, de Deco P, Xu H, et al. Incidence, predictors and clinical management of hyperkalemia in new users of mineralocorticoid receptor antagonists. Eur J of Heart Fail. 2018;20(8):1217-1226.
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. SPS® Suspension [prescribing information]. 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. 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.
ACEi=angiotensin-converting enzyme inhibitor; ARB=angiotensin II receptor blocker; CKD=chronic kidney disease; HF=heart failure; HK=hyperkalemia; K+=potassium; MRA=mineralocorticoid receptor antagonist; RAASi=renin‐angiotensin‐aldosterone system inhibitor.
Reference: 1. Data on File, US-63248, AZPLP.
ACEi=angiotensin-converting enzyme inhibitor; ARB=angiotensin II receptor blocker; CKD=chronic kidney disease; HK=hyperkalemia; K+=potassium; RAASi=renin‐angiotensin‐aldosterone system inhibitor.
Reference: 1. Data on File, US-86969, AZPLP.
ACEi=angiotensin-converting enzyme inhibitor; ARB=angiotensin II receptor blocker; CKD=chronic kidney disease; HK=hyperkalemia; K+=potassium; RAASi=renin‐angiotensin‐aldosterone system inhibitor.
Reference: 1. Data on File, US-63248, AZPLP.
ACEi=angiotensin-converting enzyme inhibitor; ARB=angiotensin II receptor blocker; CKD=chronic kidney disease; HF=heart failure; K+=potassium; MRA=mineralocorticoid receptor antagonist; RAASi=renin‐angiotensin‐aldosterone system inhibitor.
Reference: 1. Data on File, US-77519, AZPLP.
CI=confidence interval; CKD-chronic kidney disease; ED=emergency department; ESKD=end-stage kidney disease; FDA=Food and Drug Administration; HK=hyperkalemia; IRR=incidence rate ratio; K+=potassium; LIDI=long interdialytic interval; qd=once daily; qod=every other day; SIDI=short interdialytic interval; tid=three times daily; US=United States.
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. SPS® Suspension [prescribing information]. Farmville, NC: CMP Pharma, Inc; 2021. 5. Veltassa® (patiromer) [package insert]. Redwood City, CA: Vifor Pharma, Inc; 2023. 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. 7. Data on File, REF-217791, AZPLP. 8. Data on File, REF-237731, AZPLP. 9. Data on File, US-63248, AZPLP. 10. 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.
CI=confidence interval; CKD-chronic kidney disease; ED=emergency department; ESKD=end-stage kidney disease; FDA=Food and Drug Administration; HK=hyperkalemia; IRR=incidence rate ratio; K+=potassium; LIDI=long interdialytic interval; qd=once daily; qod=every other day; SIDI=short interdialytic interval; tid=three times daily; US=United States.
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. SPS® Suspension [prescribing information]. Farmville, NC: CMP Pharma, Inc; 2021. 5. Veltassa® (patiromer) [package insert]. Redwood City, CA: Vifor Pharma, Inc; 2023. 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. 7. Data on File, REF-217791, AZPLP. 8. Data on File, REF-237731, AZPLP. 9. Data on File, US-63248, AZPLP. 10. 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.
CI=confidence interval; CKD-chronic kidney disease; ED=emergency department; ESKD=end-stage kidney disease; FDA=Food and Drug Administration; HK=hyperkalemia; IRR=incidence rate ratio; K+=potassium; LIDI=long interdialytic interval; qd=once daily; qod=every other day; SIDI=short interdialytic interval; tid=three times daily; US=United States.
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. SPS® Suspension [prescribing information]. Farmville, NC: CMP Pharma, Inc; 2021. 5. Veltassa® (patiromer) [package insert]. Redwood City, CA: Vifor Pharma, Inc; 2023. 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. 7. Data on File, REF-217791, AZPLP. 8. Data on File, REF-237731, AZPLP. 9. Data on File, US-63248, AZPLP. 10. 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.
FDA=Food and Drug Administration; 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. 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. 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. 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. Data on File, US-77519, AZPLP. 6. 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.
ACEi=angiotensin-converting enzyme inhibitor; ARB=angiotensin II receptor blocker; ARNI=angiotensin receptor-neprilysin inhibitor; HK=hyperkalemia; K+=potassium; MRA=mineralocorticoid receptor antagonist; qd=once daily; qod=every other day; RAASi=renin-angiotensin-aldosterone system; tid=three times daily.
References: 1. LOKELMA® (sodium zirconium cyclosilicate) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024. 2. Kidney Disease: Improving Global Outcomes (KDIGO) KD Work Group. KDIGO 2024 clinical practice guideline for evaluation and management of chronic kidney disease. Kidney Int. 2024;105(4S):S117-S314. 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 Guidelines. J Am Coll Cardiol. 2022;79(17):e263-e421. 4. 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.
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). Accessed September 12, 2024. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/207078Orig1s000MedR.pdf 4. Data on File, REF-262719. AZPLP. 5. 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; LIDI=long interdialytic interval; qod=every other day; 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.
K+=potassium.
References: 1. Data on File, US-63248, AZPLP. 2. Formulary Data are provided by Fingertip Formulary® and are current as of 3/13/2025.
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.