HYPERKALEMIA RISK
As a Primary Care Physician, managing hyperkalemia 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
In patients with CKD and HK,
The serious consequences of HK can cause disruptions in care
In retrospective analyses:
All-cause inpatient hospitalizations during 12-month follow-up in patients with Stage 3 or 4 CKD and recurrent HK* vs without HK† (n=4549 matched‡ pairs)4
All-cause mortality in patients with Stage 3 or 4 CKD and recurrent HK* vs without HK† (n=6337 matched§ pairs)5
LOKELMA® (sodium zirconium cyclosilicate) is not indicated to reduce the risk of death or progression to ESKD or hospitalization.2
REVOLUTIONIZE III was a retrospective cohort study of the US claims and EHR database comparing clinical and economic outcomes of matched patients with Stage 3 or 4 CKD with recurrent HK vs without HK from January 2016 to August 2022. Patients were followed from the index date of recurrent HK and without HK cohorts until time to death, end of data or enrollment, or ≥7 days of outpatient K+ binder use.4,5
KEY LIMITATIONS: Given the definition of recurrent HK utilized, patients with an elevated K+ value without a diagnosis code for HK were not captured in the study. Residual confounding may be present due to unmeasured variables that cannot be ruled out.4,6
*
Patients with an index HK (≥1 HK diagnosis and ≥1 HK lab value within 7 days of each other) and an additional HK diagnosis or a serum K+ lab value >5.0 mEq/L during the 12-month baseline period.4,5
†
Patients with index normokalemia event (any K+ lab value 3.5–5.0 mEq/L) and no HK diagnosis or lab value <3.5 or >5.0 mEq/L at any point.4,5
‡
Patients with recurrent HK were first matched to those without HK on: CKD Stage 3 or 4, RAASi use, CV events, HF, type I or II diabetes during baseline and 15-day post-index window and Medicare medical coverage during baseline. A logistic regression model was then used to generate the propensity score.4
§
Patients with recurrent HK were first matched to those without HK on: CKD Stage 3 or 4, CV events, HF, type I or II DM, HTN and proteinuria during baseline, and RAASi therapy on index date. A logistic regression model was then used to generate the propensity score.5,6
||
HRs were calculated using cause-specific Cox models; median time to all-cause mortality was not reached in either cohort.5
Patients with HK are likely to experience future recurrences7
In an RWE study of patients with hyperkalemia and Stage 3 or 4 CKD, the percentage of patients with HK recurrence¶ following an MNT visit increased in those with prior recurrence and the average time between each recurrence decreased.
¶
Recurrent hyperkalemia was defined as a serum K+ >5.0 mEq/L that was at least 7 days apart from a prior lab evidence of hyperkalemia.7
REVOLUTIONIZE I STUDY DESIGN: A retrospective, observational study of US EHR that evaluated the recurrence of hyperkalemia following an MNT visit within 30 days of lab-confirmed hyperkalemia diagnosis in adults with Stage 3 or 4 CKD between January 2019 and October 2022. The index date was the date corresponding to the date of MNT visit plus 7 days. Patients were followed up for 6 months post-MNT. Patients were censored when they died or initiated outpatient K+ binder. There were no pre-determined K+ serum monitoring levels. Hyperkalemia was ascertained from facility-based encounters or outpatient encounter study visits and K+ measurements between these encounters were unknown.7
KEY LIMITATIONS: The contents of standardized curriculums used during the MNT visit and adherence to the dietary counseling was unknown. The impact of other pharmacological therapy, including those used for inpatient management of acute hyperkalemia events that could have potentially affected K+ levels were not tracked, and patients were not censored if received. Causality cannot be inferred. The percent of patients was calculated from the number of patients experiencing a recurrence in the preceding recurrent event group, not from the total patient population. For this reason, a patient might have been counted more than once in multiple groups.7
RAASi MODIFICATION
In patients with CKD and HK,
The serious consequences of HK can cause disruptions in care
In retrospective analyses:
Risk of progression to ESKD# with RAASi modification** in patients with Stage 3 or 4 CKD and/or HF and HK—CKD subgroup analysis (n=11,873)8
LOKELMA® (sodium zirconium cyclosilicate) is not indicated to reduce the risk of death or progression to ESKD or 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 or 4 and/or HF with an index HK episode (based on ICD codes) and ≥1 filled RAASi prescription within 6 months before index HK. 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 or up-titrated RAASi following index HK episode. Data represents a subgroup of 11,873 patients with CKD (diagnosis code or eGFR) evaluated following an index HK event. Patients with CKD who discontinued (n=2460) or down-titrated RAASi (n=460) vs those who maintained or uptitrated RAASi (n=4586) following HK were associated with a 74% and 60% increased risk of progression to ESKD, respectively.8,9
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 (K+ ≥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.9
#
Initiation of hemodialysis or a diagnosis of ESKD or CKD Stage 5 in any position recorded in hospital, emergency, or outpatient setting.9
**
RAASi included ACEi, ARB, ARNI, and MRA. RAASi down-titration was defined as decrease in previously prescribed RAASi by >25% and discontinuation was defined as no fill of a new prescription within 90 days after index.8,9
††
Adjusted for age, sex, history of HK, diabetes, HF, CKD including stage, and baseline use of RAASi.8
Have you considered the risks of RAASi modification for managing hyperkalemia in your patients?
Learn how LOKELMA can help treat hyperkalemia
You are now about to leave the LOKELMA website.
The site you are about to visit is maintained by a third party who is solely responsible for its contents. AstraZeneca provides this link as a service to website visitors. AstraZeneca is not responsible for the privacy policy of any third-party website. We encourage you to read the privacy policy of every website you visit.
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. 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 7/17/2023.
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. 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 7/17/2023.
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.