Proven efficacy in a broad range of patients¹

Choose LOKELMA to treat hyperkalemia¹

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.

ADULT PATIENTS NOT ON DIALYSIS
ADULT PATIENTS ON DIALYSIS

LOKELMA is proven to help patients achieve and maintain normal K⁺ levels¹

Rapid reductions in serum K⁺ levels¹

LOKELMA is the only K⁺ binder with reductions measured in as early as 1 hour^1,3-5*

Primary endpoint was met: Demonstrating a greater reduction in serum K⁺ levels over the 48-hour initial treatment period with LOKELMA 10 g tid compared to placebo (P<0.001).^1,3

*IN STUDY 1: In as early as 1 hour after the first dose of LOKELMA 10 g, reduction in K⁺ levels was observed in patients. The study met its primary endpoint, demonstrating a greater reduction in serum K⁺ levels over the 48-hour initial treatment period with LOKELMA 10 g tid compared to placebo (P<0.001).^1,3

Limitation of Use: LOKELMA should not be used as an emergency treatment for life-threatening hyperkalemia because of its delayed onset of action.

STUDY 1: Mean serum K⁺ in the initial phase over 48 hours³

IN STUDY 1, reduction in K⁺ levels was observed in patients after first dose of LOKELMA 10 g as early as 1 hour.³

Limitation of Use: LOKELMA should not be used as an emergency treatment for life-threatening hyperkalemia because of its delayed onset of action.

STUDY 1 DESIGN: In the initial phase of a multicenter, two-part, double-blind, randomized, placebo-controlled, Phase 3 trial, 753 patients received placebo or 1.25 g, 2.5 g, 5 g, or 10 g LOKELMA tid for the initial 48 hours.^1,3

Sustained reductions in serum K⁺ levels¹

LOKELMA sustained^† normokalemia^‡ with continued treatment for up to 1 year^1,6,7

IN STUDY 2: LOKELMA-treated patients (n=258) with hyperkalemia who achieved normokalemia^‡ at 48 hours were included in the double-blind, randomized, maintenance phase of the study.^1,6

^†Primary endpoint was met: Mean serum K⁺ levels on Days 8-29 were lower with LOKELMA 5 g, 10 g, and 15 g vs placebo (4.8 mEq/L, 4.5 mEq/L, and 4.4 mEq/L vs 5.1 mEq/L, respectively; P≤0.001 for all doses).^1,6

IN STUDY 2 EXTENSION: Patients (N=123) who continued LOKELMA in the open-label extension phase sustained^† normokalemia^‡ for up to 11 months.^1,7

^‡Normokalemia was defined as K⁺ levels between 3.5 mEq/L and 5.0 mEq/L.^1,6,7

STUDY 2: Mean serum K⁺ in the initial phase at 48 hours^1,6

Average serum K⁺ levels decreased from 5.6 mEq/L to 4.5 mEq/L with LOKELMA 10 g tid for 48 hours^1,6

STUDY 2 EXTENSION: Mean serum K⁺ levels in patients who completed a 28-day randomized maintenance phase and continued on LOKELMA for 11 months¹

Discontinuing LOKELMA resulted in increased K⁺ levels

~17% of patients had serum K⁺ levels over 5.5 mEq/L in only 7 days⁷

STUDY 2 DESIGN: After the open-label initial phase of a multicenter, two-part, Phase 3 trial, in which 258 patients received 10 g LOKELMA tid for 48 hours, patients who achieved normokalemia were randomized to receive 5 g, 10 g, or 15 g LOKELMA or placebo once daily for 28 days in the maintenance phase. 123 patients who completed the maintenance phase participated in the 11-month, open-label extension study.^1,6

STUDY 2 EXTENSION DESIGN: Patients who were included in the 28-day randomized maintenance phase of Study 2 had the option to continue treatment with LOKELMA in an open-label extension phase for up to 11 months (N=123). The LOKELMA dose was titrated in 5-g increments (to 5 g qod up to 15 g qd) based on i-STAT K⁺ levels.^1,7

Treating HK may enable guideline-recommended RAASi therapy^8,9

In a prespecified exploratory analysis of Study 3,

Nearly 9 of 10 Patients Continued RAASi Therapy While Taking LOKELMA Long Term

In a prespecified exploratory analysis of Study 3,

continued RAASi therapy while taking LOKELMA long term.¹⁰

In the 483 patients on RAASi therapy at baseline, during the maintenance phase of Study 3, a 12-month, open-label study evaluating LOKELMA in patients with hyperkalemia:

74% of patients had no change in RAASI dose
13% had an increase in RAASi dose^§
14% had a decrease in RAASi dose^§
11% of patients discontinued RAASi

Among 263 RAASi-naïve participants, 14% initiated RAASi therapy.

The primary endpoints included the percentage of patients who achieved normokalemia (K⁺=3.5–5.0 mEq/L), during the initial phase (n=746; 99%) and the percentage of patients who maintained mean serum K⁺ ≤5.1 mEq/L during Months 3-12 of the maintenance phase (achieved by 88%). The mean baseline K⁺ was 5.6 mEq/L.^1,10

^§Patients were counted more than once if they required more than 1 RAASi adjustment, so the total percentage across all 4 categories may exceed 100%.¹⁰

STUDY 3 DESIGN: LOKELMA was evaluated for long-term efficacy in 751 patients with hyperkalemia in an open-label, single-arm, 12-month, Phase 3 study. Following the initial-phase treatment of LOKELMA 10 g tid, patients who achieved normokalemia (K⁺=3.5–5.0 mEq/L) within 72 hours (n=746; 99%) entered the maintenance phase. For maintenance treatment, the initial dose of LOKELMA was 5 g qd and was adjusted to a minimum of 5 g qod up to a maximum of 15 g qd, based on i-STAT K⁺ level. The primary endpoints included the percentage of patients who achieved normokalemia during the initial phase and the percentage of patients who maintained mean serum K⁺ ≤5.1 mEq/L during Months 3-12 of the maintenance phase (achieved by 88% of patients).^1,10 89% of patients continued RAASi use while taking LOKELMA.¹⁰ RAASi therapy included ACEi, ARB, and MRA.¹⁰

Review the real-world evidence study that evaluated long-term vs short-term use of LOKELMA

SEE THE REAL-WORLD DATA

Choose a treatment proven to be safe and generally well tolerated

REVIEW THE SAFETY PROFILE FOR LOKELMA

LOKELMA achieved and sustained lower predialysis K⁺ levels vs placebo^1,3

LOKELMA is the only FDA-approved K⁺ binder with efficacy and safety results and dosing information in the label for adult patients with hyperkalemia on chronic hemodialysis¹

STUDY 4:

41% of patients treated with LOKELMA (n=97) achieved the primary endpoint compared to 1% of patients in the placebo group (n=99; P<0.001)^1,3
Responders maintained predialysis serum K⁺ between 4.0–5.0 mEq/L during at least 3 of 4 hemodialysis treatments after the LIDI and did not receive rescue therapy* during the evaluation period^1,3

LOKELMA sustained lower predialysis K⁺ levels in patients on hemodialysis with continued treatment¹

*Rescue therapy was defined as any urgent therapeutic intervention considered necessary to reduce serum K⁺ in the setting of severe hyperkalemia (defined by protocol as >6.0 mEq/L). Rescue therapy use was left to the investigator's clinical judgment to be given in accordance with local practice guidelines.³

Mean predialysis serum K⁺ levels over time in patients on chronic hemodialysis¹

Serum K⁺ levels elevated after treatment discontinued

STUDY 4 DESIGN: DIALIZE was a double-blind, placebo-controlled trial in patients with end-stage kidney disease on chronic hemodialysis (≥3 months) and persistent hyperkalemia^† (n=196) who were randomized to receive LOKELMA 5 g or placebo once daily on non-dialysis days. In the initial 4-week period the dose could be adjusted weekly in 5-g increments up to 15 g qd on non-dialysis days to achieve predialysis serum K⁺ levels between 4.0 mEq/L and 5.0 mEq/L after the LIDI. The dose at the end of the dose-adjustment period was maintained throughout the 4-week evaluation period. Baseline mean predialysis serum K⁺ levels after the LIDI were 5.8 mEq/L in the LOKELMA group and 5.9 mEq/L in the placebo group.^1,3

^†Persistent hyperkalemia defined as predialysis serum K⁺ >5.4 mEq/L after the LIDI and >5.0 mEq/L after at least one SIDI.³

Choose a treatment proven to be safe and generally well tolerated

REVIEW THE SAFETY PROFILE FOR LOKELMA

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 .

IMPORTANT SAFETY INFORMATION FOR LOKELMA^® (sodium zirconium cyclosilicate)

+

Ca²⁺=calcium; GI=gastrointestinal; HK=hyperkalemia; K⁺=potassium; Mg²⁺=magnesium; qod=every other day; SPS=sodium polystyrene sulfonate.

References: 1. LOKELMA^® (sodium zirconium cyclosilicate) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024. 2. Stavros F, Yang A, Leon A, Nuttall M, Rasmussen HS. Characterization of structure and function of ZS-9, a K⁺ selective ion trap. PLoS One. 2014;9(12):e114686. 3. SPS^® Suspension [prescribing information]. Farmville, NC: CMP Pharma, Inc; 2021. 4. Palmer BF. Potassium binders for hyperkalemia in chronic kidney disease–diet, renin-angiotensin-aldosterone system inhibitor therapy, and hemodialysis. Mayo Clin Proc. 2020;95(2):339-354.

ACEi=angiotensin-converting enzyme inhibitor; ARB=angiotensin II receptor blocker; ARNI=angiotensin receptor-neprilysin inhibitor; CI=confidence interval; CKD=chronic kidney disease; DM=diabetes mellitus; ED=emergency department; eGFR=estimated glomerular filtration rate; EHR=electronic health record; ESKD=end-stage kidney disease; HD=hemodialysis; HF=heart failure; HFrEF=heart failure with reduced ejection fraction; HK=hyperkalemia; HR=hazard ratio; HTN=hypertension; ICD=International Classification of Diseases; IDN=integrated delivery network; K⁺=potassium; MACE=major adverse cardiovascular event; MACE+=major adverse cardiovascular event plus hospitalization for unstable angina; 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. 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. 3. Bakris G, Agiro A, Mu F, et al. Consequences of recurrent hyperkalemia on cardiovascular outcomes and mortality. JACC Adv. 2024;3(11):101331. 4. Data on File, REF-197797, AZPLP. 5. Data on File, REF-196652, AZPLP. 6. Rastogi A, Pollack CV Jr, Lesén E, et al. Association between reduced RAASi therapy and progression to ESKD in hyperkalemic CKD patients. Presented at: American Society of Nephrology (ASN) Kidney Week 2023; November 2-5, 2023; Philadelphia, PA. Poster TH-PO1028. 7. 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; ATLAS=Advanced Mapping Tactics for Learning Analysis; eLAAD=electronic longitudinal access and adjudication data; GDMT=guideline-directed medical therapy; HK=hyperkalemia; K⁺=potassium; MRA=mineralocorticoid receptor antagonist; RAASi=renin-angiotensin-aldosterone system inhibitor; US=United States.

ACEi=angiotensin-converting enzyme inhibitor; ARB=angiotensin II receptor blocker; K⁺=potassium; MRA=mineralocorticoid receptor antagonist; qd=once daily; qod=every other day; RAASi=renin-angiotensin-aldosterone system inhibitor; tid=three times a day.

References: 1. LOKELMA^® (sodium zirconium cyclosilicate) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024. 2. Data on File, US-108426, AZPLP. 3. Packham DK, Rasmussen HS, Lavin PT, et al. Sodium zirconium cyclosilicate in hyperkalemia [article and supplementary material]. N Engl J Med. 2015;372(3):222-231. 4. SPS^® Suspension [prescribing information]. Farmville, NC: CMP Pharma, Inc; 2021. 5. Veltassa^® (patiromer) [package insert]. Redwood City, CA: Vifor Pharma, Inc; 2023. 6. Kosiborod M, Rasmussen HS, Lavin P, et al. Effect of sodium zirconium cyclosilicate on potassium lowering for 28 days among outpatients with hyperkalemia: the HARMONIZE randomized clinical trial. JAMA. 2014;312(21):2223-2233. 7. Roger SD, Spinowitz BS, Lerma EV, et al. Efficacy and safety of sodium zirconium cyclosilicate for treatment of hyperkalemia: an 11-month open-label extension of HARMONIZE. Am J Nephrol. 2019;50(6):473-480. 8. Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2024 clinical practice guideline for evaluation and management of chronic kidney disease. Kidney Int. 2024;105(4S):S117-S314. 9. Heidenreich PA, Bozkurt B, Aguilar D, et al. 2022 AHA/ACC/HFSA guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2022;145(18):e895-e1032. 10. Spinowitz BS, Fishbane S, Pergola PE, et al. Sodium zirconium cyclosilicate among individuals with hyperkalemia: a 12-month phase 3 study. Clin J Am Soc Nephrol. 2019;14(6):798-809.

K⁺=potassium; LIDI=long interdialytic interval; qd=once daily; SIDI=short interdialytic interval.

References: 1. LOKELMA^® (sodium zirconium cyclosilicate) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024. 2. Data on File, US-108426, AZPLP. 3. Fishbane S, Ford M, Fukagawa M, et al. A phase 3b, randomized, double-blind, placebo-controlled study of sodium zirconium cyclosilicate for reducing the incidence of predialysis hyperkalemia. J Am Soc Nephrol. 2019;30(9):1723-1733.

CKD=chronic kidney disease; DM=diabetes mellitus; HF=heart failure; HTN=hypertension; qd=once daily.

References: 1. LOKELMA^® (sodium zirconium cyclosilicate) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024. 2. Data on File, US-108426, AZPLP. 3. Spinowitz BS, Fishbane S, Pergola PE, et al. Sodium zirconium cyclosilicate among individuals with hyperkalemia: a 12-month phase 3 study. Clin J Am Soc Nephrol. 2019;14(6):798-809. 4. U.S. Food & Drug Administration. Drug Approval Package: LOKELMA (sodium zirconium cyclosilicate) Medical Review(s). Accessed January 28, 2026. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/207078Orig1s000MedR.pdf

GI=gastrointestinal; K⁺=potassium; SAEs=serious adverse events.

References: 1. LOKELMA^® (sodium zirconium cyclosilicate) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024. 2. Data on File, US-108426, AZPLP. 3. Fishbane S, Ford M, Fukagawa M, et al. A phase 3b, randomized, double-blind, placebo-controlled study of sodium zirconium cyclosilicate for reducing the incidence of predialysis hyperkalemia. J Am Soc Nephrol. 2019;30(9):1723-1733.

K⁺=potassium; qd=once daily; tid=three times a day.

References: 1. LOKELMA^® (sodium zirconium cyclosilicate) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024. 2. Data on File, US-108426, AZPLP. 3. Kosiborod M, Rasmussen HS, Lavin P, et al. Effect of sodium zirconium cyclosilicate on potassium lowering for 28 days among outpatients with hyperkalemia: the HARMONIZE randomized clinical trial. JAMA. 2014;312(21):2223-2233. 4. Packham DK, Rasmussen HS, Lavin PT, et al. Sodium zirconium cyclosilicate in hyperkalemia [article and supplementary material]. N Engl J Med. 2015;372(3):222-231. 5. Spinowitz BS, Fishbane S, Pergola PE, et al; ZS-005 Study Investigators. Sodium zirconium cyclosilicate among individuals with hyperkalemia: a 12-month phase 3 study. Clin J Am Soc Nephrol. 2019;14(6):798-809. 6. Roger SD, Spinowitz BS, Lerma EV, et al. Efficacy and safety of sodium zirconium cyclosilicate for treatment of hyperkalemia: an 11-month open-label extension of HARMONIZE. Am J Nephrol. 2019;50(6):473-480.

K⁺=potassium; LIDI=long interdialytic interval.

References: 1. LOKELMA^® (sodium zirconium cyclosilicate) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024. 2. Data on File, US-108426, AZPLP. 3. Kosiborod M, Rasmussen HS, Lavin P, et al. Effect of sodium zirconium cyclosilicate on potassium lowering for 28 days among outpatients with hyperkalemia: the HARMONIZE randomized clinical trial. JAMA. 2014;312(21):2223-2233.

EGWP=Employer Group Waiver Plans; FEHBP=Federal Employees Health Benefits Program; HCP=healthcare professional; K⁺=potassium; MA=Medicare Advantage; PACE=Program of All-Inclusive Care for the Elderly; PBM=Pharmacy Benefit Manager; PCP=primary care physician; PDP=prescription drug plan; SN=special needs.

References: 1. Data on File, US-108426, AZPLP. 2. Formulary Data are provided by Fingertip Formulary^® and are current as of 3/13/2025.

Reference: 1. Data on File, US-108426, AZPLP.

ACEi=angiotensin-converting enzyme inhibitor; ARB=angiotensin II receptor blocker; ARNI=angiotensin receptor-neprilysin inhibitor; CI=confidence interval; CKD=chronic kidney disease; CV=cardiovascular; ED=emergency department; eGFR=estimated glomerular filtration rate; 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; K⁺=potassium; MACE=major adverse cardiovascular event; MACE+=major adverse cardiovascular event plus hospitalization for unstable angina; MNT=medical nutrition therapy; MRA=mineralocorticoid receptor antagonist; RAASi=renin‐angiotensin‐aldosterone system inhibitor; RWE=real-world evidence; SD=standard deviation; US=United States.

References: 1. 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. 2. Bakris G, Agiro A, Greatsinger A, et al. Economic burden of recurrent hyperkalemia in patients with chronic kidney disease. J Manag Care Spec Pharm. 2024;30(11):1261-1275. 3. Data on File, REF-197797, AZPLP. 4. Rastogi A, Pollack CV Jr, Lesén E, et al. Association between reduced RAASi therapy and progression to ESKD in hyperkalemic CKD patients. Presented at: American Society of Nephrology (ASN) Kidney Week 2023; November 2-5, 2023; Philadelphia, PA. Poster TH-PO1028. 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 hyperkalaemia in new users of mineralocorticoid receptor antagonists. Eur J Heart Fail. 2018;20(8):1217-1226.

CI=confidence interval; CKD=chronic kidney disease; ED=emergency department; ESKD=end-stage kidney disease; HD=hemodialysis; HK=hyperkalemia; IRR=inter-rater reliability; K⁺=potassium; SD=standard deviation; US=United States.

References: 1. Data on File, REF-217791, AZPLP. 2. Data on File, US-108426, AZPLP. 3. Data on File, US-63248, AZPLP.

Proven efficacy in a broad range of patients1

Choose LOKELMA to treat hyperkalemia1

LOKELMA is proven to help patients achieve and maintain normal K+ levels1

VIEW STUDY 1 DATA

STUDY DESIGN

VIEW STUDY 2 DATA

VIEW STUDY 2 EXTENSION DATA

Discontinuing LOKELMA resulted in increased K+ levels

STUDY DESIGNS

Treating HK may enable guideline-recommended RAASi therapy8,9