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LOKELMA® (sodium zirconium cyclosilicate) is indicated for the treatment of hyperkalaemia in adult patients.
The recommended starting dose of LOKELMA for the correction phase is 10g three times daily within 24 to 48 hours. The recommended starting dose for maintenance therapy is 5g once daily, which may be titrated up to 10g daily or down to 5g once every other day, as needed. No more than 10g once daily should be used for maintenance therapy.
LOKELMA should only be administered on non-dialysis days. The recommended starting dose is 5g once daily. To establish normokalaemia, the dose may be titrated up or down weekly based on the pre-dialysis serum potassium value after the long-term dialytic interval (LIDI). The dose could be adjusted at intervals of one week in increments of 5g up to 15g once daily on non-dialysis days.
In the 48-hour, open-label correction phase of the HARMONIZE study1,2:
*In an emergency situation, standard of care should be used in line with local or national hyperkalaemia management guidelines2
Adapted from Kosiborod, et al (2014)2
Error bars indicate 95% confidence intervals2
LOKELMA consistently reduced serum potassium from baseline, regardless of2:
Additionally, patients with higher potassium levels at baseline experienced greater reductions in serum potassium2
Adapted from Kosiborod et al (2014)2
*<60 mL/min/1.73 m2.
Error bars indicate 95% confidence intervals
In the 11-month open-label extension phase of the HARMONIZE study, 88% of the patients who were receiving LOKELMA maintained an average potassium of <5.1 mmol/L1,3
Adapted from LOKELMA Summary of Product Characteristics1
Error bars indicate 95% confidence intervals2
*Please note that the recommended starting dose for maintenance therapy for non-dialysis patients with LOKELMA is 5 g once daily, which may be titrated to 10 g once daily as needed. No more than 10 g once daily should be used for maintenance therapy for non- dialysis patients. The 5 g once-daily dose can be down-titrated to 5 g every other day1.
In a prespecified exploratory analysis of a 12-month study, 87% of patients continued or had their RAASi dose increased while taking LOKELMA4
11% of patients receiving RAASi therapy at baseline (n=483) discontinued RAASi during the 12-month open-label trial4
Among patients on RAASi therapy (n=483) during the maintenance phase of ZS-005, a 12-month, open-label study evaluating LOKELMA in patients not on dialysis with hyperkalaemia4:
Of the 263 RAAS-naïve patients at baseline, 14% initiated RAASi therapy during the study4
GALVINISE was a retrospective, propensity matched cohort study of closed US medical and pharmacy claims evaluating HK-related hospitalisations or ED visits in adult outpatients who initiated SZC (index date) between January 2019 and December 2022^8,9a
In the short-term and long-term LOKELMA cohorts, respectively.
Note: a CKD defined by diagnosis code and ESKD by any diagnosis code for ESKD or by a diagnosis code for ESKD, stage 5 CKD or unspecified ESKD;18,9b Patients were propensity score matched based on the duration of SZC therapy and were followed for 6 months after index date or until they were censored (re-initiated SZC after ≥30 day gap of discontinuation, initiated another K+ binder, at the end of data availability, or death);8,9 cDuration of SZC use was the sum of the days of supply for all SZC prescriptions during the follow-up period starting from index date to censoring date or date of SZC discontinuation8,9.
Observational studies are associated with limitations*. Real world evidence should be interpreted in the context of randomised control trials.
dMaintained RAASi was defined as stabilised or up-titrated RAASi5,6
aSubgroup analysis by CKD and/or HF was not evaluated in Spain due to limited sample size5,6
bP<0.00015,6
cP=0.00205,6
*Despite balancing cohorts on potential baseline confounders using propensity score matching,some risk of residual confounding may remain even after adjustment6,7.
In the DIALIZE study, 41% of patients receiving LOKELMA achieved K+ 4.0-5.0 mmol/L in at least 3 of 4 haemodialysis sessions following the LIDI, without need for rescue therapy vs 1% for Placebo (p<0.001)10.
Adapted from Fishbane, et al (2019)10
Error bars represent 95% confidence intervals10
HARMONIZE (ZS-004) was a Phase III, multicentre, randomized, double-blind, multiphase, placebo-controlled study evaluating the safety and efficacy of LOKELMA in 258 patients with hyperkalaemia2
*In an emergency situation, standard of care should be used in line with local or national guidelines2
Correction phase2: participants received LOKELMA 10g three times daily, administered for 48 hours
Maintenance phase2: patients who achieved normokalaemia (3.5-5.0 mmol/L) by the morning of study Day 3 (n=237) then proceeded to the randomized phase, where they were randomized to receive LOKELMA 5g, 10g, an unlicensed dose, or placebo, once daily for 28 days.
Open-label extension study (HARMONIZE OLE, ZS-004E)3: patients were eligible for the extension phase if they completed the randomized dosing phase (study Day 29 visit) or discontinued due to hypo- or hyperkalaemia and were able to start ZS-004E dosing within 2 days after their last ZS-004 dose. Patients were required to have potassium values ranging from 3.5-6.2 mmol/L at ZS-004 study Day 29 visit, or a mean value ranging from 3.5-6.2 mmol/L for two consecutive measurements at 0 and 60 minutes on acute phase Day 1/maintenance phase Day 1 if they discontinued ZS-004 study due to hypo- or hyperkalaemia.
Eligible patients continued with LOKELMA 10g once daily, which could be titrated to 5g or an unlicensed dose, in the 11-month, open-label extension study.3
Treatment was discontinued on study exit (Day 365).1
Initial study (correction and maintenance phases): mean serum potassium level in each LOKELMA group vs placebo on days 8-29.2
Extension phase: proportion of subjects with mean serum potassium values ≤5.1 mmol/L during Extended Dosing Study Days 8-337.3
Initial study (correction and maintenance phases)2:
Extension phase:
Study ZS-005 was a 12-month, multicentre, open-label, single-arm, phase 3 trial to investigate the long-term safety and efficacy of LOKELMA in patients with hyperkalaemia.4
Adapted from Spinowitz et al. (2019)4
Error bars indicate 95% confidence intervals
*Off-drug values collected 7 (±1) days after the last administration of LOKELMA; the extended maintenance group contained a small proportion (12%) of patients who were treated with an unlicensed dose once daily4
**The recommended starting dose for maintenance therapy for non-dialysis patients with LOKELMA is 5 g once daily, which may be titrated to 10 g once daily as needed. No more than 10 g once daily should be used for maintenance therapy for non- dialysis patients. The 5 g once-daily dose can be down-titrated to 5 g every other day1
Correction phase4: hyperkalaemic patients (n=751) with serum potassium levels of ≥5.1 mmol/L received a 10g dose of LOKELMA three times daily for 24-72 hours.
Maintenance phase4: patients (n=746) who achieved normokalaemia (3.5-5.0 mmol/L) during the open-label phase were enrolled in the extended dosing phase and received 5g of LOKELMA once daily. Potassium levels were assessed throughout the first month and every 4 weeks thereafter until month 12. During the extension phase the dosages were adjusted based on potassium, with patients taking either 5g, 10g or an unlicensed dose once daily or 5g every other day to maintain normokalaemia without dietary or medication restrictions.
Adapted from Spinowitz et al. (2019)4
*Patients who achieved normokalaemia (K+ 3.5–5.0 mmol/L) as measured by the point-of-care i-STAT device at any point during the acute phase were immediately eligible to enter the 12-month extended dosing phase and received OD treatment with LOKELMA4
Primary endpoints4
Secondary endpoints4
The DIALIZE study is the first, double-blind, randomized, placebo-controlled, phase 3b multicentre trial to determine the efficacy and safety of LOKELMA in haemodialysis patients with hyperkalaemia.10
During the evaluation period, 41% of LOKELMA-treated patients achieved K+ 4.0-5.0 mmol/L in at least 3 of 4 haemodialysis sessions following the LIDI, without need for rescue therapy vs 1% for placebo (OR, 68.8; 95% CI, 10.9-2810.9; p<0.001)10
The post-hoc analysis showed the proportion of patients who maintained serum potassium level between 3.5 and 5.5 mmol/L on at least 3 out of 4 dialysis treatments after LIDI during the evaluation period was 70% in the LOKELMA group and 21% in the placebo group.1
Overall, 40 patients (41.7%) had an AE in the LOKLEMA group, and 46 patients (46.5%) had an AE in the placebo group. Most AEs reported were mild or moderate intensity. The most common AEs by system organ class were gastrointestinal disorders, with 19 patients (19.8%) in the LOKELMA group and 17 patients (17.2%) in the placebo group. Infections were reported in 12 patients (12.5%) in the LOKELMA group and 9 patients (9.1%) in the placebo group.10
Please refer to the LOKELMA SmPC for more information on adverse events
The study included a 1-week screening period, an 8-week treatment period (4 weeks for dose titration and 4 weeks for evaluation on stable dose), and a 2 week (±3 days) follow-up period, ending with a final visit.10
196 patients with ESRD managed for ≥3 months before randomization by haemodialysis three times weekly, and who had persistent hyperkalaemia despite adequate haemodialysis during the 1-week screening period, were included.10
Screening period: screening began on the day of haemodialysis after the long interdialytic interval (day -7), included the haemodialysis treatments after the two short interdialytic intervals on days -5 and -3, and was completed on the day before randomization.10
Treatment period: patients were randomized 1:1 to receive orally a starting dose of LOKELMA 5g or placebo once daily on non-dialysis days. During dose titration, the doses of LOKELMA and placebo were adjusted weekly over 4 weeks to attain normokalaemia, defined as achieving and maintaining a pre-dialysis serum potassium concentration of 4.0-5.0 mmol/L after the long interdialytic interval. Doses were titrated in 5 g increments to a maximum dose of 15 g once daily on non-dialysis days. Treatment was maintained at a stable dose during the 4-week evaluation period.10
Primary endpoint: the proportion of patients who, during the 4-week evaluation phase, maintained a pre-dialysis serum potassium concentration of 4.0-5.0 mmol/L during at least 3 of 4 haemodialysis treatments following the long interdialytic interval and who did not require urgent rescue therapy.10
Secondary endpoint: the proportion of patients requiring any urgent rescue intervention to reduce serum potassium in the setting of severe hyperkalaemia (>6.0 mmol/L).10
Safety outcomes: included assessment of AEs, laboratory parameters/vital signs, ECG and IDWG10
aThe LOKLEMA and No K+ binder groups were similar in terms of baseline demographics (age and sex), comorbidities (CKD, arrhythmia, HF, coronary heart disease, diabetes, and proteinuria), comedications (RAASi, α-blockers, β-blockers, β-agonists, cardiac glycosides, calcium channel blockers, calcium gluconate, diuretics (any), loop diuretics, thiazide diuretics, insulin, sodium bicarbonate, nonsteroidal anti-inflammatory drugs, and sodium-glucose cotransporter-2 inhibitors), hyperkalaemia (index severity and recurrent/new onset), history of K+ binder use, and estimated glomerular filtration rate5,6:
Dosing and administration
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AE=adverse event; CI=confidence interval; CKD=chronic kidney disease; ECG=electrocardiography; eGFR=estimated glomerular filtration rate; ESRD=end stage renal disease; HF=heart failure; IDWG=interdialytic weight gain; IQR=interquartile range; LIDI=long interdialytic interval; OD=once daily; OR=odds ratio; R=ratio; RAASi=renin-angiotensin-aldosterone inhibitor; RWE=real-world evidence; TDS=three times a day.
GB-70043 September 2025
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