• Burden of hyperkalemia in patients on hemodialysis
  • EFFICACY IN DIALYSIS PATIENTS

Hyperkalemia is prevalent in patients on hemodialysis and poses risks of hospitalization and mortality2,3

38% of hemodialysis patients at US dialysis centers in August 2019 had hyperkalemia (n=7938)

Despite receiving in-center hemodialysis, 38% of patients presented at US dialysis centers in August 2019 with hyperkalemia (n=7938)*2

In a retrospective observational study, where hyperkalemia was defined as K+ ≥5.5 mEq/L

Prevalence of hyperkalemia was found to be 2.4x higher in hemodialysis patients during the day after the long interdialytic interval vs the day after the short interdialytic interval†4

Prevalence of Hyperkalemia following Long Interdialytic Interval vs Short Interdialytic Interval

The short interdialytic interval was defined as a single day between sessions.

The long interdialytic interval was defined as multiple days between sessions.

*Data from the DOPPS Practice Monitor using the most recent (single) monthly pre-dialysis values of serum K+ levels from the national sample of >11,000 patients in >200 US hemodialysis centers. Note: Hyperkalemia is defined as K+ ≥ 5.0 mEq/L. Timing of K+ measurement in relation to the hemodialysis schedule, whether after a long or short interdialytic interval, is unknown.2

A retrospective observational study from the USRDS of hemodialysis patients (N=36,888) during 2010 with ≥6 hemodialysis sessions and ≥1 K+ measurement. Serum K+ was typically measured once a month during routine sessions. The hemodialysis schedule was 3 times weekly.4

Rate of hyperkalemia was computed as a ratio of total number of hyperkalemia episodes and cumulative follow-up time in months. The LIDI rate was calculated based on hyperkalemia episodes identified on the day after the LIDI and the SIDI rate was calculated based on hyperkalemia episodes identified on the day after the SIDI.4

DOPPS=Dialysis Outcomes and Practice Patterns Study; HK=hyperkalemia; LIDI=long interdialytic interval; SIDI=short interdialytic interval; USRDS=United States Renal Data System.

Hospital Icon

In a retrospective observational study of ESRD patients receiving thrice-weekly hemodialysis (n=52,734), serum K+ ≥5.5 mEq/L was associated with increased adjusted risk of all-cause hospitalization*5

HYPERKALEMIA IS ASSOCIATED WITH AN INCREASED RISK OF ALL-CAUSE AND CV MORTALITY IN PATIENTS RECEIVING HEMODIALYSIS†3

Hyperkalemia is associated with an increased risk of all-cause and cv mortality in patients receiving hemodialysis

Graph reproduced from Torlén et al. 2012.

LOKELMA® (sodium zirconium cyclosilicate) is not indicated to reduce the risk of death or hospitalizations.1

*Based on an analysis of 533,889 qualifying serum K+ measurements from US Medicare adult patients at a large dialysis organization with at least 1 K+ measurement between January 2010 and December 2011. Serum K+ measurements were generally performed monthly immediately prior to HD on the first or second treatment day after the long weekend (ie, Monday or Wednesday for a Monday-Wednesday-Friday schedule). Analyses were adjusted for covariates including demographics, comorbidities, and laboratory values.5

Analysis of 111,434 hemodialysis patients with follow-up data from an observational cohort study conducted in US DaVita facilities between July 2001 and June 2006. Hyperkalemia defined as K+ ≥5.0 mEq/L. The timing of K+ measurement in relation to the hemodialysis cycle and schedule was not described in the study. Data was adjusted for demographics, comorbidities, and laboratory values.3

Reference group was hemodialysis patients with serum K+ between 4.0 and 4.5 mEq/L.3

§Each patient had K+ measurements performed at least monthly. The average of all repeated measures was done quarterly for 20 calendar quarters to calculate the time-averaged serum K+.3

CV=cardiovascular; ESRD=end-stage renal disease; HD=hemodialysis.

Treat persistent hyperkalemia in patients on chronic hemodialysis

STUDY 4: Met its primary endpoint of a proportion of patients classified as responders, defined as patients who maintained a pre-dialysis serum K+ between 4.0-5.0 mEq/L on at least 3 out of 4 dialysis treatments after the long interdialytic interval and who did not receive rescue therapy* during the evaluation period.1

41% of patients treated with LOKELMA (n=97) were responders compared to 1% of patients in the placebo group (n=99) (P<0.001)1

RESPONDERS TO TREATMENT

Responders of LOKELMA vs Placebo

STUDY 4 DESIGN: DIALIZE was a double-blind, placebo-controlled trial in patients with end-stage renal 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 pre-dialysis serum K levels between 4.0 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 pre-dialysis serum K levels after the LIDI were 5.8 mEq/L in the LOKELMA group and 5.9 mEq/L in the placebo group.1,6

*Rescue therapy was defined as any urgent therapeutic intervention considered necessary to reduce serum K in the setting of severe hyperkalemia (serum K >6.0 mEq/L). Rescue therapy use was left to the investigator's clinical judgment to be given in accordance with local practice patterns.6

Persistent hyperkalemia defined as pre-dialysis serum K+ >5.4 mEq/L after the LIDI and >5.0 mEq/L after at least one SIDI.6

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

LOKELMA sustained pre-dialysis K+ levels in patients on hemodialysis with continued treatment1

MEAN PRE-DIALYSIS SERUM K+ LEVELS OVER TIME IN PATIENTS ON CHRONIC HEMODIALYSIS1

LOKELMA sustained pre-dialysis K+ levels in patients on hemodialysis with continued treatment

F/U=follow-up period.

The displayed error bars correspond to 95% confidence intervals.

n=number of patients with non-missing K+ measurements at a particular visit.

EXPLORE DOSING FOR ALL PATIENTS

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.

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.

DOSING

  • Non-hemodialysis Patients
    For initial treatment of hyperkalemia, the recommended starting dose is 10 g administered three times a day up to 48 hours. For maintenance treatment, the recommended starting dose is 10 g once daily. Monitor serum potassium and adjust dose of LOKELMA at 1-week intervals or longer in increments of 5 g based on serum potassium and desired target range. The recommended maintenance dose range is from 5 g every other day to 15 g daily. Discontinue or decrease the dose of LOKELMA if serum potassium is below the desired target range.
  • Hemodialysis Patients
    For patients on chronic hemodialysis, administer LOKELMA only on non‑dialysis days. The recommended starting dose is 5 g once daily on non-dialysis days. Consider a starting dose of 10 g once daily on non-dialysis days in patients with serum potassium greater than 6.5 mEq/L. Monitor serum potassium and adjust the dose of LOKELMA based on the pre-dialysis serum potassium value after the long interdialytic interval and desired target range. During initiation and after dose adjustment, assess serum potassium after one week. Discontinue or decrease the dose of LOKELMA if serum potassium falls below the desired target range based on pre-dialysis value after the long interdialytic interval or the patient develops clinically significant hypokalemia. The recommended maintenance dose range is from 5 g to 15 g once daily, on non-dialysis days.

Please read full Prescribing Information 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.

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.

DOSING

  • Non-hemodialysis Patients
    For initial treatment of hyperkalemia, the recommended starting dose is 10 g administered three times a day up to 48 hours. For maintenance treatment, the recommended starting dose is 10 g once daily. Monitor serum potassium and adjust dose of LOKELMA at 1-week intervals or longer in increments of 5 g based on serum potassium and desired target range. The recommended maintenance dose range is from 5 g every other day to 15 g daily. Discontinue or decrease the dose of LOKELMA if serum potassium is below the desired target range.
  • Hemodialysis Patients
    For patients on chronic hemodialysis, administer LOKELMA only on non‑dialysis days. The recommended starting dose is 5 g once daily on non-dialysis days. Consider a starting dose of 10 g once daily on non-dialysis days in patients with serum potassium greater than 6.5 mEq/L. Monitor serum potassium and adjust the dose of LOKELMA based on the pre-dialysis serum potassium value after the long interdialytic interval and desired target range. During initiation and after dose adjustment, assess serum potassium after one week. Discontinue or decrease the dose of LOKELMA if serum potassium falls below the desired target range based on pre-dialysis value after the long interdialytic interval or the patient develops clinically significant hypokalemia. The recommended maintenance dose range is from 5 g to 15 g once daily, on non-dialysis days.

Please read full Prescribing Information for LOKELMA.