Lowering K+ in adult patients with Hyperkalemia on RAAS inhibitors can be complex.

Among patients on RAAS inhibitor therapy (n=520) during the maintenance phase* of Study 3, a 12-month, open-label study evaluating LOKELMA in patients with hyperkalemia, 37 initiated therapy during the maintenance phase and 483 were on therapy at baseline. Of those 483 patients:

NO CHANGE IN RAAS INHIBITOR DOSE (n=357)1

NO CHANGE IN RAAS INHIBITOR DOSE (n=357)1

  • 13% of patients (n=62) increased their RAAS inhibitor dose1‡
  • 14% of patients (n=69) decreased their dose1‡
  • 11% of patients (n=51) discontinued their dose1
  • 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§ within 72 hours (n=746; 99%) entered the maintenance phase. For maintenance treatment, the initial dosage 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 serum potassium 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 potassium ≤5.1 mEq/L during months 3-12 of the maintenance phase.1,2

*Excluded 5 patients who discontinued RAAS inhibitor therapy prior to their first dose of the study drug.1

Based on a retrospective analysis of the changes in RAAS inhibitor use during the maintenance phase of a 12-month, open-label study.1

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

§Normokalemia was defined as serum potassium levels between 3.5 and 5 mEq/L.1

qd=once daily; qod=every other day; RAAS=renin-angiotensin-aldosterone system; tid=3 times a day.

Review LOKELMA's safety profile

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 see 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 see full Prescribing Information for LOKELMA.