Becker's Hospital Review

LOKELMA ® (sodium zirconium cyclosilicate) for oral suspension Brief Summary of Prescribing Information. For complete prescribing information consult official package insert. INDICATIONS AND USAGE LOKELMA is indicated for the treatment of hyperkalemia in adults. Limitation of Use LOKELMA should not be used as an emergency treatment for life-threatening hyperkalemia because of its delayed onset of action [see Clinical Pharmacology (12.2) and Clinical Studies (14) in the full Prescribing Information]. DOSAGE AND ADMINISTRATION Recommended Dosage For initial treatment of hyperkalemia, the recommended dose of LOKELMA is 10 g administered three times a day for up to 48 hours. Administer LOKELMA orally as a suspension in water [see Dosage and Administration (2.3) in the full Prescribing Information]. For continued treatment, the recommended dose is 10 g once daily. Monitor serum potassium and adjust the dose of LOKELMA based on the serum potassium level and desired target range. During maintenance treatment, up-titrate based on the serum potassium level at intervals of 1-week or longer and in increments of 5 g. Decrease the dose of LOKELMA or discontinue if the serum potassium is below the desired target range. The recommended maintenance dose range is from 5 g every other day to 15 g daily. Dosage Adjustment for Patients on Chronic Hemodialysis 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 inter-dialytic interval and desired target range. During initiation and after a dose adjustment, assess serum potassium after one week. The recommended maintenance dose range is from 5 g to 15 g once daily, on non-dialysis days. Discontinue or decrease the dose of LOKELMA if: • serum potassium falls below the desired target range based on the pre-dialysis value after the long interdialytic interval, or; • the patient develops clinically significant hypokalemia Reconstitution and Administration In general, other oral medications should be administered at least 2 hours before or 2 hours after LOKELMA [see Drug Interactions (7) in the full Prescribing Information]. Instruct patients to empty the entire contents of the packet(s) into a drinking glass containing approximately 3 tablespoons of water or more if desired. Stir well and drink immediately. If powder remains in the drinking glass, add water, stir and drink immediately. Repeat until no powder remains to ensure the entire dose is taken. CONTRAINDICATIONS None. WARNINGS AND PRECAUTIONS Gastrointestinal Adverse Events in Patients with Motility Disorders Avoid use of LOKELMA in patients with severe constipation, bowel obstruction or impaction, including abnormal post-operative bowel motility disorders, because LOKELMA has not been studied in patients with these conditions and 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 (e.g., heart failure or renal disease). Advise patients to adjust dietary sodium, if appropriate. Increase the dose of diuretics as needed [see Adverse Reactions (6) in the full Prescribing Information]. In a clinical trial of LOKELMA in patients on chronic hemodialysis in which most patients were treated with doses of 5 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 (e.g., 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 following adverse reactions are discussed in greater detail elsewhere in the label: • Edema [see Warnings and Precautions (5.2) in the full Prescribing Information]. Clinical Studies Experience Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice. The total exposure to LOKELMA in the safety and efficacy clinical trials of patients not on dialysis with hyperkalemia was 1,760 patients with 652 patients exposed to LOKELMA for at least 6 months and 507 patients exposed for at least one year. The population (n=1,009) in the placebo-controlled trials included patients aged 22 to 96 years, females (n=454), Caucasians (n=859) and Blacks (n=130). Patients had hyperkalemia in association with comorbid diseases such as chronic kidney disease, heart failure, and diabetes mellitus. In placebo-controlled trials in which patients who were not on dialysis were treated with once daily doses of LOKELMA for up to 28 days, edema was reported in 4.4% of patients receiving 5 g, 5.9% of patients receiving 10 g and 16.1% of patients receiving 15 g LOKELMA compared to 2.4% of patients receiving placebo. In longer-term uncontrolled trials in which most patients were maintained on doses <15 g once daily, adverse reactions of edema (edema, generalized edema and peripheral edema) were reported in 8% to 11% of patients. Laboratory Abnormalities In clinical trials in patients who were not on dialysis, 4.1% of LOKELMA-treated patients developed hypokalemia with a serum potassium value less than 3.5 mEq/L, which resolved with dosage reduction or discontinuation of LOKELMA. In a clinical trial of LOKELMA in patients on chronic hemodialysis, 5% of patients developed pre-dialysis hypokalemia (serum potassium <3.5 mEq/L) in both the LOKELMA and placebo groups; 3% and 1% of patients developed a serum potassium < 3.0 mEq/L in the LOKELMA and placebo groups, respectively. DRUG INTERACTIONS LOKELMA can transiently increase gastric pH. As a result, LOKELMA can change the absorption of co-administered drugs that exhibit pH-dependent solubility, potentially leading to altered efficacy or safety of these drugs when taken close to the time LOKELMA is administered. In general, other oral medications should be administered at least 2 hours before or 2 hours after LOKELMA [see Dosage and Administration (2.3) and Clinical Pharmacology (12.3) in the full Prescribing Information]. LOKELMA is not expected to impact systemic exposure of drugs that do not exhibit pH-dependent solubility and so spacing is not needed if it has been determined that the concomitant medication does not exhibit pH-dependent solubility. USE IN SPECIFIC POPULATIONS Pregnancy Risk Summary LOKELMA is not absorbed systemically following oral administration and maternal use is not expected to result in fetal exposure to the drug. Lactation Risk Summary LOKELMA is not absorbed systemically following oral administration, and breastfeeding is not expected to result in exposure of the child to LOKELMA. Pediatric Use Safety and effectiveness in pediatric patients have not been established. Geriatric Use Of the total number of subjects in clinical studies of LOKELMA, 58% were age 65 and over, while 25% were 75 and over. No overall differences in safety or effectiveness were observed between these patients and younger patients. PATIENT COUNSELING INFORMATION Dosing Instruct the patient how to reconstitute LOKELMA for administration. Inform the patient that it is necessary to drink the full dose [see Dosage and Administration (2.3) in the full Prescribing Information]. Instruct dialysis patients who experience acute illness (e.g., decreased oral intake of food or fluids, diarrhea) to contact the health care provider. The dose of LOKELMA may need to be adjusted [see Warnings and Precautions (5.3) in the full Prescribing Information]. Diagnostic Testing Advise patients to notify their physician prior to an abdominal X-ray [see Warnings and Precautions (5.4) in the full Prescribing Information]. Drug Interactions Advise patients who are taking other oral medications to separate dosing of LOKELMA by at least 2 hours (before or after) [see Drug Interactions (7) in the full Prescribing Information]. Diet Advise patients to adjust dietary sodium, if appropriate [see Warnings and Precautions (5.2) in the full Prescribing Information]. U.S. Patent No: 6332985, 8808750, 8877255, 8802152, 9592253 ©AstraZeneca 2022 Manufactured by: AstraZeneca Pharmaceuticals LP, Wilmington, DE 19850 09/22 US-73797 3/23

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