Lokelma

1 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 . LOKELMA is a potassium binder 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.

2 DOSAGE AND ADMINISTRATION • Recommended starting dose is 10 g administered three times a day for up to 48 hours. • For maintenance treatment, recommended dose is 10 g once daily. Adjust dose at one-week intervals as needed (by 5 g daily) to obtain desired serum potassium target range. Patients on Chronic Hemodialysis • Recommended starting dose is 5 g once daily on non-dialysis days. See full Prescribing Information for additional dosing instructions, as well as reconstitution and administration instructions for the oral suspension.

2.1Recommended 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 . 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.

2.2Dosage 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

2.3Reconstitution and Administration In

general, other oral medications should be administered at least 2 hours before or 2 hours after LOKELMA . 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.

5 WARNINGS AND PRECAUTIONS • Gastrointestinal Adverse Events in Patients with Motility Disorders. • Edema. • Hypokalemia in patients on hemodialysis. • LOKELMA has radio-opaque properties and, therefore, may give the appearance typical of an imaging agent during abdominal X-ray procedures.

5.1Gastrointestinal 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.

5.2Edema 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 . 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.

5.3Hypokalemia 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.

5.4Diagnostic Tests

LOKELMA has radio-opaque properties and, therefore, may give the appearance typical of an imaging agent during abdominal X-ray procedures .

None. None.

8.1Pregnancy Risk Summary

LOKELMA is not absorbed systemically following oral administration and maternal use is not expected to result in fetal exposure to the drug.

The following adverse reactions are discussed in greater detail elsewhere in the label: • Edema . Most common adverse reactions with LOKELMA: mild to moderate edema. To report SUSPECTED ADVERSE REACTIONS, contact AstraZeneca at 1-800-236-9933 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1Clinical 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.

In a pooled analysis of clinical studies conducted in countries with a predominantly Asian population, constipation occurred in patients receiving LOKELMA with an estimated incidence of 9% and 5% for the 10 g and 5 g dose respectively. Constipation was resolved with dose adjustment or treatment discontinuation. No cases of constipation were reported in patients receiving placebo.

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.