Sodium zirconium cyclosilicate is an oral potassium binder indicated for the treatment of hyperkalemia in adults, including patients with end-stage renal disease receiving chronic hemodialysis. Sodium zirconium cyclosilicate is not appropriate for the rapid correction of life-threatening hyperkalemia because of its delayed onset of action. Sodium zirconium cyclosilicate can transiently increase gastric pH and change the absorption of coadministered drugs that exhibit pH-dependent solubility, possibly leading to altered efficacy or safety of the other drug if administered temporally to sodium zirconium cyclosilicate; dose separation is necessary.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Oral Administration
Oral Solid Formulations
-In general, administer other oral medications at least 2 hours before or 2 hours after sodium zirconium cyclosilicate. Transient increases in gastric pH around the time of sodium zirconium cyclosilicate administration may alter the absorption of medications that exhibit pH-dependent solubility. Altering the absorption of medications that are simultaneously coadministered with sodium zirconium cyclosilicate may reduce their efficacy or increase the risk for adverse effects.
Oral Liquid Formulations
Powder for oral suspension
-Empty the entire contents of the packet(s) into a drinking glass containing about 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.
Dose-dependent, mild to moderate edema has been reported with the use of sodium zirconium cyclosilicate in patients not receiving dialysis. During clinical trials, edema was reported in 4.4% of patients receiving sodium zirconium cyclosilicate 5 g/day, 5.9% of patients receiving 10 g/day, and 16.1% of patients receiving 15 g/day compared to 2.4% of patients receiving placebo. In long-term uncontrolled trials in which most patients were maintained on sodium zirconium cyclosilicate doses less than 15 g/day, edema, including generalized edema or peripheral edema, was reported in 8% to 11% of sodium zirconium cyclosilicate-treated patients. In a clinical trial of sodium zirconium cyclosilicate 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 sodium zirconium cyclosilicate and placebo groups. Monitor for signs of edema, particularly in patients who have sodium intake restrictions or are prone to fluid overload (e.g., heart failure or renal disease). Increase the dose of diuretics as needed, and advise patients to adjust dietary sodium, if appropriate. Each 5 g dose of sodium zirconium cyclosilicate contains approximately 400 mg of sodium.
During clinical trials of patients who were not on dialysis, hypokalemia (serum potassium less than 3.5 mEq/L) developed in 4.1% of patients treated with sodium zirconium cyclosilicate. In a clinical trial of sodium zirconium cyclosilicate in patients on chronic hemodialysis, 5% of patients developed pre-dialysis hypokalemia (serum potassium less than 3.5 mEq/L) in both the sodium zirconium cyclosilicate and placebo groups; serum potassium less than 3 mEq/L was observed in 3% of patients in the sodium zirconium cyclosilicate group and 1% of patients in the placebo group. Monitor serum potassium and adjust the dosage based on the desired target range. Hypokalemia resolved with sodium zirconium cyclosilicate dose reduction or discontinuation. Additionally, sodium zirconium cyclosilicate causes a small, dose-dependent increase in serum bicarbonate concentrations. Increases in serum bicarbonate concentrations of 1.1 mmol/L at 5 g/day, 2.3 mmol/L at 10 g/day, and 2.6 mmol/L at 15 g/day were reported with sodium zirconium cyclosilicate compared to a mean increase of 0.6 mmol/L in patients treated with placebo. The clinical significance of any increase in serum bicarbonate is unclear.
Constipation occurred in 5% and 9% of patients receiving 5 g/day and 10 g/day, respectively, of sodium zirconium cyclosilicate in a pooled analysis of clinical studies conducted in countries with a predominantly Asian population. Constipation resolved with dose adjustment or treatment discontinuation. No cases of constipation were reported in patients receiving placebo.
Avoid sodium zirconium cyclosilicate use in patients with severe constipation, GI obstruction, or fecal impaction, including abnormal post-operative bowel motility disorders. Sodium zirconium cyclosilicate has not been studied in patients with these conditions and may be ineffective and worsen gastrointestinal conditions.
Monitor for signs of edema, particularly in patients who have a sodium restriction or are prone to fluid overload (e.g., heart failure or renal disease). Increase the dose of diuretics as needed, and advise patients to adjust dietary sodium, if appropriate. Each 5 g dose of sodium zirconium cyclosilicate contains approximately 400 mg of sodium.
Dialysis patients may be prone to acute illness that can increase the risk of hypokalemia on sodium zirconium cyclosilicate (e.g., illnesses associated with decreased oral intake, diarrhea). Adjust the sodium zirconium cyclosilicate dose based on potassium concentrations in these settings.
Administration of sodium zirconium cyclosilicate may result in diagnostic test interference. Sodium zirconium cyclosilicate has radio-opaque properties and therefore may give the appearance typical of an imaging agent during abdominal X-ray procedures.
Sodium zirconium cyclosilicate is not systemically absorbed after oral administration, and maternal use during pregnancy is not expected to result in fetal exposure to the drug.
Sodium zirconium cyclosilicate is not systemically absorbed after oral administration, and breast-feeding is not expected to result in exposure of the child to the drug.
For the treatment of hyperkalemia:
Oral dosage:
Adults: 10 g PO 3 times daily for up to 48 hours, initially, then 10 g PO once daily. Monitor serum potassium and adjust the dosage based on desired target range. Increase the dosage in increments of 5 g at intervals of 1 week or longer to achieve desired target, and decrease the dosage or discontinue therapy if serum potassium is below the desired target. The recommended maintenance dosage range is 5 g every other day to 15 g once daily.
Maximum Dosage Limits:
-Adults
30 g/day PO.
-Geriatric
30 g/day PO.
-Adolescents
Safety and efficacy have not been established.
-Children
Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
-Neonates
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Patients with Renal Impairment Dosing
Chronic hemodialysis
The recommended initial dose is 5 g PO once daily on non-dialysis days; consider a starting dose of 10 g PO once daily on non-dialysis days in patients with serum potassium more than 6.5 mEq/L. Monitor serum potassium and adjust the dose of sodium zirconium cyclosilicate based on the pre-dialysis serum potassium concentration after the long inter-dialytic interval and desired target range. During initiation and after a dose adjustment, assess serum potassium after 1 week. The recommended maintenance dose is 5 to 15 g PO once daily on non-dialysis days. Discontinue or decrease the dose if serum potassium falls below the desired target range or the patient develops clinically significant hypokalemia.
*non-FDA-approved indication
In general, administer oral medications at least 2 hours before or 2 hours after sodium zirconium cyclosilicate. Transient increases in gastric pH at the time of administration may alter medication absorption and reduce efficacy or increase toxicity.
Sodium zirconium cyclosilicate is a potassium binder with a high affinity for potassium ions. It is a non-absorbed zirconium silicate that preferentially captures potassium in exchange for hydrogen and sodium, even in the presence of other cations such as calcium or magnesium. Sodium zirconium cyclosilicate increases fecal potassium excretion through binding of potassium in the lumen of the gastrointestinal tract. Binding of potassium reduces the concentration of free potassium in the gastrointestinal lumen resulting in lower serum potassium concentrations.
Sodium zirconium cyclosilicate is administered orally. Sodium zirconium cyclosilicate is insoluble and does not undergo enzymatic metabolism. It is recovered in the feces with no evidence of systemic absorption.
Affected cytochrome P450 isoenzymes and drug transporters: none
-Route-Specific Pharmacokinetics
Oral Route
In healthy subjects, sodium zirconium cyclosilicate 5 or 10 g once daily for 4 days caused a dose-dependent increase in fecal potassium excretion and corresponding dose-dependent decreases in urinary potassium excretion and serum potassium concentrations. In hyperkalemic patients treated with sodium zirconium cyclosilicate 10 g PO 3 times daily for 48 hours, reductions in serum potassium were observed 1 hour after initiation of therapy and continued to decline over 48 hours. Patients with higher starting serum potassium concentrations or receiving a higher dose experienced greater reductions in serum potassium. In patients not continuing sodium zirconium cyclosilicate, potassium concentrations increased. Zirconium concentrations in urine and blood were similar (i.e., either undetectable or around the lower limit of quantification) in treated and untreated patients.