Zirconium Cyclosilicate (Monograph)

Brand name: Lokelma
Drug class: Potassium-removing Agents
Chemical name: disodium;2,2,4,4,6,6-hexahydroxyl-1,3,5,2,4,6-trioxatrisilinane;zirconium
Molecular formula: Na_~1.5H_~0.5ZrSi₃O₉•2–3H₂O
CAS number: 242800-27-7

Medically reviewed by Drugs.com on Apr 19, 2024. Written by ASHP.

Introduction

Nonabsorbed cation-exchange crystalline compound used for the removal of excess potassium.^{1 2 3 5}

Uses for Zirconium Cyclosilicate

Hyperkalemia

Treatment of hyperkalemia.^{1 2 3 8}

Has been shown to reduce elevated serum potassium concentrations and maintain normal serum potassium concentrations in patients with hyperkalemia.^{1 2 3 4 8 9 10}

Degree of reduction in serum potassium concentrations appears to be greater in patients with higher serum potassium concentrations at baseline.¹

Efficacy maintained during continued treatment for up to 1 year in clinical studies.^{1 8}

Not used as an emergency treatment for life-threatening hyperkalemia because of delayed onset of action.¹

Zirconium Cyclosilicate Dosage and Administration

Administration

Oral Administration

Administer orally as a suspension.¹

Administer ≥2 hours before or ≥2 hours after other oral drugs.¹ (See Drugs that Exhibit pH-dependent Solubility under Interactions.)

Preparation of Oral Suspension

Empty entire contents of packet(s) containing sodium zirconium cyclosilicate into a glass containing approximately 45 mL of water, or more if desired.¹ Stir thoroughly and administer immediately.¹

If any powder remains in glass after initial administration, add more water, stir, and administer immediately; repeat, as needed, until the entire dose is administered.¹

Dosage

Adults

Hyperkalemia

Oral

Initial treatment: 10 g 3 times daily for up to 48 hours.¹

Maintenance therapy: 10 g once daily.¹ Monitor serum potassium concentration; dosage may be increased (in 5-g increments at intervals of ≥1 week, up to 15 g daily) or decreased, or therapy may be discontinued based on serum potassium concentration and desired target range.¹ Usual maintenance dosage is 5 g every other day to 15 g once daily.¹

Prescribing Limits

Adults

Hyperkalemia

Oral

Maximum 15 g once daily for maintenance therapy.^{1 4}

Special Populations

Hepatic Impairment

No special dosage recommendations.¹

Renal Impairment

No special dosage recommendations.¹

Geriatric Patients

No special dosage recommendations.¹

Cautions for Zirconium Cyclosilicate

Contraindications

• Manufacturer states none known.¹

Warnings/Precautions

Worsening of GI Motility Disorders

Not evaluated in patients with severe constipation, bowel obstruction, or fecal impaction, including abnormal postoperative bowel motility disorders.¹ Avoid use in such patients because the drug may not be effective and may worsen GI conditions.¹

Edema

Each 5-g dose of sodium zirconium cyclosilicate contains approximately 400 mg of sodium; possible risk of edema if sodium is absorbed from preparation.¹ In clinical trials, edema was generally mild to moderate in severity and was more common in patients receiving higher dosages (i.e., 15 g once daily).¹

Monitor for signs of edema, especially in patients who should restrict their sodium intake or have conditions predisposing them to fluid overload (e.g., heart failure, renal disease).¹ Advise patients to reduce dietary sodium intake, if appropriate.¹ Increase dosage of concomitant diuretics as needed.¹

Specific Populations

Pregnancy

Not expected to result in fetal exposure if used during pregnancy because sodium zirconium cyclosilicate is not absorbed systemically following oral administration.¹

Lactation

Breast-feeding not expected to result in infant exposure because sodium zirconium cyclosilicate is not absorbed systemically following oral administration.¹

Pediatric Use

Safety and efficacy not established in pediatric patients.¹

Geriatric Use

No overall differences in efficacy observed between geriatric patients and younger adults.¹

Renal Impairment

Patients with renal disease may be at greater risk for edema.¹ (See Edema under Cautions.)

Common Adverse Effects

Edema,^{1 3} hypokalemia.^{1 2 3}

Drug Interactions

Drugs that Exhibit pH-dependent Solubility

Sodium zirconium cyclosilicate causes transient increases in gastric pH and can affect solubility (and consequent bioavailability) of certain pH-dependent drugs.^{1 4} Administer sodium zirconium cyclosilicate ≥2 hours before or ≥2 hours after other oral drugs unless it is determined that the other drug does not exhibit pH-dependent solubility.¹

Drugs that Inhibit the Renin-angiotensin-aldosterone System

Concomitant use does not appear to alter pharmacokinetics of renin-angiotensin-aldosterone system inhibitors.^{1 6}

Specific Drugs

Zirconium Cyclosilicate Pharmacokinetics

Absorption

Bioavailability

Not absorbed systemically after oral administration.^{1 5 6 7}

Onset

1–6 hours.^{1 10 11}

Duration

4–12 hours.¹¹

Food

Binds potassium in food.³

Elimination

Metabolism

Not metabolized.^{1 6 7}

Elimination Route

Excreted in feces.¹

Stability

Storage

Oral

Powder for Suspension

15–30°C.¹

Actions

• Highly selective inorganic cation-exchange crystalline compound that preferentially captures potassium in exchange for hydrogen (i.e., protons) and sodium.^{1 2 3 5 6}

• High specificity for potassium attributed to the drug's chemical composition and crystal structure.⁵ Exhibits high affinity for potassium, even in the presence of other cations (e.g., calcium, magnesium); >25 times more selective for potassium than for calcium and magnesium.^{1 5}

• Binds potassium throughout the entire lumen of the GI tract (including the acidic condition of the duodenum and potassium in food), resulting in reduced concentrations of free potassium in the GI lumen, increased fecal potassium excretion, and decreased serum potassium concentrations.^{1 2 3 5 7}

• Potassium-binding capacity of sodium zirconium cyclosilicate is 9.3 times that of sodium polystyrene sulfonate.⁵

• Demonstrates dose-dependent increases in fecal potassium excretion and decreases in urinary potassium excretion and serum potassium concentrations.^{1 6} Reductions in serum potassium concentration observed ≤1 hour after first dose and maintained with continued therapy.^{1 2}

• Causes mild, dose-dependent increases in serum bicarbonate concentrations and mild increases in urinary pH and reductions in BUN;^{1 6} clinical importance of such effects not known.¹

Advice to Patients

• Importance of instructing patients regarding proper preparation and administration of sodium zirconium cyclosilicate, including importance of taking the full dose.¹

• Importance of informing patients who are taking other oral drugs to administer these drugs ≥2 hours before or ≥2 hours after administration of sodium zirconium cyclosilicate.¹

• Risk of edema.¹ Importance of advising patients that reduced dietary sodium intake may be required.¹

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.¹

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.¹

• Importance of informing patients of other important precautionary information.¹ (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Frequently asked questions

• How does the drug Lokelma work?

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