Introduction
Lokelma (sodium zirconium cyclosilicate) is a potassium-binding medication approved by the FDA for the treatment of hyperkalemia in adults. It represents a novel therapeutic approach to managing elevated potassium levels, offering a selective ion-exchange mechanism that differs from traditional potassium-lowering agents.
Mechanism of Action
Lokelma works through a selective potassium ion-exchange mechanism. The compound is a non-absorbed zirconium silicate that preferentially captures potassium ions in the gastrointestinal tract, particularly in the colon where potassium concentrations are highest. The crystal structure of sodium zirconium cyclosilicate forms a three-dimensional framework with pores that specifically trap potassium ions while having minimal effect on other cations like calcium and magnesium. This captured potassium is then excreted in the feces, thereby reducing systemic potassium levels.
Indications
Lokelma is indicated for the treatment of hyperkalemia in adults. The FDA-approved labeling includes:
- Acute treatment of hyperkalemia with a starting dose of 10 g three times daily for up to 48 hours
- Maintenance treatment of hyperkalemia for chronic management
Dosage and Administration
Initial (Acute) Treatment:- 10 g orally three times daily for up to 48 hours
- Administer at least 2 hours before or 2 hours after other oral medications
- 10 g orally once daily
- Dose may be titrated based on serum potassium levels:
- Increase to 15 g once daily if potassium remains >5.0 mEq/L - Decrease to 5 g once daily if potassium is <3.5 mEq/L - Maximum dose: 15 g once daily
Administration:- Mix powder with 3 tablespoons (45 mL) of water immediately before administration
- Stir well and consume entire mixture
- Do not heat or microwave the suspension
- Administer at least 2 hours before or after other oral medications
- Renal impairment: No dosage adjustment required
- Hepatic impairment: No dosage adjustment required
- Elderly: No specific dosage adjustment recommended
Pharmacokinetics
Absorption: Not systemically absorbed. Acts locally in the gastrointestinal tract. Distribution: Confined to the gastrointestinal lumen with no measurable systemic exposure. Metabolism: Not metabolized. No cytochrome P450 interactions. Elimination: Excreted unchanged in feces. Half-life: Not applicable due to lack of systemic absorption.Contraindications
- Hypersensitivity to sodium zirconium cyclosilicate or any component of the formulation
- Patients with rare hereditary problems of fructose intolerance (contains sorbitol)
Warnings and Precautions
Gastrointestinal Adverse Reactions: Edema and constipation were reported in clinical trials. Use with caution in patients with severe constipation, bowel obstruction, or impaction. Electrolyte Effects: May cause hypokalemia. Monitor serum potassium levels and adjust dosage accordingly. Sodium Content: Contains approximately 400 mg of sodium per 5 g dose. Consider in patients with heart failure, hypertension, or renal impairment who may be sensitive to sodium loads. Concomitant Medication Administration: Administer at least 2 hours before or after other oral medications to avoid potential binding interactions.Drug Interactions
Reduced Absorption of Other Medications:- Lokelma may decrease absorption of concomitantly administered oral medications
- Administer other oral medications at least 2 hours before or after Lokelma
- Particularly important for medications with narrow therapeutic indices:
- Levothyroxine - Antipsychotics (e.g., chlorpromazine) - Certain antibiotics - Antifungals - Immunosuppressants
No Known Metabolic Interactions: As Lokelma is not systemically absorbed, it does not interact with cytochrome P450 enzymes or transport proteins.Adverse Effects
Common Adverse Reactions (≥2%):- Edema (14.3%)
- Hypokalemia (5.6%)
- Constipation (4.8%)
- Diarrhea (4.4%)
- Nausea (2.2%)
- Abdominal discomfort (2.0%)
- Severe hypokalemia (<3.0 mEq/L)
- Gastrointestinal obstruction (rare)
Monitoring Parameters
Baseline:- Serum potassium level
- Serum magnesium and calcium levels
- Assessment of gastrointestinal function
- Assessment of volume status
- Serum potassium levels:
- Initially: Within 1 week of starting therapy - During titration: At least monthly - Once stable: Periodically as clinically indicated
- Monitor for signs and symptoms of hypokalemia
- Monitor for gastrointestinal adverse effects
- Assess volume status in patients at risk for fluid overload
Patient Education
Administration Instructions:- Mix powder with water immediately before taking
- Do not swallow powder dry
- Take at least 2 hours before or after other medications
- Do not heat or microwave the mixture
- Regular blood tests will be needed to monitor potassium levels
- Report any swelling, especially in legs or feet
- Report persistent constipation or abdominal discomfort
- Report symptoms of low potassium: muscle weakness, cramps, palpitations
- Maintain consistent potassium intake unless otherwise directed
- Follow any prescribed dietary potassium restrictions
- Be aware of sodium content if on sodium-restricted diet
- Severe constipation or abdominal pain
- Significant swelling
- Muscle weakness or cramps
- Irregular heartbeat
References
1. FDA prescribing information: Lokelma (sodium zirconium cyclosilicate). 2018. 2. Packham DK, Rasmussen HS, Lavin PT, et al. Sodium zirconium cyclosilicate in hyperkalemia. N Engl J Med. 2015;372(3):222-231. 3. Kosiborod M, Rasmussen HS, Lavin P, et al. Effect of sodium zirconium cyclosilicate on potassium lowering for 28 days among outpatients with hyperkalemia: The HARMONIZE randomized clinical trial. JAMA. 2014;312(21):2223-2233. 4. Ash SR, Singh B, Lavin PT, et al. A phase 2 study on the treatment of hyperkalemia in patients with chronic kidney disease suggests that the selective potassium trap, ZS-9, is safe and efficient. Kidney Int. 2015;88(2):404-411. 5. Roger SD, Lavin PT, Lerma EV, et al. Long-term safety and efficacy of sodium zirconium cyclosilicate for hyperkalemia in patients with kidney disease: A phase 3, open-label, multi-center study. Lancet. 2017;389(10067):815-822.