Side Effect Profile of Lokelma (Sodium Zirconium Cyclosilicate)
The most common adverse effects of Lokelma are gastrointestinal symptoms (constipation, diarrhea, nausea) and dose-dependent edema, with hypokalemia being a less frequent but important concern requiring monitoring. 1, 2, 3
Primary Adverse Effects
Gastrointestinal Effects
- Gastrointestinal disorders represent the most frequently reported adverse effects, including constipation, diarrhea, and nausea 1, 4
- These symptoms are generally mild to moderate in severity 5, 6
- Importantly, unlike sodium polystyrene sulfonate (SPS/Kayexalate), Lokelma has not been associated with intestinal necrosis or serious gastrointestinal injury in randomized trials 2
- The FDA label advises avoiding Lokelma in patients with severe constipation, bowel obstruction, or impaction, as it has not been studied in these populations and may worsen gastrointestinal conditions 3
Edema (Dose-Dependent)
- Edema incidence increases significantly with dose escalation: 2% at 5g daily, 6% at 10g daily, and 14-16% at 15g daily 1, 4, 3
- This adverse effect is generally mild to moderate in severity 3
- Each 5g dose contains approximately 400mg of sodium (1200mg per 10g dose during correction phase, 400-1200mg daily during maintenance) 1, 4, 3
- Monitor for peripheral edema, particularly in patients who should restrict sodium intake or are prone to fluid overload (heart failure, renal disease) 3
- Adjust dietary sodium and increase diuretics as needed 3
Hypokalemia
- Hypokalemia is less common but clinically significant, particularly in hemodialysis patients who may be prone to acute illnesses that increase this risk 2, 3
- In long-term studies, only 1% of patients experienced serum potassium <3.0 mmol/L, and 5% experienced levels of 3.0-3.4 mmol/L 7
- Regular serum potassium monitoring is essential: assess after one week during initiation and after dose adjustments to avoid hypokalemia and guide dosing 1
Metabolic Effects
Bicarbonate Elevation
- Lokelma causes a dose-dependent increase in serum bicarbonate concentrations, which may provide additional benefit for patients with metabolic acidosis 4
- Increases of 1.1 mmol/L with 5g daily, 2.3 mmol/L with 10g daily, and 2.6 mmol/L with 15g daily have been documented 4
Drug Interactions
- Lokelma can bind other medications throughout the GI tract, reducing their absorption 1
- The FDA label recommends administering other oral medications at least 2 hours before or 2 hours after Lokelma 3
Overall Safety Profile
- The tolerability profile is generally similar to placebo over 28 days, with consistent safety maintained over long-term use (up to 12 months) 5, 7
- In a 12-month study of 751 participants, 66% experienced adverse events during maintenance phase, with 22% experiencing serious adverse events 7
- Eight deaths (1%) occurred, none considered related to Lokelma 7
- Hypertension incidence was lower with Lokelma compared to sodium polystyrene sulfonate 8
Important Clinical Caveats
- Lokelma is radio-opaque and may appear as an imaging agent during abdominal X-ray procedures 3
- Not recommended for emergency treatment of life-threatening hyperkalemia due to delayed onset of action (begins at 1-2 hours); use insulin/glucose, beta-agonists, or dialysis first 1
- In hemodialysis patients, there was no difference in mean interdialytic weight gain (fluid retention measure) between Lokelma and placebo groups 3