Sevelamer: Indication and Clinical Use
Sevelamer is a non-calcium, non-metal phosphate binder used to control elevated serum phosphorus (hyperphosphatemia) in patients with chronic kidney disease (CKD), particularly those on dialysis. 1
Primary Indication
- Sevelamer is FDA-approved for controlling serum phosphorus in CKD patients on dialysis. 1
- The medication works by binding dietary phosphate in the gastrointestinal tract, preventing its absorption and enhancing fecal excretion. 2, 3
When to Initiate Sevelamer
Start sevelamer when serum phosphorus exceeds target levels despite dietary restriction:
- CKD Stages 3-4: Initiate when serum phosphorus >4.6 mg/dL despite dietary phosphorus restriction to 800-1,000 mg/day. 4
- CKD Stage 5 (dialysis): Initiate when serum phosphorus >5.5 mg/dL despite dietary restriction. 4, 5
Target Phosphorus Levels
- CKD Stages 3-4: Target serum phosphorus 2.7-4.6 mg/dL. 4, 5
- CKD Stage 5 (dialysis): Target serum phosphorus 3.5-5.5 mg/dL. 4, 5
Preferred First-Line Scenarios
Sevelamer should be used as first-line therapy (instead of calcium-based binders) in high-risk patients with any of the following: 4
- Hypercalcemia (corrected total calcium >10.2 mg/dL). 6, 4
- Low PTH levels (<150 pg/mL), indicating adynamic bone disease where calcium loads cannot be incorporated and predispose to extraskeletal calcification. 4, 5
- Elevated calcium-phosphorus product (>55 mg²/dL²), which increases risk of metastatic calcification. 4, 5
- Existing severe vascular calcification, as sevelamer prevents progression while calcium-based binders cause significant progression. 6, 5
- Excessive calcium intake from binders (>1,500-2,000 mg elemental calcium/day). 6, 4
Dosing and Administration
- Start with 800 mg three times daily with meals. 4
- Administer 10-15 minutes before or during meals to maximize phosphate binding, as the medication must be taken with food. 5
- Adjust dose by one tablet per meal every 2 weeks based on serum phosphorus response. 4
- Monitor serum phosphorus monthly following initiation, then adjust to achieve target levels. 5, 7
Combination Therapy Indications
Add sevelamer to calcium-based binders when: 4
- Persistent hyperphosphatemia (>5.5 mg/dL) occurs despite monotherapy with calcium-based binders.
- Patient already receives >1,500 mg elemental calcium from binders alone.
- Total calcium intake approaches or exceeds 2,000 mg/day from all sources (diet, binders, dialysate). 6
Additional Clinical Benefits Beyond Phosphate Control
Sevelamer provides cardiovascular and metabolic advantages: 6, 5
- Prevents progression of aortic and coronary artery calcification in patients with baseline vascular calcification, while calcium-based binders show significant progression. 6, 5
- Reduces LDL cholesterol by 15-34% and total cholesterol significantly. 6, 4, 3
- Lowers incidence of hypercalcemic episodes compared to calcium-based binders. 6, 2
- May reduce C-reactive protein levels, suggesting anti-inflammatory effects. 4, 3
- Potential mortality benefit in incident dialysis patients, though evidence is mixed in prevalent dialysis populations. 4, 2
Formulation Considerations
- Sevelamer carbonate is a buffered form that increases serum bicarbonate, making it preferable in patients at risk for metabolic acidosis. 4, 8
- Sevelamer hydrochloride may cause mild metabolic acidosis. 9, 8
Monitoring Parameters
- Serum phosphorus: Monthly during titration, then regularly once stable. 5, 7
- Serum calcium: Monitor for hypocalcemia, especially with concurrent calcimimetics. 4, 7
- PTH levels: Every 3 months to detect oversuppression. 4, 7
- Calcium-phosphorus product: Maintain <55 mg²/dL² to reduce metastatic calcification risk. 4
Common Pitfalls
- Major pill burden (average 7 tablets daily) seriously compromises adherence and may unacceptably decrease quality of life. 7
- Must be taken with meals for efficacy; phosphate binders work by binding dietary phosphorus in the GI tract. 5
- Higher acquisition costs than calcium-based binders, though potentially justified by prevention of vascular calcification and cardiovascular benefits. 5, 9