Sevelamer: Indication and Laboratory Effects
Sevelamer is a non-calcium, non-metal phosphate binder used to control elevated serum phosphorus levels in patients with chronic kidney disease on dialysis, and it primarily lowers serum phosphate while also reducing serum calcium levels. 1
Primary Indication
- Sevelamer hydrochloride is FDA-approved specifically for controlling serum phosphorus in CKD patients on dialysis (hemodialysis or peritoneal dialysis). 1
- The safety and efficacy in CKD patients not yet on dialysis have not been established by the FDA. 1
Laboratory Values Affected
Serum Phosphorus (Primary Effect)
- Sevelamer binds dietary phosphate in the gastrointestinal tract, preventing its absorption and enhancing fecal excretion, thereby lowering serum phosphorus levels. 2, 3
- It achieves phosphorus control equivalent to calcium-based binders, meeting K/DOQI target ranges of 3.5-5.5 mg/dL for dialysis patients. 4, 5
- The National Kidney Foundation recommends initiating sevelamer when serum phosphorus exceeds 5.5 mg/dL in CKD stage 5 patients despite dietary restriction. 5
Serum Calcium (Secondary Effect)
- Sevelamer does not contain calcium and therefore does not raise serum calcium levels—in fact, it generally reduces serum calcium to a greater extent than calcium-based binders. 4, 2
- Patients on sevelamer experience significantly fewer hypercalcemic episodes compared to those on calcium-based phosphate binders. 4, 2
- The K/DOQI guidelines recommend sevelamer when patients require more than 2,000 mg/day of elemental calcium from calcium-based binders to avoid excessive calcium intake. 6, 4
Additional Laboratory Effects
- Sevelamer reduces LDL cholesterol by 15-31% and total cholesterol significantly compared to calcium-based binders. 4, 3, 7
- It lowers C-reactive protein levels, suggesting anti-inflammatory effects. 3, 8
- Sevelamer reduces the calcium-phosphorus product, which should be maintained below 55 mg²/dL². 6, 5
Specific Clinical Scenarios for Sevelamer Use
The National Kidney Foundation and K/DOQI guidelines identify four key situations where sevelamer is preferred over calcium-based binders: 6, 4, 5
- Hypercalcemia: When serum calcium exceeds 10.2 mg/dL, switch from calcium-based binders to sevelamer. 6, 5
- Elevated calcium-phosphorus product: When the product exceeds 55 mg²/dL². 6, 5
- Low PTH levels: When intact PTH is below 150 pg/mL on two consecutive measurements, indicating risk of adynamic bone disease. 5
- Severe vascular or soft-tissue calcification: Sevelamer prevents progression of coronary and aortic calcification, while calcium-based binders show significant progression. 4, 5
Dosing and Monitoring
- Start with one to two 800 mg tablets or two to four 400 mg tablets three times daily with meals. 1
- Adjust by one tablet per meal every two weeks to achieve target serum phosphorus of 3.5-5.5 mg/dL. 1
- Monitor serum phosphorus every 2-4 weeks during titration, then monthly once stable. 9
- Monitor serum calcium for hypocalcemia, especially with concurrent calcimimetics. 9
- Monitor intact PTH levels every 3 months. 9
Important Caveats
- Serious gastrointestinal complications including dysphagia, bowel obstruction, bleeding ulcers, colitis, and perforation have been reported with sevelamer, some requiring hospitalization and surgery. 1
- The most common reasons for discontinuation are gastrointestinal adverse reactions including dyspepsia, diarrhea, nausea, and constipation. 1
- Sevelamer is contraindicated in patients with bowel obstruction or known hypersensitivity to the drug. 1
- When total elemental calcium intake from diet and binders exceeds 2,000 mg/day, strongly consider adding sevelamer to reduce calcium load. 6