Sevelamer Dosing for Hyperphosphatemia in CKD
Recommended Starting Dose
Start sevelamer at 800 mg three times daily with meals, then titrate by one tablet per meal every 2 weeks based on serum phosphorus response. 1, 2
Initiation Criteria by CKD Stage
- CKD Stages 3-4: Initiate sevelamer when serum phosphorus exceeds 4.6 mg/dL despite dietary phosphorus restriction 1, 3
- CKD Stage 5 (dialysis): Initiate when serum phosphorus exceeds 5.5 mg/dL despite dietary restriction 1, 3
- Dietary restriction alone (800-1,000 mg/day) is often insufficient, as urinary phosphorus excretion may paradoxically increase by 50% over time despite low-phosphorus diets 1
Target Phosphorus Levels
- CKD Stages 3-4: Target serum phosphorus 2.7-4.6 mg/dL 1, 3
- CKD Stage 5: Target serum phosphorus 3.5-5.5 mg/dL 1, 3, 2
Dose Titration Protocol
- Adjust dose by one 800 mg tablet per meal (or two 400 mg tablets) every 2 weeks based on serum phosphorus response 1, 2
- Typical maintenance doses range from 2.4 g/day up to 7.1 g/day (average in clinical trials) 4
- The FDA label confirms starting with one or two 800 mg tablets (or two to four 400 mg tablets) three times daily with meals 2
Preferred Clinical Scenarios for Sevelamer
Sevelamer should be prioritized as first-line therapy in specific high-risk populations:
- Hypercalcemia: When serum calcium >10.2 mg/dL 3
- Low PTH: When PTH levels <150 pg/mL on two consecutive measurements 3
- Vascular calcification: Patients with existing severe vascular or soft-tissue calcifications 1, 3
- Calcium restriction needed: When total calcium intake approaches 2,000 mg/day or calcium from binders alone exceeds 1,500 mg/day 1, 3
The American College of Cardiology recommends sevelamer as first-line therapy for CKD patients on dialysis, especially in these high-risk scenarios 1
Combination Therapy Strategy
- Consider combining sevelamer with calcium-based binders when persistent hyperphosphatemia (>5.5 mg/dL) occurs despite monotherapy 1, 3
- Critical safety limit: Ensure total elemental calcium intake (dietary + binders) does not exceed 2,000 mg/day, and calcium from binders alone should not exceed 1,500 mg/day 1, 3
- Maintain calcium-phosphorus product <55 mg²/dL² to reduce metastatic calcification risk 1, 3
Monitoring Parameters
- During titration: Monitor serum phosphorus every 2-4 weeks, then monthly once stable 5
- Serum calcium: Maintain within normal range, preferably toward lower end (8.4-9.5 mg/dL) 3
- PTH levels: Monitor every 3 months 5
- Calcium-phosphorus product: Keep <55 mg²/dL² 1, 3
Additional Clinical Benefits
- Sevelamer reduces LDL cholesterol by 15-34% and total cholesterol by 17-34% 1
- May reduce C-reactive protein levels, suggesting anti-inflammatory effects 1
- Attenuates progression of arterial calcifications compared to calcium-based binders and may provide mortality benefit in incident dialysis patients 1
- Sevelamer carbonate (buffered form) increases serum bicarbonate, making it preferable in patients at risk for metabolic acidosis 1
Important Safety Considerations
- Contraindications: Bowel obstruction and known hypersensitivity to sevelamer 2
- Serious GI risks: Dysphagia, bowel obstruction, bleeding GI ulcers, colitis, ulceration, necrosis, and perforation have been reported, some requiring hospitalization and surgery 2
- Drug interactions: Sevelamer binds ciprofloxacin and mycophenolate mofetil; dose these medications separately from sevelamer 2
- Most common adverse reactions leading to discontinuation are gastrointestinal in nature 2