What is the recommended dose and usage of Sevelamer (sevelamer) for treating hyperphosphatemia in patients with chronic kidney disease (CKD)?

Sevelamer Dosing and Administration for Hyperphosphatemia in CKD

Start sevelamer at 800 mg three times daily with meals (or 400 mg tablets, two to four tablets three times daily), then titrate by one tablet per meal every 2 weeks based on serum phosphorus response, targeting 3.5-5.5 mg/dL in dialysis patients (CKD Stage 5) and 2.7-4.6 mg/dL in non-dialysis CKD Stages 3-4. 1, 2

When to Initiate Sevelamer

• Initiate sevelamer in CKD Stages 3-4 when serum phosphorus exceeds 4.6 mg/dL despite dietary phosphorus restriction 1
• Initiate in CKD Stage 5 (dialysis) when serum phosphorus exceeds 5.5 mg/dL despite dietary restriction 1
• Sevelamer is particularly indicated as first-line therapy in patients with hypercalcemia, low PTH levels, or existing vascular calcification 1

Dosing Algorithm

Starting Dose

• Begin with 800 mg tablets, one tablet three times daily with meals 1, 2
• Alternatively, use 400 mg tablets, two to four tablets three times daily with meals 2

Titration Schedule

• Adjust dose by one tablet per meal every 2 weeks based on serum phosphorus response 1, 2
• Continue titration until target serum phosphorus is achieved 1

Target Levels

• CKD Stage 5 (dialysis): 3.5-5.5 mg/dL 1
• CKD Stages 3-4 (non-dialysis): 2.7-4.6 mg/dL 1

Combination Therapy Considerations

Add sevelamer to calcium-based binders when persistent hyperphosphatemia (>5.5 mg/dL) occurs despite monotherapy, or when elemental calcium intake from binders exceeds 1,500 mg/day. 3, 1

• The K/DOQI guidelines strongly recommend adding a non-calcium phosphate binder when calcium-containing binders provide >2,000 mg total elemental calcium 3
• Combination therapy prevents excessive calcium loading while maintaining phosphorus control 1

Monitoring Parameters

Frequency

• Monitor serum phosphorus every 2-4 weeks during dose titration, then monthly once stable 4
• Check intact PTH levels every 3 months 4
• Monitor serum calcium regularly to detect hypocalcemia, especially with concurrent calcimimetics 4, 1

Safety Targets

• Maintain calcium-phosphorus product <55 mg²/dL² to reduce metastatic calcification risk 1
• Monitor for hypocalcemia when using sevelamer with calcimimetics 4

Important Clinical Considerations

Advantages Over Calcium-Based Binders

• Sevelamer reduces LDL cholesterol by 15-34% and total cholesterol by 17-34% 1, 5
• Sevelamer attenuates progression of arterial calcifications compared to calcium-based binders 1, 5
• Lower risk of hypercalcemic episodes compared to calcium-containing phosphate binders 3, 6
• May reduce C-reactive protein levels, suggesting anti-inflammatory effects 5, 7

Sevelamer Carbonate vs Hydrochloride

• Sevelamer carbonate is a buffered form that increases serum bicarbonate, making it preferable in patients at risk for metabolic acidosis 1, 8
• Both formulations have equivalent phosphate-binding efficacy 8
• Sevelamer carbonate has fewer gastrointestinal side effects than hydrochloride 5

Critical Safety Warnings

Gastrointestinal Risks

• Serious cases of dysphagia, bowel obstruction, bleeding GI ulcers, colitis, ulceration, necrosis, and perforation have been reported with sevelamer, some requiring hospitalization and surgery 2
• Cases of fecal impaction, ileus, bowel obstruction, and bowel perforation have occurred 2
• Most common adverse reactions are gastrointestinal: dyspepsia, diarrhea, nausea, constipation, vomiting, and abdominal distension 2

Contraindications

• Bowel obstruction 2
• Known hypersensitivity to sevelamer or excipients 2

Drug Interactions

• Sevelamer binds ciprofloxacin and mycophenolate mofetil—dose these drugs separately from sevelamer 2
• When clinically significant drug interactions are expected, separate timing of administration and monitor clinical responses or blood levels 2
• Sevelamer does not alter pharmacokinetics of digoxin, enalapril, iron, metoprolol, or warfarin 2

Adherence Considerations

Sevelamer requires an average of 7 tablets daily, which creates significant pill burden that can compromise adherence. 4

• Achieving normal phosphorus may not be possible or may unacceptably decrease quality of life due to pill burden 4
• Consider lanthanum carbonate (requiring only 4 tablets daily) when pill burden is a major adherence concern 4
• Patient education and continuous monitoring with renal dietitians are essential for adequate phosphorus control 3

Pediatric Use

Sevelamer is the only calcium- and aluminum-free phosphate binder with proven efficacy and safety in children with CKD. 1