What is Sevelamer (phosphate binder)?

What is Sevelamer Tablet?

Sevelamer is a non-calcium, non-aluminum, non-magnesium phosphate binder indicated for controlling serum phosphorus levels in patients with chronic kidney disease (CKD) on dialysis. 1

Mechanism of Action

Sevelamer is a polymeric amine (specifically poly(allylamine hydrochloride) crosslinked with epichlorohydrin) that binds dietary phosphate in the gastrointestinal tract through ionic and hydrogen bonding. 1 The polymer contains multiple protonated amine groups that interact with phosphate molecules, preventing phosphate absorption and lowering serum phosphorus concentrations. 1, 2

Importantly, sevelamer is not systemically absorbed, making the risk of systemic toxicity extremely low. 1

Clinical Indications

• Primary indication: Control of hyperphosphatemia in patients with CKD Stage 5 (on dialysis) 1
• Preferred situations:
  • When total elemental calcium intake from calcium-based phosphate binders exceeds 2,000 mg/day 3
  • Patients with hypercalcemia (corrected total calcium >10.2 mg/dL) 3
  • Patients with low parathyroid hormone levels (at risk for adynamic bone disease) 3
  • Presence of severe vascular calcification 3

Formulations and Dosing

Available forms: 1, 4

• Tablets: 400 mg and 800 mg
• Powder for oral suspension (sevelamer carbonate)
• Two salt forms: sevelamer hydrochloride and sevelamer carbonate

Standard dosing: 1

• Starting dose: One to two 800 mg tablets OR two to four 400 mg tablets three times daily with meals
• Titration: Adjust by one tablet per meal at two-week intervals to achieve target serum phosphorus of 3.5 to 5.5 mg/dL

Administration: Tablets should be swallowed whole with meals. 1 However, recent evidence suggests crushed tablets may be administered via enteral feeding tubes when necessary, though this is off-label. 5

Additional Clinical Benefits Beyond Phosphate Control

Sevelamer provides cardiovascular and metabolic advantages over calcium-based phosphate binders: 3

• Prevents progression of vascular calcification: In dialysis patients, sevelamer prevented progression of aortic and coronary artery calcification, while calcium-based binders showed significant progression 3
• Lowers LDL cholesterol: Decreases total and LDL cholesterol by 15-31% (observed after 2 weeks of therapy) 3, 1
• Reduces hypercalcemia risk: Significantly fewer hypercalcemic episodes compared to calcium-based binders 3
• Mortality benefit: The RIND trial suggested mortality reduction in incident dialysis patients receiving sevelamer for a median of 44 months 3

Important Safety Considerations and Adverse Effects

Gastrointestinal effects are the most common adverse reactions: 1

• Dyspepsia (12%), diarrhea (5%), nausea (5%), constipation (4%), vomiting (3%), abdominal distension (3%)
• Most common reason for treatment discontinuation

Serious gastrointestinal complications (rare but important): 1

• Dysphagia, bowel obstruction, bleeding GI ulcers, colitis, ulceration, necrosis, and perforation have been reported
• Some cases required hospitalization and surgery
• Fecal impaction and ileus have occurred 1

Metabolic acidosis: Sevelamer hydrochloride can cause reduction in serum bicarbonate levels due to chloride ion exchange. 3 This led to development of sevelamer carbonate, which provides buffering capacity. 4, 6

Vitamin deficiencies: Sevelamer binds bile acids and may reduce absorption of fat-soluble vitamins (A, D, E, K). 1 Consider vitamin supplementation during therapy.

Drug interactions: 1

• Significantly reduces ciprofloxacin bioavailability by ~50% (administer separately)
• Decreases mycophenolate mofetil absorption by 26-36% (dose separately)
• May increase TSH levels in patients on levothyroxine (monitor thyroid function)
• May affect cyclosporine and tacrolimus levels in transplant patients

Contraindications

• Bowel obstruction 1
• Known hypersensitivity to sevelamer or any excipients 1

Guideline Recommendations

The K/DOQI guidelines strongly recommend: 3

• Adding a non-calcium, non-magnesium, non-aluminum phosphate binder (such as sevelamer) when calcium-containing phosphate binders exceed 2,000 mg total elemental calcium content
• Limiting total calcium intake from diet and binders to under 2,000 mg/day (ideally 1,000-1,500 mg/day)
• Switching to sevelamer when corrected total serum calcium exceeds 10.2 mg/dL

In pediatric CKD patients, sevelamer is the only calcium- and aluminum-free phosphate binder with proven efficacy and safety, studied in 47 children across randomized controlled trials. 3

Clinical Pearls

• Pill burden is substantial: Multiple large tablets with each meal can compromise adherence 3
• Not absorbed systemically: Overdose risk is minimal; doses up to 14 g/day have been given safely 1
• Cost consideration: Sevelamer is significantly more expensive than calcium-based or aluminum-based binders 3
• Individualize therapy: Balance phosphate control, calcium load, cardiovascular risk factors, cost, and patient tolerance when selecting phosphate binders 3