What is Renvela (sevelamer hydrochloride), a phosphate binder?

Renvela (Sevelamer Hydrochloride): A Phosphate Binder for Chronic Kidney Disease

Renvela (sevelamer hydrochloride) is a non-calcium, non-metal phosphate binder indicated for controlling serum phosphorus in patients with chronic kidney disease on dialysis, with evidence suggesting it may reduce mortality and slow vascular calcification compared to calcium-based binders. 1

Mechanism of Action and Formulation

• Sevelamer is a polymeric amine that binds dietary phosphate in the gastrointestinal tract
• It is hydrophilic but insoluble in water, consisting of poly(allylamine hydrochloride) crosslinked with epichlorohydrin 1
• Available as film-coated tablets containing either 800 mg or 400 mg of sevelamer hydrochloride 1
• Unlike calcium-based phosphate binders, sevelamer does not contribute to calcium load or risk of hypercalcemia 2

Clinical Indications

• Primary indication: Control of serum phosphorus in patients with chronic kidney disease on dialysis 1
• Most appropriate for patients with:
  • Hyperphosphatemia despite dietary restrictions
  • Hypercalcemia or low PTH levels
  • Evidence of vascular or soft tissue calcifications
  • High cardiovascular risk profiles 2

Dosing and Administration

• Starting dose: One or two 800 mg tablets OR two to four 400 mg tablets three times per day with meals 1
• Dose titration: Adjust by one tablet per meal at two-week intervals based on serum phosphorus levels 1
• Target phosphorus levels: 3.5-5.5 mg/dL for dialysis patients 2
• Must be taken with meals to effectively bind dietary phosphate 2
• Other medications should be taken at least 1 hour before or 3 hours after sevelamer to minimize potential interactions 2

Clinical Benefits

• Effectively controls serum phosphorus comparable to calcium-based binders 3
• Associated with fewer episodes of hypercalcemia compared to calcium-based binders 2
• May reduce progression of vascular calcification 3, 2
• Additional cardiovascular benefits through reduction of LDL cholesterol levels 2, 4
• May improve overall survival in patients new to dialysis compared to calcium-based binders 5

Monitoring Parameters

• Monthly monitoring of:
  • Serum phosphorus
  • Serum calcium
  • Calcium-phosphorus product (target <55 mg²/dL²)
  • Parathyroid hormone levels 2

Side Effects and Safety Considerations

Common Side Effects

• Gastrointestinal issues: dyspepsia, constipation, diarrhea, nausea, vomiting 1, 4
• Approximately 72% of patients may report mild flatulence, nausea, or indigestion 4

Serious Adverse Events

• Rare but serious: dysphagia, bowel obstruction, bleeding gastrointestinal ulcers, colitis, perforation 1
• Case reports of gastrointestinal bleeding associated with sevelamer crystal deposition 6
• Symptoms typically resolve after discontinuation of the medication 6

Contraindications

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

Combination Therapy Approach

When monotherapy fails to adequately control phosphorus levels:

• Consider combination of sevelamer with calcium-based binders
• Ensure total elemental calcium from calcium-based binders does not exceed 1,500 mg/day
• Total calcium intake (dietary + binders) should not exceed 2,000 mg/day 2

Practical Considerations

• Higher cost compared to calcium-based binders may limit accessibility 7
• High pill burden may affect adherence 2
• For patients with persistent hyperphosphatemia despite optimal binder therapy, consider increasing dialysis frequency or duration 2

Clinical Decision Algorithm

1. Initial Assessment:

   • Check serum phosphorus, calcium, PTH levels
   • Assess cardiovascular risk and presence of vascular calcifications

2. Patient Selection for Sevelamer:

   • First-line for patients with hypercalcemia, low PTH, vascular calcifications
   • Consider for patients at risk of hypercalcemic episodes

3. Treatment Initiation:

   • Start with 800-1600 mg with each meal
   • Ensure administration with meals

4. Monitoring and Adjustment:

   • Check phosphorus levels every 2 weeks during titration
   • Adjust by one tablet per meal until target phosphorus (3.5-5.5 mg/dL) is reached
   • Once stable, monitor monthly

5. Management of Inadequate Response:

   • Consider combination therapy with calcium-based binders
   • Evaluate dialysis adequacy and consider increasing frequency/duration
   • Reinforce dietary phosphate restriction

Sevelamer represents an important therapeutic option for hyperphosphatemia management in dialysis patients, particularly those with cardiovascular risk factors or calcium-related concerns.