What are the differences between Velphoro (sucroferric oxyhydroxide) and sevelamer (sevelamer carbonate/hydrochloride) as oral phosphate binders in chronic kidney disease?

Key Differences Between Velphoro and Sevelamer

Both Velphoro (sucroferric oxyhydroxide) and sevelamer are effective non-calcium phosphate binders for controlling serum phosphorus in CKD patients on dialysis, but Velphoro offers a significantly lower pill burden (3-4 tablets daily versus 7-10 tablets daily) with equivalent phosphate control, while sevelamer provides additional cardiovascular benefits through LDL cholesterol reduction and prevention of vascular calcification progression. 1, 2, 3

Mechanism and Composition

• Velphoro is an iron-based phosphate binder containing sucroferric oxyhydroxide, approved for adults and pediatric patients ≥9 years of age on dialysis 4
• Sevelamer is a non-absorbable polymer anion-exchange resin (available as sevelamer hydrochloride or carbonate) that binds phosphate in the gastrointestinal tract without containing calcium or metal 5, 6

Efficacy in Phosphate Control

• Both agents achieve comparable serum phosphorus reduction and maintain levels within K/DOQI target range (3.5-5.5 mg/dL for dialysis patients) 1, 3
• In head-to-head trials, Velphoro at 1000-3000 mg/day was noninferior to sevelamer carbonate at 4800-14,400 mg/day for lowering serum phosphorus over 24-52 weeks 1, 3
• Serum phosphorus reductions are rapid with both agents, occurring by Week 8 and sustained long-term 7, 3

Pill Burden and Adherence

• Velphoro requires substantially fewer tablets: mean 3.4-4.0 tablets daily versus 7.6-10.1 tablets daily for sevelamer 1, 7, 3
• Treatment adherence is significantly better with Velphoro: 79-86% adherence rates versus 60-77% with sevelamer 7, 3
• This reduced pill burden may be particularly valuable in patients struggling with polypharmacy 8

Dosing and Administration

• Velphoro starting dose: 500 mg three times daily with meals for adults and pediatric patients ≥12 years; 500 mg twice daily for ages 9-<12 years; tablets must be chewed or crushed, not swallowed whole 4
• Sevelamer starting dose: 800 mg three times daily with meals, adjusted by one tablet per meal every 2 weeks based on serum phosphorus response 9
• Both agents must be taken with meals to maximize phosphate binding efficacy 10, 9

Cardiovascular Effects

• Sevelamer provides unique cardiovascular benefits: reduces LDL cholesterol by 15-31% and total cholesterol significantly compared to calcium-based binders 11, 6, 2
• Sevelamer prevents progression of vascular calcification: in patients with baseline calcification, calcium-based binders show significant progression while sevelamer shows no progression 11, 6
• Sevelamer reduces all-cause mortality: meta-analysis shows 46% reduction in all-cause mortality (RR 0.54) compared to calcium-based binders in dialysis patients 2
• Velphoro has not demonstrated these cardiovascular benefits in published trials 1, 3

Effects on Calcium and PTH

• Both agents avoid calcium loading: neither contains calcium, reducing hypercalcemia risk compared to calcium-based binders 10, 1
• Sevelamer lowers serum calcium more: mean reduction of 0.4 mg/dL and significantly fewer hypercalcemic episodes (RR 0.30) versus calcium-based binders 10, 2
• Sevelamer increases PTH levels: end-of-treatment intact PTH is 32.9 pg/ml higher with sevelamer versus calcium-based binders, which may be beneficial in preventing adynamic bone disease 2

Iron Parameters and Monitoring

• Velphoro increases serum ferritin over time but maintains stable transferrin saturation (TSAT), iron, and hemoglobin concentrations with no evidence of iron accumulation over 1 year 3
• Patients with hemochromatosis or iron accumulation disorders were excluded from Velphoro trials and require careful monitoring if treated 4
• Sevelamer has no effect on iron parameters 6

Adverse Effects

• Velphoro: most common adverse events are discolored feces (12%, due to iron content) and diarrhea (6%); gastrointestinal events are mild, transient, and decrease over time 4, 1, 3
• Sevelamer: gastrointestinal events include nausea, vomiting, constipation, and diarrhea; sevelamer carbonate formulation has fewer GI side effects than hydrochloride form 6, 7
• Sevelamer may cause metabolic acidosis with the hydrochloride formulation, while sevelamer carbonate increases serum bicarbonate 11, 9
• Withdrawal rates due to adverse events are higher with Velphoro (18.5%) versus sevelamer (8.0%) in some studies 7

Drug Interactions

• Velphoro: take acetylsalicylic acid, cephalexin, and doxycycline at least 1 hour before; take levothyroxine at least 4 hours before; can be given concomitantly with calcitriol, ciprofloxacin, digoxin, enalapril, furosemide, statins, and many other common medications 4
• Sevelamer: similar precautions apply for medications where reduced bioavailability would be clinically significant; consider separating administration timing 9

Clinical Decision Algorithm

Choose Velphoro when:

• Pill burden and adherence are major concerns (requires 60% fewer tablets than sevelamer) 1, 3
• Patient has swallowing difficulties or polypharmacy issues 8
• Cost is not prohibitive and cardiovascular benefits of sevelamer are not critical

Choose Sevelamer when:

• Patient has hypercalcemia, low PTH (<150 pg/mL), or elevated calcium-phosphorus product (>55 mg²/dL²) 10, 9
• Patient has existing severe vascular calcification or high cardiovascular risk requiring prevention of calcification progression 11, 6
• Patient has elevated LDL cholesterol requiring lipid-lowering effects 6, 2
• Patient is an incident dialysis patient where mortality benefit has been demonstrated 9, 6
• Patient has hemochromatosis or iron accumulation disorders (absolute contraindication to Velphoro) 4

Avoid Velphoro in:

• Patients with hemochromatosis or iron accumulation diseases 4
• Patients with peritonitis during peritoneal dialysis, significant gastric/hepatic disorders, or recent major GI surgery (not studied) 4

Cost Considerations

• Both non-calcium binders have higher acquisition costs than calcium-based binders 11, 8
• The cost may be justified by Velphoro's improved adherence through reduced pill burden and sevelamer's prevention of vascular calcification and potential mortality reduction 11, 8, 2