Introduction
Sevelamer is a phosphate-binding medication used primarily in patients with chronic kidney disease (CKD) to manage hyperphosphatemia. Available as sevelamer carbonate and sevelamer hydrochloride, this non-calcium, non-aluminum phosphate binder represents an important therapeutic option for preventing complications associated with elevated serum phosphate levels in renal impairment.
Mechanism of Action
Sevelamer is a polymeric compound that binds dietary phosphate in the gastrointestinal tract through ion-exchange and hydrogen bonding mechanisms. Unlike calcium-based binders, sevelamer does not contain metal ions and works by capturing phosphate molecules in the gut, forming an insoluble complex that is excreted in feces rather than absorbed systemically. This reduces the intestinal absorption of phosphate, thereby lowering serum phosphate concentrations.
Indications
- Management of hyperphosphatemia in patients with chronic kidney disease on dialysis
- Reduction of serum phosphorus in patients with end-stage renal disease
- Off-label uses may include hyperphosphatemia management in non-dialysis dependent CKD patients
Dosage and Administration
Initial dose: 800-1600 mg orally with meals, titrated based on serum phosphorus levels Maintenance dose: Typically 2400-4800 mg daily divided with meals Administration: Should be taken with meals and adequate fluid intake Special populations:- No dosage adjustment required in hepatic impairment
- Not recommended in patients with bowel obstruction
- Elderly patients: Use standard dosing with monitoring
Pharmacokinetics
Absorption: Not absorbed systemically; acts locally in the gastrointestinal tract Distribution: Confined to the gastrointestinal lumen Metabolism: No hepatic metabolism Elimination: Excreted unchanged in feces Protein binding: Not applicable due to lack of systemic absorptionContraindications
- Hypersensitivity to sevelamer or any component of the formulation
- Bowel obstruction
- Hypophosphatemia
- Fecal impaction (relative contraindication)
Warnings and Precautions
- GI effects: May cause constipation, intestinal obstruction, perforation
- Vitamin deficiencies: May reduce absorption of fat-soluble vitamins (A, D, E, K)
- Drug interactions: May bind to and decrease absorption of other oral medications
- Electrolyte imbalances: Monitor for hypophosphatemia, hypocalcemia
- Swallowing difficulties: Tablets should be taken whole, not crushed
Drug Interactions
- Oral medications: May decrease absorption of many drugs including:
- Anticonvulsants (phenytoin, valproic acid) - Antifungals (ketoconazole) - Thyroid hormones (levothyroxine) - Quinolone antibiotics - Warfarin
- Administration recommendation: Administer other medications at least 1 hour before or 3 hours after sevelamer
Adverse Effects
Common (>10%):- Gastrointestinal disorders (constipation, diarrhea, nausea, vomiting, abdominal pain)
- Dyspepsia
- Flatulence
- Bowel obstruction/perforation
- Fecal impaction
- Severe hypophosphatemia
- Metabolic acidosis (with sevelamer hydrochloride formulation)
Monitoring Parameters
- Serum phosphorus levels (every 2-4 weeks initially, then quarterly when stable)
- Serum calcium levels
- Electrolyte panel including bicarbonate
- Vitamin D levels (annually)
- Bowel function and symptoms
- Adherence assessment
- Nutritional status
Patient Education
- Take with meals and adequate fluid intake
- Swallow tablets whole; do not crush or chew
- Separate administration from other medications by at least 1 hour
- Report persistent constipation, abdominal pain, or difficulty swallowing
- Maintain consistent dietary habits while on therapy
- Regular monitoring of blood levels is essential
- Notify all healthcare providers about sevelamer use
- Be aware of potential vitamin deficiency risks
References
1. National Kidney Foundation. KDOQI Clinical Practice Guideline for Nutrition in CKD: 2020 Update. Am J Kidney Dis. 2020;76(3 Suppl 1):S1-S107. 2. Sevelamer prescribing information. U.S. Food and Drug Administration. 3. Block GA, et al. Mineral metabolism, mortality, and morbidity in maintenance hemodialysis. J Am Soc Nephrol. 2004;15(8):2208-2218. 4. Tonelli M, et al. Effect of sevelamer on phosphorus and lipid levels in patients with chronic kidney disease. Nephrol Dial Transplant. 2009;24(3):971-975. 5. Clinical Pharmacology [database online]. Tampa, FL: Elsevier; 2023. 6. Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Work Group. KDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of chronic kidney disease-mineral and bone disorder (CKD-MBD). Kidney Int Suppl. 2009;(113):S1-S130.