Sevelamer Hydrochloride

• Approved Indications:
• Treatment and management of hyperphosphatemia in adult and pediatric patients (≥6 years) with chronic kidney disease (CKD) who are on hemodialysis or peritoneal dialysis.
• Used to reduce serum phosphate levels, thereby preventing complications such as secondary hyperparathyroidism and vascular calcification.
• Off-label or Clinically Accepted Uses:
• Management of hyperphosphatemia in non-dialysis-dependent CKD patients, under clinical supervision.

• Adults:
• Initial dose usually ranges from 800 mg to 1600 mg orally three times daily with meals.
• Dose adjustment is based on serum phosphate levels, commonly increased or decreased in 800 mg to 1600 mg increments.
• Maximum total daily dose is typically 12 grams, divided over three meals.
• Pediatrics (≥6 years):
• Initial dose typically 400 mg to 800 mg orally three times daily with meals.
• Dose titrated according to serum phosphate concentration.
• Elderly:
• Follow adult dosing guidelines; monitor for tolerability and response.
• Special Populations:
• No dose adjustment required for mild to moderate hepatic impairment.
• Use with caution in patients with gastrointestinal motility disorders.
• Administration:
• Tablets should be swallowed whole with meals; do not crush or chew.
• Powder formulation can be mixed with water and ingested immediately.
• Consistent timing with meals enhances phosphate binding.
• Duration:
• Long-term, as dictated by ongoing serum phosphate levels and clinical status.

Sevelamer hydrochloride is a non-absorbed, cross-linked polymer that binds phosphate ions in the gastrointestinal tract through ionic and hydrogen bonding. By forming insoluble complexes with dietary phosphate, it prevents phosphate absorption, facilitating fecal excretion. This reduction in serum phosphate levels decreases the risk of secondary hyperparathyroidism and vascular calcification in patients with CKD. Unlike calcium-based binders, sevelamer hydrochloride does not elevate serum calcium, minimizing the risk of hypercalcemia-related complications.

• Absorption:
  Not absorbed systemically; acts locally in the gastrointestinal lumen.
• Distribution:
  Confined to the GI tract; no systemic distribution.
• Metabolism:
  Not metabolized.
• Elimination:
  Excreted unchanged in feces bound to phosphate.
• Onset of Action:
  Serum phosphate reduction typically observed within days.
• Half-life:
  Not applicable due to lack of systemic absorption.

• Pregnancy:
  Classified as FDA Pregnancy Category B. Animal studies have shown no evidence of fetal harm; however, human data are limited. Use only if clearly needed and benefits outweigh risks.
• Lactation:
  Minimal systemic absorption suggests low risk during breastfeeding. Caution is advised due to limited data.

• Primary: Phosphate binder
• Subclass: Non-calcium, non-metal polymer phosphate binder

• Hypersensitivity to sevelamer hydrochloride or any excipients.
• Presence of bowel obstruction or severe gastrointestinal motility disorders.

• Use with caution in patients with constipation, gastrointestinal motility disorders, or history of bowel obstruction.
• Monitor patients for signs of bowel obstruction such as abdominal pain or constipation.
• Monitor serum phosphate, calcium, and bicarbonate periodically during treatment.
• Risk of metabolic acidosis; monitor serum bicarbonate especially in patients prone to acid-base disturbances.
• Avoid tablet formulation in patients with swallowing difficulties.

• Common:
  Gastrointestinal complaints such as nausea, vomiting, diarrhea, constipation, abdominal pain, and flatulence.
• Serious but Rare:
  Intestinal obstruction or fecal impaction.
  Metabolic acidosis.
  Hypocalcemia when used without calcium supplementation.
• Side effects are often dose-related and improve with dosage adjustment.

• May impair absorption of oral drugs such as ciprofloxacin, levothyroxine, and mycophenolate mofetil.
• Other oral medications should be administered at least 1 hour before or 3 hours after sevelamer hydrochloride.
• No known significant effects on cytochrome P450 enzymes.

• KDIGO 2020 guidelines recommend non-calcium phosphate binders such as sevelamer hydrochloride to manage hyperphosphatemia in CKD to reduce vascular calcification risk.
• Emphasis on individualized dosing guided by serum phosphate levels.
• Updated recommendations highlight monitoring for metabolic acidosis during therapy.

• Store at controlled room temperature: 20°C to 25°C (68°F to 77°F).
• Protect from moisture, heat, and light exposure.
• Keep container tightly closed.
• Do not freeze.