Sevelamer (Renagel) binds to phosphate in the gastrointestinal tract inhibiting the absorption of dietary phosphate. It does not affect the absorption of calcium, aluminum, or bicarbonate.

Sevelamer Uses:

• Control of serum phosphorous:

  • It is used to controls serum phosphorous in CKD patients on hemodialysis.

Sevelamer (Renagel) Dose in Adults

Note: Sevelamer carbonate and sevelamer hydrochloride dosing are similar; the same dose (on a mg per mg basis) should be utilized when switching from one product to another.

Sevelamer (Renagel) Dose to Control serum phosphorous levels: Oral:

• Patients not taking a phosphate binder:

  • Initial: 800 to 1,600 mg thrice a day with meals; serum phosphorous levels may deterrmine the initial dose:
    • >5.5 mg/dL to <7.5 mg/dL: 800 mg 3 times daily
    • ≥7.5 mg/dL to <9 mg/dL: 1,200 to 1,600 mg thrice a day
    • ≥9 mg/dL: 1,600 mg thrice a day
  • Maintenance dose adjustment based on serum phosphorous concentration (goal range of 3.5 to 5.5 mg/dL; maximum dose studied was equivalent to 13 g/day [sevelamer hydrochloride] or 14 g/day [sevelamer carbonate]):
    • >5.5 mg/dL: Dose should be increased by 400 to 800 mg per meal at an interval of 2 weeks
    • 5 to 5.5 mg/dL: Current dose should be maintained
    • <3.5 mg/dL: Dose should be decreased by 400 to 800 mg per meal

• Dosage adjustment when switching between phosphate-binder products:

  • • Calcium acetate 667mg equals ~800 mg sevelamer (carbonate or hydrochloride)

  • Conversion based on dose per meal:

    • Calcium acetate 667 mg: Convert to 800 mg Renagel/Renvela
    • Calcium acetate 1,334 mg: Convert to 1,600 mg as Renagel/Renvela (800 mg tablets x 2) or 1,200 mg as Renagel (400 mg tablets x 3)
    • Calcium acetate 2,001 mg: Convert to 2,400 mg as Renagel/Renvela (800 mg tablets x 3) or 2,000 mg as Renagel (400 mg tablets x 5)

Sevelamer (Renagel) Dose in Childrens

Note: Phosphate binding capacity: 400mg of Sevelamer HCl binds almost 32 mg of phosphate & 800 mg binds ~64 mg of phosphate.

Sevelamer (Renagel) Dose in the treatment of Hyperphosphatemia in children:

Sevelamer carbonate (Renvela):

• Children ≥6 years and Adolescents: Oral:

  • Patients not taking a phosphate binder: Initial:

    • BSA ≥0.75 to <1.2 m²: 800 mg thrice a day with meals; dose should be titrated as per need by 400 mg per dose at 2-week intervals.
    • BSA ≥1.2 m²: 1,600 mg thrice a day with meals; dose should be titrated as per need by 800 mg per dose at 2-week intervals.

  • Dosage adjustment when switching from calcium acetate to sevelamer carbonate:

    • Calcium acetate 667 mg equals almost 800 mg sevelamer; conversion based on dose per meal:
      • Calcium acetate 667 mg: Convert to 800 mg sevelamer carbonate
      • Calcium acetate 1,334 mg: Convert to 1,600 mg sevelamer carbonate
      • Calcium acetate 2,001 mg: Convert to 2,400 mg sevelamer carbonate

Sevelamer hydrochloride (Renagel): 

• Infants ≥10 months and Children <2 years:

  • Oral: Mean final dose of 140 ± 86 mg/kg/day (5.38 ± 3.24 g/day) was reported in a small trial (n=18, age range: 10 months to 18 years) to have achieved the targeted serum phosphorus level.
  • Prior phosphate binder dose and serum phosphorus concentrations determined the initial dose.
  • According to a case report of a 19-month old, an initial dose of 100 mg/kg/day divided every 8 hours with titration up to 130 mg/kg/day was reported to effectively cause a decrease in serum phosphorus levels.

• Children ≥2 years and Adolescents:

  • Oral: Initial dose: 400 or 800 mg thrice a day administered with meals;
  • The dose should be titrated at monthly intervals in 1,200 mg/day increments (ie, 400 mg at each meal) to achieve a target phosphorus level;
  • The final mean range: 140 to 163 mg/kg/day (5.38 to 6.7 g/day);

• Dosage adjustment when switching from calcium acetate to sevelamer hydrochloride:

  • Calcium acetate 667mg equals almost 800 mg sevelamer; conversion based on dose per meal.

Sevelamer (Renagel) dose in hyperphosphatemia, pretreatment of oral and enteral nutrition:

• Oral: 800 mg tablets or powder is added to 400 mL of breast milk or 100 mL of infant formula milk, tube feeding, or cow's milk;
• The mixture is kept for 10 minutes. A precipitate is formed at the bottom of the mixture.
• It has been shown to reduce the phosphate levels by up to 85% or more when added to breast milk, 42% when added to cow's milk, 48% to tube feeding, and 68% when added to infant formula.

Pregnancy Risk Category: C

• Sevelamer cannot be absorbed systemically. However, it can cause a decrease in maternal absorption fat-soluble vitamins or folic acid. Supplementation may be necessary.

Use during breastfeeding:

• Sevelamer cannot be absorbed systemically and breastfeeding is not considered unsafe.
• It can cause a decrease in maternal absorption for fat-soluble vitamins or folic acid. Supplementation may be necessary.

Dose in Kidney Disease:

No dosage adjustments are provided in the manufacturer's labeling (has not been studied).

Dose in Liver disease:

No dosage adjustments are provided in the manufacturer's labeling.

Common Side Effects of Sevelamer (Renagel):

• Endocrine & metabolic:

  • Metabolic acidosis

• Gastrointestinal:

  • Vomiting
  • Nausea
  • Diarrhea
  • Dyspepsia

Less Common Side Effects of Sevelamer (Renagel):

• Gastrointestinal:

  • Abdominal Pain
  • Constipation
  • Flatulence
  • Peritonitis

Contraindications to Sevelamer (Renagel):

• Hypersensitivity to sevelamer and any other component of the formulation
• Obstructive GI

Canadian labeling: Additional contraindications not in US labeling

• Hypophosphatemia
• Active mucosal injury (eg. necrosis, perforation and ulcerative colitis, GI bleeding, etc.)

Warnings and precautions

• Gastrointestinal effects:

  • There have been reports of obstruction and perforation in the bowel. Tablet formulation has been associated with dysphagia, esophageal retention and tablet formulation.
  • Patients with swallowing problems should switch to suspension formulation.

• Gastrointestinal Disease:

  • Patients with GI disorders such as dysphagia, swallowing problems, severe gastrointestinal motility disorders (including severe constipation) or major gastrointestinal surgery should be cautious.

Sevelamer: Drug Interaction

Monitoring parameters:

• Serum chemistries(including bicarbonate and chloride)
• Serum calcium, phosphorus, and parathyroid hormone (PTH): Frequency of measurement is determined by the presence and magnitude of abnormalities, the rate of progression of chronic kidney disease (CKD), and the use of treatments for chronic kidney disease-mineral and bone disorder (CKD-MBD):
• CKD stage G3a to G3b:
  • Serum calcium and phosphate should be done every 6 to 12 months
  • PTH: Frequency determined by baseline level and progression of CKD
• CKD stage G4:
  • Serum calcium and phosphate should be done every 3 to 6 months and PTH  at every 6 to 12 months interval
• CKD stage G5 and G5D:
  • • Serum calcium and phosphate should be done every 1 to 3 months and PTH  at every 3 to 6 months interval
• Periodic 24-hour urinary calcium and phosphorus
• Magnesium levels
• Alkaline phosphatase annually( more frequently with raised PTH) in the presence of elevated PTH)
• Creatinine, BUN, albumin
• Intact parathyroid hormone (iPTH) every 3 to 12 months based on the severity of CKD

How to administer Sevelamer (Renagel)?

Administer with meals.

Powder for oral suspension:

• An oral suspension in water may be prepared using the directed amount of water appropriate for the packet size or the entire content of the packet may be premixed with a small amount of food or beverage (do not heat or add to heated foods or liquids).
• Consume the preparation consumed immediately or within 30 minutes.
• Resuspended oral suspension in water immediately before drinking.

Tablets:

• Should be swallowed as a whole; not to be crushed or chewed.

Mechanism of action of Sevelamer (Renagel):

• Sevelamer, a polymeric compound, binds phosphate within the intestinal lumen and limits its absorption.
• It also decreases serum concentrations of phosphate without altering calcium, bicarbonate, or aluminum concentrations.

The beginning of actionThe reduction of serum phosphorus takes approximately 1-2 weeks.

Absorption: Not absorbed systemsically.

International Brand Names of Sevelamer:

• Renagel
• Renvela
• ACCEL-Sevelamer
• Eurolamer
• Inophos
• Invela
• Lameraseve
• Postiline
• Renagel
• Renosev
• Renvela
• Sevel
• Tasermity

Sevelamer Brand Names in Pakistan: