Sevelamer is a medication primarily used to lower high levels of phosphate in people with chronic kidney disease (CKD). High levels of phosphate can occur in CKD because the kidneys are not functioning properly to remove phosphate from the body. Sevelamer works by binding to phosphate in the digestive tract, preventing it from being absorbed into the bloodstream.

By lowering phosphate levels, sevelamer helps to prevent complications associated with high phosphate levels, such as bone problems and cardiovascular disease, which are common in people with CKD.

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 Adult

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:

Sevelamer is a medicine used to control high levels of phosphorus in the blood, which is common in people with kidney disease.

For Patients Not Taking Any Phosphate Binder Initially:

• Start with 800 to 1,600 milligrams (mg) taken three times daily with meals.
• The initial dose depends on the level of phosphorus in the blood:
  • If phosphorus is between 5.5 and less than 7.5 milligrams per deciliter (mg/dL), take 800 mg three times daily.
  • If it's between 7.5 and less than 9 mg/dL, take 1,200 to 1,600 mg three times daily.
  • If it's 9 mg/dL or higher, take 1,600 mg three times daily.
• Adjust the dose based on blood phosphorus levels:
  • If phosphorus is above 5.5 mg/dL, increase the dose by 400 to 800 mg per meal every two weeks.
  • If it's between 3.5 and 5.5 mg/dL, maintain the current dose.
  • If it's below 3.5 mg/dL, decrease the dose by 400 to 800 mg per meal.

Dosage Adjustment When Switching Between Phosphate-Binder Products:

• 667 mg of calcium acetate is roughly equal to 800 mg of sevelamer (whether carbonate or hydrochloride).
• To convert from calcium acetate to sevelamer:
  • If you were taking 667 mg of calcium acetate, switch to 800 mg of Renagel or Renvela.
  • If you were taking 1,334 mg of calcium acetate, switch to 1,600 mg of Renagel or Renvela (either two 800 mg tablets or three 400 mg tablets).
  • If you were taking 2,001 mg of calcium acetate, switch to 2,400 mg of Renagel or Renvela (either three 800 mg tablets or five 400 mg tablets).

Sevelamer (Renagel) Dose in Children

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) for Children ≥6 years and Adolescents:

• If not currently taking any phosphate binder:
  • For body surface area (BSA) ≥0.75 to <1.2 m²: Start with 800 mg three times daily with meals, adjust by 400 mg per dose every two weeks as needed.
  • For BSA ≥1.2 m²: Start with 1,600 mg three times daily with meals, adjust by 800 mg per dose every two weeks as needed.
• When switching from calcium acetate:
  • Convert 667 mg of calcium acetate to about 800 mg of sevelamer carbonate.
  • For example, if taking 667 mg of calcium acetate, switch to 800 mg of sevelamer carbonate; if taking 1,334 mg of calcium acetate, switch to 1,600 mg of sevelamer carbonate, and so on.

Sevelamer Hydrochloride (Renagel) for Infants ≥10 months, Children <2 years, Children ≥2 years, and Adolescents:

• For Infants ≥10 months and Children <2 years: The dosage varies, but typically starts around 100 mg/kg/day and may be titrated up to 130 mg/kg/day.
• For Children ≥2 years and Adolescents:
  • Initial dose: 400 or 800 mg three times daily with meals.
  • Titrate monthly in 1,200 mg/day increments to target phosphorus level.
  • Final dose range is usually around 140 to 163 mg/kg/day.
• When switching from calcium acetate:
  • Convert 667 mg of calcium acetate to about 800 mg of sevelamer hydrochloride, adjusting based on dose per meal.

These instructions should help in understanding how Sevelamer is dosed for different age groups and when switching from other phosphate binders.

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

For managing hyperphosphatemia in situations like oral or enteral nutrition:

Preparation:

• Take 800 mg of sevelamer (either tablets or powder form).
• Mix it with up to 400 mL of breast milk, 100 mL of infant formula, tube feeding, or cow's milk.
• Let it sit for 10 minutes.
• Afterward, carefully pour off the liquid from the bottom where the solid part has settled.

Effectiveness:

• Experience has shown significant reductions in phosphate levels:
  • More than 85% reduction in breast milk.
  • About 42% reduction in cow's milk.
  • Approximately 48% reduction in tube feeding.
  • Around 68% reduction in infant formula.

This method can help reduce phosphate levels effectively as part of oral or enteral nutrition.

Pregnancy Risk Category: C

• Sevelamer doesn't get absorbed into the body, but it might affect how well a mother absorbs certain vitamins like fat-soluble vitamins and folic acid.
• This means that she may need extra supplements of these vitamins to make sure she's getting enough.

Use during breastfeeding:

• Sevelamer doesn't get absorbed into the body, so if a mother is breastfeeding while taking it, it's not expected to affect the baby.
• However, it could lower the mother's absorption of important vitamins like fat-soluble vitamins and folic acid.
• In such cases, she might need to take extra supplements to make up for this.

Sevelamer Dose in Kidney Disease:

• The manufacturer's labeling for sevelamer doesn't include any dosage adjustments specifically for people with renal impairment because this hasn't been studied.
• In other words, there isn't enough information available to determine how the dosage should be adjusted for individuals with kidney problems.

Sevelamer Dose in Liver disease:

• The manufacturer's labeling for sevelamer doesn't provide any specific dosage adjustments for individuals with hepatic impairment.
• This means there aren't established guidelines for changing the dosage based on liver function.

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):

• Sevelamer is contraindicated in individuals who have a hypersensitivity to sevelamer itself or any ingredient in the formulation, as well as in cases of bowel obstruction.
• In Canadian labeling, additional contraindications not found in US labeling include hypophosphatemia and active mucosal injury, such as necrosis, perforation, ulcerative colitis, or gastrointestinal bleeding.
• These conditions pose risks that make the use of sevelamer inadvisable due to potential complications.

Warnings and precautions

Gastrointestinal effects:

• Gastrointestinal effects associated with sevelamer include rare but serious issues like bowel obstruction and perforation.
• Additionally, dysphagia (difficulty swallowing) and esophageal tablet retention (tablets getting stuck in the esophagus) have been reported, particularly with the tablet form.
• It's recommended to consider switching to the suspension formulation for patients with a history of swallowing disorders to minimize the risk of these complications.
• This precaution helps ensure safe and effective treatment while reducing the likelihood of potential adverse events related to swallowing difficulties.

Gastrointestinal Disease:

• In patients with gastrointestinal disorders like dysphagia, swallowing issues, severe gastrointestinal motility disorders (such as severe constipation), or significant gastrointestinal surgery, sevelamer should be used with caution.
• These conditions can potentially complicate the use of sevelamer and may require careful monitoring to ensure its safe and effective use.

Sevelamer: Drug Interaction

Monitoring parameters:

Monitoring Serum Chemistries and Other Parameters

• Serum Bicarbonate and Chloride:
  • Regular monitoring of these levels is important for assessing acid-base balance and electrolyte status.
• Serum Calcium, Phosphorus, and Parathyroid Hormone (PTH):
  • Frequency of measurement depends on CKD stage and treatment:
    • CKD stage G3a to G3b: Every 6 to 12 months for calcium and phosphate; PTH frequency based on baseline level and CKD progression.
    • CKD stage G4: Every 3 to 6 months for calcium and phosphate; PTH every 6 to 12 months.
    • CKD stage G5 and G5D: Every 1 to 3 months for calcium and phosphate; PTH every 3 to 6 months.
• Other Parameters:
  • Periodic monitoring of 24-hour urinary calcium, phosphorus, and magnesium.
  • Alkaline phosphatase levels checked every 12 months or more frequently if PTH is elevated.
  • Regular assessment of creatinine, blood urea nitrogen (BUN), and albumin levels.
  • Intact parathyroid hormone (iPTH) measured every 3 to 12 months depending on CKD severity.

How to administer Sevelamer (Renagel)?

• Administer with Meals:
  • Sevelamer should be taken with meals to maximize its effectiveness.
• Powder for Oral Suspension:
  • Prepare the suspension in water using the directed amount of water for the packet size.
  • Alternatively, the entire content of the packet may be mixed with a small amount of food or beverage.
  • Do not heat or add to heated foods or liquids.
  • Consume the preparation immediately or within 30 minutes.
  • Oral suspension in water may need to be resuspended immediately before drinking.
• Tablets:
  • Swallow the tablets whole.
  • Do not crush, chew, or break them.

Mechanism of action of Sevelamer (Renagel):

• Sevelamer, which is a polymeric compound, works by binding to phosphate in the intestines.
• This action reduces the absorption of phosphate into the bloodstream, leading to lower levels of phosphate in the blood.
• Importantly, sevelamer achieves this without affecting the concentrations of calcium, aluminum, or bicarbonate in the body.
• This targeted action helps in managing high phosphate levels while maintaining the balance of other essential minerals and compounds in the body.

Onset of Action

• Reduction in serum phosphorus levels typically occurs within 1-2 weeks of starting treatment with sevelamer. Studies by Burke (1997) and Chertow (1997) have demonstrated this effect.

Absorption

• Sevelamer is not absorbed into the bloodstream, meaning it does not enter the systemic circulation.
• Instead, it remains in the gastrointestinal tract where it exerts its action on phosphate binding.
• Therefore, sevelamer is not systemically absorbed by the body.

International Brand Names of Sevelamer:

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

Sevelamer Brand Names in Pakistan: