Usage
Sevelamer is prescribed to control serum phosphorus levels in patients with chronic kidney disease (CKD), particularly those on dialysis (hemodialysis or peritoneal dialysis). It is also used in adult CKD patients not on dialysis who have serum phosphorus levels ≥ 1.78 mmol/L. It is classified as a phosphate binder.
Sevelamer works by binding to dietary phosphate in the gastrointestinal tract, preventing its absorption and thereby reducing serum phosphorus levels.
Alternate Names
Sevelamer is available in two forms: sevelamer hydrochloride and sevelamer carbonate. Brand names include Renagel (sevelamer hydrochloride) and Renvela (sevelamer carbonate).
How It Works
Pharmacodynamics: Sevelamer lowers serum phosphate levels by binding to dietary phosphate in the gut, forming an insoluble complex that is excreted in the feces. This reduces the phosphate load absorbed into the bloodstream. It does not contain calcium and therefore does not contribute to hypercalcemia, a common issue with calcium-based phosphate binders. Sevelamer hydrochloride can lower serum bicarbonate and contribute to metabolic acidosis. Sevelamer carbonate has less of an effect on serum bicarbonate.
Pharmacokinetics: Sevelamer is not absorbed systemically after oral administration. It acts locally in the gastrointestinal tract. It binds phosphate in the gut and is eliminated through the feces. No metabolism by CYP enzymes is involved.
Dosage
Standard Dosage
Adults:
The initial dose is typically 800 mg to 1600 mg (1 to 2 tablets or 0.8 g to 1.6 g of powder) three times a day with meals. This can also be expressed as 2.4 g to 4.8 g per day. The dose is then adjusted based on serum phosphorus levels with the goal of achieving and maintaining serum phosphorus levels within the target range (typically 3.5-5.5 mg/dL or 1.13-1.78 mmol/L). Titration usually involves adjusting the dose by 800 mg (or one 800 mg tablet or 0.8g of powder) three times per day at 2-week (or 2-4 week) intervals.
Children (6 years and older):
Dosing is based on body surface area (BSA):
- BSA 0.75 to <1.2 m²: 800 mg three times a day with meals. Titrate by 400 mg increments at 2-week intervals.
- BSA ≥1.2 m²: 1600 mg three times a day with meals. Titrate by 800 mg increments at 2-week intervals.
Special Cases:
- Elderly Patients: No specific dosage adjustment is required, but caution is advised, usually starting at the low end of the dosing range.
- Patients with Renal Impairment: No dosage adjustment is needed as sevelamer is not absorbed systemically.
- Patients with Hepatic Dysfunction: No dosage adjustment is required based on current clinical studies.
- Patients with Comorbid Conditions: Concurrent use of sevelamer with other medications may require dose adjustments of those other medications. Monitoring and dose adjustment of the other medication is recommended.
Clinical Use Cases
Sevelamer’s dosage is based on serum phosphorus levels, not specific clinical situations like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations.
Dosage Adjustments
Dose adjustments are based on serum phosphorus levels. The dose is typically increased in increments of 800 mg three times a day at 2-week intervals until the desired phosphorus level is achieved.
Side Effects
Common Side Effects:
Nausea, vomiting, diarrhea, constipation, abdominal pain, dyspepsia, flatulence.
Rare but Serious Side Effects:
Dysphagia, bowel obstruction, gastrointestinal bleeding, ulceration, and perforation.
Long-Term Effects:
Potential for metabolic acidosis (with sevelamer hydrochloride), deficiencies in fat-soluble vitamins (A, D, E, and K) and folic acid (due to binding in the GI tract).
Adverse Drug Reactions (ADR):
Severe allergic reactions including hives, itching, rash, swelling of the face, lips, tongue, or throat, difficulty breathing.
Contraindications
Bowel obstruction, hypersensitivity to sevelamer or its components, hypophosphatemia.
Drug Interactions
Sevelamer can bind to various medications, reducing their absorption. Clinically significant interactions may occur with ciprofloxacin, mycophenolate mofetil, levothyroxine, cyclosporine, tacrolimus, and some other medications. It is important to administer interacting medications separately from sevelamer (typically 1 hour before or 3 hours after sevelamer).
Pregnancy and Breastfeeding
Sevelamer is not systemically absorbed and is not expected to pose a risk to the fetus or breastfeeding infant. However, it can reduce the absorption of fat-soluble vitamins and folic acid, so supplementation may be necessary. As always, the risk-benefit should be considered before administering during pregnancy and breastfeeding.
Drug Profile Summary
- Mechanism of Action: Binds to dietary phosphate in the GI tract, reducing absorption and lowering serum phosphorus levels.
- Side Effects: Nausea, vomiting, diarrhea, constipation, abdominal pain; rarely, bowel obstruction, bleeding, perforation.
- Contraindications: Bowel obstruction, hypersensitivity.
- Drug Interactions: Ciprofloxacin, mycophenolate mofetil, levothyroxine, cyclosporine, tacrolimus.
- Pregnancy & Breastfeeding: Not absorbed systemically; consider vitamin supplementation.
- Dosage: Adults: starting 800-1600 mg TID with meals; titrate based on serum phosphorus. Children (≥6 years): BSA-based dosing.
- Monitoring Parameters: Serum phosphorus, calcium, bicarbonate, and fat-soluble vitamins (especially vitamin D).
Popular Combinations
Sevelamer is often used in combination with calcium supplements, vitamin D, and its analogues to manage mineral bone disease in CKD. It is also frequently part of a comprehensive treatment plan that includes dietary phosphate restriction.
Precautions
- General Precautions: Monitor serum phosphorus, calcium, bicarbonate, and fat-soluble vitamins. Assess for history of bowel obstruction, dysphagia or gastrointestinal disorders.
- Specific Populations: As described in the dedicated section above.
- Lifestyle Considerations: Adherence to a low-phosphate diet is essential.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Sevelamer?
A: Adults: Initial dose is 800-1600 mg three times daily with meals. Titrate every 2-4 weeks to achieve target serum phosphorus levels (usually between 3.5-5.5 mg/dL). Children (≥6 years): dose based on body surface area. Refer to the detailed dosage section for specifics.
Q2: What is the mechanism of action of Sevelamer?
A: Sevelamer binds to dietary phosphate in the gut, preventing absorption and thereby lowering serum phosphorus.
Q3: What are the main differences between sevelamer hydrochloride (Renagel) and sevelamer carbonate (Renvela)?
A: Sevelamer hydrochloride can cause metabolic acidosis because it releases hydrochloric acid, while Sevelamer carbonate is less likely to do so.
Q4: What are the common side effects of Sevelamer?
A: Common side effects are gastrointestinal, including nausea, vomiting, diarrhea, constipation, and abdominal pain.
Q5: Are there any serious side effects I should be aware of?
A: Yes, rare but serious side effects include dysphagia, bowel obstruction, gastrointestinal bleeding, ulceration, or perforation.
Q6: Can Sevelamer be used in pregnant or breastfeeding women?
A: Sevelamer is not systemically absorbed, therefore it is thought to pose minimal risk to the fetus or nursing infant. However, it can reduce the absorption of fat-soluble vitamins and folic acid, so supplementation is often recommended.
Q7: How should I monitor patients on Sevelamer?
A: Regularly monitor serum phosphorus, calcium, bicarbonate, and fat-soluble vitamin levels. Monitor for signs of gastrointestinal complications.
Q8: What are the contraindications for using Sevelamer?
A: Bowel obstruction, hypersensitivity to sevelamer, and hypophosphatemia.
Q9: Does Sevelamer interact with other medications?
A: Yes, it can reduce the absorption of several medications, including ciprofloxacin, mycophenolate mofetil, and levothyroxine. These medications should be administered separately from sevelamer (1 hour before or 3 hours after Sevelamer).
Q10: What should I advise my patients regarding their diet while taking Sevelamer?
A: Patients should follow a phosphate-restricted diet as advised by a dietitian or nephrologist. This is crucial for maximizing the effectiveness of Sevelamer.
