What is the appropriate dosing for Sevelamer (Renagel), a phosphate binder?

From the Guidelines

Sevelamer should be dosed at 800-1600 mg three times daily with meals for adults with chronic kidney disease who have elevated phosphate levels, with a maximum recommended daily dose of 13 grams, as supported by the most recent guideline update 1. When initiating sevelamer, start with 800 mg three times daily and adjust based on serum phosphate levels, aiming for a target of 3.5-5.5 mg/dL. It is essential to take sevelamer with meals for optimal phosphate binding and to swallow tablets whole without crushing or chewing. Key considerations for sevelamer dosing include:

• Sevelamer hydrochloride (Renagel) and sevelamer carbonate (Renvela) are the available formulations, with carbonate generally causing fewer gastrointestinal side effects 1.
• Sevelamer works by binding dietary phosphate in the gut, preventing its absorption and helping to control hyperphosphatemia, which is crucial for preventing complications like secondary hyperparathyroidism and vascular calcification in kidney disease.
• Common side effects include constipation, nausea, and vomiting, and regular monitoring of phosphate levels is essential to ensure appropriate dosing. The most recent guideline update 1 emphasizes the importance of basing decisions about phosphate-lowering treatment on progressively or persistently elevated serum phosphate levels, rather than using these treatments for prevention in patients with normal phosphate levels.

From the FDA Drug Label

The recommended starting dose of sevelamer hydrochloride tablets is 800 to 1600 mg, which can be administered as one or two 800 mg sevelamer hydrochloride tablets or two to four 400 mg sevelamer hydrochloride tablets, with meals based on serum phosphorus level. Table 1 provides recommended starting doses of sevelamer hydrochloride tablets for patients not taking a phosphate binder Table 1: Starting Dose for Dialysis Patients Not Taking a Phosphate Binder Serum Phosphorus Sevelamer Hydrochloride Tablets 800 mg Sevelamer Hydrochloride Tablets 400 mg

5.5 and <7.5 mg/dL 1 tablet three times daily with meals 2 tablets three times daily with meals ≥7. 5 and <9 mg/dL 2 tablets three times daily with meals 3 tablets three times daily with meals ≥9 mg/dL 2 tablets three times daily with meals 4 tablets three times daily with meals Dose Titration for All Patients Taking Sevelamer Hydrochloride Tablets. Adjust dosage based on the serum phosphorus concentration with a goal of lowering serum phosphorus to 5. 5 mg/dL or less. Increase or decrease by one tablet per meal at two-week intervals as necessary.

The recommended starting dose of sevelamer hydrochloride tablets is 800 to 1600 mg, administered with meals based on serum phosphorus level.

• For patients not taking a phosphate binder, the starting dose can be:

• 1 tablet (800 mg) three times daily with meals for serum phosphorus levels >5.5 and <7.5 mg/dL
• 2 tablets (800 mg) three times daily with meals for serum phosphorus levels ≥7.5 and <9 mg/dL
• 2 tablets (800 mg) three times daily with meals for serum phosphorus levels ≥9 mg/dL

• Dose titration should be based on serum phosphorus concentration, with a goal of lowering serum phosphorus to 5.5 mg/dL or less.
• The dose can be increased or decreased by one tablet per meal at two-week intervals as necessary 2.

From the Research

Sevelamer Dosing

• Sevelamer is a phosphate binder used to control serum phosphorus levels in patients with chronic kidney disease (CKD) 3, 4, 5, 6, 7.
• The dosing of sevelamer varies depending on the patient's serum phosphorus level and kidney function 4, 5.
• Sevelamer carbonate is an improved, buffered form of sevelamer hydrochloride, and has been shown to be effective in reducing serum phosphorus levels in patients with CKD who are not on dialysis 4.
• The primary efficacy parameter for sevelamer carbonate is the change from baseline in serum phosphorus, and secondary measures include the percentage of serum phosphorus responders, changes in serum lipids, calcium-phosphorus product, and bicarbonate 4.

Efficacy and Safety

• Sevelamer has been shown to be effective in reducing serum phosphorus levels and slowing the progression of coronary and aortic calcification in patients with CKD 6, 7.
• Sevelamer has also been shown to have a beneficial effect on vascular calcification progression, bone disease, and survival in some hemodialysis patient populations 7.
• The most common adverse events associated with sevelamer are gastrointestinal in nature 5, 7.
• Sevelamer carbonate has been shown to be well-tolerated and have fewer side effects from the gastrointestinal tract compared to sevelamer hydrochloride tablets 7.

Comparison to Other Phosphate Binders

• Sevelamer has been compared to other phosphate binders, such as calcium acetate, and has been shown to be less effective in controlling serum phosphorus levels but with a lower risk of hypercalcemia and cardiovascular calcification 6.
• Sevelamer has also been compared to lanthanum, another non-calcium phosphate binder, and has been shown to have similar efficacy and safety profiles 3.