General Information

Renagel (sevelamer hydrochloride) is a phosphate binder.

Renagel is specifically indicated for the control of serum phosphorus in patients with chronic kidney disease (CKD) on dialysis.

Renagel is supplied as 800 mg tablets designed for oral administration. The recommended initial dose is as follows:

Patients not taking a phosphate binder:

Renagel 800 to 1600 mg, which can be administered as one or two 800 mg Renagel tablets with meals based on serum phosphorus level

Patients Switching From Calcium Acetate:

In a study in 84 CKD patients on hemodialysis, a similar reduction in serum phosphorus was seen with equivalent doses (approximately mg for mg) of Renagel and calcium acetate.

Dose Titration for All Patients Taking Renagel:

Dosage should be adjusted based on the serum phosphorus concentration with a goal of lowering serum phosphorus to 5.5 mg/dL or less.

Mechanism of Action

Renagel (sevelamer hydrochloride) is a non-absorbed binding crosslinked polymer. It contains multiple amines separated by one carbon from the polymer backbone. These amines exist in a protonated form in the intestine and interact with phosphate molecules through ionic and hydrogen bonding. By binding phosphate in the dietary tract and decreasing absorption, sevelamer hydrochloride lowers the phosphate concentration in the serum.

Side Effects

Adverse events associated with the use of Renagel may include, but are not limited to, the following:

• Vomiting
• Nausea
• Diarrhea
• Dyspepsia
• Abdominal pain
• Flatulence
• Constipation

Clinical Trial Results

The FDA approval of Renagel was based on six clinical trials: one double-blind placebo controlled 2-week study; two open-label uncontrolled 8-week studies and three active-controlled open-label studies with treatment durations of 8 to 52 weeks. Three of the active-controlled studies are described:

Active-Control, Crossover Study in Hemodialysis Patients
This trial enrolled 84 subjects on hemodialysis who were hyperphosphatemic (serum phosphorus > 6.0 mg/dL). Following a two-week phosphate binder washout period, subjects were randomized to receive Renagel and active control for eight weeks each. Treatment periods were separated by a two-week phosphate binder washout period. Subjects started on treatment three times per day with meals. Over each eight-week treatment period, at three separate time points the dose of Renagel could be titrated up 1 capsule or tablet per meal (3 per day) to control serum phosphorus, the dose of active control could also be altered to attain phosphate control. Both treatments significantly decreased mean serum phosphorus by about 2 mg/dL.

Active-Control, Parallel Study in Hemodialysis Patients
This trial enrolled 200 CKD patients on hemodialysis who were hyperphosphatemic (serum phosphorus > 5.5 mg/dL). Following a two-week phosphate binder washout period, subjects were randomized to receive Renagel 800 mg tablets or an active control. The two treatments produced similar decreases in serum phosphorus. At week 52, using last- observation-carried-forward, Renagel and control both significantly decreased mean serum phosphorus.

Active-Control, Parallel Study in Peritoneal Dialysis Patients
This trial enrolled 143 subjects on peritoneal dialysis who were hyperphosphatemic (serum phosphorus > 5.5 mg/dL). Following a two-week phosphate binder washout period, subjects were randomized to receive Renagel or active control open label for 12 weeks. Average daily Renagel dose at the end of treatment was 5.9 g (range 0.8 to 14.3 g). There were statistically significant changes in serum phosphorus (p < 0.001) for Renagel (-1.6 mg/dL from baseline of 7.5 mg/dL), similar to the active control.