Currently Enrolling Trials
Renagel is a sevelamer hydrochloride tablet in 800 mg and 400 mg doses for the treatment of high levels of serum phosphorus in patients with end-stage renal disease (ESRD). It is available by prescription only. The FDA approved Renagel in October 1998 for the same indication, but in a capsule formulation.
Hyperphosphatemia is characterized by elevated serum phosphorus levels, a substance typically excreted through normal digestive processes. If left untreated, hyperphosphatemia can lead to brittle bone disease and calcification of the circulatory system. Before the availability of Renagel®, the most common forms of treatment were aluminum and calcium phosphate binders, both of which are associated with dose-limiting toxicities. Both calcium-free and aluminum-free, Renagel® enables the aggressive treatment of hyperphosphatemia without the associated risks of other treatments. (From Company Website)
Three phase II studies and two phase III studies were conducted to test the efficacy of Renagel Capsules in lowering serum phosphorus in ESRD patients on hemodialysis. The phase III studies varied in treatment duration ranging from 2 to 12 weeks and the phase II studies lasted a duration of 8 weeks. Four of the 5 studies were open-label dose-titration studies. One of the phase II studies was a placebo-controlled study. The phase III crossover study, described below, had a control arm. About half the patients from these studies (N=192) were treated with Renagel Capsules in a long-term open-label extension study of 44 weeks. (Information taken from FDA Label)
Renagel is contraindicated in patients with hypophosphatemia or bowel obstruction, patients known to be hypersensitive to sevelamer hydrochloride or to any of its constituents.
Side effects observed in clinical trials were similar for patients taking Renagel as for those taking placebo. Common side effects include, but are not limited to:
Effects of Renagel on pregnant women has not been studied, but the drug was shown to cause reduced or irregular ossification of fetal bones, probably due to a reduced absorption of fat-soluble vitamin D, in test animals. Reduced amounts of other vitamins during pregnancy were also found in test animals given the drug.
Mechanism of Action
Patients with end-stage renal disease (ESRD) retain phosphorus and can develop hyperphosphatemia. High serum phosphorus can precipitate serum calcium resulting in ectopic calcification. When the product of serum calcium and phosphorus concentrations (Ca x P) exceeds 66, there is an increased risk that ectopic calcification will occur. Hyperphosphatemia plays a role in the development of secondary hyperparathyroidism in renal insufficiency. An increase in parathyroid hormone (PTH) levels is characteristic of patients with chronic renal failure. Increased levels of PTH can lead to osteitis fibrosa, a bone disease. A decrease in serum phosphorus may decrease serum PTH levels.
Treatment of hyperphosphatemia includes reduction in dietary intake of phosphate, inhibition of intestinal phosphate absorption with phosphate binders, and removal of phosphate with dialysis. Renagel taken with meals has been shown to decrease serum phosphorus concentrations in patients with ESRD who are on hemodialysis. All clinical studies were conducted with Renagel Capsules. In vitro studies have shown that the capsule and tablet formulations bind phosphate to a similar extent. Since Renagel does not contain aluminum, it does not cause aluminum intoxication.
Renagel treatment also results in a lowering of low-density lipoprotein (LDL) and total serum cholesterol levels. (From Company Website)
For more information on end-stage renal disease (ESRD) see: Lycos Health