General Information Sevelamer Hydrochloride
Renagel is sevelamer hydrochloride tablets in 800 mg and 400 mg doses to treat high levels of serum phosphorus in patients with end-stage renal disease (ESRD). It is available only by prescription. FDA approved Renagel in October 1998 over the same instructions, but in the capsule of the drug.
Hyperphosphatemia is characterized by elevated serum phosphorous, a substance usually derived through the normal process of digestion. 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 of aluminum and calcium phosphate binders, both of which are associated with dose-limiting toxicity. Both calcium-free and aluminum-free, Renagel ® allows aggressive treatment of hyperphosphatemia without the associated risks of other treatments. (From the company’s website)
Clinical results Sevelamer Hydrochloride
Three phase II studies and two Phase III studies were conducted to test the effectiveness of Renagel capsules in reducing serum phosphorus in patients with ESRD on hemodialysis. Phase III studies varied in treatment duration from 2 to 12 weeks, while the second stage of the study lasted 8 weeks. Four of 5 studies were open-label dose titration study. One of the Phase II study was a placebo-controlled study. Crossover phase III studies, described below, were the control group. About half of the patients from these studies (N = 192) treated with Renagel Capsules in a long-term open-label extension study of 44 weeks. (Information taken from FDA Label)
Side Effects Sevelamer Hydrochloride
Renagel is contraindicated in patients with hypophosphatemia or bowel obstruction, patients know that hypersensitivity to sevelamer hydrochloride or any of its components.
Side effects observed in clinical trials were similar for patients receiving Renagel for those who took placebo. Common side effects include, but are not limited to:
• Nausea
• constipation
• diarrhea
• flatulence
• indigestion
Renagel impact on pregnant women has not been studied, but the drug has been shown to reduce or irregular ossification of fetal bones, probably due to decreased absorption fat-soluble vitamin D, the experimental animals. Reducing the number of other vitamins during pregnancy were also found in experimental animals given the drug.
Mechanism of action Sevelamer Hydrochloride
Patients with end-stage renal disease (ESRD) retain phosphorus and can develop hyperphosphatemia. High serum phosphorus may accelerate the calcium in the blood serum as a result of ectopic calcification. When the product of serum calcium and phosphorus (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 failure. Increased parathyroid hormone (PTH) levels characteristic of patients with chronic renal failure. Increased PTH can lead to osteitis fibrosa, bone disease. Reduction in serum phosphorus may decrease serum PTH.
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 that reducing serum phosphorus in patients with chronic renal failure who are on hemodialysis. All clinical studies were conducted with Renagel capsules. In vitro studies have shown that capsule and tablet formulations bind phosphate to the same extent. Since Renagel does not contain aluminum, it does not cause aluminum intoxication.
