Randomized Crossover Study of the Efficacy and Safety of Sevelamer Hydrochloride and Lanthanum Carbonate in Japanese Patients Undergoing Hemodialysis

Abstract

Insufficient control of serum calcium and phosphate levels in patients undergoing hemodialysis is associated with increased mortality. As commonly used calcium-containing phosphate binders can cause arterial calcification, newly developed calcium-free phosphate binders, such as sevelamer hydrochloride (SH) and lanthanum carbonate (LC), have received much attention. We assessed the efficacy and safety of SH and LC treatment in Japanese patients undergoing hemodialysis in a prospective randomized open blinded endpoint (PROBE) crossover study. Forty-two patients were randomized to receive SH or LC for 13 weeks, with the dosages adjusted every 2 weeks, followed by treatment with the other drug for another 13 weeks. The average daily doses of SH and LC were 2971 ± 1464 mg and 945 ± 449 mg, respectively. The mean dosage ratio of SH to LC was 3.05, which was maintained throughout the treatment period. SH and LC were similarly effective at controlling serum calcium and phosphate levels in the majority of patients (78-93%). A few serious adverse events (AEs) involving the biliary system occurred during the LC treatment period, but they were not considered to be treatment-induced. Although the incidence of constipation, the most common treatment-related AE, was higher during the SH period (27% vs. 5%; P < 0.05), no difference was observed in total treatment-related AEs. This study demonstrates that SH and LC are comparable treatments for controlling serum phosphate and calcium levels, and that both compounds are safe and well-tolerated in Japanese patients undergoing hemodialysis.

Sevelamer Carbonate and Lanthanum Usage Evaluation and Cost Considerations at a Veteran's Affairs Medical Center

“…7 The average daily dose in the current review was significantly higher when compared to Kasai et al's review where the average daily dose was 945 mg for lanthanum and 2,971 mg for sevelamer hydrochloride. 11 This dose disparity correlated to decreased tablet burden in favor of lanthanum as seen in this study, which has been associated with a potentially positive influence on patient adherence. This study demonstrated a potential prescription cost savings for the medical center of approximately $4,500 monthly or $54,000 annually, if all study patients prescribed less than or equal to 9,600 mg of sevelamer carbonate per day were converted to lanthanum therapy.…”

“…5,10,11 Although lanthanum and sevelamer carbonate are only approved in ESRD patients, this evaluation along with previous literature support use in CKD stage 3-5 as well. 5,17 Both groups included a similar portion of patients who had active prescriptions for calcium acetate.…”

“…A prospective randomized crossover trial of non-VA patients by Kasai et al assessed the safety and efficacy of lanthanum compared to sevelamer hydrochloride in 42 dialysis patients. 11 It showed similar efficacy in reduction of serum phosphorus with an average daily dose of 945 ± 449 mg for lanthanum and 2,971 ± 1,464 mg for sevelamer hydrochloride. Commonly reported adverse events in the literature are similar between lanthanum and sevelamer carbonate, with cumulative incidence of gastrointestinal intolerance and constipation at roughly 10% to 13%.…”

“…While comparison studies by both Prajapati et al and Kasai et al did not detect differences in tablet burden between lanthanum and sevelamer hydrochloride, a study by Vemuri et al determined that lanthanum therapy required significantly fewer tablets per day. 3,7,11 The decrease in tablet burden of lanthanum appeared to have a positive influence on patient adherence.…”

Comparative analysis of the phosphate-binding effects of sucroferric oxyhydroxide, ferric citrate, and lanthanum carbonate

“…However, arterial media calcification was observed in patients undergoing hemodialysis who consumed Ca-containing phosphate binders [6]. Randomized controlled trials on sevelamer and lanthanum in Japanese patients indicated identical levels of phosphate-binding efficacy [7]. Isakova et al also reported that treatment with phosphorus binders independently decreased mortality in patients [8].…”