Lanthanum carbonate

1 INDICATIONS AND USAGE Lanthanum carbonate chewable tablets are phosphate binder indicated to reduce serum phosphate in patients with end- stage renal disease (ESRD). Management of elevated serum phosphorus levels in patients with ESRD usually includes all of the following: reduction in dietary intake of phosphate, removal of phosphate by dialysis, and reduction of intestinal phosphate absorption with phosphate binders. Lanthanum carbonate chewable tablets are phosphate binder indicated to reduce serum phosphate in patients with end- stage renal disease (ESRD). ( 1 )

6 ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in other sections of the labeling: Gastrointestinal Adverse Effects [see Warnings and Precautions (5.1) ] In controlled trials, the most common adverse reactions that were more frequent (≥ 5% difference vs. placebo) in lanthanum carbonate were nausea, vomiting, and abdominal pain. ( 6.1 ) The following adverse reactions have been identified during post-approval use of lanthanum carbonate: constipation, dyspepsia, allergic skin reactions, and tooth injury while chewing the tablet. ( 6.2 ) To report SUSPECTED ADVERSE REACTIONS, contact Exelan pharmaceutical,Inc. at 1-866-604-3268 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Overall, the safety profile of Lanthanum carbonate chewable tablets has been studied in over 5,200 subjects in completed clinical trials. The most common adverse reactions for Lanthanum carbonate chewable tablets were gastrointestinal events,such as nausea,vomiting and abdominal pain and they generally abated over time with continued dosing. In double-blind, placebo-controlled studies where a total of 180 and 95 patients with ESRD were randomized to lanthanum carbonate chewable tablet and placebo, respectively, for 4 to 6 weeks of treatment, the most common reactions that were more frequent (≥5% difference) in the lanthanum carbonate group were nausea, vomiting, and abdominal pain (Table 1). Table 1. Adverse Reactions * That Were More Common on Lanthanum Carbonate in Placebo-Controlled, Double-Blind Studies with Treatment Periods of 4 to 6 Weeks LANTHANUM CARBONATE % (N=180) Placebo % (N=95) Nausea 11 5 Vomiting 9 4 Abdominal Pain 5 0 In an open-label, long-term 2- year extension study in 93 patients who had transitioned from other studies, resulting in a total of up to 6 years treatment, mean baseline values and changes in transaminases were similar to those observed in the earlier comparative studies, with little change during treatment. The safety of lanthanum carbonate was studied in two long-term, open-label clinical trials, which included 1,215 patients treated with lanthanum carbonate and 944 with alternative therapy. Fourteen percent (14%) of patients treated with lanthanum carbonate chewable tablets discontinued treatment due to adverse events. Gastrointestinal adverse reactions, such as nausea, diarrhea, and vomiting were the most common types of event leading to discontinuation. In pooled active comparator controlled clinical trials, hypocalcemia was noted with an incidence of approximately 5% in both lanthanum and active comparator groups. A nonclinical study and a phase 1 study have shown reduced absorption of calcium in the intestine with lanthanum carbonate treatment. In a crossover study in 72 healthy individuals comparing lanthanum carbonate chewable tablets to lanthanum carbonate oral powder, gastrointestinal adverse reactions such as nausea, diarrhea and vomiting were more common for the oral powder formulation (18%) than for the chewable tablets (7%). 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of lanthanum carbonate. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Cases of constipation, intestinal perforation, intestinal obstruction, ileus, subileus, dyspepsia, allergic skin reactions, hypophosphatemia, and tooth injury while chewing the tablet have been reported.