Pharmacology Update

Lanthanum Carbonate Tablets (FosrenalTM)

By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD

A new non-aluminum, non-calcium, phosphate binder has been approved by the FDA. Lanthanum is a naturally occurring, rare earth element with strong phosphate binding capacity. The trivalent cation is marketed as the carbonate by Shire USA as FosrenalTM.

Indications

Lanthanum is indicated to reduce phosphate in patients with end-stage renal disease.1

Dosage

The recommended initial dose is 750 mg - 1500 mg daily taken as divided doses with meals. The dose should be titrated every 2-3 weeks and generally at increments of 750 mg until the desired serum phosphate level is achieved. Most patients require 1500 mg to 3000 mg daily. Serum phosphate should be monitored during titration as on a regular basis after reaching an effective dose. Tablets should be chewed completely before swallowing and should be taken with or immediately after meals.1

Lanthanum carbonate is supplied as 250 mg and 500 mg tablets.

Potential Advantages

Lanthanum carbonate is formulated as a chewable tablet and can be taken without water. The incidence of hypercalcemia was lower for lanthanum than calcium.2-4 It has low water solubility and low bioavailability (< 0.002%).1 Compared to calcium carbonate, lanthanum carbonate is less likely to lead to renal osteodystropy.4

Potential Disadvantages

Fourteen percent of patients in comparative, open labeled studies discontinued therapy due to side effects. These include nausea, diarrhea, and vomiting.1 Other side effects include dialysis graft occlusion and abdominal pain. The mean plasma lanthanum level after long-term therapy is approximately 0.6 ng/mL. The long-term health effect of lanthanum is not known.

Comments

Lanthanum has similar phosphate binding capacity to aluminum hydroxide and better than calcium at pH 3 and similar at pH 5.2,3 In a phase III, double-blind, dose-titration study (n = 163), compared lanthanum to placebo in hemodialysis patients. Lanthanum decreased serum phosphorus from 7.69 mg/dL to 5.94 mg/dL compared to placebo, 7.39 mg/dL to 7.85 mg/dl; P <0.0001.5 In addition, the calcium × phosphorus product and parathyroid hormone levels were also significantly lower with lanthanum. The greatest difference in adverse events between lanthanum and placebo were dialysis graft occlusion (6.0% vs 2.3%) and vomiting (6.0% vs 2.3%). Other side effects associated with lanthanum were nausea and diarrhea. In a comparative study (n = 833), lanthanum produced lower calcium × phosphorus product than calcium carbonate. Clinically significant hypercalcemia occurred in 20.2% of patients who received calcium carbonate compared to 0.4% with lanthanum.6 In 2 long-term studies, one 6 months and the other 2 years, lanthanum had the same efficacy as alternative phosphate binders (calcium salts, aluminum salts, sevelamer).1,3 The long-term safety of chronic, albeit low, levels of lanthanum is not known. The cost of lanthanum was not available at the time of this review.

Clinical Implications

Lanthanum provides an alternative to sevelamer as a non-aluminum and non-calcium phosphate binder. While calcium and aluminum salts are effective binders, the former causes hypercalcium and the latter, poses systemic toxicity.7 Sevelamer is very expensive and has the potential to bind certain fat-soluble vitamins but reduces LDL-cholesterol and does not cause hypercalcemia.7

Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente; Asst. Clinical Professor of Medicine, University of California, San Francisco. Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA. Both are Associate Editors of Internal Medicine Alert.

References

1. Fosrenal Product Information. Shire USA, Inc. October 2004.

2. Swainston T, Scott L. Drugs. 2004;64(9):985-996.

3. Loghman-Adham M. Drug Safety. 2003;26:1093-1115.

4. D’Haese PC, et al. Kidney Int(Suppl). 2003;(85): S73-S76.

5. Joy MS, Finn A. Am J Kidney Dis. 2003;42(1): 96-107.

6. Hutchism AJ, et al. Abstract Presented at the annual meeting of the American Society of Nephrology. 2002;Nov 1-4: Philadelphia (Penn).

7. Albaaj F, Hutchison AJ. Drugs. 2003;63(6):577-596.