FOSRENOL.com: For Health Care Providers – Well-Established Safety Profile

Contrary to what some may believe, FOSRENOL^® does not have the toxicities associated with aluminum^1-4

^aRenal excretion of FOSRENOL^® is 0.000031% vs >95% for aluminum; based on animal models, biliary excretion of FOSRENOL^® is 79% vs <2% for aluminum.^5,12,18

Signs of aluminum toxicity (eg, encephalopathy, osteomalacia) typically become apparent after 1 to 2 years on dialysis^16,19
The safety of FOSRENOL^® has been studied in over 5500 patients²⁰

—Despite the challenge of CKD Stage 5 mortality for long-term data, a number of patients (N=22) taking FOSRENOL^® have been followed for more than 5 years

FOSRENOL^® has not shown signs of aluminum-like toxicity^1-4

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Important Safety Information

The most common adverse events were gastrointestinal, such as nausea and vomiting, and generally abated over time with continued dosing
The most common side effects leading to discontinuation in clinical trials were gastrointestinal events (nausea, vomiting, and diarrhea)
Other side effects reported in trials included dialysis graft complications, headache, abdominal pain, and hypotension
Although studies were not designed to detect differences in risk of fracture and mortality, there were no differences demonstrated in patients treated with FOSRENOL^® compared to alternative therapy for up to 3 years
The duration of treatment exposure and time of observation in the clinical program were too short to conclude that FOSRENOL^® does not affect the risk of fracture or mortality beyond 3 years
While lanthanum has been shown to accumulate in the GI tract, liver, and bone in animals, the clinical significance in humans is unknown
Patients with acute peptic ulcer, ulcerative colitis, Crohn’s disease, or bowel obstruction were not included in FOSRENOL^® clinical studies. Caution should be used in patients with these conditions
FOSRENOL^® should not be taken by patients who are nursing or pregnant
FOSRENOL^® should not be taken by patients who are under 18 years of age

References

Malluche HH; on behalf of the Lanthanum Study Group. Safety of lanthanum carbonate on bone: a 2-year randomized, comparator-controlled trial. Poster presented at: the National Kidney Foundation Clinical Meeting; May 4-8, 2005; Washington, DC.
D’Haese PC, Spasovski GB, Sikole A, et al. A multicenter study on the effects of lanthanum carbonate (Fosrenol) and calcium carbonate on renal bone disease in dialysis patients. Kidney Int. 2003;63(suppl 85):S73-S78.
Freemont AJ, Hoyland JA, Denton J; on behalf of the Lanthanum Carbonate SPD405-303 Study Group. The effects of lanthanum carbonate and calcium carbonate on bone abnormalities in patients with end-stage renal disease. Clin Nephrol. 2005;64(6):428-437.
Altmann P, Barnett ME, Finn WF; on behalf of the SPD405-307 Lanthanum Carbonate Study Group. Cognitive function in stage 5 chronic kidney disease patients on hemodialysis: no adverse effects of lanthanum carbonate compared with standard phosphate-binder therapy. Kidney Int. 2007;71(3):252-259.
Pennick M, Dennis K, Damment SJP. Absolute bioavailability and disposition of lanthanum in healthy human subjects administered lanthanum carbonate. J Clin Pharmacol. 2006;46(7):738-746.
Priest ND, Talbot RJ, Austin JG, et al. The bioavailability of 26Al-labelled aluminium citrate and aluminium hydroxide in volunteers. Biometals. 1996;9(3):221-228.
Moore PB, Day JP, Taylor GA, Ferrier IN, Fifield LK, Edwardson JA. Absorption of aluminium-26 in alzhemier’s disease, measured using accelerator mass spectrometry. Dement Geriatr Cogn Disord. 2000;11(2):66-69.
Finn WF; on behalf of the SPD 405-307 Lanthanum Study Group. Lanthanum carbonate versus standard therapy for the treatment of hyperphosphatemia: safety and efficacy in chronic maintenance hemodialysis patients. Clin Nephrol. 2006;65(3):191-202.
Joy MS, Finn WF; on behalf of the LAM-302 Study Group. Randomized, double-blind, placebo-controlled, dose-titration, phase III study assessing the efficacy and tolerability of lanthanum carbonate: a new phosphate binder for the treatment of hyperphosphatemia. Am J Kidney Dis. 2003;42(1):96-107.
Hutchison AJ, Maes B, Vanwalleghem J, et al. Efficacy, tolerability, and safety of lanthanum carbonate in hyperphosphatemia: a 6-month, randomized, comparative trial versus calcium carbonate. Nephron Clin Pract. 2005;100(1):c8-19.
Damment SJP, Pennick M. Systemic lanthanum is excreted in the bile of rats. Toxicol Lett. 2007;171(1-2):69-77.
Yokel RA, McNamara PJ. Aluminum toxicokinetics: an updated minireview. Pharmacol Toxicol. 2001;88(4):159-167.
Hutchison AJ, Pratt RD. Lanthanum carbonate: no evidence of adverse effects on liver with up to 6 years of treatment in patients with stage 5 CKD. Poster presented at: the 39th annual meeting of the American Society of Nephrology; November 14-19, 2006; San Diego, CA. Abstract F-PO093.
Verbueken AH, Van de Vyver, Van Grieken RE, et al. Ultrastructural localization of aluminum in patients with dialysis-associated osteomalacia. Clin Chem. 1984;30(5):763-768.
Spasovski GB, Sikole A, Gelev S, et al. Evolution of bone and plasma concentration of lanthanum in dialysis patients before, during 1 year of treatment with lanthanum carbonate and after 2 years of follow-up. Nephrol Dial Transplant. 2006;21(8):2217-2224.
Ward MK, Feest TG, Ellis HA, Parkinson IS, Kerr DNS. Osteomalacic dialysis osteodystrophy: evidence for a water-borne aetiological agent, probably aluminium. Lancet. 1978;1(8069):841-845.
Altmann P, Dhanesha U, Hamon C, Cunningham J, Blair J, Marsh F. Disturbance of cerebral function by aluminium in haemodialysis patients without overt aluminium toxicity. Lancet. 1989;2(8653):7-12.
Albaaj F, Hutchison AJ. Lanthanum carbonate for the treatment of hyperphosphatemia in renal failure and dialysis patients. Expert Opin Pharmacother. 2005;6(2):319-328.
K/DOQI Clinical Practice Guidelines for Bone Metabolism and Disease in Chronic Kidney Disease. http://www.kidney.org/professionals/kdoqi/guidelines_bone/Guide11.htm. Accessed January 3, 2008.
Data on file, Shire US Inc., SPD 405-03.

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FOS-00024 07/08