Reclast (zoledronic acid)

Reclast is a bisphosphonic acid inhibitor of osteoclastic bone resorption. Once administered, it rapidly moves to bone and preferentially localizes at sites of high bone turnover.

Reclast is specifically indicated for the treatment of Paget's disease of bone in men and women.

Reclast is supplied as a sterile solution designed for intravenous infusion. The recommended initial dose of the drug is a 5 mg infusion administered intravenously via a vented infusion line. The infusion time must not be less than 15 minutes given over a constant infusion rate.

FDA Approval
FDA approval of Reclast was based on the results of two 6- month randomized, double blind trials. Subjects enrolled in the studies received one infusion of 5-mg Reclast or oral daily doses of 30 mg-risedronate for 2 months. Therapeutic response was defined as either normalization of serum alkaline phosphatase (SAP) or a reduction of at least 75% from baseline in total SAP excess at the end of 6 months. SAP excess was defined as the difference between the measured level and midpoint of normal range. Combined data showed that 96% of the subjects treated with Reclast achieved therapeutic response compared to 74% of those treated with risedronate. At six months, 89% of the Reclast treated subjects achieved normalization of SAP levels versus 58% of those treated with risedronate (p<0.0001). In subjects who had previously received treatment with oral bisphosphonates, 96% reached therapeutic response rates compared to 55% for risedronate. In treatment naïve subjects, therapeutic response to Reclast was 98% compared to 86% of those receiving risedronate. In subjects with symptomatic pain at screening, therapeutic response rates were 94% and 70% for Reclast and risedronate respectively. For subjects without pain at screening, therapeutic response rates were 100% and 82% for Reclast and risedronate respectively.

Ongoing Study Commitments

• Novartis has agreed to perform a registry study to determine the incidence of hypocalcemia post Reclast treatment in patients with Paget’s Disease.
  Protocol Submission: September 2007
  Study Start: March 2008
  Final Report Submission: September 2010

Adverse events associated with the use of Reclast may include, but are not limited to, the following:

• Influenza like illness
• Headache
• Dizziness
• Nausea
• Arthralgia
• Bone pain
• Pyrexia

Reclast is a bisphosphonic acid inhibitor of osteoclastic bone resorption. Once administered, it rapidly moves to bone and preferentially localizes at sites of high bone turnover. The main molecular target of zoledronic acid in the osteoclast is the enzyme farnesyl pyrophosphate synthase which catalyses the formation of a key cellular intermediate in isoprenoid metabolic pathways.

Hosking D, Lyles K, Brown JP, Fraser WD, Miller P, Curiel MD, Devogelaer JP, Hooper M, Su G, Zelenakas K, Pak J, Fashola T, Saidi Y, Eriksen EF, Reid IR Long-term control of bone turnover in Paget's disease with zoledronic acid and risedronate. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 2007 Jan;22(1):142-8

Griz L, Colares V, Bandeira F Treatment of Paget's disease of bone: importance of the zoledronic acid. Arquivos brasileiros de endocrinologia e metabologia 2006 Oct;50(5):845-51.

Reid IR, Miller P, Lyles K, Fraser W, Brown JP, Saidi Y, Mesenbrink P, Su G, Pak J, Zelenakas K, Luchi M, Richardson P, Hosking D Comparison of a single infusion of zoledronic acid with risedronate for Paget's disease. The New England journal of medicine 2005 Sep 1;353(9):898-908.

Maricic M The use of zoledronic acid for Paget's disease of bone. Current osteoporosis reports 2006 Mar;4(1):40-4

For additional information regarding Reclast or Paget's disease, please visit the Reclast web page.