Reclast (zoledronic acid)
Company: Novartis
Approval Status: Approved August 2007
Treatment for: postmenopausal osteoporosis
Areas: Musculoskeletal; Obstetrics/Gynecology
Possible similar drugs: Reclast
| General Information | Clinical Results | Side Effects | Mechanism of Action | Literature References | Additional Information |
General Information
Reclast (zoledronic acid) is 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 treatment of osteoporosis in postmenopausal women.
Reclast is supplied as 5 mg in a 100 mL ready to infuse solution for intravenous administration. The recommended initial dose of the drug is a 5 mg infusion once a year given intravenously over no less than 15 minutes.
Clinical Results
FDA Approval
FDA approval of Reclast was based on the results of a clinical
trial. This randomized, double-blind, placebo -controlled,
multinational study enrolled 7,736 women aged 65-89 years with
osteoporosis. The subjects were stratified into two groups Stratum
I: no concomitant use of osteoporosis therapy or Stratum II:
baseline concomitant use of osteoporosis therapies which included
calcitonin, raloxifene, tamoxifen and hormone replacement therapy.
Reclast was administered once a year for three consecutive years,
as a single 5 mg dose in 100 mL solution infused over at least 15
minutes, for a total of three doses. All subjects received 1000 to
1500 mg of elemental calcium plus 400 to 1200 IU of vitamin D
supplementation per day. The subjects in Stratum I were evaluated
annually for incidence of vertebral fractures. The subjects in
Stratum I and II were evaluated for the incidence of hip and other
clinical fractures. The primary endpoints were the incidence of
morphometric vertebral fractures at 3 years and the incidence of
hip fractures over a median duration of 3 years.
Effect on vertebral fractures over three
years
Reclast significantly reduced the incidence of new vertebral
fractures over three years compared to placebo. In the Reclast arm,
there was a 3.3% rate of at least one new vertebral fracture versus
10.9% in the placebo arm (p <0.0001) for a 7.6% absolute
reduction in fracture incidence and 70% reduction in fracture
incidence.
Effect on hip fracture over three
years
Reclast demonstrated a 1.1% absolute reduction and 41% relative
reduction in the risk of hip fractures over a median duration of 3
years. The hip fracture event rate was 1.4% for Reclast -treated
subjects compared to 2.5% for placebo -treated subjects.
Reclast also had a positive effect over placebo in the following areas:
Bone Mineral Density
Reclast significantly increased BMD at the lumbar spine, total hip
and femoral neck, relative to treatment with placebo at time points
12, 24, and 36 months. Treatment with Reclast resulted in a 6.7%
increase in BMD at the lumbar spine, 6.0 % at the total hip, and
5.1% at the femoral neck, over 3 years as compared to placebo.
Bone Histology
Bone biopsy specimens were obtained between months 33 and 36 from
82 subjects treated with 3 annual doses of Reclast. Qualitative,
quantitative and micro CT assessments showed bone of normal
architecture and quality without mineralization defects.
Effect on Height
Over the three-year study standing height was measured annually
using a stadiometer. The Reclast group revealed less height loss
compared to placebo (4.2 mm vs. 7.0 mm, respectively
(p<0.001)).
Side Effects
Adverse events associated with the use of Reclast may include, but are not limited to, the following:
- Arthralgia
- Pyrexia
- Hypertension
- Headache
- Myalgia
- Pain in Extremity
- Influenza-like Illness
- Nausea
Mechanism of Action
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.
Literature References
Devogelaer JP, Brown JP, Burckhardt P, Meunier PJ, Goemaere S, Lippuner K, Body JJ, Samsioe G, Felsenberg D, Fashola T, Sanna L, Ortmann CE, Trechsel U, Krasnow J, Eriksen EF, Garnero P Zoledronic acid efficacy and safety over five years in postmenopausal osteoporosis. Osteoporosis International 2007 Sep;18(9):1211-8
Black DM, Delmas PD, Eastell R, Reid IR, Boonen S, Cauley JA, Cosman F, Lakatos P, Leung PC, Man Z, Mautalen C, Mesenbrink P, Hu H, Caminis J, Tong K, Rosario-Jansen T, Krasnow J, Hue TF, Sellmeyer D, Eriksen EF, Cummings SR; HORIZON Pivotal Fracture Trial Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. The New England Journal of Medicine 2007 May 3;356(18):1809-22
Rackoff PJ, Sebba A Optimizing administration of bisphosphonates in women with postmenopausal osteoporosis. Treatments in Endocrinology 2005;4(4):245-51
Sartori L, Adami S, Filipponi P, Crepaldi G Injectable bisphosphonates in the treatment of postmenopausal osteoporosis. Aging Clinical and Experimental Research 2003 Aug;15(4):271-83
Reid IR, Brown JP, Burckhardt P, Horowitz Z, Richardson P, Trechsel U, Widmer A, Devogelaer JP, Kaufman JM, Jaeger P, Body JJ, Brandi ML, Broell J, Di Micco R, Genazzani AR, Felsenberg D, Happ J, Hooper MJ, Ittner J, Leb G, Mallmin H, Murray T, Ortolani S, Rubinacci A, Saaf M, Samsioe G, Verbruggen L, Meunier PJ Intravenous zoledronic acid in postmenopausal women with low bone mineral density. The New England Journal of Medicine 2002 Feb 28;346(9):653-61
Additional Information
For additional information regarding Reclast or postmenopausal osteoporosis, please visit the Reclast web page.
The FDA drug information shown here is licensed from Thomson CenterWatch. The information provided here is for general educational purposes only and does not constitute medical or pharmaceutical advice which should be sought from qualified medical and pharmaceutical advisers.
