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Medical Areas: Endocrinology | Oncology
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Zometa (zoledronic acid)
The following drug information is obtained from various newswires, published
medical journal articles, and medical conference presentations.
Approval Status: Approved August 2001
Treatment Area: Hypercalcemia of malignancy
Zometa 4 mg (zoledronic acid for injection) has been approved
for the treatment of hypercalcemia of malignancy (HCM), a common
life-threatening metabolic complication associated with cancer.
Zometa is an intravenous bisphosphonate that works by inhibiting
the breakdown of bone (resorption).
HCM affects more than 10% of all cancer patients and occurs most
frequently with breast cancer, multiple myeloma and non-small cell
lung cancer. This condition occurs when factors made by cancer
cells over-stimulate osteoclasts, which are cells responsible for
bone resorption. The over-stimulation results in an increased rate
of bone breakdown and the release of excess calcium into the
bloodstream. The kidneys are unable to cope with the excessively
high calcium levels and the calcium remains in the blood, leading
to complications such as dehydration, fatigue, nausea, vomiting,
confusion and coma.
Zometa was evaluated in two multicenter, randomized,
double-blind trials in which it was compared to Aredia
(pamidronate) 90 mg. The trials included 275 evaluable subjects,
and treatment groups were generally well balanced in terms of age,
sex, race and tumor types. Treatment with a single dose of either
Zometa 4 mg or 8 mg was compared to a single dose of Aredia 90
Data revealed that the proportion of subjects with normalization
of corrected serum calcium (CSC) by day 10 were 88% and 70% for
Zometa 4 mg and Aredia 90 mg, respectively. The risk of renal
toxicity with Zometa 8 mg was shown to be significantly greater
than that seen with Zometa 4 mg - notably, no additional benefit
was seen with the higher dosage.
Zometa also demonstrated positive results in secondary efficacy
variables. Results showed that time to relapse was 30 days for
Zometa 4 mg and 17 days for Aredia 90 mg. Duration of complete
response, or the maintenance of normalized calcium levels, was 32
days for Zometa 4 mg and 18 days for Aredia 90 mg.
In general, adverse reactions to Zometa were mild and
short-lived. Adverse events reported by subjects in clinical trials
include (but are not limited to) the following:
- Abdominal pain
Mechanism of Action
The principle pharmacologic action of zoledronic acid is
inhibition of bone resorption. Although the antiresorptive
mechanism is not completely understood, several factors are thought
to contribute to this action. In vitro, zoledronic acid inhibits
osteoclastic activity and induces osteoclast apoptosis. Zoledronic
acid also blocks the osteoclastic resorption of mineralized bone
and cartilage through its binding to bone. Zoledronic acid inhibits
the increased osteoclastic activity and skeletal calcium release
induced by various stimulatory factors released by tumors. (from
Zometa Prescribing Information)
Zometa has been approved for the treatment of HCM in several
countries, including Switzerland, Brazil, Canada and Australia.
Novartis also plans to submit a supplemental application to the
FDA for Zometa in the treatment of bone metastasis.
For additional information on Zometa, please visit the product
web site at www.zometa.com.