Zoledronate (Zometa, Novartis)

Zoledronate is the latest bisphosphonate to be approved by the FDA for intravenous treatment of hypercalcemia as a result of a malignancy. Even more recently (February, 2002), zoledronate was approved for treatment of bone metastasis. In general, bisphosphonates bind to the bone matrix to decrease osteoclastic activity which prevents bone resorption. It has been shown that first skeletal-related events and a reduction of skeletal related events can occur with the administration of bisphosphonates.

Zoledronate is a highly potent bisphosphonate that has demonstrated a 40 to 850 fold greater potency than pamidronate. In clinical trials, a single dose of zoledronate was significantly more effective than pamidronate at normalizing corrected serum calcium in patients with malignancy related hypercalcemia.

In other clinical trials, zoledronate was compared to pamidronate (Aredia) in patients with bone metastasis. The results revealed zoledronate to be well tolerated and to be as effective in preventing skeletal complications as compared to pamidronate.

Zoledronate was also found to be more effective in reducing the requirement for radiation therapy to the bone and in reducing the incidence of skeletal complications.

Like other bisphosphonates, zoledronate is not metabolized and can remain in the bone for months to years. Approximately 50% is excreted in the urine within 24 hours with the remaining amount binding to the bone and slowly released into the circulation. The half-life of zoledronate in the plasma is about seven days.

The dose of zoledronate is 4 mg administered intravenously over 15 minutes in 100 cc of normal saline (or 5% dextrose) every 3 to 4 weeks. Initially the drug is reconstituted in 4 ml of sterile water. The most common adverse effects of zoledronate include bone pain, nausea, fatigue, and fever occurring less than 15% of the time. Other adverse effects reported included constipation, anemia, dyspnea, arthralgia, myalgia, and renal toxicity. All these adverse effects are similar to pamidronate. The cost of zoledronate is $856.38 per 4 mg vial compared to $839.60 for a 20mg vial of pamidronate. Further clinical trials are being conducted in patients with Paget’s disease and post-menopausal osteoporosis.

Intravenous bisphosphonates are the current standard of care for the treatment of hypercalcemia and bone metastasis. Although zoledronate has been found to be as effective as pamidronate, the decrease infusion time provides an benefit with greater patient convenience and less nursing monitoring time.

Author (2001). Zoledronate (Zometa). The medical Letter, 43(1120), 109-112. Berenson, J. R., Rosen, L. S., Howell, A., et al. (2001). Zoledronic acid reduces skeletal-related events in patients with osteolytic metastases. Cancer, 91, 1191-1200. Major, P. Lortholary, A., Hon, J., et al. (2001).

Zoledronic acid is superior to pamidronate in the treatment of hypercalcemia of malignancy: a pooled analysis of two randomized, controlled clinical trials. Journal of Clinical Oncology, 19, 558-567. Rosen, L. S., Gordon, D., Kaminski, M., et al. (2001). Zoledronic acid versus pamidronate in the treatment of skeletal metastases in patients with breast cancer or osteolytic lesions of multiple myeloma: A phase III, double-blind comparative trial. The Cancer Journal, 7, 377-387.