| Item |
Information |
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Drug Groups
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approved |
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Description
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Zoledronate (zoledronic acid, marketed by Novartis under the trade names Zometa and Reclast) is a bisphosphonate. Zometa is used to prevent skeletal fractures in patients with cancers such as multiple myeloma and prostate cancer. It can also be used to treat hypercalcemia of malignancy and can be helpful for treating pain from bone metastases.
An annual dose of Zoledronate may also prevent recurring fractures in patients with a previous hip fracture.
Zoledronate is a single 5 mg infusion for the treatment of Paget's disease of bone. In 2007, the FDA also approved Reclast for the treatment of postmenopausal osteoporosis. |
| Indication |
For the treatment of hypercalcemia of malignancy. Also for the treatment of patients with multiple myeloma and patients with documented bone metastases from solid tumors, in conjunction with standard antineoplastic therapy. In May of 2007, the drug was approved for treatment of Paget’s Disease. |
| Pharmacology |
Zoledronate is a bisphosphonic acid which is an inhibitor of osteoclastic bone resorption. Zoledronate is used to prevent osteoporosis and skeletal fractures, particularly in patients with cancers such as multiple myeloma and prostate cancer. It can also be used to treat hypercalcemia, particularly hypercalcemia of malignancy. It can also be helpful for treating pain from bone metastases. |
| Toxicity |
There is no experience of acute overdose. Two patients received zoledronate (32 mg) over 5 minutes in clinical trials. Neither patient experienced any clinical or laboratory toxicity. Overdosage may cause clinically significant hypocalcemia, hypophosphatemia, and hypomagnesemia. |
| Affected Organisms |
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Humans and other mammals |
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| Biotransformation |
Zoledronate does not inhibit human P450 enzymes in vitro and does not undergo biotransformation in vivo. |
| Absorption |
Poorly absorbed (oral absorption is about 1% of what intravenous absorption is). |
| Half Life |
146 hours |
| Protein Binding |
Approximately 22% bound in human plasma, independent of the concentration. However, Canadian product information states binding to human plasma protein is approximately 56%. |
| Elimination |
In 64 patients with cancer and bone metastases, on average (± s.d.) 39 ± 16% of the administered zoledronic acid dose was recovered in the urine within 24 hours, with only trace amounts of drug found in urine post-Day 2. |
| Clearance |
* Renal cl=3.7 +/- 2.0 L/h |
| References |
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Lyles KW, Colon-Emeric CS, Magaziner JS, Adachi JD, Pieper CF, Mautalen C, Hyldstrup L, Recknor C, Nordsletten L, Moore KA, Lavecchia C, Zhang J, Mesenbrink P, Hodgson PK, Abrams K, Orloff JJ, Horowitz Z, Eriksen EF, Boonen S: Zoledronic Acid and Clinical Fractures and Mortality after Hip Fracture. N Engl J Med. 2007 Sep 26;.
[Pubmed]
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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. N Engl J Med. 2002 Feb 28;346(9):653-61.
[Pubmed]
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Durie BG, Katz M, Crowley J: Osteonecrosis of the jaw and bisphosphonates. N Engl J Med. 2005 Jul 7;353(1):99-102; discussion 99-102.
[Pubmed]
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