| Systematic (IUPAC) name | |
|---|---|
| [1-hydroxy-2-(1H-imidazol-1-yl)ethane-1,1-diyl]bis(phosphonic acid) | |
| Clinical data | |
| AHFS/Drugs.com | monograph |
| MedlinePlus | a605023 |
| Licence data | EMA:Link, US FDA:link |
| Pregnancy cat. | D (U.S.) |
| Legal status | ℞-only (U.S.) |
| Routes | Intravenous |
| Pharmacokinetic data | |
| Protein binding | 22% |
| Metabolism | Nil |
| Half-life | 146 hours |
| Excretion | Renal (partial) |
| Identifiers | |
| CAS number | 118072-93-8 |
| ATC code | M05BA08 |
| PubChem | CID 68740 |
| DrugBank | APRD01294 |
| UNII | 70HZ18PH24 |
| KEGG | D08689 |
| ChEMBL | CHEMBL924 |
| Chemical data | |
| Formula | C5H10N2O7P2 |
| Mol. mass | 272.09 g/mol |
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Zoledronic acid (INN) or zoledronate (marketed by Novartis under the trade names Zometa, Zomera, Aclasta and Reclast) is a bisphosphonate. Zometa is used to prevent skeletal fractures in patients with cancers such as multiple myeloma and prostate cancer, as well as for treating osteoporosis.[1] It can also be used to treat hypercalcemia of malignancy and can be helpful for treating pain from bone metastases.
An annual dose of zoledronic acid may also prevent recurring fractures in patients with a previous hip fracture.[2]
Reclast is a single 5 mg infusion for the treatment of Paget's disease of bone. In 2007, the U.S. Food and Drug Administration (FDA) also approved Reclast for the treatment of postmenopausal osteoporosis.
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In all cases administration is by intravenous infusion over a minimum of 15 minutes.
As Zometa (4 mg every three weeks) for bone complications of cancer.
Zometa has been demonstrated to reduce significantly the risk of skeletal complications in breast cancer patients with bone metastases.
It can be administered at home rather than in hospital. Such administration has shown safety and quality-of-life benefits in breast cancer patients with bone metastases.[3]
As Aclasta (5 mg infusion once per year) for treatment of osteoporosis in men and post-menopausal women at increased risk of fracture.
Zoledronate has shown significant benefits versus placebo over three years, with a reduced number of vertebral fractures and improved markers of bone density.[4][5]
Zomera (zoledronic acid for injection) is indicated for the treatment of hypercalcemia of malignancy.[6]
Zomera is indicated for the treatment of patients with multiple myeloma and patients with documented bone metastases from solid tumors, in conjunction with standard antineoplastic therapy.[6]
As Reclast a single dose of 5 mg is used for the treatment of Paget's disease.
Side effects can include fatigue, anemia, muscle aches, fever, and/or swelling in the feet or legs. Flu-like symptoms are commonly experienced after the first zoledronate infusion, although not subsequent infusions, and are thought to occur because of its potential to activate human γδ T cells (gamma/delta T cells).
Zoledronate is rapidly processed via the kidneys; consequently its administration is not recommended for patients with reduced renal function or kidney disease.[7]Some cases of acute renal failure requiring dialysis or having a fatal outcome, following Reclast use, have been reported to theU.S. Food and Drug Administration (FDA)[8].
A rare complication that has been recently observed in cancer patients being treated with bisphosphonates is osteonecrosis of the jaw. This has mainly been seen in patients with multiple myeloma treated with zoledronate who have had dental extractions.[9]
Zoledronic acid has been found to have a direct antitumour effect as well as synergistically augmenting the effects of other antitumor agents in osteosarcoma cells.[10]
An increase in Disease-Free Survival (DFS) was found in the ABCSG-12 trial, in which 1,803 premenopausal women with endocrine-responsive early breast cancer received anastrozole with zoledronic acid.[11] A retrospective analysis of the AZURE trial data revealed a DFS survival advantage, particularly where estrogen had been reduced.[12]
In a meta-analysis of trials where upfront zoledronic acid was given to prevent aromatase inhibitor-associated bone loss, active cancer recurrence appeared to be reduced.[13] The results of clinical studies of adjuvant treatment on early-stage hormone-receptor-positive breast-cancer patients under hormonal treatment - especially with the bisphosphonate zoledronic acid - caused excitement because they demonstrated an additive effect on decreasing disease relapses at bone or other sites. A number of clinical and in vitro and in vivo preclinical studies, which are either ongoing or have just ended, are investigating the mechanisms and antitumoral activity of bisphosphonates.[14] Ongoing large trials testing bisphosphonates as adjuvant treatment of breast cancer include NSABP B-34,[15] the NATAN trial,[16] and SWOG-S0307.[17] A 2010 review concluded that "adding zoledronic acid 4 mg intravenously every 6 months to endocrine therapy in premenopausal women with hormone receptor-positive early breast cancer ... is cost-effective from a US health care system perspective."[18]
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