Zoledronate
Encyclopedia
Zoledronic acid or zoledronate (marketed by Novartis
under the trade names Zometa, Zomera, Aclasta and Reclast) is a bisphosphonate
. Zometa is used to prevent skeletal fracture
s in patients with cancer
s such as multiple myeloma
and prostate cancer
, as well as for treating osteoporosis
. 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.
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
.
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.
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.
for the treatment of hypercalcemia of malignancy.
.
, 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 kidney
s; consequently its administration is not recommended for patients with reduced renal function
or kidney disease.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).
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.
with zoledronic acid. A retrospective analysis of the AZURE trial data revealed a DFS survival advantage, particularly where estrogen had been reduced.
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. 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. Ongoing large trials testing bisphosphonates as adjuvant treatment of breast cancer include NSABP B-34, the NATAN trial, and SWOG-S0307. 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."
Novartis
Novartis International AG is a multinational pharmaceutical company based in Basel, Switzerland, ranking number three in sales among the world-wide industry...
under the trade names Zometa, Zomera, Aclasta and Reclast) is a bisphosphonate
Bisphosphonate
Bisphosphonates are a class of drugs that prevent the loss of bone mass, used to treat osteoporosis and similar diseases...
. Zometa is used to prevent skeletal fracture
Fracture
A fracture is the separation of an object or material into two, or more, pieces under the action of stress.The word fracture is often applied to bones of living creatures , or to crystals or crystalline materials, such as gemstones or metal...
s in patients with cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
s such as multiple myeloma
Multiple myeloma
Multiple myeloma , also known as plasma cell myeloma or Kahler's disease , is a cancer of plasma cells, a type of white blood cell normally responsible for the production of antibodies...
and prostate cancer
Prostate cancer
Prostate cancer is a form of cancer that develops in the prostate, a gland in the male reproductive system. Most prostate cancers are slow growing; however, there are cases of aggressive prostate cancers. The cancer cells may metastasize from the prostate to other parts of the body, particularly...
, as well as for treating osteoporosis
Osteoporosis
Osteoporosis is a disease of bones that leads to an increased risk of fracture. In osteoporosis the bone mineral density is reduced, bone microarchitecture is deteriorating, and the amount and variety of proteins in bone is altered...
. 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.
Reclast is a single 5 mg infusion for the treatment of Paget's disease of bone
Paget's disease of bone
Paget's disease is a chronic disorder that can result in enlarged and misshapen bones. The excessive breakdown and formation of bone tissue causes affected bone to weaken, resulting in pain, misshapen bones, fractures, and arthritis in the joints near the affected bones...
. In 2007, the U.S. Food and Drug Administration
Food and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
(FDA) also approved Reclast for the treatment of postmenopausal osteoporosis
Osteoporosis
Osteoporosis is a disease of bones that leads to an increased risk of fracture. In osteoporosis the bone mineral density is reduced, bone microarchitecture is deteriorating, and the amount and variety of proteins in bone is altered...
.
Approvals and indications
In all cases administration is by intravenous infusion over a minimum of 15 minutes.Bone complications of cancer
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.
Osteoporosis
As Aclasta (5 mg infusion once per year) for treatment of osteoporosisOsteoporosis
Osteoporosis is a disease of bones that leads to an increased risk of fracture. In osteoporosis the bone mineral density is reduced, bone microarchitecture is deteriorating, and the amount and variety of proteins in bone is altered...
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.
Hypercalcemia of malignancy
Zomera (zoledronic acid for injection) is indicatedIndication (medicine)
In medicine, an indication is a valid reason to use a certain test, medication, procedure, or surgery. The opposite of indication is contraindication.-Drugs:...
for the treatment of hypercalcemia of malignancy.
Multiple myeloma and bone metastases of solid tumors
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.Pagets disease
As Reclast a single dose of 5 mg is used for the treatment of Paget's diseasePaget's disease
Sir James Paget, a surgeon and pathologist, described several diseases, including:* Paget's disease of bone * Paget's disease of the breast* Paget-Schroetter disease* Extramammary Paget's disease...
.
Side effects
Side effects can include fatigueFatigue (physical)
Fatigue is a state of awareness describing a range of afflictions, usually associated with physical and/or mental weakness, though varying from a general state of lethargy to a specific work-induced burning sensation within one's muscles...
, anemia
Anemia
Anemia is a decrease in number of red blood cells or less than the normal quantity of hemoglobin in the blood. However, it can include decreased oxygen-binding ability of each hemoglobin molecule due to deformity or lack in numerical development as in some other types of hemoglobin...
, muscle aches, fever
Fever
Fever is a common medical sign characterized by an elevation of temperature above the normal range of due to an increase in the body temperature regulatory set-point. This increase in set-point triggers increased muscle tone and shivering.As a person's temperature increases, there is, in...
, and/or swelling
Edema
Edema or oedema ; both words from the Greek , oídēma "swelling"), formerly known as dropsy or hydropsy, is an abnormal accumulation of fluid beneath the skin or in one or more cavities of the body that produces 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 kidney
Kidney
The kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...
s; consequently its administration is not recommended for patients with reduced renal function
Renal function
Renal function, in nephrology, is an indication of the state of the kidney and its role in renal physiology. Glomerular filtration rate describes the flow rate of filtered fluid through the kidney...
or kidney disease.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
Food and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
(FDA).
A rare complication that has been recently observed in cancer patients being treated with bisphosphonates is osteonecrosis of the jaw
Osteonecrosis of the jaw
Osteonecrosis of the jaw is a severe bone disease that affects the maxilla and the mandible. Various forms of ONJ have been described over the last 160 years, and a number of causes have been suggested in the literature...
. This has mainly been seen in patients with multiple myeloma
Multiple myeloma
Multiple myeloma , also known as plasma cell myeloma or Kahler's disease , is a cancer of plasma cells, a type of white blood cell normally responsible for the production of antibodies...
treated with zoledronate who have had dental extractions.
Research
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.With hormone therapy for breast cancer
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 anastrozoleAnastrozole
Anastrozole is an aromatase-inhibiting drug approved for treatment of breast cancer after surgery, as well as for metastasis in both pre and post-menopausal women. The severity of breast cancer is increased by estrogen, as sex hormones cause hyperplasia, and differentiation at estrogen receptor...
with zoledronic acid. A retrospective analysis of the AZURE trial data revealed a DFS survival advantage, particularly where estrogen had been reduced.
In a meta-analysis of trials where upfront zoledronic acid was given to prevent aromatase inhibitor
Aromatase inhibitor
Aromatase inhibitors are a class of drugs used in the treatment of breast cancer and ovarian cancer in postmenopausal women. AIs may also be used off-label to treat or prevent gynaecomastia in men....
-associated bone loss, active cancer recurrence appeared to be reduced. 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. Ongoing large trials testing bisphosphonates as adjuvant treatment of breast cancer include NSABP B-34, the NATAN trial, and SWOG-S0307. 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."
Contraindications
- Poor renal function (e.g. CrClRenal functionRenal function, in nephrology, is an indication of the state of the kidney and its role in renal physiology. Glomerular filtration rate describes the flow rate of filtered fluid through the kidney...
<30 mL/min) - Hypocalcemia
- Pregnancy
- Paralysis
External links
- http://www.multiplemyeloma.org/treatments/3.06.html
- http://www.us.zometa.com/info/index.jsp
- http://www.zometa.com/index.jsp
- http://www.reclast.com/