Zoledronic acid

Source: Wikipedia, the free encyclopedia.
Zoledronic acid
Clinical data
Trade namesReclast, Zometa, others[1]
Other nameszoledronate
AHFS/Drugs.comMonograph
MedlinePlusa605023
License data
Pregnancy
category
Routes of
administration		Intravenous
Drug classBisphosphonate[3]
ATC code
Legal status
Legal status
Pharmacokinetic data
Protein binding22%
MetabolismNil
Elimination half-life146 hours
ExcretionKidney (partial)
Identifiers
  • [1-hydroxy-2-(1H-imidazol-1-yl)ethane-1,1-diyl]bis(phosphonic acid)
JSmol)
  • O=P(O)(O)C(O)(Cn1ccnc1)P(=O)(O)O
  • InChI=1S/C5H10N2O7P2/c8-5(15(9,10)11,16(12,13)14)3-7-2-1-6-4-7/h1-2,4,8H,3H2,(H2,9,10,11)(H2,12,13,14)
  • Key:XRASPMIURGNCCH-UHFFFAOYSA-N
 ☒NcheckY (what is this?)  (verify)

Zoledronic acid, also known as zoledronate and sold under the brand name Zometa

injection into a vein.[3]

Common side effects include

osteoclast cells and thus decreases the breakdown of bone.[3]

Zoledronic acid was patented in 1986 and approved for medical use in the United States in 2001.[3][5] It is on the World Health Organization's List of Essential Medicines.[6][7]

Medical uses

Bone complications of cancer

Zoledronic acid is used to prevent

hypercalcaemia of malignancy and can be helpful for treating pain from bone metastases.[9]

It can be given at home rather than in hospital. Such use has shown safety and quality-of-life benefits in people with breast cancer and bone metastases.[10]

Osteoporosis

Zoledronic acid, in brand name products Aclasta and Reclast among others,[11] may be given as a 5 mg infusion once per year for treatment of osteoporosis in men and post-menopausal women at increased risk of fracture.[12]

In 2007, the U.S. Food and Drug Administration (FDA) also approved it for the treatment of postmenopausal osteoporosis.[13][14]

Other

Zoledronic acid may be used for treatment of osteogenesis imperfecta.[15]

A single 5 mg dose of zoledronic acid is used for the treatment of Paget's disease.[medical citation needed][16]

Contraindications

Side effects

Side effects can include

gamma delta T cell
(γδ T cells).

Kidneys

There is a risk of severe renal impairment. Appropriate hydration is important before administration, as is adequate

hypocalcaemia, and for ten days following Aclasta in patients with Paget's disease of the bone. Monitoring for other mineral metabolism disorders and the avoidance of invasive dental procedures for those who develop osteonecrosis of the jaw is recommended.[18]

Zoledronate is rapidly processed via the

renal function or kidney disease.[19] Some cases of acute kidney injury either requiring dialysis or having a fatal outcome following Reclast use have been reported to the U.S. Food and Drug Administration (FDA).[20] This assessment was confirmed by the European Medicines Agency (EMA), whose Committee for Medicinal Products for Human Use (CHMP) specified new contraindications for the medication on 15 December 2011, which include hypocalcaemia and severe renal impairment with a creatinine clearance of less than 35 ml/min.[21]

Bone

Osteonecrosis of the jaw

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 zoledronic acid who have had dental extractions.[22]

Atypical fractures

After approving the drug on 8 July 2009, the

bisphosphonates, including zoledronic acid, after several cases of atypical fractures were reported.[23] In 2008, the EMA's Pharmacovigilance Working Party (PhVWP) noted that alendronic acid was associated with an increased risk of atypical fracture of the femur that developed with low or no trauma. In April 2010, the PhVWP noted that further data from both the published literature and post-marketing reports were now available which suggested that atypical stress fractures of the femur may be a class effect. The European Medicines Agency then reviewed all case reports of stress fractures in patients treated with bisphosphonates, relevant data from the published literature, and data provided by the companies which market bisphosphonates. The Agency recommended that doctors who prescribe bisphosphonate-containing medicines should be aware that atypical fractures may occur rarely in the femur, especially after long-term use, and that doctors who are prescribing these medicines for the prevention or treatment of osteoporosis should regularly review the need for continued treatment, especially after five or more years of use.[23]

Pharmacology

As a

nitrogenous bisphosphonate, zoledronic acid is a potent inhibitor of bone resorption, allowing the bone-forming cells time to rebuild normal bone and allowing bone remodeling.[24]
[25]

Relative potency[26]
Bisphosphonate Relative potency
Etidronate 1
Tiludronate 10
Pamidronate 100
Alendronate 100-500
Ibandronate 500-1000
Risedronate 1000
Zoledronate 5000

Research

Zoledronic acid has been found to have a direct antitumor effect and to synergistically augment the effects of other antitumor agents in osteosarcoma cells.[27]

Zoledronic acid has shown significant benefits versus placebo over three years, with a reduced number of

vertebral fractures and improved markers of bone density.[28][14] An annual dose of zoledronic acid may also prevent recurring fractures in patients with a previous hip fracture.[12]

Zoledronic acid also attenuates accumulation of

DNA damage in mesenchymal stem cells and protects their function.[29]

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 anastrozole with zoledronic acid.[30] A retrospective analysis of the AZURE trial data revealed a DFS survival advantage, particularly where estrogen had been reduced.[31]

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.[32]

As of 2010 "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 mechanism of action and antitumoral activity of bisphosphonates."[33]

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".[34]

References

  1. ^ "International trade names for zoledronic acid". Drugs.com. Retrieved 14 January 2015.
  2. ^ a b "Zoledronic acid Use During Pregnancy". Drugs.com. 1 June 2020. Retrieved 19 October 2020.
  3. ^ a b c d e f g h i j "Zoledronic Acid". The American Society of Health-System Pharmacists. Retrieved 8 December 2017.
  4. ^ "PRESS RELEASE: Novartis's Reclast Receives FDA Approval FOR Women With Postmenopausal Osteoporosis". FierceBiotech. 20 August 2007. Retrieved 2021-09-02.
  5. ISBN 9783527607495
    .
  6. hdl:10665/325771
    . WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
  7. hdl:10665/345533
    . WHO/MHP/HPS/EML/2021.02.
  8. ^ National Prescribing Service (2009). "Zoledronic Acid for Osteoporosis". Medicines Update, Available at "Zoledronic acid (Aclasta) for osteoporosis: National Prescribing Service Ltd NPS". Archived from the original on April 23, 2010. Retrieved January 20, 2010.
  9. ^ "Zomera prescribing information" (PDF). Novartis Pharmaceuticals Corporation. U.S. Food and Drug Administration. April 2014.
  10. PMID 15870721
    .
  11. S2CID 22079489
    .
  12. ^
    PMID 17878149
    .
  13. ^ "Biotech PRESS RELEASE: Novartis's Reclast Receives FDA Approval FOR Women With Postmenopausal Osteoporosis" (Press release). FierceBiotech, A Division of Questex A FierceMarkets Publication. August 20, 2007. Retrieved 2018-03-27.
  14. ^
    S2CID 71443125
    .
  15. PMID 27760454
    .
  16. ^ "Paget's Disease of Bone". www.rheumatology.org. Retrieved 2015-07-09.
  17. PMID 20332498
    .
  18. ^ "NPS MedicineWise" (PDF). Archived from the original (PDF) on 2016-03-04. Retrieved 2014-01-25.
  19. ^ "Zometa 4mg/5ml Concentrate for Solution for Infusion". medicines.org.uk. Archived from the original on 2010-02-24. Retrieved 2010-02-24.
  20. ^ "FDA Alert: Reclast (zoledronic acid): Drug Safety Communication - New Contraindication and Updated Warning on Kidney Impairment". drugs.com.
  21. ^ "European Medicines Agency - Human medicines". europa.eu. Archived from the original on 2015-09-25. Retrieved 2012-04-03.
  22. PMID 16000365
    .
  23. ^ a b "European Medicines Agency - Human medicines". europa.eu. Archived from the original on 2013-01-19. Retrieved 2012-04-03.
  24. ^ "Aclasta label- Australia" (PDF). Archived from the original (PDF) on 2016-03-04. Retrieved 2014-01-25.
  25. ^ "Bisphosphonates". International Osteoporosis Foundation. Retrieved 30 July 2022.
  26. OCLC 868299888
    .
  27. PMID 20514467
    .
  28. PMID 11870242
    .
  29. PMID 26679354
    .
  30. PMID 19213681
    .
  31. PMID 20234364
    .
  32. S2CID 23710758
    .
  33. S2CID 26073229
    .
  34. PMID 20705558
    .

External links
Retrieved from "https://en.wikipedia.org/w/index.php?title=Zoledronic_acid&oldid=1216013249"