Zoledronic acid: Difference between revisions

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| tradename = Reclast, Zometa, others<ref name=drugs.comINT>{{cite web | work = Drugs.com | url = https://www.drugs.com/international/zoledronic-acid.html | title = International trade names for zoledronic acid | access-date = 14 January 2015 | archive-date = 4 March 2016 | archive-url = https://web.archive.org/web/20160304174708/http://www.drugs.com/international/zoledronic-acid.html | url-status = live }}</ref>

| pregnancy_AU_comment = <ref name="Drugs.com pregnancy">{{cite web | title=Zoledronic acid Use During Pregnancy | website=Drugs.com | date=1 June 2020 | url=https://www.drugs.com/pregnancy/zoledronic-acid.html | access-date=19 October 2020 | archive-date=16 November 2021 | archive-url=https://web.archive.org/web/20211116031757/https://www.drugs.com/pregnancy/zoledronic-acid.html | url-status=live }}</ref>

| pregnancy_US pregnancy_category = D

'''Zoledronic acid''', also known as '''zoledronate''' and sold under the brand name '''Zometa''' among others,<ref name="PR">{{Cite webpress release|title=PRESS RELEASE: Novartis's Reclast Receives FDA Approval FORfor Women With Postmenopausal Osteoporosis|url=https://www.fiercebiotech.com/biotech/press-release-novartis-s-reclast-receives-fda-approval-for-women-postmenopausal|access-date=2 September 2021-09-02|website=FierceBiotech|date=20 August 2007|archive-date=28 March 2018|languagearchive-url=https://web.archive.org/web/20180328102418/https://www.fiercebiotech.com/biotech/press-release-novartis-s-reclast-receives-fda-approval-for-women-postmenopausal|url-status=enlive}}</ref> by [[Novartis]] among others, is a [[medication]] used to treat a number of [[bone disease]]s.<ref name=AHFS2017>{{cite web|title=Zoledronic Acid|url=https://www.drugs.com/monograph/zoledronic-acid.html|publisher=The American Society of Health-System Pharmacists|access-date= 8 December 2017|archive-date=15 December 2017|archive-url=https://web.archive.org/web/20171215143502/https://www.drugs.com/monograph/zoledronic-acid.html|url-status=live}}</ref> These include [[osteoporosis]], [[hypercalcemia|high blood calcium]] due to [[cancer]], [[osteolytic lesion|bone breakdown]] due to cancer, [[Paget's disease of bone]]<ref name="AHFS2017" /> and [[Duchenne muscular dystrophy]] (DMD). It is given by [[intravenous|injection into a vein]].<ref name=AHFS2017/>

Zoledronic acid was patented in 1986 and approved for medical use in the United States in 2001.<ref name=AHFS2017/><ref name=Fis2006>{{cite book | vauthors = Fischer J, Ganellin CR |title=Analogue-based Drug Discovery |date=2006 |publisher=John Wiley & Sons |isbn=9783527607495 |page=524 |url=https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA524 |language=en |access-date=2 June 2020 |archive-date=14 January 2023 |archive-url=https://web.archive.org/web/20230114101028/https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA524 |url-status=live }}</ref> It is on the [[WHO Model List of Essential Medicines|World Health Organization's List of Essential Medicines]].<ref name="WHO21stWHO23rd">{{cite book | vauthors = ((World Health Organization)) | title = WorldThe Healthselection Organizationand model listuse of essential medicines 2023: 21stweb listannex 2019 | year = 2019 | hdl = 10665/325771 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MVP/EMP/IAU/2019.06. LicenseA: CC BY-NC-SA 3.0 IGO | hdl-access=free }}</ref><ref name="WHO22nd">{{cite book | vauthors = ((World Health Organization)) | title = World Health Organization model list of essential medicines: 22nd23rd list (20212023) | year = 20212023 | hdl = 10665/345533371090 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MHP/HPS/EML/20212023.02 | hdl-access=free }}</ref>

Zoledronic acid is used to prevent [[Bone fracture|bone fractures]] in patients with [[cancer]]s such as [[multiple myeloma]] and [[prostate cancer]], as well as for treating [[osteoporosis]].<ref>National Prescribing Service (2009). "Zoledronic Acid for Osteoporosis". ''Medicines Update'', Available at {{cite web|url=http://www.nps.org.au/consumers/publications/medicine_update/issues/Zoledronic_acid |title=Zoledronic acid (Aclasta) for osteoporosis: National Prescribing Service Ltd NPS |access-date=January 20, January 2010 |url-status=dead |archive-url=https://web.archive.org/web/20100423105839/http://www.nps.org.au/consumers/publications/medicine_update/issues/zoledronic_acid |archive-date=April 23, April 2010 }}</ref> It can also be used to treat [[hypercalcemia|hypercalcaemia]] of malignancy and can be helpful for treating pain from [[Bone metastasis|bone metastases]].<ref name=zomera>{{cite web | title = Zomera prescribing information | url = https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021223s028lbl.pdf | work = Novartis Pharmaceuticals Corporation | publisher = U.S. Food and Drug Administration | date = April 2014 | access-date = 10 October 2023 | archive-date = 19 June 2022 | archive-url = https://web.archive.org/web/20220619191125/http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021223s028lbl.pdf | url-status = live }}</ref>

Zoledronic acid, inis brandused namefor productsthe '''Aclasta'''treatment of [[osteoporosis]] in men and '''Reclast'''post-menopausal amongwomen others,at increased risk of fracture.<ref>{{cite journal | vauthors = Dhillon S | title = Zoledronic Acid (Reclast^®, Aclasta^®): A Review in Osteoporosis | journal = Drugs | volume = 76 | issue = 17 | pages = 1683–1697 | date = November 2016 | pmid = 27864686 | doi = 10.1007/s40265-016-0662-4 | s2cid = 22079489 }}</ref> may be given as a 5&nbsp;mg infusion once per year for treatment of [[osteoporosis]] in men and post-menopausal women at increased risk of fracture.<ref name="Lyles">{{cite journal | vauthors = Lyles KW, Colón-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 | display-authors = 6 | title = Zoledronic acid and clinical fractures and mortality after hip fracture | journal = The New England Journal of Medicine | volume = 357 | issue = 18 | pages = 1799–1809 | date = November 2007 | pmid = 17878149 | pmc = 2324066 | doi = 10.1056/NEJMoa074941 }}</ref>

In 2007, the U.S.US [[Food and Drug Administration]] (FDA) also approved itzoledronic acid for the treatment of postmenopausal [[osteoporosis]].<ref>{{cite press release | url name="PR" https://www.fiercebiotech.com/biotech/press-release-novartis-s-reclast-receives-fda-approval-for-women-postmenopausal | title = Biotech PRESS RELEASE: Novartis's Reclast Receives FDA Approval FOR Women With Postmenopausal Osteoporosis | publisher = FierceBiotech, A Division of Questex A FierceMarkets Publication | date = August 20, 2007 | access-date = 2018-03-27}}</ref><ref name="black">{{cite journal | vauthors = Black DM, Delmas PD, Eastell R, Reid IR, Boonen S, Cauley JA, Cosman F, Lakatos P, Leung PC, Man Z, Mautalen C, Mesenbrink P, Hu H, Caminis J, Tong K, Rosario-Jansen T, Krasnow J, Hue TF, Sellmeyer D, Eriksen EF, Cummings SR | display-authors = 6 | title = Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis | journal = The New England Journal of Medicine | volume = 356 | issue = 18 | pages = 1809–1822 | date = May 2007 | pmid = 17476007 | doi = 10.1056/nejmoa067312 | s2cid = 71443125 | doi-access = free }}</ref>

There is a risk of severe renal impairment. Appropriate hydration is important before administration, as is adequate [[calcium]] and [[vitamin D]] intake before Aclasta therapy in patients with [[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.<ref>{{Cite web | url=http://www.nps.org.au/__data/assets/pdf_file/0006/60945/nvcaclin.pdf | title=NPS MedicineWise | access-date=2014-01-25 January 2014 | archive-url=https://web.archive.org/web/20160304042644/http://www.nps.org.au/__data/assets/pdf_file/0006/60945/nvcaclin.pdf | archive-date=4 March 2016-03-04 | url-status=dead }}</ref>

Zoledronate is rapidly processed via the [[kidney]]s; consequently its administration is not recommended for patients with reduced [[renal function]] or kidney disease.<ref>{{cite web|url=http://emc.medicines.org.uk/medicine/14062/SPC/Zometa+4mg+5ml+Concentrate+for+Solution+for+Infusion/|title=Zometa 4mg/5ml Concentrate for Solution for Infusion|work=medicines.org.uk|access-date=2010-02-24 February 2010|archive-url=https://web.archive.org/web/20100224070712/http://www.emc.medicines.org.uk/medicine/14062/SPC/Zometa%204mg%205ml%20Concentrate%20for%20Solution%20for%20Infusion|archive-date=2010-02-24 February 2010|url-status=dead}}</ref> 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).<ref>{{cite web|url=https://www.drugs.com/fda/reclast-zoledronic-acid-safety-communication-new-updated-warning-kidney-impairment-13020.html|title=FDA Alert: Reclast (zoledronic acid): Drug Safety Communication - New Contraindication and Updated Warning on Kidney Impairment|work=drugs.com|access-date=23 January 2018|archive-date=3 March 2016|archive-url=https://web.archive.org/web/20160303233016/http://www.drugs.com/fda/reclast-zoledronic-acid-safety-communication-new-updated-warning-kidney-impairment-13020.html|url-status=live}}</ref> 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.<ref>{{cite web|url=http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/000595/smops/Positive/human_smop_000319.jsp&mid=WC0b01ac058001d127|title=European Medicines Agency - Human medicines|work=europa.eu|access-date=3 April 2012-04-03|archive-date=2015-09-25 September 2015|archive-url=https://web.archive.org/web/20150925101429/http://www.ema.europa.eu/ema/index.jsp?curl=pages%2Fmedicines%2Fhuman%2Fmedicines%2F000595%2Fsmops%2FPositive%2Fhuman_smop_000319.jsp&mid=WC0b01ac058001d127|url-status=dead}}</ref>

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 extraction]]s.<ref>{{cite journal | vauthors = Durie BG, Katz M, Crowley J | title = Osteonecrosis of the jaw and bisphosphonates | journal = The New England Journal of Medicine | volume = 353 | issue = 1 | pages = 99–102; discussion 99–102 | date = July 2005 | pmid = 16000365 | doi = 10.1056/NEJM200507073530120 | url = https://dipot.ulb.ac.be/dspace/bitstream/2013/357907/3/nejm200507073530120.pdf | access-date = 25 June 2023 | archive-date = 21 August 2023 | archive-url = https://web.archive.org/web/20230821192750/https://dipot.ulb.ac.be/dspace/bitstream/2013/357907/3/nejm200507073530120.pdf | url-status = live }}</ref>

After approving the drug on 8in July 2009, the [[European Medicines Agency]] conducted a class review of all [[bisphosphonates]], including zoledronic acid, after several cases of atypical fractures were reported.<ref name="ema.europa.eu">{{cite web|url=http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/public_health_alerts/2011/04/human_pha_detail_000027.jsp&mid=WC0b01ac058001d126|title=European Medicines Agency - Human medicines|work=europa.eu|access-date=3 April 2012-04-03|archive-date=19 January 2013-01-19|archive-url=https://web.archive.org/web/20130119221003/http://www.ema.europa.eu/ema/index.jsp?curl=pages%2Fmedicines%2Fhuman%2Fpublic_health_alerts%2F2011%2F04%2Fhuman_pha_detail_000027.jsp&mid=WC0b01ac058001d126|url-status=dead}}</ref> 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.<ref name="ema.europa.eu"/>

As a [[bisphosphonates#Nitrogenous|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]].<ref>{{Cite web |url=http://www.nps.org.au/__data/assets/pdf_file/0006/60945/nvcaclin.pdf |title=Aclasta label- Australia |access-date=2014-01-25 January 2014 |archive-url=https://web.archive.org/web/20160304042644/http://www.nps.org.au/__data/assets/pdf_file/0006/60945/nvcaclin.pdf |archive-date=4 March 2016-03-04 |url-status=dead }}</ref>

|+Relative potency<ref>{{Cite book|title=Essentials of medical pharmacology | vauthors = Tripathi KD |isbn=9789350259375 |edition= Seventh|location=New Delhi | publisher = Jaypee Brothers Medical Publishers, Ltd. |oclc=868299888|date = 2013-09-30 September 2013}}</ref>