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{{Short description|Chemical compound}}
{{Use dmy dates|date=July 2024}}
{{cs1 config |name-list-style=vanc |display-authors=6}}
{{Drugbox
{{Drugbox
| Verifiedfields = changed
| Verifiedfields = changed
| verifiedrevid = 396274597
| verifiedrevid = 396274597
| image = Zoledronic acid.svg
| image = Zoledronic acid.svg
| width = 180px
| width = 180
| alt =
| image2 = Zoledronic-acid-from-xtal-2003-3D-balls.png
| image2 = Zoledronic-acid-from-xtal-2003-3D-balls.png
| alt2 =


<!--Clinical data-->
<!--Clinical data-->
| tradename = Reclast, Zometa, others<ref name=drugs.comINT>Drugs.com [https://www.drugs.com/international/zoledronic-acid.html International trade names for zoledronic acid] Page accessed Jan 14, 2015</ref>
| 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>
| Drugs.com = {{drugs.com|monograph|zoledronic_acid}}
| Drugs.com = {{drugs.com|monograph|zoledronic_acid}}
| MedlinePlus = a605023
| MedlinePlus = a605023
| licence_EU = yes
| DailyMedID = Zoledronic_acid
| DailyMedID = Zoledronic_acid
| licence_US = Zoledronic_acid
| pregnancy_AU = B3
| pregnancy_AU = B3
| 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}}</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 = D
| pregnancy_category =
| pregnancy_US_comment = <ref name="Drugs.com pregnancy" />
| pregnancy_category=
| dependency_liability =
| addiction_liability =
| routes_of_administration = [[Intravenous therapy|Intravenous]]
| routes_of_administration = [[Intravenous therapy|Intravenous]]
| class = [[Bisphosphonate]]<ref name=AHFS2017/>
| class = [[Bisphosphonate]]<ref name=AHFS2017/>
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| legal_US = Rx-only
| legal_US = Rx-only
| legal_EU = Rx-only
| legal_EU = Rx-only
| legal_EU_comment = <ref>{{cite web | title=Zometa EPAR | website=European Medicines Agency | date=20 March 2001 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/zometa | access-date=5 July 2024 | archive-date=7 June 2023 | archive-url=https://web.archive.org/web/20230607133720/https://www.ema.europa.eu/en/medicines/human/EPAR/zometa | url-status=live }}</ref>


<!--Pharmacokinetic data-->
<!--Pharmacokinetic data-->
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<!-- Definition and medical uses -->
<!-- Definition and medical uses -->
'''Zoledronic acid''', also known as '''zoledronate''' and sold under the brand name '''Zometa'''<ref>{{Cite web|title=PRESS RELEASE: Novartis's Reclast Receives FDA Approval FOR Women With Postmenopausal Osteoporosis|url=https://www.fiercebiotech.com/biotech/press-release-novartis-s-reclast-receives-fda-approval-for-women-postmenopausal|access-date=2021-09-02|website=FierceBiotech|language=en}}</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}}</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''', also known as '''zoledronate''' and sold under the brand name '''Zometa''' among others,<ref name="PR">{{Cite press release|title=Novartis's Reclast Receives FDA Approval for 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|website=FierceBiotech|date=20 August 2007|archive-date=28 March 2018|archive-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=live}}</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/>


<!-- Side effects and mechanisms -->
<!-- Side effects and mechanisms -->
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<!-- History and culture -->
<!-- History and culture -->
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 |last1=Fischer |first1=Jnos |last2=Ganellin |first2=C. Robin |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}}</ref> It is on the [[WHO Model List of Essential Medicines|World Health Organization's List of Essential Medicines]].<ref name="WHO21st">{{cite book | vauthors = ((World Health Organization)) | title = World Health Organization model list of essential medicines: 21st list 2019 | year = 2019 | hdl = 10665/325771 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO | hdl-access=free }}</ref>
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="WHO23rd">{{cite book | vauthors = ((World Health Organization)) | title = The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023) | year = 2023 | hdl = 10665/371090 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MHP/HPS/EML/2023.02 | hdl-access=free }}</ref>


==Medical uses==
==Medical uses==
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===Bone complications of cancer===
===Bone complications of cancer===


Zoledronic acid 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]].<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=Archived copy |access-date=January 20, 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, 2010 }}</ref> It can also be used to treat [[hypercalcemia]] of malignancy and can be helpful for treating pain from bone metastases.<ref name=zomera>http://www.health.gov.il/units/pharmacy/trufot/alonim/533.pdf Zomera prescribing information</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=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=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>


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.<ref>{{cite journal | pmid = 15870721 | doi=10.1038/sj.bjc.6602551 | volume=92 | issue=10 | title=Zoledronic acid significantly improves pain scores and quality of life in breast cancer patients with bone metastases: a randomised, crossover study of community vs hospital bisphosphonate administration | pmc=2361764 | date=May 2005 | journal=Br. J. Cancer | pages=1869–76 | vauthors=Wardley A, Davidson N, Barrett-Lee P, Hong A, Mansi J, Dodwell D, Murphy R, Mason T, Cameron D | display-authors = 6 }}</ref>
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.<ref>{{cite journal | vauthors = Wardley A, Davidson N, Barrett-Lee P, Hong A, Mansi J, Dodwell D, Murphy R, Mason T, Cameron D | display-authors = 6 | title = Zoledronic acid significantly improves pain scores and quality of life in breast cancer patients with bone metastases: a randomised, crossover study of community vs hospital bisphosphonate administration | journal = British Journal of Cancer | volume = 92 | issue = 10 | pages = 1869–1876 | date = May 2005 | pmid = 15870721 | pmc = 2361764 | doi = 10.1038/sj.bjc.6602551 }}</ref>


===Osteoporosis===
===Osteoporosis===
Zoledronic acid, in brand name products '''Aclasta''' and '''Reclast''' among others,<ref>{{cite-web |url=https://pubmed.ncbi.nlm.nih.gov/27864686/ |title=Zoledronic Acid (Reclast®, Aclasta®): A Review in Osteoporosis |pmid=27864686}}</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 K, etal |title=Zoledronic Acid and Clinical Fractures and Mortality after Hip Fracture |journal=N. Engl. J. Med. |volume= 357|issue= 18|pages= 1799–809|year=2007 |pmid=17878149|doi=10.1056/NEJMoa074941|pmc=2324066}}</ref>
Zoledronic acid, in brand name products '''Aclasta''' and '''Reclast''' among others,<ref>{{cite journal | vauthors = Dhillon S | title = Zoledronic Acid (Reclast<sup>®</sup>, Aclasta<sup>®</sup>): 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. [[Food and Drug Administration]] (FDA) also approved it for the treatment of postmenopausal [[osteoporosis]].<ref>{{cite press release | url = 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 | s2cid = 71443125 | display-authors = 6 | date = May 2007 | title = Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis | journal = N Engl J Med | volume = 356 | issue = 18| pages = 1809–22 | doi=10.1056/nejmoa067312 | pmid=17476007}}</ref>
In 2007, the US [[Food and Drug Administration]] (FDA) also approved it for the treatment of postmenopausal [[osteoporosis]].<ref name="PR" /><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>


===Other===
===Other===


Zoledronic acid may be used for treatment of [[osteogenesis imperfecta]].<ref>{{cite journal |last1=Dwan |first1=K |last2=Phillipi |first2=CA |last3=Steiner |first3=RD |last4=Basel |first4=D |title=Bisphosphonate therapy for osteogenesis imperfecta. |journal=The Cochrane Database of Systematic Reviews |date=19 October 2016 |volume=10 |pages=CD005088 |doi=10.1002/14651858.CD005088.pub4 |pmid=27760454|pmc=6611487 }}</ref>
Zoledronic acid may be used for treatment of [[osteogenesis imperfecta]].<ref>{{cite journal | vauthors = Dwan K, Phillipi CA, Steiner RD, Basel D | title = Bisphosphonate therapy for osteogenesis imperfecta | journal = The Cochrane Database of Systematic Reviews | volume = 2016 | issue = 10 | pages = CD005088 | date = October 2016 | pmid = 27760454 | pmc = 6611487 | doi = 10.1002/14651858.CD005088.pub4 }}</ref>


A single 5&nbsp;mg dose of zoledronic acid is used for the treatment of [[Paget's disease of bone|Paget's disease]].{{mcn|date=January 2014}}<ref>{{Cite web|url = http://www.rheumatology.org/Practice/Clinical/Patients/Diseases_And_Conditions/Paget_s_Disease_of_Bone/|website = www.rheumatology.org|access-date = 2015-07-09|title=Paget's Disease of Bone}}</ref>
A single 5&nbsp;mg dose of zoledronic acid is used for the treatment of [[Paget's disease of bone|Paget's disease]].{{medcn|date=January 2014}}<ref>{{Cite web|url = http://www.rheumatology.org/Practice/Clinical/Patients/Diseases_And_Conditions/Paget_s_Disease_of_Bone/|website = www.rheumatology.org|access-date = 9 July 2015|title = Paget's Disease of Bone|archive-date = 9 July 2015|archive-url = https://web.archive.org/web/20150709201909/http://www.rheumatology.org/Practice/Clinical/Patients/Diseases_And_Conditions/Paget_s_Disease_of_Bone/|url-status = live}}</ref>


==Contraindications==
==Contraindications==
*Poor renal function (e.g. [[renal function|CrCl]]<30 mL/min)<ref>{{cite journal | last1 = Vondracek | first1 = S. F. | title = Managing osteoporosis in postmenopausal women | journal = American Journal of Health-System Pharmacy | volume = 67 | issue = 7 Suppl 3 | pages = S9–19 | year = 2010 | pmid = 20332498 | doi = 10.2146/ajhp100076 }}</ref>
*Poor [[kidney function]] (e.g. estimated glomerular filtration rate less than 30 mL/min)<ref>{{cite journal | vauthors = Vondracek SF | title = Managing osteoporosis in postmenopausal women | journal = American Journal of Health-System Pharmacy | volume = 67 | issue = 7 Suppl 3 | pages = S9-19 | date = April 2010 | pmid = 20332498 | doi = 10.2146/ajhp100076 }}</ref>
*[[Hypocalcaemia]]
*[[Hypocalcaemia]]
*Pregnancy
*Pregnancy
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==Side effects==
==Side effects==
Side effects can include [[fatigue (physical)|fatigue]], [[anemia]], [[muscle pain|muscle aches]], [[fever]], and/or [[Edema|swelling]] in the feet or legs. [[Flu-like symptoms]] are common after the first infusion, although not subsequent infusions, and are thought to occur because of its potential to activate human [[γδ T cells]] (gamma/delta T cells).
Side effects can include [[fatigue (physical)|fatigue]], [[anemia]], [[muscle pain|muscle aches]], [[fever]], and/or [[Edema|swelling]] in the feet or legs. [[Flu-like symptoms]] are common after the first infusion, although not subsequent infusions, and are thought to occur because of its potential to activate human [[γδ T cells|gamma delta T cell]] (γδ T cells).


===Kidneys===
===Kidneys===
There is a risk of severe renal impairment. Appropriate [[Fluid replacement|hydration]] is important prior to administration, as is adequate [[calcium]] and [[vitamin D]] intake prior to Aclasta therapy in patients with preexisting [[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 | archive-url=https://web.archive.org/web/20160304042644/http://www.nps.org.au/__data/assets/pdf_file/0006/60945/nvcaclin.pdf | archive-date=2016-03-04 | url-status=dead }}</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=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 | 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|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|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}}</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}}</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=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=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|archive-date=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>


===Bone===
===Bone===
====Osteonecrosis of the jaw====
====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 extraction]]s.<ref>{{cite journal |vauthors=Durie BG, Katz M, Crowley J |title=Osteonecrosis of the jaw and bisphosphonates |journal=N. Engl. J. Med. |volume=353 |issue=1 |pages=99–102; discussion 99–102 |year=2005 |pmid=16000365 |doi=10.1056/NEJM200507073530120}}</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>


====Atypical fractures====
====Atypical fractures====
After approving the drug on 8 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}}</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"/>
After approving the drug in 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|archive-date=19 January 2013|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"/>


==Pharmacology==
==Pharmacology==
Zoledronic acid slows down [[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 |archive-url=https://web.archive.org/web/20160304042644/http://www.nps.org.au/__data/assets/pdf_file/0006/60945/nvcaclin.pdf |archive-date=2016-03-04 |url-status=dead }}</ref>
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=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 |url-status=dead }}</ref>
<ref>{{cite web |url=https://www.osteoporosis.foundation/health-professionaBisphosphonatesls/treatment/bisphosphonates |title=Bisphosphonates |date= |website=International Osteoporosis Foundation |access-date=30 July 2022 |quote= }}{{Dead link|date=July 2024 |bot=InternetArchiveBot |fix-attempted=yes }}</ref>


{| class="wikitable"
{| class="wikitable"
|+Relative potency<ref>{{Cite book|title=Essentials of medical pharmacology|last=D.|first=Tripathi, K.|isbn=9789350259375|edition= Seventh|location=New Delhi|oclc=868299888|date = 2013-09-30}}</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 = 30 September 2013}}</ref>
!Bisphosphonate
!Bisphosphonate
!Relative potency
!Relative potency
Line 141: Line 142:


==Research==
==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.<ref>{{cite journal | pmid = 20514467 | volume=24 | issue=1 | title=Zoledronic acid inhibits proliferation of human fibrosarcoma cells with induction of apoptosis, and shows combined effects with other anticancer agents |date=July 2010 | journal=Oncol. Rep. | pages=233–9 |vauthors=Koto K, Murata H, Kimura S, etal | doi=10.3892/or_00000851| doi-access=free }}</ref>
Zoledronic acid has been found to have a direct antitumor effect and to synergistically augment the effects of other antitumor agents in [[osteosarcoma]] cells.<ref>{{cite journal | vauthors = Koto K, Murata H, Kimura S, Horie N, Matsui T, Nishigaki Y, Ryu K, Sakabe T, Itoi M, Ashihara E, Maekawa T, Fushiki S, Kubo T | display-authors = 6 | title = Zoledronic acid inhibits proliferation of human fibrosarcoma cells with induction of apoptosis, and shows combined effects with other anticancer agents | journal = Oncology Reports | volume = 24 | issue = 1 | pages = 233–239 | date = July 2010 | pmid = 20514467 | doi = 10.3892/or_00000851 | doi-access = free }}</ref>


Zoledronic acid has shown significant benefits versus placebo over three years, with a reduced number of [[vertebral fracture]]s and improved markers of bone density.<ref>{{cite journal |vauthors=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 |title=Intravenous zoledronic acid in postmenopausal women with low bone mineral density |journal=N. Engl. J. Med. |volume=346 |issue=9 |pages=653–61 |year=2002 |pmid=11870242 |doi=10.1056/NEJMoa011807}}</ref><ref name="black"/> An annual dose of zoledronic acid may also prevent recurring fractures in patients with a previous hip fracture.<ref name="Lyles"/>
Zoledronic acid has shown significant benefits versus placebo over three years, with a reduced number of [[vertebral fracture]]s and improved markers of bone density.<ref>{{cite journal | vauthors = 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 | display-authors = 6 | title = Intravenous zoledronic acid in postmenopausal women with low bone mineral density | journal = The New England Journal of Medicine | volume = 346 | issue = 9 | pages = 653–661 | date = February 2002 | pmid = 11870242 | doi = 10.1056/NEJMoa011807 | doi-access = free }}</ref><ref name="black"/> An annual dose of zoledronic acid may also prevent recurring fractures in patients with a previous hip fracture.<ref name="Lyles"/>

Zoledronic acid also attenuates accumulation of [[DNA damage]] in [[mesenchymal stem cell]]s and protects their function.<ref>{{Cite journal | doi=10.1002/stem.2255| pmid=26679354| pmc=4832316|title = Zoledronate Attenuates Accumulation of DNA Damage in Mesenchymal Stem Cells and Protects Their Function| journal=Stem Cells| volume=34| issue=3| pages=756–767|year = 2016|last1 = Misra|first1 = Juhi| last2=Mohanty| first2=Sindhu T.| last3=Madan| first3=Sanjeev| last4=Fernandes| first4=James A.| last5=Hal Ebetino| first5=F.| last6=Russell| first6=R. Graham G.| last7=Bellantuono| first7=Ilaria}}</ref>


===With hormone therapy for breast cancer===
===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.<ref>{{cite journal | pmid = 19213681 | doi=10.1056/NEJMoa0806285 | volume=360 | title=Endocrine therapy plus zoledronic acid in premenopausal breast cancer | date=February 2009 | journal=N. Engl. J. Med. | pages=679–91 | vauthors=Gnant M, Mlineritsch B, Schippinger W, Luschin-Ebengreuth G, Pöstlberger S, Menzel C, Jakesz R, Seifert M, Hubalek M, Bjelic-Radisic V, Samonigg H, Tausch C, Eidtmann H, Steger G, Kwasny W, Dubsky P, Fridrik M, Fitzal F, Stierer M, Rücklinger E, Greil R, Marth C | issue=7 | display-authors = 6 }}</ref> A retrospective analysis of the AZURE trial data revealed a DFS survival advantage, particularly where estrogen had been reduced.<ref>{{cite journal |vauthors=Coleman RE, Winter MC, Cameron D, etal |title=The effects of adding zoledronic acid to neoadjuvant chemotherapy on tumour response: exploratory evidence for direct anti-tumour activity in breast cancer |journal=Br. J. Cancer |volume=102 |issue=7 |pages=1099–105 |date=March 2010 |pmid=20234364 |pmc=2853093 |doi=10.1038/sj.bjc.6605604 }}</ref>
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.<ref>{{cite journal | vauthors = Gnant M, Mlineritsch B, Schippinger W, Luschin-Ebengreuth G, Pöstlberger S, Menzel C, Jakesz R, Seifert M, Hubalek M, Bjelic-Radisic V, Samonigg H, Tausch C, Eidtmann H, Steger G, Kwasny W, Dubsky P, Fridrik M, Fitzal F, Stierer M, Rücklinger E, Greil R, Marth C | display-authors = 6 | title = Endocrine therapy plus zoledronic acid in premenopausal breast cancer | journal = The New England Journal of Medicine | volume = 360 | issue = 7 | pages = 679–691 | date = February 2009 | pmid = 19213681 | doi = 10.1056/NEJMoa0806285 | doi-access = free }}</ref> A retrospective analysis of the AZURE trial data revealed a DFS survival advantage, particularly where estrogen had been reduced.<ref>{{cite journal | vauthors = Coleman RE, Winter MC, Cameron D, Bell R, Dodwell D, Keane MM, Gil M, Ritchie D, Passos-Coelho JL, Wheatley D, Burkinshaw R, Marshall SJ, Thorpe H | display-authors = 6 | title = The effects of adding zoledronic acid to neoadjuvant chemotherapy on tumour response: exploratory evidence for direct anti-tumour activity in breast cancer | journal = British Journal of Cancer | volume = 102 | issue = 7 | pages = 1099–1105 | date = March 2010 | pmid = 20234364 | pmc = 2853093 | doi = 10.1038/sj.bjc.6605604 }}</ref>
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.<ref name="pmid18515735">{{cite journal | pmid = 18515735 | doi=10.1634/theoncologist.2007-0206 | volume=13 | issue=5 | title=Integrated analysis of zoledronic acid for prevention of aromatase inhibitor-associated bone loss in postmenopausal women with early breast cancer receiving adjuvant letrozole |date=May 2008 | journal=Oncologist | pages=503–14 |vauthors=Brufsky A, Bundred N, Coleman R, etal }}</ref>
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.<ref name="pmid18515735">{{cite journal | vauthors = Brufsky A, Bundred N, Coleman R, Lambert-Falls R, Mena R, Hadji P, Jin L, Schenk N, Ericson S, Perez EA | display-authors = 6 | title = Integrated analysis of zoledronic acid for prevention of aromatase inhibitor-associated bone loss in postmenopausal women with early breast cancer receiving adjuvant letrozole | journal = The Oncologist | volume = 13 | issue = 5 | pages = 503–514 | date = May 2008 | pmid = 18515735 | doi = 10.1634/theoncologist.2007-0206 | s2cid = 23710758 }}</ref>
{{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."<ref>{{cite journal | pmid = 20977404 | doi=10.1517/14656566.2010.523699 | volume=11 | issue=16 | title=The role of zoledronic acid in the adjuvant treatment of breast cancer: current perspectives |date=November 2010 | journal=Expert Opin Pharmacother | pages=2715–25 |vauthors=Tonyali O, Arslan C, Altundag K | s2cid=26073229 }}</ref>
{{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."<ref>{{cite journal | vauthors = Tonyali O, Arslan C, Altundag K | title = The role of zoledronic acid in the adjuvant treatment of breast cancer: current perspectives | journal = Expert Opinion on Pharmacotherapy | volume = 11 | issue = 16 | pages = 2715–2725 | date = November 2010 | pmid = 20977404 | doi = 10.1517/14656566.2010.523699 | s2cid = 26073229 }}</ref>


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".<ref>{{cite journal | pmid = 20705558 | doi=10.3816/CBC.2010.n.034 | volume=10 | issue=4 | title=Cost-effectiveness of zoledronic acid plus endocrine therapy in premenopausal women with hormone-responsive early breast cancer |date=August 2010 | journal=Clin. Breast Cancer | pages=267–74 |vauthors=Delea TE, Taneja C, Sofrygin O, Kaura S, Gnant M }}</ref>
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".<ref>{{cite journal | vauthors = Delea TE, Taneja C, Sofrygin O, Kaura S, Gnant M | title = Cost-effectiveness of zoledronic acid plus endocrine therapy in premenopausal women with hormone-responsive early breast cancer | journal = Clinical Breast Cancer | volume = 10 | issue = 4 | pages = 267–274 | date = August 2010 | pmid = 20705558 | doi = 10.3816/CBC.2010.n.034 }}</ref>


==References==
== References ==
{{Reflist}}
{{Reflist}}

== External links ==
* {{cite web | url = https://druginfo.nlm.nih.gov/drugportal/name/zoledronic%20acid%20monohydrate | publisher = U.S. National Library of Medicine | work = Drug Information Portal | title = Zoledronic acid }}


{{Bisphosphonates}}
{{Bisphosphonates}}
{{Portal bar | Medicine}}
{{Portal bar | Medicine}}
{{Authority control}}


{{DEFAULTSORT:Zoledronic Acid}}
{{DEFAULTSORT:Zoledronic Acid}}
[[Category:Bisphosphonates]]
[[Category:Bisphosphonates]]
[[Category:Farnesyl pyrophosphate synthase inhibitors]]
[[Category:Farnesyl pyrophosphate synthase inhibitors]]
[[Category:Novartis brands]]
[[Category:Drugs developed by Novartis]]
[[Category:Imidazoles]]
[[Category:Imidazoles]]
[[Category:World Health Organization essential medicines]]
[[Category:World Health Organization essential medicines]]

Revision as of 19:18, 5 July 2024

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)
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
PDB ligand
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC5H10N2O7P2
Molar mass272.090 g·mol−1
3D model (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 among others,[5] by Novartis among others, is a medication used to treat a number of bone diseases.[3] These include osteoporosis, high blood calcium due to cancer, bone breakdown due to cancer, Paget's disease of bone[3] and Duchenne muscular dystrophy (DMD). It is given by injection into a vein.[3]

Common side effects include fever, joint pain, high blood pressure, diarrhea, and feeling tired.[3] Serious side effects may include kidney problems, low blood calcium, and osteonecrosis of the jaw.[3] Use during pregnancy may result in harm to the baby.[3] It is in the bisphosphonate family of medications.[3] It works by blocking the activity of 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][6] It is on the World Health Organization's List of Essential Medicines.[7]

Medical uses

Bone complications of cancer

Zoledronic acid is used to prevent bone fractures in patients with cancers such as multiple myeloma and prostate cancer, as well as for treating osteoporosis.[8] It can also be used to treat 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 US Food and Drug Administration (FDA) also approved it for the treatment of postmenopausal osteoporosis.[5][13]

Other

Zoledronic acid may be used for treatment of osteogenesis imperfecta.[14]

A single 5 mg dose of zoledronic acid is used for the treatment of Paget's disease.[medical citation needed][15]

Contraindications

Side effects

Side effects can include fatigue, anemia, muscle aches, fever, and/or swelling in the feet or legs. Flu-like symptoms are common after the first infusion, although not subsequent infusions, and are thought to occur because of its potential to activate human 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 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.[17]

Zoledronate is rapidly processed via the kidneys; consequently its administration is not recommended for patients with reduced renal function or kidney disease.[18] 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).[19] 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.[20]

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.[21]

Atypical fractures

After approving the drug in July 2009, the European Medicines Agency conducted a class review of all bisphosphonates, including zoledronic acid, after several cases of atypical fractures were reported.[22] 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.[22]

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.[23] [24]

Relative potency[25]
Bisphosphonate Relative potency
Etidronate 1
Tiludronate 10
Pamidronate 100
Alendronate 100-500
Ibandronate 500-1000
Risedronate 1000
Zoledronate 5000

Forschung

Zoledronic acid has been found to have a direct antitumor effect and to synergistically augment the effects of other antitumor agents in osteosarcoma cells.[26]

Zoledronic acid has shown significant benefits versus placebo over three years, with a reduced number of vertebral fractures and improved markers of bone density.[27][13] An annual dose of zoledronic acid may also prevent recurring fractures in patients with a previous hip fracture.[12]

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.[28] A retrospective analysis of the AZURE trial data revealed a DFS survival advantage, particularly where estrogen had been reduced.[29]

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.[30]

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."[31]

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".[32]

References

  1. ^ "International trade names for zoledronic acid". Drugs.com. Archived from the original on 4 March 2016. Retrieved 14 January 2015.
  2. ^ "Zoledronic acid Use During Pregnancy". Drugs.com. 1 June 2020. Archived from the original on 16 November 2021. Retrieved 19 October 2020.
  3. ^ a b c d e f g h i j "Zoledronic Acid". The American Society of Health-System Pharmacists. Archived from the original on 15 December 2017. Retrieved 8 December 2017.
  4. ^ "Zometa EPAR". European Medicines Agency. 20 March 2001. Archived from the original on 7 June 2023. Retrieved 5 July 2024.
  5. ^ a b "Novartis's Reclast Receives FDA Approval for Women With Postmenopausal Osteoporosis". FierceBiotech (Press release). 20 August 2007. Archived from the original on 28 March 2018. Retrieved 2 September 2021.
  6. ^ Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 524. ISBN 9783527607495. Archived from the original on 14 January 2023. Retrieved 2 June 2020.
  7. ^ World Health Organization (2023). The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023). Geneva: World Health Organization. hdl:10665/371090. WHO/MHP/HPS/EML/2023.02.
  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 23 April 2010. Retrieved 20 January 2010.
  9. ^ "Zomera prescribing information" (PDF). Novartis Pharmaceuticals Corporation. U.S. Food and Drug Administration. April 2014. Archived (PDF) from the original on 19 June 2022. Retrieved 10 October 2023.
  10. ^ Wardley A, Davidson N, Barrett-Lee P, Hong A, Mansi J, Dodwell D, et al. (May 2005). "Zoledronic acid significantly improves pain scores and quality of life in breast cancer patients with bone metastases: a randomised, crossover study of community vs hospital bisphosphonate administration". British Journal of Cancer. 92 (10): 1869–1876. doi:10.1038/sj.bjc.6602551. PMC 2361764. PMID 15870721.{{cite journal}}: CS1 maint: overridden setting (link)
  11. ^ Dhillon S (November 2016). "Zoledronic Acid (Reclast®, Aclasta®): A Review in Osteoporosis". Drugs. 76 (17): 1683–1697. doi:10.1007/s40265-016-0662-4. PMID 27864686. S2CID 22079489.
  12. ^ a b Lyles KW, Colón-Emeric CS, Magaziner JS, Adachi JD, Pieper CF, Mautalen C, et al. (November 2007). "Zoledronic acid and clinical fractures and mortality after hip fracture". The New England Journal of Medicine. 357 (18): 1799–1809. doi:10.1056/NEJMoa074941. PMC 2324066. PMID 17878149.{{cite journal}}: CS1 maint: overridden setting (link)
  13. ^ a b Black DM, Delmas PD, Eastell R, Reid IR, Boonen S, Cauley JA, et al. (May 2007). "Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis". The New England Journal of Medicine. 356 (18): 1809–1822. doi:10.1056/nejmoa067312. PMID 17476007. S2CID 71443125.{{cite journal}}: CS1 maint: overridden setting (link)
  14. ^ Dwan K, Phillipi CA, Steiner RD, Basel D (October 2016). "Bisphosphonate therapy for osteogenesis imperfecta". The Cochrane Database of Systematic Reviews. 2016 (10): CD005088. doi:10.1002/14651858.CD005088.pub4. PMC 6611487. PMID 27760454.
  15. ^ "Paget's Disease of Bone". www.rheumatology.org. Archived from the original on 9 July 2015. Retrieved 9 July 2015.
  16. ^ Vondracek SF (April 2010). "Managing osteoporosis in postmenopausal women". American Journal of Health-System Pharmacy. 67 (7 Suppl 3): S9-19. doi:10.2146/ajhp100076. PMID 20332498.
  17. ^ "NPS MedicineWise" (PDF). Archived from the original (PDF) on 4 March 2016. Retrieved 25 January 2014.
  18. ^ "Zometa 4mg/5ml Concentrate for Solution for Infusion". medicines.org.uk. Archived from the original on 24 February 2010. Retrieved 24 February 2010.
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