zoledronic acid
Trade name: zometa
Approved
Aug 20, 2001
Zoledronic acid (Reclast, Aclasta, Zometa) is an intravenous, highly potent amino-bisphosphonate approved worldwide, including in the USA, EU and Japan for use in patients with primary or secondary osteoporosis or low bone mass (approved indications vary between countries). Its high affinity to and long half-life in bone, and long duration of action allow for once-yearly administration, which has the potential to improve adherence to therapy. Zoledronic acid once yearly for up to 3 years improved bone mineral density (BMD) at several skeletal sites, reduced fracture risk and bone turnover, and/or preserved bone structure and mass relative to placebo in clinical studies in patients with primary or secondary osteoporosis. While additional benefits were seen when treatment was continued for up to 6 years, as evidenced by a reduced risk of vertebral fractures and higher BMD relative to 3 years’ therapy, there was the minimal advantage of treatment beyond 6 years. Therefore, in patients with low fracture risk, treatment discontinuation should be considered after approximately 5 years’ therapy. Zoledronic acid administered annually or once in 2 years was also effective in preventing bone loss in patients with low bone mass. Zoledronic acid was generally well tolerated, with the most common adverse events (AEs) being transient, mild-to-moderate post-infusion symptoms, which decreased with subsequent infusions. — NCATS
Clinical trial activity
349 trials · 274 clinical orgs · 37 marketing orgs
Earliest trial started Aug 1, 1998 (NCT00003884)
Timeline
1990s
2000s
2010s
- Jan 25, 2010
Hospira — NDA Secondary Org
- Sep 27, 2011
Dr. Reddy's Laboratories — Marketing Organization
- Mar 4, 2013
Mylan — Marketing Organization
- Mar 4, 2013
Sun Pharmaceuticals — Marketing Organization
- Mar 4, 2013
Esteve Labs — Marketing Organization
- Mar 4, 2013
Actavis — Marketing Organization
- Mar 12, 2013
Emcure — Marketing Organization
- Mar 12, 2013
Avet Lifesciences — Marketing Organization
- May 7, 2013
Pharmaceutics International, Inc. — Marketing Organization
- May 7, 2013
Chartwell Pharmaceuticals — Marketing Organization
- Jun 3, 2013
Hikma — Marketing Organization
- Aug 2, 2013
Inforlife — NDA Secondary Org
- Aug 5, 2013
Gland Pharma Ltd — Marketing Organization
- Sep 23, 2013
Inforlife — Marketing Organization
- May 22, 2014
Epic Pharma Llc — Marketing Organization
- May 29, 2014
Cipla — Marketing Organization
- Aug 21, 2014
Akorn, Inc. — Marketing Organization
- Sep 4, 2014
USV — Marketing Organization
- Nov 24, 2014
Sagent Pharmaceuticals, Inc. — Marketing Organization
- Mar 19, 2015
Hospira — Marketing Organization
- Apr 23, 2015
Fresenius — Marketing Organization
- Dec 28, 2015
Pfizer — NDA Secondary Org
- Feb 9, 2016
Pfizer — Marketing Organization
- Sep 26, 2016
Aurobindo Pharma — Marketing Organization
- Sep 26, 2016
Eugia Pharma — Marketing Organization
- Nov 28, 2016
Accord Research — Marketing Organization
- Oct 27, 2017
Puniska — Marketing Organization
- Oct 27, 2017
Amneal Pharmaceuticals — Marketing Organization
- Dec 29, 2017
BPI — Marketing Organization
- Jun 29, 2018
Fosun — Marketing Organization
- May 15, 2019
Shilpa Medicare Ltd. — Marketing Organization
2020s
- Feb 19, 2020
Ingenus Pharmaceuticals — Marketing Organization
- Feb 19, 2020
Novast Labs — Marketing Organization
- Jun 5, 2023
Meitheal — Marketing Organization
- Jun 5, 2023
Eu Yan Sang — Marketing Organization
Indications
Approved for
Studied for
- Adenocarcinoma · Phase 1
- Alveolar Bone Loss · Phase 4
- Amenorrhea · Phase 3
- Anemia, Sickle Cell · Phase 1/Phase 2
- Ankle Joint · Phase 4
- Anterior Cruciate Ligament Injuries · Phase 1
- Arthritis, Rheumatoid · Phase 3
- Arthroplasty · Phase 4
- Ascites · Phase 1/Phase 2
- Bariatric Surgery · Phase 4
- beta-Thalassemia · Phase 3
- Bone Density · Phase 4
- Bone Diseases · Phase 4
- Bone Diseases, Metabolic · Phase 4
- Bone Marrow Diseases · Phase 3
- Bone Marrow Transplantation · Phase 2/Phase 3
- Bone Neoplasms · Phase 4
- Bone Resorption · Phase 2/Phase 3
- Brain Neoplasms · Phase 2
- Breast Diseases · Phase 2
- Breast Neoplasms · Phase 4
- Carcinoma, Ductal · Phase 2
- Carcinoma, Hepatocellular · Phase 3
- Carcinoma, Intraductal, Noninfiltrating · Phase 2
- Carcinoma, Non-Small-Cell Lung · Phase 4
- Carcinoma, Renal Cell · Phase 4
- Charcot-Marie-Tooth Disease · Phase 2/Phase 3
- Chondrosarcoma · Phase 1
- Chordoma · Phase 1/Phase 2
- Chronic Kidney Disease-Mineral and Bone Disorder · Phase 4
- Chronic Periodontitis · Phase 4
- Complex Regional Pain Syndromes · Phase 3
- Critical Illness · Phase 2
- Crohn Disease · Phase 3
- Cystic Fibrosis · Phase 4
- Denosumab · Phase 4
- Desmoplastic Small Round Cell Tumor · Phase 1/Phase 2
- Diabetes Complications · Phase 2/Phase 3
- Drugs, Investigational · Phase 4
- Drug Therapy · Phase 2
- Esophageal Neoplasms · Phase 1
- Fallopian Tubes · Early Phase 1
- Femur Head Necrosis · Phase 3
- Fractures, Bone · Phase 4
- Functional Status · Phase 3
- Gastrointestinal Neoplasms · Phase 2
- Genes, erbB-2 · Phase 2
- Giant Cell Tumor of Bone · Phase 3
- Hamartoma · Early Phase 1
- Healthy Volunteers · Phase 1
- Heart Transplantation · Phase 2/Phase 3
- Hematologic Diseases · Phase 1
- Hematologic Neoplasms · Phase 3
- Hematopoietic Stem Cell Transplantation · Phase 1
- Hereditary Breast and Ovarian Cancer Syndrome · Phase 2
- Hip Fractures · Phase 4
- HIV · Phase 4
- HIV Infections · Phase 4
- Hodgkin Disease · Phase 1
- Hyperparathyroidism, Primary · Phase 4
- Hypocalcemia · Phase 4
- Intraocular Pressure · Phase 2
- Kidney Neoplasms · Phase 2
- Leiomyosarcoma · Phase 2
- Leukemia · Phase 2
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive · Phase 2
- Leukemia, Myeloid, Acute · Phase 1
- Lewy Body Disease · Phase 4
- Liver Transplantation · Phase 4
- Low Back Pain · Phase 2
- Lung Neoplasms · Phase 4
- Lung Transplantation · Phase 4
- Lymphoma · Phase 3
- Lymphoma, Non-Hodgkin · Phase 3
- Macular Degeneration · Phase 2
- Mesothelioma · Phase 2
- Multiple Sclerosis · Phase 3
- Multiple System Atrophy · Phase 4
- Muscular Atrophy · Phase 2
- Musculoskeletal Diseases · Phase 3
- Myelodysplastic Syndromes · Phase 2
- Myeloproliferative Disorders · Phase 1
- Myoepithelioma · Phase 1/Phase 2
- Myositis · Phase 3
- Nasopharyngeal Neoplasms · Phase 2
- Neoplasm Metastasis · Phase 4
- Neoplasms · Phase 4
- Neoplasms by Site · Phase 2
- Nerve Sheath Neoplasms · Phase 1/Phase 2
- Neuroblastoma · Phase 1/Phase 2
- Neuroectodermal Tumors, Primitive · Phase 1
- Orthopedics · Phase 2
- Osteoarthritis · Phase 1
- Osteoarthritis, Hip · Phase 4
- Osteogenesis Imperfecta · Phase 4
- Osteoma, Osteoid · Phase 3
- Osteonecrosis · Phase 2
- Osteoporotic Fractures · Phase 4
- Osteosarcoma · Phase 2/Phase 3
- Ovarian Diseases · Early Phase 1
- Ovarian Neoplasms · Phase 2
- Paget Disease, Extramammary · Phase 4
- Pain · Phase 4
- Pancreatic Neoplasms · Phase 2
- Parkinson Disease · Phase 4
- Parkinsonian Disorders · Phase 4
- Periodontitis · Phase 4
- Plasmacytoma · Phase 3
- Pleural Effusion, Malignant · Phase 4
- Pneumonia · Phase 4
- Postmenopause · Phase 3
- Precancerous Conditions · Phase 2
- Precursor Cell Lymphoblastic Leukemia-Lymphoma · Phase 2
- Primary Myelofibrosis · Phase 2
- Primary Prevention · Phase 3
- Progeria · Phase 2
- Reflex Sympathetic Dystrophy · Phase 3
- Rhabdoid Tumor · Phase 1/Phase 2
- Rhabdomyosarcoma · Phase 1/Phase 2
- Sarcoma · Phase 3
- Sarcoma, Alveolar Soft Part · Phase 1/Phase 2
- Sarcoma, Clear Cell · Phase 1/Phase 2
- Sarcoma, Ewing · Phase 3
- Sarcoma, Synovial · Phase 1/Phase 2
- Sarcopenia · Phase 4
- Skeleton · Phase 4
- Small Cell Lung Carcinoma · Phase 2
- Spinal Cord Injuries · Phase 4
- Spondylolisthesis · Phase 3
- Stomach Neoplasms · Phase 1/Phase 2
- Supranuclear Palsy, Progressive · Phase 4
- Thalassemia · Phase 4
- Traumatology · Phase 2
- Triple Negative Breast Neoplasms · Phase 3
- Urination Disorders · Phase 3
- Urologic Neoplasms · Phase 2
- Uterine Cervical Neoplasms · Phase 2
- Zoledronic Acid · Phase 4
Mechanism of action
- Farnesyl diphosphate synthaseINHIBITOR
FDPS inhibitor
Binds to the bone matrix (hydroxyapatite), and when the bone starts to be reabsorbed the compound is released and taken up by osteoclasts, inhibiting protein prenylation of the GTPases involved in the formation of the ruffled border
Approval history
- approvedPriority reviewAug 20, 2001
Chemistry & pharmacology
SMILES
OC(CN1C=CN=C1)(P(O)(O)=O)P(O)(O)=O- Mol. weight
- 272.0896 g/mol
- Lipinski Ro5
- Pass
- Rule of 3
- No
- Chirality
- Achiral Molecule
- Inorganic
- No
- Polymer
- No
- Delivery
- Parenteral
- Availability
- Prescription Only
Oral
No
Parenteral
Yes
Topical
No
Sources
- WikipediaZoledronic acid ↗
- NCATS70HZ18PH24 ↗
- ChEMBLCHEMBL924 ↗
- ChEMBLCHEMBL4303669 ↗
Also known as
- (1-hydroxy-2-(1h-imidazol-1-yl)ethylidene)bisphosphonic acid
- (1-hydroxy-2-(1h-imidazol-1-yl)ethylidene)bisphosphonic acid
- (1-hydroxy-2-imidazol-1-ylethylidene)diphosphonic acid
- (1-hydroxy-2-imidazol-1-ylethylidene)diphosphonic acid
- 2-(imidazol-1-yl)-1-hydroxyethylidene-1,1-bisphosphonic acid
- aclasta
- aclasta
- ak156
- anhydrous zoledronic acid
- anhydrous zoledronic acid
- cgp 42'446
- cgp-42446
- cgp-42446
- cgp-42446
- cgp-42'446
- cgp 42446a
- jtt305
- jtt 305
- jtt-305
- mk5442
- mk 5442
- mk-5442
- mk-5442
- mk-5442
- novartis brand of zoledronic acid
- reclast
- reclast
- t121
- zerlinda
- zol
- zol
- zoledronate
- zoledronate
- zoledronate
- zoledronate
- zoledronate
- zoledronic acid
- zoledronic acid
- zoledronic acid
- zoledronic acid
- zoledronic acid
- zoledronic acid
- zoledronic acid
- zoledronic acid
- zoledronic acid
- zoledronic acid
- zoledronic acid
- zoledronic acid
- zoledronic acid anhydrous
- zoledronic acid anhydrous
- zoledronic acid, anhydrous
- zoledronic acid, anhydrous
- zoledronic acid hydrate
- zoledronic acid monohydrate
- zoledronic acid monohydrate
- zoledronic acid / zoledronic acid monohydrate
- zometa
- zometa
- zometa
- zometa
- zometa
- zometa
Clinical trials
| NCT ID | Phase | Start date | Sponsor(s) |
|---|---|---|---|
| NCT07281586 | Phase 4 | Jan 1, 2026 | National Taiwan University |
| NCT07056478 | Phase 3 | Jan 1, 2026 | City University of Hong Kong |
| NCT06876636 | N/A | Mar 10, 2025 | Xijing Hospital |
| NCT06859580 | Phase 4 | Mar 1, 2025 | Aarhus University |
| NCT06625190 | Phase 1/Phase 2 (Phase 2) | Feb 28, 2025 | University of Florida |
| NCT06762730 | Phase 4 | Dec 9, 2024 | Hebrew University, Technion University, Tel Aviv University |
| NCT06513624 | Phase 1 | Nov 30, 2024 | A*Star, National University of Singapore |
| NCT06374459 | Phase 1/Phase 2 (Phase 2) | Nov 30, 2024 | Aclaris Therapeutics, Inc., Department of Defense, Washington University in St. Louis |
| NCT06533865 | Phase 3 | Oct 1, 2024 | Harvard University |
| NCT06759064 | Phase 1/Phase 2 (Phase 2) | Sep 12, 2024 | Shandong University |
| NCT06643780 | Phase 4 | Apr 9, 2024 | Chinese University of Hong Kong, City University of Hong Kong |
| NCT06221072 | Phase 3 | Apr 5, 2024 | Shanghai JMT-Bio Inc. |
| NCT06023420 | Phase 1/Phase 2 (Phase 2) | Feb 1, 2024 | Chinese University of Hong Kong |
| NCT06118905 | Phase 4 | Jan 1, 2024 | University of Pittsburgh |
| NCT06135298 | Phase 4 | Dec 1, 2023 | Aksaray University Training and Research Hospital, Lund University |
| NCT05204836 | Phase 1 | Dec 1, 2023 | University of Calgary |
| NCT06059222 | Phase 4 | Oct 2, 2023 | Aarhus University |
| NCT05906056 | N/A | May 12, 2023 | University of Ioannina |
| NCT05866172 | Phase 3 | May 10, 2023 | Sun Yat-Sen University |
| NCT05755854 | Phase 1 | May 3, 2023 | Anhui Medical University |
Organizations
Research & Development (274)
| Organization | Org type | Trials | As lead sponsor | Phases | Earliest year |
|---|---|---|---|---|---|
| Novartis | For profit | 129 | 78 | 5 | 1998 |
| National Cancer Institute (NCI) | Government | 31 | 9 | 4 | 1999 |
| Harvard University | Academic/Hospital | 13 | 10 | 3 | 2001 |
| Amgen | For profit | 11 | 7 | 3 | 2006 |
| Mayo Clinic | Academic/Hospital | 7 | 3 | 3 | 2002 |
| Department of Veteran Affairs | Government | 6 | 2 | 3 | 2004 |
| University of Pittsburgh | Academic/Hospital | 6 | 5 | 2 | 2007 |
| Aarhus University | Academic/Hospital | 5 | 5 | 2 | 2012 |
| National Institute on Aging (NIA) | Government | 5 | 0 | 2 | 2007 |
| Sun Yat-Sen University | Academic/Hospital | 5 | 5 | 4 | 2005 |
| University of California, San Francisco | Academic/Hospital | 5 | 3 | 4 | 2005 |
| University of Ottawa | Academic/Hospital | 5 | 5 | 2 | 2012 |
| University of Texas at Houston | Academic/Hospital | 5 | 5 | 3 | 2004 |
| Chinese University of Hong Kong | Academic/Hospital | 4 | 1 | 3 | 2005 |
| Department of Defense | Government | 4 | 0 | 3 | 2010 |
| National Institutes of Health (NIH) | Government | 4 | 0 | 2 | 2007 |
| Roche | For profit | 4 | 3 | 2 | 2005 |
| University of Alabama, Birmingham | Academic/Hospital | 4 | 3 | 4 | 2005 |
| University of Oslo | Academic/Hospital | 4 | 3 | 3 | 2017 |
| University of Wisconsin | Academic/Hospital | 4 | 4 | 2 | 2000 |
Marketing (51)
| Organization | Org type | Relationship | Date |
|---|---|---|---|
| Accord Research | For profit | MKTG | Nov 28, 2016 |
| Actavis | For profit | MKTG | Mar 4, 2013 |
| Akorn, Inc. | For profit | MKTG | Aug 21, 2014 |
| Akorn, Inc. | For profit | SYN | May 22, 2014 |
| Amneal Pharmaceuticals | For profit | MKTG | Oct 27, 2017 |
| Apotex | For profit | MKTG | Apr 15, 2009 |
| Apotex | For profit | SYN | Dec 24, 2015 |
| Aurobindo Pharma | For profit | MKTG | Sep 26, 2016 |
| Avet Lifesciences | For profit | MKTG | Mar 12, 2013 |
| BPI | For profit | MKTG | Dec 29, 2017 |
| BPI | For profit | SYN | Dec 29, 2017 |
| Chartwell Pharmaceuticals | For profit | MKTG | May 7, 2013 |
| Cipla | For profit | SYN | Oct 27, 2017 |
| Cipla | For profit | MKTG | May 29, 2014 |
| Dr. Reddy's Laboratories | For profit | MKTG | Sep 27, 2011 |
| Dr. Reddy's Laboratories | For profit | SYN | Nov 19, 2018 |
| Emcure | For profit | MKTG | Mar 12, 2013 |
| Epic Pharma Llc | For profit | MKTG | May 22, 2014 |
| Esteve Labs | For profit | SYN | Mar 4, 2013 |
| Esteve Labs | For profit | MKTG | Mar 4, 2013 |
| Eu Yan Sang | For profit | MKTG | Jun 5, 2023 |
| Eugia Pharma | For profit | MKTG | Sep 26, 2016 |
| Fosun | For profit | MKTG | Jun 29, 2018 |
| Fresenius | For profit | MKTG | Apr 23, 2015 |
| Gland Pharma Ltd | For profit | MKTG | Aug 5, 2013 |
| Gland Pharma Ltd | For profit | MKTG | Aug 18, 2016 |
| Hikma | For profit | MKTG | Jun 3, 2013 |
| Hospira | For profit | NDA2 | Jan 25, 2010 |
| Hospira | For profit | MKTG | Mar 19, 2015 |
| Inforlife | For profit | NDA2 | Aug 2, 2013 |
| Inforlife | For profit | MKTG | Sep 23, 2013 |
| Ingenus Pharmaceuticals | For profit | MKTG | Feb 19, 2020 |
| Meitheal | For profit | MKTG | Jun 5, 2023 |
| Mylan | For profit | MKTG | Mar 4, 2013 |
| Novartis | For profit | SYN | Aug 17, 2007 |
| Novartis | For profit | NDA | Aug 20, 2001 |
| Novast Labs | For profit | MKTG | Feb 19, 2020 |
| Pfizer | For profit | MKTG | Feb 9, 2016 |
| Pfizer | For profit | NDA2 | Dec 28, 2015 |
| PharmaForce, Inc | For profit | MKTG | May 20, 2009 |
| Pharmaceutics International, Inc. | For profit | MKTG | May 7, 2013 |
| Puniska | For profit | MKTG | Oct 27, 2017 |
| Sagent Pharmaceuticals, Inc. | For profit | MKTG | Nov 24, 2014 |
| Sagent Pharmaceuticals, Inc. | For profit | SYN | Nov 24, 2014 |
| Sandoz | For profit | MKTG | Apr 16, 2007 |
| Shilpa Medicare Ltd. | For profit | MKTG | May 15, 2019 |
| Shilpa Medicare Ltd. | For profit | MKTG | May 15, 2019 |
| Sun Pharmaceuticals | For profit | MKTG | Mar 4, 2013 |
| Teva | For profit | MKTG | Jun 9, 2009 |
| USV | For profit | SYN | Sep 4, 2014 |
| USV | For profit | MKTG | Sep 4, 2014 |