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Details

Stereochemistry ACHIRAL
Molecular Formula C5H10N2O7P2
Molecular Weight 272.0899
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ZOLEDRONIC ACID ANHYDROUS

SMILES

c1cn(CC(O)(P(=O)(O)O)P(=O)(O)O)cn1

InChI

InChIKey=XRASPMIURGNCCH-UHFFFAOYSA-N
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)

HIDE SMILES / InChI
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.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Zometa

Approved Use

INDICATIONS AND USAGE Hypercalcemia of Malignancy. Zometa® (zoledronic acid for injection) is indicated for the treatment of hypercalcemia of malignancy. Vigorous saline hydration, an integral part of hypercalcemia therapy, should be initiated promptly and an attempt should be made to restore the urine output to about 2 L/day throughout treatment. Mild or asymptomatic hypercalcemia may be treated with conservative measures (i.e., saline hydration, with or without loop diuretics). Patients should be hydrated dequately throughout the treatment, but overhydration, especially in those patients who have cardiac failure, must be avoided. Diuretic therapy should not be employed prior to correction of hypovolemia. The safety and efficacy of Zometa in the treatment of hypercalcemia associated with hyperparathyroidism or with other non-tumor-related conditions has not been established. Multiple Myeloma and Bone Metastases of Solid Tumors. Zometa is indicated for the treatment of patients with multiple myeloma and patients with documented bone metastases from solid tumors, in conjunction with standard antineoplastic therapy. Prostate cancer should have progressed after treatment with at least one hormonal therapy

Launch Date

998179200000
Primary
Zometa

Approved Use

INDICATIONS AND USAGE Hypercalcemia of Malignancy. Zometa® (zoledronic acid for injection) is indicated for the treatment of hypercalcemia of malignancy. Vigorous saline hydration, an integral part of hypercalcemia therapy, should be initiated promptly and an attempt should be made to restore the urine output to about 2 L/day throughout treatment. Mild or asymptomatic hypercalcemia may be treated with conservative measures (i.e., saline hydration, with or without loop diuretics). Patients should be hydrated dequately throughout the treatment, but overhydration, especially in those patients who have cardiac failure, must be avoided. Diuretic therapy should not be employed prior to correction of hypovolemia. The safety and efficacy of Zometa in the treatment of hypercalcemia associated with hyperparathyroidism or with other non-tumor-related conditions has not been established. Multiple Myeloma and Bone Metastases of Solid Tumors. Zometa is indicated for the treatment of patients with multiple myeloma and patients with documented bone metastases from solid tumors, in conjunction with standard antineoplastic therapy. Prostate cancer should have progressed after treatment with at least one hormonal therapy

Launch Date

998179200000
Primary
Zometa

Approved Use

INDICATIONS AND USAGE Hypercalcemia of Malignancy. Zometa® (zoledronic acid for injection) is indicated for the treatment of hypercalcemia of malignancy. Vigorous saline hydration, an integral part of hypercalcemia therapy, should be initiated promptly and an attempt should be made to restore the urine output to about 2 L/day throughout treatment. Mild or asymptomatic hypercalcemia may be treated with conservative measures (i.e., saline hydration, with or without loop diuretics). Patients should be hydrated dequately throughout the treatment, but overhydration, especially in those patients who have cardiac failure, must be avoided. Diuretic therapy should not be employed prior to correction of hypovolemia. The safety and efficacy of Zometa in the treatment of hypercalcemia associated with hyperparathyroidism or with other non-tumor-related conditions has not been established. Multiple Myeloma and Bone Metastases of Solid Tumors. Zometa is indicated for the treatment of patients with multiple myeloma and patients with documented bone metastases from solid tumors, in conjunction with standard antineoplastic therapy. Prostate cancer should have progressed after treatment with at least one hormonal therapy

Launch Date

998179200000
Primary
Zometa

Approved Use

INDICATIONS AND USAGE Hypercalcemia of Malignancy. Zometa® (zoledronic acid for injection) is indicated for the treatment of hypercalcemia of malignancy. Vigorous saline hydration, an integral part of hypercalcemia therapy, should be initiated promptly and an attempt should be made to restore the urine output to about 2 L/day throughout treatment. Mild or asymptomatic hypercalcemia may be treated with conservative measures (i.e., saline hydration, with or without loop diuretics). Patients should be hydrated dequately throughout the treatment, but overhydration, especially in those patients who have cardiac failure, must be avoided. Diuretic therapy should not be employed prior to correction of hypovolemia. The safety and efficacy of Zometa in the treatment of hypercalcemia associated with hyperparathyroidism or with other non-tumor-related conditions has not been established. Multiple Myeloma and Bone Metastases of Solid Tumors. Zometa is indicated for the treatment of patients with multiple myeloma and patients with documented bone metastases from solid tumors, in conjunction with standard antineoplastic therapy. Prostate cancer should have progressed after treatment with at least one hormonal therapy

Launch Date

998179200000
Primary
Zometa

Approved Use

INDICATIONS AND USAGE Hypercalcemia of Malignancy. Zometa® (zoledronic acid for injection) is indicated for the treatment of hypercalcemia of malignancy. Vigorous saline hydration, an integral part of hypercalcemia therapy, should be initiated promptly and an attempt should be made to restore the urine output to about 2 L/day throughout treatment. Mild or asymptomatic hypercalcemia may be treated with conservative measures (i.e., saline hydration, with or without loop diuretics). Patients should be hydrated dequately throughout the treatment, but overhydration, especially in those patients who have cardiac failure, must be avoided. Diuretic therapy should not be employed prior to correction of hypovolemia. The safety and efficacy of Zometa in the treatment of hypercalcemia associated with hyperparathyroidism or with other non-tumor-related conditions has not been established. Multiple Myeloma and Bone Metastases of Solid Tumors. Zometa is indicated for the treatment of patients with multiple myeloma and patients with documented bone metastases from solid tumors, in conjunction with standard antineoplastic therapy. Prostate cancer should have progressed after treatment with at least one hormonal therapy

Launch Date

998179200000
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
264 ng/mL
4 mg single, intravenous
dose: 4 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
ZOLEDRONIC ACID plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
420 ng × h/mL
4 mg single, intravenous
dose: 4 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
ZOLEDRONIC ACID plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
39 h
4 mg single, intravenous
dose: 4 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
ZOLEDRONIC ACID plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
16 mg 1 times / 4 weeks multiple, intravenous
Highest studied dose
Dose: 16 mg, 1 times / 4 weeks
Route: intravenous
Route: multiple
Dose: 16 mg, 1 times / 4 weeks
Sources:
unhealthy, 40-79 years
Health Status: unhealthy
Age Group: 40-79 years
Sex: M+F
Sources:
16 mg single, intravenous
Highest studied dose
Dose: 16 mg
Route: intravenous
Route: single
Dose: 16 mg
Sources:
unhealthy, 54 years (range: 34–73 years)
Health Status: unhealthy
Age Group: 54 years (range: 34–73 years)
Sex: M+F
Sources:
Other AEs: Skeletal pain, Fever...
Other AEs:
Skeletal pain (30%)
Fever (20%)
Anorexia (20%)
Diarrhea (20%)
Constipation (10%)
Nausea (20%)
Myalgia (20%)
Arthralgia (10%)
Anemia (30%)
Rigors (20%)
Coughing (20%)
Leg edema (10%)
Urinary tract infection (10%)
Fatigue (40%)
Sources:
AEs

AEs

AESignificanceDosePopulation
Arthralgia 10%
16 mg single, intravenous
Highest studied dose
Dose: 16 mg
Route: intravenous
Route: single
Dose: 16 mg
Sources:
unhealthy, 54 years (range: 34–73 years)
Health Status: unhealthy
Age Group: 54 years (range: 34–73 years)
Sex: M+F
Sources:
Constipation 10%
16 mg single, intravenous
Highest studied dose
Dose: 16 mg
Route: intravenous
Route: single
Dose: 16 mg
Sources:
unhealthy, 54 years (range: 34–73 years)
Health Status: unhealthy
Age Group: 54 years (range: 34–73 years)
Sex: M+F
Sources:
Leg edema 10%
16 mg single, intravenous
Highest studied dose
Dose: 16 mg
Route: intravenous
Route: single
Dose: 16 mg
Sources:
unhealthy, 54 years (range: 34–73 years)
Health Status: unhealthy
Age Group: 54 years (range: 34–73 years)
Sex: M+F
Sources:
Urinary tract infection 10%
16 mg single, intravenous
Highest studied dose
Dose: 16 mg
Route: intravenous
Route: single
Dose: 16 mg
Sources:
unhealthy, 54 years (range: 34–73 years)
Health Status: unhealthy
Age Group: 54 years (range: 34–73 years)
Sex: M+F
Sources:
Anorexia 20%
16 mg single, intravenous
Highest studied dose
Dose: 16 mg
Route: intravenous
Route: single
Dose: 16 mg
Sources:
unhealthy, 54 years (range: 34–73 years)
Health Status: unhealthy
Age Group: 54 years (range: 34–73 years)
Sex: M+F
Sources:
Coughing 20%
16 mg single, intravenous
Highest studied dose
Dose: 16 mg
Route: intravenous
Route: single
Dose: 16 mg
Sources:
unhealthy, 54 years (range: 34–73 years)
Health Status: unhealthy
Age Group: 54 years (range: 34–73 years)
Sex: M+F
Sources:
Diarrhea 20%
16 mg single, intravenous
Highest studied dose
Dose: 16 mg
Route: intravenous
Route: single
Dose: 16 mg
Sources:
unhealthy, 54 years (range: 34–73 years)
Health Status: unhealthy
Age Group: 54 years (range: 34–73 years)
Sex: M+F
Sources:
Fever 20%
16 mg single, intravenous
Highest studied dose
Dose: 16 mg
Route: intravenous
Route: single
Dose: 16 mg
Sources:
unhealthy, 54 years (range: 34–73 years)
Health Status: unhealthy
Age Group: 54 years (range: 34–73 years)
Sex: M+F
Sources:
Myalgia 20%
16 mg single, intravenous
Highest studied dose
Dose: 16 mg
Route: intravenous
Route: single
Dose: 16 mg
Sources:
unhealthy, 54 years (range: 34–73 years)
Health Status: unhealthy
Age Group: 54 years (range: 34–73 years)
Sex: M+F
Sources:
Nausea 20%
16 mg single, intravenous
Highest studied dose
Dose: 16 mg
Route: intravenous
Route: single
Dose: 16 mg
Sources:
unhealthy, 54 years (range: 34–73 years)
Health Status: unhealthy
Age Group: 54 years (range: 34–73 years)
Sex: M+F
Sources:
Rigors 20%
16 mg single, intravenous
Highest studied dose
Dose: 16 mg
Route: intravenous
Route: single
Dose: 16 mg
Sources:
unhealthy, 54 years (range: 34–73 years)
Health Status: unhealthy
Age Group: 54 years (range: 34–73 years)
Sex: M+F
Sources:
Anemia 30%
16 mg single, intravenous
Highest studied dose
Dose: 16 mg
Route: intravenous
Route: single
Dose: 16 mg
Sources:
unhealthy, 54 years (range: 34–73 years)
Health Status: unhealthy
Age Group: 54 years (range: 34–73 years)
Sex: M+F
Sources:
Skeletal pain 30%
16 mg single, intravenous
Highest studied dose
Dose: 16 mg
Route: intravenous
Route: single
Dose: 16 mg
Sources:
unhealthy, 54 years (range: 34–73 years)
Health Status: unhealthy
Age Group: 54 years (range: 34–73 years)
Sex: M+F
Sources:
Fatigue 40%
16 mg single, intravenous
Highest studied dose
Dose: 16 mg
Route: intravenous
Route: single
Dose: 16 mg
Sources:
unhealthy, 54 years (range: 34–73 years)
Health Status: unhealthy
Age Group: 54 years (range: 34–73 years)
Sex: M+F
Sources:
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer


Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
no
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
no
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Metastatic bone disease and tumour-induced hypercalcaemia: the role of bisphosphonates.
2001 Jun
FDA grants priority review for ZOMETA.
2001 Oct
Bisphosphonates in the treatment of metastatic breast cancer.
2001 Oct
The use of zoledronic acid, a novel, highly potent bisphosphonate, for the treatment of hypercalcemia of malignancy.
2002
The new bisphosphonate, Zometa (zoledronic acid), decreases skeletal complications in both osteolytic and osteoblastic lesions: a comparison to pamidronate.
2002
U.S. Food and Drug Administration drug approval summaries: imatinib mesylate, mesna tablets, and zoledronic acid.
2002
The role of bisphosphonates in breast cancer management: review article.
2002
FDA approves ZOMETA for treatment of cancer-related bone complications.
2002 Apr
Bisphosphonates: biological response modifiers in breast cancer.
2002 Aug
Highly potent geminal bisphosphonates. From pamidronate disodium (Aredia) to zoledronic acid (Zometa).
2002 Aug 15
Advances in the biology and treatment of myeloma bone disease.
2002 Dec
The anti-tumour activity of bisphosphonates.
2002 Dec
Disease modifying and anti-nociceptive effects of the bisphosphonate, zoledronic acid in a model of bone cancer pain.
2002 Dec
Monosodium [1-hydroxy-2-(1H-imidazol-3-ium-4-yl)ethane-1,1-diyl]bis(phosphonate) tetrahydrate (monosodium isozoledronate).
2002 Dec
Pharmacological treatments for prostate cancer.
2002 Dec
The role of osteoclastic activity in prostate cancer skeletal metastases.
2002 Feb
Distinct mechanisms of bisphosphonate action between osteoblasts and breast cancer cells: identity of a potent new bisphosphonate analogue.
2002 Feb
The effects of local administration of Zoledronate solution on the tooth movement and periodontal ligament.
2002 Jul
New drugs 2002, part III.
2002 Jul
Osteoporosis: challenges and new opportunities for therapy.
2002 Jul
Bisphosphonates for cancer patients: why, how, and when?
2002 Jul
Zoledronate once-yearly increases bone mineral density--implications for osteoporosis.
2002 Jul
Adaptive dose finding for phase I clinical trials of drugs used for chemotherapy of cancer.
2002 Jul 15
An investigation of bone resorption and Dictyostelium discoideum growth inhibition by bisphosphonate drugs.
2002 Jul 4
Electrolyte abnormalities with zoledronic acid therapy.
2002 Jul-Aug
Zoledronic acid. A bisphosphonate for hypercalcemia of malignancy and osteolytic metastases.
2002 Jul-Aug
Novel approaches to the management of bone metastases in patients with breast cancer.
2002 Jun
Bisphosphonates influence the proliferation and the maturation of normal human osteoblasts.
2002 Jun
Bisphosphonates and osteoporosis.
2002 Jun 27
Bisphosphonates inhibit stromelysin-1 (MMP-3), matrix metalloelastase (MMP-12), collagenase-3 (MMP-13) and enamelysin (MMP-20), but not urokinase-type plasminogen activator, and diminish invasion and migration of human malignant and endothelial cell lines.
2002 Mar
Treatment of malignant hypercalcaemia.
2002 May
The bisphosphonate zoledronic acid impairs Ras membrane [correction of impairs membrane] localisation and induces cytochrome c release in breast cancer cells.
2002 May 6
Pharmacokinetics and pharmacodynamics of zoledronic acid in cancer patients with bone metastases.
2002 Nov
Severe increase in creatinine with hypocalcaemia in thalidomide-treated myeloma patients receiving zoledronic acid infusions.
2002 Nov
Pamidronate causes apoptosis of plasma cells in vivo in patients with multiple myeloma.
2002 Nov
Bisphosphonates inhibit angiogenesis in vitro and testosterone-stimulated vascular regrowth in the ventral prostate in castrated rats.
2002 Nov 15
Development and validation of a highly sensitive RIA for zoledronic acid, a new potent heterocyclic bisphosphonate, in human serum, plasma and urine.
2002 Nov 7
The use of bisphosphonates in patients with breast cancer.
2002 Nov-Dec
Bisphosphonate therapy in multiple myeloma: past, present, future.
2002 Nov-Dec
Zoledronic acid improves the mechanical properties of normal and healing bone.
2002 Nov-Dec
Zoledronic acid.
2002 Nov-Dec
Gateways to clinical trials.
2002 Oct
Zoledronic acid: new preparation. Just a me-too: no advance in hypercalcemia of malignancy.
2002 Oct
Intravenous zoledronic acid in postmenopausal women with low bone mineral density.
2002 Oct
The IL-6 receptor super-antagonist Sant7 enhances antiproliferative and apoptotic effects induced by dexamethasone and zoledronic acid on multiple myeloma cells.
2002 Oct
Use of zoledronate to treat osteoblastic versus osteolytic lesions in a severe-combined-immunodeficient mouse model.
2002 Oct 1
A randomized, placebo-controlled trial of zoledronic acid in patients with hormone-refractory metastatic prostate carcinoma.
2002 Oct 2
Novel antiangiogenic effects of the bisphosphonate compound zoledronic acid.
2002 Sep
American Society of Clinical Oncology clinical practice guidelines: the role of bisphosphonates in multiple myeloma.
2002 Sep 1
[Bisphosphonates in bone metastases. Fewer fractures, less pain].
2002 Sep 26
Patents

Patents

Sample Use Guides

The maximum recommended dose of Zometa in hypercalcemia of malignancy is 4 mg. The 4 mg dose must be given as a single-dose intravenous infusion over no less than 15 minutes.
Route of Administration: Intravenous
For the transfection of the T24 human bladder cancer cells, pCMV6 empty vector (OriGene, Rockville, MD, USA) and pCMV6 TAp73 vector were transfected into cells using Lipofectamine™ 2000 (Invitrogen Life Technologies). After 6 h, the medium was refreshed and cultured for 48 h. Then the cells were treated with ZA (200 μM).
Name Type Language
ZOLEDRONIC ACID ANHYDROUS
Common Name English
PHOSPHONIC ACID, (1-HYDROXY-2-(1H-IMIDAZOL-1-YL)ETHYLIDENE)BIS-
Common Name English
ANHYDROUS ZOLEDRONIC ACID
Common Name English
(1-HYDROXY-2-IMIDAZOL-1-YLETHYLIDENE)DIPHOSPHONIC ACID
Systematic Name English
ZOLEDRONIC ACID [INN]
Common Name English
ZOLEDRONIC ACID [WHO-DD]
Common Name English
NSC-721517
Code English
ZOLEDRONIC ACID [MI]
Common Name English
ZOLEDRONATE
Common Name English
Classification Tree Code System Code
NDF-RT N0000175579
Created by admin on Fri Jun 25 21:48:50 UTC 2021 , Edited by admin on Fri Jun 25 21:48:50 UTC 2021
WHO-ATC M05BA08
Created by admin on Fri Jun 25 21:48:50 UTC 2021 , Edited by admin on Fri Jun 25 21:48:50 UTC 2021
FDA ORPHAN DRUG 130899
Created by admin on Fri Jun 25 21:48:50 UTC 2021 , Edited by admin on Fri Jun 25 21:48:50 UTC 2021
NCI_THESAURUS C443
Created by admin on Fri Jun 25 21:48:50 UTC 2021 , Edited by admin on Fri Jun 25 21:48:50 UTC 2021
NDF-RT N0000007707
Created by admin on Fri Jun 25 21:48:50 UTC 2021 , Edited by admin on Fri Jun 25 21:48:50 UTC 2021
Code System Code Type Description
FDA UNII
70HZ18PH24
Created by admin on Fri Jun 25 21:48:50 UTC 2021 , Edited by admin on Fri Jun 25 21:48:50 UTC 2021
PRIMARY
RXCUI
1546014
Created by admin on Fri Jun 25 21:48:50 UTC 2021 , Edited by admin on Fri Jun 25 21:48:50 UTC 2021
PRIMARY RxNorm
EPA CompTox
118072-93-8
Created by admin on Fri Jun 25 21:48:50 UTC 2021 , Edited by admin on Fri Jun 25 21:48:50 UTC 2021
PRIMARY
INN
7254
Created by admin on Fri Jun 25 21:48:50 UTC 2021 , Edited by admin on Fri Jun 25 21:48:50 UTC 2021
PRIMARY
MERCK INDEX
M11658
Created by admin on Fri Jun 25 21:48:50 UTC 2021 , Edited by admin on Fri Jun 25 21:48:50 UTC 2021
PRIMARY Merck Index
EVMPD
SUB00176MIG
Created by admin on Fri Jun 25 21:48:50 UTC 2021 , Edited by admin on Fri Jun 25 21:48:50 UTC 2021
PRIMARY
CAS
118072-93-8
Created by admin on Fri Jun 25 21:48:50 UTC 2021 , Edited by admin on Fri Jun 25 21:48:50 UTC 2021
PRIMARY
NCI_THESAURUS
C80120
Created by admin on Fri Jun 25 21:48:50 UTC 2021 , Edited by admin on Fri Jun 25 21:48:50 UTC 2021
PRIMARY
EVMPD
SUB12624MIG
Created by admin on Fri Jun 25 21:48:50 UTC 2021 , Edited by admin on Fri Jun 25 21:48:50 UTC 2021
PRIMARY
DRUG BANK
DB00399
Created by admin on Fri Jun 25 21:48:50 UTC 2021 , Edited by admin on Fri Jun 25 21:48:50 UTC 2021
PRIMARY
PUBCHEM
68740
Created by admin on Fri Jun 25 21:48:50 UTC 2021 , Edited by admin on Fri Jun 25 21:48:50 UTC 2021
PRIMARY