An official website of the United States government

Goserelin

PubChem CID
5311128
Structure
Goserelin_small.png
Molecular Formula
Synonyms
  • goserelin
  • 65807-02-5
  • Zoladex
  • Decapeptide I
  • Goserelinum
Molecular Weight
1269.4 g/mol
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Dates
  • Create:
    2005-12-16
  • Modify:
    2025-01-10
Description
Goserelin is an organic molecular entity.
Goserelin is a synthetic hormone. In men, it stops the production of the hormone testosterone, which may stimulate the growth of cancer cells. In women, goserelin decreases the production of the hormone estradiol (which may stimulate the growth of cancer cells) to levels similar to a postmenopausal state. When the medication is stopped, hormone levels return to normal.
Goserelin is a Gonadotropin Releasing Hormone Receptor Agonist. The mechanism of action of goserelin is as a Gonadotropin Releasing Hormone Receptor Agonist.
See also: Goserelin Acetate (has salt form).

1 Structures

1.1 2D Structure

Chemical Structure Depiction
Goserelin.png

1.2 3D Status

Conformer generation is disallowed since too many atoms, too flexible

2 Biologic Description

SVG Image
SVG Image
IUPAC Condensed
H-Pyr-His-Trp-Ser-Tyr-D-Ser(tBu)-Leu-Arg-Pro-NHNHCONH2
Sequence
XHWSYXLRP
IUPAC
L-pyroglutamyl-L-histidyl-L-tryptophyl-L-seryl-L-tyrosyl-O-tert-butyl-D-seryl-L-leucyl-L-arginyl-N'-carbamoyl-L-prolinehydrazide

3 Names and Identifiers

3.1 Computed Descriptors

3.1.1 IUPAC Name

(2S)-N-[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2R)-1-[[(2S)-1-[[(2S)-1-[(2S)-2-[(carbamoylamino)carbamoyl]pyrrolidin-1-yl]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-[(2-methylpropan-2-yl)oxy]-1-oxopropan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]-5-oxopyrrolidine-2-carboxamide
Computed by Lexichem TK 2.7.0 (PubChem release 2021.10.14)

3.1.2 InChI

InChI=1S/C59H84N18O14/c1-31(2)22-40(49(82)68-39(12-8-20-64-57(60)61)56(89)77-21-9-13-46(77)55(88)75-76-58(62)90)69-54(87)45(29-91-59(3,4)5)74-50(83)41(23-32-14-16-35(79)17-15-32)70-53(86)44(28-78)73-51(84)42(24-33-26-65-37-11-7-6-10-36(33)37)71-52(85)43(25-34-27-63-30-66-34)72-48(81)38-18-19-47(80)67-38/h6-7,10-11,14-17,26-27,30-31,38-46,65,78-79H,8-9,12-13,18-25,28-29H2,1-5H3,(H,63,66)(H,67,80)(H,68,82)(H,69,87)(H,70,86)(H,71,85)(H,72,81)(H,73,84)(H,74,83)(H,75,88)(H4,60,61,64)(H3,62,76,90)/t38-,39-,40-,41-,42-,43-,44-,45+,46-/m0/s1
Computed by InChI 1.0.6 (PubChem release 2021.10.14)

3.1.3 InChIKey

BLCLNMBMMGCOAS-URPVMXJPSA-N
Computed by InChI 1.0.6 (PubChem release 2021.10.14)

3.1.4 SMILES

CC(C)C[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N1CCC[C@H]1C(=O)NNC(=O)N)NC(=O)[C@@H](COC(C)(C)C)NC(=O)[C@H](CC2=CC=C(C=C2)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC3=CNC4=CC=CC=C43)NC(=O)[C@H](CC5=CN=CN5)NC(=O)[C@@H]6CCC(=O)N6
Computed by OEChem 2.3.0 (PubChem release 2024.12.12)

3.2 Molecular Formula

C59H84N18O14
Computed by PubChem 2.2 (PubChem release 2021.10.14)

3.3 Other Identifiers

3.3.1 CAS

65807-02-5

3.3.2 Deprecated CAS

70280-59-0

3.3.3 European Community (EC) Number

3.3.4 UNII

3.3.5 ChEBI ID

3.3.6 ChEMBL ID

3.3.7 DrugBank ID

3.3.8 DSSTox Substance ID

3.3.9 HMDB ID

3.3.10 KEGG ID

3.3.11 Metabolomics Workbench ID

3.3.12 NCI Thesaurus Code

3.3.13 Nikkaji Number

3.3.14 Pharos Ligand ID

3.3.15 RXCUI

3.3.16 Wikidata

3.3.17 Wikipedia

3.4 Synonyms

3.4.1 MeSH Entry Terms

  • Acetate, Goserelin
  • Goserelin
  • Goserelin Acetate
  • ICI 118630
  • ICI-118630
  • ICI118630
  • Zoladex

3.4.2 Depositor-Supplied Synonyms

4 Chemical and Physical Properties

4.1 Computed Properties

Property Name
Molecular Weight
Property Value
1269.4 g/mol
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
XLogP3-AA
Property Value
-1.5
Reference
Computed by XLogP3 3.0 (PubChem release 2021.10.14)
Property Name
Hydrogen Bond Donor Count
Property Value
17
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Hydrogen Bond Acceptor Count
Property Value
16
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Rotatable Bond Count
Property Value
32
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Exact Mass
Property Value
1268.64143943 Da
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Monoisotopic Mass
Property Value
1268.64143943 Da
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Topological Polar Surface Area
Property Value
496 Ų
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Heavy Atom Count
Property Value
91
Reference
Computed by PubChem
Property Name
Formal Charge
Property Value
0
Reference
Computed by PubChem
Property Name
Complexity
Property Value
2560
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Isotope Atom Count
Property Value
0
Reference
Computed by PubChem
Property Name
Defined Atom Stereocenter Count
Property Value
9
Reference
Computed by PubChem
Property Name
Undefined Atom Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Defined Bond Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Undefined Bond Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Covalently-Bonded Unit Count
Property Value
1
Reference
Computed by PubChem
Property Name
Compound Is Canonicalized
Property Value
Yes
Reference
Computed by PubChem (release 2021.10.14)

4.2 Experimental Properties

4.2.1 Physical Description

Solid

4.2.2 Solubility

Soluble
2.83e-02 g/L

4.2.3 LogP

-2
-2

4.2.4 Other Experimental Properties

Off-white powder. Freely soluble in acetic acid; soluble in water, 0.1M HCl, 0.1M NaCl, dimethylformamide, dimethylsulfoxide. Insoluble in acetone, chloroform, ether. /Acetate/
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 780
Solid. Freely soluble in glacial acetic acid /Acetate/
Wishart DS et al; DrugBank: a comprehensive resource for in silico drug discovery and exploration. Nucleic Acids Res. 2007 Dec 11. Available from, as of May 21, 2008: https://www.drugbank.ca/index.html

4.3 Chemical Classes

4.3.1 Drugs

4.3.1.1 Human Drugs
Human drug -> Prescription
Hormones and antihormones

5 Spectral Information

5.1 Mass Spectrometry

5.1.1 MS-MS

1 of 2
Spectra ID
Ionization Mode
Positive
Top 5 Peaks

1269.65601 100

1226.64648 1.10

Thumbnail
Thumbnail
2 of 2
Spectra ID
Ionization Mode
Negative
Top 5 Peaks

1267.64819 100

1224.61084 1.39

Thumbnail
Thumbnail

5.1.2 LC-MS

1 of 3
View All
MS Category
Experimental
MS Type
LC-MS
MS Level
MS2
Precursor Type
[M-H]-
Precursor m/z
1267.634
Instrument
Thermo Q Exactive HF
Instrument Type
LC-ESI-QFT
Ionization Mode
negative
Collision Energy
HCD (NCE 20-30-40%)
Retention Time
7.831617
Top 5 Peaks

1224.62805 100

1194.61816 73.77

670.27441 72.44

449.26291 70.62

1267.63354 29.74

Thumbnail
Thumbnail
2 of 3
View All
MS Category
Experimental
MS Type
LC-MS
MS Level
MS2
Precursor Type
[M+H]+
Precursor m/z
1269.652
Instrument
SCIEX TripleTOF 6600
Instrument Type
LC-ESI-QTOF
Ionization Mode
positive
Collision Energy
35 eV
Retention Time
7.4844
Top 5 Peaks

1269.65601 100

1226.64648 1.10

1252.61658 0.33

1252.64148 0.30

1265.71362 0.25

Thumbnail
Thumbnail

7 Chemical Vendors

8 Drug and Medication Information

8.1 Drug Indication

Goserelin is indicated for: - Use in combination with flutamide for the management of locally confined carcinoma of the prostate - Palliative treatment of advanced carcinoma of the prostate - The management of endometriosis - Use as an endometrial-thinning agent prior to endometrial ablation for dysfunctional uterine bleeding - Use in the palliative treatment of advanced breast cancer in pre- and perimenopausal women

8.2 LiverTox Summary

Goserelin is a parenterally administered, gonadotropin releasing hormone (GnRH) agonist which causes an inhibition of estrogen and androgen production and is used predominantly to treat prostate cancer. Goserelin has been associated with a modest rate of serum enzyme elevations during therapy, but has not been convincingly linked to instances of clinically apparent acute liver injury.

8.3 Drug Classes

Antineoplastic Agents

8.4 WHO Essential Medicines

Drug
Drug Classes
Hormones and antihormones
Formulation
Indication
(1) Malignant neoplasms of breast; (2) Malignant neoplasms of prostate

8.5 FDA National Drug Code Directory

8.6 Drug Labels

Drug and label

8.7 Clinical Trials

8.7.1 ClinicalTrials.gov

8.7.2 EU Clinical Trials Register

8.7.3 NIPH Clinical Trials Search of Japan

8.8 Therapeutic Uses

Goserelin acetate is used for the palliative treatment of advanced prostate cancer. Therapy with a GnRH agonist (e.g., goserelin) currently is considered one of several first-line options for hormonal therapy in patients with prostate cancer ... .
American Society of Health System Pharmacists. AHFS Drug Information 2008. Bethesda, Maryland 2008, p. 1080
Goserelin is used for the palliative treatment of endometriosis. The manufacturer states that experience with goserelin in the management of this condition has been limited to women 18 years of age and older who received consecutive therapy ... with the drug for 6 months. Goserelin, like other GnRH analogs, produces a reversible hypoestrogenic state, which is thought to be principally responsible for the beneficial effects observed in endometriosis. A 6-month course of goserelin therapy can provide symptomatic (e.g., pain) relief and a reduction in endometriotic lesions; some degree of improvement has persisted in many patients for at least 6 months following completion of therapy. Substantial improvement of clinical symptoms usually occurs within 4 weeks of initiation of goserelin therapy.
American Society of Health System Pharmacists. AHFS Drug Information 2008. Bethesda, Maryland 2008, p. 1080
Goserelin is used in the palliative treatment of advanced breast cancer in premenopausal and perimenopausal women. In a multicenter, randomized, controlled clinical trial in women with estrogen- or progesterone-receptor-positive breast cancer, goserelin therapy or oophorectomy was associated with objective response rates (complete or partial responses) of 22-31 or 12-27%, time to treatment failure of 6-6.7 or 4-5.5 months, and median survival time of 33.2 or 33.6 months, respectively. In addition, subjective response, characterized by relief of pain and improved performance status, was reported in 48 or 50% of women receiving goserelin or undergoing surgery, respectively.
American Society of Health System Pharmacists. AHFS Drug Information 2008. Bethesda, Maryland 2008, p. 1080
Goserelin is used as an endometrial-thinning agent prior to endometrial ablation procedures for the treatment of dysfunctional uterine bleeding. In women with dysfunctional uterine bleeding, administration of goserelin (two doses of goserelin (3.6 mg each) given 4 weeks apart) prior to surgery suppressed endometrial growth, reduced uterine size and endometrial thickness, and facilitated surgical ablation.
American Society of Health System Pharmacists. AHFS Drug Information 2008. Bethesda, Maryland 2008, p. 1080
For more Therapeutic Uses (Complete) data for GOSERELIN (10 total), please visit the HSDB record page.

8.9 Drug Warnings

May cause fetal harm; embryotoxicity and fetotoxicity demonstrated in animals. Before initiating goserelin therapy in women, pregnancy must be excluded. Women of childbearing potential should be advised to avoid pregnancy while receiving the drug and use an effective nonhormonal method of contraception during goserelin therapy and continue contraception until the return of menses or for at least 12 weeks following subcutaneous implantation of the last 3.6-mg dose of goserelin. No adequate and well-controlled studies to date in humans. If a patient with endometriosis or undergoing endometrial thinning becomes pregnant during goserelin therapy, the drug should be discontinued and the patient should be advised about potential fetal hazard. In addition, if used during pregnancy (i.e., in women with advanced breast cancer), apprise of potential fetal hazard. Although continuous use of goserelin usually inhibits ovulation and stops menstruation, contraception is not ensured.
American Society of Health System Pharmacists. AHFS Drug Information 2008. Bethesda, Maryland 2008, p. 1081
As with other GnRH agonists, worsening (flare) of signs and/or symptoms (e.g., increased bone pain) of prostate or breast cancer and/or development of new manifestations occasionally have occurred during the initial weeks of therapy with goserelin. Development of these effects apparently results from goserelin-induced transient increases in serum testosterone (in men) or estrogen (in women) concentrations during the initial weeks of therapy. Concomitant therapy with an antiandrogen (e.g., bicalutamide, flutamide, nilutamide) 1 week before and during the first few weeks of goserelin therapy has been used to minimize the development of disease flare in men with prostate cancer.
American Society of Health System Pharmacists. AHFS Drug Information 2008. Bethesda, Maryland 2008, p. 1081
Cases of spinal cord compression and/or ureteral obstruction have been reported in men with prostate cancer receiving GnRH agonists. If spinal cord compression or renal impairment develops, standard treatment of these complications should be instituted, and in extreme cases, an immediate orchiectomy should be considered. Goserelin should be administered with caution to patients at particular risk of developing spinal cord compression or ureteral obstruction and these patients should be observed closely during the first month of therapy. Patients with spinal cord compression or ureteral obstruction should receive appropriate treatment for these conditions prior to initiating therapy with goserelin.
American Society of Health System Pharmacists. AHFS Drug Information 2008. Bethesda, Maryland 2008, p. 1081
Since goserelin exerts pharmacologic effects on the uterus and cervix and may cause an increase in cervical resistance, cervical dilation should be performed carefully in patients undergoing endometrial ablation following use of goserelin as an endometrial thinning agent.
American Society of Health System Pharmacists. AHFS Drug Information 2008. Bethesda, Maryland 2008, p. 1081
For more Drug Warnings (Complete) data for GOSERELIN (18 total), please visit the HSDB record page.

9 Pharmacology and Biochemistry

9.1 Pharmacodynamics

The pharmacokinetics of goserelin have been determined in both male and female healthy volunteers and patients. In these studies, goserelin was administered as a single 250µg (aqueous solution) dose and as a single or multiple 3.6 mg depot dose by subcutaneous route.

9.2 MeSH Pharmacological Classification

Antineoplastic Agents, Hormonal
Antineoplastic agents that are used to treat hormone-sensitive tumors. Hormone-sensitive tumors may be hormone-dependent, hormone-responsive, or both. A hormone-dependent tumor regresses on removal of the hormonal stimulus, by surgery or pharmacological block. Hormone-responsive tumors may regress when pharmacologic amounts of hormones are administered regardless of whether previous signs of hormone sensitivity were observed. The major hormone-responsive cancers include carcinomas of the breast, prostate, and endometrium; lymphomas; and certain leukemias. (From AMA Drug Evaluations Annual 1994, p2079) (See all compounds classified as Antineoplastic Agents, Hormonal.)

9.3 FDA Pharmacological Classification

1 of 2
FDA UNII
0F65R8P09N
Active Moiety
GOSERELIN
Pharmacological Classes
Established Pharmacologic Class [EPC] - Gonadotropin Releasing Hormone Receptor Agonist
Pharmacological Classes
Mechanisms of Action [MoA] - Gonadotropin Releasing Hormone Receptor Agonists
FDA Pharmacology Summary
Goserelin is a Gonadotropin Releasing Hormone Receptor Agonist. The mechanism of action of goserelin is as a Gonadotropin Releasing Hormone Receptor Agonist.
2 of 2
Non-Proprietary Name
GOSERELIN
Pharmacological Classes
Gonadotropin Releasing Hormone Receptor Agonist [EPC]; Gonadotropin Releasing Hormone Receptor Agonists [MoA]

9.4 ATC Code

S76 | LUXPHARMA | Pharmaceuticals Marketed in Luxembourg | Pharmaceuticals marketed in Luxembourg, as published by d'Gesondheetskeess (CNS, la caisse nationale de sante, www.cns.lu), mapped by name to structures using CompTox by R. Singh et al. (in prep.). List downloaded from https://cns.public.lu/en/legislations/textes-coordonnes/liste-med-comm.html. Dataset DOI:10.5281/zenodo.4587355

L - Antineoplastic and immunomodulating agents

L02 - Endocrine therapy

L02A - Hormones and related agents

L02AE - Gonadotropin releasing hormone analogues

L02AE03 - Goserelin

9.5 Absorption, Distribution and Excretion

Absorption
Inactive orally, rapidly absorbed following subcutaneous administration.
Route of Elimination
Clearance of goserelin following subcutaneous administration of a radiolabeled solution of goserelin was very rapid and occurred via a combination of hepatic and urinary excretion. More than 90% of a subcutaneous radiolabeled solution formulation dose of goserelin was excreted in urine.
Volume of Distribution
44.1 ± 13.6 L [subcutaneous administration of 250 mcg]
Clearance
121 +/- 42.4 mL/min [prostate cancer with 10.8 mg depot]
The apparent volume of distribution determined after subcutaneous administration of 250 ug aqueous solution of goserelin was 44.1 + or - 13.6 liters for healthy males. The plasma protein binding of goserelin was found to be 27%.
US Natl Inst Health; DailyMed. Current Medication Information. Zoladex. March, 2007. Available from, as of June 26, 2008: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?id=4207
The overall pharmacokinetic profile of goserelin following administration of a Zoladex 10.8 mg depot to patients with prostate cancer was determined. The initial release of goserelin from the depot was relatively rapid resulting in a peak concentration at 2 hours after dosing. From Day 4 until the end of the 12-week dosing interval, the sustained release of goserelin from the depot produced reasonably stable systemic exposure. ... There is no clinically significant accumulation of goserelin following administration of four depots administered at 12-week intervals.
US Natl Inst Health; DailyMed. Current Medication Information. Zoladex. March, 2007. Available from, as of June 26, 2008: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?id=4207
The pharmacokinetics of goserelin have been determined in healthy male volunteers and patients. In healthy males, radiolabeled goserelin was administered as a single 250 ug (aqueous solution) dose by the subcutaneous route. The absorption of radiolabeled drug was rapid, and the peak blood radioactivity levels occurred between 0.5 and 1.0 hour after dosing.
US Natl Inst Health; DailyMed. Current Medication Information. Zoladex. March, 2007. Available from, as of June 26, 2008: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?id=4207
Clearance of goserelin following subcutaneous administration of a radiolabeled solution of goserelin was very rapid and occurred via a combination of hepatic and urinary excretion. More than 90% of a subcutaneous radiolabeled solution formulation dose of goserelin was excreted in urine. Approximately 20% of the dose recovered in urine was accounted for by unchanged goserelin.
US Natl Inst Health; DailyMed. Current Medication Information. Zoladex. March, 2007. Available from, as of June 26, 2008: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?id=4207
Goserelin is a synthetic decapeptide analogue of luteinising hormone-releasing hormone (LHRH). For experimental purposes it has been administered subcutaneously as an aqueous solution, but for therapeutic use it is formulated as subcutaneous depots releasing goserelin over periods of 1 (3.6 mg) or 3 (10.8 mg) months. Pharmacokinetic data have been generated using a specific radioimmunoassay. When administered as a solution, goserelin is rapidly absorbed and eliminated from serum with a mean elimination half-life (t1/2beta) of 4.2 hours in males and 2.3 hours in females. The shapes of the observed serum goserelin profiles following administration of the depots are primarily determined by the rate of goserelin release from the biodegradable lactide-glycolide copolymer matrix over periods of 1 or 3 months. There is no clinically relevant accumulation of goserelin during multiple administration of these depots. Goserelin is extensively metabolized prior to excretion. Its pharmacokinetics are unaffected by hepatic impairment, but the mean t1/2beta increases to 12.1 hours in patients with severe renal impairment. This suggests that the total renal clearance (renal metabolism and unchanged drug) is decreased in patients with renal dysfunction. It is unnecessary to adjust the dose or administration interval when the depot formulations are administered to elderly patients or to those with impaired renal or hepatic function. ...
Cockshott ID; Clin Pharmacokinet 39 (1): 27-48 (2000)

9.6 Metabolism / Metabolites

Hepatic
Metabolism of goserelin, by hydrolysis of the C-terminal amino acids, is the major clearance mechanism. The major circulating component in serum appeared to be 1-7 fragment, and the major component present in urine of one healthy male volunteer was 5-10 fragment. The metabolism of goserelin in humans yields a similar but narrow profile of metabolites to that found in other species. All metabolites found in humans have also been found in toxicology species.
US Natl Inst Health; DailyMed. Current Medication Information. Zoladex. March, 2007. Available from, as of June 26, 2008: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?id=4207

9.7 Biological Half-Life

4-5 hours
When administered as a solution, goserelin is rapidly absorbed and eliminated from serum with a mean elimination half-life (t1/2beta) of 4.2 hours in males and 2.3 hours in females.
Cockshott ID; Clin Pharmacokinet 39 (1): 27-48 (2000)
Subjects with impaired renal function (creatinine clearance less than 20 mL/min) had a serum elimination half-life of 12.1 hours compared to 4.2 hours for subjects with normal renal function.
US Natl Inst Health; DailyMed. Current Medication Information. Zoladex. March, 2007. Available from, as of June 26, 2008: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?id=4207

9.8 Mechanism of Action

Goserelin is a synthetic decapeptide analogue of LHRH. Goserelin acts as a potent inhibitor of pituitary gonadotropin secretion when administered in the biodegradable formulation. The result is sustained suppression of LH and serum testosterone levels.
Zoladex is a synthetic decapeptide analogue of LHRH. Zoladex acts as a potent inhibitor of pituitary gonadotropin secretion when administered in the biodegradable formulation. Following initial administration, ZOLADEX causes an initial increase in serum-luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels with subsequent increases in serum levels of testosterone. Chronic administration of Zoladex leads to sustained suppression of pituitary gonadotropins, and serum levels of testosterone consequently fall into the range normally seen in surgically castrated men approximately 21 days after initiation of therapy. This leads to accessory sex organ regression. In animal and in in vitro studies, administration of goserelin resulted in the regression or inhibition of growth of the hormonally sensitive dimethylbenzanthracene (DMBA)-induced rat mammary tumor and Dunning R3327 prostate tumor. In clinical trials using Zoladex 3.6 mg with follow-up of more than 2 years, suppression of serum testosterone to castrate levels has been maintained for the duration of therapy.
US Natl Inst Health; DailyMed. Current Medication Information. Zoladex. March, 2007. Available from, as of June 26, 2008: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?id=4207

9.9 Human Metabolite Information

9.9.1 Cellular Locations

Membrane

10 Use and Manufacturing

10.1 Uses

Treatment of prostate cancer
Hardman, J.G., L.E. Limbird, P.B., A.G. Gilman. Goodman and Gilman's The Pharmacological Basis of Therapeutics. 11th ed. New York, NY: McGraw-Hill, 2006., p. 1504
THERAP CAT: Antineoplastic (hormonal)
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 780

Use (kg) in USA (2002): 1

Consumption (g per capita) in the USA (2002): 3.13e-06

Calculated removal (%): 1.9

10.2 Impurities

[4-D-serine]goserelin; [9-D-proline]goserelin; [5-D-tyrosine]goserelin; [2-D-histidine]goserelin; [7-D-leucine]goserelin; [6-[O-(1,1-dimethylethyl)-L-serine]]goserelin; 1-carbamoylyl-2-[5-oxo-L-prolyl-L-histidyl-L-tryptophyl-L-seryl-L-tyrosyl-O-(1,1-dimethylethyl)-D-seryl-L-leucyl-L-arginyl]diazane; 5-oxo-L-prolyl-L-histidyl-L-tryptophyl-L-seryl-L-tyrosyl-O-(1,1-dimethylethyl)-D-seryl-L-leucyl-L-arginyl-L-prolinohydrazide; [1-(5-oxo-D-proline)]goserelin; endo-8a,8b-di-L-proline-goserelin; endo-8a-L-proline-goserelin; O4-acetylgoserelin
Council of Europe, European Directorate for the Quality of Medicines. European Pharmacopoeia, 5th Ed., Volume 2; Strasbourg, France, p.1687 (2004)

10.3 Formulations / Preparations

Parenteral: Implants: 3.6 mg (of goserelin) Zoladex (available as prefilled disposable syringe) (AstraZeneca); 10.8 mg (of goserelin) Zoladex (available as prefilled disposable syringe) (AstraZeneca). /Goserelin acetate/
American Society of Health System Pharmacists. AHFS Drug Information 2008. Bethesda, Maryland 2008, p. 1082

11 Identification

11.1 Analytic Laboratory Methods

Analyte: goserelin; matrix: chemical identification; procedure: nuclear magnetic resonance spectrometry with comparison to standards
Council of Europe, European Directorate for the Quality of Medicines. European Pharmacopoeia, 5th Ed., Volume 2; Strasbourg, France, p.1687 (2004)
Analyte: goserelin; matrix: chemical identification; procedure: retention time of the major peak of the liquid chromatogram with comparison to standards
Council of Europe, European Directorate for the Quality of Medicines. European Pharmacopoeia, 5th Ed., Volume 2; Strasbourg, France, p.1687 (2004)
Analyte: goserelin; matrix: chemical identification; procedure: amino acid analysis
Council of Europe, European Directorate for the Quality of Medicines. European Pharmacopoeia, 5th Ed., Volume 2; Strasbourg, France, p.1687 (2004)
Analyte: goserelin; matrix: pharmaceutical preparation (solution); procedure: capillary zone electrophoresis with ultraviolet detection at 214 nm and mass spectrometry
Hoitink MA et al; J Chromatogr A 776: 319-327 (1997). As cited in: Lunn G; HPLC and CE Methods for Pharmaceutical Analysis. CD-ROM. New York, NY: John Wiley & Sons (2000)
For more Analytic Laboratory Methods (Complete) data for GOSERELIN (6 total), please visit the HSDB record page.

12 Safety and Hazards

12.1 Hazards Identification

12.1.1 GHS Classification

Pictogram(s)
Irritant
Health Hazard
Signal
Danger
GHS Hazard Statements

H317 (94.4%): May cause an allergic skin reaction [Warning Sensitization, Skin]

H332 (94.4%): Harmful if inhaled [Warning Acute toxicity, inhalation]

H334 (94.4%): May cause allergy or asthma symptoms or breathing difficulties if inhaled [Danger Sensitization, respiratory]

Precautionary Statement Codes

P233, P260, P261, P271, P272, P280, P284, P302+P352, P304+P340, P317, P321, P333+P317, P342+P316, P362+P364, P403, and P501

(The corresponding statement to each P-code can be found at the GHS Classification page.)

ECHA C&L Notifications Summary

Aggregated GHS information provided per 18 reports by companies from 2 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown.

12.1.2 Hazard Classes and Categories

Skin Sens. 1 (94.4%)

Acute Tox. 4 (94.4%)

Resp. Sens. 1 (94.4%)

12.2 Accidental Release Measures

12.2.1 Disposal Methods

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.
/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ All contaminated disposables should be contained in sealable bags for transfer to larger waste containers. /Antineoplastic agents/
McEvoy, G.K. (ed.). American Hospital Formulary Service- Drug Information 2004. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2004 (Plus Supplements)., p. 875
/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ All bottles must be discarded as contaminated waste after decontamination of the biohazard cabinet. All protective apparel (gown, gloves, goggles, and respirator) should be discarded as contaminated waste. /Antineoplastic agents/
McEvoy, G.K. (ed.). American Hospital Formulary Service- Drug Information 2004. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2004 (Plus Supplements)., p. 875
/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ The contaminated filters must be removed, bagged in thick plastic and prepared for disposal in a hazardous waste dump site or incinerator licensed by the Environmental Protection Agency (EPA). /Antineoplastic agents/
McEvoy, G.K. (ed.). American Hospital Formulary Service- Drug Information 2004. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2004 (Plus Supplements)., p. 875
For more Disposal Methods (Complete) data for GOSERELIN (8 total), please visit the HSDB record page.

12.2.2 Preventive Measures

/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Accidental contamination of the health-care environment, resulting in exposure of personnel, patients, visitors, and family members to hazardous substances, is prevented by maintaining the physical integrity and security of packages of hazardous drugs. 1. Access to all areas where hazardous drugs are stored is limited to specified authorized staff. 2. A method should be present for identifying to personnel those drugs that require special precautions (eg, cytotoxics). One way to accomplish this is to apply appropriate warning labels to all hazardous drug containers, shelves, and bins where the drug products are stored. ... 3. A method of identifying, for patients and family members, those drugs that require special precautions in the home should be in place. This may be accomplished in the health-care setting, by providing specific labeling for discharge medications, along with written instructions. 4. Methods for identifying shipping cartons of hazardous drugs should be required from manufacturers and distributors of these drugs. 5. Written procedures for handling damaged packages of hazardous drugs should be maintained. Personnel involved in shipping and receiving hazardous drugs should be trained in these procedures, including the proper use of protective garments and equipment. Damaged shipping cartons of hazardous drugs should be received and opened in an isolated area (eg, in a laboratory fume hood, if available, not in a vertical laminar airflow biological safety cabinet used for preparing sterile products). /Antineoplastic agents/
McEvoy, G.K. (ed.). American Hospital Formulary Service- Drug Information 2004. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2004 (Plus Supplements)., p. 875
/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Facilities (eg, shelves, carts, counters, and trays) for storing hazardous drugs are designed to prevent breakage and to limit contamination in the event of leakage. Bins, shelves with barriers at the front, or other design features that reduce the chance of drug containers falling to the floor should be used. Hazardous drugs requiring refrigeration should be stored separately from nonhazardous drugs in individual bins designed to prevent breakage and to contain leakage. /Antineoplastic agents/
McEvoy, G.K. (ed.). American Hospital Formulary Service- Drug Information 2004. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2004 (Plus Supplements)., p. 875
/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Until the reproductive risks (or lack thereof) associated with handling hazardous drugs within a safety program have been substantiated, staff who are pregnant or breast-feeding should be allowed to avoid contact with these drugs. Policies should be in effect that provide these individuals with alternative tasks or responsibilities if they so desire. /Antineoplastic agents/
McEvoy, G.K. (ed.). American Hospital Formulary Service- Drug Information 2004. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2004 (Plus Supplements)., p. 875
/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ The pharmacy should provide access to information on toxicity, treatment of acute exposure (if available), chemical inactivators, solubility and stability of hazardous drugs (including investigational agents) used in the workplace. /Antineoplastic agents/
McEvoy, G.K. (ed.). American Hospital Formulary Service- Drug Information 2004. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2004 (Plus Supplements)., p. 875
For more Preventive Measures (Complete) data for GOSERELIN (20 total), please visit the HSDB record page.

12.3 Exposure Control and Personal Protection

12.3.1 Personal Protective Equipment (PPE)

/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Protective apparel: Disposable closed-front gown or coveralls, disposable utility gloves over disposable latex gloves, NIOSH-approved air-purifying half-mask respirator equipped with a high efficiency filter, and eye protection should be worn. /Antineoplastic agents/
McEvoy, G.K. (ed.). American Hospital Formulary Service- Drug Information 2004. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2004 (Plus Supplements)., p. 875
/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Class 100 clean-air work stations, both horizontal and vertical airflow (with no containment characteristics), are inappropriate engineering controls for handling hazardous drugs because they provide no personnel protection and permit environmental contamination. Although there are no engineering controls designed specifically for the safe handling of hazardous chemicals as sterile products, Class II contained vertical-flow biological safety cabinets (biohazard cabinets) have been adopted for this use. Biohazard cabinetry is, however, designed for the handling of infectious agents, not hazardous chemicals. ... Based on design, ease of use, and cost considerations, Class II contained-vertical-flow biohazard cabinetry is currently recommended for use in preparing sterile doses of hazardous drugs. Class II cabinetry design and performance specifications are defined in NSF Standard 49. Biological safety cabinets selected for use with hazardous drugs should meet NSF Standard 49 specifications to ensure the maximum protection from these engineering controls. /Antineoplastic agents/
McEvoy, G.K. (ed.). American Hospital Formulary Service- Drug Information 2004. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2004 (Plus Supplements)., p. 875
/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Workers should wear powder free, disposable surgical latex gloves of good quality when preparing hazardous drugs. Selection criteria for gloves should include thickness (especially at the fingertips where stress is the greatest), fit, length, and tactile sensation. ... The practice of double gloving is supported by research that indicates that many glove materials vary in drug permeability even within lots; therefore, double gloving is recommended. ... In general, surgical latex gloves fit better, have appropriate elasticity for double gloving and maintaining the integrity of the glove-gown interface, and have sufficient tactile sensation (even during double gloving) for stringent aseptic procedures. ... Powdered gloves should be avoided. /Antineoplastic agents/
McEvoy, G.K. (ed.). American Hospital Formulary Service- Drug Information 2004. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2004 (Plus Supplements)., p. 875
/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Workers who are not protected by the containment environment of a biohazard cabinet should use respiratory protection when handling hazardous drugs. Respiratory protection should be an adjunct to and not a substitute for engineering controls. Surgical masks of all types provide no respiratory protection against powdered or liquid aerosols of hazardous drugs. In situations where workers may be exposed to potential eye contact with hazardous drugs, an appropriate plastic face shield or splash goggles should be worn. /Antineoplastic agents/
McEvoy, G.K. (ed.). American Hospital Formulary Service- Drug Information 2004. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2004 (Plus Supplements)., p. 875
/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ During compounding of hazardous drugs (eg, crushing, dissolving, and preparing an ointment), workers should wear low permeability gowns and double gloves. Compounding should take place in a protective area such as a disposable glove box. If compounding must be done in the open, an area away from drafts and traffic must be selected, and the worker should use appropriate respiratory protection. /Antineoplastic agents/
McEvoy, G.K. (ed.). American Hospital Formulary Service- Drug Information 2004. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2004 (Plus Supplements)., p. 875

12.4 Transport Information

12.4.1 Shipment Methods and Regulations

/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Methods for transporting hazardous drugs to the health-care setting should be consistent with environmental protection and national or local regulations for transporting hazardous substances. When hazardous drugs are being transported to the home-care setting, appropriate containers (eg, lined cardboard boxes) and procedures should be used to prevent breakage and contain leakage. ... The drugs must be securely capped or sealed and properly packaged and protected during transport to reduce further the chance of breakage and spillage in a public area such as a corridor or elevator. /Antineoplastic agents/
McEvoy, G.K. (ed.). American Hospital Formulary Service- Drug Information 2004. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2004 (Plus Supplements)., p. 875

12.5 Regulatory Information

12.5.1 FDA Requirements

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl goserelin acetate, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Goserelin acetate/
DHHS/FDA; Electronic Orange Book-Approved Drug Products with Therapeutic Equivalence Evaluations. Available from, as of August 1, 2008: https://www.fda.gov/cder/ob/

13 Toxicity

13.1 Toxicological Information

13.1.1 Hepatotoxicity

Goserelin has been associated with mild serum enzyme elevations during therapy in 3% to 5% of patients, but values above 3 times the upper limit of normal are rare, being reported in less than 1% of recipients. The serum enzyme elevations during goserelin therapy have generally been transient and asymptomatic, resolving even with drug continuation and rarely requiring dose modification or discontinuation. Despite use for several decades, goserelin has been linked to only a single, and not entirely convincing, case of clinically apparent liver injury. Routine monitoring of patients for liver test abnormalities is not recommended.

Likelihood score: D (possible, rare cause of clinically apparent liver injury).

13.1.2 Drug Induced Liver Injury

Compound
goserelin
DILI Annotation
Ambiguous DILI-concern
Severity Grade
3
Label Section
Adverse reactions
References

M Chen, V Vijay, Q Shi, Z Liu, H Fang, W Tong. FDA-Approved Drug Labeling for the Study of Drug-Induced Liver Injury, Drug Discovery Today, 16(15-16):697-703, 2011. PMID:21624500 DOI:10.1016/j.drudis.2011.05.007

M Chen, A Suzuki, S Thakkar, K Yu, C Hu, W Tong. DILIrank: the largest reference drug list ranked by the risk for developing drug-induced liver injury in humans. Drug Discov Today 2016, 21(4): 648-653. PMID:26948801 DOI:10.1016/j.drudis.2016.02.015

13.1.3 Acute Effects

13.1.4 Antidote and Emergency Treatment

Emergency and supportive measures. Maintain an open airway and assist ventilation if necessary. Treat coma, seizures, hypotension, and arrhythmias if they occur. Treat nausea and vomiting with metoclopramide and fluid loss caused by gastroenteritis with intravenous crystalloid fluids. /Antineoplastic agents/
Olson, K.R. (Ed.); Poisoning & Drug Overdose. 5th ed. Lange Medical Books/McGraw-Hill. New York, N.Y. 2007., p. 101
Bone marrow depression should be treated with the assistance of an experienced hematologist or oncologist. /Antineoplastic agents/
Olson, K.R. (Ed.); Poisoning & Drug Overdose. 5th ed. Lange Medical Books/McGraw-Hill. New York, N.Y. 2007., p. 100
Decontamination. Administer activated charcoal orally if conditions are appropriate. Gastric lavage is not necessary after small to moderate ingestions if activated charcoal can be given promptly. /Antineoplastic agents/
Olson, K.R. (Ed.); Poisoning & Drug Overdose. 5th ed. Lange Medical Books/McGraw-Hill. New York, N.Y. 2007., p. 107
Enhanced elimination. Because of the rapid intracellular incorporation of most of these agents, dialysis and other extracorporeal removal procedures are generally not effective. /Antineoplastic agents/
Olson, K.R. (Ed.); Poisoning & Drug Overdose. 5th ed. Lange Medical Books/McGraw-Hill. New York, N.Y. 2007., p. 107

13.1.5 Medical Surveillance

/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ There is no method available for routine monitoring of personnel for evidence of hazardous drug exposure. Tests for the presence of mutagens or chromosomal damage are not drug specific and are of value only in controlled studies. Chemical analysis of urine for the presence of hazardous drugs at the sensitivity level needed to detect occupational exposure is limited to a few drugs and is not yet commercially available. /Antineoplastic agents/
McEvoy, G.K. (ed.). American Hospital Formulary Service- Drug Information 2004. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2004 (Plus Supplements)., p. 875

13.1.6 Human Toxicity Excerpts

/CASE REPORTS/ Relapsing polychondritis is a chronic rheumatologic disorder of unknown etiology. Cutaneous manifestations occur in nearly half of the patients and often precede cartilaginous involvement. ... The case of a man with a history of prostatic adenocarcinoma who underwent monthly injections of goserelin (Zoladex), an LH-RH analogue /is presented/. Five months after the beginning of the treatment, he presented cutaneous manifestations, which then recurred monthly, after each goserelin injection. After goserelin interruption and replacement with another treatment (cyproterone acetate), the patient was asymptomatic for 2 months. A cutaneous relapse then occurred followed by a typical cartilaginous involvement. ...
Labarthe MP et al; Dermatology 195 (4): 391-4 (1997)
/CASE REPORTS/ A 30-year old female who initially had typical endometriosis treated according to a standard regimen later developed numerous highly vascular endometrial polyps on the vagina, cervix, ureter, serosal surfaces of the uterus, pouch of Douglas (POD) and other areas of pelvic peritoneum as well as the endometrium 8 months after withdrawal of treatment with Zoladex gonadotrophin releasing hormone (GnRH) agonist used for treatment of this disease. /It is/ postulate/d/ that these polyps developed as a rebound phenomenon upon withdrawal of Zoladex. /Zoladex/
Othman NH et al; Aust N Z J Obstet Gynaecol 36 (2): 216-8 (1996)
/CASE REPORTS/ Women suffering from endometriosis are treated with long-acting analogues of gonadotropin-releasing hormone (GnRH). This is a case of hypersensitivity reaction to a goserelin acetate implant that manifested as an anaphylactic reaction. This is the first report of a hypersensitivity reaction to the GnRH analogue, goserelin acetate (Zoladex). /Zoladex/
Raj SG et al; Am J Med Sci 312 (4): 187-90 (1996)
/CASE REPORTS/ An 8-year-old girl with idiopathic central precocious puberty experienced multiple episodes of anaphylaxis after receiving a goserelin acetate implant. She was hospitalized and treated with epinephrine, antihistamine, and corticosteroids. The goserelin implant was surgically excised; however, anaphylactic symptoms continued for 4 days after excision. Less severe systemic symptoms recurred 6 weeks after removal; these were possibly due to leakage of the depot drug into subcutaneous tissues. It was noted that 3 years earlier, the patient had developed a similar, milder systemic allergic reaction to leuprolide acetate that required treatment with oral prednisone and antihistamines. Intradermal testing yielded positive results for leuprolide. Gonadotropin-releasing hormone (GnRH) analogs, including leuprolide acetate and goserelin acetate, are commonly prescribed for patients with prostatic carcinoma, endometriosis, and precocious puberty. A literature review identified a single case report of a systemic hypersensitivity reaction involving goserelin acetate and several reports of systemic hypersensitivity reactions associated with leuprolide acetate. ... No reports of systemic reactions to GnRH analogs in pediatric patients /were found/. ...
Lam C et al; Pharmacotherapy 26 (12): 1811-5 (2006)
For more Human Toxicity Excerpts (Complete) data for GOSERELIN (9 total), please visit the HSDB record page.

13.1.7 Non-Human Toxicity Excerpts

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Subcutaneous implant of Zoladex in male and female rats once every 4 weeks for 1 year and recovery for 23 weeks at doses of about 80 and 150 ug/kg (males) and 50 and 100 ug/kg (females) daily (about 3 to 9 times the recommended human dose on a mg/sq m basis) resulted in an increased incidence of pituitary adenomas. An increased incidence of pituitary adenomas was also observed following subcutaneous implant of Zoladex in rats at similar dose levels for a period of 72 weeks in males and 101 weeks in females. The relevance of the rat pituitary adenomas to humans has not been established. Subcutaneous implants of Zoladex every 3 weeks for 2 years delivered to mice at doses of up to 2400 ug/kg/day (about 70 times the recommended human dose on a mg/sq m basis) resulted in an increased incidence of histiocytic sarcoma of the vertebral column and femur.
US Natl Inst Health; DailyMed. Current Medication Information. Zoladex. March, 2007. Available from, as of June 26, 2008: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?id=4207
/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Administration of goserelin led to changes that were consistent with gonadal suppression in both male and female rats as a result of its endocrine action. In male rats administered 500-1000 ug/kg/day (about 30-60 times the recommended human dose on a mg/sq m basis), a decrease in weight and atrophic histological changes were observed in the testes, epididymis, seminal vesicle and prostate gland with complete suppression of spermatogenesis. In female rats administered 50-1000 ug/kg/day (about 3-60 times the recommended daily human dose on a mg/sq m basis), suppression of ovarian function led to decreased size and weight of ovaries and secondary sex organs; follicular development was arrested at the antral stage and the corpora lutea were reduced in size and number. Except for the testes, almost complete histologic reversal of these effects in males and females was observed several weeks after dosing was stopped; however, fertility and general reproductive performance were reduced in those that became pregnant after goserelin was discontinued. Fertile matings occurred within 2 weeks after cessation of dosing, even though total recovery of reproductive function may not have occurred before mating took place; and, the ovulation rate, the corresponding implantation rate, and number of live fetuses were reduced.
US Natl Inst Health; DailyMed. Current Medication Information. Zoladex. March, 2007. Available from, as of June 26, 2008: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?id=4207
/GENOTOXICITY/ Mutagenicity tests using bacterial and mammalian systems for point mutations and cytogenetic effects have provided no evidence for mutagenic potential.
US Natl Inst Health; DailyMed. Current Medication Information. Zoladex. March, 2007. Available from, as of June 26, 2008: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?id=4207

13.1.8 Protein Binding

27.3%

13.2 Ecological Information

13.2.1 Probable Routes of Human Exposure

/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ ... exposure may be through inadvertent ingestion of the drug on foodstuffs (eg, workers' lunches), inhalation of drug dusts or droplets or direct skin contact. /Antineoplastic agents/
McEvoy, G.K. (ed.). American Hospital Formulary Service- Drug Information 2004. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2004 (Plus Supplements)., p. 875

14 Associated Disorders and Diseases

15 Literature

15.1 Consolidated References

15.2 NLM Curated PubMed Citations

15.3 Springer Nature References

15.4 Chemical Co-Occurrences in Literature

15.5 Chemical-Gene Co-Occurrences in Literature

15.6 Chemical-Disease Co-Occurrences in Literature

16 Patents

16.1 Depositor-Supplied Patent Identifiers

16.2 WIPO PATENTSCOPE

16.3 Chemical Co-Occurrences in Patents

16.4 Chemical-Disease Co-Occurrences in Patents

16.5 Chemical-Gene Co-Occurrences in Patents

17 Interactions and Pathways

17.1 Chemical-Target Interactions

17.2 Drug-Drug Interactions

18 Biological Test Results

18.1 BioAssay Results

19 Classification

19.1 MeSH Tree

19.2 NCI Thesaurus Tree

19.3 ChEBI Ontology

19.4 KEGG: ATC

19.5 KEGG: Target-based Classification of Drugs

19.6 KEGG: Drug Groups

19.7 WHO ATC Classification System

19.8 FDA Pharm Classes

19.9 ChemIDplus

19.10 IUPHAR / BPS Guide to PHARMACOLOGY Target Classification

19.11 ChEMBL Target Tree

19.12 UN GHS Classification

19.13 NORMAN Suspect List Exchange Classification

19.14 EPA DSSTox Classification

19.15 FDA Drug Type and Pharmacologic Classification

19.16 EPA Substance Registry Services Tree

19.17 MolGenie Organic Chemistry Ontology

20 Information Sources

  1. ChEBI
  2. DrugBank
    LICENSE
    Creative Common's Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/legalcode)
    https://www.drugbank.ca/legal/terms_of_use
  3. FDA Pharm Classes
    LICENSE
    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  4. LiverTox
  5. NCI Thesaurus (NCIt)
    LICENSE
    Unless otherwise indicated, all text within NCI products is free of copyright and may be reused without our permission. Credit the National Cancer Institute as the source.
    https://www.cancer.gov/policies/copyright-reuse
  6. Open Targets
    LICENSE
    Datasets generated by the Open Targets Platform are freely available for download.
    https://platform-docs.opentargets.org/licence
  7. ChEMBL
    LICENSE
    Access to the web interface of ChEMBL is made under the EBI's Terms of Use (http://www.ebi.ac.uk/Information/termsofuse.html). The ChEMBL data is made available on a Creative Commons Attribution-Share Alike 3.0 Unported License (http://creativecommons.org/licenses/by-sa/3.0/).
    http://www.ebi.ac.uk/Information/termsofuse.html
  8. ChemIDplus
    ChemIDplus Chemical Information Classification
    https://pubchem.ncbi.nlm.nih.gov/source/ChemIDplus
  9. EPA DSSTox
    CompTox Chemicals Dashboard Chemical Lists
    https://comptox.epa.gov/dashboard/chemical-lists/
  10. European Chemicals Agency (ECHA)
    LICENSE
    Use of the information, documents and data from the ECHA website is subject to the terms and conditions of this Legal Notice, and subject to other binding limitations provided for under applicable law, the information, documents and data made available on the ECHA website may be reproduced, distributed and/or used, totally or in part, for non-commercial purposes provided that ECHA is acknowledged as the source: "Source: European Chemicals Agency, http://echa.europa.eu/". Such acknowledgement must be included in each copy of the material. ECHA permits and encourages organisations and individuals to create links to the ECHA website under the following cumulative conditions: Links can only be made to webpages that provide a link to the Legal Notice page.
    https://echa.europa.eu/web/guest/legal-notice
    N-[1-[[1-[[1-[[1-[[1-[[1-[[1-[2-[(carbamoylamino)carbamoyl]pyrrolidin-1-yl]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-[(2-methylpropan-2-yl)oxy]-1-oxopropan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-3-(3H-imidazol-4-yl)-1-oxopropan-2-yl]-5-oxopyrrolidine-2-carboxamide
    https://echa.europa.eu/substance-information/-/substanceinfo/100.212.024
    N-[1-[[1-[[1-[[1-[[1-[[1-[[1-[2-[(carbamoylamino)carbamoyl]pyrrolidin-1-yl]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-[(2-methylpropan-2-yl)oxy]-1-oxopropan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-3-(3H-imidazol-4-yl)-1-oxopropan-2-yl]-5-oxopyrrolidine-2-carboxamide (EC: 686-281-6)
    https://echa.europa.eu/information-on-chemicals/cl-inventory-database/-/discli/details/217097
  11. FDA Global Substance Registration System (GSRS)
    LICENSE
    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  12. Hazardous Substances Data Bank (HSDB)
  13. Human Metabolome Database (HMDB)
    LICENSE
    HMDB is offered to the public as a freely available resource. Use and re-distribution of the data, in whole or in part, for commercial purposes requires explicit permission of the authors and explicit acknowledgment of the source material (HMDB) and the original publication (see the HMDB citing page). We ask that users who download significant portions of the database cite the HMDB paper in any resulting publications.
    http://www.hmdb.ca/citing
  14. ClinicalTrials.gov
    LICENSE
    The ClinicalTrials.gov data carry an international copyright outside the United States and its Territories or Possessions. Some ClinicalTrials.gov data may be subject to the copyright of third parties; you should consult these entities for any additional terms of use.
    https://clinicaltrials.gov/ct2/about-site/terms-conditions#Use
  15. Comparative Toxicogenomics Database (CTD)
    LICENSE
    It is to be used only for research and educational purposes. Any reproduction or use for commercial purpose is prohibited without the prior express written permission of NC State University.
    http://ctdbase.org/about/legal.jsp
  16. IUPHAR/BPS Guide to PHARMACOLOGY
    LICENSE
    The Guide to PHARMACOLOGY database is licensed under the Open Data Commons Open Database License (ODbL) https://opendatacommons.org/licenses/odbl/. Its contents are licensed under a Creative Commons Attribution-ShareAlike 4.0 International License (http://creativecommons.org/licenses/by-sa/4.0/)
    https://www.guidetopharmacology.org/about.jsp#license
    Guide to Pharmacology Target Classification
    https://www.guidetopharmacology.org/targets.jsp
  17. Therapeutic Target Database (TTD)
  18. DailyMed
  19. Drug Induced Liver Injury Rank (DILIrank) Dataset
    LICENSE
    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  20. Drugs@FDA
    LICENSE
    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  21. WHO Model Lists of Essential Medicines
    LICENSE
    Permission from WHO is not required for the use of WHO materials issued under the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Intergovernmental Organization (CC BY-NC-SA 3.0 IGO) license.
    https://www.who.int/about/policies/publishing/copyright
  22. EU Clinical Trials Register
  23. National Drug Code (NDC) Directory
    LICENSE
    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  24. NORMAN Suspect List Exchange
    LICENSE
    Data: CC-BY 4.0; Code (hosted by ECI, LCSB): Artistic-2.0
    https://creativecommons.org/licenses/by/4.0/
    GOSERELIN ACETATE
    NORMAN Suspect List Exchange Classification
    https://www.norman-network.com/nds/SLE/
  25. Japan Chemical Substance Dictionary (Nikkaji)
  26. KEGG
    LICENSE
    Academic users may freely use the KEGG website. Non-academic use of KEGG generally requires a commercial license
    https://www.kegg.jp/kegg/legal.html
    Anatomical Therapeutic Chemical (ATC) classification
    http://www.genome.jp/kegg-bin/get_htext?br08303.keg
    Target-based classification of drugs
    http://www.genome.jp/kegg-bin/get_htext?br08310.keg
  27. MassBank of North America (MoNA)
    LICENSE
    The content of the MoNA database is licensed under CC BY 4.0.
    https://mona.fiehnlab.ucdavis.edu/documentation/license
  28. Metabolomics Workbench
  29. NIPH Clinical Trials Search of Japan
  30. NLM RxNorm Terminology
    LICENSE
    The RxNorm Terminology is created by the National Library of Medicine (NLM) and is in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from NLM. Credit to the U.S. National Library of Medicine as the source is appreciated but not required. The full RxNorm dataset requires a free license.
    https://www.nlm.nih.gov/research/umls/rxnorm/docs/termsofservice.html
  31. WHO Anatomical Therapeutic Chemical (ATC) Classification
    LICENSE
    Use of all or parts of the material requires reference to the WHO Collaborating Centre for Drug Statistics Methodology. Copying and distribution for commercial purposes is not allowed. Changing or manipulating the material is not allowed.
    https://www.whocc.no/copyright_disclaimer/
  32. Pharos
    LICENSE
    Data accessed from Pharos and TCRD is publicly available from the primary sources listed above. Please respect their individual licenses regarding proper use and redistribution.
    https://pharos.nih.gov/about
  33. Springer Nature
  34. Wikidata
  35. Wikipedia
  36. Medical Subject Headings (MeSH)
    LICENSE
    Works produced by the U.S. government are not subject to copyright protection in the United States. Any such works found on National Library of Medicine (NLM) Web sites may be freely used or reproduced without permission in the U.S.
    https://www.nlm.nih.gov/copyright.html
    Antineoplastic Agents, Hormonal
    https://www.ncbi.nlm.nih.gov/mesh/68018931
  37. PubChem
  38. GHS Classification (UNECE)
  39. EPA Substance Registry Services
  40. MolGenie
    MolGenie Organic Chemistry Ontology
    https://github.com/MolGenie/ontology/
  41. PATENTSCOPE (WIPO)
CONTENTS