Ganirelix

Identification

Summary

Ganirelix is a GnRH antagonist used in assisted reproduction in women undergoing controlled ovarian hyperstimulation to control ovulation by inhibiting the premature LH surges.

Brand Names

Fyremadel, Orgalutran

Generic Name

Ganirelix

DrugBank Accession Number

DB06785

Background

Ganirelix is a synthetic decapeptide and a competitive gonadotropin-releasing hormone (GnRH) antagonist. Derived from endogenous GnRH, ganirelix has amino acid substitutions. Ganirelix is indicated for controlled ovarian hyperstimulation in assisted reproduction techniques.⁵ The first case of pregnancy achieved after the use of ganirelix in an assisted reproduction program was reported in 1998.² Ganirelix was first approved by the FDA on July 29, 1999.⁷

Type

Small Molecule

Groups

Approved

Structure

Download

MOLSDFPDBSMILESInChI

Similar Structures

Structure for Ganirelix (DB06785)

×

Close

Weight

Average: 1570.35
Monoisotopic: 1568.8423035

Chemical Formula

C₈₀H₁₁₃ClN₁₈O₁₃

Synonyms

• Ganirelix

External IDs

• Org 37462
• RS 26306
• SML0241

Poor quality drug data slowing you down?

Unlock 38% more drug discovery time and eliminate decision-making doubts with this one-stop guide to quality drug data.

Download eBook

Poor quality drug data slowing you down?

Download eBook

Pharmacology

Indication

Ganirelix is indicated for the inhibition of premature luteinizing hormone (LH) surges in women undergoing controlled ovarian hyperstimulation for assisted reproduction techniques (ART).^4,5

Reduce drug development failure rates

Build, train, & validate machine-learning models
with evidence-based and structured datasets.

See how

Build, train, & validate predictive machine-learning models with structured datasets.

See how

Associated Therapies

• Controlled ovarian hyperstimulation therapy

Contraindications & Blackbox Warnings

Prevent Adverse Drug Events Today

Tap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.

Learn more

Avoid life-threatening adverse drug events with our Clinical API

Learn more

Pharmacodynamics

Ganirelix modulates the hypothalamic-pituitary-gonadal axis by causing a rapid, profound, reversible suppression of endogenous gonadotropins. During controlled ovarian stimulation, it suppresses luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion from the pituitary gland.⁴ Unlike GnRH agonists that causes an initial increase in gonadotropin levels, ganirelix does not cause this effect before premature LH surge inhibition.¹ Ganirelix is also not associated with hypo‐estrogenic side effects, flare‐up, and a long down‐regulation period induced by GnRH agonists.³

In patients undergoing controlled ovarian stimulation, the median duration of ganirelix treatment was five days.⁴ In one study, multiple-dose administration of 0.25 mg ganirelix decreased serum LH, FSH and estradiol (E2) concentrations from baseline by 74, 32, and 25% after the last dose, respectively.¹ Serum hormone levels returned to pre-treatment levels within two days after the last injection.^4,5

Mechanism of action

Gonadotropin-releasing hormone (GnRH) is a hypothalamus-derived releasing hormone responsible for the synthesis and release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) from the anterior pituitary.² At midcycle, a large increase in GnRH release results in an LH surge, which leads to several physiologic actions such as ovulation, resumption of meiosis in the oocyte, and luteinization. Luteinization results in a rise in serum progesterone with an accompanying decrease in estradiol levels.⁵

Controlled ovarian hyperstimulation (COH) is performed in conjunction with other interventions like in vitro fertilization (IVF) during assisted reproductive technology (ART).³ COH is beneficial as it allows the scheduling of IVF treatments.² During this intervention, inhibiting premature surges of LH is important because premature elevated LH levels can hinder effective multiple follicular maturation ³ and can lead to an undesirable increase in progesterone levels.¹ Ganirelix aims to suppress premature LH surges by competitively blocking the GnRH receptors on the pituitary gonadotroph and subsequent transduction pathways. Ganirelix-induced suppression of gonadotropin secretion is rapid and reversible. The suppression of pituitary LH secretion by ganirelix is more pronounced than that of FSH. An initial release of endogenous gonadotropins has not been detected with ganirelix, which is consistent with an antagonist effect.⁵

Target	Actions	Organism
AGonadotropin-releasing hormone receptor	antagonist	Humans

Absorption

Ganirelix is rapidly absorbed following subcutaneous administration with a mean absolute bioavailability of approximately 91%.⁵ It has a T_max ranging from one to two hours.^4,5 Ganirelix reaches steady-state serum concentrations after three days of administration.⁵

Volume of distribution

The mean (SD) volume of distribution of ganirelix in healthy females following subcutaneous administration of a single 250-mcg dose is 43.7 (11.4) L.⁵

Protein binding

In vitro protein binding to human plasma is 81.9%.⁵

Metabolism

The metabolites are small peptide fragments formed by enzymatic hydrolysis of ganirelix at restricted sites.⁴ The 1–4 peptide and 1–6 peptide of ganirelix are the primary metabolites observed in the feces.⁵

Route of elimination

Following single-dose intravenous administration of radiolabeled ganirelix to healthy female volunteers, Ganirelix is the major compound present in the plasma (50–70% of total radioactivity in the plasma) up to 4 hours and urine (17.1–18.4% of administered dose) up to 24 hours. Ganirelix is not found in the feces. On average, 97.2% of the total radiolabeled ganirelix dose is recovered in the feces and urine (75.1% and 22.1%, respectively) over 288 h following intravenous single dose administration of 1 mg [¹⁴C]-ganirelix. Urinary excretion is virtually complete in 24 h, whereas fecal excretion starts to plateau 192 h after dosing.⁵

Half-life

The elimination half-life (t½) following subcutaneous administration of a single 250-mcg dose is approximately 13 hours.^4,5

Clearance

Clearance following subcutaneous administration of a single 250-mcg dose is approximately 2.4 L/h.⁴

Adverse Effects

Improve decision support & research outcomes

With structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!

See the data

Improve decision support & research outcomes with our structured adverse effects data.

See a data sample

Toxicity

LD₅₀ in rats was 40 mg/kg following subcutaneous administration.⁶

There have been no reports of overdosage with ganirelix in humans.⁵ Clinical studies with subcutaneous administration of ganirelix at single doses up to 12 mg did not show systemic adverse reactions. In acute toxicity studies in rats and monkeys, non-specific toxic symptoms such as hypotension and bradycardia were only observed after intravenous administration of ganirelix over 1 and 3 mg/kg, respectively. As there is no known antidote for ganirelix, the drug should be discontinued in case of an overdose.⁴

Pathways

Not Available

Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">

Not Available

Interactions

Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">

This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.

Not Available

Food Interactions

No interactions found.

Products

Drug product information from 10+ global regions

Our datasets provide approved product information including:
dosage, form, labeller, route of administration, and marketing period.

Access now

Access drug product information from over 10 global regions.

Access now

Product Ingredients

Ingredient	UNII	CAS	InChI Key
Ganirelix acetate	56U7906FQW	129311-55-3	OVBICQMTCPFEBS-SATRDZAXSA-N

Brand Name Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End	Region	Image
Ganirelix Acetate	Injection, solution	250 ug/0.5mL	Subcutaneous	Organon USA Inc.	1999-07-29	Not applicable
Ganirelix Acetate	Injection, solution	250 ug/0.5mL	Subcutaneous	Organon LLC	2021-06-01	Not applicable
Ganirelix Gedeon Richter	Injection, solution	0.25 mg/0.5mL	Subcutaneous	Chemical Works Of Gedeon Richter Plc. (Gedeon Richter Plc.)	2022-07-25	Not applicable
Ganirelix Gedeon Richter	Injection, solution	0.25 mg/0.5mL	Subcutaneous	Chemical Works Of Gedeon Richter Plc. (Gedeon Richter Plc.)	2022-07-25	Not applicable
Orgalutran	Injection, solution	0.25 mg/0.5mL	Subcutaneous	N.V. Organon	2016-09-08	Not applicable

Generic Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End	Region	Image
Fyremadel	Injection, solution	250 ug/0.5mL	Subcutaneous	Ferring Pharmaceuticals Inc.	2022-02-28	Not applicable
Ganirelix Acetate	Injection, solution	250 ug/0.5mL	Subcutaneous	Meitheal Pharmaceuticals Inc.	2022-06-06	Not applicable
Ganirelix Acetate	Injection, solution	250 ug/0.5mL	Subcutaneous	Ferring Pharmaceuticals Inc.	2019-01-01	Not applicable
Ganirelix Acetate	Injection, solution	250 ug/0.5mL	Subcutaneous	Gland Pharma Limited	2023-02-28	Not applicable
Ganirelix Acetate	Injection, solution	250 ug/0.5mL	Subcutaneous	Lupin Pharmaceuticals, Inc.	2024-02-01	Not applicable

Categories

ATC Codes

H01CC01 — Ganirelix

• H01CC — Anti-gonadotropin-releasing hormones
• H01C — HYPOTHALAMIC HORMONES
• H01 — PITUITARY AND HYPOTHALAMIC HORMONES AND ANALOGUES
• H — SYSTEMIC HORMONAL PREPARATIONS, EXCL. SEX HORMONES AND INSULINS

Drug Categories

• Amino Acids, Peptides, and Proteins
• Anti-Gonadotropin-Releasing Hormones
• Decreased GnRH Secretion
• Gonadotropin Releasing Hormone Receptor Antagonists
• Gonadotropin-releasing Hormone Antagonists
• Gonadotropin-Releasing Hormone, antagonists & inhibitors
• Hormone Antagonists
• Hormones
• Hormones, Hormone Substitutes, and Hormone Antagonists
• Hypothalamic Hormones
• Nerve Tissue Proteins
• Neuropeptides
• Oligopeptides
• Peptide Hormones
• Peptides
• Pituitary and Hypothalamic Hormones and Analogues
• Pituitary Hormone-Releasing Hormones
• Proteins
• Systemic Hormonal Preparations, Excl. Sex Hormones and Insulins

Chemical TaxonomyProvided by Classyfire

Description

This compound belongs to the class of organic compounds known as polypeptides. These are peptides containing ten or more amino acid residues.

Kingdom

Organic compounds

Super Class

Organic Polymers

Class

Polypeptides

Sub Class

Not Available

Direct Parent

Polypeptides

Alternative Parents

Peptides / Tyrosine and derivatives / Phenylalanine and derivatives / Leucine and derivatives / N-acyl-alpha amino acids and derivatives / Proline and derivatives / Serine and derivatives / Alpha amino acid amides / Alanine and derivatives / Naphthalenes / Amphetamines and derivatives / Pyrrolidinecarboxamides / N-acylpyrrolidines / Chlorobenzenes / 1-hydroxy-2-unsubstituted benzenoids / Aryl chlorides / N-acyl amines / Pyridines and derivatives / Tertiary carboxylic acid amides / Heteroaromatic compounds / Acetamides / Secondary carboxylic acid amides / Primary carboxylic acid amides / Guanidines / Carboximidamides / Azacyclic compounds / Propargyl-type 1,3-dipolar organic compounds / Carbonyl compounds / Organochlorides / Organopnictogen compounds / Primary alcohols / Organic oxides / Hydrocarbon derivatives

show 23 more

Substituents

1-hydroxy-2-unsubstituted benzenoid / Acetamide / Alanine or derivatives / Alcohol / Alpha peptide / Alpha-amino acid amide / Alpha-amino acid or derivatives / Amphetamine or derivatives / Aromatic heteropolycyclic compound / Aryl chloride / Aryl halide / Azacycle / Benzenoid / Carbonyl group / Carboxamide group / Carboximidamide / Carboxylic acid derivative / Chlorobenzene / Fatty acyl / Fatty amide / Guanidine / Halobenzene / Heteroaromatic compound / Hydrocarbon derivative / Leucine or derivatives / Monocyclic benzene moiety / N-acyl-alpha amino acid or derivatives / N-acyl-amine / N-acylpyrrolidine / N-substituted-alpha-amino acid / Naphthalene / Organic 1,3-dipolar compound / Organic nitrogen compound / Organic oxide / Organic oxygen compound / Organochloride / Organohalogen compound / Organoheterocyclic compound / Organonitrogen compound / Organooxygen compound / Organopnictogen compound / Phenol / Phenylalanine or derivatives / Polypeptide / Primary alcohol / Primary carboxylic acid amide / Proline or derivatives / Propargyl-type 1,3-dipolar organic compound / Pyridine / Pyrrolidine / Pyrrolidine carboxylic acid or derivatives / Pyrrolidine-2-carboxamide / Secondary carboxylic acid amide / Serine or derivatives / Tertiary carboxylic acid amide / Tyrosine or derivatives

show 46 more

Molecular Framework

Aromatic heteropolycyclic compounds

External Descriptors

Not Available

Affected organisms

• Humans and other mammals

Chemical Identifiers

UNII

IX503L9WN0

CAS number

124904-93-4

InChI Key

GJNXBNATEDXMAK-PFLSVRRQSA-N

InChI

InChI=1S/C80H113ClN18O13/c1-9-84-79(85-10-2)88-38-17-15-24-60(70(104)94-62(41-49(5)6)71(105)93-61(25-16-18-39-89-80(86-11-3)87-12-4)78(112)99-40-20-26-68(99)77(111)90-50(7)69(82)103)92-73(107)64(44-53-30-35-59(102)36-31-53)97-76(110)67(48-100)98-75(109)66(46-55-21-19-37-83-47-55)96-74(108)65(43-52-28-33-58(81)34-29-52)95-72(106)63(91-51(8)101)45-54-27-32-56-22-13-14-23-57(56)42-54/h13-14,19,21-23,27-37,42,47,49-50,60-68,100,102H,9-12,15-18,20,24-26,38-41,43-46,48H2,1-8H3,(H2,82,103)(H,90,111)(H,91,101)(H,92,107)(H,93,105)(H,94,104)(H,95,106)(H,96,108)(H,97,110)(H,98,109)(H2,84,85,88)(H2,86,87,89)/t50-,60-,61+,62+,63-,64+,65-,66-,67+,68+/m1/s1

IUPAC Name

(2R)-6-{[bis(ethylamino)methylidene]amino}-N-[(1S)-1-{[(2S)-6-{[bis(ethylamino)methylidene]amino}-1-[(2S)-2-{[(1R)-1-carbamoylethyl]carbamoyl}pyrrolidin-1-yl]-1-oxohexan-2-yl]carbamoyl}-3-methylbutyl]-2-[(2S)-2-[(2S)-2-[(2R)-2-[(2R)-3-(4-chlorophenyl)-2-[(2R)-2-acetamido-3-(naphthalen-2-yl)propanamido]propanamido]-3-(pyridin-3-yl)propanamido]-3-hydroxypropanamido]-3-(4-hydroxyphenyl)propanamido]hexanamide

SMILES

CCNC(NCC)=NCCCC[C@@H](NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](CO)NC(=O)[C@@H](CC1=CC=CN=C1)NC(=O)[C@@H](CC1=CC=C(Cl)C=C1)NC(=O)[C@@H](CC1=CC2=CC=CC=C2C=C1)NC(C)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN=C(NCC)NCC)C(=O)N1CCC[C@H]1C(=O)N[C@H](C)C(N)=O

References

Synthesis Reference

"Patent Link":http://www.google.ca/patents/US5767082

General References

1. Gillies PS, Faulds D, Balfour JA, Perry CM: Ganirelix. Drugs. 2000 Jan;59(1):107-11; discussion 112-3. doi: 10.2165/00003495-200059010-00007. [Article]
2. Out HJ, Mannaerts BM: The gonadotrophin-releasing hormone antagonist ganirelix--history and introductory data. Hum Fertil (Camb). 2002 Feb;5(1):G5-10; discussion G10-2, G41-8. doi: 10.1080/1464727992000199771. [Article]
3. Al-Inany HG, Youssef MA, Ayeleke RO, Brown J, Lam WS, Broekmans FJ: Gonadotrophin-releasing hormone antagonists for assisted reproductive technology. Cochrane Database Syst Rev. 2016 Apr 29;4:CD001750. doi: 10.1002/14651858.CD001750.pub4. [Article]
4. EMA Approved Drug Products: Ganirelix Gedeon Richter (Ganirelix) Subcutaneous Injection [Link]
5. DailyMed Label: Ganirelix Acetate Subcutaneous Injection [Link]
6. Organon: Ganirelix MSDS [Link]
7. FDA Drug Approval Package: Antagon (Ganirelix Acetate) [Link]

External Links

KEGG Drug

D08010

PubChem Compound

16130957

PubChem Substance

310264884

ChemSpider

17287671

BindingDB

50102454

RxNav

35825

ChEBI

135910

ChEMBL

CHEMBL1251

RxList

RxList Drug Page

Drugs.com

Drugs.com Drug Page

PDRhealth

PDRhealth Drug Page

Wikipedia

Ganirelix

Clinical Trials

Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">

Phase	Status	Purpose	Conditions	Count
4	Completed	Other	Infertility	1
4	Completed	Treatment	Controlled Ovarian Stimulation	1
4	Completed	Treatment	Egg Donation	1
4	Completed	Treatment	Fertility / Optimal Stimulation Protocol / Reproductive Endocrinology	1
4	Completed	Treatment	Infertile Women Undergoing Assisted Reproductive Technology (ART)	1

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Not Available

Dosage Forms

Form	Route	Strength
Injection, solution	Subcutaneous	0.25 MG/0.5ML
Injection	Subcutaneous	250 ug/0.5mL
Injection, solution	Subcutaneous	250 ug/0.5mL
Injection, solution	Parenteral	0.25 mg/0.5ml
Solution	Subcutaneous	250 mcg / 0.5 mL
Injection	Subcutaneous	0.25 mg/0.5ml
Solution	Subcutaneous	0.25 mg
Injection, solution		0.25 MG/0.5ML
Solution	Subcutaneous	0.5 mg/1ml

Prices

Not Available

Patents

Patent Number	Pediatric Extension	Approved	Expires (estimated)	Region
US5767082	No	1998-06-16	2015-06-16
US6653286	No	2003-11-25	2018-06-16

Properties

State

Solid

Experimental Properties

Property	Value	Source
boiling point (°C)	100	https://www.organon.com/docs/product/safety-data-sheets/Ganirelix%20Formulation_HH_NZ_6N.pdf

Predicted Properties

Property	Value	Source
Water Solubility	0.00531 mg/mL	ALOGPS
logP	3.42	ALOGPS
logP	1.62	Chemaxon
logS	-5.5	ALOGPS
pKa (Strongest Acidic)	9.5	Chemaxon
pKa (Strongest Basic)	12.14	Chemaxon
Physiological Charge	2	Chemaxon
Hydrogen Acceptor Count	20	Chemaxon
Hydrogen Donor Count	16	Chemaxon
Polar Surface Area	451.49 Å2	Chemaxon
Rotatable Bond Count	44	Chemaxon
Refractivity	423.46 m3·mol-1	Chemaxon
Polarizability	170.37 Å3	Chemaxon
Number of Rings	6	Chemaxon
Bioavailability	0	Chemaxon
Rule of Five	No	Chemaxon
Ghose Filter	No	Chemaxon
Veber's Rule	No	Chemaxon
MDDR-like Rule	Yes	Chemaxon

Predicted ADMET Features

Not Available

Spectra

Mass Spec (NIST)

Not Available

Spectra

Spectrum	Spectrum Type	Splash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)	Predicted LC-MS/MS	splash10-0uk9-0111980001-50b80a68eb8f15e2ff95
Predicted MS/MS Spectrum - 10V, Negative (Annotated)	Predicted LC-MS/MS	splash10-00r2-0000091000-d6c65729ec708f8cbb78
Predicted MS/MS Spectrum - 20V, Positive (Annotated)	Predicted LC-MS/MS	splash10-0udi-6101891101-cff9641980fa2939c155
Predicted MS/MS Spectrum - 20V, Negative (Annotated)	Predicted LC-MS/MS	splash10-0kmi-1000390000-554f5836ca0d0ad9ebb1
Predicted MS/MS Spectrum - 40V, Positive (Annotated)	Predicted LC-MS/MS	splash10-0006-2501492000-792219b7c2c4c65c4070
Predicted MS/MS Spectrum - 40V, Negative (Annotated)	Predicted LC-MS/MS	splash10-0fk9-3300890200-37c2c16b9b5af194ccff

Chromatographic Properties

Collision Cross Sections (CCS)

Adduct	CCS Value (Å2)	Source type	Source
[M-H]-	365.06674	predicted	DeepCCS 1.0 (2019)
[M+H]+	366.7238	predicted	DeepCCS 1.0 (2019)
[M+Na]+	372.8806	predicted	DeepCCS 1.0 (2019)

Targets

Build, predict & validate machine-learning models

Use our structured and evidence-based datasets to unlock new
insights and accelerate drug research.

Learn more

Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.

Learn more

Details1. Gonadotropin-releasing hormone receptor

Kind

Protein

Organism

Humans

Pharmacological action

Yes

Actions

Antagonist

General Function

Peptide binding

Specific Function

Receptor for gonadotropin releasing hormone (GnRH) that mediates the action of GnRH to stimulate the secretion of the gonadotropic hormones luteinizing hormone (LH) and follicle-stimulating hormone...

Gene Name

GNRHR

Uniprot ID

P30968

Uniprot Name

Gonadotropin-releasing hormone receptor

Molecular Weight

37730.355 Da

References

1. Oberye J, Mannaerts B, Huisman J, Timmer C: Local tolerance, pharmacokinetics, and dynamics of ganirelix (Orgalutran) administration by Medi-Jector compared to conventional needle injections. Hum Reprod. 2000 Feb;15(2):245-9. [Article]
2. DailyMed Label: Ganirelix Acetate Subcutaneous Injection [Link]
3. EMA Approved Drug Products: Ganirelix Gedeon Richter (Ganirelix) Subcutaneous Injection [Link]

×

Identify potential medication risks

Easily compare up to 40 drugs with our drug interaction checker.

Get severity rating, description, and management advice.

Learn more

Drug created at September 14, 2010 16:21 / Updated at February 02, 2024 22:52