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
Structure for Ganirelix (DB06785)
- Weight
- Average: 1570.35
Monoisotopic: 1568.8423035 - Chemical Formula
- C80H113ClN18O13
- Synonyms
- Ganirelix
- External IDs
- Org 37462
- RS 26306
- SML0241
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
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- Contraindications & Blackbox Warnings
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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 antagonistHumans - Absorption
Ganirelix is rapidly absorbed following subcutaneous administration with a mean absolute bioavailability of approximately 91%.5 It has a Tmax 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
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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
- Not Available
Interactions
- Drug Interactions
- 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
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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 US 
Ganirelix Acetate Injection, solution 250 ug/0.5mL Subcutaneous Organon LLC 2021-06-01 Not applicable US 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 EU 
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 EU Orgalutran Injection, solution 0.25 mg/0.5mL Subcutaneous N.V. Organon 2016-09-08 Not applicable EU Orgalutran Solution 250 mcg / 0.5 mL Subcutaneous Organon Canada Inc. 2002-08-23 Not applicable Canada 
Orgalutran Injection, solution 0.25 mg/0.5mL Subcutaneous N.V. Organon 2016-09-08 Not applicable EU - 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. 2021-12-14 Not applicable US Ganirelix Acetate Injection, solution 250 ug/0.5mL Subcutaneous Meitheal Pharmaceuticals Inc. 2022-06-06 Not applicable US Ganirelix Acetate Injection, solution 250 ug/0.5mL Subcutaneous Ferring Pharmaceuticals Inc. 2019-01-01 Not applicable US Ganirelix Acetate Injection 250 ug/0.5mL Subcutaneous Amphastar Pharmaceuticals, Inc. 2022-06-20 Not applicable US Ganirelix Acetate Injection, solution 250 ug/0.5mL Subcutaneous Sun Pharmaceutical Industries, Inc. 2019-11-07 2020-01-18 US
Categories
- ATC Codes
- H01CC01 — Ganirelix
- 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 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 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
- 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]
- 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]
- 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]
- EMA Approved Drug Products: Ganirelix Gedeon Richter (Ganirelix) Subcutaneous Injection [Link]
- DailyMed Label: Ganirelix Acetate Subcutaneous Injection [Link]
- Organon: Ganirelix MSDS [Link]
- FDA Drug Approval Package: Antagon (Ganirelix Acetate) [Link]
- External Links
- KEGG Drug
- D08010
- PubChem Compound
- 16130957
- PubChem Substance
- 310264884
- ChemSpider
- 17287671
- BindingDB
- 50102454
- 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
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 4 Completed Treatment Infertility 2 4 Completed Treatment Infertility / IVF Treatment 1 4 Completed Treatment Infertility / Premature Ovarian Failure (POF) 1 4 Recruiting Treatment Infertility / IVF 2 4 Recruiting Treatment IVF 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 Solution Subcutaneous 250 mcg / 0.5 mL Injection, solution Injection Subcutaneous 0.25 mg/0.5ml Solution Subcutaneous 0.25 mg 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 US US6653286 No 2003-11-25 2018-06-16 US
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 Not Available Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS Not Available
Targets
- 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
- 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]
- DailyMed Label: Ganirelix Acetate Subcutaneous Injection [Link]
- EMA Approved Drug Products: Ganirelix Gedeon Richter (Ganirelix) Subcutaneous Injection [Link]
Drug created at September 14, 2010 16:21 / Updated at October 06, 2022 03:22