Elagolix

Identification

Summary

Elagolix is a gonadotropin releasing hormone receptor antagonist used to treat moderate to severe pain in endometriosis.

Brand Names

Oriahnn 28 Day Kit, Orilissa

Generic Name

Elagolix

DrugBank Accession Number

DB11979

Background

Elagolix has been used in trials studying the basic science and treatment of Endometriosis, Folliculogenesis, Uterine Fibroids, Heavy Uterine Bleeding, and Heavy Menstrual Bleeding. As of 24 July 2018, however, the U.S. Food and Drug Administration (FDA) approved AbbVie's elagolix under the brand name Orilissa as the first and only oral gonadotropin-releasing hormone (GnRH) antagonist specifically developed for women with moderate to severe endometriosis pain ⁷.

It has been determined that endometriosis is one of the most common gynecologic disorders in the United States ^4,5,6. In particular, estimates suggest that one in ten women of reproductive age is affected by endometriosis and experience debilitating pain symptoms ^4,5,6. Moreover, women who are affected by this condition can suffer for up to six to ten years and visit multiple physicians before receiving a proper diagnosis ^4,5,6. Subsequently, as Orilissa (elagolix) was approved by the FDA under priority review ⁷, this expedited new approval gives healthcare professionals another valuable option for treating the potentially unmet needs of women who are affected by endometriosis, depending on their specific type and severity of endometriosis pain.

Type

Small Molecule

Groups

Approved, Investigational

Structure

Similar Structures

Weight: Average: 631.6
Monoisotopic: 631.210561893
Chemical Formula: C₃₂H₃₀F₅N₃O₅

Synonyms

Elagolix

External IDs

ABT-620
NBI 56418
NBI-56418

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

Elagolix is a gonadotropin-releasing hormone (GnRH) receptor antagonist indicated for the management of moderate to severe pain associated with endometriosis ^Label.

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 Conditions

Indication Type	Indication	Combined Product Details	Approval Level	Age Group	Patient Characteristics	Dose Form
Used in combination to treat	Heavy menstrual bleeding	Combination Product in combination with: Norethisterone (DB00717), Estradiol (DB00783)	••••••••••••	•••••••••••••		•••••••
Management of	Moderate to severe pain		••••••••••••			••••••

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

During a three menstrual cycle study in healthy women, an elagolix 150 mg once daily regimen and a 200 mg twice daily regimen resulted in an ovulation rate of about 50% and 32%, respectively ^Label. In Phase 3 trials in women with endometriosis, elagolix caused a dose-dependent reduction in median estradiol concentrations to approximately 42 pg/mL for the 150 mg once daily regimen and 12 pg/mL for the 200 mg twice daily regimen ^Label.

Furthermore, the effect of elagolix on the QTc interval was investigated in a randomized, placebo- and positive-controlled, open-label, single-dose, crossover thorough QTc study in 48 healthy adult premenopausal women ^Label. Elagolix concentrations in subjects administered a single dose of 1200 mg was seventeen times higher than the concentration in subjects given elagolix 200 mg twice daily. Nevertheless, there was no clinically relevant prolongation of the QTc interval ^Label.

Mechanism of action

Endometriosis develops when tissue that is similar to the kind that is normally located in the uterus starts to grow outside of the uterus ^4,6. Such growth leads to various symptoms like pain during periods, pelvic pain between periods, and pain during sexual intercourse ^4,6. The growths themselves are referred to as lesions and frequently develop on the ovaries, fallopian tubes, and other areas around the uterus, including the bowel or bladder ^4,6. The growth of these lesions is dependent upon the estrogen hormone ⁴.

Elagolix is an orally-administered, nonpeptide small molecule gonadotropin-releasing hormone (GnRH) receptor antagonist that inhibits endogenous GnRH signaling by binding competitively to GnRH receptors in the pituitary gland ^Label,1,2,3. Administration of elagolix results in dose-dependent suppression of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), leading to decreased blood concentrations of the ovarian sex hormones, estradiol and progesterone.

Target	Actions	Organism
UGonadotropin-releasing hormone receptor	antagonist	Humans

Absorption

The Tmax of elagolix is reported as being 1.0 hours ^Label. The effect of a high-fat meal (relative to fasting) can result in a reduction of the AUC and Cmax by as much as 24% and 36%, respectively ^Label.

Volume of distribution

The apparent volume of distribution at steady state (Vdss/F) of elagolix is reported to be 1674 for a 150 mg daily regimen and 881 for a 200 mg twice daily regimen ^Label.

Protein binding

The percentage bound to human plasma proteins for elagolix has been documented as 80% ^Label.

Metabolism

Elagolix is predominantly metabolized by the CYP3A family of isoenzymes despite participating in minor metabolic pathways with the CYP2D6, CYP2C8, and uridine glucuronosyl transferases (UGTs) enzymes as well ^Label. The primary metabolite of elagolix, referred to as NBI-61962 (R-(+)-4-{2-[5-(2-fluoro-3-hydroxy-phenyl)-3-(2-fluoro-6-trifluoromethyl-benzyl)-4-methyl-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-yl]-1-phenyl-ethylamino}-butyrate) ², is not believed to possess any significant biologic activity due to its low plasma exposure and an observed potency that is exceptionally less than the parent elagolix compound (Ki value of 3.5 compared to 0.9 nM) ¹.

Route of elimination

The primary route of elimination of elagolix is via hepatic metabolism ^Label.

Half-life

The terminal phase elimination half-life of elagolix is recorded as being 4 to 6 hours ^Label.

Clearance

The oral clearance (CL/F) of elagolix is 123 L/hr for a 150 mg once daily regimen and 144 L/hr for a 200 mg twice daily regimen ^Label.

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

In case of overdose, monitor the patient for any signs or symptoms of adverse reactions and initiate appropriate symptomatic treatment, as needed ^Label. Common adverse reactions of elagolix include hot flush, headache, nausea, insomnia, mood alterations, amenorrhea, depression, anxiety, arthralgia, bone loss, changes in menstrual bleeding patterns, suicidal ideation and behavior, exacerbation of existing mood disorders, and/or hepatic transaminase elevations ^Label.

The recommended duration of use for elagolix is up to 24 months for the 150 mg once daily dose and up to six months for the 200 mg twice daily dose, as it causes a dose-dependent decrease in bone mineral density (BMD) ^Label. BMD loss is greater with increasing duration of use and may not be completely reversible after stopping treatment ^Label. For women with moderate hepatic impairment, the recommended dosage is 150 mg once daily for up to six months ^Label.

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.

Drug	Interaction
Integrate drug-drug interactions in your software
Abatacept	The metabolism of Elagolix can be increased when combined with Abatacept.
Abemaciclib	The serum concentration of Abemaciclib can be increased when it is combined with Elagolix.
Abiraterone	The metabolism of Elagolix can be decreased when combined with Abiraterone.
Abrocitinib	The serum concentration of Elagolix can be increased when it is combined with Abrocitinib.
Acebutolol	The metabolism of Elagolix can be decreased when combined with Acebutolol.

Food Interactions

Administer calcium supplement. This will minimize the risk of bone mineral density loss.
Administer vitamin supplements. Administer Vitamin D supplements to minimize the risk of bone mineral density loss.
Take at the same time every day.
Take with or without food.

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
Elagolix sodium	5948VUI423	832720-36-2	DQYGXRQUFSRDCH-UQIIZPHYSA-M

Brand Name Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Orilissa	Tablet, film coated	200 mg/1	Oral	AbbVie Inc.	2018-07-23	Not applicable
Orilissa	Tablet	200 mg	Oral	Abbvie	2019-05-24	Not applicable
Orilissa	Tablet, film coated	150 mg/1	Oral	AbbVie Inc.	2018-07-23	Not applicable
Orilissa	Tablet	150 mg	Oral	Abbvie	2018-10-30	Not applicable

Mixture Products

Name	Ingredients	Dosage	Route	Labeller	Marketing Start	Marketing End	Region	Image
Oriahnn	Elagolix sodium (300 mg/1) + Elagolix sodium (300 mg/1) + Estradiol (1 mg/1) + Norethisterone (0.5 mg/1)	Capsule; Kit	Oral	AbbVie Inc.	2020-05-29	Not applicable
Oriahnn	Elagolix sodium (300 mg/1) + Elagolix sodium (300 mg/1) + Estradiol (1 mg/1) + Norethisterone (0.5 mg/1)	Capsule; Kit	Oral	AbbVie Inc.	2020-05-29	Not applicable

Chemical Identifiers

UNII: 5B2546MB5Z
CAS number: 834153-87-6
InChI Key: HEAUOKZIVMZVQL-VWLOTQADSA-N
InChI: InChI=1S/C32H30F5N3O5/c1-19-28(21-11-6-14-26(45-2)29(21)34)30(43)40(18-25(20-9-4-3-5-10-20)38-16-8-15-27(41)42)31(44)39(19)17-22-23(32(35,36)37)12-7-13-24(22)33/h3-7,9-14,25,38H,8,15-18H2,1-2H3,(H,41,42)/t25-/m0/s1
IUPAC Name: 4-{[(1R)-2-[5-(2-fluoro-3-methoxyphenyl)-3-{[2-fluoro-6-(trifluoromethyl)phenyl]methyl}-4-methyl-2,6-dioxo-1,2,3,6-tetrahydropyrimidin-1-yl]-1-phenylethyl]amino}butanoic acid
SMILES: COC1=CC=CC(=C1F)C1=C(C)N(CC2=C(C=CC=C2F)C(F)(F)F)C(=O)N(C[C@H](NCCCC(O)=O)C2=CC=CC=C2)C1=O

References

General References

Ezzati M, Carr BR: Elagolix, a novel, orally bioavailable GnRH antagonist under investigation for the treatment of endometriosis-related pain. Womens Health (Lond). 2015 Jan;11(1):19-28. doi: 10.2217/whe.14.68. [Article]
Struthers RS, Nicholls AJ, Grundy J, Chen T, Jimenez R, Yen SS, Bozigian HP: Suppression of gonadotropins and estradiol in premenopausal women by oral administration of the nonpeptide gonadotropin-releasing hormone antagonist elagolix. J Clin Endocrinol Metab. 2009 Feb;94(2):545-51. doi: 10.1210/jc.2008-1695. Epub 2008 Nov 25. [Article]
Melis GB, Neri M, Corda V, Malune ME, Piras B, Pirarba S, Guerriero S, Orru M, D'Alterio MN, Angioni S, Paoletti AM: Overview of elagolix for the treatment of endometriosis. Expert Opin Drug Metab Toxicol. 2016 May;12(5):581-8. doi: 10.1517/17425255.2016.1171316. [Article]
Giudice LC: Clinical practice. Endometriosis. N Engl J Med. 2010 Jun 24;362(25):2389-98. doi: 10.1056/NEJMcp1000274. [Article]
Nnoaham KE, Hummelshoj L, Webster P, d'Hooghe T, de Cicco Nardone F, de Cicco Nardone C, Jenkinson C, Kennedy SH, Zondervan KT: Impact of endometriosis on quality of life and work productivity: a multicenter study across ten countries. Fertil Steril. 2011 Aug;96(2):366-373.e8. doi: 10.1016/j.fertnstert.2011.05.090. Epub 2011 Jun 30. [Article]
U.S. Department of Health and Human Services (2002): Endometriosis [File]
AbbVie Orilissa (elagolix) FDA Approval Press Release [File]

External Links

PubChem Compound: 11250647
PubChem Substance: 347828301
ChemSpider: 9425680
RxNav: 2049846
ChEMBL: CHEMBL1208155
ZINC: ZINC000049888891
PDBe Ligand: F5O
Wikipedia: Elagolix

PDB Entries

7br3

FDA label

Download (631 KB)

MSDS

Download (174 KB)

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	Treatment	Uterine Fibroids (Leiomyomas)	1
4	Recruiting	Basic Science	Cerebrovascular Diseases	1
4	Recruiting	Treatment	Mild Autonomous Cortisol Excess	1
4	Unknown Status	Screening	Ovulation; Failure or Lack of	1
3	Active Not Recruiting	Treatment	Heavy Menstrual Bleeding / Uterine Fibroids (Leiomyomas)	1

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Not Available

Dosage Forms

Form	Route	Strength
Capsule; kit	Oral
Tablet	Oral	150 mg
Tablet	Oral	200 mg
Tablet, film coated	Oral	150 mg/1
Tablet, film coated	Oral	200 mg/1

Prices

Not Available

Patents

Patent Number	Pediatric Extension	Approved	Expires (estimated)
US7419983	No	2008-09-02	2024-07-06
US7462625	No	2008-12-09	2021-01-25
US7176211	No	2007-02-13	2024-07-06
US7179815	No	2007-02-20	2021-03-07
US7056927	No	2006-06-06	2024-09-10
US6872728	No	2005-03-29	2021-01-25
US10537572	No	2020-01-21	2036-09-01
US10682351	No	2020-06-16	2036-09-01
US10881659	No	2021-01-05	2034-03-14
US11045470	No	2021-06-29	2034-03-14
US11344551	No	2014-03-14	2034-03-14
US11459305	No	2008-11-07	2028-11-07
US11542239	No	2019-07-23	2039-07-23
US11690854	No	2018-04-19	2038-04-19
US11690845	No	2020-08-27	2040-08-27
US11707464	No	2014-03-14	2034-03-14

Properties

State

Solid

Experimental Properties

Property	Value	Source
water solubility	<1 mg/mL	MSDS

Predicted Properties

Property	Value	Source
Water Solubility	0.00243 mg/mL	ALOGPS
logP	4.68	ALOGPS
logP	3.14	Chemaxon
logS	-5.4	ALOGPS
pKa (Strongest Acidic)	3.86	Chemaxon
pKa (Strongest Basic)	9.04	Chemaxon
Physiological Charge	0	Chemaxon
Hydrogen Acceptor Count	6	Chemaxon
Hydrogen Donor Count	2	Chemaxon
Polar Surface Area	99.18 Å²	Chemaxon
Rotatable Bond Count	12	Chemaxon
Refractivity	156.06 m³·mol^-1	Chemaxon
Polarizability	59.44 Å³	Chemaxon
Number of Rings	4	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	splash10-01q9-0000019000-5354d9542253910051c5
Predicted MS/MS Spectrum - 10V, Negative (Annotated)	Predicted LC-MS/MS	splash10-02ai-0200069000-592627011bd95608a81b
Predicted MS/MS Spectrum - 20V, Positive (Annotated)	Predicted LC-MS/MS	splash10-00c0-3900042000-65df6769c47b85b710c5
Predicted MS/MS Spectrum - 20V, Negative (Annotated)	Predicted LC-MS/MS	splash10-056r-2100191000-66214eaf5e9c52b8b3d5
Predicted MS/MS Spectrum - 40V, Positive (Annotated)	Predicted LC-MS/MS	splash10-0kdi-0220961000-887730a8833892a0695b
Predicted MS/MS Spectrum - 40V, Negative (Annotated)	Predicted LC-MS/MS	splash10-0i29-0203691000-0ead50cdf45cc159795a

Chromatographic Properties

Collision Cross Sections (CCS)

Adduct	CCS Value (Å²)	Source type	Source
[M-H]-	230.15904	predicted	DeepCCS 1.0 (2019)
[M+H]+	231.98392	predicted	DeepCCS 1.0 (2019)
[M+Na]+	237.58974	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: Unknown
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

Chen C, Wu D, Guo Z, Xie Q, Reinhart GJ, Madan A, Wen J, Chen T, Huang CQ, Chen M, Chen Y, Tucci FC, Rowbottom M, Pontillo J, Zhu YF, Wade W, Saunders J, Bozigian H, Struthers RS: Discovery of sodium R-(+)-4-{2-[5-(2-fluoro-3-methoxyphenyl)-3-(2-fluoro-6-[trifluoromethyl]benzyl)-4 -methyl-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-yl]-1-phenylethylamino}butyrate (elagolix), a potent and orally available nonpeptide antagonist of the human gonadotropin-releasing hormone receptor. J Med Chem. 2008 Dec 11;51(23):7478-85. doi: 10.1021/jm8006454. [Article]

Enzymes

Details1. Cytochrome P450 3A Subfamily (Protein Group)

Kind: Protein group
Organism: Humans
Pharmacological action: No
Actions: Substrate

General Function: Vitamin d3 25-hydroxylase activity
Specific Function: Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...

Components:

Name	UniProt ID
Cytochrome P450 3A4	P08684
Cytochrome P450 3A43	Q9HB55
Cytochrome P450 3A5	P20815
Cytochrome P450 3A7	P24462

Details2. Cytochrome P450 2D6

Kind: Protein
Organism: Humans
Pharmacological action: No
Actions: Substrate

General Function: Steroid hydroxylase activity
Specific Function: Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name: CYP2D6
Uniprot ID: P10635
Uniprot Name: Cytochrome P450 2D6
Molecular Weight: 55768.94 Da

Details3. Cytochrome P450 2C8

Kind: Protein
Organism: Humans
Pharmacological action: No
Actions: Substrate

General Function: Steroid hydroxylase activity
Specific Function: Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name: CYP2C8
Uniprot ID: P10632
Uniprot Name: Cytochrome P450 2C8
Molecular Weight: 55824.275 Da

Transporters

Details1. P-glycoprotein 1

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate
Inhibitor
Curator comments: Elagolix is both a substrate and inhibitor of P-glycoprotein. The effect of concomitant use of P-glycoprotein inhibitors or inducers on the pharmacokinetics of elagolix is unknown.

General Function: Xenobiotic-transporting atpase activity
Specific Function: Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name: ABCB1
Uniprot ID: P08183
Uniprot Name: Multidrug resistance protein 1
Molecular Weight: 141477.255 Da

Details2. Solute carrier organic anion transporter family member 1B1

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate

General Function: Sodium-independent organic anion transmembrane transporter activity
Specific Function: Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostagland...
Gene Name: SLCO1B1
Uniprot ID: Q9Y6L6
Uniprot Name: Solute carrier organic anion transporter family member 1B1
Molecular Weight: 76447.99 Da

Drug created at October 20, 2016 21:07 / Updated at February 20, 2024 23:55

Elagolix

Identification

Structure for Elagolix (DB11979)

Pharmacology

Interactions

Products

Categories

Chemical Identifiers

References

Clinical Trials

Pharmacoeconomics

Properties

Spectra

Collision Cross Sections (CCS)

Targets

References

Enzymes

Components:

Transporters