Identification

Name
Elvitegravir
Accession Number
DB09101  (DB05618)
Type
Small Molecule
Groups
Approved
Description

Elvitegravir is a human immunodeficiency virus type 1 (HIV-1) integrase strand transfer inhibitor (INSTI) used for the treatment of HIV-1 infection in antiretroviral treatment-experienced adults. Because integrase is necessary for viral replication, inhibition prevents the integration of HIV-1 DNA into the host genome and thereby blocks the formation of the HIV-1 provirus and resulting propagation of the viral infection. Although available as a single dose tablet, elvitegravir must be used in combination with an HIV protease inhibitor coadministered with ritonavir and another antiretroviral drug.

It was developed by the pharmaceutical company Gilead Sciences, which licensed EVG from Japan Tobacco in March 2008. The drug gained approval by the U.S. Food and Drug Administration on August 27, 2012 for use in adult patients starting HIV treatment for the first time as part of the fixed dose combination known as Stribild. On September 24, 2014 the FDA approved Elvitegravir (tradename Vitekta) as a single pill formulation.

Structure
Thumb
Synonyms
  • 6-(3-chloro-2-fluorobenzyl)-1-[(2S)-1-hydroxy-3-methylbutan-2-yl]-7-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid
  • elvitégravir
  • EVG
  • GS 9137
External IDs
GS 9137 / GS-9137 / GS9137 / JTK 303 / JTK-303 / JTK303
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
VitektaTablet, film coated150 mg/1OralGilead Sciences2014-09-242017-02-28Us
VitektaTablet85 mgOralGilead Sciences2015-04-212017-01-09Canada
VitektaTablet, film coated85 mg/1OralGilead Sciences2014-09-242017-02-28Us
VitektaTablet150 mgOralGilead Sciences2015-04-212017-01-09Canada
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
GenvoyaElvitegravir (150 mg) + Cobicistat (150 mg) + Emtricitabine (200 mg) + Tenofovir alafenamide (10 mg)Tablet, film coatedOralGilead Sciences Ireland Uc2015-11-19Not applicableEu
GenvoyaElvitegravir (150 mg/1) + Cobicistat (150 mg/1) + Emtricitabine (200 mg/1) + Tenofovir alafenamide fumarate (10 mg/1)TabletOralA-S Medication Solutions2015-11-05Not applicableUs
GenvoyaElvitegravir (150 mg) + Cobicistat (150 mg) + Emtricitabine (200 mg) + Tenofovir alafenamide (10 mg)Tablet, film coatedOralGilead Sciences Ireland Uc2015-11-19Not applicableEu
GenvoyaElvitegravir (150 mg/1) + Cobicistat (150 mg/1) + Emtricitabine (200 mg/1) + Tenofovir alafenamide fumarate (10 mg/1)TabletOralGilead Sciences2015-11-05Not applicableUs
GenvoyaElvitegravir (150 mg/1) + Cobicistat (150 mg/1) + Emtricitabine (200 mg/1) + Tenofovir alafenamide fumarate (10 mg/1)TabletOralRemedy Repack2017-06-07Not applicableUs
GenvoyaElvitegravir (150 mg) + Cobicistat (150 mg) + Emtricitabine (200 mg) + Tenofovir alafenamide (10 mg)TabletOralGilead Sciences2016-02-03Not applicableCanada
StribildElvitegravir (150 mg) + Cobicistat (150 mg) + Emtricitabine (200 mg) + Tenofovir disoproxil fumarate (300 mg)TabletOralGilead Sciences2012-12-20Not applicableCanada
StribildElvitegravir (150 mg/1) + Cobicistat (150 mg/1) + Emtricitabine (200 mg/1) + Tenofovir disoproxil fumarate (300 mg/1)Tablet, film coatedOralGilead Sciences2012-08-27Not applicableUs
StribildElvitegravir (150 mg/1) + Cobicistat (150 mg/1) + Emtricitabine (200 mg/1) + Tenofovir disoproxil fumarate (300 mg/1)Tablet, film coatedOralAvera McKennan Hospital2015-10-28Not applicableUs
StribildElvitegravir (150 mg/1) + Cobicistat (150 mg/1) + Emtricitabine (200 mg/1) + Tenofovir disoproxil fumarate (300 mg/1)Tablet, film coatedOralState of Florida DOH Central Pharmacy2014-01-01Not applicableUs
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
VitektaElvitegravir (85 mg)Tablet, film coatedOralGilead Sciences2013-11-132017-05-29Eu
VitektaElvitegravir (150 mg)Tablet, film coatedOralGilead Sciences2013-11-132017-05-29Eu
Categories
UNII
4GDQ854U53
CAS number
697761-98-1
Weight
Average: 447.884
Monoisotopic: 447.124878763
Chemical Formula
C23H23ClFNO5
InChI Key
JUZYLCPPVHEVSV-LJQANCHMSA-N
InChI
InChI=1S/C23H23ClFNO5/c1-12(2)19(11-27)26-10-16(23(29)30)22(28)15-8-14(20(31-3)9-18(15)26)7-13-5-4-6-17(24)21(13)25/h4-6,8-10,12,19,27H,7,11H2,1-3H3,(H,29,30)/t19-/m1/s1
IUPAC Name
6-[(3-chloro-2-fluorophenyl)methyl]-1-[(2S)-1-hydroxy-3-methylbutan-2-yl]-7-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid
SMILES
[H][C@@](CO)(C(C)C)N1C=C(C(O)=O)C(=O)C2=C1C=C(OC)C(CC1=C(F)C(Cl)=CC=C1)=C2

Pharmacology

Indication

Elvitegravir in combination with an HIV protease inhibitor coadministered with ritonavir and with other antiretroviral drug(s) is indicated for the treatment of HIV-1 infection in antiretroviral treatment-experienced adults.

Associated Conditions
Pharmacodynamics
Not Available
Mechanism of action

Elvitegravir is an HIV-1 integrase strand transfer inhibitor (INSTI). Integrase is an HIV-1 encoded enzyme that is required for viral replication. Inhibition of integrase prevents the integration of HIV-1 DNA into host genomic DNA, blocking the formation of the HIV-1 provirus and propagation of the viral infection. Elvitegravir does not inhibit human topoisomerases I or II.

TargetActionsOrganism
AIntegrase
inhibitor
Human immunodeficiency virus 1
Absorption

Following oral administration of elvitegravir and ritonavir with food, in HIV-1 infected subjects, peak elvitegravir plasma concentrations were observed approximately 4 hours post-dose.

Volume of distribution
Not Available
Protein binding

Elvitegravir is 98–99% bound to human plasma proteins

Metabolism

Elvitegravir undergoes primarily oxidative metabolism via CYP3A, and is secondarily glucuronidated via UGT1A1/3 enzymes. Metabolites are found in the plasma at very low concentrations, displayed considerably lower anti-HIV activity, and did not contribute to the overall antiviral activity of elvitegravir.

Route of elimination

Following oral administration of [14C]elvitegravir/ritonavir, 94.8% of the dose was recovered in feces, while 6.7% was recovered in urine as metabolites.

Half life

The median terminal plasma half-life following administration of elvitegravir and ritonavir was approximately 8.7 hours.

Clearance
Not Available
Toxicity

The most common adverse reactions reported for elvitegravir use during clinical trials include nausea, vomiting, and diarrhea. Less common side effects occurring in <2% of patients, include abdominal pain, dyspepsia, fatigue, insomnia, rash, depression, suicidal ideation, and suicidal attempt.

Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of (R)-warfarin can be decreased when combined with Elvitegravir.
(S)-WarfarinThe metabolism of (S)-Warfarin can be decreased when combined with Elvitegravir.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Elvitegravir.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Elvitegravir.
5-androstenedioneThe metabolism of 5-androstenedione can be decreased when combined with Elvitegravir.
6-Deoxyerythronolide BThe metabolism of Elvitegravir can be decreased when combined with 6-Deoxyerythronolide B.
6-O-benzylguanineThe metabolism of 6-O-benzylguanine can be decreased when combined with Elvitegravir.
AbemaciclibThe metabolism of Abemaciclib can be decreased when combined with Elvitegravir.
AbirateroneThe metabolism of Abiraterone can be decreased when combined with Elvitegravir.
AcalabrutinibThe metabolism of Elvitegravir can be decreased when combined with Acalabrutinib.
Food Interactions
Not Available

References

General References
  1. Pommier Y, Johnson AA, Marchand C: Integrase inhibitors to treat HIV/AIDS. Nat Rev Drug Discov. 2005 Mar;4(3):236-48. [PubMed:15729361]
  2. Schafer JJ, Squires KE: Integrase inhibitors: a novel class of antiretroviral agents. Ann Pharmacother. 2010 Jan;44(1):145-56. doi: 10.1345/aph.1M309. Epub 2009 Dec 29. [PubMed:20040702]
  3. Hazuda DJ, Felock P, Witmer M, Wolfe A, Stillmock K, Grobler JA, Espeseth A, Gabryelski L, Schleif W, Blau C, Miller MD: Inhibitors of strand transfer that prevent integration and inhibit HIV-1 replication in cells. Science. 2000 Jan 28;287(5453):646-50. [PubMed:10649997]
  4. Luo ZG, Tan JJ, Zeng Y, Wang CX, Hu LM: Development of integrase inhibitors of quinolone acid derivatives for treatment of AIDS: an overview. Mini Rev Med Chem. 2010 Oct;10(11):1046-57. [PubMed:21044030]
  5. Metifiot M, Vandegraaff N, Maddali K, Naumova A, Zhang X, Rhodes D, Marchand C, Pommier Y: Elvitegravir overcomes resistance to raltegravir induced by integrase mutation Y143. AIDS. 2011 Jun 1;25(9):1175-8. doi: 10.1097/QAD.0b013e3283473599. [PubMed:21505303]
  6. Lee JS, Calmy A, Andrieux-Meyer I, Ford N: Review of the safety, efficacy, and pharmacokinetics of elvitegravir with an emphasis on resource-limited settings. HIV AIDS (Auckl). 2012;4:5-15. doi: 10.2147/HIV.S20993. Epub 2012 Jan 12. [PubMed:22347806]
  7. Wills T, Vega V: Elvitegravir: a once-daily inhibitor of HIV-1 integrase. Expert Opin Investig Drugs. 2012 Mar;21(3):395-401. doi: 10.1517/13543784.2012.658914. Epub 2012 Feb 10. [PubMed:22321026]
  8. Adams JL, Greener BN, Kashuba AD: Pharmacology of HIV integrase inhibitors. Curr Opin HIV AIDS. 2012 Sep;7(5):390-400. doi: 10.1097/COH.0b013e328356e91c. [PubMed:22789987]
  9. Smith RA, Raugi DN, Pan C, Coyne M, Hernandez A, Church B, Parker K, Mullins JI, Sow PS, Gottlieb GS: Three main mutational pathways in HIV-2 lead to high-level raltegravir and elvitegravir resistance: implications for emerging HIV-2 treatment regimens. PLoS One. 2012;7(9):e45372. doi: 10.1371/journal.pone.0045372. Epub 2012 Sep 18. [PubMed:23028968]
External Links
PubChem Compound
5277135
PubChem Substance
310265026
ChemSpider
4441060
BindingDB
50183273
ChEBI
72289
ChEMBL
CHEMBL204656
HET
ELV
RxList
RxList Drug Page
Wikipedia
Elvitegravir
ATC Codes
J05AR18 — Emtricitabine, tenofovir alafenamide, elvitegravir and cobicistatJ05AR09 — Emtricitabine, tenofovir disoproxil, elvitegravir and cobicistatJ05AX11 — Elvitegravir
AHFS Codes
  • 08:18.08.12 — HIV Integrase Inhibitors
PDB Entries
3l2u / 3l2w
FDA label
Download (435 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedNot AvailableHuman Immunodeficiency Virus (HIV)2
1CompletedOtherHIV-DDI1
1CompletedTreatmentInsulin Resistance1
1RecruitingPreventionHuman Immunodeficiency Virus (HIV) Infections1
1RecruitingTreatmentInsulin Resistance1
2CompletedTreatmentAcquired Immune Deficiency Syndrome (AIDS) / Human Immunodeficiency Virus (HIV) Infections1
2CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections1
2CompletedTreatmentHuman Immunodeficiency Virus (HIV) / Human Immunodeficiency Virus (HIV) Infections1
2Not Yet RecruitingTreatmentHuman Immunodeficiency Virus (HIV) Infections1
2, 3CompletedTreatmentAcquired Immune Deficiency Syndrome (AIDS) / Human Immunodeficiency Virus (HIV) Infections1
2, 3CompletedTreatmentHuman Immunodeficiency Virus (HIV)1
2, 3TerminatedTreatmentAcquired Immune Deficiency Syndrome (AIDS) / Human Immunodeficiency Virus (HIV) Infections1
3Active Not RecruitingTreatmentChronic Hepatitis C Virus (HCV) Infection / Human Immunodeficiency Virus (HIV)1
3Active Not RecruitingTreatmentHuman Immunodeficiency Virus (HIV)1
3Active Not RecruitingTreatmentHuman Immunodeficiency Virus (HIV) / Human Immunodeficiency Virus (HIV) Infections2
3Active Not RecruitingTreatmentInfection, Human Immunodeficiency Virus I3
3CompletedTreatmentAcquired Immune Deficiency Syndrome (AIDS) / Human Immunodeficiency Virus (HIV) Infections5
3CompletedTreatmentAcquired Immune Deficiency Syndrome (AIDS) / Human Immunodeficiency Virus (HIV) Infections / Human Immunodeficiency Virus Type 1 (HIV-1)1
3CompletedTreatmentAcquired Immune Deficiency Syndrome (AIDS) / Human Immunodeficiency Virus (HIV) / Human Immunodeficiency Virus (HIV) Infections1
3CompletedTreatmentHBV / Human Immunodeficiency Virus (HIV)1
3CompletedTreatmentHepatitis C Virus (HCV) Infection / Infection, Human Immunodeficiency Virus I1
3CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections1
3CompletedTreatmentHuman Immunodeficiency Virus (HIV) / Human Immunodeficiency Virus (HIV) Infections4
3CompletedTreatmentInfection, Human Immunodeficiency Virus I2
3Enrolling by InvitationTreatmentHIV Risk1
4CompletedHealth Services ResearchHuman Immunodeficiency Virus (HIV)1
4CompletedPreventionHuman Immunodeficiency Virus (HIV)2
4CompletedTreatmentAcquired Immune Deficiency Syndrome (AIDS) / Human Immunodeficiency Virus (HIV) / Sleep disorders and disturbances1
4CompletedTreatmentHepatitis C Infection / Human Immunodeficiency Virus (HIV) Infections1
4CompletedTreatmentInfection, Human Immunodeficiency Virus I1
4RecruitingSupportive CareHuman Immunodeficiency Virus (HIV)1
4RecruitingTreatmentAntiretroviral Therapy Intolerance / Patients Compliance1
4RecruitingTreatmentBone Diseases, Metabolic / Chronic Hepatitis C Virus (HCV) Infection / Co-Infection / HIV-1-infection / Human Immunodeficiency Virus Infection(HIV)/Acquired Immunodeficiency Syndrome (AIDS) / Intravenous Drug Usage / Methadone Dependence / Opioid Dependence / Substance Abuse1
4RecruitingTreatmentHuman Immunodeficiency Virus (HIV) Infections1
4RecruitingTreatmentHuman Immunodeficiency Virus (HIV) Infections / Severe Immunosuppression1
Not AvailableCompletedBasic ScienceHuman Immunodeficiency Virus (HIV)1
Not AvailableCompletedTreatmentHuman Immunodeficiency Virus (HIV)1
Not AvailableNot Yet RecruitingTreatmentHuman Immunodeficiency Virus Infection(HIV)/Acquired Immunodeficiency Syndrome (AIDS)1
Not AvailableRecruitingNot AvailableBone Diseases / Chronic Hepatitis B in HIV Patient / Kidney Injury1
Not AvailableRecruitingNot AvailableHuman Immunodeficiency Virus (HIV)1
Not AvailableRecruitingNot AvailableHuman Immunodeficiency Virus (HIV) / Illicit Drug User1
Not AvailableRecruitingTreatmentHuman Immunodeficiency Virus (HIV) Infections1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Tablet, film coatedOral
TabletOral
TabletOral150 mg
TabletOral85 mg
Tablet, film coatedOral150 mg/1
Tablet, film coatedOral150 mg
Tablet, film coatedOral85 mg
Tablet, film coatedOral85 mg/1
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US7800788No2002-02-022022-02-02Us
US5914331Yes1998-01-022018-01-02Us
US6043230Yes1998-01-252018-01-25Us
US5814639Yes1997-03-292017-03-29Us
US6642245Yes2001-05-042021-05-04Us
US6703396Yes2001-09-092021-09-09Us
US5922695Yes1998-01-252018-01-25Us
US5935946Yes1998-01-252018-01-25Us
US5977089Yes1998-01-252018-01-25Us
US8592397No2004-01-132024-01-13Us
US8716264No2004-01-132024-01-13Us
US8148374No2009-09-032029-09-03Us
US7635704No2006-10-262026-10-26Us
US7176220No2003-11-202023-11-20Us
US8981103No2006-10-262026-10-26Us
US8633219No2010-04-242030-04-24Us
US9296769No2012-08-152032-08-15Us
US7803788No2002-02-022022-02-02Us
US8754065No2012-08-152032-08-15Us
US7390791No2002-05-072022-05-07Us
US9457036No2004-01-132024-01-13Us
US9744181No2004-01-132024-01-13Us
US9891239No2009-09-032029-09-03Us
US10039718No2012-10-042032-10-04Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubility<0.3 mcg/mLNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.00652 mg/mLALOGPS
logP3.66ALOGPS
logP4.67ChemAxon
logS-4.8ALOGPS
pKa (Strongest Acidic)6.16ChemAxon
pKa (Strongest Basic)-0.53ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area87.07 Å2ChemAxon
Rotatable Bond Count7ChemAxon
Refractivity116.26 m3·mol-1ChemAxon
Polarizability44.8 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0002-0004900000-925d782802c34a81f43a

Taxonomy

Description
This compound belongs to the class of organic compounds known as quinoline carboxylic acids. These are quinolines in which the quinoline ring system is substituted by a carboxyl group at one or more positions.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Quinolines and derivatives
Sub Class
Quinoline carboxylic acids
Direct Parent
Quinoline carboxylic acids
Alternative Parents
Hydroquinolones / Hydroquinolines / Pyridinecarboxylic acids / Anisoles / Alkyl aryl ethers / Chlorobenzenes / Fluorobenzenes / Aryl chlorides / Aryl fluorides / Vinylogous amides
show 11 more
Substituents
Quinoline-3-carboxylic acid / Dihydroquinolone / Dihydroquinoline / Pyridine carboxylic acid / Pyridine carboxylic acid or derivatives / Anisole / Alkyl aryl ether / Halobenzene / Fluorobenzene / Chlorobenzene
show 26 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
organofluorine compound, aromatic ether, monochlorobenzenes, quinolone, quinolinemonocarboxylic acid (CHEBI:72289)

Targets

Kind
Protein
Organism
Human immunodeficiency virus 1
Pharmacological action
Yes
Actions
Inhibitor
General Function
Zinc ion binding
Specific Function
Not Available
Gene Name
pol
Uniprot ID
Q7ZJM1
Uniprot Name
Integrase
Molecular Weight
32226.645 Da

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
Inhibitor
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...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Drug Interactions & Labeling - FDA [Link]
2. UDP-glucuronosyltransferase 1A1
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate

Drug created on September 16, 2015 15:56 / Updated on November 14, 2018 12:57