Identification

Name
Elvitegravir
Accession Number
DB09101
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.

Elvitegravir was first licensed from Japan Tobacco in 2008 and developed by Gilead Sciences. It was FDA approved on August 27, 2012. On September 24, 2014, the FDA approved the single pill form of elvitegravir.

Type
Small Molecule
Groups
Approved
Structure
Thumb
Weight
Average: 447.884
Monoisotopic: 447.124878763
Chemical Formula
C23H23ClFNO5
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
  • Elvitegravir
  • EVG
  • GS 9137
External IDs
  • GS 9137
  • GS-9137
  • GS9137
  • JTK 303
  • JTK-303
  • JTK303

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
Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
Learn More
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
Adverse Effects
Learn about our commercial Adverse Effects data.
Learn More
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
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.
DrugInteraction
AbametapirThe serum concentration of Elvitegravir can be increased when it is combined with Abametapir.
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 Acalabrutinib can be decreased when combined with Elvitegravir.
AcenocoumarolThe serum concentration of Acenocoumarol can be decreased when it is combined with Elvitegravir.
AdenineThe metabolism of Elvitegravir can be decreased when combined with Adenine.
Adenovirus type 7 vaccine liveThe therapeutic efficacy of Adenovirus type 7 vaccine live can be decreased when used in combination with Elvitegravir.
AlbendazoleThe metabolism of Albendazole can be decreased when combined with Elvitegravir.
AlectinibThe metabolism of Alectinib can be decreased when combined with Elvitegravir.
AlfuzosinThe metabolism of Alfuzosin can be decreased when combined with Elvitegravir.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
  • Avoid St. John's Wort. This herb induces the CYP3A metabolism of elvitegravir. Therefore, it may reduce the serum concentration of elvitegravir and its effectiveness.
  • Take separate from antacids. Take at least 2 hours before or after antacids.
  • Take with food.

Products

Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
VitektaTablet85 mgOralGilead Sciences2015-04-212017-01-09Canada flag
VitektaTablet, film coated150 mgOralGilead Sciences2013-11-132017-05-29EU flag
VitektaTablet, film coated150 mg/1OralGilead Sciences2014-09-242017-02-28US flag
VitektaTablet, film coated85 mgOralGilead Sciences2013-11-132017-05-29EU flag
VitektaTablet150 mgOralGilead Sciences2015-04-212017-01-09Canada flag
VitektaTablet, film coated85 mg/1OralGilead Sciences2014-09-242017-02-28US flag
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
GenvoyaElvitegravir (150 mg) + Cobicistat (150 mg) + Emtricitabine (200 mg) + Tenofovir alafenamide (10 mg)Tablet, film coatedOralGilead Sciences Ireland Uc2015-11-19Not applicableEU flag
GenvoyaElvitegravir (150 mg/1) + Cobicistat (150 mg/1) + Emtricitabine (200 mg/1) + Tenofovir alafenamide fumarate (10 mg/1)TabletOralREMEDYREPACK INC.2017-06-06Not applicableUS flag
GenvoyaElvitegravir (150 mg) + Cobicistat (150 mg) + Emtricitabine (200 mg) + Tenofovir alafenamide (10 mg)TabletOralGilead Sciences2016-02-03Not applicableCanada flag
GenvoyaElvitegravir (150 mg/1) + Cobicistat (150 mg/1) + Emtricitabine (200 mg/1) + Tenofovir alafenamide fumarate (10 mg/1)TabletOralA-S Medication Solutions2015-11-052018-07-31US flag
GenvoyaElvitegravir (150 mg) + Cobicistat (150 mg) + Emtricitabine (200 mg) + Tenofovir alafenamide (10 mg)Tablet, film coatedOralGilead Sciences Ireland Uc2015-11-19Not applicableEU flag
GenvoyaElvitegravir (150 mg/1) + Cobicistat (150 mg/1) + Emtricitabine (200 mg/1) + Tenofovir alafenamide fumarate (10 mg/1)TabletOralGilead Sciences, Inc.2015-11-05Not applicableUS flag
StribildElvitegravir (150 mg/1) + Cobicistat (150 mg/1) + Emtricitabine (200 mg/1) + Tenofovir disoproxil fumarate (300 mg/1)Tablet, film coatedOralGilead Sciences, Inc.2012-08-27Not applicableUS flag
StribildElvitegravir (150 mg/1) + Cobicistat (150 mg/1) + Emtricitabine (200 mg/1) + Tenofovir disoproxil fumarate (300 mg/1)Tablet, film coatedOralREMEDYREPACK INC.2017-08-162020-05-01US flag
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 flag
StribildElvitegravir (150 mg) + Cobicistat (150 mg) + Emtricitabine (200 mg) + Tenofovir disoproxil fumarate (300 mg)TabletOralGilead Sciences2012-12-20Not applicableCanada flag

Categories

ATC Codes
J05AR09 — Emtricitabine, tenofovir disoproxil, elvitegravir and cobicistatJ05AX11 — ElvitegravirJ05AR18 — Emtricitabine, tenofovir alafenamide, elvitegravir and cobicistat
Drug Categories
Chemical TaxonomyProvided by Classyfire
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
Alcohol / Alkyl aryl ether / Anisole / Aromatic heteropolycyclic compound / Aryl chloride / Aryl fluoride / Aryl halide / Azacycle / Benzenoid / Carboxylic acid
show 26 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
organofluorine compound, aromatic ether, monochlorobenzenes, quinolone, quinolinemonocarboxylic acid (CHEBI:72289)

Chemical Identifiers

UNII
4GDQ854U53
CAS number
697761-98-1
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][[email protected]@](CO)(C(C)C)N1C=C(C(O)=O)C(=O)C2=C1C=C(OC)C(CC1=C(F)C(Cl)=CC=C1)=C2

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]
PubChem Compound
5277135
PubChem Substance
310265026
ChemSpider
4441060
BindingDB
50183273
RxNav
1306286
ChEBI
72289
ChEMBL
CHEMBL204656
ZINC
ZINC000013682481
PDBe Ligand
ELV
RxList
RxList Drug Page
Wikipedia
Elvitegravir
AHFS Codes
  • 08:18.08.12 — HIV Integrase Inhibitors
PDB Entries
3l2u / 3l2w
FDA label
Download (435 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Active Not RecruitingOtherHuman Immunodeficiency Virus (HIV) Infections1
4CompletedHealth Services ResearchHuman Immunodeficiency Virus (HIV) Infections1
4CompletedOtherHealthy Volunteers1
4CompletedPreventionHuman Immunodeficiency Virus (HIV) Infections2
4CompletedTreatment2- HIV Infection1
4CompletedTreatmentAcquired Immune Deficiency Syndrome (AIDS) / Human Immunodeficiency Virus (HIV) Infections / Sleep disorders and disturbances1
4CompletedTreatmentHepatitis C Infection / Human Immunodeficiency Virus (HIV) Infections1
4CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections2
4CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Severe Immunosuppression1
4CompletedTreatmentHuman Immunodeficiency Virus Type 1 (HIV-1) Infection1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
TabletOral
Tablet, film coatedOral
Tablet, coatedOral150 mg
TabletOral150 mg
TabletOral85 mg
Tablet, film coatedOral150 mg
Tablet, film coatedOral150 mg/1
Tablet, film coatedOral85 mg/1
Tablet, film coatedOral85 mg
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US7800788No2010-09-212022-02-02US flag
US5914331Yes1999-06-222018-01-02US flag
US6043230Yes2000-03-282018-01-25US flag
US5814639Yes1998-09-292017-03-29US flag
US6642245Yes2003-11-042021-05-04US flag
US6703396Yes2004-03-092021-09-09US flag
US5922695Yes1999-07-132018-01-25US flag
US5935946Yes1999-08-102018-01-25US flag
US5977089Yes1999-11-022018-01-25US flag
US8592397No2013-11-262024-01-13US flag
US8716264No2014-05-062024-01-13US flag
US8148374No2012-04-032029-09-03US flag
US7635704No2009-12-222026-10-26US flag
US7176220No2007-02-132023-11-20US flag
US8981103No2015-03-172026-10-26US flag
US8633219No2014-01-212030-04-24US flag
US9296769No2016-03-292032-08-15US flag
US7803788No2010-09-282022-02-02US flag
US8754065No2014-06-172032-08-15US flag
US7390791No2008-06-242022-05-07US flag
US9457036No2016-10-042024-01-13US flag
US9744181No2017-08-292024-01-13US flag
US9891239No2018-02-132029-09-03US flag
US10039718No2018-08-072032-10-04US flag
Additional Data Available
  • Filed On
    Filed On

    The date on which a patent was filed with the relevant government.

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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

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
Humans
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. FDA label: Stribild [File]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Protein homodimerization activity
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the...
Gene Name
UGT1A4
Uniprot ID
P22310
Uniprot Name
UDP-glucuronosyltransferase 1-4
Molecular Weight
60024.535 Da

Drug created on September 16, 2015 15:56 / Updated on October 25, 2020 09:16

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