# Etravirine

> Mediated Wiki article. Canonical URL: https://mediated.wiki/source/Etravirine
> Markdown URL: https://mediated.wiki/source/Etravirine.md
> Source: https://en.wikipedia.org/wiki/Etravirine
> Source revision: 1352070686
> License: Creative Commons Attribution-ShareAlike 4.0 International (https://creativecommons.org/licenses/by-sa/4.0/)

{{Short description|Medication used for the treatment of HIV}}
{{Use dmy dates|date=August 2024}}
{{cs1 config |name-list-style=vanc |display-authors=6}}
{{Infobox drug
| Verifiedfields = changed
| Watchedfields = changed
| verifiedrevid = 443748530
| image = Etravirine structure.svg
| image_class = skin-invert-image
| width = 150
| alt = 
| image2 = Etravirine ball-and-stick model.png
| width2 = 185
| alt2 = 

<!-- Clinical data -->
| pronounce = {{IPAc-en|ˌ|ɛ|t|r|ə|ˈ|v|ɪ|r|iː|n}}<br />{{respell|ET|rə|VIR|een}}
| tradename = Intelence
| Drugs.com = {{drugs.com|monograph|etravirine}}
| MedlinePlus = a608016
| DailyMedID = Etravirine
| pregnancy_AU = B1
| pregnancy_AU_comment = 
| pregnancy_category = 
| routes_of_administration = [By mouth](/source/By_mouth)
| class = 
| ATC_prefix = J05
| ATC_suffix = AG04
| ATC_supplemental = 

<!-- Legal status -->
| legal_AU = S4
| legal_AU_comment = 
| legal_BR = <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C4, C5, D1, D2, E, F -->
| legal_BR_comment = 
| legal_CA = Schedule VI
| legal_CA_comment = 
| legal_DE = <!-- Anlage I, II, III or Unscheduled -->
| legal_DE_comment = 
| legal_NZ = <!-- Class A, B, C -->
| legal_NZ_comment = 
| legal_UK = POM
| legal_UK_comment = 
| legal_US = Rx-only
| legal_US_comment = <ref name="Intelence FDA label">{{cite web | title=Intelence- etravirine tablet | website=DailyMed | date=15 August 2023 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=6a9cbc29-9f15-4b24-8d86-206b82887f3d | access-date=14 August 2024}}</ref>
| legal_EU = Rx-only
| legal_EU_comment = <ref name="Intelence EPAR">{{cite web | title=Intelence EPAR | website=[European Medicines Agency](/source/European_Medicines_Agency) (EMA) | date=28 August 2008 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/intelence | access-date=14 August 2024}} Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.</ref>
| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV -->
| legal_UN_comment = 
| legal_status = <!-- For countries not listed above -->

<!-- Pharmacokinetic data -->
| bioavailability = 
| protein_bound = 99.9%
| metabolism = [Liver](/source/Liver) ([CYP3A4](/source/CYP3A4), [CYP2C9](/source/CYP2C9) & [CYP2C19](/source/CYP2C19)-mediated)
| metabolites = 
| onset = 
| elimination_half-life = 41±20 hours
| duration_of_action = 
| excretion = Faeces (93.7%), urine (1.2%)

<!-- Identifiers -->
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 269055-15-4
| PubChem = 193962
| IUPHAR_ligand = 
| DrugBank_Ref = {{drugbankcite|changed|drugbank}}
| DrugBank = DB06414
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 168313
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 0C50HW4FO1
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D04112
| ChEBI = 
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 308954
| NIAID_ChemDB = 105156
| PDB_ligand = 65B
| synonyms = TMC125

<!-- Chemical and physical data -->
| IUPAC_name = 4-[6-Amino-5-bromo-2-[(4-cyanophenyl)amino] pyrimidin-4-yl]oxy-3,5-dimethylbenzonitrile
| C=20 | H=15 | Br=1 | N=6 | O=1
| SMILES = N#Cc3cc(c(Oc1nc(nc(c1Br)N)Nc2ccc(C#N)cc2)c(c3)C)C
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C20H15BrN6O/c1-11-7-14(10-23)8-12(2)17(11)28-19-16(21)18(24)26-20(27-19)25-15-5-3-13(9-22)4-6-15/h3-8H,1-2H3,(H3,24,25,26,27)
| StdInChI_comment = 
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = PYGWGZALEOIKDF-UHFFFAOYSA-N
| density = 
| density_notes = 
| melting_point = 
| melting_high = 
| melting_notes = 
| boiling_point = 
| boiling_notes = 
| solubility = 
| sol_units = 
| specific_rotation = 
}}

'''Etravirine''' ('''ETR'''<ref>{{cite web |publisher=[Department of Health and Human Services](/source/Department_of_Health_and_Human_Services) |work=Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents |url=http://aidsinfo.nih.gov/guidelines/html/1/adult-and-adolescent-arv-guidelines/34/appendix-a--key-to-acronyms |archive-url=https://web.archive.org/web/20120831103819/http://www.aidsinfo.nih.gov/guidelines/html/1/adult-and-adolescent-arv-guidelines/34/appendix-a--key-to-acronyms |url-status=dead |archive-date=31 August 2012 |title=Appendix A: Key to Acronyms }}</ref>), sold under the brand name '''Intelence''' is an [antiretroviral medication](/source/antiretroviral_medication) used for the treatment of [HIV](/source/HIV).<ref name="Intelence FDA label" /> Etravirine is a human immunodeficiency virus type 1 (HIV-1) [non-nucleoside reverse transcriptase inhibitor](/source/non-nucleoside_reverse_transcriptase_inhibitor) (NNRTI).<ref name="Intelence FDA label" /> Unlike agents in the class, resistance to other NNRTIs does not seem to confer resistance to etravirine.<ref>{{cite journal | vauthors = Stellbrink HJ | title = Antiviral drugs in the treatment of AIDS: what is in the pipeline ? | journal = European Journal of Medical Research | volume = 12 | issue = 9 | pages = 483–495 | date = October 2007 | pmid = 17933730 }}</ref> Etravirine is marketed by [Janssen](/source/Janssen_Pharmaceuticals), a [subsidiary](/source/subsidiary) of [Johnson & Johnson](/source/Johnson_%26_Johnson). In January 2008, the US [Food and Drug Administration](/source/Food_and_Drug_Administration) (FDA) approved its use for people with established resistance to other drugs, making it the 30th anti-HIV drug approved in the United States and the first to be approved in 2008.<ref>{{cite web |url=http://ap.google.com/article/ALeqM5iCFQR1SKu681KqBBwrXJg1B6q5PAD8U8MS3G0 |title=FDA Approves HIV Drug Etravirine |publisher=[Associated Press](/source/Associated_Press) |date=18 January 2008 }}{{dead link|date=November 2012|bot=Legobot}}</ref> It was also approved for use in Canada in April 2008.<ref>{{cite press release |title=First New NNRTI in Nearly a Decade to Benefit Canadians with HIV/AIDS |publisher=Janssen-Ortho Inc. |date=1 April 2008 |url=http://www.janssen-ortho.com/JOI/pdf_files/INTELENCE_Press_Release_E.pdf |access-date=9 July 2008 |url-status=dead |archive-url=https://web.archive.org/web/20101102080713/http://janssen-ortho.com/JOI/pdf_files/INTELENCE_Press_Release_E.pdf |archive-date=2 November 2010 }}</ref>

Etravirine is licensed in the United States, Canada, Israel, Russia, Australia, New Zealand, and the European Union,<ref>{{cite web |url=http://www.tibotec.com/news/detail.jhtml?itemname=news_48 |publisher=Tibotec |title=Intelence receives marketing authorisation in the European Union for HIV combination therapy |access-date=29 August 2008 |url-status=dead |archive-url=https://web.archive.org/web/20110928020018/http://www.tibotec.com/news/detail.jhtml?itemname=news_48 |archive-date=28 September 2011 }}</ref> and is under regulatory review in Switzerland.<ref>{{cite web |url=http://www.aidsmap.com/en/news/46E8FC38-3BB8-4DDD-9FEC-D6BFD5DD69AA.asp |publisher=[aidsmap](/source/aidsmap) |title=Etravirine (TMC125, ''Intelence'') granted accelerated approval in US |access-date=24 January 2008 |archive-url=https://web.archive.org/web/20100102225629/http://aidsmap.com/en/news/46E8FC38-3BB8-4DDD-9FEC-D6BFD5DD69AA.asp |archive-date=2 January 2010 |url-status=dead }}</ref>

==Medical uses ==
In the US, etravirine is [indicated](/source/indicated) for the treatment of HIV-1 infection in treatment-experienced patients aged two years of age and older.<ref name="Intelence FDA label" />

In the EU, etravirine, in combination with a boosted protease inhibitor and other antiretrovirals, is indicated for the treatment of human-immunodeficiency-virus-type-1 (HIV-1) infection in antiretroviral-treatment-experienced people aged six years of age and older.<ref name="Intelence EPAR" />

==Contraindication==
People with rare hereditary problems of [galactose](/source/galactose) intolerance, the Lapp [lactase deficiency](/source/lactase_deficiency) or [glucose-galactose malabsorption](/source/glucose-galactose_malabsorption) should not take this etravine.<ref>{{cite web |title=Etravine: Summary of product characteristics |url=http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000900/WC500034180.pdf |page=5 |publisher=[EMEA](/source/European_Medicines_Agency) |access-date=13 July 2011 |archive-date=20 August 2016 |archive-url=https://web.archive.org/web/20160820115226/http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000900/WC500034180.pdf |url-status=dead }}</ref>

== Adverse effects ==
In 2009, the FDA prescribing information for etravirine was modified to include "postmarketing reports of cases of [Stevens–Johnson syndrome](/source/Stevens%E2%80%93Johnson_syndrome), [toxic epidermal necrolysis](/source/toxic_epidermal_necrolysis), and [erythema multiforme](/source/erythema_multiforme), as well as [hypersensitivity](/source/hypersensitivity) reactions characterized by rash, constitutional findings, and sometimes organ dysfunction, including [liver failure](/source/liver_failure)."<ref>{{cite web |url=https://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm180579.htm |archive-url=https://web.archive.org/web/20090829172944/http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm180579.htm |url-status=dead |archive-date=29 August 2009 |title=FDA Medwatch Safety Information |website=[Food and Drug Administration](/source/Food_and_Drug_Administration) |access-date=27 August 2009 }}</ref>

==Mechanism of action==
Etravirine is a second-generation [non-nucleoside reverse transcriptase inhibitor](/source/non-nucleoside_reverse_transcriptase_inhibitor) (NNRTI), designed to be active against HIV with mutations that confer resistance to the two most commonly prescribed first-generation NNRTIs, mutation K103N for [efavirenz](/source/efavirenz) and Y181C for [nevirapine](/source/nevirapine).<ref name="David Evans">{{cite web |url=http://www.aidsmeds.com/articles/etravirine_tmc125_hiv_2042_13846.shtml |title=Etravirine—Countdown to Launch |access-date=2 February 2008 | vauthors = Evans D |date=15 January 2008 |publisher=AIDSmeds.com |archive-date=19 January 2008 |archive-url=https://web.archive.org/web/20080119222616/http://www.aidsmeds.com/articles/etravirine_tmc125_hiv_2042_13846.shtml |url-status=dead }}</ref> This potency appears to be related to etravirine's flexibility as a molecule. Etravirine is a [diarylpyrimidine](/source/diarylpyrimidine) (DAPY), a type of [organic molecule](/source/organic_molecule) with some [conformational isomerism](/source/conformational_isomerism) that can bind the enzyme [reverse transcriptase](/source/reverse_transcriptase) in multiple [conformations](/source/Protein_conformation), allowing for a more robust interaction between etravirine and the enzyme, even in the presence of mutations.<ref name="pmid15115397">{{cite journal | vauthors = Das K, Clark AD, Lewi PJ, Heeres J, De Jonge MR, Koymans LM, Vinkers HM, Daeyaert F, Ludovici DW, Kukla MJ, De Corte B, Kavash RW, Ho CY, Ye H, Lichtenstein MA, Andries K, Pauwels R, De Béthune MP, Boyer PL, Clark P, Hughes SH, Janssen PA, Arnold E | title = Roles of conformational and positional adaptability in structure-based design of TMC125-R165335 (etravirine) and related non-nucleoside reverse transcriptase inhibitors that are highly potent and effective against wild-type and drug-resistant HIV-1 variants | journal = Journal of Medicinal Chemistry | volume = 47 | issue = 10 | pages = 2550–2560 | date = May 2004 | pmid = 15115397 | doi = 10.1021/jm030558s }}</ref>

==Chemistry==

Etravine forms as colourless [orthorhombic](/source/Orthorhombic_crystal_system) crystals in space group Pna2<sub>1</sub>.<ref name=":0">{{Cite journal | vauthors = Rajput L, Sanphui P, Desiraju GR |date=7 August 2013 |title=New Solid Forms of the Anti-HIV Drug Etravirine: Salts, Cocrystals, and Solubility |journal=Crystal Growth & Design |volume=13 |issue=8 |pages=3681–3690 |doi=10.1021/cg4007058 |bibcode=2013CrGrD..13.3681R |issn=1528-7483}}</ref> The structures of these and of a number of solvate and salt forms have been reported.<ref name=":0" /><ref>{{cite journal | vauthors = Muresan-Pop M, Macavei S, Turza A, Borodi G | title = New solvates and a salt of the anti-HIV compound etravirine | journal = Acta Crystallographica Section C: Structural Chemistry | volume = 77 | issue = Pt 11 | pages = 698–706 | date = November 2021 | pmid = 34738540 | doi = 10.1107/S2053229621010482 | s2cid = 243761396 }}</ref>

== Research==

Etravine has been studied for use in a [drug repositioning](/source/drug_repositioning) application. Etravirine was shown to cause an increase in [frataxin](/source/frataxin) production.<ref>{{cite journal | vauthors = Alfedi G, Luffarelli R, Condò I, Pedini G, Mannucci L, Massaro DS, Benini M, Toschi N, Alaimo G, Panarello L, Pacini L, Fortuni S, Serio D, Malisan F, Testi R, Rufini A | title = Drug repositioning screening identifies etravirine as a potential therapeutic for friedreich's ataxia | journal = Movement Disorders | volume = 34 | issue = 3 | pages = 323–334 | date = March 2019 | pmid = 30624801 | doi = 10.1002/mds.27604 | s2cid = 58567610 }}</ref>

== References ==
{{Reflist}}

{{Antiretroviral drug}}
{{Portal bar | Medicine | Viruses }}
{{Authority control}}

Category:CYP3A4 inducers
Category:Hepatotoxins
Category:Non-nucleoside reverse transcriptase inhibitors
Category:Aminopyrimidines
Category:Drugs developed by Johnson & Johnson
Category:Nitriles
Category:Organobromides
Category:Belgian inventions
Category:Diaryl ethers

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Adapted from the Wikipedia article [Etravirine](https://en.wikipedia.org/wiki/Etravirine) by Wikipedia contributors ([contributor history](https://en.wikipedia.org/wiki/Etravirine?action=history)). Available under [Creative Commons Attribution-ShareAlike 4.0 International](https://creativecommons.org/licenses/by-sa/4.0/). Changes may have been made.