Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2012/12/07 21:24:57」(JST)

wiki en

Etravirine (ETR^[1], brand name Intelence, formerly known as TMC125) is a drug used for the treatment of HIV. Etravirine is a non-nucleoside reverse transcriptase inhibitor (NNRTI). Unlike the currently available agents in the class, resistance to other NNRTIs does not seem to confer resistance to etravirine.^[2] Etravirine is marketed by Tibotec, a subsidiary of Johnson & Johnson. In January 2008, the Food and Drug Administration approved its use for patients 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.^[3] It was also approved for use in Canada on April 1, 2008.^[4]

Etravirine is licensed in the United States, Canada, Israel and the European Union,^[5] and is under regulatory review in Switzerland, Russia and Australia.^[6]

Indications and dosage

Etravirine, in combination with other anti-retrovirals, is indicated for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in antiretroviral treatment-experienced adult patients, who have evidence of viral replication and HIV-1 strains resistant to a non-nucleoside reverse transcriptase inhibitor (NNRTI) and other antiretroviral agents.

The recommended dose of etravirine is 200 mg (2 x 100 mg tablets, or 1 x 200 mg tablet as of 03/18/2011) taken twice daily following a meal. The type of food does not affect the exposure to etravirine.^[7]

Contraindication

Each 100 mg etravirine tablet contains 160 mg of lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.^[8]

Mechanism of action

Etravirine is a second-generation 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 and Y181C for nevirapine.^[9] This potency appears to be related to etravirine's flexibility as a molecule. Etravirine is a diarylpyrimidine (DAPY), a type of organic molecule with some conformational isomerism that can bind the enzyme reverse transcriptase in multiple conformations, allowing for a more robust interaction between etravirine and the enzyme, even in the presence of mutations.^[10] Other diarylpyrimidine-analogues are currently being developed as potential anti-HIV agents, notably rilpivirine.

Warnings and risks

In 2009, the prescribing information for etravirine was modified to include "postmarketing reports of cases of Stevens–Johnson syndrome, toxic epidermal necrolysis and erythema multiforme, as well as hypersensitivity reactions characterized by rash, constitutional findings, and sometimes organ dysfunction, including hepatic failure. Intelence therapy should be immediately discontinued when signs and symptoms of severe skin or hypersensitivity reactions develop."^[11]

External links

Manufacturer's site
Prescribing information
AIDS map
AIDS meds
Etravirine bound to proteins in the PDB

References

^ U.S. Department of Health and Human Services: Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents, Appendix A: Key to Acronyms
^ Stellbrink HJ (October 2007). "Antiviral drugs in the treatment of AIDS: what is in the pipeline ?". Eur. J. Med. Res. 12 (9): 483–95. PMID 17933730.
^ FDA Approves HIV Drug Etravirine, Associated Press, January 18, 2008.^{[dead link]}
^ "First New NNRTI in Nearly a Decade to Benefit Canadians with HIV/AIDS" (Press release). Janssen-Ortho Inc.. 2008-04-01. http://www.janssen-ortho.com/JOI/pdf_files/INTELENCE_Press_Release_E.pdf. Retrieved 2008-07-09.
^ "Intelence receives marketing authorisation in the European Union for HIV combination therapy". Tibotec. http://www.tibotec.com/news/detail.jhtml?itemname=news_48. Retrieved 2008-08-29.
^ "Etravirine (TMC125, Intelence) granted accelerated approval in US". aidsmap. http://www.aidsmap.com/en/news/46E8FC38-3BB8-4DDD-9FEC-D6BFD5DD69AA.asp. Retrieved 2008-01-24.
^ "Intelence prescribing information" (pdf). FDA. http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022187s008lbl.pdf. Retrieved January 2012.
^ "Etravine: Summary of product characteristics". EMEA. p. 5. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000900/WC500034180.pdf. Retrieved July 2011.
^ Evans, David (2008-01-15). "Etravirine—Countdown to Launch". AIDSmeds.com. http://www.aidsmeds.com/articles/etravirine_tmc125_hiv_2042_13846.shtml. Retrieved 2008-02-02.
^ 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; Clark (2004). "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". J. Med. Chem. 47 (10): 2550–60. doi:10.1021/jm030558s. PMID 15115397.
^ "FDA Medwatch Safety Information". http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm180579.htm. Retrieved 2009-08-27.

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

1. 非ヌクレオシド系逆転写酵素阻害剤の薬理学 pharmacology of non nucleoside reverse transcriptase inhibitors
2. HIV抗レトロウイルス療法に関する臨床試験：非ヌクレオシド系逆転写酵素阻害剤 clinical trials of hiv antiretroviral therapy non nucleoside reverse transcriptase inhibitors
3. 治療経験のある薬剤耐性HIV感染患者における抗レトロウイルス療法の選択 selection of antiretroviral therapy for the treatment experienced patient with drug resistant hiv infection
4. 妊娠時の抗レトロウイルス剤：非ヌクレオシド系逆転写酵素阻害剤 antiretroviral medications in pregnancy non nucleoside reverse transcriptase inhibitors
5. 抗レトロウイルス療法の潜在的副作用に関するHIV感染患者を対象としたカウンセリング counseling hiv infected patients regarding potential side effects of antiretroviral therapy

English Journal

Telaprevir-based therapy in patients coinfected with chronic hepatitis C virus infection and HIV: INSIGHT study.

Montes ML1, Nelson M2, Girard PM3, Sasadeusz J4, Horban A5, Grinsztejn B6, Zakharova N7, Rivero A8, Durant J9, Ortega-Gonzalez E10, Lathouwers E11, Janssen K11, Ouwerkerk-Mahadevan S11, Witek J12, González-García J1.
The Journal of antimicrobial chemotherapy.J Antimicrob Chemother.2016 Jan;71(1):244-50. doi: 10.1093/jac/dkv323. Epub 2015 Oct 19.
OBJECTIVES: INSIGHT (ClinicalTrials.gov NCT01513941) evaluated the efficacy, safety and pharmacokinetics of telaprevir-based therapy and specific antiretroviral agents in hepatitis C virus genotype 1 (HCV-1)/HIV-1-coinfected patients.PATIENTS AND METHODS: Open-label, Phase IIIb, multicentre study of
PMID 26483516

High prevalence of PI resistance in patients failing second-line ART in Vietnam.

Thao VP1, Quang VM2, Day JN3, Chinh NT2, Shikuma CM4, Farrar J3, Vinh Chau NV2, Thwaites GE3, Dunstan SJ5, Le T6.
The Journal of antimicrobial chemotherapy.J Antimicrob Chemother.2015 Dec 11. pii: dkv385. [Epub ahead of print]
BACKGROUND: There are limited data from resource-limited settings on antiretroviral resistance mutations that develop in patients failing second-line PI ART.METHODS: We performed a cross-sectional virological assessment of adults on second-line ART for ≥6 months between November 2006 and December
PMID 26661398

Nanoparticle-Based ARV Drug Combinations for Synergistic Inhibition of Cell-Free and Cell-Cell HIV Transmission.

Jiang Y1, Cao S1, Bright DK2, Bever AM2, Blakney AK1, Suydam IT2, Woodrow KA1.
Molecular pharmaceutics.Mol Pharm.2015 Dec 7;12(12):4363-74. doi: 10.1021/acs.molpharmaceut.5b00544. Epub 2015 Nov 18.
Nanocarrier-based drug delivery systems are playing an emerging role in human immunodeficiency virus (HIV) chemoprophylaxis and treatment due to their ability to alter the pharmacokinetics and improve the therapeutic index of various antiretroviral (ARV) drug compounds used alone and in combination.
PMID 26529558

Japanese Journal

Long-term successful control of super-multidrug-resistant human immunodeficiency virus type 1 infection by a novel combination therapy of raltegravir, etravirine, and boosted-darunavir

NAKAMURA Hitomi,MIYAZAKI Naoko,HOSOYA Noriaki,KOGA Michiko,ODAWARA Takashi,KIKUCHI Tadashi,KOIBUCHI Tomohiko,KAWANA TACHIKAWA Ai,FUJII Takeshi,MIURA Toshiyuki,IWAMOTO Aikichi
Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 17(1), 105-110, 2011-02-01
NAID 10027816880

LC-MS/MS determination of etravirine in rat plasma and its application in pharmacokinetic studies

ABOBO Cyril V.,WU Lei,JOHN Jyothy,JOSEPH Mathew K.,BATES Theodore R.,LIANG Dong
Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 878(30), 3181-3186, 2010-11-15
NAID 10028044119

Validation of a rapid and sensitive high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) assay for the simultaneous determination of existing and new antiretroviral compounds

ELSE Laura,WATSON Victoria,TJIA John,HUGHES Andrew,SICCARDI Marco,KHOO Saye,BACK David
Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 878(19), 1455-1465, 2010-06-01
NAID 10028036864

Related Pictures

Pillbox - National Library of Medicine Etr Stock Photos & Etr Stock Images - Alamy Intelence 200mg dosage strength approved - MPR Etravirine « New Drug Approvals New Drug Review 2008 Etravirine,269055-15-4, manufacturers, suppliers, India, China Etravirine: Information from Answers.com

★リンクテーブル★

リンク元

「エトラビリン」

Etravirine
Systematic (IUPAC) name
	4-[6-Amino-5-bromo-2- [(4-cyanophenyl)amino] pyrimidin-4-yl]oxy- 3,5-dimethylbenzonitrile
Clinical data
AHFS/Drugs.com	monograph
MedlinePlus	a608016
Licence data	EMA:Link, US FDA:link
Pregnancy cat.	B
Legal status	Schedule VI (CA) ℞-only (US)
Routes	oral
Pharmacokinetic data
Protein binding	99.9%
Metabolism	Hepatic (CYP3A4, CYP2C9, CYP2C19)
Half-life	41 hours
Excretion	Fecal
Identifiers
CAS number	269055-15-4
ATC code	J05AG04
PubChem	CID 193962
DrugBank	DB07191
ChemSpider	168313
UNII	0C50HW4FO1
KEGG	D04112
ChEMBL	CHEMBL308954
NIAID ChemDB	105156
Chemical data
Formula	C20H15BrN6O
Mol. mass	435.28 g/mol
	SMILES N#Cc3cc(c(Oc1nc(nc(c1Br)N)Nc2ccc(C#N)cc2)c(c3)C)C;
	InChI InChI=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) ; Key:PYGWGZALEOIKDF-UHFFFAOYSA-N ;
(what is this?) (verify);

　　[★]

英: etravirine
商: エトラビリン
関: 抗ウイルス剤

[1] U.S. Department of Health and Human Services: Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents, Appendix A: Key to Acronyms

[2] Stellbrink HJ (October 2007). "Antiviral drugs in the treatment of AIDS: what is in the pipeline ?". Eur. J. Med. Res. 12 (9): 483–95. PMID 17933730.

[3] FDA Approves HIV Drug Etravirine, Associated Press, January 18, 2008.^{[dead link]}

[4] "First New NNRTI in Nearly a Decade to Benefit Canadians with HIV/AIDS" (Press release). Janssen-Ortho Inc.. 2008-04-01. http://www.janssen-ortho.com/JOI/pdf_files/INTELENCE_Press_Release_E.pdf. Retrieved 2008-07-09.

[5] "Intelence receives marketing authorisation in the European Union for HIV combination therapy". Tibotec. http://www.tibotec.com/news/detail.jhtml?itemname=news_48. Retrieved 2008-08-29.

[6] "Etravirine (TMC125, Intelence) granted accelerated approval in US". aidsmap. http://www.aidsmap.com/en/news/46E8FC38-3BB8-4DDD-9FEC-D6BFD5DD69AA.asp. Retrieved 2008-01-24.

[7] "Intelence prescribing information" (pdf). FDA. http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022187s008lbl.pdf. Retrieved January 2012.

[8] "Etravine: Summary of product characteristics". EMEA. p. 5. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000900/WC500034180.pdf. Retrieved July 2011.

[David_Evans-9] Evans, David (2008-01-15). "Etravirine—Countdown to Launch". AIDSmeds.com. http://www.aidsmeds.com/articles/etravirine_tmc125_hiv_2042_13846.shtml. Retrieved 2008-02-02.

[pmid15115397-10] 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; Clark (2004). "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". J. Med. Chem. 47 (10): 2550–60. doi:10.1021/jm030558s. PMID 15115397.

[11] "FDA Medwatch Safety Information". http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm180579.htm. Retrieved 2009-08-27.

匿名

検索

案内

案内

etravirine