EFAVIRENZ

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C14H9ClF3NO2
Molecular Weight	315.675
Optical Activity	( - )
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

FC(F)(F)[C@]1(OC(=O)NC2=C1C=C(Cl)C=C2)C#CC3CC3

InChI

InChIKey=XPOQHMRABVBWPR-ZDUSSCGKSA-N

InChI=1S/C14H9ClF3NO2/c15-9-3-4-11-10(7-9)13(14(16,17)18,21-12(20)19-11)6-5-8-1-2-8/h3-4,7-8H,1-2H2,(H,19,20)/t13-/m0/s1

HIDE SMILES / InChI

Molecular Formula	C14H9ClF3NO2
Molecular Weight	315.675
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	1 / 1
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: http://www.drugbank.ca/drugs/DB00625
Curator's Comment: Description was created based on several sources, including

Efavirenz (brand names Sustiva® and Stocrin®) is a non-nucleoside reverse transcriptase inhibitor (NNRTI) and is used as part of highly active antiretroviral therapy (HAART) for the treatment of a human immunodeficiency virus (HIV) type 1. For HIV infection that has not previously been treated, efavirenz and lamivudine in combination with zidovudine or tenofovir is the preferred NNRTI-based regimen. Efavirenz is also used in combination with other antiretroviral agents as part of an expanded postexposure prophylaxis regimen to prevent HIV transmission for those exposed to materials associated with a high risk for HIV transmission.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Human immunodeficiency virus 1 33 Target ID: CHEMBL378 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19469474	Inhibitor 8228	4.0 nM [EC50]
Leishmania infantum 2 Target ID: CHEMBL612848 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27249967	Inhibitor 8228	26.1 µM [IC50]
Estrogen receptor alpha 127 Target ID: CHEMBL206 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20408889	Modulator 822	52.0 µM [IC50]
Human immunodeficiency virus type 1 reverse transcriptase 47 Target ID: CHEMBL247 Sources: http://www.drugbank.ca/drugs/DB00625	Inhibitor 8228	20.0 nM [EC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
HIV-1 infection 150 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020972s038lbl.pdf	Primary		Approved 8360	SUSTIVA Approved Use SUSTIVA is a non-nucleoside reverse transcriptase inhibitor indicated in combination with other antiretroviral agents for the treatment of human immunodeficiency virus type 1 infection. Launch Date 9.05904E11

C_max

Value	Dose	Co-administered	Analyte	Population
12.9 μM DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/020972s057,021360s045lbl.pdf	600 mg 1 times / day steady-state, oral dose: 600 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		EFAVIRENZ plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
7.04 μg/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/020972s057,021360s045lbl.pdf	300 mg 1 times / day steady-state, oral dose: 300 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		EFAVIRENZ plasma	Homo sapiens population: UNHEALTHY age: CHILD sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
184 μM × h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/020972s057,021360s045lbl.pdf	600 mg 1 times / day steady-state, oral dose: 600 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		EFAVIRENZ plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
257.56 μM × h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/020972s057,021360s045lbl.pdf	300 mg 1 times / day steady-state, oral dose: 300 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		EFAVIRENZ plasma	Homo sapiens population: UNHEALTHY age: CHILD sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
40 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/020972s057,021360s045lbl.pdf	600 mg 1 times / day steady-state, oral dose: 600 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		EFAVIRENZ plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
0.5% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/020972s057,021360s045lbl.pdf	600 mg 1 times / day steady-state, oral dose: 600 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		EFAVIRENZ plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
3 g single, oral Overdose Dose: 3 g Route: oral Route: single Dose: 3 g Sources: https://pubmed.ncbi.nlm.nih.gov/23077707	unhealthy, 12 years n = 1 Health Status: unhealthy Condition: HIV infection Age Group: 12 years Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/23077707	Sources: https://pubmed.ncbi.nlm.nih.gov/23077707
600 mg 1 times / day multiple, oral Recommended Dose: 600 mg, 1 times / day Route: oral Route: multiple Dose: 600 mg, 1 times / day Co-administed with:: abacavir(300 mg q12h) nelfinavir(1250 mg q12h) Sources: https://pubmed.ncbi.nlm.nih.gov/11418896	unhealthy, 33 years n = 1 Health Status: unhealthy Condition: HIV infection Age Group: 33 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/11418896	Disc. AE: Mania... AEs leading to discontinuation/dose reduction: Mania (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/11418896
25 mg/kg 1 times / day steady, oral Highest studied dose Dose: 25 mg/kg, 1 times / day Route: oral Route: steady Dose: 25 mg/kg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/28483965	unhealthy, 33.9 months (range: 29.2–40.2 months) n = 52 Health Status: unhealthy Condition: HIV infection Age Group: 33.9 months (range: 29.2–40.2 months) Sex: M+F Population Size: 52 Sources: https://pubmed.ncbi.nlm.nih.gov/28483965	Sources: https://pubmed.ncbi.nlm.nih.gov/28483965
800 mg 1 times / day steady, oral Highest studied dose Dose: 800 mg, 1 times / day Route: oral Route: steady Dose: 800 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/30792988	unhealthy, 37.3 years n = 67 Health Status: unhealthy Condition: tuberculosis Age Group: 37.3 years Sex: M+F Population Size: 67 Sources: https://pubmed.ncbi.nlm.nih.gov/30792988	Disc. AE: Hallucination, Dizziness... AEs leading to discontinuation/dose reduction: Hallucination (1 patient) Dizziness (1 patient) Insomnia (1 patient) Hepatotoxicity (1 patient) Skin rash (1 patient) Pruritus (1 patient) Rash (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/30792988

AEs

AE	Significance	Dose	Population
Mania	1 patient Disc. AE	600 mg 1 times / day multiple, oral Recommended Dose: 600 mg, 1 times / day Route: oral Route: multiple Dose: 600 mg, 1 times / day Co-administed with:: abacavir(300 mg q12h) nelfinavir(1250 mg q12h) Sources: https://pubmed.ncbi.nlm.nih.gov/11418896	unhealthy, 33 years n = 1 Health Status: unhealthy Condition: HIV infection Age Group: 33 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/11418896
Dizziness	1 patient Disc. AE	800 mg 1 times / day steady, oral Highest studied dose Dose: 800 mg, 1 times / day Route: oral Route: steady Dose: 800 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/30792988	unhealthy, 37.3 years n = 67 Health Status: unhealthy Condition: tuberculosis Age Group: 37.3 years Sex: M+F Population Size: 67 Sources: https://pubmed.ncbi.nlm.nih.gov/30792988
Hallucination	1 patient Disc. AE	800 mg 1 times / day steady, oral Highest studied dose Dose: 800 mg, 1 times / day Route: oral Route: steady Dose: 800 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/30792988	unhealthy, 37.3 years n = 67 Health Status: unhealthy Condition: tuberculosis Age Group: 37.3 years Sex: M+F Population Size: 67 Sources: https://pubmed.ncbi.nlm.nih.gov/30792988
Hepatotoxicity	1 patient Disc. AE	800 mg 1 times / day steady, oral Highest studied dose Dose: 800 mg, 1 times / day Route: oral Route: steady Dose: 800 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/30792988	unhealthy, 37.3 years n = 67 Health Status: unhealthy Condition: tuberculosis Age Group: 37.3 years Sex: M+F Population Size: 67 Sources: https://pubmed.ncbi.nlm.nih.gov/30792988
Insomnia	1 patient Disc. AE	800 mg 1 times / day steady, oral Highest studied dose Dose: 800 mg, 1 times / day Route: oral Route: steady Dose: 800 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/30792988	unhealthy, 37.3 years n = 67 Health Status: unhealthy Condition: tuberculosis Age Group: 37.3 years Sex: M+F Population Size: 67 Sources: https://pubmed.ncbi.nlm.nih.gov/30792988
Pruritus	1 patient Disc. AE	800 mg 1 times / day steady, oral Highest studied dose Dose: 800 mg, 1 times / day Route: oral Route: steady Dose: 800 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/30792988	unhealthy, 37.3 years n = 67 Health Status: unhealthy Condition: tuberculosis Age Group: 37.3 years Sex: M+F Population Size: 67 Sources: https://pubmed.ncbi.nlm.nih.gov/30792988
Rash	1 patient Disc. AE	800 mg 1 times / day steady, oral Highest studied dose Dose: 800 mg, 1 times / day Route: oral Route: steady Dose: 800 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/30792988	unhealthy, 37.3 years n = 67 Health Status: unhealthy Condition: tuberculosis Age Group: 37.3 years Sex: M+F Population Size: 67 Sources: https://pubmed.ncbi.nlm.nih.gov/30792988
Skin rash	1 patient Disc. AE	800 mg 1 times / day steady, oral Highest studied dose Dose: 800 mg, 1 times / day Route: oral Route: steady Dose: 800 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/30792988	unhealthy, 37.3 years n = 67 Health Status: unhealthy Condition: tuberculosis Age Group: 37.3 years Sex: M+F Population Size: 67 Sources: https://pubmed.ncbi.nlm.nih.gov/30792988

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:119486	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:119486
ChemicalBook	CB7181559	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB7181559
MolPort	MolPort-003-983-924	https://www.molport.com/shop/molecule-link/MolPort-003-983-924
ZINC	ZINC000002020233	http://zinc15.docking.org/substances/ZINC000002020233
eMolecules	2735350	https://www.emolecules.com/cgi-bin/more?vid=2735350

PubMed

Title	Date	PubMed
Antiretroviral therapy in pregnancy: a focus on safety.	2001	11522121
A single amino acid change at Leu-188 in the reverse transcriptase of HIV-2 and SIV renders them sensitive to non-nucleoside reverse transcriptase inhibitors.	2001	11402860
High prevalence of genotypic and phenotypic HIV-1 drug-resistant strains among patients receiving antiretroviral therapy in Abidjan, Côte d'Ivoire.	2001 Apr 15	11391173
A pilot study of the use of mycophenolate mofetil as a component of therapy for multidrug-resistant HIV-1 infection.	2001 Apr 15	11391161
Antiretroviral rounds. When success is a pain.	2001 Aug	11547461
Antiretrovirals: simultaneous determination of five protease inhibitors and three nonnucleoside transcriptase inhibitors in human plasma by a rapid high-performance liquid chromatography--mass spectrometry assay.	2001 Aug	11477320
Antiviral drugs: current state of the art.	2001 Aug	11418355
Preliminary data of a prospective study on neuropsychiatric side effects after initiation of efavirenz.	2001 Aug 1	11468421
Efavirenz as a substitute for protease inhibitors in HIV-1-infected patients with undetectable plasma viral load on HAART: a median follow-up of 64 weeks.	2001 Aug 15	11511822
Non-nucleoside reverse transcriptase inhibitor failure impairs HIV-RNA responses to efavirenz-containing salvage antiretroviral therapy.	2001 Aug 17	11504994
Structure-based design, synthesis, and biological evaluation of conformationally restricted novel 2-alkylthio-6-[1-(2,6-difluorophenyl)alkyl]-3,4-dihydro-5-alkylpyrimidin-4(3H)-ones as non-nucleoside inhibitors of HIV-1 reverse transcriptase.	2001 Aug 2	11472208
Solution structures and reactivities of the mixed aggregates derived from n-butyllithium and vicinal amino alkoxides.	2001 Aug 22	11506560
Antiretroviral therapy for previously treated patients.	2001 Aug 9	11496858
Nelfinavir, efavirenz, or both after the failure of nucleoside treatment of HIV infection.	2001 Aug 9	11496850
Quinoxalinylethylpyridylthioureas (QXPTs) as potent non-nucleoside HIV-1 reverse transcriptase (RT) inhibitors. Further SAR studies and identification of a novel orally bioavailable hydrazine-based antiviral agent.	2001 Feb 1	11462972
Protease-sparing regimen in a real-life practice with naïve patients: an equal opportunity approach?	2001 Jan-Feb	11590510
Eruptive cheilitis: a new adverse effect in reactive HIV-positive patients subjected to high activity antiretroviral therapy (HAART). Presentation of six clinical cases.	2001 Jan-Feb	11488127
Predictors of protease inhibitor-associated adverse events.	2001 Jul	11478584
The steady-state pharmacokinetics of efavirenz and nevirapine when used in combination in human immunodeficiency virus type 1-infected persons.	2001 Jul 1	11398107
Manic syndrome associated with efavirenz overdose.	2001 Jul 15	11418896
Synthesis and evaluation of novel quinolinones as HIV-1 reverse transcriptase inhibitors.	2001 Jul 23	11459666
Gynecomastia without lipodystrophy syndrome in HIV-infected men treated with efavirenz.	2001 Jul 27	11504970
Management of sudden psychiatric disorders related to efavirenz.	2001 Jul 6	11426084
Metformin in an HIV-infected patient with protease inhibitor-induced diabetic ketoacidosis.	2001 Jul-Aug	11485138
In vitro anti-HIV-1 synergy between non-nucleoside reverse transcriptase inhibitors nevirapine and efavirenz.	2001 Jun	11491419
Limits of deep salvage antiretroviral therapy with nelfinavir plus either efavirenz or nevirapine, in highly pre-treated patients with HIV disease.	2001 Jun	11397623
[Vertical trasmission of human immunodeficiency virus (HIV) and other sexually transmitted infections (STI)].	2001 Jun	11395690
Efavirenz plasma concentrations and efficiency.	2001 Jun 15	11416729
Phenotypic hypersusceptibility to non-nucleoside reverse transcriptase inhibitors in treatment-experienced HIV-infected patients: impact on virological response to efavirenz-based therapy.	2001 Jun 15	11416714
Use of MM-PBSA in reproducing the binding free energies to HIV-1 RT of TIBO derivatives and predicting the binding mode to HIV-1 RT of efavirenz by docking and MM-PBSA.	2001 Jun 6	11457384
Efavirenz-induced acute eosinophilic hepatitis.	2001 May	11434632
Efavirenz-induced photoallergic dermatitis in HIV.	2001 May 25	11400003
High-performance liquid chromatographic method for the determination of HIV-1 non-nucleoside reverse transcriptase inhibitor efavirenz in plasma of patients during highly active antiretroviral therapy.	2001 May 5	11393699
[Apropos of atypical melancholia with Sustiva (efavirenz)].	2001 May-Jun	11488260
[Drug interactions with antiretroviral agents].	2001 May-Jun	11475806
Other issues: penetration into sanctuary sites, immune reconstitution and NNRTI sequencing.	2001 Nov	11589825
Factors affecting adherence and convenience in antiretroviral therapy.	2001 Nov	11589824
Comparison of NNRTIs in antiretroviral-experienced patients.	2001 Nov	11589823
Comparison of NNRTIs in antiretroviral-naïve patients.	2001 Nov	11589822
The role of NNRTIs in antiretroviral combination therapy: an introduction.	2001 Nov	11589821
New developments in anti-HIV chemotherapy.	2001 Nov	11562282
The stereoselective targeting of a specific enzyme-substrate complex is the molecular mechanism for the synergic inhibition of HIV-1 reverse transcriptase by (R)-(-)-PPO464: a novel generation of nonnucleoside inhibitors.	2001 Nov 30	11572864
Thiosugars. VIII. Preparation of new 4'-thio-L-lyxo pyrimidine nucleoside analogues.	2001 Sep	11580190
Mismatched double-stranded RNA (polyI-polyC(12)U) is synergistic with multiple anti-HIV drugs and is active against drug-sensitive and drug-resistant HIV-1 in vitro.	2001 Sep	11448730
Efavirenz-induced psychosis.	2001 Sep 28	11579266
Response to first protease inhibitor- and efavirenz-containing antiretroviral combination therapy. The Swiss HIV Cohort Study.	2001 Sep 28	11579241
Structural mechanisms of drug resistance for mutations at codons 181 and 188 in HIV-1 reverse transcriptase and the improved resilience of second generation non-nucleoside inhibitors.	2001 Sep 28	11575933
Evolution of anti-HIV drug candidates. Part 3: Diarylpyrimidine (DAPY) analogues.	2001 Sep 3	11527705
Comparison of initial combination antiretroviral therapy with a single protease inhibitor, ritonavir and saquinavir, or efavirenz.	2001 Sep 7	11546943
Switching from protease inhibitors to the non-nuke efavirenz.	2001 Spring	11570089

Patents

Sample Use Guides

In Vivo Use Guide

SUSTIVA should be taken orally once daily on an empty stomach, preferably at bedtime. • Recommended adult dose: 600 mg. • With voriconazole, increase voriconazole maintenance dose to 400 mg every 12 hours and decrease SUSTIVA dose to 300 mg once daily using the capsule formulation.

Route of Administration: Oral

In Vitro Use Guide

10 pM efavirenz completely inhibited 0.5 U HIV RT.

Substance Class	Chemical Created by `admin` on `Wed Jul 05 23:14:14 UTC 2023` Edited by `admin` on `Wed Jul 05 23:14:14 UTC 2023`
Record UNII	JE6H2O27P8
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

EFAVIRENZ

Official Name

English

L-743726

Code

English

EFAVIRENZ [USP MONOGRAPH]

Common Name

English

SUSTIVA

Brand Name

English

(S)-6-Chloro-4-(cyclopropylethynyl)-1,4-dihydro-4-(trifluoromethyl)-2H-3,1-benzoxazin-2-one

Systematic Name

English

EFAVIRENZ [EMA EPAR]

Common Name

English

NSC-742403

Code

English

DMP-266

Code

English

EFAVIRENZ [MI]

Common Name

English

EFAVIRENZ [VANDF]

Common Name

English

EFAVIRENZ [ORANGE BOOK]

Common Name

English

EFAVIRENZ [WHO-IP]

Common Name

English

EFAVIRENZ [USAN]

Common Name

English

EFAVIRENZUM [WHO-IP LATIN]

Common Name

English

EFAVIRENZ [HSDB]

Common Name

English

EFAVIRENZ [JAN]

Common Name

English

VIRADAY

Brand Name

English

efavirenz [INN]

Common Name

English

(4S)-6-Chloro-4-(2-cyclopropylethynyl)-1,4-dihydro-4-(trifluoromethyl)-2H-3,1-benzoxazin-2-one

Systematic Name

English

TELURA COMPONENT EFAVIRENZ

Brand Name

English

Efavirenz [WHO-DD]

Common Name

English

2H-3,1-Benzoxazin-2-one, 6-chloro-4-(2-cyclopropylethynyl)-1,4-dihydro-4-(trifluoromethyl)-, (4S)-

Systematic Name

English

STOCRIN

Brand Name

English

EFAVIRENZ [USP-RS]

Common Name

English

EFAVIRENZ TEVA

Brand Name

English

EFV

Common Name

English

EFAVIRENZ [MART.]

Common Name

English

EFAVIRENZ COMPONENT OF ATRIPLA

Common Name

English

ATRIPLA COMPONENT EFAVIRENZ

Common Name

English

(-)-Efavirenz

Common Name

English

Classification Tree Code System Code

NDF-RT

N0000009948