Banner
targets (1) enzymes (6)
for drugs
Identification
Name Efavirenz
Accession Number DB00625 (APRD00059, DB07709)
Type small molecule
Groups approved
Description

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.
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
EFV
Salts Not Available
Brand names
Name Company
Stocrin
Sustiva
Brand mixtures Not Available
Categories
  • Anti-HIV Agents
  • Nonnucleoside Reverse Transcriptase Inhibitors
  • Reverse Transcriptase Inhibitors
CAS number 154598-52-4
Weight Average: 315.675
Monoisotopic: 315.027390859
Chemical Formula C14H9ClF3NO2
InChI Key InChIKey=XPOQHMRABVBWPR-ZDUSSCGKSA-N
InChI
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
Plain Text
IUPAC Name
(4S)-6-chloro-4-(2-cyclopropylethynyl)-4-(trifluoromethyl)-2,4-dihydro-1H-3,1-benzoxazin-2-one
SMILES
FC(F)(F)[C@]1(OC(=O)NC2=C1C=C(Cl)C=C2)C#CC1CC1
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Benzyl Alcohols and Derivatives
  • Carbamates and Derivatives
  • Halobenzenes
  • Anilines
Substructures
  • Benzyl Alcohols and Derivatives
  • Alkynes
  • Carbamates and Derivatives
  • Cyclopropane and Derivatives
  • Ethers
  • Benzene and Derivatives
  • Aryl Halides
  • Halobenzenes
  • Heterocyclic compounds
  • Aromatic compounds
  • Anilines
Pharmacology
Indication For use in combination treatment of HIV infection (AIDS)
Pharmacodynamics Efavirenz (dideoxyinosine, ddI) is an oral nucleoside reverse transcriptase inhibitor (NRTI). It is a synthetic purine derivative and, similar to zidovudine, zalcitabine, and stavudine. Efavirenz was originally approved specifically for the treatment of HIV infections in patients who failed therapy with zidovudine. Currently, the CDC recommends that Efavirenz be given as part of a three-drug regimen that includes another nucleoside reverse transcriptase inhibitor (e.g., lamivudine, stavudine, zidovudine) and a protease inhibitor or efavirenz when treating HIV infection.
Mechanism of action Similar to zidovudine, efavirenz inhibits the activity of viral RNA-directed DNA polymerase (i.e., reverse transcriptase). Antiviral activity of efavirenz is dependent on intracellular conversion to the active triphosphorylated form. The rate of efavirenz phosphorylation varies, depending on cell type. It is believed that inhibition of reverse transcriptase interferes with the generation of DNA copies of viral RNA, which, in turn, are necessary for synthesis of new virions. Intracellular enzymes subsequently eliminate the HIV particle that previously had been uncoated, and left unprotected, during entry into the host cell. Thus, reverse transcriptase inhibitors are virustatic and do not eliminate HIV from the body. Even though human DNA polymerase is less susceptible to the pharmacologic effects of triphosphorylated efavirenz, this action may nevertheless account for some of the drug's toxicity.
Absorption Not Available
Volume of distribution Not Available
Protein binding 99.5-99.75%
Metabolism Efavirenz is principally metabolized by the cytochrome P450 system to hydroxylated metabolites with subsequent glucuronidation of these hydroxylated metabolites. These metabolites are essentially inactive against HIV-1.
Route of elimination Nearly all of the urinary excretion of the radiolabeled drug was in the form of metabolites.
Half life 40-55 hours
Clearance Not Available
Toxicity Not Available
Affected organisms
  • Human Immunodeficiency Virus
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Bristol myers squibb co
  • Bristol myers squibb pharma co
Packagers
Dosage forms
Form Route Strength
Capsule Oral
Tablet Oral
Prices
Unit description Cost Unit
Sustiva 600 mg tablet 21.68 USD tablet
Sustiva 200 mg capsule 7.37 USD capsule
Sustiva 100 mg capsule 3.34 USD capsule
Sustiva 50 mg capsule 1.84 USD capsule
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Country Patent Number Approved Expires (estimated)
United States 6238695 1999-04-06 2019-04-06
United States 5811423 1992-08-07 2012-08-07
Canada 2279198 2009-04-14 2018-02-02
Canada 2101572 2001-08-28 2013-07-29
Properties
State solid
Experimental Properties
Property Value Source
melting point 139-141 °C Not Available
logP 4.6 Not Available
Predicted Properties
Property Value Source
water solubility 8.55e-03 g/l ALOGPS
logP 3.89 ALOGPS
logP 4.46 ChemAxon
logS -4.6 ALOGPS
pKa (strongest acidic) 12.52 ChemAxon
pKa (strongest basic) -1.5 ChemAxon
physiological charge 0 ChemAxon
hydrogen acceptor count 2 ChemAxon
hydrogen donor count 1 ChemAxon
polar surface area 38.33 ChemAxon
rotatable bond count 3 ChemAxon
refractivity 71.34 ChemAxon
polarizability 26.81 ChemAxon
References
Synthesis Reference Not Available
General Reference
  1. Ren J, Bird LE, Chamberlain PP, Stewart-Jones GB, Stuart DI, Stammers DK: Structure of HIV-2 reverse transcriptase at 2.35-A resolution and the mechanism of resistance to non-nucleoside inhibitors. Proc Natl Acad Sci U S A. 2002 Oct 29;99(22):14410-5. Epub 2002 Oct 17. Pubmed
External Links
Resource Link
KEGG Drug D00896 Link_out
KEGG Compound C08088 Link_out
PubChem Compound 64139 Link_out
PubChem Substance 46506827 Link_out
ChemSpider 57715 Link_out
BindingDB 2483 Link_out
ChEBI 119486 Link_out
ChEMBL 119486 Link_out
Therapeutic Targets Database DAP000709 Link_out
PharmGKB PA449441 Link_out
HET EFZ Link_out
Drug Product Database 2246045 Link_out
RxList http://www.rxlist.com/cgi/generic/efaviren.htm Link_out
Drugs.com http://www.drugs.com/cdi/efavirenz.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Efavirenz Link_out
ATC Codes
  • J05AG03
AHFS Codes
  • 08:18.08.16
PDB Entries Not Available
FDA label show (154 KB)
MSDS show (57.6 KB)
Interactions
Drug Interactions
Drug Interaction
Alprazolam The antiviral agent, efavirenz, may increase the effect and toxicity of the benzodiazepine, alprazolam.
Astemizole Increased risk of cardiotoxicity and arrhythmias
Atazanavir Efavirenz decreases the levels/effects of atazanavir
Atorvastatin Efavirenz may decrease the serum concentration of atorvastatin by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of atorvastatin if efavirenz is initiated, discontinued or dose changed.
Cisapride Increased risk of cardiotoxicity and arrhythmias
Clarithromycin Efavirenz decreases levels of clarithromycin
Cyclosporine Efavirenz decreases the levels of cyclosporine
Dihydroergotamine Efavirenze may increase the adverse/toxic effects of dihydroergotamine. Concomitant therapy is contraindicated.
Dihydroergotoxine The antiretroviral agent may increase the ergot derivative toxicity
Eltrombopag Affects hepatic enzyme CYP2C9/10 metabolism and may increase the level of eltrombopag.
Ergotamine The antiretroviral agent may increase the ergot derivative toxicity
Estradiol valerate/Dienogest Affects CYP3A4 metabolism, decreases or effects levels of Estradiol valerate/Dienogest.
Etravirine Efavirenz may cause a significant decrease in plasma levels of etravirine and a loss of efficacy. Combination of two NNRTIs has not been demonstrated to be of benefit to HIV therapy.
Indinavir Efavirenz decreases the effect of indinavir
Lovastatin Efavirenz may decrease the serum concentration of lovastatin by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of lovastatin if efavirenz is initiated, discontinued or dose changed.
Methadone Efavirenz may decrease the serum concentration of methadone by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of methadone if efavirenz is initiated, discontinued or dose changed.
Methylergonovine The antiretroviral agent may increase the ergot derivative toxicity
Methysergide The antiretroviral agent may increase the ergot derivative toxicity
Midazolam The antiviral agent, efavirenz, may increase the effect and toxicity of the benzodiazepine, midazolam.
Saquinavir Efavirenz decreases the effect of saquinavir
Simvastatin Efavirenz may decrease the serum concentration of simvastatin. Monitor for changes in the therapeutic and adverse effects of simvastatin if efavirenz is initiated, discontinued or dose changed.
St. John's Wort St. John's Wort decreases the antiretroviral effect
Tamsulosin Efavirenz, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Efavirenz is initiated, discontinued, or dose changed.
Telithromycin Efavirenz may decrease the plasma concentration of Telithromycin. Consider alternate therapy.
Temsirolimus Efavirenz may increase the metabolism of Temsirolimus decreasing its efficacy. Concomitant therapy should be avoided.
Terfenadine Increased risk of cardiotoxicity and arrhythmias
Tipranavir Efavirenz may alter the serum concentration Tipranavir. Monitor for changes in Tipranavir therapeutic and adverse effects if Efavirenz is initiated, discontinued or dose changed.
Tolterodine Efavirenz may decrease the metabolism and clearance of Tolterodine. Adjust Tolterodine dose and monitor for efficacy and toxicity.
Tramadol Efavirenz may decrease the effect of Tramadol by increasing Tramadol metabolism and clearance.
Trazodone The CYP3A4 inhibitor and inducer, Efavirenz, may alter Trazodone efficacy/toxicity by altering Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Efavirenz is initiated, discontinued or dose changed.
Triazolam The antiviral agent, efavirenz, may increase the effect and toxicity of the benzodiazepine, triazolam.
Voriconazole Efavirenze may decrease the serum concentration of voriconazole likely by increasing its metabolism. Voriconazole may increase the serum concentration of efavirenz by decreasing its metabolism. Consider alternate therapy or adjust doses and monitor for reduced voriconazole efficacy and increased efavirenz adverse effects during concomitant therapy.
Food Interactions
  • Avoid excessive or chronic alcohol consumption.
  • Take without regard to meals.
Targets

1. Reverse transcriptase

Pharmacological action: yes
Actions: inhibitor
UniProt ID: Q5DNL9 Link_out

References:
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Xia Q, Radzio J, Anderson KS, Sluis-Cremer N: Probing nonnucleoside inhibitor-induced active-site distortion in HIV-1 reverse transcriptase by transient kinetic analyses. Protein Sci. 2007 Aug;16(8):1728-37. Pubmed
  4. Lindberg J, Sigurdsson S, Lowgren S, Andersson HO, Sahlberg C, Noreen R, Fridborg K, Zhang H, Unge T: Structural basis for the inhibitory efficacy of efavirenz (DMP-266), MSC194 and PNU142721 towards the HIV-1 RT K103N mutant. Eur J Biochem. 2002 Mar;269(6):1670-7. Pubmed
Enzymes

1. Cytochrome P450 2C19

Actions: inhibitor

Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine

UniProt ID: P33261 Link_out
Gene: CYP2C19 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

2. Cytochrome P450 2C9

Actions: inhibitor

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S- warfarin, diclofenac, phenytoin, tolbutamide and losartan

UniProt ID: P11712 Link_out
Gene: CYP2C9
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

3. Cytochrome P450 2B6

Actions: substrate, inhibitor, inducer

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics

UniProt ID: P20813 Link_out
Gene: CYP2B6 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
  2. Hesse LM, von Moltke LL, Shader RI, Greenblatt DJ: Ritonavir, efavirenz, and nelfinavir inhibit CYP2B6 activity in vitro: potential drug interactions with bupropion. Drug Metab Dispos. 2001 Feb;29(2):100-2. Pubmed
  3. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  4. Walsky RL, Astuccio AV, Obach RS: Evaluation of 227 drugs for in vitro inhibition of cytochrome P450 2B6. J Clin Pharmacol. 2006 Dec;46(12):1426-38. Pubmed
  5. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

4. Cytochrome P450 3A4

Actions: substrate, inhibitor, inducer

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 reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

5. Cytochrome P450 1A2

Actions: inhibitor

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen

UniProt ID: P05177 Link_out
Gene: CYP1A2
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

6. Cytochrome P450 2D6

Actions: inhibitor

Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants

UniProt ID: P10635 Link_out
Gene: CYP2D6 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19