- Overview
- Properties
- Genetics
- Related Genes
- Related Drugs
- Related Diseases
- Datasets
- Downloads/LinkOuts
Overview
| Generic Names: | EFV; efavirenz |
|---|---|
| Trade Names: | Stocrin; Sustiva |
| PharmGKB Accession Id: | PA449441 |
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.
(source:
Drug Bank)
Indication
For use in combination treatment of HIV infection (AIDS) (source: Drug Bank)
ATC Therapeutic Category
- J05AG:Non-nucleoside reverse transcriptase inhibitors
Pharmacology, Interactions, and Contraindications
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. (source: Drug Bank)
Pharmacology
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. (source: Drug Bank)
Food Interactions
Avoid excessive or chronic alcohol consumption.
Take without regard to meals.
(source:
Drug Bank)
Absorption, Distribution, Metabolism, Elimination & Toxicity
Biotransformation
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. (source: Drug Bank)
Protein Binding
99.5-99.75% (source: Drug Bank)
Isomeric SMILES Code:
C1CC1C#C[C@]2(C3=C(C=CC(=C3)Cl)NC(=O)O2)C(F)(F)F (source: Drug Bank)
In-Depth Annotations (
)
-
rs1045642
at chr7:86976581
in
ABCB1
Risk or phenotype-associated allele: T allele, TT genotype. Phenotype: Association with decreased virologic failure (p = 0.05, TT vs. CC/CT), decreased drug resistance (OR = 0.56, p = 0.05), and increased toxicity-related treatment failure (p = 0.05) with efavirenz (EFV); however, no association with nelfinavir (NLF) or efavirenz response (e.g. increase in CD4 T cell count) (p > 0.1) nor nelfinavir or efavirenz exposure. Study size: 504 (340 efavirenz, 348 nelfinavir, 184 both drugs). Study population/ethnicity: Subset of larger study of 504 (49% whites, 31% blacks, 19% Hispanics from the USA and Italy) randomized antiretroviral-naive HIV-1 patients who were administered efavirenz plus two nucleoside analogues. Significance metric(s): p = 0.05 (ERV: less virologic failure, drug resistance, tox-related Tx failure); p > 0.1 (EFV/NLF response); not significant (EFV/NLF exposure). Type of association: GN; PK; PD; TOX; ADR.- Variant Name:
- ABCB1:3435T>C, Ile1145Ile
- Related Drugs:
- efavirenz, nelfinavir
- Related Diseases:
- HIV
- Evidence:
-
PMID:16267764
http://www.pharmgkb.org/.../variant.jsp#ImportantVariantInformationforABCB1-3435
-
rs3745274
at chr19:46204681
in
CYP2A7P1,
CYP2B6
CYP2B6:516G>T is part of the CYP2B6 haplotype. It has been associated with lower activity and response to NNRTIs. See VIP annotation for more details.- Variant Name:
- CYP2B6:516G>T; part of CYP2B6*6; CYP2B6:Gln172His
- Related Drugs:
- efavirenz, nevirapine
- Evidence:
-
http://www.pharmgkb.org/.../variant.jsp
-
rs28399499
at chr19:46210061
in
CYP2A7P1,
CYP2B6
This variant is the only protein coding change in the CYP2B6*18 allele. Its phenotype with respect to drugs is unclear. See VIP annotation for more details.- Variant Name:
- CYP2B6:983T>C; CYP2B6:Ile328Thr; part of CYP2B6*18
- Related Drugs:
- bupropion, efavirenz, nevirapine
- Evidence:
-
http://www.pharmgkb.org/.../variant.jsp
-
rs3211371
at chr19:46214555
in
CYP2A7P1,
CYP2B6
CYP2B6:1459C>T has been reported to reduce CYP2B6 protein expression in human liver and brain. Impact on drug response is somewhat contradictory, see VIP annotation for details.- Variant Name:
- CYP2B6:1459C>T; CYP2B6:Arg487Cys; part of CYP2B6*1C, CYP2B6*5, CYP2B6*7
- Related Drugs:
- bupropion, efavirenz, mephenytoin, nevirapine, nicotine
- Evidence:
-
http://www.pharmgkb.org/.../variant.jsp
Curated Annotations (
)
-
rs1045642
at chr7:86976581
in
ABCB1
In a study of HIV patients in South Africa, participants who experienced hepatotoxicity were less likely to have at least one T allele of the variant ABCB1:3435C>T.- Variant Name:
- ABCB1:3435C>T, MDR1 3435C>T
- Related Drugs:
- efavirenz
- Related Diseases:
- HIV
- Evidence:
-
PMID:16912957
-
rs1045642
at chr7:86976581
in
ABCB1
Decreased risk of hepatotoxicity was associated with ABCB1:3435C>T in a study of HIV patients receiving either efavirenz- or nevirapine-containing drug regimens.- Variant Name:
- ABCB1:3435C>T, MDR1 3435C>T
- Related Drugs:
- efavirenz, nevirapine
- Related Diseases:
- HIV
- Evidence:
-
PMID:16912956
-
rs1045642
at chr7:86976581
in
ABCB1
Risk or phenotype-associated allele: TT allele. Phenotype: Increased efavirenz and nelfinavir response after 6 months treatment. Study size: 123. Study population/ethnicity: White HIV patients. Significance metric(s): p = 0.0001. Type of association: GN; PD.- Variant Name:
- ABCB1:3435T>C, Ile1145Ile
- Related Drugs:
- efavirenz, nelfinavir
- Related Diseases:
- HIV
- Evidence:
-
PMID:11809184
-
rs1045642
at chr7:86976581
in
ABCB1
Risk or phenotype-associated allele: none. Phenotype: Efavirenz and lopinavir plasma levels. Study size: 67. Study population/ethnicity: HIV patients. Significance metric(s): not available from abstract. Type of association: GN; PK.- Variant Name:
- ABCB1:3435T>C, Ile1145Ile
- Related Drugs:
- efavirenz, lopinavir
- Evidence:
-
PMID:14711599
-
rs3745274
at chr19:46204681
in
CYP2A7P1,
CYP2B6
This variant in exon 4 together with K262R in exon 5 are the determining SNP of the *6 allele. *6 occurs with high frequency across different populations. A study in human liver microsomes found the CYP2B6*6 allele was significantly associated with a pronounced decrease in CYP2B6 expression and activity, as well as a low rate of efavirenz 8-hydroxylation. In a study in HIV-1 patients treated with efavirenz, the mean plasma efavirenz concentration of patients with CYP2B6 *6/*6 was significantly higher than that of patients with genotypes *6 heterozygote or without alleles *6. In vitro expression studies found the 516G>T variant as the causal sequence variation for severely decreased expression and function associated with CYP2B6*6.- Variant Name:
- CYP2B6: 516G>T; Q172H
- Related Drugs:
- efavirenz
- Related Diseases:
- HIV Infections
- Evidence:
-
PMID:15194512
PMID:17559344
PMID:17638512
PMID:18171905
-
rs36079186
at chr19:46204758
in
CYP2A7P1,
CYP2B6
The CYP2B6*27 allele shows an 85% decrease in enzyme activity leading to high plasma levels of efavirenz in patients.- Variant Name:
- CYP2B6*27, CYP2B6:593T>C, CYP2B6:M198T
- Related Drugs:
- efavirenz
- Evidence:
-
PMID:17235330
-
rs28399499
at chr19:46210061
in
CYP2A7P1,
CYP2B6
This variant in exon 7 defines the CYP2B6*18 allele and is part of the *16 allele. Recombinant expression of this variant resulted in an undetectable expression and activity in COS-1 cells but expression of a protein with reduced activity in insect cells. The I328T variant was found in HIV patients with strongly elevated plasma concentrations of efavirenz, especially in individuals of African descent.- Variant Name:
- CYP2B6: 983T>C; I328T
- Related Drugs:
- efavirenz
- Evidence:
-
PMID:16272958
PMID:16495778
PMID:17638512
http://www.cypalleles.ki.se/cyp2b6.htm
-
rs34097093
at chr19:46210210
in
CYP2A7P1,
CYP2B6
The CYP2B6:1132C>T variant results in a truncated protein and high plasma levels of efavirenz in patients.- Variant Name:
- CYP2B6*28, CYP2B61132C>T, CYP2B6:R378X
- Related Drugs:
- efavirenz
- Evidence:
-
PMID:17235330
The following genes are in curated knowledge about this drug.
| Gene | Relationship | Evidence | |
|---|---|---|---|
|
ABCB1 |
|
Publications, Variants |
|
CYP2A6 |
|
Publications |
|
|
CYP2A7P1 |
|
Variants |
|
|
CYP2B6 |
|
Publications, Variants |
|
|
CYP2C19 |
|
Publications |
|
|
CYP2D6 |
|
Publications |
|
|
CYP3A4 |
|
Publications |
|
|
DRD2 |
|
Publications |
|
|
NR1I2 |
|
Publications |
|
|
NR1I3 |
|
Publications |
|
|
ORM1 |
|
Publications |
|
|
ORM2 |
|
Publications |
|
|
UGT1A1 |
|
Publications |
A list of non-curated publications that mention this drug along with other genes is available.
Drug Targets
The following drugs are in curated knowledge about this drug.
| Drug | Relationship | Evidence | |
|---|---|---|---|
|
|
rifampin |
|
Publications |
|
|
tamoxifen |
|
Publications |
|
|
warfarin |
|
Publications |
A list of non-curated publications that mention this drug along with other drugs is available.
Drug Interactions
| Drug | Description | |
|---|---|---|
| alprazolam |
|
The antiviral agent increases the effect and toxicity of benzodiazepine (source: Drug Bank) |
| astemizole |
|
Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank) |
| atazanavir |
|
Efavirenz decreases the levels/effects of atazanavir (source: Drug Bank) |
| atorvastatin |
|
The NNRT inhibitor increases the effect and toxicity of the statin (source: Drug Bank) |
| cisapride |
|
Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank) |
| clarithromycin |
|
Efavirenz decreases levels of clarithromycin (source: Drug Bank) |
| cyclosporine |
|
Efavirenz decreases the levels of cyclosporine (source: Drug Bank) |
| indinavir |
|
Efavirenz decreases the effect of indinavir (source: Drug Bank) |
| lovastatin |
|
The NNRT inhibitor increases the effect and toxicity of the statin (source: Drug Bank) |
| methadone |
|
The antiretroviral agent decreases the effect of mathadone (source: Drug Bank) |
| methylergonovine |
|
The antiretroviral agent may increase the ergot derivative toxicity (source: Drug Bank) |
| midazolam |
|
The antiviral agent increases the effect and toxicity of benzodiazepine (source: Drug Bank) |
| saquinavir |
|
Efavirenz decreases the effect of saquinavir (source: Drug Bank) |
| simvastatin |
|
The NNRT inhibitor increases the effect and toxicity of the statin (source: Drug Bank) |
| terfenadine |
|
Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank) |
| triazolam |
|
The antiviral agent increases the effect and toxicity of benzodiazepine (source: Drug Bank) |
| voriconazole |
|
Efavirenz decreases the levels/effect of voriconazole (source: Drug Bank) |
Curated Information
The following diseases are in curated knowledge about this drug.
| Disease | Relationship | Evidence | |
|---|---|---|---|
|
|
HIV |
|
Publications, Variants |
|
|
HIV Infections |
|
Publications, Variants |
|
|
Leukemia |
|
Publications |
Non-Curated Information
A list of non-curated publications that mention this drug along with other diseases is available.
Additional Datasets
These datasets are minimally curated and are sorted alphabetically by title.
LinkOuts
Common Searches
Search PubMed
Search Medline Plus
Search PubChem
Search CTD
Non-Curated Publications
A list of non-curated publications that mention this drug is available.