Efavirenz - Article Sustiva
|Systematic (IUPAC) name|
|8-chloro-5-(2-cyclopropylethynyl)- 5-(trifluoromethyl)- 4-oxa-2-azabicyclo [4.4.0]deca- 7,9,11-trien-3-one|
|Mol. weight||315.675 g/mol|
|Metabolism||Hepatic (CYP3A4 and CYP2B6-mediated)|
|Half life||40-55 hours|
|Excretion||Renal and fecal|
|Pregnancy cat.|| |
|Legal status|| |
POM (UK), â„ž-only (U.S.)
Efavirenz (brand names SustivaÂ® and StocrinÂ®) 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.
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.
Efavirenz was approved by the Food and Drug Administration (FDA) on September 21, 1998, making it the fourteenth approved antiretroviral drug.
Mode of action
Efavirenz falls in the non-nucleoside reverse transcriptase inhibitor (NNRTI) class of antiretrovirals. Both nucleoside and non-nucleoside RTIs inhibit the same target, the reverse transcriptase enzyme, an essential viral enzyme which transcribes viral RNA into DNA. Unlike nucleoside RTIs, which bind at the enzyme's active site, NNRTIs bind within a pocket termed the NNRTI pocket.
Efavirenz is not effective against HIV-2, as the pocket of the HIV-2 reverse transcriptase has a different structure, which confers intrinsic resistance to the NNRTI class.
As all NNRTIs bind within the same pocket, viral strains which are resistant to efavirenz are usually also resistant to the other NNRTIs, nevirapine and delavirdine. The most common mutation observed after efavirenz treatment is K103N, which is also observed with other NNRTIs.
- Efavirenz is metabolized in the liver, and possesses both inhibitory and inducing effects on the 3A4 isoform of the cytochrome P450 system. This means efavirenz may interact with other drugs metabolized in the liver, requiring either increased or decreased dosages.
- Efavirenz lowers blood levels of most protease inhibitors. Dosages of amprenavir, atazanavir, or indinavir may need to be increased. The blood levels of saquinavir are dramatically lowered, so that the two drugs cannot be used simultaneously.
- St John's wort and garlic supplements may decrease efavirenz blood levels.
- Psychiatric symptoms, including insomnia, confusion, memory loss, and depression, are common
- Rash, nausea, dizziness and headache may occur
- Efavirenz can cause birth defects and should not be used in women who might become pregnant
- Safety in children has not been established
- Use of efavirenz can produce a false positive result in some urine tests for marijuana
Chemical structure & state of matter
Efavirenz is chemically described as (S)-6-chloro-(cyclopropylethynyl)-1,4-dihydro-4-(trifluoromethyl)-2H-3,1-benzoxazin-2-one. Its empirical formula is C14H9ClF3NO2. Efavirenz is a white to slightly pink crystalline powder with a molecular mass of 315.68 g/mol. It is practically insoluble in water (<10 Âµg/mL).
- ^ Ren J, Bird LE, Chamberlain PP, et al. (2002) Structure of HIV-2 reverse transcriptase at 2.35-A resolution and the mechanism of resistance to non-nucleoside inhibitors. Proc Natl Acad Sci USA 99: 14410â€“15
- ^ Sustiva (efavirenz) capsules and tablets. Product information (April 2005)
- ^ DHHS panel. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents (May 4, 2006). (Available for download from AIDSInfo)