Efavirenz

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.

The usual adult dose is 600 mg once a day taken on an empty stomach at bedtime.

Efavirenz was combined with the popular HIV medication Truvada and approved by the FDA in July of 2006, under the brand name Atripla. This was done to simplify the drug regimen for the many patients who take these two medications in combination.

History

Efavirenz was approved by the Food and Drug Administration (FDA) on September 21, 1998, making it the 14th 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.

Drug interactions

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.

Adverse effects

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 µg/mL).

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