Efavirenz
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Efavirenz
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| Systematic (IUPAC) name | |
| 8-chloro-5-(2-cyclopropylethynyl)- 5-(trifluoromethyl)- 4-oxa-2-azabicyclo [4.4.0]deca- 7,9,11-trien-3-one | |
| Identifiers | |
| CAS number | |
| ATC code | J05 |
| PubChem | |
| DrugBank | |
| Chemical data | |
| Formula | C14H9ClF3NO2 |
| Mol. mass | 315.675 g/mol |
| Pharmacokinetic data | |
| Bioavailability | ? |
| Protein binding | 99.5-99.75% |
| Metabolism | Hepatic (CYP3A4 and CYP2B6-mediated) |
| Half life | 40-55 hours |
| Excretion | Renal and fecal |
| Therapeutic considerations | |
| Pregnancy cat. |
D (U.S.) |
| Legal status |
POM (UK), ℞-only (U.S.) |
| Routes | Oral |
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.
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[edit] History
Efavirenz was approved by the Food and Drug Administration (FDA) on September 21, 1998, making it the 14th approved antiretroviral drug.
[edit] Indications
Efavirenz is used to treat HIV infection. It is never used alone and is always given in combination with other drugs. The decision on when to start treatment should take into account CD4 count, HIV viral load, treatment history, resistance profiles and patient preference.
Since the preliminary publication of the results of the ACTG 5142 trial in 2006 which compared efavirenz against lopinavir, efavirenz has been used as first line treatment in preference to the protease inhibitors. The ACTG 5095 trial showed that the potency of efavirenz is maintained at all CD4 counts and HIV viral loads.
[edit] 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.[1]
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.[2]
[edit] Dosing
The usual adult dose of efavirenz is 600mg per day (usually given at bedtime); or 800mg daily when given concurrently with rifampicin as part of treatment of co-infection with tuberculosis.
[edit] 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.
[edit] 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[3]
- Safety in children has not been established
- Use of efavirenz can produce a false positive result in some urine tests for marijuana
[edit] 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).
[edit] Reference
- ^ 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: 14410–15. PMID 12386343.
- ^ 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)
[edit] External links
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| Anti-herpesvirus | Aciclovir, Cidofovir, Docosanol, Famciclovir, Fomivirsen, Foscarnet, Ganciclovir, Idoxuridine, Penciclovir, Trifluridine, Tromantadine, Valaciclovir, Valganciclovir, Vidarabine |
| Anti-influenza agents | Amantadine, Arbidol, Oseltamivir, Peramivir, Rimantadine, Zanamivir |
| Antiretrovirals: NRTIs | Abacavir, Didanosine, Emtricitabine, Lamivudine, Stavudine, Zalcitabine, Zidovudine |
| Antiretrovirals: NtRTIs | Tenofovir |
| Antiretrovirals: NNRTIs | Efavirenz, Delavirdine, Nevirapine, Loviride |
| Antiretrovirals: PIs | Amprenavir, Atazanavir, Darunavir, Fosamprenavir, Indinavir, Lopinavir, Nelfinavir, Ritonavir, Saquinavir, Tipranavir |
| Antiretrovirals: Fusion inhibitors | Enfuvirtide |
| Other antiviral agents | Adefovir, Fomivirsen, Imiquimod, Inosine, Interferon, Podophyllotoxin, Ribavirin, Viramidine |
