|Systematic (IUPAC) name|
|Trade names||Sustiva, Stocrin etc.|
|Pregnancy cat.||D (U.S.)|
|Legal status||POM (UK), ℞-only (U.S.)|
|Metabolism||Hepatic (CYP2A6 and CYP2B6-mediated)|
|Excretion||Renal and fecal|
|Mol. mass||315.675 g/mol|
|(what is this?)|
Efavirenz (EFV, brand names Sustiva, Stocrin, Efavir etc.) 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, the United States Department of Health and Human Services Panel on Antiretroviral Guidelines currently recommends the use of efavirenz in combination with tenofovir/emtricitabine (Truvada) as one of the preferred NNRTI-based regimens in adults and adolescents.
Efavirenz is also used in combination with other antiretroviral agents as part of an expanded postexposure prophylaxis regimen to reduce the risk of HIV infection in people exposed to a significant risk (e.g. needlestick injuries, certain types of unprotected sex etc.).
Efavirenz was combined with the popular HIV medication Truvada, which consists of tenofovir and emtricitabine, all of which are reverse transcriptase inhibitors. This combination of three medications approved by the U.S. Food and Drug Administration (FDA) in July 2006 under the brand name Atripla, provides HAART in a single tablet taken once a day. It results in a simplified drug regimen for many patients.
Efavirenz was approved by the FDA on September 21, 1998, making it the 14th approved antiretroviral drug.
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.
Mechanism of action
Efavirenz falls in the 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 act allosterically by binding to a distinct site away from the active site known as 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 most 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 is both a substrate and inducer of the 2B6 and 3A4 isoforms 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. This can result in incomplete inhibition of viral replication, which can allow multidrug-resistant viruses to evolve. This condition can be potentially fatal.
- St John's wort and garlic supplements may decrease efavirenz blood levels.
- Psychiatric symptoms, including insomnia, nightmares, confusion, memory loss, and depression, are common, and more serious symptoms such as psychosis may occur in patients with compromised liver or kidney function.
- Rash, nausea, dizziness and headache may occur
- A general guideline about efavirenz and pregnancy states that efavirenz can cause birth defects and should not be used in women who might become pregnant. A later study, however, found no increased risk of overall birth defects among women exposed to efavirenz during the first trimester of pregnancy compared with exposure to other antiretroviral drugs.
- Safety in children has not been established
- Use of efavirenz can produce a false positive result in some urine tests for marijuana 
Abuse of efavirenz by crushing and smoking the tablets for supposed hallucinogenic and dissociative effects has been reported in South Africa, where it is used in a mixture known as whoonga. This is believed to be because of activity at a side target, the 5-HT2A receptor, which is better known as the target of drugs such as LSD. David E. Nichols suggested that the drug (or a metabolite) act as a PAM (positive allosteric modulator) for a body chemical which produced the effects although he didn't suggest a candidate or candidates.
As with most HIV treatments, efavirenz is quite expensive. A one month supply of 600 mg tablets costed approximately $550 in April 2008. Some emerging countries have opted to purchase Indian generics such as Efavir by Cipla Ltd for a fraction of the cost. In Thailand, one month supply of Efavirenz + Truvada, as of June 2012, costs THB 2900 ($90), there's also a social program for poorer patients who can't afford even this price. In South Africa, a license has been granted to generics giant Aspen Pharmacare to manufacture, and distribute to Sub-Saharan Africa, a cost-effective antiretroviral drug.
- Sustiva (USA, Bristol-Myers Squibb)
- Stocrin (EU, MSD)
- Aspen Efavirenz (Sub-Saharan Africa, Aspen Pharmacare)
Generic brands India:
- E.F (McNeil & Argus)
- Efavir (Cipla)
- Efcure (Emcure Pharmaceuticals)
- Efferven (Ranbaxy Laboratories)
- Estiva (Hetero)
- Evirenz (Alkem Laboratories)
- Viranz (Aurobindo Pharma)
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).
- "Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents". Retrieved 10 May 2013.
- 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 (22): 14410–15. doi:10.1073/pnas.222366699. PMC 137897. PMID 12386343.
- Sustiva (efavirenz) capsules and tablets. Product information (April 2005)
- Cespedes, MS; Aberg, JA (2006). "Neuropsychiatric complications of antiretroviral therapy.". Drug safety : an international journal of medical toxicology and drug experience 29 (10): 865–74. doi:10.2165/00002018-200629100-00004. PMID 16970510.
- Hasse, B; Günthard, HF; Bleiber, G; Krause, M (2005). "Efavirenz intoxication due to slow hepatic metabolism". Clinical Infectious Diseases 40 (3): e22–3. doi:10.1086/427031. PMID 15668854.
- Lowenhaupt, EA; Matson, K; Qureishi, B; Saitoh, A; Pugatch, D (2007). "Psychosis in a 12-year-old HIV-positive girl with an increased serum concentration of efavirenz". Clinical Infectious Diseases 45 (10): e128–30. doi:10.1086/522764. PMID 17968817.
- DHHS panel. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents (October 10, 2006). (Available for download from AIDSInfo)
- Ford, N.; Mofenson, L.; Kranzer, K.; Medu, L.; Frigati, L.; Mills, E. J.; Calmy, A. (2010). "Safety of efavirenz in first-trimester of pregnancy: A systematic review and meta-analysis of outcomes from observational cohorts". AIDS 24 (10): 1461–1470. doi:10.1097/QAD.0b013e32833a2a14. PMID 20479637.
- Rossi, S; Yaksh, T; Bentley, H; Van Den Brande, G; Grant, I; Ellis, R (2006). "Characterization of interference with 6 commercial delta9-tetrahydrocannabinol immunoassays by efavirenz (glucuronide) in urine". Clinical chemistry 52 (5): 896–7. doi:10.1373/clinchem.2006.067058. PMID 16638958.
- Röder, CS; Heinrich, T; Gehrig, AK; Mikus, G (2007). "Misleading results of screening for illicit drugs during efavirenz treatment". AIDS (London, England) 21 (10): 1390–1. doi:10.1097/QAD.0b013e32814e6b3e. PMID 17545727.
- IOL: Thugs get high on stolen Aids drugs
- Getting high on HIV drugs in S Africa. BBC News, 8 December 2008.
- 'No Turning Back': Teens Abuse HIV Drugs. ABC News, April 6, 2009.
- Gatch, M. B.; Kozlenkov, A.; Huang, R. Q.; Yang, W.; Nguyen, J. D.; González-Maeso, J.; Rice, K. C.; France, C. P.; Dillon, G. H.; Forster, M. J.; Schetz, J. A. (2013). "The HIV Antiretroviral Drug Efavirenz has LSD-Like Properties". Neuropsychopharmacology. doi:10.1038/npp.2013.135. PMID 23702798.
- Dr. David E. Nichols - Personal Communication may 24 2014
- Price listed on http://drugstore.com website, 4/20/2008
- IndiaDaily - A new trend in emerging nations - Brazil opts for Indian generic drug ignoring US pharmaceutical giant Merck’s patent on AIDS drug Efavirenz
- Patrick Lumumba Osewe; Yvonne Korkoi Nkrumah; Emmanuel K. Sackey (15 June 2008). Improving Access to HIV/AIDS Medicines in Africa: Trade-Related Aspects of Intellectual Property Rights (TRIPS) Flexibilities Utilization. World Bank Publications. pp. 35–39. ISBN 978-0-8213-7544-0. Retrieved 30 June 2012.
- Drugsupdate.com generic brands list: http://www.drugsupdate.com/brand/generic/Efavirenz/87
- Sütterlin, S., Vögele, C., & Gauggel, S. (2010). Neuropsychiatric complications of Efavirenz therapy: suggestions for a new research paradigm. The Journal of Neuropsychiatry and Clinical Neurosciences, 22(4), 361-369.