|Trade names||Sustiva, others|
|By mouth (capsules, tablets)|
|Onset of action||3–5 hours|
|Defined daily dose||600 mg|
|Bioavailability||40–45% (under fasting conditions)|
|Metabolism||Hepatic (CYP2A6 and CYP2B6-mediated)|
|Elimination half-life||40–55 hours|
|Excretion||Urine (14–34%) and feces (16–61%)|
|Chemical and physical data|
|Molar mass||315.68 g·mol−1|
|3D model (JSmol)|
Efavirenz (EFV), sold under the brand names Sustiva among others, is an antiretroviral medication used to treat and prevent HIV/AIDS. It is generally recommended for use with other antiretrovirals. It may be used for prevention after a needlestick injury or other potential exposure. It is sold both by itself and in combination as efavirenz/emtricitabine/tenofovir. It is taken by mouth once a day.
Common side effects include rash, nausea, headache, feeling tired, and trouble sleeping. Some of the rashes may be serious such as Stevens–Johnson syndrome. Other serious side effects include depression, thoughts of suicide, liver problems, and seizures. It is not safe for use during pregnancy. It is a non-nucleoside reverse transcriptase inhibitor (NNRTI) and works by blocking the function of reverse transcriptase.
Efavirenz was approved for medical use in the United States in 1998. It is on the World Health Organization's List of Essential Medicines. As of 2016, it is available as a generic medication. The wholesale cost in the developing world is about US$3.27 to 9.15 per month. As of 2015 the cost for a typical month of medication in the United States is more than US$200.
- 1 Medical uses
- 2 Side effects
- 3 Interactions
- 4 Mechanism of action
- 5 Chemistry
- 6 History
- 7 Society and culture
- 8 References
- 9 External links
For HIV infection that has not previously been treated, the United States Department of Health and Human Services Panel on Antiretroviral Guidelines recommends the use of efavirenz in combination with tenofovir/emtricitabine (Truvada) as one of the preferred NNRTI-based regimens in adults and adolescents and children.
Efavirenz is also used in combination with other antiretroviral agents as part of an expanded post-exposure 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.).
Pregnancy and breastfeeding
The defined daily dose is 600 mg (by mouth). The dose in those who weight more than 40 kg is 600 mg once per day, in those 25 to 40 kg it is 400 mg once per day, in those who 14 to 25 kg it is 300 mg once per day and in those 10 to 14 kg it is 200 mg once per day.
Neuropsychiatric effects are the most common adverse effects, and include disturbed sleep (including nightmares, insomnia, disrupted sleep, and daytime fatigue), dizziness, headaches, vertigo, blurred vision, anxiety, and cognitive impairment (including fatigue, confusion, and memory and concentration problems), and depression, including suicidal thinking. Some people experience euphoria.
People who have taken this medication before and experienced an allergic reaction should avoid taking further efavirenz dosages. Hypersensitivity reactions include Steven-Johnson syndrome, toxic skin eruptions, and erythema multiforme.
Efavirenz is broken down in the liver by enzymes that belong to the cytochrome P450 system, which include both CYP2B6 and CYP3A4. Efavirenz is a substrate of these enzymes and can decrease the metabolism of other drugs that require the same enzymes. However, efavirenz also induces these enzymes, which means the enzyme activity is enhanced and the metabolism of other drugs broken down by CYP2B6 and CYP3A4 can be increased. People who are taking both efavirenz and other drugs metabolized by the same enzymes might need the dose of their drugs to be increased or decreased.
One group of drugs that efavirenz affects is protease inhibitors, which are used for HIV/AIDS. Efavirenz will lower the blood levels of most protease inhibitors, including aprenavir, atazanavir, and indinavir. At lowered levels, protease inhibitors may not be effective in people taking both drugs, which means the virus that causes HIV/AIDS won't be stopped from replicating and may become resistant to the protease inhibitor.
Efavirenz also affects antifungal drugs, which are used for fungal infections such as urinary tract infections. Similar to the effect seen with protease inhibitors, efavirenz lowers the blood levels of antifungal drugs like voriconazole, itraconazole, ketoconazole, and posaconazole. As a result of lowered levels, antifungal drugs may not be effective in people taking both drugs, which means that the fungi that cause the infection may become resistant to the antifungal.
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. Nucleoside reverse-transcriptase inhibitors (NRTIs) and efavirenz have different binding targets, so cross-resistance is unlikely; the same is true with regard to efavirenz and protease inhibitors.
As of 2016 the mechanism of efavirenz' neuropsychiatric adverse effects was not clear. Efavirenz appears to have neurotoxicity, possibly by interfering with mitochondrial function, which may in turn possibly be caused by inhibiting creatine kinase but also possibly by disrupting mitochondrial membranes or by interfering with nitric oxide signalling. Some neuropsychiatric adverse effects may be mediated through cannabinoid receptors, or through activity at the 5-HT2A receptor, but efavirenz interacts with many CNS receptors, so this is not clear. The neuropsychiatric adverse effects are dose-dependent.
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).
Efavirenz was approved by the FDA on September 21, 1998
In late-2018, Thailand's Government Pharmaceutical Organization (GPO) announced that it will produce efavirenz after receiving WHO approval. Efavirenz code name is DMP 266, discovered by Du pont Pharma. European countries are set to receive the license for manufacturing of Efavirenz in May 1999.
Society and culture
A one-month supply of 600 mg tablets costs approximately US$1,010 in July 2016. In 2007, Merck provided Efavirenz in certain developing countries and countries largely affected by HIV for about US$0.65 per day. Some emerging countries have opted to purchase Indian generics.
In Thailand, a one-month supply of efavirenz + Truvada, as of June 2012, cost 2,900 baht (US$90), and there is a social program for patients who cannot afford the medication. As of 2018[update] Thailand will produce efavirenz domestically. Its Government Pharmaceutical Organization product costs 180 baht per bottle of thirty 600 mg tablets. The imported version in Thailand retails for more than 1,000 baht per bottle. GPO will devote 2.5 percent of its manufacturing capacity to make 42 million efavirenz pills in 2018, allowing it to serve export markets as well as domestic. The Philippines alone will order about 300,000 bottles of efavirenz for 51 million baht.
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 and nyaope.
As of 2016, efavirenz was marketed in various jurisdictions under the brand names Adiva, Avifanz, Efamat, Efatec, Efavir, Efavirenz, Efcure, Eferven, Efrin, Erige, Estiva, Evirenz, Filginase, Stocrin, Sulfina V, Sustiva, Virorrever, and Zuletel.
As of 2016, the combination of efavirenz, tenofovir, and emtricitabine was marketed in various jurisdictions under the brand names Atripla, Atroiza, Citenvir, Oditec, Teevir, Trustiva, Viraday, and Vonavir.
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