Efavirenz

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Efavirenz
Efavirenz.svg
Efavirenz ball-and-stick model.png
Clinical data
Pronunciation /ɪˈfævɪrɛnz/ i-FAV-i-renz
Trade names Sustiva, Stocrin, others [1]
Other namesEFV
AHFS/Drugs.com Monograph
MedlinePlus a699004
License data
Pregnancy
category
  • AU:D
Routes of
administration
By mouth (capsules, tablets)
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability 40–45% (under fasting conditions)
Protein binding 99.5–99.75%
Metabolism Liver (CYP2A6 and CYP2B6-mediated)
Onset of action 3–5 hours
Elimination half-life Single-dose: 52–76 h [5]
Multi-dose: 40–55 h [5]
Excretion Kidney (14–34%) and feces (16–61%)
Identifiers
  • (4S)-6-Chloro-4-(2-cyclopropylethynyl)-4-(trifluoromethyl)-2,4-dihydro-1H-3,1-benzoxazin-2-one
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
NIAID ChemDB
PDB ligand
CompTox Dashboard (EPA)
ECHA InfoCard 100.149.346 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C14H9ClF3NO2
Molar mass 315.68 g·mol−1
3D model (JSmol)
  • O=C1Nc2ccc(Cl)cc2[C@@](C#CC2CC2)(C(F)(F)F)O1
  • InChI=1S/C14H9ClF3NO2/c15-9-3-4-11-10(7-9)13(14(16,17)18,21-12(20)19-11)6-5-8-1-2-8/h3-4,7-8H,1-2H2,(H,19,20)/t13-/m0/s1 Yes check.svgY
  • Key:XPOQHMRABVBWPR-ZDUSSCGKSA-N Yes check.svgY
   (verify)

Efavirenz (EFV), sold under the brand names Sustiva among others, is an antiretroviral medication used to treat and prevent HIV/AIDS. [1] It is generally recommended for use with other antiretrovirals. [1] It may be used for prevention after a needlestick injury or other potential exposure. [1] It is sold both by itself and in combination as efavirenz/emtricitabine/tenofovir. [1] It is taken by mouth. [1]

Contents

Common side effects include rash, nausea, headache, feeling tired, and trouble sleeping. [1] Some of the rashes may be serious such as Stevens–Johnson syndrome. [1] Other serious side effects include depression, thoughts of suicide, liver problems, and seizures. [1] It is not safe for use during pregnancy. [1] It is a non-nucleoside reverse transcriptase inhibitor (NNRTI) and works by blocking the function of reverse transcriptase. [1]

Efavirenz was approved for medical use in the United States in 1998, [1] and in the European Union in 1999. [4] It is on the World Health Organization's List of Essential Medicines. [6] As of 2016, it is available as a generic medication. [7] [8]

Medical uses

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 [9] and children. [10]

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.). [11] [12]

Pregnancy and breastfeeding

Efavirenz is safe to use during the first trimester of pregnancy. [13] Efavirenz passes into breast milk and breast-fed infants may be exposed to efavirenz. [14]

Contraindications

People who have taken this medication before and experienced an allergic reaction should avoid taking further efavirenz dosages. Hypersensitivity reactions include Stevens–Johnson syndrome, toxic skin eruptions, and erythema multiforme. [3]

Adverse effects

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. [15] [16] Some people experience euphoria. [15]

Rash and nausea may occur. [3]

Use of efavirenz can produce a false positive result in some urine tests for marijuana. [17] [18]

Efavirenz may lengthen the QT interval so should not be used in people with or at risk of torsades de pointes. [19]

Efavirenz may cause convulsions in adult and pediatric populations who have a history of seizures. [3]

Interactions

Efavirenz is broken down in the liver by enzymes that belong to the cytochrome P450 system, which include both CYP2B6 and CYP3A4. [3] Efavirenz is a substrate of these enzymes and can decrease the metabolism of other drugs that require the same enzymes. [3] 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. [3] 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 amprenavir, atazanavir, and indinavir. [3] 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. [3] 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.

Pharmacology

Pharmacodynamics

Anti-HIV effects

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. [20]

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. [3] 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. [1]

Neuropsychiatric effects

Efavirenz has been found to have affinity for a variety of targets to varying degrees and appears to act as an antagonist of the serotonin 5-HT2A (specifically Gq signaling), 5-HT2B, 5-HT2C, and 5-HT3 receptors, as an inverse agonist of the serotonin 5-HT6 receptor, as a dual GABAA receptor positive allosteric modulator and orthosteric site antagonist, as a serotonin–dopamine reuptake inhibitor (SDRI), as a vesicular monoamine transporter 2 (VMAT2) inhibitor, as a monoamine oxidase inhibitor (MAOI) of MAO-A, and as an antagonist of the muscarinic acetylcholine M1 and M3 receptors. [21] [22] [23] Efavirenz produces the head-twitch response, a behavioral proxy of serotonergic psychedelic effects, in animals, and can partially substitute for LSD and MDMA in animal drug discrimination tests. [21] [24] [22] Induction of the head-twitch response and substitution for LSD by efavirenz can be abolished by serotonin 5-HT2A receptor antagonists or serotonin 5-HT2A receptor knockout. [24] Efavirenz does not substitute for cocaine or carisoprodol. [21] The drug is not self-administered and does not produce conditioned place preference (CPP) in animals. [21]

As of 2016 the mechanism of efavirenz's neuropsychiatric adverse effects was not clear. [15] [16] It appears to produce 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. [15] Some neuropsychiatric adverse effects may be mediated through cannabinoid receptors, or through activity at the serotonin 5-HT2A receptor, but efavirenz interacts with many central nervous system targets, so this is not clear. [15] The neuropsychiatric adverse effects are dose-dependent. [15] Although efavirenz appears to act as a serotonin 5-HT2A receptor antagonist, it has been suggested that it might exert functional selectivity and act as an agonist of the receptor for certain signaling pathways, which could in turn explain its hallucinogenic and LSD-like effects. [21] [24] However, this hypothesis remains to be evaluated. [21] Conversely, research suggests that efavirenz may actually be a partial agonist of the serotonin 5-HT2A receptor. [25] The effects of efavirenz in animals and humans are consistent with it being a serotonergic psychedelic. [24] [22] [26] [27] [28]

Pharmacokinetics

The onset of action of efavirenz is 3 to 5 hours[ citation needed ] and its elimination half-life is 52 to 76 hours with a single dose and 40 to 55 hours with continuous administration. [5] The shorter half-life with chronic administration may be due to induction of cytochrome P450 enzymes by efavirenz. [5]

Chemistry

Efavirenz is chemically described as (4S)-6-chloro-4-(2-cyclopropylethynyl)-4-(trifluoromethyl)-1H-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).

History

Efavirenz was approved by the FDA on 21 September 1998. [29]

On 17 February 2016, the FDA approved the generic tablet formulation to be produced by Mylan. [7] [8]

In late 2018, Thailand's Government Pharmaceutical Organization (GPO) announced that it will produce efavirenz after receiving WHO approval. [30]

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. [31]

Society and culture

Pricing information

A one-month supply of 600 mg tablets costs approximately US$1,010 in July 2016. [32] In 2007, Merck provided Efavirenz in certain developing countries and countries largely affected by HIV for about US$0.65 per day. [33] Some emerging countries have opted to purchase Indian generics. [34]

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 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. [30]

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. [35]

Recreational use

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. [36] [37] [38] [39] Researcher Hamilton Morris described efavirenz as "classically psychedelic." [26]

Brands

As of 2016, efavirenz is 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. [40]

As of 2016, the combination of efavirenz, tenofovir, and emtricitabine is marketed in various jurisdictions under the brand names Atripla, Atroiza, Citenvir, Oditec, Teevir, Trustiva, Viraday, and Vonavir. [40]

As of 2016, the combination of efavirenz, tenofovir, and lamivudine is marketed under the brand name Eflaten. [40]

Related Research Articles

<span class="mw-page-title-main">Zidovudine</span> Antiretroviral medication

Zidovudine (ZDV), also known as azidothymidine (AZT), was the first antiretroviral medication used to prevent and treat HIV/AIDS. It is generally recommended for use in combination with other antiretrovirals. It may be used to prevent mother-to-child spread during birth or after a needlestick injury or other potential exposure. It is sold both by itself and together as lamivudine/zidovudine and abacavir/lamivudine/zidovudine. It can be used by mouth or by slow injection into a vein.

The management of HIV/AIDS normally includes the use of multiple antiretroviral drugs as a strategy to control HIV infection. There are several classes of antiretroviral agents that act on different stages of the HIV life-cycle. The use of multiple drugs that act on different viral targets is known as highly active antiretroviral therapy (HAART). HAART decreases the patient's total burden of HIV, maintains function of the immune system, and prevents opportunistic infections that often lead to death. HAART also prevents the transmission of HIV between serodiscordant same-sex and opposite-sex partners so long as the HIV-positive partner maintains an undetectable viral load.

Reverse-transcriptase inhibitors (RTIs) are a class of antiretroviral drugs used to treat HIV infection or AIDS, and in some cases hepatitis B. RTIs inhibit activity of reverse transcriptase, a viral DNA polymerase that is required for replication of HIV and other retroviruses.

<span class="mw-page-title-main">Lamivudine</span> Chemical compound

Lamivudine, commonly called 3TC, is an antiretroviral medication used to prevent and treat HIV/AIDS. It is also used to treat chronic hepatitis B when other options are not possible. It is effective against both HIV-1 and HIV-2. It is typically used in combination with other antiretrovirals such as zidovudine, dolutegravir, and abacavir. Lamivudine may be included as part of post-exposure prevention in those who have been potentially exposed to HIV. Lamivudine is taken by mouth as a liquid or tablet.

<span class="mw-page-title-main">Emtricitabine</span> Antiretroviral drug used to treat HIV infection

Emtricitabine, with trade name Emtriva, is a nucleoside reverse-transcriptase inhibitor (NRTI) for the prevention and treatment of HIV infection in adults and children. In 2019, it was the 494th most commonly prescribed medication in the United States, with more than 3 thousand prescriptions.

<span class="mw-page-title-main">Tenofovir disoproxil</span> Antiviral drug used to treat or prevent HIV and hepatitis infections

Tenofovir disoproxil, sold under the brand name Viread among others, is a medication used to treat chronic hepatitis B and to prevent and treat HIV/AIDS. It is generally recommended for use with other antiretrovirals. It may be used for prevention of HIV/AIDS among those at high risk before exposure, and after a needlestick injury or other potential exposure. It is sold both by itself and together in combinations such as emtricitabine/tenofovir, efavirenz/emtricitabine/tenofovir, and elvitegravir/cobicistat/emtricitabine/tenofovir. It does not cure HIV/AIDS or hepatitis B. It is available by mouth as a tablet or powder.

<span class="mw-page-title-main">Nevirapine</span> Chemical compound

Nevirapine (NVP), sold under the brand name Viramune among others, is a medication used to treat and prevent HIV/AIDS, specifically HIV-1. It is generally recommended for use with other antiretroviral medications. It may be used to prevent mother to child spread during birth but is not recommended following other exposures. It is taken by mouth.

<span class="mw-page-title-main">Delavirdine</span> Chemical compound

Delavirdine (DLV) is a non-nucleoside reverse transcriptase inhibitor (NNRTI) marketed by ViiV Healthcare. It is used as part of highly active antiretroviral therapy (HAART) for the treatment of human immunodeficiency virus (HIV) type 1. It is presented as the mesylate. The recommended dosage is 400 mg, three times a day.

<span class="mw-page-title-main">Darunavir</span> Antiretroviral medication

Darunavir (DRV), sold under the brand name Prezista among others, is an antiretroviral medication used to treat and prevent HIV/AIDS. It is generally recommended for use with other antiretrovirals. It is often used with low doses of ritonavir or cobicistat to increase darunavir levels. It may be used for prevention after a needlestick injury or other potential exposure. It is taken by mouth once to twice a day.

<span class="mw-page-title-main">Efavirenz/emtricitabine/tenofovir</span> Combination drug for HIV

Efavirenz/emtricitabine/tenofovir, sold under the brand name Atripla among others, is a fixed-dose combination antiretroviral medication used to treat HIV/AIDS. It contains efavirenz, emtricitabine, and tenofovir disoproxil. It can be used by itself or together with other antiretroviral medications. It is taken by mouth.

<span class="mw-page-title-main">Raltegravir</span> Chemical compound

Raltegravir, sold under the brand name Isentress, is an antiretroviral medication used, together with other medication, to treat HIV/AIDS. It may also be used, as part of post exposure prophylaxis, to prevent HIV infection following potential exposure. It is taken by mouth.

<span class="mw-page-title-main">Resistance mutation (virology)</span> Virus mutation

A resistance mutation is a mutation in a virus gene that allows the virus to become resistant to treatment with a particular antiviral drug. The term was first used in the management of HIV, the first virus in which genome sequencing was routinely used to look for drug resistance. At the time of infection, a virus will infect and begin to replicate within a preliminary cell. As subsequent cells are infected, random mutations will occur in the viral genome. When these mutations begin to accumulate, antiviral methods will kill the wild type strain, but will not be able to kill one or many mutated forms of the original virus. At this point a resistance mutation has occurred because the new strain of virus is now resistant to the antiviral treatment that would have killed the original virus. Resistance mutations are evident and widely studied in HIV due to its high rate of mutation and prevalence in the general population. Resistance mutation is now studied in bacteriology and parasitology.

<span class="mw-page-title-main">Etravirine</span> Medication used for the treatment of HIV

Etravirine (ETR,), sold under the brand name Intelence is an antiretroviral medication used for the treatment of HIV. Etravirine is a human immunodeficiency virus type 1 (HIV-1) non-nucleoside reverse transcriptase inhibitor (NNRTI). Unlike agents in the class, resistance to other NNRTIs does not seem to confer resistance to etravirine. Etravirine is marketed by Janssen, a subsidiary of Johnson & Johnson. In January 2008, the US Food and Drug Administration (FDA) approved its use for people with established resistance to other drugs, making it the 30th anti-HIV drug approved in the United States and the first to be approved in 2008. It was also approved for use in Canada in April 2008.

<span class="mw-page-title-main">Elvitegravir</span> Chemical compound

Elvitegravir (EVG) is an integrase inhibitor used to treat HIV infection. It was developed by the pharmaceutical company Gilead Sciences, which licensed EVG from Japan Tobacco in March 2008. The drug gained approval by the U.S. Food and Drug Administration on August 27, 2012, for use in adult patients starting HIV treatment for the first time as part of the fixed dose combination known as Stribild. On September 24, 2014, the FDA approved Elvitegravir as a single pill formulation under the trade name Vitekta. On November 5, 2015, the FDA approved the drug for use in patients affected with HIV-1 as a part of a second fixed dose combination pill known as Genvoya.

<span class="mw-page-title-main">Rilpivirine</span> HIV treatment

Rilpivirine, sold under the brand names Edurant and Rekambys, is a medication, developed by Tibotec, used for the treatment of HIV/AIDS. It is a second-generation non-nucleoside reverse transcriptase inhibitor (NNRTI) with higher potency, longer half-life and reduced side-effect profile compared with older NNRTIs such as efavirenz.

<span class="mw-page-title-main">Stampidine</span> Medication

Stampidine is an experimental nucleoside reverse transcriptase inhibitor (NRTI) with anti-HIV activity.

<span class="mw-page-title-main">HIV disease–related drug reaction</span>

HIV disease–related drug reaction is an adverse drug reaction caused by drugs used for the treatment of HIV/AIDS.

Non-nucleoside reverse-transcriptase inhibitors (NNRTIs) are antiretroviral drugs used in the treatment of human immunodeficiency virus (HIV). NNRTIs inhibit reverse transcriptase (RT), an enzyme that controls the replication of the genetic material of HIV. RT is one of the most popular targets in the field of antiretroviral drug development.

Discovery and development of nucleoside and nucleotide reverse-transcriptase inhibitors began in the 1980s when the AIDS epidemic hit Western societies. NRTIs inhibit the reverse transcriptase (RT), an enzyme that controls the replication of the genetic material of the human immunodeficiency virus (HIV). The first NRTI was zidovudine, approved by the U.S. Food and Drug Administration (FDA) in 1987, which was the first step towards treatment of HIV. Six NRTI agents and one NtRTI have followed. The NRTIs and the NtRTI are analogues of endogenous 2´-deoxy-nucleoside and nucleotide. Drug-resistant viruses are an inevitable consequence of prolonged exposure of HIV-1 to anti-HIV drugs.

<span class="mw-page-title-main">Bictegravir/emtricitabine/tenofovir alafenamide</span> Fixed dose combination HIV drug

Bictegravir/emtricitabine/tenofovir alafenamide, sold under the brand name Biktarvy, is a fixed-dose combination antiretroviral medication for the treatment of HIV/AIDS. It contains bictegravir, a human immunodeficiency virus type 1 (HIV-1) integrase strand transfer inhibitor; emtricitabine, an HIV-1 nucleoside analog reverse transcriptase inhibitor; and tenofovir alafenamide, an HIV-1 nucleoside analog reverse transcriptase inhibitor.

References

  1. 1 2 3 4 5 6 7 8 9 10 11 12 13 "Efavirenz". The American Society of Health-System Pharmacists. Archived from the original on 17 November 2016. Retrieved 28 November 2016.
  2. "Product monograph brand safety updates". Health Canada . 7 July 2016. Retrieved 3 April 2024.
  3. 1 2 3 4 5 6 7 8 9 10 "Sustiva- efavirenz capsule, gelatin coated Sustiva- efavirenz capsule, gelatin coated Sustiva- efavirenz tablet, film coated". DailyMed. 29 October 2019. Retrieved 15 October 2020.
  4. 1 2 "Stocrin EPAR". European Medicines Agency (EMA). 17 September 2018. Retrieved 15 October 2020.
  5. 1 2 3 4 https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020972s038lbl.pdf
  6. World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl: 10665/325771 . WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
  7. 1 2 "Efavirenz Drug Profile". DrugPatentWatch. Archived from the original on 10 November 2016. Retrieved 9 November 2016.
  8. 1 2 "Efavirenz: FDA-Approved Drugs". U.S. Food and Drug Administration (FDA). Retrieved 25 April 2020.
  9. "Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents". 14 July 2016. Archived from the original on 23 May 2013.
  10. "Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection". NIH AIDSinfo. 1 March 2016. Archived from the original on 15 November 2016.
  11. Kuhar DT, Henderson DK, Struble KA, Heneine W, Thomas V, Cheever LW, et al. (September 2013). "Updated US Public Health Service guidelines for the management of occupational exposures to human immunodeficiency virus and recommendations for postexposure prophylaxis". Infection Control and Hospital Epidemiology. 34 (9): 875–92. doi:10.1086/672271. PMID   23917901. S2CID   17032413.
  12. "Antiretroviral Postexposure Prophylaxis After Sexual, Injection-Drug Use, or Other Nonoccupational Exposure to HIV in the United States =" (PDF). Centers for Disease Control and Prevention. Archived (PDF) from the original on 27 January 2017. Retrieved 7 November 2016.
  13. Ford N, Mofenson L, Shubber Z, Calmy A, Andrieux-Meyer I, Vitoria M, et al. (March 2014). "Safety of efavirenz in the first trimester of pregnancy: an updated systematic review and meta-analysis". AIDS. 28 (Suppl 2): S123-31. doi: 10.1097/qad.0000000000000231 . PMID   24849471. S2CID   39329729.
  14. Waitt CJ, Garner P, Bonnett LJ, Khoo SH, Else LJ (July 2015). "Is infant exposure to antiretroviral drugs during breastfeeding quantitatively important? A systematic review and meta-analysis of pharmacokinetic studies". The Journal of Antimicrobial Chemotherapy. 70 (7): 1928–41. doi:10.1093/jac/dkv080. PMC   4472329 . PMID   25858354.
  15. 1 2 3 4 5 6 Treisman GJ, Soudry O (October 2016). "Neuropsychiatric Effects of HIV Antiviral Medications". Drug Safety. 39 (10): 945–57. doi:10.1007/s40264-016-0440-y. PMID   27534750. S2CID   6809436.
  16. 1 2 Apostolova N, Funes HA, Blas-Garcia A, Galindo MJ, Alvarez A, Esplugues JV (October 2015). "Efavirenz and the CNS: what we already know and questions that need to be answered". The Journal of Antimicrobial Chemotherapy. 70 (10): 2693–708. doi: 10.1093/jac/dkv183 . PMID   26203180.
  17. Rossi S, Yaksh T, Bentley H, van den Brande G, Grant I, Ellis R (May 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.
  18. Röder CS, Heinrich T, Gehrig AK, Mikus G (June 2007). "Misleading results of screening for illicit drugs during efavirenz treatment". AIDS. 21 (10): 1390–1. doi: 10.1097/QAD.0b013e32814e6b3e . PMID   17545727.
  19. Abdelhady AM, Shugg T, Thong N, Lu JB, Kreutz Y, Jaynes HA, et al. (October 2016). "Efavirenz Inhibits the Human Ether-A-Go-Go Related Current (hERG) and Induces QT Interval Prolongation in CYP2B6*6*6 Allele Carriers". Journal of Cardiovascular Electrophysiology. 27 (10): 1206–1213. doi:10.1111/jce.13032. PMC   5065384 . PMID   27333947.
  20. Ren J, Bird LE, Chamberlain PP, Stewart-Jones GB, Stuart DI, Stammers DK (October 2002). "Structure of HIV-2 reverse transcriptase at 2.35-A resolution and the mechanism of resistance to non-nucleoside inhibitors". Proceedings of the National Academy of Sciences of the United States of America. 99 (22): 14410–5. Bibcode:2002PNAS...9914410R. doi: 10.1073/pnas.222366699 . PMC   137897 . PMID   12386343.
  21. 1 2 3 4 5 6 Zareifopoulos N, Lagadinou M, Karela A, Pouliasi F, Economou I, Tsigkou A, Velissaris D (October 2020). "Efavirenz as a psychotropic drug". Eur Rev Med Pharmacol Sci. 24 (20): 10729–10735. doi:10.26355/eurrev_202010_23433. PMID   33155233.
  22. 1 2 3 Zareifopoulos N, Lagadinou M, Karela A, Kyriakopoulou O, Velissaris D (August 2020). "Neuropsychiatric Effects of Antiviral Drugs". Cureus. 12 (8): e9536. doi: 10.7759/cureus.9536 . PMC   7465925 . PMID   32905132.
  23. Dalwadi DA, Kim S, Amdani SM, Chen Z, Huang RQ, Schetz JA (August 2016). "Molecular mechanisms of serotonergic action of the HIV-1 antiretroviral efavirenz". Pharmacol Res. 110: 10–24. doi:10.1016/j.phrs.2016.04.028. PMC   4914440 . PMID   27157251.
  24. 1 2 3 4 Gatch MB, Kozlenkov A, Huang RQ, Yang W, Nguyen JD, González-Maeso J, Rice KC, France CP, Dillon GH, Forster MJ, Schetz JA (November 2013). "The HIV antiretroviral drug efavirenz has LSD-like properties". Neuropsychopharmacology. 38 (12): 2373–2384. doi:10.1038/npp.2013.135. PMC   3799056 . PMID   23702798.
  25. "The Anti-Hiv Drug Efavirenz: A Challenge on Molecular Mechanisms of Drug Associated Neurocognitive Disorders". ProQuest. ProQuest   3039370014 . Retrieved 1 December 2024.
  26. 1 2 Morris, Hamilton (9 April 2014). "Getting High on HIV Medication". YouTube. VICE. Retrieved 1 December 2024.
  27. Jaster AM, de la Fuente Revenga M, González-Maeso J (July 2022). "Molecular targets of psychedelic-induced plasticity". J Neurochem. 162 (1): 80–88. doi:10.1111/jnc.15536. PMC   9068831 . PMID   34741320.
  28. Jaster AM, González-Maeso J (September 2023). "Mechanisms and molecular targets surrounding the potential therapeutic effects of psychedelics". Mol Psychiatry. 28 (9): 3595–3612. doi:10.1038/s41380-023-02274-x. PMC   11078317 . PMID   37759040.
  29. "Drug Approval Package: Sustiva (efavirenz) NDA# 20-972". U.S. Food and Drug Administration (FDA). 15 December 2011. Retrieved 25 April 2020.
  30. 1 2 Wipatayotin A (3 November 2018). "Thailand gets nod to make HIV/Aids drug". Bangkok Post. Retrieved 3 November 2018.
  31. "Efavirenz (Sustiva)". aidsmap. June 2017.
  32. "Cost Considerations and Antiretroviral Therapy | Adult and Adolescent ARV Guidelines | AIDSinfo". AIDSinfo. Archived from the original on 17 November 2016. Retrieved 16 November 2016.
  33. "Merck & Co., Inc., Again Reduces Price of Stocrin (Efavirenz) for Patients in Least Developed Countries and Countries Hardest Hit by Epidemic". Drugs.com MedNews. Archived from the original on 14 July 2014.
  34. "A new trend in emerging nations - Brazil opts for Indian generic drug ignoring US pharmaceutical giant Merck's patent on AIDS drug Efavirenz". IndiaDaily. Archived from the original on 19 February 2008.
  35. Osewe PL, Korkoi Nkrumah Y, Sackey EK (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.
  36. "Thugs get high on stolen Aids drugs". IOL News. 12 May 2007. Archived from the original on 6 August 2013.
  37. "Getting high on HIV drugs in S Africa". BBC News. 8 December 2008. Archived from the original on 9 December 2008.
  38. "'No Turning Back': Teens Abuse HIV Drugs". ABC News. 6 April 2009. Archived from the original on 8 April 2009.
  39. "Getting High On HIV Medication". Vice. 4 July 2014. Archived from the original on 11 April 2014 via YouTube.
  40. 1 2 3 "International brands for Efavirenz". Drugs.com. Archived from the original on 10 November 2016. Retrieved 10 November 2016.