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| {{drugbox | | __NOTOC__ |
| | IUPAC_name = 8-chloro-5-(2-cyclopropylethynyl)- 5-(trifluoromethyl)- 4-oxa-2-azabicyclo [4.4.0]deca- 7,9,11-trien-3-one
| | {{Efavirenz}} |
| | image = Efavirenz.png
| | {{CMG}} |
| | width = 133
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| | CAS_number = 154598-52-4
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| | ATC_prefix = J05
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| | ATC_suffix = AG03
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| | PubChem = 64139
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| | DrugBank = APRD00059
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| | C = 14 | H = 9 | Cl = 1 | F = 3 | N = 1 | O = 2
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| | molecular_weight = 315.675 [[Gram|g]]/[[Mole (unit)|mol]]
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| | bioavailability =
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| | protein_bound = 99.5-99.75%
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| | metabolism = [[Liver|Hepatic]] ([[CYP3A4]] and [[CYP2B6]]-mediated)
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| | elimination_half-life = 40-55 hours
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| | excretion = [[Kidney|Renal]] and fecal
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| | pregnancy_category = D <small>([[United States|U.S.]])</small>
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| | legal_status = POM <small>([[United Kingdom|UK]])</small>, ℞-only <small>(U.S.)</small>
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| | routes_of_administration = Oral
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| }} | |
| <!-- FAIR USE of Efavirenz_Sustiva.gif: see image description page at http://en.wikipedia.org/wiki/Image:Efavirenz_Sustiva.gif for rationale -->
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| '''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.
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| For HIV infection that has not previously been treated, the [[United States Department of Health and Human Services]] Panel on
| | ==Overview== |
| Antiretroviral Guidelines currently recommends the use of efavirenz in combination with [[lamivudine]]/[[zidovudine]] or [[tenofovir]]/[[emtricitabine]] as the preferred NNRTI-based regimens in adults and adolescents.
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| 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.
| | ==Category== |
| | Antiretroviral drug |
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| The usual adult dose is 600 [[Milligram|mg]] once a day. It is usually taken on an empty stomach at bedtime to reduce [[neurological]] and [[psychiatric]] adverse effects.
| | ==US Brand Names== |
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| Efavirenz was combined with the popular [[HIV]] [[medication]] [[Truvada]], which consists of [[tenofovir]] and [[emtricitabine]], all of which are [[reverse transcriptase inhibitor]]s. This combination of three medications approved by the [[FDA]] in July of 2006 under the brand name [[Atripla]], provides highly active antiretroviral therapy ([[HAART]]) in a single tablet taken once a day. It results in a simplified drug regimen for many patients. | | ==FDA Package Insert== |
| | ''' [[Efavirenz description|Description]]''' |
| | '''| [[Efavirenz clinical pharmacology|Clinical Pharmacology]]''' |
| | '''| [[Efavirenz microbiology|Microbiology]]''' |
| | '''| [[Efavirenz indications and usage|Indications and Usage]]''' |
| | '''| [[Efavirenz contraindications|Contraindications]]''' |
| | '''| [[Efavirenz warnings and precautions|Warnings and Precautions]]''' |
| | '''| [[Efavirenz adverse reactions|Adverse Reactions]]''' |
| | '''| [[Efavirenz overdosage|Overdosage]]''' |
| | '''| [[Efavirenz clinical studies|Clinical Studies]]''' |
| | '''| [[Efavirenz dosage and administration|Dosage and Administration]]''' |
| | '''| [[Efavirenz compatibility reconstitution and stability|Compatibility, Reconstitution, and Stability]]''' |
| | '''| [[Efavirenz directions for use|Directions For Use]]''' |
| | '''| [[Efavirenz how supplied|How Supplied]]''' |
| | '''| [[Efavirenz labels and packages|Labels and Packages]]''' |
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| ==History== | | ==Mechanism of Action== |
| Efavirenz was approved by the [[Food and Drug Administration]] (FDA) on [[September 21]], [[1998]], making it the 14th approved antiretroviral drug.
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| ==Indications==
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| 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]], [[viral load|HIV viral load]], treatment history, resistance profiles and patient preference.
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| 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 inhibitor]]s. The [[ACTG 5095]] trial showed that the potency of efavirenz is maintained at all [[CD4 count]]s and [[viral load|HIV viral loads]].
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| ==Mode of action==
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| 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.
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| 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.<ref>{{cite journal | author=Ren J, Bird LE, Chamberlain PP, ''et al.'' | year=2002 | title=Structure of HIV-2 reverse transcriptase at 2.35-A resolution and the mechanism of resistance to non-nucleoside inhibitors | journal=Proc Natl Acad Sci USA | volume=99 | pages=14410–15 | id=PMID 12386343}}</ref>
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| 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.<ref>[http://www.bms.com/cgi-bin/anybin.pl?sql=select+PPI+from+TB_PRODUCT_PPI+where+PPI_SEQ=94&key=PPI Sustiva (efavirenz) capsules and tablets. Product information (April 2005)]</ref>
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| ==Dosing==
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| 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]].
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| ==Drug interactions==
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| *Efavirenz is metabolized in the liver, and possesses both inhibitory and inducing effects on the [[CYP3A4|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.
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| *Efavirenz lowers blood levels of most [[protease inhibitor (pharmacology)|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.
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| *[[St John's wort]] and [[garlic]] supplements may decrease efavirenz blood levels.
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| ==Adverse effects==
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| *Psychiatric symptoms, including [[insomnia]], [[confusion]], [[memory loss]], and [[depression (mood)|depression]], are common
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| *[[Rash]], [[nausea]], [[dizziness]] and [[headache]] may occur
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| *Efavirenz can cause [[birth defects]] and should not be used in women who might become pregnant<ref name="dhhs">DHHS panel. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents (October 10, 2006). (Available for download from [http://www.aidsinfo.nih.gov/Guidelines/GuidelineDetail.aspx?MenuItem=Guidelines&Search=Off&GuidelineID=7&ClassID=1 AIDSInfo])</ref>
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| *Safety in children has not been established
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| *Use of efavirenz can produce a [[false positive]] result in some urine tests for [[cannabis (drug)|marijuana]]
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| *Abuse of efavirenz for supposed [[hallucinogenic]] and [[dissociative]] effects has been reported in South Africa <ref>http://www.iol.co.za/index.php?from=rss_South+Africa&set_id=1&click_id=13&art_id=vn20070512085358794C523744</ref>
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| ==Pricing Information==
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| As with most [[HIV]] treatments, efavirenz is quite expensive. A common dose of 600mg daily in industrialized countries will usually cost about $1400 USD for a single month supply. Some emerging countries have opted to purchase Indian generics<ref>http://www.indiadaily.com/editorial/16665.asp</ref> such as Efavir by Cipla Ltd<ref>www.cipla.com</ref> for a fraction of the cost. Some online pharmacies carry the generic for about $10 per 600mg pill.
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| <!-- The following section may be redundant, since much of its information is already contained in the drugbox.-->
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| ==Chemical structure & state of matter==
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| Efavirenz is chemically described as (S)-6-chloro-(cyclopropylethynyl)-1,4-dihydro-4-(trifluoromethyl)-2H-3,1-benzoxazin-2-one. Its empirical formula is C<sub>14</sub>H<sub>9</sub>ClF<sub>3</sub>NO<sub>2</sub>. 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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| ==References== | | ==References== |
| <references/>
| | {{Reflist|2}} |
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| ==External links==
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| *[http://www.sustiva.com/managehiv/sustiva/home/index.jsp?BV_UseBVCookie=Yes Manufacturer's site]
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| *[http://www.bms.com/cgi-bin/anybin.pl?sql=select+PPI+from+TB_PRODUCT_PPI+where+PPI_SEQ=94&key=PPI Prescribing information]
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| {{HIVpharm}} | |
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| [[Category:Non-nucleoside reverse transcriptase inhibitors]]
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| [[fr:Éfavirenz]] | | [[Category:Antibiotics]] |
| [[th:อีฟาวิเรนซ์]] | | [[Category:Wikinfect]] |
| [[zh:依法韦仑]]
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| {{WikiDoc Sources}}
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