إيفاڤيرنز

إيفاڤيرنز
البيانات السريرية
فئة السلامة; أثناء الحمل	D (U.S.);
مسارات; الدواء	Oral
رمز ATC	J05AG03 (WHO) ;
الحالة القانونية
الحالة القانونية	POM (UK), ℞-only (U.S.);
بيانات الحركية الدوائية
ارتباط الپروتين	99.5-99.75%
الأيض	Hepatic (CYP3A4 and CYP2B6-mediated)
Elimination half-life	40-55 hours
الإخراج	Renal and fecal
المعرفات
	IUPAC name (4S)-6-chloro-4-(2-cyclopropylethynyl)-4-(trifluoromethyl)-2,4-dihydro-1H-3,1-benzoxazin-2-one;
رقم CAS	154598-52-4;
PubChem CID	64139;
DrugBank	APRD00059;
CompTox Dashboard (EPA)	DTXSID9046029 ;
ECHA InfoCard	100.149.346
Chemical and physical data
التركيب	C14H9ClF3NO2
الكتلة المولية	315.675 g/mol
3D model (JSmol)	Interactive image;
	SMILES Clc1ccc2NC(=O)O[C@@](C#CC3CC3)(c2c1)C(F)(F)F;

'Efavirenz'إيفاڤيرنز (أسماؤه التجارية Sustiva و Stocrin) يكون non-nucleoside reverse transcriptase inhibitor (NNRTI) وهو يستعمل كجزء من علاج شديد الفعالية مضاد للفيروسات (HAART) لعلاج مرض نقص المناعة المكتسب النوع 1 (HIV) type 1.

لعدوى الإيدز التى لم يتم علاجها من قبل , [[الولايات المتحدة وزارة الصحة والخدمات البشرية, فإن الفريق المعنى بإرشادات العلاجات الخاصة بمضادات الإيدز أشار بإستعمال إيفاڤيرنز مع أضافةlamivudine/zidovudine (Combivir) أو tenofovir/emtricitabine (Truvada) كتركيب مفضلNNRTI- من أنظمة مبنية لعلاج البالغين والمراهقين.

يستعمل إيفاڤيرنز' أيضا بإضافة antiretroviral أدوية expanded postexposure prophylaxis علاجات لمنع الإصابة للمختلطين بالمرضى , والمعرضين لتناول مواد ترتبط بخطورة ما في عدوى الإيدز.

الجرعة للبالغين 600 مج مرة يوميا. تؤخذ على معدة خاوية عندما يحين وقت النوم لتقليل الآثار الجانبية العصبيةو النفسية .

إيفاڤيرنز' أستخدم مع أدوية الإيدز المعروفة أو المنتشرة HIV علاجات Truvada, التى تتكون منtenofovir و emtricitabine, وكل هذه العلاجاتreverse transcriptase inhibitors. هذا التركيب من 3 علاجات أقرته FDA في يوليو 2006 تحت الإسم التجارى Atripla, يعطى فعالية علاجية شديدة ضد الفيروس (HAART) في صورة قرص واحد يؤخذ يوميا.ونتج عن ذلك تبسيط للعلاج بالنسبة لكثير من المرضى .

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التاريخ

Efavirenz was approved by the Food and Drug Administration (FDA) on September 21, 1998, making it the 14th approved antiretroviral drug.

الإستعمالات

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.

نظرية العمل

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 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.^[2]

الجرعات

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.

التفاعلات الدوائية

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.

الآثار الجانبية

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
Abuse of efavirenz for supposed hallucinogenic and dissociative effects has been reported in South Africa ^[4]^[5]

معلومات عن التسعير

As with most HIV treatments, efavirenz is quite expensive. A one month supply of 600mg tablets cost approximately $550 in April 2008^[6]. Some emerging countries have opted to purchase Indian generics^[7] such as Efavir by Cipla Ltd^[8] for a fraction of the cost.

الخواص الكيمائية

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).

المراجع

^ 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. doi:10.1073/pnas.222366699. PMID 12386343. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
^ 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 (October 10, 2006). (Available for download from AIDSInfo)
^ IOL: Thugs get high on stolen Aids drugs
^ Getting high on HIV drugs in S Africa. BBC News, 8 December 2008.
^ 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
^ www.cipla.com

الروابط الخارجية

قالب:أدوية الإيدز

الكلمات الدالة:

[1] 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. doi:10.1073/pnas.222366699. PMID 12386343. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)

[2] Sustiva (efavirenz) capsules and tablets. Product information (April 2005)

[dhhs-3] DHHS panel. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents (October 10, 2006). (Available for download from AIDSInfo)

[4] IOL: Thugs get high on stolen Aids drugs

[5] Getting high on HIV drugs in S Africa. BBC News, 8 December 2008.

[6] Price listed on http://drugstore.com website, 4/20/2008

[7] IndiaDaily - A new trend in emerging nations - Brazil opts for Indian generic drug ignoring US pharmaceutical giant Merck’s patent on AIDS drug Efavirenz

[8] www.cipla.com

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