Nevirapine, نيڤيرابين يسوق تحت الأسم التجاري Viramune (Boehringer Ingelheim), is a non-nucleoside reverse transcriptase inhibitor (NNRTI) يستعمل لعلاج عدوىHIV-1 الإيدز.

وكمثل جميع أنواع أدوية antiretroviral, فإن الإيدز سرعان ما يبدى مقاومة, إذا أستخدم نيڤيرابين بمفرده, لذا فإن العلاج المقرر يتكون من مجموعة من ثلاثة أنواع أوأكثر من مضادات الفيروس. .

التاريخ

أكتشف نيڤيرابين بواسطة Hargrave et al. at Boehringer Ingelheim Pharmaceuticals, Inc. , واحدة من Boehringer Ingelheim مجموعة شركات . ويتم تغطيته بواسطة براءة أميريكية رقم 5,366,972 وببراءات خارجية مماثلة. نيڤيرابين كان أول NNRTI يقر بواسطةFood and Drug Administration (FDA) في الولايات المتحدة الأميريكية. تم الموافقة عليه 21 يونيو, 1996 للبالغين سبتمبر 11, 1998 وللأطفال. وأجيز في أوروبا عام 1997.

طريقة العمل

نيڤيرابينيفشل في مجموعة non-nucleoside reverse transcriptase inhibitor (NNRTI) مضادات الفيروس. Both nucleoside and non-nucleoside RTIs تثبط نفس الهدف , أنزيم reverse transcriptase , وهوأنزيم فعال يمتلكه الفيروس ويقوم بنسخ الرنا الفيروسي الى دنا . وليس كمثل nucleoside RTIs , الذى يلتصق بالجزء الحيوى من , NNRTIs يلتصق بالفيروس داخل جيب يسمى جيب NNRTI.

نيڤيرابين ليس فعالا ضد HIV-2, حيث حتى جيبHIV-2 يعاكس transcriptase الذى يمتلك هجريبا مختلفا , ويبدى مقاومة داخلية الى NNRTI class.

المقاومة لنيڤيرابين تتكون سريعا, أذا لم يتم إحباط عملية نسخ دنا الفيروس سريعا . The most common mutations observed after nevirapine treatment are Y181C and K103N, which are also observed with other NNRTIs. As all NNRTIs bind within the same pocket, viral strains which are resistant to nevirapine are usually also resistant to the other NNRTIs, efavirenz and delavirdine.

الفعالية السريرية

Nevirapine in triple combination therapy has been shown to suppress viral load effectively when used as initial antiretroviral therapy (i.e., in antiretroviral-naive patients). Some clinical trials have demonstrated comparable HIV suppression with nevirapine-based regimens to that achieved with protease inhibitors (PIs) or efavirenz. Although concerns have been raised about nevirapine-based regimens in those starting therapy with high viral load or low CD4 count, some analyses suggest that nevirapine may be effective in these patients.

Nevirapine may also form a useful component of salvage regimens after virological failure, usually in combination with one or more PIs as well as nRTIs, especially in those who have not previously taken an NNRTI.

الآثار الجانبية

The most common adverse effect of nevirapine is the development of mild or moderate rash (13%). Severe or life-threatening skin reactions have been observed in 1.5% of patients, including Stevens-Johnson syndrome, toxic epidermal necrolysis and hypersensitivity.

Nevirapine may cause severe or life-threatening liver toxicity, usually emerging in the first six weeks of treatment. In 2000, the U.S. Food and Drug Administration issued a black box label on nevirapine, warning that it could cause severe liver damage, including liver failure. Unacceptably high risk of serious liver symptoms in certain patient groups (women with CD4 count >250 and men >400) has led the U.S. DHSS to recommend the restriction of nevirapine use to those at lower risk, unless the benefit to the patient clearly outweighs the risk; although in the 2NN study which found these CD4 limits, the effect was seen only in patients recruited from Thailand. More recent studies on the use of Nevirapine in people with higher CD4 cell counts have come to the following conclusion: Treatment-experienced patients who start NVP-based combination therapy with low pre–ART and high current CD4 cell counts and an undetectable VL have a similar likelihood for discontinuing NVP therapy because of hypersensitivity reactions (HSRs), compared with treatment-naive patients with low CD4 cell counts. This suggests that NVP-based combination therapy may be safely initiated in such patients. However, in similar patients with a detectable VL, it is prudent to continue to adhere to current CD4 cell count thresholds. The U.S. Public Health Service Task Force advocates caution in the use of nevirapine in pregnancy due to toxicity issues, which may be exacerbated during pregnancy.

التفاعلات الدوائية

Significant lowering of nevirapine levels occurs with the anti-tuberculosis drug, rifampicin, and the drugs should not be administered together.

Nevirapine is an inducer of cytochrome P450 isoenzymes CYP3A4 and CYP2B6. It reduces the levels of several co-administered drugs including the antiretrovirals efavirenz, indinavir, lopinavir, nelfinavir and saquinavir, as well as clarithromycin, ketoconazole, forms of hormonal contraception, and methadone.

منع إنتنطق العدوى من الأم الى الطفل

A single dose of nevirapine given to both mother and child reduced the rate of HIV transmission by almost 50% compared with a very short course of zidovudine (AZT) prophylaxis, in a clinical trial in Uganda. A subsequent study in تايلند showed that prophylaxis with single-dose nevirapine in addition to zidovudine is more effective than zidovudine alone. These and other trials have led the World Health Organization to endorse the use of single-dose nevirapine prophylaxis in many developing world settings as a cost-effective way of reducing mother-to-child transmission. However, in the United States the Ugandan study was deemed flawed and as of 2006 the FDA has not approved of such nevirapine prophylaxis. Another clinical trial, Using Nevirapine to Prevent Mother-to-Child HIV Transmission During Breastfeeding is scheduled for completion in March 2011.

A major concern with this approach is that NNRTI resistance mutations are commonly observed in both mothers and infants after single-dose nevirapine, and may compromise the response to future NNRTI-containing regimens. A short course of maternal zidovudine/lamivudine is recommended by the U.S. Public Health Service Task Force to reduce this risk.

جدل في أفريقيا

U.S. President George W. Bush's $500 million plan to help combat the African AIDS epidemic includes nevirapine, among other medications and programs. Nevirapine has also been tested in trials in Africa, some of which have been highly controversial.

South African President Thabo Mbeki accused the الولايات المتحدة of using Africans as "guinea pigs". Questions regarding the efficacy of the antiretroviral nevirapine when compared with its side effects were the main stated reason for President Mbeki's concern. Until recently, however, Mbeki endorsed claims by some scientists that HIV is not the cause of AIDS—findings which are considered well outside the realm of reasonable scientific thought by the vast majority of the scientific community.

المراجع

نطقب:HIVpharm

نطقب:أدوية الإيدز