Nevirapine
Clinical data | |
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Trade names | Viramune |
AHFS/Drugs.com | Monograph |
MedlinePlus | a600035 |
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Routes of administration | By mouth |
ATC code | |
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Pharmacokinetic data | |
Bioavailability | 93% ± 9% |
Metabolism | Liver |
Elimination half-life | 45 hours |
Excretion | Kidney: <6% (Parent drug) Bile duct <5% (Parent drug) |
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Nevirapine (NVP), sold under the brand name Viramune among others, is a medication used to treat and prevent
Common side effects include rash, headache, nausea, feeling tired, and
Nevirapine was approved for medical use in the United States in 1996.
Medical uses
Nevirapine is used in people six years of age and older infected with HIV-1 as part of combination antiretroviral treatment (ART or cART). Monotherapy with nevirapine is not indicated due to rapid emergence of resistance.[3][4]
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).[8] Some clinical trials have demonstrated comparable HIV suppression with nevirapine-based regimens to that achieved with regimens based on a protease inhibitor (PI)[9][10] or efavirenz.[11]
This drug is generally only to be considered for use if the CD4 cell count is very low.[3]
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 this group of people.[11]
Nevirapine may also form a useful component of salvage regimens after virological failure, usually in combination with one or more PIs as well as
Dosing in children is based on body surface area (BSA),[3] however, weight-based dosing algorithms have been released. These guidelines include dosing algorithms for as young as newborn babies.[12]
Preventing mother-to-child transmission
Although 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.[13], that trial was found in an Associated Press investigation to be riddled with "sloppy recordkeeping" and possibly fraud.[14] A subsequent study in Thailand showed that prophylaxis with single-dose nevirapine in addition to zidovudine is more effective than zidovudine alone.[15] 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 [16] and as of 2006 the FDA has not approved of such nevirapine prophylaxis.[17] However, supporters of HIVNET 012 experiment argued that the flaws in this experiment were largely due to bureaucratic incompetence, while the findings regarding the safety and efficacy of single-dose nevirapine from this study were scientifically solid and too important to discard.[18] Moreover, it was argued that holding African researchers who operated under resource-poor situations to the same moral and procedural standards to their Western counterparts was unrealistic, and would further marginalize African researchers' role in the science community and impede the progress of African science.[19] Another clinical trial, Using Nevirapine to Prevent Mother-to-Child HIV Transmission During Breastfeeding, was completed in September 2013.[20]
A major concern with this approach is that NNRTI resistance mutations are commonly observed in both mothers and infants after single-dose nevirapine,[21] and may compromise the response to future NNRTI-containing regimens.[22] A short course of maternal Lamivudine/zidovudine is recommended by the U.S. Public Health Service Task Force to reduce this risk.[23]
Nonoccupational Post-Exposure Prophylaxis
Nevirapine is contraindicated for non-occupational post-exposure-prophylaxis including for pregnant and nonpregnant women due to severe liver toxicity.[24]
Adverse effects
The most common adverse effect of nevirapine is the development of mild or moderate rash (13%).[25][26] Severe or life-threatening skin reactions have been observed in 1.5% of patients, including Stevens–Johnson syndrome, toxic epidermal necrolysis and hypersensitivity.[25]
Nevirapine may cause severe or life-threatening liver toxicity, usually emerging in the first six weeks of treatment.
Cases of
The U.S. Food and Drug Administration recommends stopping nevirapine if a person experiences:[4]
- sign and symptoms of liver issues such as hepatitis
- increased transaminases in addition to rash or systemic symptoms
- formation of rash with systemic symptoms
- severe skin or hypersensitivity reactions
Additionally, the U.S. FDA recommends close monitoring during the first 6 weeks of therapy for the above symptoms as there is high risk during this time. Continued monitoring is recommended for up to the first 18 weeks of treatment. If a patient experiences hepatitis plus rash or other systemic symptoms, or severe hypersensitivity or skin rash, nevirapine should not be restarted.[4]
Drug interactions
Nevirapine is a substrate for liver CYP3A and CYP2B6 enzymes. Concomitant administration of drugs that are inhibitors of these enzymes may increase serum nevirapine levels significantly. Some examples of these drugs include ritonavir, fosamprenavir, and fluconazole. On the other hand, drugs that are inducers of these enzymes such as rifampicin may lower serum nevirapine levels.[30][18]
In addition, concomitant use of St. John's wort (Hypericum perforatum, which has been shown to induce CYP3A4 and CYP1A2[31]) or St. John's wort containing products may significantly lower nevirapine levels.[30]
Nevirapine is an inducer of
Mechanism of action
Nevirapine falls in the non-nucleoside reverse transcriptase inhibitor (NNRTI) class of antiretrovirals.[32] 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 polymerase active site, NNRTIs bind to a hydrophobic pocket in the subdomain of p66 which is about 10 angstrom away from the active site (known as the NNRTI pocket). Therefore, this NNRTI-binding pocket will inhibit reverse transcription in a way that is distinct to the NRTIs.[33]
Nevirapine 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.[34]
Resistance to nevirapine develops rapidly if viral replication is not completely suppressed.[8] The most common mutations observed after nevirapine treatment are Y181C and K103N, which are also observed with other NNRTIs.[25][35] 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. However, second generation NNRTIs like rilpivirine and etravirine are effective in treatment for HIV strains resistant to nevirapine and other first generation drugs in that same class.
History
Nevirapine was discovered by Karl D. Hargrave and colleagues at Boehringer Ingelheim Pharmaceuticals, Inc., one of the
Society and culture
Former U.S. President George W. Bush's PEPFAR funding of $500 million to help combat the African AIDS epidemic included nevirapine, among other medications and programs.
In South Africa, the Treatment Action Campaign successfully sued the government over its failure to make nevirapine widely available. In Minister of Health v Treatment Action Campaign the Constitutional Court of South Africa ordered the government to immediately "remove the restrictions that prevent Nevirapine from being made available for the purpose of reducing the risk of mother-to-child transmission of HIV at public hospitals and clinics that are not research and training sites [and] permit and facilitate the use of Nevirapine for the purpose of reducing the risk of mother-to-child transmission of HIV and to make it available for this purpose at hospitals and clinics when in the judgement of the attending medical practitioner acting in consultation with the medical superintendent of the facility concerned this is medically indicated, which shall if necessary include that the mother concerned has been appropriately tested and counselled."[36][37]
References
- FDA. Retrieved 22 Oct 2023.
- ^ "Prescription medicines: registration of new generic medicines and biosimilar medicines, 2017". Therapeutic Goods Administration (TGA). 21 June 2022. Retrieved 30 March 2024.
- ^ a b c d "Viramune- nevirapine suspension Viramune- nevirapine tablet". DailyMed. 28 October 2019. Retrieved 19 November 2020.
- ^ a b c d e f "Viramune- nevirapine tablet, extended release". DailyMed. 25 October 2019. Retrieved 19 November 2020.
- ^ a b c d e f g h i j "Nevirapine". The American Society of Health-System Pharmacists. Archived from the original on 20 December 2016. Retrieved 3 December 2016.
- ISBN 9781284057560.
- hdl:10665/325771. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
- ^ PMID 9544767.
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- ^ S2CID 20933620.
- ^ "Panel on Antiretroviral Therapy and Medical Management of HIV-Infected Children: Guidelines for the use of antiretroviral agents in pediatric HIV infection". AIDSinfo, U.S. Department of Health and Human Services (HHS). March 2016. Archived from the original on 2016-11-07. Retrieved 2016-11-05.
- S2CID 6740488.
- ^ Solomon J. "Research Flawed on Key AIDS Medicine".
- PMID 15247338.
- ^ The HIVNET 012 Study and the Safety and Effectiveness of Nevirapine in Preventing Mother-to-Infant Transmission of HIV, "The HIVNET 012 Study and the Safety and Effectiveness of Nevirapine in Preventing Mother-to-Infant Transmission of HIV". Archived from the original on 2009-02-01. Retrieved 2009-01-23.
- ^ Celia Farber, "Out of Control: AIDS and the Corruption of Science" Farber C (March 2006). "[Article] Out of control, by Celia Farber". Harper's Magazine. Vol. March 2006. Archived from the original on 2009-05-04. Retrieved 2009-06-11.
- S2CID 26027925.
- ^ Lock, M. & Nguyen, V 2010, an Anthropology of Biomedicine, Malden, Wiley-Blackwell.
- ^ "Using Nevirapine to Prevent Mother-to-Child HIV Transmission During Breastfeeding - Full Text View - ClinicalTrials.gov". Archived from the original on 2008-12-05. Retrieved 2009-01-23.
- PMID 15942889.
- PMID 15247339.
- ^ a b Panel on Treatment of HIV-Infected Pregnant Women and Prevention of Perinatal Transmission. Recommendations for use of antiretroviral drugs in pregnant HIV-1-infected women for maternal health and interventions to reduce perinatal HIV transmission in the United States. "Recommendations for Use of Antiretroviral Drugs in Pregnant HIV-1-Infected Women for Maternal Health and Interventions to Reduce Perinatal HIV Transmission in the United States | National Prevention Information Network | Connecting public health professionals with trusted information and each other". Archived (PDF) from the original on 2014-04-12. Retrieved 2014-04-11.. Accessed 16 November 2016.
- ^ "Updated guidelines for antiretroviral postexposure prophylaxis after sexual, injection drug use, or other nonoccupational exposure to HIV—United States, 2016". Centers for Disease Control.
- ^ a b c d e Viramune (nevirapine) tablets; Viramune (nevirapine) oral suspension prescribing information Archived 2006-11-12 at the Wayback Machine
- ^ "Facts sheet from the AIDS Treatment Data Network". Archived from the original on 2006-01-13. Retrieved 2006-01-16.
- ^ a b DHHS panel. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents (May 4, 2006). (Available for download from AIDSInfo Archived 2006-05-06 at the Wayback Machine)
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- PMID 18271750.
- ^ a b "VIRAMUNE® (nevirapine) Prescribing Information" (PDF). Archived (PDF) from the original on 2016-11-08.
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- ^ Budlender S, Marcus G, Ferreira NM (October 2014). Public interest litigation and social change in South Africa: Strategies, tactics and lessons (PDF). The Atlantic Philanthropies.
- ^ "Minister of Health and Others v Treatment Action Campaign and Others (No 2) (CCT8/02) [2002] ZACC 15; 2002 (5) SA 721; 2002 (10) BCLR 1033 (5 July 2002)". South African Legal Information Institute. 5 July 2002. Retrieved 31 January 2022.