nevirapine
Regulatory sources consulted
Approved indications
- Combination treatment of adults, adolescents, and children with HIV-1 infection.
Contraindications
Absolute
- Hypersensitivity to nevirapine.
- Severe hepatic impairment or transaminases >5 times the upper limit before starting.
- Moderate or severe hepatic impairment.
- Use for HIV post-exposure prophylaxis.
Clinical warnings
- It can cause severe or fatal hepatotoxicity, especially during the first 18 weeks; monitor transaminases and symptoms closely early in treatment. Do not restart nevirapine after clinical hepatitis, symptomatic transaminase elevation, or a severe skin reaction. — CIMA/AEMPS, ficha técnica 76844
- It may cause severe rash, Stevens-Johnson syndrome, toxic epidermal necrolysis, or DRESS; stop immediately for a severe or systemic reaction. Do not restart nevirapine after clinical hepatitis, symptomatic transaminase elevation, or a severe skin reaction. — CIMA/AEMPS, ficha técnica 76844
- In women with CD4 >250 cells/mm³ and men with CD4 >400, start only if benefit clearly outweighs hepatotoxicity risk. — CIMA/AEMPS, ficha técnica 76844
Drug interactions
- ModerateSt John’s wort
Mechanism: Enzyme induction reduces nevirapine and may cause virologic failure.
Recommendation: Do not combine.
CIMA/AEMPS, ficha técnica 76844
- HighRifampicin, azoles, hormonal contraceptives, and other CYP substrates
Mechanism: Nevirapine induces CYP3A/CYP2B6 and may reduce concentrations of multiple drugs.
Recommendation: Review each combination; use additional nonhormonal contraception and monitor efficacy.
CIMA/AEMPS, ficha técnica 76844
- HighWarfarin
Mechanism: Enzyme induction may increase or decrease anticoagulation.
Recommendation: Monitor INR closely when starting, adjusting, or stopping nevirapine.
CIMA/AEMPS, ficha técnica 76844
Adverse events
Common (≥1%)
Rash, nausea, fatigue, fever, headache, and increased liver tests
Rare but serious
Fulminant hepatitis, liver failure, Stevens-Johnson syndrome, toxic epidermal necrolysis, and DRESS
Pregnancy and lactation
It may be used during pregnancy when clinically indicated. People with HIV receiving treatment should not breastfeed to prevent transmission and exposure.
Recent literature (PubMed)
Despite considerable progress in preventing mother-to-child transmission (PMTCT) of human immunodeficiency virus (HIV), eliminating paediatric HIV has not been achieved. Extended postnatal prophylaxis (ePNP), defined as prophylaxis administered to an HIV-exposed child after PMTCT perinatal prophylaxis ends, has been evaluated and is now proposed as an improved approach towards elimination. This approach should be urgently incorporated into international PMTCT recommendations. The antiretroviral drugs most commonly studied as ePNP, either alone or in combination, are lamivudine, nevirapine, lopinavir/ritonavir and zidovudine. In this study, we examined the efficacy, safety, pharmacology, genetic barrier to resistance and practicality of various ePNP regimens. Regimens combining multiple antiretroviral drugs are no more effective than single-drug regimens in terms of protective efficacy but they are associated with increased toxicity. On the basis of these criteria, we recommend lamivudine as the preferred ePNP drug or nevirapine as an alternative. Guided by maternal HIV viral load, ePNP may be particularly indicated, as it could ensure that the prophylaxis provides the greatest benefit/risk to children at highest risk. Long-acting injectable antiretroviral drugs and broadly neutralising antibodies (bNAbs) have yet to be fully evaluated in neonates, infants and children; however, they may offer new alternatives in the future.
Human immunodeficiency virus (HIV) causes acquired immunodeficiency syndrome (AIDS), a lethal disease that is prevalent worldwide. According to the Joint United Nations Programme on HIV/AIDS (UNAIDS) data, 38.4 million people worldwide were living with HIV in 2021. Viral reverse transcriptase (RT) is an excellent target for drug intervention. Nucleoside reverse transcriptase inhibitors (NRTIs) were the first class of approved antiretroviral drugs. Later, a new type of non-nucleoside reverse transcriptase inhibitors (NNRTIs) were approved as anti-HIV drugs. Zidovudine, didanosine, and stavudine are FDA-approved NRTIs, while nevirapine, efavirenz, and delavirdine are FDA-approved NNRTIs. Several agents are in clinical trials, including apricitabine, racivir, elvucitabine, doravirine, dapivirine, and elsulfavirine. This review addresses HIV-1 structure, replication cycle, reverse transcription, and HIV drug targets. This study focuses on NRTIs and NNRTIs, their binding sites, mechanisms of action, FDA-approved drugs and drugs in clinical trials, their resistance and adverse effects, their molecular docking studies, and highly active antiretroviral therapy (HAART).
The sources, ecotoxicological impact, and potential remediation strategies of antiretroviral drugs (ARVDs) as emerging contaminants in surface waters are reviewed based on recent literature. The occurrence of ARVDs in water bodies raises concern because many communities in Africa depend on rivers for water resources. Southern Africa is a potential hotspot regarding ARVD contamination due to relatively high therapeutic application and detection thereof in water bodies. Efavirenz and nevirapine are the most persistent in effluents and are prevalent in surface water based on environmental concentrations. Whereas the highest concentration of efavirenz reported in Kenya was 12.4 µg L-1 , concentrations as high as 119 and 140 µg L-1 have been reported in Zambia and South Africa, respectively. Concentrations of ARVDs ranging from 670 to 34 000 ng L-1 (influents) and 540 to 34 000 ng L-1 (effluents) were determined in wastewater treatment plants in South Africa, compared with Europe, where reported concentrations range from less than limit of detection (LOD) to 32 ng L-1 (influents) and less than LOD to 22 ng L-1 (effluents). The present African-based review suggests the need for comprehensive toxicological and risk assessment of these emerging pollutants in Africa, with the intent of averting environmental hazards and the development of sustainable remediation strategies. Environ Toxicol Chem 2022;41:247-262. © 2021 SETAC.