Nevirapine is a non-nucleoside reverse transcriptase inhibitor (NNRTI) used in the treatment of HIV/AIDS. It was developed in the 1990s and approved for medical use in 1996, making it one of the first NNRTIs introduced into antiretroviral therapy. Nevirapine works by directly inhibiting reverse transcriptase, an essential enzyme for HIV replication, through a mechanism distinct from nucleoside analogues.
Its history is marked by its role in expanding combination antiretroviral therapy, particularly in resource-limited settings due to its affordability and effectiveness. Nevirapine has also been widely used in the prevention of mother-to-child transmission of HIV. However, its use is associated with significant adverse effects, including severe hepatotoxicity and skin reactions such as Stevens–Johnson syndrome, which led to careful patient selection and monitoring guidelines.
BRAND NAMES
Viramune (original and most widely recognized brand)
Viramune XR (extended-release formulation)
MECHANISM OF ACTION
Nevirapine is a non-nucleoside reverse transcriptase inhibitor (NNRTI) that directly binds to the HIV-1 reverse transcriptase enzyme. It forms a hydrophobic pocket close to the enzyme’s active site, inducing a conformational change that disrupts its catalytic activity. This inhibits both RNA-dependent and DNA-dependent DNA polymerase functions, ultimately preventing HIV-1 replication.
PHARMACOKINETICS
Absorption
Nevirapine is rapidly and almost completely absorbed, and its absorption is not significantly affected by food.
Distribution
It has a volume of distribution of approximately (1.21 \pm 0.09) L/kg.
Metabolism: The drug is extensively metabolized in the liver, mainly by CYP3A4 and CYP2B6 enzymes.
Metabolism
Nevirapine is extensively metabolized in the liver, primarily through the cytochrome P450 enzyme system, especially CYP3A4 and CYP2B6. It undergoes oxidative metabolism, producing several hydroxylated metabolites, which are then further processed by glucuronidation to form water-soluble compounds.
Elimination
It is primarily eliminated in urine (over 80%) as conjugated metabolites, with only a small amount of unchanged drug excreted renally.
PHARMACODYNAMICS
Nevirapine (NVP) is a non-nucleoside reverse transcriptase inhibitor (NNRTI) that directly binds to HIV-1 reverse transcriptase, inhibiting its RNA- and DNA-dependent DNA polymerase activity and thereby preventing viral replication. It is a strong antiretroviral agent but has a low genetic barrier to resistance, which can develop quickly if used as monotherapy, so it must be used in combination with other antiretroviral drugs.
ADMINISTRATION
Nevirapine is an HIV-1 non-nucleoside reverse transcriptase inhibitor (NNRTI) that is taken orally in combination with other antiretroviral medications. To reduce the risk of rash, a mandatory 14-day lead-in phase is required, using 200 mg once daily in adults or 150 mg/m² daily in pediatric patients. After this period, adults typically switch to a maintenance dose of 200 mg twice daily. The oral suspension should be shaken thoroughly before use.
DOSAGE AND STRENGTH
Nevirapine is available as 200 mg tablets, 400 mg extended-release tablets, and an oral suspension (commonly 50 mg/5 mL). In adults, treatment usually starts with a 14-day lead-in dose of 200 mg once daily to lower the risk of rash, followed by a maintenance dose of 200 mg twice daily or 400 mg once daily for the extended-release form. In children, the dose is calculated based on body weight or body surface area (mg/m²) and adjusted according to response and tolerability.
FOOD INTERACTIONS
Nevirapine can be taken with or without food, as food does not significantly affect its absorption or efficacy. There are no specific dietary restrictions; however, St. John’s wort should be avoided because it can greatly reduce drug levels. Excessive alcohol intake should also be avoided, as it may increase the risk of liver toxicity.
CONTRAINDICATIONS
Nevirapine is contraindicated in patients with severe liver impairment (Child-Pugh Class B or C), baseline AST/ALT levels more than five times the upper limit of normal, or a history of serious hypersensitivity reactions such as Stevens-Johnson syndrome or severe hepatotoxicity. It is also not recommended for post-exposure prophylaxis and should not be initiated in women with CD4 counts above 250 cells/mm³ or men with CD4 counts above 400 cells/mm³.
SIDE EFFECTS
Can cause severe skin rash and liver toxicity
Risk is highest in first 6–18 weeks
Common effects: nausea, fatigue, headache, diarrhea
Seek help if jaundice, dark urine, or severe rash occurs
OVER DOSE
Nevirapine overdose, typically at doses of 800–1800 mg/day, can lead to serious acute symptoms such as edema, erythema nodosum, fatigue, fever, headache, and insomnia. It may also cause vomiting, vertigo, and in some cases, mania. There is no specific antidote for overdose, so treatment is mainly supportive and symptomatic, including discontinuation of the drug and organ support. The most significant risks involve severe hepatotoxicity and skin reactions.
TOXICITY
Nevirapine (NVP) is an antiretroviral medication that can cause significant and sometimes life-threatening toxicity, most commonly presenting as severe liver reactions often accompanied by rash. The greatest risk occurs during the first 18 weeks of therapy, with liver toxicity reported in about 1%–6% of patients. Higher risk is seen in women with CD4 counts above 250 cells/mm³ and men with CD4 counts above 400 cells/mm³.
