efavirenz

Efavirenz is an antiretroviral medication in the non-nucleoside reverse transcriptase inhibitor (NNRTI) class, used as part of combination therapy to treat HIV-1 infection. It is available as a standalone drug and in fixed-dose combinations, such as efavirenz with tenofovir disoproxil fumarate and emtricitabine (a commonly used regimen known by brand names in various markets), and in other multi-drug products used to simplify dosing.

Mechanism of action: efavirenz binds directly to an allosteric site on HIV-1 reverse transcriptase, inhibiting the enzyme and preventing conversion of viral RNA into DNA. This action blocks viral replication. It has little activity against HIV-2 and is not active against nonretroviral pathogens.

Pharmacokinetics and administration: efavirenz is taken orally and is absorbed more predictably on an empty stomach; high-fat meals can markedly increase exposure and worsen adverse effects. A typical adult dose is 600 mg once daily, usually taken at bedtime to mitigate central nervous system effects. It is primarily metabolized by cytochrome P450 enzymes, especially CYP2B6, with additional involvement of CYP3A4; because of its enzymatic effects, it can interact with many other drugs, including hormonal contraceptives, rifampin, warfarin, and certain antivirals.

Safety and adverse effects: common adverse effects include central nervous system symptoms such as dizziness, insomnia, restlessness, and vivid dreams. Other potential side effects include rash, hepatotoxicity, and lipid abnormalities. Rare but serious reactions can include severe rash or hepatic injury.

Pregnancy considerations: efavirenz is generally categorized as pregnancy category D; animal studies showed teratogenic risk, particularly neural tube defects. In pregnancy, the benefits and risks must be weighed, and many guidelines recommend avoiding efavirenz during the first trimester if alternatives are available.

Summary: efavirenz remains a widely used NNRTI in HIV-1 treatment, valued for once-daily dosing but requiring attention to drug interactions, CNS side effects, and pregnancy considerations.