|Main uses||Treat and prevent HIV/AIDS|
|Side effects||Rash, diarrhea, nausea, peripheral nerve problems, headache|
|Typical dose||200 mg BID|
|Metabolism||Liver (CYP3A4, CYP2C9 & CYP2C19-mediated)|
|Elimination half-life||41±20 hours|
|Excretion||Faeces (93.7%), urine (1.2%)|
|Chemical and physical data|
|Molar mass||435.285 g·mol−1|
|3D model (JSmol)|
Etravirine (ETR) sold under the brand name Intelence, is a medication used to treat and prevent HIV/AIDS. It is used in people who have been previously treated, together with other antiretroviral medications. It is taken by mouth twice per day.
Common side effects include rash, diarrhea, nausea, peripheral nerve problems, and headache. Other side effects may include Stevens-Johnson syndrome, immune reconstitution syndrome, and lipodystrophy. Safety in pregnancy is unclear. It is a non-nucleoside reverse transcriptase inhibitor (NNRTI), which blocks reverse transcriptase.
Etravirine was approved for medical use in the Canada, Europe, and the United States in 2008. It is available as a generic medication. In the United Kingdom a month of treatment costs the NHS about £300 as of 2021. This amount in the United States costs about 380 USD.
Etravirine, in combination with other anti-retrovirals, is indicated for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in antiretroviral treatment-experienced adults, who have evidence of viral replication and HIV-1 strains resistant to a non-nucleoside reverse transcriptase inhibitor (NNRTI) and other antiretroviral agents.
Unlike some agents in the class, resistance to other NNRTIs does not seem to confer resistance to etravirine.
The recommended dose of etravirine is 200 mg (2 x 100 mg tablets, or 1 x 200 mg tablet) taken twice daily following a meal. The type of food does not affect the exposure to etravirine.
In 2009, the prescribing information for etravirine was modified to include "postmarketing reports of cases of Stevens–Johnson syndrome, toxic epidermal necrolysis and erythema multiforme, as well as hypersensitivity reactions characterized by rash, constitutional findings, and sometimes organ dysfunction, including liver failure. Intelence therapy should be immediately discontinued when signs and symptoms of severe skin or hypersensitivity reactions develop."
Each 100 mg etravirine tablet contains 160 mg of lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Mechanism of action
Etravirine is a second-generation non-nucleoside reverse transcriptase inhibitor (NNRTI), designed to be active against HIV with mutations that confer resistance to the two most commonly prescribed first-generation NNRTIs, mutation K103N for efavirenz and Y181C for nevirapine. This potency appears to be related to etravirine's flexibility as a molecule. Etravirine is a diarylpyrimidine (DAPY), a type of organic molecule with some conformational isomerism that can bind the enzyme reverse transcriptase in multiple conformations, allowing for a more robust interaction between etravirine and the enzyme, even in the presence of mutations. Other diarylpyrimidine-analogues are currently being used as anti-HIV agents, notably rilpivirine.
Society and culture
In a paper etravirine was shown to cause an increase in frataxin production. Frataxin deficiency is a key component to Friedreich's ataxia, a genetically inherited disease that causes the progressive loss of coordination and muscle strength leading to motor incapacitation and the full-time use of a wheelchair.
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- Alfedi, Giulia; Luffarelli, Riccardo; Condò, Ivano; Pedini, Giorgia; Mannucci, Liliana; Massaro, Damiano S.; Benini, Monica; Toschi, Nicola; Alaimo, Giorgia; Panarello, Luca; Pacini, Laura; Fortuni, Silvia; Serio, Dario; Malisan, Florence; Testi, Roberto; Rufini, Alessandra (2019). "Drug repositioning screening identifies etravirine as a potential therapeutic for friedreich's ataxia". Movement Disorders. 34 (3): 323–334. doi:10.1002/mds.27604. PMID 30624801. S2CID 58567610.