Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027497 (nausea)
 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Etravirine (TMC125) is a next-generation non-nucleoside reverse transcriptase inhibitor (NNRTI) that is being developed for the treatment of HIV-1 infections. The drug was recently approved by the US FDA to be used in combination with other anti-HIV medications. Etravirine is a highly flexible diarylpyrimidine compound, with favorable binding interactions toward mutant HIV strains as well as wild-type virus. This conformation confers an increased genetic barrier to resistance compared with other NNRTIs: multiple mutations are required before there is a decrease in susceptibility to etravirine; whereas, only one mutation (K103N) is typically needed to confer high-level resistance to the first-generation NNRTIs. In vitro, etravirine is predominantly metabolized by cytochrome P450 (CYP)3A4 and CYP2C (2C9, 2C18 and 2C19). In vivo, the most important metabolic pathway for etravirine is methyl hydroxylation, with subsequent glucuronidation of the metabolites. Etravirine is an inducer of CYP3A4 and a weak inhibitor of CYP2C9, CYP2C19 and P-glycoprotein. In Phase II and III trials in treatment-experienced patients, treatment with etravirine led to better virological suppression than placebo. In the DUET I and II trials (Phase III), approximately 60% of the etravirine group achieved a confirmed viral load of less than 50 copies/ml at week 24, compared with approximately 40% in the placebo arm. The mean change in viral load at week 24 was -2.34 (standard deviation: 1.31) and -1.68 (1.40) log(10) copies/ml in the etravirine and placebo groups, respectively. The presence of three or more NNRTI-associated mutations at baseline negatively influenced the outcome. There were no safety concerns and no major differences in frequency or severity of side effects between etravirine and placebo groups, with the exception of rash. Furthermore, the overall rate of discontinuation due to any adverse event was similar between the etravirine and placebo groups. The most common adverse events reported were rash and nausea.
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PMID:Etravirine for the treatment of HIV infection. 1866 9

Etravirine is the first next-generation nonnucleoside reverse-transcriptase inhibitor (NNRTI) that is approved for the treatment of HIV infection in patients who have experienced virologic failure while receiving an NNRTI-containing regimen. The drug is taken as two 100-mg tablets twice daily after a meal. Because the drug is metabolized by cytochrome P450 isoenzymes, it cannot be coadministered with a number of other drugs (fosamprenavir, high-dose ritonavir, atazanavir, rifampin, and several antiepileptic medications). Etravirine demonstrates potent in vitro activity against wild-type and NNRTI-resistant strains of HIV. In vitro resistance and treatment failure is associated with the development of multiple NNRTI resistance mutations other than the K103N mutation. Several large clinical studies have documented the benefit of adding etravirine to an optimized background regimen in patients with virologic failure who are infected with multidrug-resistant HIV. The major adverse effects of etravirine therapy are nausea and rash, which are typically self-limiting and do not lead to treatment discontinuation.
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PMID:Etravirine, a next-generation nonnucleoside reverse-transcriptase inhibitor. 1927 97

(1) After failure of several successive antiretroviral regimens, HIV-infected patients are normally treated with an optimised regimen based on resistance profiling, combined with tipranavir or darunavir and also an antiretroviral belonging to another class (maraviroc, enfuvirtide or raltegravir); (2) Etravirine is a non-nucleoside reverse transcriptase inhibitor first authorized for sale in the European Union in 2008; (3) Its clinical evaluation is based on two double-blind trials of identical design in a total of 1200 patients with multiple prior treatment failures. The patients received an optimised antiretroviral regimen including darunavir and ritonavir, plus either etravirine or placebo. After 24 weeks of treatment the proportion of patients whose viral load was below 50 copies/ml was higher in the etravirine group than in the placebo group (56.3% versus 33.6%), provided enfuvirtide was not introduced at the same time as etravirine; (4) The main known adverse effect of etravirine is potentially severe skin rash; nausea, vomiting and hypercholesterolaemia can also occur; (5) Etravirine has a high potential for drug-drug interactions, due to its inducing and inhibitory effects on various cytochrome P450 isoenzymes; (6) Etravirine is an additional option for HIV-infected patients with multiple treatment failure.
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PMID:Etravirine: new drug. Multidrug-resistant HIV: another option. 1963 14