Etravirine

435.284

435.28

1592732-453-0

0C50HW4FO1

DTXSID30181412

C73195

J05AG04|J - Antiinfectives for systemic use

121

4.5

1.439 g/cm³

255-257 °C

339.3±34.3 °C

1.703

-20°C Freezer

P264, P270, P273, P301+P312, P330, P501

H302

|Warning|H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]|P264, P270, P273, P301+P312, P330, and P501|Aggregated GHS information provided by 8 companies from 2 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Serum aminotransferase elevations occur in a high proportion of patients on etravirine therapy, but increases above 5 times the upper limit of normal occur in only 2% to 3% of patients; this rate may be higher in patients who have hepatitis C coinfection. In most studies, the rate of liver enzyme elevations was no different in etravirine treated than among in comparator arms. In large clinical trials as well as open access studies, there were no reported instances of clinically apparent liver injury attributed to etravirine.

Plasma protein binding is about 99.9% in vitro. In vitro, 99.6% is bound to albumin, and 97.66% - 99.02% is bound to 1-alpha glycoprotein.

Indicated as an adjunct therapy in the treatment of adult HIV-1 infections resistant to therapy with other NNRTIs and antiretroviral agents.|FDA Label|Intelence, in combination with a boosted protease inhibitor and other antiretroviral medicinal products, is indicated for the treatment of human-immunodeficiency-virus-type-1 (HIV-1) infection in antiretroviral-treatment-experienced adult patients and in antiretroviral-treatment-experienced paediatric patients from six years of age.This indication is based on week-48 analyses from two phase-III trials in highly pretreated patients where Intelence was investigated in combination with an optimised background regimen (OBR) which included darunavir/ritonavir. The indication in paediatric patients is based on 48-week analyses of a single-arm, phase-II trial in antiretroviral-treatment-experienced paediatric patients.|Treatment of human immunodeficiency virus (HIV-1) infection

Etravirine is a nonnucleoside reverse transcriptase inhibitor used in combination with other agents in the therapy of human immunodeficiency virus (HIV) infection and the acquired immunodeficiency syndrome (AIDS). Etravirine has been associated with transient serum aminotransferase elevations and with hypersensitivity reactions that can be associated with liver injury including acute liver failure.

Antiviral Agents

Clinical trials have shown no prolongation of QT intervals on electrocardiograms after 8 days of dosing.

Inhibitors of reverse transcriptase (RNA-DIRECTED DNA POLYMERASE), an enzyme that synthesizes DNA on an RNA template. (See all compounds classified as Reverse Transcriptase Inhibitors.)

Maximum oral absorption is achieved in 2.5-4 hours. Absorption is unaffected by the concomitant use of oral ranitidine or omeprazole, which decrease gastric acidity. Administration under fasting conditions resulted in a near 50% decrease in systemic exposure (AUC) when compared to administration after a meal.|After a 800mg dose of radio-labelled etraverine, 93.7% was found to undergo fecal elimination, with 81.2% - 86.4% eliminated unchanged. 1.2% of the dose was renally eliminated, changed. Etravirine is dialyzable (hemodialysis).|Distribution of etravirine into compartments other than plasma has not been evaluated in humans.|Renal clearance of etravirine is negligible (<1.2%), thus no dose adjustments are required in patients with renal impairment. Clearance is shown to be reduced in patients with Hepatitis B and/or co-infection, however, the safety profile of etravirine does not call for dosage adjustments.

Metabolized (in vitro) by the liver CYP450 enzymes: CYP3A4, CYP2C9, CYP2C19. The major metabolites formed by a methyl hydroxylation of the dimethylbenzonitrile moiety retained less than 90% of etravirine's activity.

Half life of 9.05-41 hours.

Etravirine exerts its effects via direct inhibition of the reverse transcriptase enzyme of human immunodeficiency virus type 1 (HIV-1). It directly binds reverse transcriptase and consequently blocks DNA-dependent and RNA-dependent polymerase activity. Etravirine does not inhibit human DNA polymerase alpha, beta or gamma.

4-((6-amino-5-bromo-2-((4-cyanophenyl)amino)-4-pyrimidinyl)oxy)-3,5-dimethyl-benzonitrile

Human drugs -> Intelence -> EMA Drug Category|Non-nucleoside reverse transcriptase inhibitors, Antivirals for systemic use -> Human pharmacotherapeutic group|Human Drugs -> EU pediatric investigation plans|Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients