Etravirine
Encyclopedia
Etravirine is a drug
used for the treatment of HIV
. Etravirine is a non-nucleoside reverse transcriptase inhibitor (NNRTI). Unlike the currently available agents in the class, resistance to other NNRTIs does not seem to confer resistance to etravirine. Etravirine is marketed by Tibotec
, a subsidiary
of Johnson & Johnson
. In January 2008, the Food and Drug Administration
approved its use for patients with established resistance to other drugs, making it the 30th anti-HIV drug approved in the United States and the first to be approved in 2008. It was also approved for use in Canada on April 1, 2008.
Etravirine is licensed in the United States
, Canada
and the European Union
, and is under regulatory review in Switzerland
, Russia
and Australia
.
immunodeficiency virus type 1 (HIV-1) infection in antiretroviral treatment-experienced adult patients, who have evidence of viral replication and HIV-1 strains resistant to a non-nucleoside reverse transcriptase inhibitor (NNRTI) and other antiretroviral agents.
The recommended dose of etravirine is 200 mg (2 x 100 mg tablets, or 1 x 200 mg tablet as of 03/18/2011) taken twice daily following a meal. The type of food does not affect the exposure to etravirine.
. Patients with rare hereditary problems of galactose
intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption
should not take this medicine.
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 developed as potential anti-HIV agents, notably rilpivirine
.
and erythema multiforme
, as well as hypersensitivity
reactions characterized by rash, constitutional findings, and sometimes organ dysfunction, including hepatic failure. Intelence therapy should be immediately discontinued when signs and symptoms of severe skin or hypersensitivity reactions develop."
Drug
A drug, broadly speaking, is any substance that, when absorbed into the body of a living organism, alters normal bodily function. There is no single, precise definition, as there are different meanings in drug control law, government regulations, medicine, and colloquial usage.In pharmacology, a...
used for the treatment of HIV
HIV
Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...
. Etravirine is a non-nucleoside reverse transcriptase inhibitor (NNRTI). Unlike the currently available agents in the class, resistance to other NNRTIs does not seem to confer resistance to etravirine. Etravirine is marketed by Tibotec
Tibotec
Tibotec is a pharmaceutical company with a focus on research and development for the treatment of infectious diseases such as HIV , and Hepatitis C...
, a subsidiary
Subsidiary
A subsidiary company, subsidiary, or daughter company is a company that is completely or partly owned and wholly controlled by another company that owns more than half of the subsidiary's stock. The subsidiary can be a company, corporation, or limited liability company. In some cases it is a...
of Johnson & Johnson
Johnson & Johnson
Johnson & Johnson is an American multinational pharmaceutical, medical devices and consumer packaged goods manufacturer founded in 1886. Its common stock is a component of the Dow Jones Industrial Average and the company is listed among the Fortune 500....
. In January 2008, the Food and Drug Administration
Food and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
approved its use for patients with established resistance to other drugs, making it the 30th anti-HIV drug approved in the United States and the first to be approved in 2008. It was also approved for use in Canada on April 1, 2008.
Etravirine is licensed in the United States
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...
, Canada
Canada
Canada is a North American country consisting of ten provinces and three territories. Located in the northern part of the continent, it extends from the Atlantic Ocean in the east to the Pacific Ocean in the west, and northward into the Arctic Ocean...
and the European Union
European Union
The European Union is an economic and political union of 27 independent member states which are located primarily in Europe. The EU traces its origins from the European Coal and Steel Community and the European Economic Community , formed by six countries in 1958...
, and is under regulatory review in Switzerland
Switzerland
Switzerland name of one of the Swiss cantons. ; ; ; or ), in its full name the Swiss Confederation , is a federal republic consisting of 26 cantons, with Bern as the seat of the federal authorities. The country is situated in Western Europe,Or Central Europe depending on the definition....
, Russia
Russia
Russia or , officially known as both Russia and the Russian Federation , is a country in northern Eurasia. It is a federal semi-presidential republic, comprising 83 federal subjects...
and Australia
Australia
Australia , officially the Commonwealth of Australia, is a country in the Southern Hemisphere comprising the mainland of the Australian continent, the island of Tasmania, and numerous smaller islands in the Indian and Pacific Oceans. It is the world's sixth-largest country by total area...
.
Indications and dosage
Etravirine, in combination with other anti-retrovirals, is indicated for the treatment of humanimmunodeficiency virus type 1 (HIV-1) infection in antiretroviral treatment-experienced adult patients, who have evidence of viral replication and HIV-1 strains resistant to a non-nucleoside reverse transcriptase inhibitor (NNRTI) and other antiretroviral agents.
The recommended dose of etravirine is 200 mg (2 x 100 mg tablets, or 1 x 200 mg tablet as of 03/18/2011) taken twice daily following a meal. The type of food does not affect the exposure to etravirine.
Contraindication
Each 100 mg etravirine tablet contains 160 mg of lactoseLactose
Lactose is a disaccharide sugar that is found most notably in milk and is formed from galactose and glucose. Lactose makes up around 2~8% of milk , although the amount varies among species and individuals. It is extracted from sweet or sour whey. The name comes from or , the Latin word for milk,...
. Patients with rare hereditary problems of galactose
Galactose
Galactose , sometimes abbreviated Gal, is a type of sugar that is less sweet than glucose. It is a C-4 epimer of glucose....
intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption
Glucose-galactose malabsorption
Glucose-galactose malabsorption is a condition in which the cells lining the intestine cannot take in the sugars glucose and galactose, which prevents proper digestion of these molecules and larger molecules made from them....
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 efavirenzEfavirenz
Efavirenz is a non-nucleoside reverse transcriptase inhibitor and is used as part of highly active antiretroviral therapy for the treatment of a human immunodeficiency virus type 1....
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
Conformational isomerism
In chemistry, conformational isomerism is a form of stereoisomerism in which the isomers can be interconverted exclusively by rotations about formally single bonds...
that can bind the enzyme reverse transcriptase
Reverse transcriptase
In the fields of molecular biology and biochemistry, a reverse transcriptase, also known as RNA-dependent DNA polymerase, is a DNA polymerase enzyme that transcribes single-stranded RNA into single-stranded DNA. It also helps in the formation of a double helix DNA once the RNA has been reverse...
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 developed as potential anti-HIV agents, notably rilpivirine
Rilpivirine
Rilpivirine is a pharmaceutical drug, developed by Tibotec, for the treatment of HIV infection. It is a second-generation non-nucleoside reverse transcriptase inhibitor with higher potency, longer half-life and reduced side-effect profile compared with older NNRTIs, such as efavirenz.Rilpivirine...
.
Warnings and risks
In 2009, the prescribing information for etravirine was modified to include "postmarketing reports of cases of Stevens–Johnson syndrome, toxic epidermal necrolysisToxic epidermal necrolysis
Toxic epidermal necrolysis is a rare, life-threatening dermatological condition that is usually induced by a reaction to medications...
and erythema multiforme
Erythema multiforme
Erythema multiforme is a skin condition of unknown cause, possibly mediated by deposition of immune complex in the superficial microvasculature of the skin and oral mucous membrane that usually follows an infection or drug exposure...
, as well as hypersensitivity
Hypersensitivity
Hypersensitivity refers to undesirable reactions produced by the normal immune system, including allergies and autoimmunity. These reactions may be damaging, uncomfortable, or occasionally fatal. Hypersensitivity reactions require a pre-sensitized state of the host. The four-group classification...
reactions characterized by rash, constitutional findings, and sometimes organ dysfunction, including hepatic failure. Intelence therapy should be immediately discontinued when signs and symptoms of severe skin or hypersensitivity reactions develop."