Emtricitabine
Encyclopedia
Emtricitabine with trade name Emtriva (formerly Coviracil), is a nucleoside
reverse transcriptase inhibitor
(NRTI) for the treatment of HIV
infection in adults and children.
Emtricitabine is also marketed in a fixed-dose combination with tenofovir (Viread) under the brand name Truvada. A fixed-dose triple combination of emtricitabine, tenofovir and efavirenz
(Sustiva, marketed by Bristol-Myers Squibb
) was approved by the U.S. Food and Drug Administration (FDA) on July 12, 2006 under the brand name Atripla.
, Dr. Raymond Schinazi and Dr. Woo-Baeg Choi of Emory University
and licensed to Triangle Pharmaceuticals by Emory in 1996. Triangle Pharmaceuticals was acquired in 2003 by Gilead Sciences
, who completed development and now market the product with the brand name Emtriva.
It was approved by the FDA July 2, 2003. It is very similar to lamivudine
(3TC) and cross-resistance between the two is near-universal.
of cytidine
. The drug works by inhibiting reverse transcriptase
, the enzyme that copies HIV RNA into new viral DNA. By interfering with this process, which is central to the replication of HIV, emtricitabine can help to lower the amount of HIV, or "viral load
", in a patient's body and can indirectly increase the number of immune system
cells (called T cell
s or CD4+ T-cells). Both of these changes are associated with healthier immune systems and decreased likelihood of serious illness.
(HBV). Among individuals with chronic HBV infection, emtricitabine treatment results in significant histologic, virologic, and biochemical improvement. The safety profile of emtricitabine during treatment is similar to that of a placebo. Emtricitabine, however, cures neither HIV nor HBV infection. In a study involving individuals with HBV infection, symptoms of infection returned in 23% of emtricitabine-treated individuals who were taken off therapy. In studies involving individuals with chronic HIV infection, viral replication also resumes when study subjects are taken off therapy.
Emtricitabine is not approved by the FDA for treatment of HBV infection. As with drugs used to treat HIV infection, drugs used to treat HBV infection may have to be used in combination to prevent the evolution of drug resistant strains. Lamivudine
is also active against HBV virus and commercially available. Like emtricitabine, lamivudine, when used on its own, does not completely suppress viral replication. This allows drug resistant strains to emerge. The effectiveness of emtricitabine in combination with other anti-HBV drugs has not been established. Clinical trials are still ongoing.
with emtricitabine is unusual. The most common treatment-related adverse events are diarrhea
, headache
, nausea
, and rash
. These symptoms are generally mild to moderate in severity, but they caused 1% of clinical trial patients to give up treatment. Skin discoloration, which is typically reported as hyperpigmentation
and usually affects either the palms of the hands or the soles
of the feet, is reported in less than 2% of individuals and is almost exclusive to patients of African origin.
Among the more severe side effects patients may experience are a hepatotoxicity
or a lactic acidosis
.
Nucleoside
Nucleosides are glycosylamines consisting of a nucleobase bound to a ribose or deoxyribose sugar via a beta-glycosidic linkage...
reverse transcriptase inhibitor
Reverse transcriptase inhibitor
Reverse-transcriptase inhibitors are a class of antiretroviral drug used to treat HIV infection, tumors, and cancer. RTIs inhibit activity of reverse transcriptase, a viral DNA polymerase enzyme that retroviruses need to reproduce.-Mechanism:...
(NRTI) 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...
infection in adults and children.
Emtricitabine is also marketed in a fixed-dose combination with tenofovir (Viread) under the brand name Truvada. A fixed-dose triple combination of emtricitabine, tenofovir and efavirenz
Efavirenz
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....
(Sustiva, marketed by Bristol-Myers Squibb
Bristol-Myers Squibb
Bristol-Myers Squibb , often referred to as BMS, is a pharmaceutical company, headquartered in New York City. The company was formed in 1989, following the merger of its predecessors Bristol-Myers and the Squibb Corporation...
) was approved by the U.S. Food and Drug Administration (FDA) on July 12, 2006 under the brand name Atripla.
History
Emtricitabine was discovered by Dr. Dennis C. LiottaDennis C. Liotta
Dennis Liotta is a Chemistry professor at Emory University in Atlanta, Georgia, United States.Liotta's fields of research are organic synthesis and medicinal chemistry. Along with Dr. Raymond F. Schinazi and Dr...
, Dr. Raymond Schinazi and Dr. Woo-Baeg Choi of Emory University
Emory University
Emory University is a private research university in metropolitan Atlanta, located in the Druid Hills section of unincorporated DeKalb County, Georgia, United States. The university was founded as Emory College in 1836 in Oxford, Georgia by a small group of Methodists and was named in honor of...
and licensed to Triangle Pharmaceuticals by Emory in 1996. Triangle Pharmaceuticals was acquired in 2003 by Gilead Sciences
Gilead Sciences
Gilead Sciences is a biopharmaceutical company that discovers, develops and commercializes therapeutics. For many years since the company was founded, the company concentrated primarily on antiviral drugs to treat patients infected with HIV, hepatitis B or influenza. In 2006, Gilead acquired two...
, who completed development and now market the product with the brand name Emtriva.
It was approved by the FDA July 2, 2003. It is very similar to lamivudine
Lamivudine
Lamivudine is a potent nucleoside analog reverse transcriptase inhibitor .It is marketed by GlaxoSmithKline with the brand names Zeffix, Heptovir, Epivir, and Epivir-HBV.Lamivudine has been used for treatment of chronic hepatitis B at a lower dose than for treatment of HIV...
(3TC) and cross-resistance between the two is near-universal.
Mode of action
Emtricitabine is an analogueAnalog (chemistry)
In chemistry, a structural analog , also known as chemical analog or simply analog, is a compound having a structure similar to that of another one, but differing from it in respect of a certain component. It can differ in one or more atoms, functional groups, or substructures, which are replaced...
of cytidine
Cytidine
Cytidine is a nucleoside molecule that is formed when cytosine is attached to a ribose ring via a β-N1-glycosidic bond...
. The drug works by inhibiting 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...
, the enzyme that copies HIV RNA into new viral DNA. By interfering with this process, which is central to the replication of HIV, emtricitabine can help to lower the amount of HIV, or "viral load
Viral load
Viral load is a measure of the severity of a viral infection, and can be calculated by estimating the amount of virus in an involved body fluid. For example, it can be given in RNA copies per milliliter of blood plasma...
", in a patient's body and can indirectly increase the number of immune system
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
cells (called T cell
T cell
T cells or T lymphocytes belong to a group of white blood cells known as lymphocytes, and play a central role in cell-mediated immunity. They can be distinguished from other lymphocytes, such as B cells and natural killer cells , by the presence of a T cell receptor on the cell surface. They are...
s or CD4+ T-cells). Both of these changes are associated with healthier immune systems and decreased likelihood of serious illness.
HIV infection
Emtricitabine is indicated in combination with other antiretroviral agents for the treatment of HIV infection in adults. Emtricitabine is commercially available and is approved by the FDA for treatment of HIV infection.HBV infection
Emtricitabine exhibits clinical activity against the hepatitis B virusHepatitis B virus
Hepatitis B is an infectious illness caused by hepatitis B virus which infects the liver of hominoidea, including humans, and causes an inflammation called hepatitis. Originally known as "serum hepatitis", the disease has caused epidemics in parts of Asia and Africa, and it is endemic in China...
(HBV). Among individuals with chronic HBV infection, emtricitabine treatment results in significant histologic, virologic, and biochemical improvement. The safety profile of emtricitabine during treatment is similar to that of a placebo. Emtricitabine, however, cures neither HIV nor HBV infection. In a study involving individuals with HBV infection, symptoms of infection returned in 23% of emtricitabine-treated individuals who were taken off therapy. In studies involving individuals with chronic HIV infection, viral replication also resumes when study subjects are taken off therapy.
Emtricitabine is not approved by the FDA for treatment of HBV infection. As with drugs used to treat HIV infection, drugs used to treat HBV infection may have to be used in combination to prevent the evolution of drug resistant strains. Lamivudine
Lamivudine
Lamivudine is a potent nucleoside analog reverse transcriptase inhibitor .It is marketed by GlaxoSmithKline with the brand names Zeffix, Heptovir, Epivir, and Epivir-HBV.Lamivudine has been used for treatment of chronic hepatitis B at a lower dose than for treatment of HIV...
is also active against HBV virus and commercially available. Like emtricitabine, lamivudine, when used on its own, does not completely suppress viral replication. This allows drug resistant strains to emerge. The effectiveness of emtricitabine in combination with other anti-HBV drugs has not been established. Clinical trials are still ongoing.
Side effects
In clinical practice, toxicityToxicity
Toxicity is the degree to which a substance can damage a living or non-living organisms. Toxicity can refer to the effect on a whole organism, such as an animal, bacterium, or plant, as well as the effect on a substructure of the organism, such as a cell or an organ , such as the liver...
with emtricitabine is unusual. The most common treatment-related adverse events are diarrhea
Diarrhea
Diarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...
, headache
Headache
A headache or cephalalgia is pain anywhere in the region of the head or neck. It can be a symptom of a number of different conditions of the head and neck. The brain tissue itself is not sensitive to pain because it lacks pain receptors. Rather, the pain is caused by disturbance of the...
, nausea
Nausea
Nausea , is a sensation of unease and discomfort in the upper stomach with an involuntary urge to vomit. It often, but not always, precedes vomiting...
, and rash
Rash
A rash is a change of the skin which affects its color, appearance or texture. A rash may be localized in one part of the body, or affect all the skin. Rashes may cause the skin to change color, itch, become warm, bumpy, chapped, dry, cracked or blistered, swell and may be painful. The causes, and...
. These symptoms are generally mild to moderate in severity, but they caused 1% of clinical trial patients to give up treatment. Skin discoloration, which is typically reported as hyperpigmentation
Hyperpigmentation
In dermatology, hyperpigmentation is the darkening of an area of skin or nails caused by increased melanin.-Causes:Hyperpigmentation may be caused by sun damage, inflammation, or other skin injuries, including those related to acne vulgaris...
and usually affects either the palms of the hands or the soles
Sole (foot)
The sole is the bottom of the foot.In humans the sole of the foot is anatomically referred to as the plantar aspect. The equivalent surface in ungulates is the hoof.- Human sole :...
of the feet, is reported in less than 2% of individuals and is almost exclusive to patients of African origin.
Among the more severe side effects patients may experience are a hepatotoxicity
Hepatotoxicity
Hepatotoxicity implies chemical-driven liver damage.The liver plays a central role in transforming and clearing chemicals and is susceptible to the toxicity from these agents. Certain medicinal agents, when taken in overdoses and sometimes even when introduced within therapeutic ranges, may injure...
or a lactic acidosis
Lactic acidosis
Lactic acidosis is a physiological condition characterized by low pH in body tissues and blood accompanied by the buildup of lactate especially D-lactate, and is considered a distinct form of metabolic acidosis. The condition typically occurs when cells receive too little oxygen , for example...
.