Article: Emtricitabine

Emtricitabine
Systematic (IUPAC) name
4-amino-5-fluoro-1- [2-(hydroxymethyl)- 1,3-oxathiolan-5-yl]- pyrimidin-2-one
Identifiers
CAS number	143491-57-0
ATC code	J05AF09
PubChem	60877
DrugBank	APRD00226
Chemical data
Formula	C8H10FN3O3S
Mol. weight	247.248 g/mol
Pharmacokinetic data
Bioavailability	?
Protein binding	Very low (less than 4%)
Metabolism	?
Half life	10 hours
Excretion	?
Therapeutic considerations
Pregnancy cat.	?
Legal status
Routes	?

Emtricitabine (FTC), with trade name Emtriva® (formerly Coviracil), is a nucleoside reverse transcriptase inhibitor (NRTI) for the treatment of HIV infection in adults.

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) has been approved by the FDA on July 12, 2006 under the brand name Atripla®.

History

Emtricitabine was discovered by Dr. Dennis Liotta, 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 3TC and cross-resistance between the two is near-universal.

Mode of action

Emtricitabine is an analogue 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 cells or CD4+ T-cells). Both of these changes are associated with healthier immune systems and decreased likelihood of serious illness.

Indications

Emtricitabine is indicated in combination with other antiretroviral agents for the treatment of HIV infection in adults. This indication is based on the analyses of plasma HIV RNA levels and CD4 cell counts in two Phase III clinical trials of Emtriva of 48 weeks duration.

It is not indicated for the treatment of chronic hepatitis B virus infection and the safety and efficacy of emtricitabine have not been established in patients co-infected with HBV and HIV. Severe acute exacerbations of hepatitis B have been reported in patients after the discontinuation of emtricitabine. The drug is however being evaluated as a potential treatment for chronic hepatitis B. These studies are ongoing.

Side-effects

In clinical practise, toxicity 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 under 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.