Emtricitabine

Emtricitabine

Systematic (IUPAC) name
4-amino-5-fluoro-1-[(2S,5R)-2-(hydroxymethyl)-1,3-oxathiolan-5-yl]-1,2-dihydropyrimidin-2-one
Clinical data
Trade names	Emtriva
AHFS/Drugs.com	monograph
MedlinePlus	a604004
Pregnancy cat.	B1(AU) B(US)
Legal status	POM (UK) ℞-only (US)
Routes	Oral
Pharmacokinetic data
Bioavailability	93%
Protein binding	Very low (less than 4%)
Metabolism	Hepatic oxidation and glucuronidation CYP system not involved
Half-life	10 hours
Excretion	Renal (86%) and fecal (14%)
Identifiers
CAS number	143491-57-0 Y
ATC code	J05AF09
PubChem	CID 60877
DrugBank	APRD00226
ChemSpider	54859 Y
UNII	G70B4ETF4S Y
KEGG	D01199 Y
ChEBI	CHEBI:31536 Y
ChEMBL	CHEMBL885 Y
Chemical data
Formula	C8H10FN3O3S
Mol. mass	247.248 g/mol
SMILES	eMolecules & PubChem
InChI InChI=1S/C8H10FN3O3S/c9-4-1-12(8(14)11-7(4)10)5-3-16-6(2-13)15-5/h1,5-6,13H,2-3H2,(H2,10,11,14)/t5-,6+/m0/s1 Y Key:XQSPYNMVSIKCOC-NTSWFWBYSA-N Y
Y(what is this?)  (verify)

Emtricitabine (FTC), 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.

History

Emtricitabine was discovered by Dr. Dennis C. Liotta, Dr. Raymond Schinazi and Dr. Woo-Baeg Choi of Emory University and licensed to Triangle Pharmaceuticals by Emory in 1996.^[1] 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.^{[citation needed]}

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

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 virus (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.^[2] In studies involving individuals with chronic HIV infection, viral replication also resumes when study subjects are taken off therapy.^[3]

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.^[4] 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, 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 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.

References

1. ^ Leaf, Clifton (September 19, 2005). "The Law of Unintended Consequences". CNN. http://money.cnn.com/magazines/fortune/fortune_archive/2005/09/19/8272884/index.htm. 
2. ^ Lim SG, Ng TM, Kung N et al. (January 2006). "A double-blind placebo-controlled study of emtricitabine in chronic hepatitis B". Arch. Intern. Med. 166 (1): 49–56. doi:10.1001/archinte.166.1.49. PMID 16401810. http://archinte.ama-assn.org/cgi/pmidlookup?view=long&pmid=16401810. 
3. ^ Oxenius A, Price DA, Günthard HF et al. (October 2002). "Stimulation of HIV-specific cellular immunity by structured treatment interruption fails to enhance viral control in chronic HIV infection". Proc. Natl. Acad. Sci. U.S.A. 99 (21): 13747–52. doi:10.1073/pnas.202372199. PMC 129766. PMID 12370434. http://www.pnas.org/cgi/pmidlookup?view=long&pmid=12370434. 
4. ^ Liu KZ, Hou W, Zumbika E, Ni Q (December 2005). "Clinical features of chronic hepatitis B patients with YMDD mutation after lamivudine therapy". J Zhejiang Univ Sci B 6 (12): 1182–7. doi:10.1631/jzus.2005.B1182. PMC 1390641. PMID 16358376. http://www.zju.edu.cn/jzus/article.php?doi=10.1631/jzus.2005.B1182. 

External links

• Emtriva Fact Sheet