Emtricitabine (FTC, Emtriva) is an antiviral drug that reduces the amount of HIV in the body. Anti-HIV drugs such as emtricitabine slow down or prevent damage to the immune system, and reduce the risk of developing AIDS-related illnesses. Emtricitabine is also active against hepatitis B virus.
Emtricitabine belongs to a class of drugs known as nucleoside reverse transcriptase inhibitors (NRTIs). When HIV infects a cell, the enzyme reverse transcriptase copies the viral single-stranded RNA genome into double-stranded viral DNA. This viral DNA is then integrated into the CD4 chromosomal DNA and can go on to reproduce in the body. Four natural nucleosides complete the DNA synthesis: adenosine, cytidine, quanosine, and thymidine. An NRTI drug substitutes a defective version of one of the nucleosides, causing premature termination of the proviral DNA chain.
Emtricitabine was developed by Triangle Pharmaceuticals and acquired by Gilead Pharmaceuticals in December 2002. Emtricitabine is marketed by Gilead as Emtriva. It was also marketed under the trade name Coviracil. Its chemical name is 2’,3’-dideoxy-5-fluoro-3’-thiacytidine.
Emtricitabine was authorised in the United States in July 2003 and in the European Union in October of that year. It was proposed, but has not been approved, as a therapy for hepatitis B.
Emtricitabine is almost always used as part of a fixed-dose combination product.
The United States Food and Drug Administration (FDA) announced in August 2004 that it had approved a once-daily combination tablet containing 200mg emtricitabine and 300mg tenofovir. The combination tablet is marketed as Truvada by Gilead worldwide. Truvada was approved in the European Union in November 2004. See Truvada for further details.
Emtricitabine is also available in a triple-drug combination tablet called Atripla. This is the first once-daily tablet containing a complete HIV treatment regimen. It contains 600mg efavirenz, 200mg emtricitabine, and 300mg tenofovir. It was approved in the United States in July 2006 and in the European Union in late 2007. See Atripla for further details.
Emtricitabine is also available as a component of the following fixed-dose products:
- Descovy (emtricitabine & tenofovir alafenamide)
- Genvoya (tenofovir alafenamide/emtricitabine/elvitegravir/cobicistat)
- Stribild (tenofovir disoproxil/emtricitabine/elvitegravir/cobicistat)
- Odefsey (tenofovir alafenamide/emtricitabine/rilpivirine)
- Eviplera (tenofovir disoproxil/emtricitabine/rilpivirine)
Several large, randomised, comparative studies have demonstrated the effectiveness of emtricitabine (Emtriva) as an anti-HIV drug. It is active against both HIV-1 and HIV-2. (Saag, 2004) (Raffi) (Gazzard) Emtricitabine is recommended as a component of first-line antiretroviral therapy in combination with tenofovir and another agent in World Health Organization, British, European and United States treatment guidelines.
Among people with hepatitis B virus, emtricitabine produces a 2 to 3 log10 reduction in hepatitis B viral load. (Gish) (Rousseau) Emtricitabine is also effective against hepatitis B virus in people with HIV co-infection, when included as part of an antiretroviral treatment regimen. After 48 weeks of treatment, over half of the people treated with emtricitabine achieve undetectable hepatitis B viral loads, a level which is similar to that in people without HIV. HIV viral loads were also reduced to below the limit of detection in 94% of the people with co-infection. (Raffi) (Harris) However, emtricitabine is not licensed for the treatment of hepatitis B infection, and severe flare-ups of hepatitis can occur when emtricitabine treatment is stopped in people with co-infection.
If not taken as part of a fixed-dose combination emtricitabine (Emtriva) is taken at a dose of one 200mg capsule once daily. It can be taken with or without food.
A liquid formulation of emtricitabine at a concentration of 10mg/ml is also available for children and people who cannot swallow hard capsules or who have kidney problems. Due to differences in bioavailability of the oral solution, a dose of 240mg (24ml) gives similar plasma levels of the drug to a 200mg capsule.
The dose of emtricitabine should be reduced in people with kidney disease, since clearance of the drug is slowed. This can be achieved by increasing the interval between capsules or by using the oral solution of emtricitabine.
The commonest side-effects that occur in people receiving emtricitabine (Emtriva) are headache, diarrhoea, nausea, and rash. In clinical trials, these have generally been of mild to moderate severity.
Skin discolouration is the only side-effect which was more common among people taking emtricitabine compared with other antiretrovirals in clinical trials. Excess pigmentation on the palms or soles of the feet was predominantly observed in non-Caucasian patients, although it was mild and did not result in treatment discontinuation. (Mondou) The mechanism and clinical significance of this side-effect are unknown.
Abnormal kidney function has been reported in two people receiving the 200mg dosage of emtricitabine.
As with all other anti-HIV drugs, strains of HIV that are resistant to emtricitabine (Emtriva) may emerge after a period of treatment. The emergence of drug-resistant strains coincides with a fall in the effectiveness of the drug. HIV can rapidly develop resistance to emtricitabine if viral load is not suppressed below the limit of detection.
The M184V/I mutation, which is associated with resistance to lamivudine (Epivir), is also the key resistance mutation for emtricitabine. (Cahn) However, this mutation develops more slowly in people taking emtricitabine. (Barroto-Esoda)
Emtricitabine is unlikely to have anti-HIV effect in people who have already developed resistance to lamivudine.
Emtricitabine (Emtriva) is excreted via the kidneys. With the exception of famciclovir (Famvir) and tenofovir (Viread), interactions between emtricitabine and other drugs that are excreted by the kidneys or that affect kidney function have not been assessed. There is no significant interaction between emtricitabine and famciclovir or tenofovir.
Emtricitabine has a low potential for interaction with other drugs, and does not inhibit metabolism by the cytochrome P450 system.
Emtricitabine (Emtriva) has been approved for paediatric use in children three months of age and older. Oral solution dosing is 6mg/kg of body weight to a maximum dose of 240mg. Children weighing over 33kg can take a 200mg capsule once daily.
The efficacy and safety of emtricitabine has been demonstrated when used as part of an initial antiretroviral therapy regimen or as second-line therapy. (Saez-Llorens)
Emtricitabine is safe to use during pregnancy. There is no evidence of adverse birth outcomes in the infants of women exposed to emtricitabine during pregnancy. (Antiretroviral Pregnancy Registry Steering Committee)
Saag M et al. Efficacy and safety of emtricitabine vs stavudine in combination therapy in antiretroviral-naive patients: a randomized trial. JAMA, 292: 180-189, 2004.
Raffi F et al. A randomised, double-blind, multi-centre comparison of emtricitabine QD to stavudine BID in treatment-naïve HIV-infected patients. Antiviral Therapy, 8: S193, 2003.
Gazzard B et al. The combination of tenofovir DF (TDF), emtricitabine (FTC) and efavirenz (EFV) has significantly greater response vs fixed dose zidovudine/lamivudine (CBV) and EFV in antiretroviral naïve patients: a 24 week preliminary analysis. 44th Interscience Conference on Antimicrobial Agents and Chemotherapy, Washington, abstract H-1137C, 2004.
Gish RG et al. Dose range study of pharmacokinetics, safety, and preliminary antiviral activity of emtricitabine in adults with hepatitis B virus infection. Antimicrobial Agents and Chemotherapy, 46: 1734-1740, 2002.
Rousseau F et al. Emtricitabine (FTC): HBV DNA viral load assessments over 36 weeks in patients with chronic HBV infection. Eighth Conference on Retroviruses and Opportunistic Infections, Chicago, abstract 559, 2001.
Raffi F et al. Anti-HBV activity of emtricitabine (FTC) in patients co-infected with HIV and hepatitis B virus. Antiviral Therapy, 8: S236, 2003.
Harris J et al. Emtricitabine therapy for hepatitis infection in HIV-1 patients co-infected with hepatitis B: antiviral response and genotypic findings in antiretroviral treatment naïve patients. Eleventh Conference on Retroviruses and Opportunistic Infections, San Francisco, abstract 836, 2004.
Mondou E et al. Incidence of skin discoloration across phase 3 clinical trials of emtricitabine (FTC). 15th International AIDS Conference, Bangkok, abstract WePeB5916, 2004.
Cahn P et al. Virologic efficacy and patterns of resistance mutations in ART-naïve patients receiving combination therapy with once-daily emtricitabine compared to twice-daily stavudine in a randomized, double-blind, multi-center clinical trial. Tenth Conference on Retroviruses and Opportunistic Infections, Boston, abstract P606, 2003.
Barroto-Esoda K et al. Lower incidence of the M184V mutation in ART naïve patients receiving combination therapy with emtricitabine (FTC) compared to lamivudine (3TC), results of a double blind equivalence trial. First International AIDS Society Conference on HIV Pathogenesis and Treatment, Buenos Aires, abstract LB-P21, 2001.
Saez-Llorens X et al. Long-term safety and efficacy results of once-daily emtricitabine-based highly active antiretroviral therapy regimens in human immunodeficiency virus-infected pediatric subjects. Pediatrics, 121: e827-835, 2008.
Antiretroviral Pregnancy Registry Steering Committee Antiretroviral pregnancy registry international interim report for 1 Jan 1989 - 31 July 2005. Registry Coordinating Center, Wilmington NC, USA at http://www.APRegistry.com, 2005.