Emtricitabine

  • Abbreviation: FTC
    Antiretroviral Subclass:
    Nucleoside reverse transcriptase inhibitors

Background

  • U.S. Manufacturer:
    Gilead Sciences

    Approval

    Emtricitabine was approved by the FDA in July 2003 for use in combination with other antiretroviral agents in adults with HIV infection. In 2005, it was approved for use in pediatric patients. In 2012, the combination of tenofovir + emtricitabine was was approved by the FDA for use as preexposure prophylaxis by HIV-uninfected adults at high risk of sexually acquired infection with HIV (see Special Uses).

    Initial approval of emtricitabine was based on the results of 2 Phase III clinical trials. A double-blind study compared emtricitabine + didanosine + efavirenz with stavudine + didanosine + efavirenz as initial treatment in individuals who had not previously received antiretroviral therapy. At 24 and 48 weeks, patients receiving emtricitabine had significantly higher rates of virologic suppression than did stavudine recipients.(1)

    An open-label trial of treatment-experienced patients with HIV RNA levels of <400 copies/mL on a lamivudine-containing regimen randomized patients either to continue lamivudine or to switch to once-daily emtricitabine, in combination with either stavudine or zidovudine and either a protease inhibitor or an NNRTI. The proportion of patients whose viral loads remained suppressed at the <400 copies/mL and <50 copies/mL level were similar in the two treatment groups.(2)

    Generic Approval

    NA

Formulations and Dosing

  • Emtricitabine is available in capsules and oral solution. Emtricitabine is available in combination with tenofovir disoproxyl fumarate (TDF) as a single tablet (Truvada) and with tenofovir alafenamide (TAF) as a single tablet (Descovy). Emtricitabine also is available in a number of multidrug  combinations, including: with bictegravir + TAF (Biktarvy), with darunavir + cobicictat + TAF (Stribild), with TDF) + efavirenz (Atripla), with TDF + rilpivirine (Complera), with TAF + rilpivirine (Odefsey), with TDF + elvitegravir + cobicistat (Stribild), and with TAF + elvitegravir + cobicistat (Genvoya).

    • There are no food restrictions.
    • Dosage adjustment is recommended in renal insufficiency.
    • Dosage reduction is not necessary in hepatic impairment.
    • Please consult product labeling for detailed dosing information.

    Adult Dosing

    Dosage Formulation Notes
    200 mg QD Capsules  

    Key to abbreviations: QD = once daily.

    Pediatric Dosing

    Age Dosage Formulation Weight
    <3 months 3 mg/kg QD Oral Solution  
    ≥3 months 6 mg/kg QD, maximum 240 mg QD Oral Solution  
      200 mg QD   >33 kg and able to swallow capsules

    Key to abbreviations: QD = once daily.

    Formulations

    blue and white capsule
    200 mg
    Image
    blue and white capsule
    dark bottle with white cap and white label
    10-mg/mL oral solution
    Image
    dark bottle with white cap and white label

Coformulations

Clinical Use

  • Initial vs Subsequent Therapy

    Adult and adolescent treatment guidelines of the U.S. Department of Health and Human Services designate a number of regimens containing emtricitabine + TDF or TAF as "recommended" regimens for initial combination therapy. The guidelines also state that lamivudine may be used in place of emtricitabine and vice versa.

    Regimens containing emtricitabine in combination with other antiretroviral medications have been shown to achieve effective viral suppression in initial therapy.

    Used in initial treatment, emtricitabine compares favorably with lamivudine and with stavudine. A randomized, double-blind study of initial treatment comparing emtricitabine (dosed daily) with lamivudine (dosed twice daily), each combined with stavudine and either nevirapine or efavirenz, showed similar rates of virologic failure at 48 weeks (Kaplan-Meier probability of virologic failure: 16% for emtricitabine vs 11% for lamivudine; p value not significant).(2) In one licensing study (see Approval), recipients of emtricitabine (dosed once daily) were more likely than recipients of stavudine (dosed twice daily) to achieve viral loads of <50 copies/mL at 48 weeks in an intent-to-treat analysis (78% for emtricitabine vs 59% for stavudine; p < 0.001).(1) Those receiving emtricitabine also had greater increases in CD4 counts at 48 weeks (mean increase 168 cells/µL vs 134 cells/µL, but this difference was not statistically significant [p = 0.15]). (1)

    Fewer data are available on the use of emtricitabine in treatment of individuals who have experienced virologic failure on an initial regimen. However, like lamivudine, emtricitabine often has an important role in subsequent therapy, even in situations wherein resistance to these agents has developed. Despite the presence of the signature emtricitabine (or lamivudine) resistance mutations, at reverse transcriptase codon 184 (M184V or M184I), emtricitabine may have a suppressive effect on HIV replication and may increase susceptibility to certain other nucleoside analogues (eg, tenofovir, zidovudine).

    Because the mutations associated with resistance to emtricitabine are identical to those conferring resistance to lamivudine (see Resistance), it is unlikely that emtricitabine will be of benefit to patients changing treatment because of lamivudine resistance.

    Studies of treated individuals with viral load ≤400 copies/mL on treatment have found that switching to emtricitabine-containing regimens does not adversely affect viral suppression in patients on regimens containing lamivudinez(2),(3)or a protease inhibitor.(4)

    Emtricitabine and lamivudine have no significant additive potency and share nearly identical resistance profiles; they should not be used together.

    Adverse Effects

    Symptomatic side effects of emtricitabine may be difficult to distinguish from those of other antiretrovirals with which it is combined. The most common adverse effects noted in clinical trials of emtricitabine with other antiviral agents were headache, diarrhea, nausea, and rash. Side effects were seldom severe, with approximately 1% of participants discontinuing participation because of these events. Skin discoloration, manifested by hyperpigmentation of the palms or soles, or both, and generally mild and asymptomatic, has been associated with emtricitabine.(5)

    Nucleoside analogues may be associated with mitochondrial toxicity leading to potentially serious long-term side effects such as lactic acidosis and disorders of lipid metabolism,(6) but the extent to which emtricitabine may contribute to such effects is not known.

    Resistance to emtricitabine may develop with only a single viral mutation in the setting of suboptimal viral suppression. It is therefore essential to emphasize patient adherence, to assess motivation, and to discuss possible side effects and strategies for their management before any regimen containing emtricitabine is initiated.

    Interactions with Other Drugs

    Emtricitabine does not appear to interact significantly with enzymes involved in drug metabolism. Clinically significant drug-drug interactions involving emtricitabine have not been identified.(5)

    Resistance

    Resistance to emtricitabine can develop quickly in the setting os suboptimal adherence or an insufficiently potent antiretroviral regimen. As with lamivudine, resistance most frequently occurs with the selection of a mutation at codon 184 (M184V or M184I). To avoid long-term treatment failure resulting from resistance, emtricitabine should be used only in regimens that are expected to be fully suppressive of viral replication.

    Implications of emtricitabine resistance for treatment with other antiretrovirals

    HIV isolates with resistance to emtricitabine by virtue of a mutation at codon 184 are cross-resistant to lamivudine and may show resistance to abacavir, but they retain sensitivity to tenofovir and zidovudine.(5)

    Implications of resistance to other antiretrovirals for treatment with emtricitabine

    HIV strains harboring mutations conferring reduced susceptibility to stavudine and zidovudine (at codons 41, 67, 70, 210, 215, or 219) or didanosine (codon 74) have been found to remain sensitive to emtricitabine.(5)

    Special Uses

    Special Use: Treatment of hepatitis B

    Emtricitabine is active against hepatitis B virus, (8)(9) but is not currently approved for treatment of hepatitis B infection. Few data are available on the safety and efficacy of emtricitabine in patients coinfected with HIV and hepatitis B.(10)(11)(15) DHHS guidelines recommend inclusion of either emtricitabine or lamivudine, plus tenofovir, in the antiretroviral regimens of patients coinfected with HIV and hepatitis B. This will result in treatment of both HIV and hepatitis B infections. Exacerbation of hepatitis B has been reported in patients after discontinuation of emtricitabine.(5)

    Special Use: Preexposure prophylaxis

    A number of studies have shown that preexposure prophylaxis (PrEP) using the combination of oral TDF and emtricitabine, taken daily by HIV-uninfected individuals, can reduce the risk of sexual acquisition of HIV.(11)(12)(13)  A study of daily oral TAF + emtricitabine in men who have sex with men showed no significant difference in protective efficacy of the two PrEP formulations.(15)

    In 2012, the FDA approved the combination of oral TDF + emtricitabine for use as PrEP by adults and adolescents at high risk of sexual acquisition of HIV. In 2021, the FDA approved the combination of oral TAF + emtricitabine for PrEP for adults and adolescents, except those who are at risk from exposure through receptive vaginal sex.

    Prophylactic TDF + emtricitabine is intended only for those who are tested and confirmed to be HIV uninfected, and as part of a comprehensive prevention strategy that includes other risk-reduction measures and adherence support. Regular ongoing HIV testing is required to identify persons who become infected with HIV while on PrEP; PrEP medications are not sufficient as treatment for established HIV infection, and in persons with HIV infection, their use risks the development of resistance to the medications.

Resources and Links

  • References

    • 1
      Saag MS, Cahn P, Raffi F, et al; FTC-301A Study Team. Efficacy and safety of emtricitabine vs stavudine in combination therapy in antiretroviral-naive patients: a randomized trial. JAMA. 2004 Jul 14;292(2):180-9.
    • 2
      Sanne I, van der Horst C, Shaw A, et al. Two randomized, controlled, equivalence trials of emtricitabine (FTC) to lamivudine (3TC). In: Program and abstracts of the XIV International AIDS Conference; July 7-12, 2002; Barcelona. Abstract TuPeB4432.
    • 3
      Ford N, Shubber Z, Hill A, et al. Comparative Efficacy of Lamivudine and Emtricitabine: A Systematic Review and Meta-Analysis of Randomized Trials. PLOS One. 2013; 8(11): e79981. doi: 10.1371/journal/oone.0079981.
    • 4
      Benson CA, van der Horst C, Lamarca A, et al. A randomized study of emtricitabine and lamivudine in stably suppressed patients with HIV. AIDS. 2004 Nov 18; 18:2269-2276.
    • 5
      Emtriva package insert. Gilead Sciences. . Available at accessdata.fda.gov
    • 6
      Moyle G. Clinical manifestations and management of antiretroviral nucleoside analog-related mitochondrial toxicity. Clin Ther. 2000 Aug;22(8):911-36; discussion 898.
    • 7
      deleted
    • 8
      Lim SG, Ng TM, Kung N, et al; Emtricitabine FTCB-301 Study Group. A double-blind placebo-controlled study of emtricitabine in chronic hepatitis B. Arch Intern Med. 2006 Jan 9;166(1):49-56.
    • 9
      Gish RG, Leung NW, Wright TL, et al. Dose range study of pharmacokinetics, safety, and preliminary antiviral activity of emtricitabine in adults with hepatitis B virus infection. Antimicrob Agents Chemother. 2002 Jun;46(6):1734-40.
    • 10
      Snow A, Harris J, Borroto-Esoda K, et al. Emtricitabine therapy for hepatitis infection with HIV+ patients co-infected with hepatitis B virus: Efficacy and genotypic findings in antiretroviral treatment-naive patients. 11th Conference on Retroviruses and Opportunistic Infections; February 8-11, 2004; San Francisco. Abstract 836.
    • 11
      Grant RM, Lama JR, Anderson PL, et al; iPrEx Study Team. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N Engl J Med. 2010 Dec 30;363(27):2587-99.
    • 12
      Baeten JM, Donnell D, Ndase P, et al; PrEP Study Team. Antiretroviral prophylaxis for HIV prevention in heterosexual men and women. N Engl J Med. 2012 Aug 2;367(5):399-410.
    • 13
      Thigpen MC, Kebaabetswe PM, Paxton LA, et al; TDF2 Study Group. Antiretroviral preexposure prophylaxis for heterosexual HIV transmission in Botswana. N Engl J Med. 2012 Aug 2;367(5):423-34.
    • 14
      Gallant J, Brunetta J, Crofoot G, et al. Efficacy and safety of switching to a single-tablet regimen of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) in HIV-1/hepatitis B coinfected adults. J Acquir Immune Defic Syndr. 2016 Nov 1;73(3):294-298. doi: 10.1097/QAI.0000000000001069.
    • 15
      Mayer KH, Molina JM, Thompson MA, et al. Emtricitabine and tenofovir alafenamide vs emtricitabine and tenofovir disoproxil fumarate for HIV pre-exposure prophylaxis (DISCOVER): primary results from a randomised, double-blind, multicentre, active-controlled, phase 3, non-inferiority trial. Lancet. 2020 Jul 25;396(10246):239-254. doi: 10.1016/S0140-6736(20)31065-5. PMID: 32711800.