Emtricitabine

247.24700

247.25

604-363-1

G70B4ETF4S

DTXSID0040129

C47509

White to off white powder|White solid from ether and methanol

J05AR03|J05AR06|J05AR|J05AR17|J05AR19|J05|J05AF09|J05AR08|J05AR09|J - Antiinfectives for systemic use

2934999090

115.67000

-0.6

1.82 g/cm3

136-140ºC

443.3ºC at 760 mmHg

221.9ºC

1.731

2.00e+00 g/L

Store at 25 deg C (77 deg F); excursions permitted to 15 deg C-30 deg C (59 deg F-86 deg F)

0mmHg at 25°C

Henry's Law constant = 1.08X10-17 atm-cu m/mole at 25 °C (est)

2.65|pKa = 2.65 (amine)

Hydroxy radical reaction rate constant = 1.34X10-10 cu cm/molec-sec at 25 °C (est)|Ozone reaction rate constant = 7.0X10-19 cu cm/molec-sec at 25 °C (est)

III

6.1

2446

3

S26-S36

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational exposure or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in soil or water; effects on animal, aquatic, and plant life; and conformance with environmental and public health regulations.

The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including emtricitabine, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

Bang LM, Scott LJ; Emtricitabine: An Antiretroviral Agent for HIV Infection; Drugs 63 (22): 2413-24 (2003)|Zapor MJ et al; Antiretrovirals, Part II: Focus on Non-protease Inhibitor Antiretrovirals (NRTIs, NNRTIs, and Fusion Inhibitors); Psychosomatics 45 (6): 524-35 (2004)|Mjodrzejewski KA, Herman RA; Emtricitabine: A Once-Daily Nucleoside Reverse Transcriptase Inhibitor; Ann Pharmacother 38 (6): 1006-14 (2004)

The LD50 of emtricitabine is not readily available.[9019,L9818] Symptoms of emtricitabine toxicity include hepatotoxicity with steatosis, as well as lactic acidosis. Treat overdose with symptomatic and supportive measures, including hemodialysis.

There is little evidence for direct hepatotoxicity of emtricitabine and it has not been specifically implicated in cases of lactic acidosis with steatosis and hepatic failure. However, patients with chronic hepatitis B can experience a flare of the underlying hepatitis during emtricitabine therapy. These flares occur either at the start therapy (treatment flares), with the development of antiviral resistance (breakthrough flares), or when therapy is abruptly stopped (withdrawal flares). Treatment flares occur in 5% to 10% of patients, are usually transient and asymptomatic, and rarely require dose modification or discontinuation of therapy. In contrast, withdrawal flares occur in 15% to 30% of patients, but can be symptomatic and severe, in rare instances (~1%) leading to acute liver failure, death or requirement for emergency liver transplantation. Patients who develop emtricitabine resistance often have relapse of disease activity after the appearance of the mutant HBV strain and rise in HBV DNA levels; this relapse can initially be severe and associated with symptoms and jaundice.

Pharmacokinetic interactions with drugs metabolized by uridine diphosphate-glucuronosyltransferase are unlikely. Emtricitabine does not inhibit glucuronosyltransferase (uridine diphosphoglucuronosyltransferase, UDP-glucuronate B-d-glucuronosyltransferase (acceptor-unspecific)), an enzyme responsible for glucuronidation.|Pharmacokinetic interactions with drugs metabolized by hepatic microsomal enzymes are unlikely. In vitro studies indicate that emtricitabine does not inhibit cytochrome P-450 (CYP) isoenzymes 1A2, 2A6, 2B6, 2C9, 2C19, 2D6, or 3A4.|At concentrations up to 14 fold higher than those observed in vivo, emtricitabine did not inhibit in vitro drug metabolism mediated by any of the following human CYP 450 isoforms: CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2C19, CYP2D6 and CYP3A4. Emtricitabine did not inhibit the enzyme responsible for glucuronidation (uridine-5'-disphosphoglucuronyl transferase). Based on the results of these in vitro experiments and the known elimination pathways of emtricitabine, the potential for CYP450 mediated interactions involving emtricitabine with other medicinal products is low.|The potential for drug interactions with emtricitabine has been studied in combination with indinavir, stavudine, famciclovir, and tenovir disoproxil fumarate. There were no clinically significant drug interactions for any of these drugs.

Emtricitabine is <4% bound to plasma proteins, mainly serum albumin.

Emtricitabine's production and use as an antiviral(1) and in the treatment of AIDS(2) may result in its release to the environment through various waste streams(SRC).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 55(SRC), determined from a structure estimation method(2), indicates that emtricitabine is expected to have high mobility in soil(SRC). Volatilization of emtricitabine from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 1.1X10-17 atm-cu m/mole(SRC), using a fragment constant estimation method(3). Emtricitabine is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.7X10-8 mm Hg at 25 °C(SRC), determined from a fragment constant method(4). Biodegradation data in soil were not available(SRC, 2013).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 55(SRC), determined from a structure estimation method(2), indicates that emtricitabine is not expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 1.1X10-17 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). According to a classification scheme(5), an estimated BCF of 3(SRC), from its log Kow of -0.43(6) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Emtricitabine is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(3). Biodegradation data in water were not available(SRC, 2013).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), emtricitabine, which has an estimated vapor pressure of 1.7X10-8 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), will exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase emtricitabine is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 2.6 hours(SRC), calculated from its rate constant of 1.3X10-10 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). The rate constant for the vapor-phase reaction of emtricitabine with ozone has been estimated as 7.0X10-19 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). This corresponds to an atmospheric half-life of about 16 days at an atmospheric concentration of 7X10+11 ozone molecules per cu cm(4). Particulate-phase emtricitabine may be removed from the air by wet or dry deposition(SRC). Emtricitabine does not absorb UV light at wavelengths >290 nm(5) and, therefore, is not expected to be susceptible to direct photolysis by sunlight(SRC).

The rate constant for the vapor-phase reaction of emtricitabine with photochemically-produced hydroxyl radicals has been estimated as 1.3X10-10 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 2.6 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). The rate constant for the vapor-phase reaction of emtricitabine with ozone has been estimated as 7.0X10-19 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(1). This corresponds to an atmospheric half-life of about 16 days at an atmospheric concentration of 7X10+11 ozone molecules per cu cm(2). Emtricitabine is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(3). Emtricitabine does not absorb UV light at wavelengths >290 nm(4) and, therefore, is not expected to be susceptible to direct photolysis by sunlight(SRC).

An estimated BCF of 3 was calculated in fish for emtricitabine(SRC), using a log Kow of -0.43(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).

Using a structure estimation method based on molecular connectivity indices(1), the Koc of emtricitabine can be estimated to be 55(SRC). According to a classification scheme(2), this estimated Koc value suggests that emtricitabine is expected to have high mobility in soil.

The Henry's Law constant for emtricitabine is estimated as 1.1X10-17 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that emtricitabine is expected to be essentially nonvolatile from water and moist soil surfaces(2). Emtricitabine is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.7X10-8 mm Hg(SRC), determined from a fragment constant method(3).

While data specific to emtricitabine were not located(2013, SRC), the literature suggests that some pharmaceutically active compounds originating from human and veterinary therapy are not eliminated completely in municipal sewage treatment plants and are therefore discharged into receiving waters(1). Wastewater treatment processes often were not designed to remove them from the effluent(2). Selected organic waste compounds may be degrading to new and more persistent compounds that may be released instead of or in addition to the parent compound(2).

Emtricitabine is distributed into human milk in low concentrations.|EXPERIMENTAL: The aim was to evaluate emtricitabine (FTC) and tenofovir (TFV) neonatal ingestion through breast milk. Median TFV and FTC breast milk doses represented 0.03% and 2%, respectively, of the proposed oral infant doses. Neonatal simulated plasma concentrations were extremely low for TFV but between the half-maximal inhibitory concentration and the adult minimal expected concentration for FTC. The rare children who will acquire HIV despite TDF-FTC therapy will need to be monitored for viral resistance acquisition.

Occupational exposure to emtricitabine may occur through inhalation of dust and dermal contact with this compound at workplaces where entecavir is produced or used. Use data indicate that the general population may be exposed to emtricitabine via medical administration of this compound for the treatment of viral infection. (SRC)

Not known whether emtricitabine is distributed into human milk; ... .

Emtricitabine is indicated in combination with other medications for the treatment of HIV-1 infections; treatment of HIV-1 infections in pediatric patients 25-35kg, treatment of HIV-1 infections in adult patients ≥35kg, for pre exposure prophylaxis of HIV-1 in adolescent and adult patients excluding those who have receptive vaginal sex; treatment of HIV-1 infections in pediatric and adult patients ≥17kg, pre exposure prophylaxis in adolescents and adults ≥35kg; treatment of HIV-1 in patients ≥12 years and ≥35kg; treatment of HIV-1 in patients weighing ≥35kg; treatment of HIV-1 in patients weighing ≥25kg; and treatment of HIV-1 in patients weighing ≥40kg.|FDA Label|Treatment of HIV-1 infection:Emtricitabine/Tenofovir disoproxil Mylan is indicated in antiretroviral combination therapy for the treatment of HIV 1 infected adults.Emtricitabine/Tenofovir disoproxil Mylan is also indicated for the treatment of HIV-1 infected adolescents, with NRTI resistance or toxicities precluding the use of first line agents.Pre-exposure prophylaxis (PrEP):Emtricitabine/Tenofovir disoproxil Mylan is indicated in combination with safer sex practices for pre-exposure prophylaxis to reduce the risk of sexually acquired HIV 1 infection in adults and adolescents at high risk.|Treatment of HIV-1 infectionEmtricitabine/Tenofovir disoproxil Zentiva is indicated in antiretroviral combination therapy for the treatment of HIV-1 infected adults.Emtricitabine/Tenofovir disoproxil Zentiva is also indicated for the treatment of HIV-1 infected adolescents, with NRTI resistance or toxicities precluding the use of first line agents.Pre-exposure prophylaxis (PrEP)Emtricitabine/Tenofovir disoproxil Zentiva is indicated in combination with safer sex practices for pre-exposure prophylaxis to reduce the risk of sexually acquired HIV-1 infection in adults and adolescents at high risk.|Atripla is a fixed-dose combination of efavirenz, emtricitabine and tenofovir disoproxil fumarate. It is indicated for the treatment of human-immunodeficiency-virus-1 (HIV-1) infection in adults with virologic suppression to HIV-1 RNA levels of < 50 copies/ml on their current combination antiretroviral therapy for more than three months. Patients must not have experienced virological failure on any prior antiretroviral therapy and must be known not to have harboured virus strains with mutations conferring significant resistance to any of the three components contained in Atripla prior to initiation of their first antiretroviral treatment regimen.The demonstration of the benefit of Atripla is primarily based on 48-week data from a clinical study in which patients with stable virologic suppression on a combination antiretroviral therapy changed to Atripla.No data are currently available from clinical studies with Atripla in treatment-naive or in heavily pretreated patients.No data are available to support the combination of Atripla and other antiretroviral agents.|Biktarvy is indicated for the treatment of adults infected with human immunodeficiency virus 1 (HIV 1) without present or past evidence of viral resistance to the integrase inhibitor class, emtricitabine or tenofovir.|Treatment of HIV-1 infection:Truvada is indicated in antiretroviral combination therapy for the treatment of HIV-1 infected adults.Truvada is also indicated for the treatment of HIV-1 infected adolescents, with NRTI resistance or toxicities precluding the use of first line agents, aged 12 to < 18 years.Pre-exposure prophylaxis (PrEP):Truvada is indicated in combination with safer sex practices for pre-exposure prophylaxis to reduce the risk of sexually acquired HIV-1 infection in adults at high risk.|Descovy is indicated in combination with other antiretroviral agents for the treatment of adults and adolescents (aged 12 years and older with body weight at least 35 kg) infected with human immunodeficiency virus type 1 (HIV-1).|Efavirenz/Emtricitabine/Tenofovir disoproxil Krka is a fixed-dose combination of efavirenz, emtricitabine and tenofovir disoproxil. It is indicated for the treatment of human immunodeficiency virus-1 (HIV-1) infection in adults aged 18 years and over with virologic suppression to HIV-1 RNA levels of < 50 copies/ml on their current combination antiretroviral therapy for more than three months. Patients must not have experienced virological failure on any prior antiretroviral therapy and must be known not to have harboured virus strains with mutations conferring significant resistance to any of the three components contained in Efavirenz/Emtricitabine/Tenofovir disoproxil Krka prior to initiation of their first antiretroviral treatment regimen.The demonstration of the benefit of efavirenz/emtricitabine/tenofovir disoproxil is primarily based on 48-week data from a clinical study in which patients with stable virologic suppression on a combination antiretroviral therapy changed to efavirenz/emtricitabine/tenofovir disoproxil.No data are currently available from clinical studies with efavirenz/emtricitabine/tenofovir disoproxil in treatment-naïve or in heavily pretreated patients.No data are available to support the combination of efavirenz/emtricitabine/tenofovir disoproxil and other antiretroviral agents.|Treatment of HIV-1 infectionEmtricitabine/tenofovir disoproxil Krka is indicated in antiretroviral combination therapy for the treatment of HIV-1 infected adults.Emtricitabine/Tenofovir disoproxil Krka is also indicated for the treatment of HIV-1 infected adolescents, with NRTI resistance or toxicities precluding the use of first line agents, aged 12 to < 18 years (see section 5.1Pre-exposure prophylaxis (PrEP)Emtricitabine/Tenofovir disoproxil Krka is indicated in combination with safer sex practices for pre-exposure prophylaxis to reduce the risk of sexually acquired HIV-1 infection in adults at high risk.|Emtricitabine/Tenofovir disoproxil Krka d.d. is indicated in antiretroviral combination therapy for the treatment of HIV-1 infected adults.Emtricitabine/Tenofovir disoproxil Krka d.d. is also indicated for the treatment of HIV-1 infected adolescents, with NRTI resistance or toxicities precluding the use of first line agents, aged 12 to < 18 years.|Efavirenz/Emtricitabine/Tenofovir disoproxil Mylan is a fixed-dose combination of efavirenz, emtricitabine and tenofovir disoproxil. It is indicated for the treatment of human immunodeficiency virus-1 (HIV-1) infection in adults aged 18 years and over with virologic suppression to HIV-1 RNA levels of < 50 copies/ml on their current combination antiretroviral therapy for more than three months. Patients must not have experienced virological failure on any prior antiretroviral therapy and must be known not to have harboured virus strains with mutations conferring significant resistance to any of the three components contained in Efavirenz/Emtricitabine/Tenofovir disoproxil Mylan prior to initiation of their first antiretroviral treatment regimen.The demonstration of the benefit of efavirenz/emtricitabine/tenofovir disoproxil is primarily based on 48-week data from a clinical study in which patients with stable virologic suppression on a combination antiretroviral therapy changed to efavirenz/emtricitabine/tenofovir disoproxil. No data are currently available from clinical studies with efavirenz/emtricitabine/tenofovir disoproxil in treatment-naïve or in heavily pretreated patients.No data are available to support the combination of efavirenz/emtricitabine/tenofovir disoproxil and other antiretroviral agents.|Treatment of adults and adolescents (aged 12 years and older with body weight at least 35 kg) infected with human immunodeficiency virus 1 (HIV 1) without known mutations associated with resistance to the non nucleoside reverse transcriptase inhibitor (NNRTI) class, tenofovir or emtricitabine and with a viral load ≤ 100,000 HIV 1 RNA copies/mL.|Symtuza is indicated for the treatment of human immunodeficiency virus type 1 (HIV‑1) infection in adults and adolescents (aged 12 years and older with body weight at least 40 kg).Genotypic testing should guide the use of Symtuza.|Efavirenz/Emtricitabine/Tenofovir disoproxil Zentiva is a fixed-dose combination of efavirenz, emtricitabine and tenofovir disoproxil.It is indicated for the treatment of human immunodeficiency virus-1 (HIV-1) infection in adults aged 18 years and over with virologic suppression to HIV-1 RNA levels of < 50 copies/ml on their current combination antiretroviral therapy for more than three months.Patients must not have experienced virological failure on any prior antiretroviral therapy and must be known not to have harboured virus strains with mutations conferring significant resistance to any of the three components contained in Efavirenz/Emtricitabine/Tenofovir disoproxil Zentiva prior to initiation of their first antiretroviral treatment regimen.The demonstration of the benefit of the combination efavirenz/emtricitabine/tenofovir disoproxil is primarily based on 48-week data from a clinical study in which patients with stable virologic suppression on a combination antiretroviral therapy changed to efavirenz/emtricitabine/tenofovir disoproxil.No data are currently available from clinical studies with combination efavirenz/emtricitabine/tenofovir disoproxil in treatment-naïve or in heavily pretreated patients.No data are available to support the combination of efavirenz/emtricitabine/tenofovir disoproxil and other antiretroviral agents.|Emtriva is indicated for the treatment of HIV-1 infected adults and children in combination with other antiretroviral agents.This indication is based on studies in treatment-naive patients and treatment-experienced patients with stable virological control. There is no experience of the use of Emtriva in patients who are failing their current regimen or who have failed multiple regimens.When deciding on a new regimen for patients who have failed an antiretroviral regimen, careful consideration should be given to the patterns of mutations associated with different medicinal products and the treatment history of the individual patient. Where available, resistance testing may be appropriate.|Eviplera is indicated for the treatment of adults infected with human immunodeficiency virus type 1 (HIV-1) without known mutations associated with resistance to the non-nucleoside reverse transcriptase inhibitor (NNRTI) class, tenofovir or emtricitabine, and with a viral load ≤ 100,000 HIV-1 RNA copies/mL. As with other antiretroviral medicinal products, genotypic resistance testing and/or historical resistance data should guide the use of Eviplera.|Genvoya is indicated for the treatment of adults and adolescents (aged 12 years and older with body weight at least 35 kg) infected with human immunodeficiency virus 1 (HIV 1) without any known mutations associated with resistance to the integrase inhibitor class, emtricitabine or tenofovir.|Treatment of human immunodeficiency virus 1 (HIV 1) infection in adults aged 18 years and over who are antiretroviral treatment-naïve or are infected with HIV 1 without known mutations associated with resistance to any of the three antiretroviral agents in Stribild.|Treatment of human immunodeficiency virus (HIV-1) infection|Prevention of human immunodeficiency virus (HIV-1) infection

Emtricitabine is a nucleoside analogue and reverse transcriptase inhibitor used in combination with other agents for treatment and prevention of human immunodeficiency virus (HIV) infection and the acquired immunodeficiency syndrome (AIDS). Emtricitabine does not appear to be a significant cause of drug induced liver injury, but may cause flares of disease in patients with underlying chronic hepatitis B virus (HBV) infection.

Antiviral Agents

Emtricitabine has known transformation products that include Flucytosine.

Antiviral Agents|Emtricitabine is used in conjunction with other antiretroviral agents for the treatment of HIV-1 infection in pediatric patients 12 years of age or older. The fixed combination containing emtricitabine and tenofovir (Truvada) can be used in conjunction with other antiretrovirals in children 12 years of age or older weighing at least 35 kg. For initial treatment of HIV-infected pediatric patients, the HHS Panel on Antiretroviral Therapy and Medical Management of HIV-infected Children recommends antiretroviral therapy with at least 3 drugs, including either a PI or NNRTI with 2 NRTIs. When PI-based or NNRTI-based regimens are used in pediatric patients, emtricitabine and (abacavir (for individuals 3 months of age or older who test negative for the HLA-B*5701 allele), tenofovir (for adolescents 12 years of age or older at Tanner stage 4 or 5), or zidovudine) are preferred dual NRTI options. A dual NRTI combination of emtricitabine and lamivudine is not recommended, because of similar resistance profiles and minimal additive antiretroviral activity. A triple NRTI regimen that includes abacavir, tenofovir, and either lamivudine or emtricitabine or a triple NRTI regimen that includes tenofovir, didanosine, and either lamivudine or emtricitabine should not be used at any time in pediatric patients because of the high rate of early virologic failure reported in antiretroviral-naive adults.|Emtricitabine has been evaluated in a randomized, open-label, multicenter study (study 303) in 440 previously treated adults (mean age: 42 years; 86% male; 64% white; 13% Hispanic; 21% African American; median baseline plasma HIV-1 RNA level: 1.7 log10 copies/mL; mean baseline CD4+ T-cell count: 527 cells/mm3) who had received a lamivudine-containing regimen that also included 2 other antiretrovirals (background regimen) for at least 12 weeks prior to study entry and had plasma HIV-1 levels of 400 copies/mL or less. Patients in this study were randomized to receive emtricitabine in conjunction with stavudine or zidovudine and PI or NNRTI or to continue their lamivudine-containing background regimen (i.e., lamivudine in conjunction with stavudine or zidovudine and a PI or NNRTI). At week 48, 77 and 67% of adults receiving the regimen that included emtricitabine and 82 and 72% of those receiving the regimen that included lamivudine had plasma HIV-1 RNA levels less than 400 or 50 copies/mL, respectively. Virologic failure (i.e., individuals who failed to achieve virologic suppression or experienced rebound after achieving virologic suppression) was reported in 7% of those receiving the emtricitabine-containing regimen and in 8% of those receiving the lamivudine-containing regimen at week 48. Administration of the emtricitabine-containing regimen resulted in a mean increase in CD4+ T-cell counts of 29 cells/mm3; administration of the lamivudine-containing regimen resulted in a mean increase in CD4+ T-cell counts of 61 cells/cu mm.|Safety and efficacy of emtricitabine used in conjunction with other antiretrovirals have been evaluated in a randomized multicenter study in treatment-naive adults (study 301A). In this study, 571 HIV-infected adults (mean age: 36 years; 85% male; 52% white; 26% Hispanic; 16% African American; median baseline plasma HIV-1 RNA level: 4.9 log10 copies/mL; mean baseline CD4+ T-cell count: 318 cells/mm3) were randomized to receive emtricitabine or stavudine in conjunction with didanosine (delayed-release capsules) and efavirenz. Results of this study indicated that an initial regimen that includes emtricitabine in conjunction with didanosine and efavirenz is as effective as an initial regimen of stavudine in conjunction with didanosine and efavirenz. At week 48, 81 and 78% of adults receiving the regimen that included emtricitabine and 68 and 59% of those receiving the regimen that included stavudine had plasma HIV-1 RNA levels less than 400 or 50 copies/mL, respectively. Virologic failure (i.e., individuals who failed to achieve virologic suppression or experienced rebound after achieving virologic suppression) at week 48 was reported in 3% of those receiving the emtricitabine-containing regimen and in 11% of those receiving the stavudine-containing regimen. At week 48, increases in CD4+ T-cell counts were greater in patients receiving the regimen that included emtricitabine (mean increase of 168 cells/mm3) than in those receiving the regimen that included stavudine (mean increase of 134 cells/mm3).|For more Therapeutic Uses (Complete) data for EMTRICITABINE (7 total), please visit the HSDB record page.

Safety and efficacy of emtricitabine have been established for treatment of HIV-1 infection in children 3 months of age and older. The pharmacokinetics and safety of emtricitabine were evaluated in a dose-finding study in 20 neonates born to HIV-infected mothers.20 1 These neonates received zidovudine prophylaxis for 6 weeks. In addition, these neonates received 2 short courses of emtricitabine (3 mg/kg daily for 4 days per course) during the first 12 weeks of life. This dose was well tolerated and was not associated with any safety issues. Systemic exposure (area under the plasma concentration-time curve [AUC]) in infants 0-3 months of age receiving emtricitabine 3 mg/kg daily was similar to that reported in children 3 months to 17 years of age receiving emtricitabine 6 mg/kg daily. All neonates were HIV-1 negative at the end of the study (6 months postpartum); efficacy of emtricitabine for the prevention or treatment of HIV was not determined.|Lactic acidosis and severe hepatomegaly with steatosis, including fatalities, have been reported in patients receiving nucleoside reverse transcriptase inhibitors (NRTIs), including emtricitabine, in conjunction with other antiretroviral agents. Most reported cases have involved women; obesity and long-term therapy with a nucleoside analog also may be risk factors.|Caution should be observed when nucleoside reverse transcriptase inhibitors are used in patients with known risk factors for liver disease; however, lactic acidosis and severe hepatomegaly with steatosis have been reported in patients with no known risk factors. Emtricitabine therapy should be interrupted in any patient with clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity (signs of hepatotoxicity include hepatomegaly and steatosis even in the absence of marked increases in serum aminotransferase concentrations).|Prior to initiation of emtricitabine therapy for the treatment of HIV-1 infection, patients should be tested for chronic hepatitis B virus (HBV). Emtricitabine is not indicated for the treatment of chronic HBV infection; safety and efficacy of the drug have not been established in patients with coexisting HBV and HIV infections. Exacerbations of HBV infection have been reported in HIV-infected patients following discontinuance of emtricitabine. Patients with HBV infection and HIV infection should be closely monitored with clinical and laboratory follow-up for at least several months after stopping emtricitabine therapy.|For more Drug Warnings (Complete) data for EMTRICITABINE (13 total), please visit the HSDB record page.

Emtricitabine-resistant isolates of HIV have been selected in vitro. Genotypic analysis of these isolates showed that the reduced susceptibility to emtricitabine was associated with a mutation in the HIV reverse transcriptase gene at codon 184 which resulted in an amino acid substitution of methionine by valine or isoleucine (M184V/I). ... In a clinical study, viral isolates from 37.5% of treatment-naive patients with virologic failure showed reduced susceptibility to emtricitabine. Genotypic analysis of these isolates showed that the resistance was due to M184V/I mutations in the HIV reverse transcriptase gene.|Emtricitabine-resistant isolates (M184V/I) were cross-resistant to lamivudine and zalcitabine but retained sensitivity to abacavir, didanosine, stavudine, tenofovir, zidovudine, and NNRTIs (delavirdine, efavirenz, and nevirapine). HIV-1 isolates containing the K65R mutation, selected in vivo by abacavir, didanosine, tenofovir, and zalcitabine, demonstrated reduced susceptibility to inhibition by emtricitabine.

Emtricitabine is a cytidine analog that competes with the natural substrate of HIV-1 reverse transcriptase to be incorporated into newly formed DNA, terminating its transcription. It is administered once daily so it has a long duration of action. Patients should be counselled regarding the risk of lactic acidosis and hepatomegaly with steatosis.

Agents used in the prophylaxis or therapy of VIRUS DISEASES. Some of the ways they may act include preventing viral replication by inhibiting viral DNA polymerase; binding to specific cell-surface receptors and inhibiting viral penetration or uncoating; inhibiting viral protein synthesis; or blocking late stages of virus assembly. (See all compounds classified as Antiviral Agents.)|Agents used to treat AIDS and/or stop the spread of the HIV infection. These do not include drugs used to treat symptoms or opportunistic infections associated with AIDS. (See all compounds classified as Anti-HIV Agents.)|Inhibitors of reverse transcriptase (RNA-DIRECTED DNA POLYMERASE), an enzyme that synthesizes DNA on an RNA template. (See all compounds classified as Reverse Transcriptase Inhibitors.)

Emtricitabine reaches a C_max of 1.8±0.7µg/mL with a T_max of 1-2 hours, and has an AUC of 10±3.1µg\*hr/mL. The bioavailability of emtricitabine capsules is 93% and the bioavailability of the oral solution is 75%. Taking emtricitabine with food decreases the C_max by 29%.[L9019|Emtricitabine is 86% recovered in the urine and 14% recovered in feces. 13% of the dose is recovered in the urine as metabolites; 9% as 3'-sulfoxide diastereomers and 4% as 2'-O-glucuronide.|The apparent central volume of distribution is 42.3L and the peripheral volume of distribution is 55.4L.|Emtricitabine has an apparent elimination rate of 15.1L/h. This rate is closely linked to creatinine clearance.|Emtricitabine is rapidly and extensively absorbed following oral administration with peak plasma concentrations occurring at 1 to 2 hours post-dose. Following multiple dose oral administration of emtriva to 20 HIV-infected subjects, the (mean + or - SD) steady state plasma emtricitabine peak concentration (Cmax) was 1.8 + or 0.7 ug/mL and the area under the plasma concentration-time curve over a 24-hour dosing interval (AUC) was 10.0 + or - 3.1 hr/ug/mL. The mean steady state plasma trough concentration at 24 hours post-dose was 0.09 ug/mL. The mean absolute bioavailability of emtriva was 93%.|In vitro binding of emtricitabine to human plasma proteins was <4% and independent of concentration over the range of 0.02 to 200 ug/mL. At peak plasma concentration, the mean plasma to blood drug concentration ratio was approximately 1.0 and the mean semen to plasma drug concentration ratio was approximately 4.0.|Time to peak concentration: 1 to 2 hours post dose|Emtricitabine is distributed into human milk in low concentrations.|For more Absorption, Distribution and Excretion (Complete) data for EMTRICITABINE (6 total), please visit the HSDB record page.

Emtricitabine is approximately 86% unmetabolized. Approximately 9% of a dose is metabolized to 3'-sulfoxide diastereomers, 4% to the 2'-O-glucuronide, and a minor amount is converted to 5-fluorocytosine.|The biotransformation of emtricitabine includes oxidation of the thiol moiety to form the 3'-sulfoxide diastereomers (approximately 9% of dose) and conjugation with glucuronic acid to form 2'-O-glucuronide (approximately 4% of dose). No other metabolites were identifiable. Emtricitabine is not metabolized by liver enzymes.

The half life of emtricitabine is approximately 10 hours.|The plasma emtricitabine half-life is approximately 10 hours.

Emtricitabine is a cytidine analog which, when phosphorylated to emtricitabine 5'-triphosphate, competes with deoxycytidine 5'-triphosphate for HIV-1 reverse transcriptase. As HIV-1 reverse transcriptase incorporates emtricitabine into forming DNA strands, new nucleotides are unable to be incorporated, leading to viral DNA chain termination. Inhibition of reverse transcriptase prevents transcription of viral RNA into DNA, therefore the virus is unable to incorporate its DNA into host DNA and replicate using host cell machinery. This reduces viral load.|Emtricitabine, a synthetic nucleoside analog of cytosine, is phosphorylated by cellular enzymes to form emtricitabine 5'-triphosphate. Emtricitabine 5'-triphosphate inhibits the activity of the HIV-1 reverse transcriptase by competing with the natural substrate deoxycytidine 5'-triphosphate and by being incorporated into nascent viral DNA which results in chain termination. Emtricitabine 5'-triphosphate is a weak inhibitor of mammalian DNA polymerase alpha, beta, epsilon and mitochondrial DNA polymerase gamma.

There is no known antidote to emtricitabine. ... If overdose occurs the patient should be monitored for signs of toxicity, and standard supportive treatment applied as necessary.|Hemodialysis treatment removes approximately 30% of the emtricitabine dose over a 3-hour dialysis period starting within 1.5 hours of emtricitabine dosing (blood flow rate of 400 mL/min and a dialysate flow rate of 600 mL/min). It is not known whether emtricitabine can be removed by peritoneal dialysis.|/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/|/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/|For more Antidote and Emergency Treatment (Complete) data for EMTRICITABINE (8 total), please visit the HSDB record page.

/SIGNS AND SYMPTOMS/ Lactic acidosis and severe hepatomegaly with steatosis, including fatalities, have been reported in patients receiving nucleoside reverse transcriptase inhibitors (NRTIs), including emtricitabine, in conjunction with other antiretroviral agents. Most reported cases have involved women; obesity and long-term therapy with a nucleoside analog also may be risk factors.

Beta L 2',3' dideoxy 5 fluoro 3' thiacytidine

Oral: Solution 10 mg/mL, Emtriva (Gilead).|Oral: Capsules: 200 mg Emtriva, (Gilead).|Trade name (emtricitabine): ETruvada (co-formulation tablet of emtricitabine and tenofovir disoproxyl fumarate) (Gilead Sciences Inc.)|Table: Emtricitabine Comination Preparations [Table#6936]

Human drugs -> Emtricitabine/Tenofovir disoproxil Mylan -> EMA Drug Category|Antivirals for systemic use -> Human pharmacotherapeutic group|Human drugs -> Emtricitabine/Tenofovir disoproxil Zentiva -> EMA Drug Category|Human drugs -> Atripla -> EMA Drug Category|Human drugs -> Biktarvy -> EMA Drug Category|Human drugs -> Truvada -> EMA Drug Category|Human drugs -> Descovy -> EMA Drug Category|Human drugs -> Efavirenz/Emtricitabine/Tenofovir disoproxil Krka -> EMA Drug Category|Human drugs -> Emtricitabine/Tenofovir disoproxil Krka -> EMA Drug Category|Human drugs -> Emtricitabine/Tenofovir disoproxil Krka d.d. -> EMA Drug Category|Human drugs -> Efavirenz/Emtricitabine/Tenofovir disoproxil Mylan -> EMA Drug Category|Human drugs -> Odefsey -> EMA Drug Category|Human drugs -> Symtuza -> EMA Drug Category|Antivirals for systemic use, Antivirals for treatment of HIV infections, combinations -> Human pharmacotherapeutic group|Human drugs -> Efavirenz/Emtricitabine/Tenofovir disoproxil Zentiva -> EMA Drug Category|Human drugs -> Emtriva -> EMA Drug Category|Human drugs -> Eviplera -> EMA Drug Category|Human drugs -> Genvoya -> EMA Drug Category|Human drugs -> Stribild -> EMA Drug Category|Antivirals for treatment of HIV infections, combinations, Antivirals for systemic use -> Human pharmacotherapeutic group|Human drugs -> Rare disease (orphan)|Human Drugs -> EU pediatric investigation plans|Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients|Pharmaceuticals -> Antiinfectives for systemic use -> Virustatics