AHFS Class:

• HIV Nucleoside and Nucleotide Reverse Transcriptase Inhibitors 8:18.08.20

Generic Name(s):

• Emtricitabine

Emtricitabine, an antiretroviral agent, is a human immunodeficiency virus (HIV) nucleoside reverse transcriptase inhibitor (NRTI).1

Treatment of HIV Infection

Emtricitabine is used in conjunction with other antiretroviral agents for the treatment of human immunodeficiency virus type 1 (HIV-1) infection.1

Emtricitabine is commercially available as a single-entity preparation and in various fixed-combination preparations that contain 2 or 3 additional antiretrovirals; refer to separate combination product monographs for information related to the specific uses of these products.1,230,232,233,235,243,244,245,246

Emtricitabine is commonly used as part of a dual-nucleoside reverse transcriptase inhibitor (NRTI) “backbone” of a fully suppressive antiretroviral regimen; consult guidelines for the most current information on recommended regimens.200,201,202 Selection of an initial antiretroviral regimen should be individualized based on factors such as virologic efficacy, toxicity, pill burden, dosing frequency, drug-drug interaction potential, resistance test results, comorbid conditions, access, and cost.200,201,202

Clinical Experience

Antiretroviral-naïve Adults and Adolescents

Safety and efficacy of a regimen of efavirenz, emtricitabine, and tenofovir disoproxil fumarate (DF) are based on results of a randomized, open-label study designed to demonstrate noninferiority of this regimen compared with a regimen of efavirenz, zidovudine, and lamivudine (study 934).1,23 In this study, 511 antiretroviral-naïve HIV-infected patients (mean age 38 years, 86% male, 59% white, 23% Black, median baseline plasma HIV-1 RNA level 5.01 log₁₀ copies/mL [range: 3.56-6.54 log₁₀ copies/mL], mean baseline CD4⁺ T-cell count 245 cells/mm³) were randomized to receive a once-daily regimen of efavirenz, emtricitabine, and tenofovir DF or a regimen of efavirenz once daily with the fixed combination of lamivudine and zidovudine (lamivudine/zidovudine; Combivir^®) twice daily.1,23 The primary measure used to assess noninferiority of the regimen of efavirenz, emtricitabine, and tenofovir DF to the regimen of efavirenz and lamivudine/zidovudine was plasma HIV-1 RNA levels at week 48, specifically, the number of patients with HIV-1 RNA levels <400 copies/mL.23 The 487 patients without baseline resistance to efavirenz who underwent randomization and received treatment were the predefined population used for the primary endpoint analysis.1,23

Through week 48, the regimen of efavirenz, emtricitabine, and tenofovir DF met the criteria for noninferiority to the regimen of efavirenz and lamivudine/zidovudine.23 At week 48, 84 or 80% of adults receiving the efavirenz, tenofovir DF, and emtricitabine regimen and 73 or 70% of adults receiving the efavirenz and lamivudine/zidovudine regimen had plasma HIV-1 RNA levels <400 or 50 copies/mL, respectively.1,23 At week 48, increases in CD4⁺ T-cell counts were greater in patients receiving the efavirenz, emtricitabine, and tenofovir DF regimen (mean increase of 190 cells/mm³) than in those receiving the efavirenz and lamivudine/zidovudine regimen (mean increase of 158 cells/mm³).1,23 Virologic failure (i.e., individuals who failed to achieve virologic suppression or experienced rebound after achieving virologic suppression) was reported in 2% of those receiving efavirenz, emtricitabine, and tenofovir DF and in 4% of those receiving efavirenz and lamivudine/zidovudine at week 48.1

At 144 weeks, 64% of adults receiving the efavirenz, emtricitabine, and tenofovir DF regimen and 56% of those receiving the efavirenz and lamivudine/zidovudine regimen had plasma HIV-1 RNA levels <50 copies/mL.1 The mean increase in CD4⁺ T-cell count from baseline in these groups was 312 and 271 cells/mm³, respectively, at 144 weeks.1

Trial 301A was a 48-week, double-blind, active-control study evaluating emtricitabine versus stavudine, both in combination with a background regimen containing didanosine and efavirenz, in 571 antiretroviral-naïve adults (mean CD4⁺ T-cell count of 318 cells/mm³ and median HIV-1 RNA levels of 4.9 log₁₀ copies/mL).1,503 The primary outcome was persistent virologic response, considered an HIV1-RNA level <400 or 50 copies/mL.503 At 48 weeks, a persistent virologic response (<400 copies/mL) was seen in 81 or 68% of patients given emtricitabine or stavudine, respectively.1 An HIV-1 RNA level <50 copies/mL was achieved in 78 or 59% of patients given emtricitabine or stavudine, respectively.1 Virologic failure (i.e., individuals who failed to achieve virologic suppression or experienced rebound after achieving virologic suppression) was reported in 3% of those receiving the emtricitabine-containing regimen and in 11% of those receiving the stavudine-containing regimen at week 48.1 Administration of the emtricitabine-containing regimen resulted in a mean increase in CD4⁺ T-cell counts of 168 cells/mm³ ; administration of the stavudine-containing regimen resulted in a mean increase in CD4⁺ T-cell counts of 134 cells/mm³.1

Antiretroviral-experienced Adults and Adolescents

Emtricitabine has been evaluated in a randomized, open-label, multicenter study (Trial 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 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.1 504 Patients in this study were randomized to receive emtricitabine in conjunction with stavudine or zidovudine and a protease inhibitor (PI) or non-nucleoside reverse transcriptase inhibitor (NNRTI) or to continue their lamivudine-containing background regimen (i.e., lamivudine in conjunction with stavudine or zidovudine and a PI or NNRTI).1

At week 48, 77 or 67% of adults receiving the regimen that included emtricitabine and 82 or 72% of those receiving the regimen that included lamivudine had plasma HIV-1 RNA levels <400 or 50 copies/mL, respectively.1 Virologic failure was reported in 7% of those receiving the emtricitabine-containing regimen and in 8% of those receiving the lamivudine-containing regimen at week 48.1 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/mm³.1

Pediatric Patients

Safety and efficacy of emtricitabine in conjunction with other antiretrovirals have been evaluated in 3 open-label, nonrandomized studies in patients 3 months to 21 years of age (mean age 7.9 years, 49% male, 15% white, 24% Hispanic, 61% Black, median baseline plasma HIV-1 RNA level 4.6 log₁₀ copies/mL, mean baseline CD4⁺ T-cell count 745 cells/mm³) who were treatment naïve or treatment experienced (i.e., virologic suppression on a lamivudine-containing regimen; emtricitabine substituted for lamivudine).1 At week 48, 86 or 73% of children had plasma HIV-1 RNA levels <400 or 50 copies/mL, respectively.1 The mean increase in CD4⁺ T-cell counts was 232 cells/mm³.1

Clinical Perspective

Therapeutic options for the treatment and prevention of human immunodeficiency virus (HIV) infection and recommendations concerning the use of antiretrovirals are continuously evolving.200,201,202 Antiretroviral therapy is recommended for all individuals with HIV regardless of CD4⁺ T-cell counts, and should be initiated as soon as possible after diagnosis of HIV and continued indefinitely.200,201,202 The primary goals of antiretroviral therapy are to achieve and maintain durable suppression of HIV viral load (as measured by plasma HIV-1 RNA levels) to a level below which drug-resistance mutations cannot emerge (i.e., below detectable limits), restore and preserve immunologic function, reduce HIV-related morbidity and mortality, improve quality of life, and prevent transmission of HIV.200,202 While the most appropriate antiretroviral regimen cannot be defined for each clinical scenario, the US Department of Health and Human Services (HHS) Panel on Antiretroviral Guidelines for Adults and Adolescents, HHS Panel on Antiretroviral Therapy and Medical Management of Children Living with HIV, and HHS Panel on Treatment of Pregnant Women with HIV Infection and Prevention of Perinatal Transmission, have developed comprehensive guidelines that provide information on selection and use of antiretrovirals for the treatment or prevention of HIV infection.200,201,202 Because of the complexity of managing patients with HIV, it is recommended that clinicians with HIV expertise be consulted when needed.200,201,202

The use of combination antiretroviral regimens that generally include 3 drugs from 2 or more drug classes is currently recommended to achieve viral suppression.200,201 In both treatment-naïve adults and children, an initial antiretroviral regimen generally consists of 2 NRTIs administered in combination with a third active antiretroviral drug from 1 of 3 drug classes: an integrase strand transfer inhibitor (INSTI), a NNRTI, or a PI with a pharmacokinetic enhancer (also known as a booster; the 2 drugs used for this purpose are cobicistat and ritonavir).200,201,202 Selection of an initial antiretroviral regimen should be individualized based on factors such as virologic efficacy, toxicity, pill burden, dosing frequency, drug-drug interaction potential, resistance-test results, comorbid conditions, access, and cost.200,201,202 In patients with comorbid infections (e.g., hepatitis B, tuberculosis), regimen selection should also consider the potential for activity against other present infections and timing of initiation relative to other anti-infective regimens.200

Emtricitabine, an NRTI, is commonly used as part of a dual-NRTI “backbone” of a fully suppressive antiretroviral regimen.200 In the 2023 HHS adult and adolescent HIV treatment guideline, emtricitabine is included in various antiretroviral regimens.200 Some of these emtricitabine-containing regimens are listed among recommended initial regimens in certain clinical situations, and include the following: bictegravir/tenofovir alafenamide/emtricitabine or dolutegravir/tenofovir (alafenamide or DF)/emtricitabine (for patients who do not have a history of using long-acting cabotegravir as preexposure prophylaxis); boosted darunavir/tenofovir (alafenamide or DF)/emtricitabine (for individuals with prior exposure to cabotegravir pending results of INSTI genotypic testing); and rilpivirine/tenofovir (alafenamide or DF)/emtricitabine (if HIV-1 RNA <100,000 copies/mL and CD4⁺ T-cell count >200 cells/mm³).200

In the 2023 HHS pediatric HIV treatment guideline, emtricitabine is included in various antiretroviral regimens.201 Emtricitabine/tenofovir alafenamide/bictegravir is recommended as a preferred INSTI-based regimen for children ≥2 years of age and weighing ≥14 kg.201 Emtricitabine/tenofovir alafenamide is recommended as a preferred dual NRTI-combination in children and adolescents weighing ≥14 kg when used with an INSTI or an NNRTI.201 Abacavir/emtricitabine is recommended as a preferred dual-NRTI combination in children ≥3 months and for full-term infants from birth to <3 months of age.201

In the 2023 HHS perinatal HIV treatment guideline, emtricitabine is included as a preferred NRTI for initial antiretroviral treatment during pregnancy, restarting antiretroviral treatment during pregnancy, as a new treatment regimen if an existing regimen is not well tolerated or not fully suppressive, or prior to pregnancy.202 Emtricitabine/tenofovir DF started as preexposure prophylaxis prior to pregnancy can be continued throughout pregnancy.202

Preexposure Prophylaxis for Prevention of HIV-1 Infection

Emtricitabine is used in combination with tenofovir DF or alafenamide for preexposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV-1 infection in at-risk HIV-negative adults and adolescents; refer to the fixed-combination product monograph for detailed information on this use.230,245

Clinical Perspective

In the 2021 CDC HIV preexposure prophylaxis guideline, several PrEP regimens are recommended based on an individual patient's characteristics to reflect the populations evaluated in pivotal clinical studies.1001 Options for PrEP include oral emtricitabine/tenofovir DF in sexually active adults and adolescents and men and women who inject drugs, oral emtricitabine/tenofovir alafenamide in men and transgender women who have sex with men, and intramuscular cabotegravir in adults and adolescents.1001

Postexposure Prophylaxis following Occupational Exposure to HIV

Emtricitabine is used in conjunction with other antiretrovirals as part of preferred and alternative regimens for postexposure prophylaxis of HIV infection following occupational exposure† (PEP) in health-care personnel and other individuals exposed via percutaneous injury (e.g., needlestick, cut with sharp object) or mucous membrane or nonintact skin (e.g., chapped, abraded, dermatitis) contact with blood, tissue, or other body fluids that might contain HIV.199

Clinical Perspective

The US Public Health Service (USPHS) states that the preferred regimen for PEP following an occupational exposure to HIV is a 3-drug regimen of raltegravir used in conjunction with emtricitabine and tenofovir DF (may be administered as the fixed combination emtricitabine/tenofovir DF; Truvada^®).199 These experts recommend several alternative regimens that include an INSTI, NNRTI, or PI and 2 NRTIs (dual NRTIs).199 The preferred dual NRTI option for use in PEP regimens is emtricitabine and tenofovir DF (may be administered as the fixed combination emtricitabine/tenofovir DF; Truvada^®); alternative dual NRTIs are tenofovir DF and lamivudine, lamivudine and zidovudine (may be administered as the fixed combination lamivudine/zidovudine; Combivir^®), or zidovudine and emtricitabine.199

Because management of occupational exposures to HIV is complex and evolving, consultation with an infectious diseases specialist, clinician with expertise in administration of antiretroviral agents, and/or the National Clinicians' Postexposure Prophylaxis Hotline (PEPline at 888-448-4911) is recommended whenever possible.199 However, initiation of PEP should not be delayed while waiting for expert consultation.199

Postexposure Prophylaxis following Nonoccupational Exposure to HIV

Emtricitabine is used in conjunction with other antiretrovirals as part of preferred and alternative regimens for postexposure prophylaxis of HIV infection following nonoccupational exposure† (nPEP) in individuals exposed to blood, genital secretions, or other potentially infectious body fluids that might contain HIV when that exposure represents a substantial risk for HIV transmission.198

Clinical Perspective

When nPEP is indicated following a nonoccupational exposure to HIV, the US Centers for Disease Control and Prevention (CDC) states that the preferred regimen in adults and adolescents 13 years of age or older with normal renal function is either raltegravir or dolutegravir used in conjunction with emtricitabine and tenofovir DF (administered as the fixed combination emtricitabine/tenofovir DF; Truvada^®).198 The alternative nPEP regimen recommended in these patients is ritonavir-boosted darunavir used in conjunction with emtricitabine/tenofovir DF (Truvada^®).198

Consultation with an infectious diseases specialist, clinician with expertise in administration of antiretroviral agents, and/or the National Clinicians' Postexposure Prophylaxis Hotline (PEPline at 888-448-4911) is recommended if nPEP is indicated in certain exposed individuals (e.g., pregnant women, children, those with medical conditions such as renal impairment) or if an antiretroviral regimen not included in the CDC guidelines is being considered, the source virus is known or likely to be resistant to antiretrovirals, or the healthcare provider is inexperienced in prescribing antiretrovirals.198 However, initiation of nPEP should not be delayed while waiting for expert consultation.198

General

Pretreatment Screening

• Test for hepatitis B virus (HBV) infection prior to or upon initiation of emtricitabine (single entity or fixed combinations).1,230,232,233,235,243,244,245,246

Patient Monitoring

• If emtricitabine (single entity or fixed combinations) is used in patients coinfected with human immunodeficiency virus (HIV) and HBV, closely monitor hepatic function (using both clinical and laboratory follow-up) for at least several months after discontinuation of therapy.1,230,232,233,235,243,244,245,246

Administration

Emtricitabine is administered orally once daily without regard to meals.1

Single-entity emtricitabine is commercially available as 200-mg capsules or an oral solution containing 10 mg/mL.1

Emtricitabine is also commercially available in the following fixed-combination tablets for oral use: emtricitabine/tenofovir DF (Truvada^®), efavirenz/emtricitabine/tenofovir DF (Atripla^®), emtricitabine/rilpivirine/tenofovir DF (Complera^®), elvitegravir/cobicistat/emtricitabine/tenofovir DF (Stribild^®), elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (Genvoya^®), emtricitabine/rilpivirine/tenofovir alafenamide (Odefsey^®), emtricitabine/tenofovir alafenamide (Descovy^®), and bictegravir/emtricitabine/tenofovir alafenamide (Biktarvy^®).230,232,233,235,243,244,245,246 See the full prescribing information for administration of each of these combination products.230,232,233,235,243,244,245,246

Emtricitabine is used in conjunction with other antiretrovirals.1 Single-entity emtricitabine should not be used concomitantly with any other emtricitabine-containing preparations.1

Store capsules at 25°C (excursions permitted to 15-30°C).1

Store oral solution at 2-8°C.1 For patient use, store at 25°C (excursions permitted to 15-30°C); use within 3 months.1

Dosage

Emtricitabine capsules and oral solution are not bioequivalent.1 Bioavailability of the oral solution is 80% relative to that of the capsule.1

Pediatric Dosage

Treatment of HIV Infection

The usual dosage of emtricitabine for the treatment of HIV-1 infection in infants 0-3 months of age is 3 mg/kg (as the oral solution containing 10 mg/mL) once daily.1

For the treatment of HIV-1 infection in pediatric patients 3 months to 17 years of age, the usual dosage of emtricitabine is 6 mg/kg (as the oral solution containing 10 mg/mL) once daily (maximum 240 mg daily).1 Alternatively, children weighing more than 33 kg who can swallow an intact capsule may receive one 200-mg capsule once daily.1

Adult Dosage

Treatment of HIV Infection

For the treatment of HIV-1 infection in adults 18 years of age or older, the usual dosage of emtricitabine is 200 mg (as the capsule) once daily.1 Alternatively, when the oral solution containing 10 mg/mL is used, the usual dosage of emtricitabine is 240 mg (24 mL) once daily.1

Preexposure Prophylaxis for Prevention of HIV-1 Infection

The fixed dose combination containing emtricitabine/tenofovir DF (Truvada^®) is used for preexposure prophylaxis (PrEP) for prevention of HIV-1 infection.230 For PrEP, the usual dosage of emtricitabine is 200 mg once daily in conjunction with other antiretrovirals; see the full prescribing information for specific dosage of emtricitabine/tenofovir DF (Truvada^®).230

Postexposure Prophylaxis following Occupational Exposure to HIV

For postexposure prophylaxis of HIV infection following occupational exposure† (PEP) in health-care personnel or other individuals, the recommended dosage of emtricitabine is 200 mg (as the capsule) once daily.199 Emtricitabine usually is used with tenofovir DF or zidovudine in conjunction with a recommended HIV integrase strand transferase inhibitor (INSTI), nonnucleoside reverse transcriptase inhibitor (NNRTI), or HIV protease inhibitor (PI).199

The preferred dual nucleoside transcriptase inhibitor (NRTI) backbone option for use in PEP† regimens is emtricitabine and tenofovir DF commonly administered as the fixed-dose combination of emtricitabine/tenofovir DF (Truvada^®).199 See the full prescribing information for specific dosage of emtricitabine/tenofovir DF (Truvada^®).230

Postexposure Prophylaxis following Nonoccupational Exposure to HIV

For postexposure prophylaxis of HIV infection following nonoccupational exposure† (nPEP) when the exposure represents a substantial risk for HIV transmission, the usual adult dosage of emtricitabine is 200 mg once daily in conjunction with other antiretrovirals.198 Emtricitabine usually is used in conjunction with tenofovir DF and a recommended or alternative INSTI, PI, or NNRTI.198

The preferred dual NRTI backbone option for use in nPEP† regimens is emtricitabine/tenofovir DF, commonly administered as the fixed-dose combination of emtricitabine/tenofovir DF (Truvada^®).198 See the full prescribing information for specific dosage of emtricitabine/tenofovir DF (Truvada^®).230

Special Populations

Hepatic Impairment

While the pharmacokinetics of emtricitabine have not been specifically studied in patients with hepatic impairment, the drug is not metabolized by liver enzymes and clinically important changes in emtricitabine metabolism are not expected if the drug is used in patients with hepatic impairment.1

Renal Impairment

When emtricitabine is used for the treatment of HIV-1 infection in adults, dosage should be adjusted in those with a creatinine clearance less than 50 mL/minute (see Table 1).1 The manufacturer states that data are insufficient to make emtricitabine dosage recommendations for treatment of HIV-1 infection in pediatric patients with renal impairment.1

Geriatric Patients

The manufacturer makes no specific dosage recommendations for geriatric patients, but recommends cautious dosage selection due to the greater frequency of decreased hepatic, renal, and/or cardiac function, and of concomitant disease and drug therapy.1

Contraindications

• Known hypersensitivity to the drug or any ingredient in the formulation.1

Warnings/Precautions

Warnings

Severe Acute Exacerbation of Hepatitis B in Patients Coinfected with Human Immunodeficiency Virus Type 1 (HIV-1) and Hepatitis B Virus (HBV)

A boxed warning regarding the risk of acute exacerbations of HBV infection after emtricitabine discontinuation in patients coinfected with HIV-1 and HBV is included in the prescribing information for emtricitabine.1 Prior to initiating emtricitabine (single-entity or fixed-combination preparations) for treatment of HIV-1 infection, the patient should be tested for chronic HBV.1,230,232,233,235,243,244,245,246

Severe acute exacerbations of HBV infection have been reported in patients coinfected with HIV-1 and HBV following discontinuance of emtricitabine.1 In some of these patients, exacerbations of HBV have been associated with hepatic decompensation and hepatic failure.1 Hepatic function should be closely monitored with clinical and laboratory follow-up for at least several months after stopping emtricitabine therapy (single-entity or fixed-combination preparations) in HIV-infected patients coinfected with HBV.1,230,232,233,235,243,244,245,246 If appropriate, initiation of treatment for HBV infection may be warranted.1,230,232,233,235,243,244,245,246

Other Warnings/Precautions

Immune Reconstitution Syndrome

Immune reconstitution syndrome has been reported in HIV-infected patients receiving multiple-drug antiretroviral therapy, including emtricitabine.1 During the initial phase of treatment, HIV-infected patients whose immune systems respond to antiretroviral therapy may develop an inflammatory response to indolent or residual opportunistic infections (e.g., Mycobacterium avium complex [MAC], M. tuberculosis , cytomegalovirus [CMV], Pneumocystis jirovecii [formerly P. carinii ]); such response may necessitate further evaluation and treatment.1

Autoimmune disorders (e.g., Graves' disease, polymyositis, Guillain-Barré syndrome) have also been reported to occur in the setting of immune reconstitution; however, the time to onset is more variable and can occur many months after initiation of antiretroviral therapy.1

Lactic Acidosis and Severe Hepatomegaly with Steatosis

Lactic acidosis and severe hepatomegaly with steatosis, including fatalities, have been reported in patients receiving HIV nucleoside reverse transcriptase inhibitors (NRTIs), including emtricitabine with or without other antiretroviral agents.1

Emtricitabine (single-entity or fixed-combination preparations) should be discontinued 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).1,230,232,233,235,243,244,245,246

Precautions Related to Use of Fixed Combinations

When emtricitabine is used in fixed combination with other drugs, the cautions, precautions, contraindications, and drug interactions associated with each drug in the fixed combination must be considered.1,230,232,233,235,243,244,245,246

Dosage Adjustment in Patients with New Onset or Worsening Renal Impairment

Reduce dosage in patients with renal impairment; emtricitabine is principally eliminated by the kidney.1

Specific Populations

Pregnancy

The Antiretroviral Pregnancy Registry (APR) monitors pregnancy outcomes in women exposed to emtricitabine during pregnancy.1 Clinicians are encouraged to register patients in the APR by calling 800-258-4263 or visiting [Web].1

Based on prospective reports to the APR, the overall risk of birth defects among live births with first-trimester exposure to emtricitabine was 2.4%, and 2.3% with second/third trimester exposure, compared to the background rate for major birth defects of 2.7% in the United States reference population of the Metropolitan Atlanta Congenital Defects Program (MACDP).1 Limitations of using an external comparator (i.e., MACDP) include differences in populations and methodology, and confounding due to the underlying disease.1 The rate of miscarriage for individual drugs is not reported in the APR.1

Additional observational data have not shown an increase in major malformations with emtricitabine exposure in pregnancy.1

Lactation

Based on published data, emtricitabine is distributed into human milk.1 It is not known whether emtricitabine affects milk production or has effects on the breast-fed infant.1

Because of the risk of adverse effects in the infant and the risk of HIV transmission, HIV-infected women should not breast-feed infants.1

Pediatric Use

Safety and efficacy of emtricitabine have been established for treatment of HIV-1 infection in children 3 months of age and older.1

The pharmacokinetics and safety of emtricitabine were evaluated in a dose-finding study in 20 neonates born to HIV-infected mothers.1 These neonates received zidovudine prophylaxis for 6 weeks.1 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.1 This dosage was not associated with any safety issues.1 Systemic exposure (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.1 All neonates were HIV-1 negative at the end of the study (6 months postpartum); the efficacy of emtricitabine for the prevention or treatment of HIV was not determined.1

Geriatric Use

Experience in those 65 years of age or older is insufficient to determine whether they respond differently to emtricitabine than younger adults.1 Dosage should be selected with caution because of age-related decreases in hepatic, renal, and/or cardiac function and potential for concomitant disease and drug therapy.1

Hepatic Impairment

Emtricitabine has not been studied in patients with hepatic impairment; impact of hepatic impairment is expected to be minimal.1

Renal Impairment

Emtricitabine is principally eliminated by the kidney and the pharmacokinetics of the drug are altered in patients with renal impairment.1 Maximum serum concentration and AUC were increased in adults with creatinine clearance less than 50 mL/minute or in those with end-stage renal disease requiring dialysis.1 The effects of renal impairment on the pharmacokinetics of emtricitabine in pediatric patients are not known.1 If renal function is impaired, dosage of single-entity emtricitabine must be adjusted based on creatinine clearance.1

Common Adverse Effects

The most common adverse reactions experienced in at least 10% of adult patients with HIV-1 treated with emtricitabine include headache, GI effects (diarrhea, nausea), fatigue, dizziness, depression, insomnia, abnormal dreams, rash, abdominal pain, asthenia, increased cough, and rhinitis.1 Adverse effects reported in children 3 months to 21 years of age receiving emtricitabine in clinical studies have been similar to those in adults, with the exception of a higher frequency of hyperpigmentation.1

In vitro studies indicate that emtricitabine does not inhibit cytochrome P-450 (CYP) isoenzymes 1A2, 2A6, 2B6, 2C9, 2C19, 2D6, or 3A4.1 Emtricitabine does not inhibit glucuronosyltransferase (uridine diphosphoglucuronosyltransferase, UDP-glucuronate β-d-glucuronosyltransferase [acceptor-unspecific]), an enzyme responsible for glucuronidation.1 The following drug interactions are based on studies using emtricitabine.1 When a fixed combination containing emtricitabine is used, interactions associated with each drug in the fixed combination should be considered.230,232,233,235,244,245,246

Drugs Metabolized by Hepatic Microsomal Enzymes

Pharmacokinetic interactions between emtricitabine and drugs metabolized by hepatic microsomal enzymes are unlikely.1

Drugs Metabolized by Uridine Diphosphate-glucuronosyltransferase

Pharmacokinetic interactions between emtricitabine and drugs metabolized by uridine diphosphate-glucuronosyltransferase are unlikely.1 Emtricitabine does not inhibit glucuronosyltransferase (uridine diphosphoglucuronosyltransferase, UDP-glucuronate β-d-glucuronosyltransferase [acceptor-unspecific]), an enzyme responsible for glucuronidation.1

Antiretroviral Agents

HIV Nonnucleoside Reverse Transcriptase Inhibitors (NNRTIs)

No in vitro evidence of antagonistic antiretroviral effects between emtricitabine and NNRTIs (e.g., delavirdine, efavirenz, nevirapine).1

HIV Nucleoside and Nucleotide Reverse Transcriptase Inhibitors (NRTIs)

No in vitro evidence of antagonistic antiretroviral effects between emtricitabine and nucleoside and HIV nucleotide reverse transcriptase inhibitors (NRTIs) (e.g., abacavir, lamivudine, tenofovir disoproxil fumarate [DF], zidovudine).1

Tenofovir

No clinically important pharmacokinetic interactions between emtricitabine and tenofovir DF.1

Zidovudine

Although not considered clinically important, concomitant use of emtricitabine (200 mg once daily for 7 days) and zidovudine (300 mg twice day for 7 days) increased zidovudine peak plasma concentrations and area under the concentration-time curve (AUC) by 17 and 13%, respectively, but did not affect emtricitabine peak plasma concentrations or AUC.1

HIV Protease Inhibitors (PIs)

No in vitro evidence of antagonistic antiretroviral effects between emtricitabine and HIV PIs (e.g., nelfinavir, ritonavir, saquinavir).1

Famciclovir

No clinically important pharmacokinetic interactions between emtricitabine and famciclovir.1

Description

Emtricitabine, a synthetic antiretroviral agent, is a human immunodeficiency virus (HIV) nucleoside reverse transcriptase inhibitor (NRTI).1 Emtricitabine is inactive until converted intracellularly to an active 5'-triphosphate metabolite.1 Following conversion to the pharmacologically active metabolite, the drug inhibits replication of human retroviruses by interfering with viral RNA-directed DNA polymerase (reverse transcriptase).1

The pharmacokinetics of emtricitabine in healthy individuals are similar to that in individuals with human immunodeficiency virus type 1 (HIV-1) infection.1 Following oral administration, emtricitabine is rapidly and extensively absorbed; peak plasma concentrations of the drug are attained within 1-2 hours.1 The mean absolute oral bioavailability of emtricitabine capsules is 93%.1 The mean absolute oral bioavailability of emtricitabine oral solution is 75%.1 Food does not appear to have a clinically important effect on emtricitabine absorption.1 Administration of emtricitabine capsules with food (approximately 1000 kcal high-fat meal) did not affect the area under the concentration-time curve (AUC) of emtricitabine, but resulted in a 29% decrease in peak plasma concentrations of the drug.1 Administration of emtricitabine oral solution with a high-fat or low-fat meal did not affect the AUC or peak plasma concentrations of emtricitabine.1 Pharmacokinetics in pediatric patients 3 months to 17 years of age receiving recommended emtricitabine dosage (6 mg/kg daily [up to 240 mg daily] as the oral solution or 200-mg capsule once daily) is similar to that reported in adults receiving 200 mg daily.1 The AUC reported in neonates receiving emtricitabine 3 mg/kg daily for 4 days is similar to that reported in children 3 months to 17 years of age receiving the recommended dosage.1 Emtricitabine is less than 4% bound to plasma proteins; binding is independent of drug concentrations over the range of 0.01-200 mcg/mL.1 Emtricitabine is distributed into human milk in low concentrations.1 Emtricitabine undergoes oxidation and conjugation with glucuronic acid.1 Intracellularly, emtricitabine is phosphorylated and converted by cellular enzymes to the active metabolite, emtricitabine 5'-triphosphate.1 Emtricitabine is eliminated in urine (86%) and feces (14%).1 The drug is eliminated in urine by glomerular filtration and active tubular secretion; 13% of a dose is recovered in urine as 3 metabolites.1 Emtricitabine is removed by hemodialysis; it is not known whether the drug is removed by peritoneal dialysis.1 The plasma elimination half-life of emtricitabine is approximately 10 hours.1 Peak plasma concentrations and AUC of emtricitabine are increased in adults with renal impairment (creatinine clearance less than 50 mL/minute or end-stage renal disease requiring dialysis) due to reduced renal clearance of the drug.1 Dosage adjustments are needed.1 The pharmacokinetics of emtricitabine are not affected by race or gender.1

Emtricitabine is active against HIV type 1 (HIV-1) and also has some in vitro activity against HIV type 2 (HIV-2).1 HIV-1 strains with reduced susceptibility to emtricitabine can be produced in vitro and strains with reduced susceptibility to the drug have emerged during emtricitabine therapy.1 These strains have contained a M184V/I mutation.1 HIV-1 strains with the M184V/I mutation have been resistant to lamivudine but retained susceptibility to didanosine, tenofovir, zidovudine, delavirdine, efavirenz, and nevirapine.1

Advice to Patients

• Inform patients of the importance of reading patient information provided by the manufacturer.1
• Advise patients that lactic acidosis and severe hepatomegaly with steatosis, including fatalities, have occurred in patients receiving emtricitabine or other NRTIs, in conjunction with other antiretrovirals.1 Advise patients to inform their clinician if symptoms suggestive of lactic acidosis or hepatotoxicity (e.g., nausea, vomiting, unusual/unexpected stomach discomfort, weakness) occur.1
• Inform patients that testing for hepatitis B virus (HBV) infection is recommended before antiretroviral therapy is initiated, and that all patients with HBV will require close medical follow-up for several months following emtricitabine discontinuation to monitor for hepatitis exacerbations.1 Advise patients to not discontinue emtricitabine without first informing their clinician.1 Also advise patients that severe acute exacerbations of HBV infection have been reported following discontinuance of emtricitabine (single-entity or fixed-combination preparations) in HIV-infected patients coinfected with HBV.1
• Inform patients that in those with advanced HIV infection, after anti-HIV treatment is initiated, signs and symptoms of inflammation from prior infections can occur, most likely due to an improvement in the body's immune response.1 Also advise patients to inform their clinician if symptoms of infection develop.1
• Advise patients to inform their clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary and herbal products, as well as concomitant medical problems such as renal impairment.1
• Advise women to inform their clinicians if they are or plan to become pregnant or plan to breast-feed.1 Inform patients that an antiretroviral pregnancy registry is available to monitor outcomes of babies born to women taking emtricitabine during pregnancy.1 Advise HIV-infected women not to breast-feed due to the risk of passing the HIV-1 virus to the baby.1
• Inform patients of other precautionary information.1

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Only references cited for selected revisions after 1984 are available electronically.

1. Gilead Sciences. Emtriva^® (emtricitabine) capsules and oral solution prescribing information. Foster City, CA; 2018 Dec.

23. Gallant JE, DeJesus E, Arribas JR et al. Tenofovir DF, emtricitabine, and efavirenz vs. zidovudine, lamivudine, and efavirenz for HIV. N Engl J Med . 2006; 354:251-60. [PubMed 16421366]

198. Centers for Disease Control and Prevention. Updated guidelines for antiretroviral postexposure prophylaxis after sexual, injection drug use, or other nonoccupational exposure to HIV - United States, 2016. From HHS AIDS Information website. Updates may be available at HIV.gov website [Web]

199. Kuhar DT, Henderson DK, Struble KA et al. Updated US Public Health Service guidelines for the management of occupational exposures to human immunodeficiency virus and recommendations for postexposure prophylaxis. Infect Control Hosp Epidemiol . 2013; 34:875-92. [PubMed 23917901]

200. Panel on Antiretroviral Guidelines for Adults and Adolescents, US Department of Health and Human Services (HHS). Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents (March 23, 2023). Updates may be available at HIV.gov website. [Web]

201. Panel on Antiretroviral Therapy and Medical Management of HIV-infected Children, US Department of Health and Human Services (HHS). Guidelines for the use of antiretroviral agents in pediatric HIV infection (January 31, 2023). Updates may be available at HIV.gov website. [Web]

202. Panel on Treatment of HIV-Infected Pregnant Women and Prevention of Perinatal Transmission, US Department of Health and Human Services (HHS). Recommendations for use of antiretroviral drugs in pregnant HIV-1-infected women for maternal health and interventions to reduce perinatal HIV transmission in the United States (January 31, 2023). Updates may be available at HIV.gov website. [Web]

230. Gilead Sciences. Truvada^® (emtricitabine/tenofovir disoproxil fumarate) tablets prescribing information. Foster City, CA; 2020 June.

232. Gilead Sciences. Atripla^® (efavirenz/emtricitabine/tenofovir disoproxil fumarate) tablets prescribing information. Foster City, CA; 2021 Dec.

233. Gilead Sciences. Complera^® (emtricitabine/rilpivirine/tenofovir disoproxil fumarate) tablets prescribing information. Foster City, CA; 2019 Nov.

235. Gilead Sciences. Stribild^® (elvitegravir, cobicistat, emtricitabine, tenofovir disoproxil fumarate) tablets prescribing information. Foster City, CA; 2021 Sep.

243. Gilead Sciences. Genvoya^® (elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide) tablets prescribing information. Foster City, CA; 2022 Jan.

244. Gilead Sciences. Odefsey^® (emtricitabine, rilpivirine, and tenofovir alafenamide) tablets prescribing information. Foster City, CA. 2021Sep.

245. Gilead Sciences. Descovy^® (emtricitabine and tenofovir alafenamide) tablets prescribing information. Foster City, CA. 2022Jan.

246. Gilead Sciences. Biktarvy^® (bictegravir/emtricitabine/tenofovir alafenamide) tablets prescribing information. Foster City, CA; 2022 Oct.

503. Saag M, Cahn P, Raffi F et al. Efficacy and safety of emtricitabine vs stavudine in combination therapy in antiretroviral-naïve patients: a randomized trial. JAMA . 2004;292(2):180-189.

504. Benson C, van der Horst C, LaMarca A et al. A randomized study of emtricitabine and lamivudine in stably suppressed patients with HIV. AIDS . 2004;18:2269-2276.

1001. US Public Health Service. Preexposure prophylaxis for the prevention of HIV infection in the United States - 2021 Update. A clinical practice guideline. From CDC website. [Web]