Emtricitabine (Monograph)

Brand name: Emtriva
Drug class: HIV Nucleoside and Nucleotide Reverse Transcriptase Inhibitors

Medically reviewed by Drugs.com on Jun 10, 2024. Written by ASHP.

Introduction

Antiretroviral; HIV nucleoside reverse transcriptase inhibitor (NRTI).

Uses for Emtricitabine

Treatment of HIV Infection

Treatment of HIV-1 infection; used in conjunction with other antiretrovirals.

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.

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. 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.

Preexposure Prophylaxis for Prevention of HIV-1 Infection (PrEP)

Used in fixed combination with tenofovir disoproxil fumarate (DF) or tenfovir alafenamide for pre-exposure 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.

Guideline-recommended 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 IM cabotegravir in adults and adolescents.

Postexposure Prophylaxis following Occupational Exposure to HIV (PEP)

Used in conjunction with other retrovirals as part of preferred and alternative regimens for postexposure prophylaxis of HIV infection following occupational exposure^{† [off-label]} (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.

USPHS recommends 3-drug regimen of raltegravir in conjunction with emtricitabine and tenofovir DF as the preferred regimen for PEP following occupational exposures to HIV. Several alternative regimens that include an integrase strand transfer inhibitor (INSTI), nonnucleoside reverse transcriptase inhibitor (NNRTI), or protease inhibitor (PI) and 2 NRTIs (dual NRTIs) also recommended. Preferred dual NRTI option for PEP regimens is emtricitabine and tenofovir DF (may be given as emtricitabine/tenofovir DF; Truvada); alternative dual NRTI options are tenofovir DF and lamivudine, lamivudine and zidovudine (may be given as lamivudine/zidovudine; Combivir), or zidovudine and emtricitabine.

Postexposure Prophylaxis following Nonoccupational Exposure to HIV (nPEP)

Used in conjunction with other antiretrovirals as part of preferred and alternative regimens forpostexposure prophylaxis of HIV infection following nonoccupational exposure^{† [off-label]} (nPEP) in individuals exposed to blood, genital secretions, or other potentially infectious body fluids that might contain HIV when the exposure represents a substantial risk for HIV transmission.

When nPEP indicated in adults and adolescents ≥13 years of age with normal renal function, CDC states preferred regimen is either raltegravir or dolutegravir used in conjunction with emtricitabine and tenofovir DF (given as emtricitabine/tenofovir DF; Truvada); alternative regimen recommended in these patients is ritonavir-boosted darunavir used in conjunction with emtricitabine/tenofovir DF (Truvada).

Emtricitabine Dosage and Administration

General

Pretreatment Screening

• Test for hepatitis B virus (HBV) infection prior to or upon initiation of emtricitabine (single entity or fixed combinations).

Patient Monitoring

• If emtricitabine (single entity or fixed combinations) used in patients coinfected with HIV and HBV, closely monitor hepatic function (using both clinical and laboratory follow-up) for at least several months after emtricitabine or fixed combinations containing emtricitabine are discontinued.

Administration

Oral Administration

Administer orally once daily without regard to meals. Use in conjunction with other antiretrovirals.

Emtricitabine is 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). See the full prescribing information for administration of each of these combination products.

Dosage

Emtricitabine capsules and oral solution are not bioequivalent.

Pediatric Patients

Treatment of HIV Infection

Oral

Solution containing 10 mg/mL in infants 0–3 months of age: 3 mg/kg once daily.

Solution containing 10 mg/mL in children and adolescents 3 months to 17 years of age: 6 mg/kg (up to a maximum of 240 mg) once daily.

Capsules in children weighing >33 kg who can swallow intact capsule: 200 mg once daily.

Adults

Treatment of HIV Infection

Oral

200-mg capsule once daily. Alternatively, 240 mg (24 mL) as the oral solution containing 10 mg/mL once daily.

Preexposure Prophylaxis for Prevention of HIV Infection (PrEP)

Oral

Usual dosage of emtricitabine for PrEP is 200 mg once daily in conjunction with other antiretrovirals. The fixed dose combination containing emtricitabine/tenofovir DF (Truvada) is used for PrEP; see the full prescribing information for specific dosage.

Postexposure Prophylaxis following Occupational Exposure to HIV (PEP)† [off-label]

Oral

Usual dosage of emtricitabine for postexposure prophylaxis following occupational exposure to HIV (PEP)^{† [off-label]} is 200 mg once daily in conjunction with other antiretrovirals. The preferred dual nucleoside reverse transcriptase inhibitor (NRTI) backbone option for use in PEP^{† [off-label]} regimens is emtricitabine and tenofovir DF, commonly administered as the fixed-dose combination of emtricitabine/tenofovir DF (Truvada). See the full prescribing information for specific dosage of emtricitabine/tenofovir DF (Truvada).

Postexposure Prophylaxis following Nonoccupational Exposure to HIV (nPEP)†

Oral

Usual dosage of emtricitabine for postexposure prophylaxis following nonoccupational exposure to HIV (nPEP)^† is 200 mg once daily in conjunction with other antiretrovirals. The preferred dual NRTI backbone option for use in nPEP^† regimens is emtricitabine and tenofovir DF, commonly administered as the fixed dose combination of emtricitabine/tenofovir DF (Truvada). See the full prescribing information for specific dosage of emtricitabine/tenofovir DF (Truvada).

Special Populations

Hepatic Impairment

Treatment of HIV Infection

Emtricitabine not metabolized by liver enzymes; not specifically studied, but clinically important changes in metabolism not expected in patients with hepatic impairment.

Renal Impairment

Treatment of HIV Infection

Oral

Reduce dosage in adults with Cl_cr <50 mL/minute (see Table 1).

Data insufficient to make specific emtricitabine dosage recommendations for pediatric patients with renal impairment.

Geriatric Patients

No specific dosage recommendations; select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.

Cautions for Emtricitabine

Contraindications

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

Warnings/Precautions

Warnings

Severe Acute Exacerbation of HBV in Patients Coinfected with HIV-1 and HBV

Test all HIV-infected patients for presence of HBV before initiating antiretroviral therapy (See boxed warning).

Severe acute exacerbations of HBV reported in patients coinfected with HIV-1 and HBV following discontinuance of emtricitabine. HBV exacerbations have been associated with hepatic decompensation and hepatic failure.

If emtricitabine (single entity or fixed combinations) used in patients coinfected with HIV and HBV, closely monitor hepatic function (using both clinical and laboratory follow-up) for at least several months after emtricitabine or fixed combinations containing emtricitabine are discontinued. If appropriate, initiation of HBV treatment may be warranted.

Other Warnings/Precautions

Immune Reconstitution Syndrome

During initial treatment, HIV-infected patients who 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]); this may necessitate further evaluation and treatment.

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

Lactic Acidosis and Severe Hepatomegaly with Steatosis

Lactic acidosis and severe hepatomegaly with steatosis (sometimes fatal) reported in patients receiving nucleoside analogs, including emtricitabine with or without other antiretrovirals.

Discontinue single-entity or fixed-combination preparations if there are clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity (e.g., hepatomegaly and steatosis even in the absence of marked increases in serum aminotransferase concentrations).

Precautions Related to Use of Fixed Combinations

When emtricitabine is used in fixed combination with other drugs, consider the cautions, precautions, contraindications, and drug interactions associated with each drug in the fixed combination.

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.

Specific Populations

Pregnancy

Antiretroviral Pregnancy Registry (APR) at 800-258-4263 or [Web].

Based on reports to the APR, 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 US reference population of the Metropolitan Atlanta Congenital Defects Program (MACDP).

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

Lactation

Distributed into human milk.

Not known whether emtricitabine affects milk production or the breast-fed infant. Due to the risk of adverse effects in the infant and risk of HIV transmission, HIV-infected women should not breast-feed infants.

Pediatric Use

Safety and efficacy of emtricitabine for treatment of HIV-1 infection in patients ≥3 months of age is supported by evidence from studies in pediatric patients. Pharmacokinetics evaluated in a limited number of neonates born to HIV-infected mothers; efficacy in preventing or treating HIV infection in these neonates not determined.

Geriatric Use

Insufficient experience in those ≥65 years of age to determine whether they respond differently to emtricitabine than younger adults.

Hepatic Impairment

Emtricitabine not metabolized by liver enzymes; any impact of hepatic impairment expected to be limited.

Renal Impairment

Principally eliminated by the kidney; pharmacokinetics altered in renal impairment. Dosage adjustment of emtricitabine necessary based on degree of renal impairment.

Common Adverse Effects

HIV-1 infected adults (≥10%): headache, GI effects (diarrhea, nausea), fatigue, dizziness, depression, insomnia, abnormal dreams, rash, abdominal pain, asthenia, increased cough, rhinitis.

HIV-1 infected pediatric patients (≥10%): skin hyperpigmentation.

Drug Interactions

Emtricitabine does not inhibit CYP1A2, 2A6,2B6, 2C9, 2C19, 2D6, or 3A4. Interactions with drugs metabolized by these CYP isoenzymes unlikely.

Emtricitabine does not inhibit glucuronosyltransferase (uridine diphosphoglucuronosyltransferase, UDP-glucuronate β-d-glucuronosyltransferase [acceptor-unspecific]), an enzyme responsible for glucuronidation. Pharmacokinetic interactions unlikely.

The following drug interactions are based on studies using emtricitabine. When a fixed combination containing emtricitabine is used, consider interactions associated with each drug in the fixed combination.

Specific Drugs

Emtricitabine Pharmacokinetics

Absorption

Bioavailability

Pharmacokinetics in healthy individuals similar to those in individuals with HIV-1 infection.

Rapidly and extensively absorbed; peak plasma concentrations of emtricitabine attained within 1–2 hours.

Capsules: Bioavailability is 93%.

Oral solution: Bioavailability is 75%.

Food

Food does not have a clinically important effect on absorption.

Special Populations

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) similar to those reported in adults receiving 200 mg daily. AUC reported in neonates receiving 3 mg/kg daily for 4 days similar to that reported in children 3 months to 17 years of age receiving the recommended dosage.

Peak plasma concentrations and AUC of emtricitabine increased in patients with renal impairment (Cl_cr <50 mL/minute or end-stage renal disease requiring dialysis) due to reduced renal clearance of the drug. Dosage adjustments needed.

Distribution

Extent

Distributed into human milk in low concentrations.

Plasma Protein Binding

<4 %.

Elimination

Metabolism

Undergoes oxidation and conjugation with glucuronic acid.

Intracellularly, emtricitabine is phosphorylated and converted by cellular enzymes to the active metabolite, emtricitabine 5′-triphosphate.

Elimination Route

Excreted in urine (86%) and feces (14%). Eliminated by glomerular filtration and active tubular secretion.

Removed by hemodialysis; not known whether removed by peritoneal dialysis.

Half-life

10 hours.

Special Populations

Renal impairment reduces clearance.

Pharmacokinetics not affected by race or gender.

Stability

Storage

Oral

Capsules

25°C (excursions permitted between 15–30°C).

Solution

2–8°C until dispensed. For patient use, store at 25°C (excursions permitted between 15–30°C); use within 3 months.

Actions and Spectrum

• Emtricitabine is an HIV NRTI. Inactive until converted intracellularly to active 5′-triphosphate metabolite.

• Active in vitro against HIV-1 and HIV-2.

• Inhibits replication of HIV by interfering with viral RNA-directed DNA polymerase (reverse transcriptase).

• HIV-1 with reduced susceptibility to emtricitabine have been produced in vitro and have emerged during therapy with the drug.

• HIV resistant to emtricitabine may be cross-resistant to some other NRTIs (e.g., lamivudine).

Advice to Patients

• Inform patients of the importance of reading patient information provided by the manufacturer.

• 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. Advise patients to inform their clinician if symptoms suggestive of lactic acidosis or hepatotoxicity (e.g., nausea, vomiting, unusual/unexpected stomach discomfort, weakness) occur.

• Inform patients that testing for HBV infection is recommended before antiretroviral therapy is initiated and that all patients infected with HBV will require close medical follow-up for several months following emtricitabine discontinuation to monitor for hepatitis exacerbations. Advise patients to not discontinue emtricitabine without first informing their clinician. 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.

• 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. Also advise patients to inform their clinician if symptoms of infection develop.

• Advise patients to inform their clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal products, as well as concomitant medical problems such as renal impairment.

• Advise women to inform their clinicians if they are or plan to become pregnant or plan to breast-feed. Inform patients that an antiretroviral pregnancy registry is available to monitor outcomes of babies born to women taking emtricitabine during pregnancy. Advise HIV-infected women not to breast-feed due to the risk of passing the HIV-1 virus to the baby.

• Inform patients of other important precautionary information.

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.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Reload page with references included

Frequently asked questions

• Truvada vs Descovy: How do they compare for HIV and PrEP?
• What is the difference between HIV treatments Odefsey and Complera?
• Genvoya vs Stribild for HIV - How do they compare?
• What drugs are contained in the HIV treatment Symtuza?

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