Emtricitabine (Monograph)

Brand name: Emtriva
Drug class: HIV Nucleoside and Nucleotide Reverse Transcriptase Inhibitors
VA class: AM800
Chemical name: 5-Fluoro-1-(2R, 5S)-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl] cytosine
Molecular formula: C₈H₁₀FN₃O₃S
CAS number: 143491-57-0

Emtricitabine is also contained as an ingredient in the following combinations:
Efavirenz, Emtricitabine, and Tenofovir Disoproxil Fumarate
Emtricitabine and Tenofovir Alafenamide
Emtricitabine and Tenofovir Disoproxil Fumarate
Emtricitabine, Rilpivirine Hydrochloride, and Tenofovir Alafenamide
Emtricitabine, Rilpivirine Hydrochloride, and Tenofovir Disoproxil Fumarate

Medically reviewed by Drugs.com on Oct 2, 2023. Written by ASHP.

Introduction

Antiretroviral; HIV nucleoside reverse transcriptase inhibitor (NRTI).^{1 200}

Uses for Emtricitabine

Treatment of HIV Infection

Treatment of HIV-1 infection in adults, adolescents, and pediatric patients;^{1 200 201 202} used in conjunction with other antiretrovirals.^{1 200 201 202}

Single-entity emtricitabine used with another NRTI (dual NRTIs) in conjunction with an HIV integrase strand transfer inhibitor (INSTI), HIV nonnucleoside reverse transcriptase inhibitor (NNRTI), or HIV protease inhibitor (PI) in INSTI-, NNRTI-, or PI-based regimens.^{200 201} Also commercially available in various fixed combinations containing emtricitabine and a tenofovir prodrug (either tenofovir alafenamide or tenofovir DF) with or without a third antiretroviral;^{230 232 233 235 243 244 245} these fixed combinations used in certain patient groups to decrease pill burden and improve compliance.^{200 201}

For initial treatment in HIV-infected adults and adolescents, experts state that emtricitabine and tenofovir alafenamide or emtricitabine and tenofovir DF are recommended dual NRTI options for use in most INSTI-, NNRTI-, and PI-based regimens.²⁰⁰

For initial treatment in antiretroviral-naive pediatric patients, experts state that emtricitabine and zidovudine is a preferred dual NRTI option for use with a recommended PI, NNRTI, or INSTI in neonates, infants, and children <12 years of age and an alternative option in adolescents ≥12 years of age in early puberty (sexual maturity rating [SMR] 3).²⁰¹ Emtricitabine and abacavir is a preferred dual NRTI option in children ≥3 months of age and in adolescents ≥12 years of age in early puberty (SMR 1–3) who are negative for HLA-B*5701.²⁰¹ Emtricitabine and tenofovir alafenamide is a preferred dual NRTI option in adolescents ≥12 years of age in early puberty (SMR 1–3) with estimated Cl_cr ≥30 mL/minute;²⁰¹ emtricitabine and tenofovir DF is an alternative dual NRTI option in adolescents ≥12 years of age at SMR 3, but use in children ≥2 years of age or adolescents at SMR 1 or 2 only in special circumstances after weighing potential risks versus benefits.²⁰¹

Because all 3 drugs have activity against both HIV and HBV, emtricitabine and tenofovir DF or emtricitabine and tenofovir alafenamide are preferred dual NRTI options for antiretroviral regimens in HIV-infected patients coinfected with HBV.²⁰⁰

Emtricitabine/tenofovir alafenamide fixed combination (Descovy) can be used in adults and adolescents ≥12 years of age weighing ≥35 kg;²⁴⁵ used in conjunction with other antiretrovirals for treatment of HIV-1.²⁴⁵

Emtricitabine/tenofovir DF fixed combination (Truvada) can be used in adults, adolescents, and children weighing ≥17 kg;^{200 230} used in conjunction with other antiretrovirals for treatment of HIV-1.²³⁰

Efavirenz/emtricitabine/tenofovir DF fixed combination (Atripla) can be used in adults and adolescents ≥12 years of age weighing ≥40 kg;²³² used alone as a complete treatment regimen or used in conjunction with other antiretrovirals.²³²

Emtricitabine/rilpivirine/tenofovir alafenamide fixed combination (Odefsey) can be used alone as a complete treatment regimen in antiretroviral-naive adults and adolescents ≥12 years of age weighing ≥35 kg with baseline plasma HIV-1 RNA levels ≤100,000 copies/mL;²⁴⁴ also can be used to replace a stable antiretroviral regimen in antiretroviral-experienced (previously treated) patients who are virologically suppressed (i.e., plasma HIV-1 RNA levels <50 copies/mL) on their current regimen for ≥6 months, have no history of treatment failure, and are infected with HIV-1 with no known substitutions associated with resistance to the components of the fixed combination.²⁴⁴

Emtricitabine/rilpivirine/tenofovir DF fixed combination (Complera) can be used alone as a complete treatment regimen in antiretroviral-naive adults and adolescents ≥12 years of age weighing ≥35 kg with baseline plasma HIV-1 RNA levels ≤100,000 copies/mL;²³³ also can be used to replace a stable antiretroviral regimen in antiretroviral-experience patients who are virologically suppressed (i.e., plasma HIV-1 RNA levels <50 copies/mL) on their current regimen for ≥6 months, are currently receiving only their first or second antiretroviral regimen, have no history of treatment failure, and have no current evidence or history of resistance to the components of the fixed combination.²³³

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

Emtricitabine/tenofovir DF (Truvada) used for preexposure prophylaxis (PrEP) in conjunction with safer sex practices to reduce the risk of sexually acquired HIV-1 in HIV-1-negative adults at high risk.^{197 230 450 457 463}

Adults at high risk include those with partner(s) known to be infected with HIV-1 or those engaging in sexual activity within a high prevalence area or social network and with ≥1 of the following factors: inconsistent or no condom use, diagnosis of sexually transmitted infections, exchange of sex for commodities (e.g., money, food, shelter, drugs), use of illicit drugs, alcohol dependence, incarceration, or partner(s) of unknown HIV-1 status with any of these risk factors.²³⁰

PrEP with emtricitabine/tenofovir DF not always effective in preventing acquisition of HIV-1 infection; must be used as part of a comprehensive prevention strategy that includes safer sex practices.²³⁰ (See Precautions Related to HIV-1 Preexposure Prophylaxis [PrEP] under Cautions.)

Postexposure Prophylaxis following Occupational Exposure to HIV (PEP)

Postexposure prophylaxis of HIV infection following occupational exposure^{† [off-label]} (PEP) in health-care personnel and others 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 Used in conjunction with other antiretrovirals.¹⁹⁹

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.¹⁹⁹ Several alternative regimens that include an INSTI, NNRTI, or PI and 2 NRTIs (dual NRTIs) also recommended.¹⁹⁹ Preferred dual NRTI option for PEP regimens is emtricitabine and tenofovir DF (may be given as emtricitabine/tenofovir DF; Truvada);¹⁹⁹ alternative dual NRTI options are tenofovir DF and lamivudine, lamivudine and zidovudine (may be given as lamivudine/zidovudine; Combivir), or zidovudine and emtricitabine.¹⁹⁹

Management of occupational exposures to HIV is complex and evolving;¹⁹⁹ consult infectious disease specialist, clinician with expertise in administration of antiretroviral agents, and/or National Clinicians’ Postexposure Prophylaxis Hotline (PEPline at 888-448-4911) whenever possible.¹⁹⁹ Do not delay initiation of PEP while waiting for expert consultation.¹⁹⁹

Postexposure Prophylaxis following Nonoccupational Exposure to HIV (nPEP)

Postexposure 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.¹⁹⁸ Used in conjunction with other antiretrovirals.¹⁹⁸

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);¹⁹⁸ alternative regimen recommended in these patients is ritonavir-boosted darunavir used in conjunction with emtricitabine/tenofovir DF (Truvada).¹⁹⁸

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

Related/similar drugs

Biktarvy, Descovy, tenofovir, Truvada, abacavir, lamivudine, Atripla

Emtricitabine Dosage and Administration

Administration

Oral Administration

Emtricitabine (Emtriva): Administer orally once daily without regard to meals.¹ Use in conjunction with other antiretrovirals.¹

Emtricitabine/tenofovir alafenamide (Descovy): Administer orally once daily without regard to meals.²⁴⁵ Use in conjunction with other antiretrovirals for treatment of HIV-1.²⁴⁵

Emtricitabine/tenofovir DF (Truvada): Administer orally once daily without regard to meals.²³⁰ Use in conjunction with other antiretrovirals for treatment of HIV-1;²³⁰ use alone as a complete regimen for PrEP for prevention of sexually transmitted HIV-1.^{197 230}

Efavirenz/emtricitabine/tenofovir DF (Atripla): Administer orally once daily on an empty stomach, preferably at bedtime.²³² Use alone as a complete regimen or in conjunction with other antiretrovirals for treatment of HIV-1.²³²

Emtricitabine/rilpivirine/tenofovir alafenamide (Odefsey): Administer orally once daily with a meal.²⁴⁴ Use alone as a complete treatment regimen.²⁴⁴

Emtricitabine/rilpivirine/tenofovir DF (Complera): Administer orally once daily with a meal.²³³ Use alone as a complete treatment regimen.²³³

Because antiretrovirals contained in the fixed combinations also may be available in single-entity or other fixed-combination preparations, take care to ensure that therapy is not duplicated if a fixed combination is used in conjunction with other antiretrovirals.^{230 232 233 244 245} (See Precautions Related to Use of Fixed Combinations under Cautions.)

Dosage

Emtricitabine (Emtriva) capsules and oral solution are not bioequivalent.¹ (See Bioavailability under Pharmacokinetics.)

Pediatric Patients

Treatment of HIV Infection

Oral

Emtricitabine (Emtriva oral solution containing 10 mg/mL) in infants 0–3 months of age: 3 mg/kg once daily.¹

Emtricitabine (Emtriva oral 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.¹

Emtricitabine (Emtriva capsules) in children weighing >33 kg who can swallow intact capsule: 200 mg once daily.¹

Emtricitabine/tenofovir alafenamide (Descovy) in adolescents ≥12 years of age weighing ≥35 kg: 1 tablet (emtricitabine 200 mg and tenofovir alafenamide 25 mg) once daily.²³⁰

Emtricitabine/tenofovir DF (Truvada) in children weighing ≥35 kg: 1 tablet (emtricitabine 200 mg and tenofovir DF 300 mg) once daily.²³⁰

Emtricitabine/tenofovir DF (Truvada) in children weighing 17 to <35 kg: Base dosage on weight and use a low-strength fixed-combination tablet.²³⁰ (see Table 1)

Efavirenz/emtricitabine/tenofovir DF (Atripla) in adolescents ≥12 years of age weighing ≥40 kg: 1 tablet (efavirenz 600 mg, emtricitabine 200 mg, and tenofovir DF 300 mg) once daily.²³²

Emtricitabine/rilpivirine/tenofovir alafenamide (Odefsey) in adolescents ≥12 years of age weighing ≥35 kg: 1 tablet (emtricitabine 200 mg, rilpivirine 25 mg, and tenofovir alafenamide 25 mg) once daily.²⁴⁴

Emtricitabine/rilpivirine/tenofovir DF (Complera) in adolescents ≥12 years of age weighing ≥35 kg: 1 tablet (emtricitabine 200 mg, rilpivirine 25 mg, and tenofovir DF 300 mg) once daily.²³³

Adults

Treatment of HIV Infection

Oral

Emtricitabine (Emtriva): 200-mg capsule once daily.¹ Alternatively, 240 mg (24 mL) as the oral solution containing 10 mg/mL once daily.¹

Emtricitabine/tenofovir alafenamide (Descovy): 1 tablet (emtricitabine 200 mg and tenofovir alafenamide 25 mg) once daily.²⁴⁵

Emtricitabine/tenofovir DF (Truvada): 1 tablet (emtricitabine 200 mg and tenofovir DF 300 mg) once daily.²³⁰

Efavirenz/emtricitabine/tenofovir DF (Atripla): 1 tablet (efavirenz 600 mg, emtricitabine 200 mg, and tenofovir DF 300 mg) once daily.²³²

Emtricitabine/rilpivirine/tenofovir alafenamide (Odefsey): 1 tablet (emtricitabine 200 mg, rilpivirine 25 mg, and tenofovir alafenamide 25 mg) once daily.²⁴⁴

Emtricitabine/rilpivirine/tenofovir DF (Complera): 1 tablet (emtricitabine 200 mg, rilpivirine 25 mg, and tenofovir DF 300 mg) once daily.²³³

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

HIV-1-negative Adults at High Risk

Oral

Emtricitabine/tenofovir DF (Truvada): 1 tablet (emtricitabine 200 mg and tenofovir DF 300 mg) once daily.²³⁰

Use PrEP only in high-risk adults confirmed to be HIV-1-negative;²³⁰ do not initiate if signs or symptoms of acute HIV-1 infection are present and recent (<1 month) exposure to HIV-1 is suspected.²³⁰ (See Precautions Related to HIV-1 Preexposure Prophylaxis [PrEP] under Cautions.)

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

Oral

Emtricitabine (Emtriva capsules): 200 mg once daily.¹⁹⁹ Use in conjunction with other antiretrovirals (see Postexposure Prophylaxis following Occupational Exposure to HIV under Uses).¹⁹⁹

Emtricitabine/tenofovir DF (Truvada): 1 tablet (emtricitabine 200 mg and tenofovir DF 300 mg) once daily.¹⁹⁹ Use in conjunction with a recommended INSTI, NNRTI, or PI (see Postexposure Prophylaxis following Occupational Exposure to HIV [PEP] under Uses).¹⁹⁹

Emtricitabine/rilpivirine/tenofovir DF (Complera): 1 tablet (emtricitabine 200 mg, rilpivirine 25 mg, and tenofovir DF 300 mg) once daily.¹⁹⁹ Use as a complete regimen for PEP.¹⁹⁹

Initiate PEP as soon as possible following occupational exposure to HIV (preferably within hours); continue for 4 weeks, if tolerated.¹⁹⁹

Postexposure Prophylaxis following Nonoccupational Exposure to HIV (nPEP)† [off-label]

Oral

Emtricitabine (Emtriva capsules): 200 mg once daily.¹⁹⁸ Usually used in conjunction with tenofovir DF and a preferred or alternative INSTI, NNRTI, or PI (see Postexposure Prophylaxis following Nonoccupational Exposure to HIV [nPEP] under Uses).¹⁹⁸

Emtricitabine/tenofovir DF (Truvada): 1 tablet (emtricitabine 200 mg and tenofovir DF 300 mg) once daily.¹⁹⁹ Use in conjunction with a preferred or alternative INSTI, NNRTI, or PI.¹⁹⁸

Emtricitabine/rilpivirine/tenofovir DF (Complera): 1 tablet (emtricitabine 200 mg, rilpivirine 25 mg, and tenofovir DF 300 mg) once daily.¹⁹⁸ Use as a complete regimen for nPEP.¹⁹⁸

Initiate nPEP as soon as possible (within 72 hours) following nonoccupational exposure that represents a substantial risk for HIV transmission and continue for 28 days.¹⁹⁸

nPEP not recommended if exposed individual seeks care >72 hours after exposure.¹⁹⁸

Prescribing Limits

Pediatric Patients

Treatment of HIV Infection

Oral

Emtricitabine (Emtriva) in children 3 months to 17 years of age: Maximum 240 mg (as the oral solution) once daily.¹

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.¹

Emtricitabine/tenofovir alafenamide (Descovy): Use usual dosage in patients with mild or moderate hepatic impairment (Child-Pugh class A or B);²⁴⁵ not studied in those with severe hepatic impairment (Child-Pugh class C).²⁴⁵

Emtricitabine/tenofovir DF (Truvada): Not studied in hepatic impairment.²³⁰

Efavirenz/emtricitabine/tenofovir DF (Atripla): Use usual dosage in patients with mild hepatic impairment;²³² caution advised.²³² Not recommended in those with moderate or severe hepatic impairment.²³²

Emtricitabine/rilpivirine/tenofovir alafenamide (Odefsey): Use usual dosage in patients with mild or moderate hepatic impairment (Child-Pugh class A or B);²⁴⁴ not studied in those with severe hepatic impairment (Child-Pugh class C).²⁴⁴

Emtricitabine/rilpivirine/tenofovir DF (Complera): Use usual dosage in patients with mild or moderate hepatic impairment (Child-Pugh class A or B);²³³ not studied in those with severe hepatic impairment (Child-Pugh class C).²³³

Renal Impairment

Treatment of HIV Infection

Oral

Emtricitabine (Emtriva): Reduce dosage in adults with Cl_cr <50 mL/minute (see Table 2).¹

Emtricitabine (Emtriva): Data insufficient to make specific emtricitabine dosage recommendations for pediatric patients with renal impairment; consider reducing dose and/or increasing dosing interval.¹

Emtricitabine/tenofovir alafenamide (Descovy): Use usual dosage in patients with estimated Cl_cr ≥30 mL/minute;²⁴⁵ not recommended in those with severe renal impairment (estimated Cl_cr <30 mL/minute).²⁴⁵

Emtricitabine/tenofovir DF (Truvada): Use usual dosage in adults with Cl_cr 50–80 mL/minute; however, monitor calculated Cl_cr, serum phosphorus, urine glucose, and urine protein.²³⁰ In adults with Cl_cr 30–49 mL/minute, reduce dosage to 1 tablet (emtricitabine 200 mg and tenofovir DF 300 mg) once every 48 hours; monitor clinical response and renal function since dosage not evaluated clinically.²³⁰ Do not use in adults with Cl_cr <30 mL/minute (including hemodialysis patients).²³⁰ Data insufficient to make dosage recommendations for treatment of HIV-1 infection in pediatric patients with renal impairment.²³⁰

Efavirenz/emtricitabine/tenofovir DF (Atripla): Use usual dosage in patients with Cl_cr ≥50 mL/minute;²³² do not use in those with estimated Cl_cr <50 mL/minute.²³²

Emtricitabine/rilpivirine/tenofovir alafenamide (Odefsey): Use usual dosage in patients with estimated Cl_cr ≥30 mL/minute;²⁴⁴ not recommended in those with severe renal impairment (estimated Cl_cr <30 mL/minute).²⁴⁴

Emtricitabine/rilpivirine/tenofovir DF (Complera): Do not use in those with moderate, severe, or end-stage renal impairment (estimated Cl_cr <50 mL/minute) or if dialysis required.²³³

Preexposure Prophylaxis for Prevention of HIV-1 Infection

Oral

Emtricitabine/tenofovir DF (Truvada): Use usual dosage in adults with Cl_cr ≥60 mL/minute; however, monitor calculated Cl_cr, serum phosphorus, urine glucose, and urine protein.²³⁰ If Cl_cr decreases, evaluate potential causes and reassess potential risks and benefits of continued use.²³⁰ Do not use if Cl_cr <60 mL/minute.²³⁰

Geriatric Patients

Select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.^{1 230 232 233}

Cautions for Emtricitabine

Contraindications

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

• Emtricitabine/tenofovir alafenamide (Descovy): Manufacturer states none known.²⁴⁵

• Emtricitabine/tenofovir DF: Do not use alone for treatment of HIV-1 infection;²³⁰ do not use for preexposure prophylaxis of HIV-1 infection in individuals with unknown or positive HIV-1 status.²³⁰ (See Precautions Related to HIV-1 Preexposure Prophylaxis [PrEP] under Cautions.)

• Efavirenz/emtricitabine/tenofovir DF (Atripla): History of clinically important hypersensitivity reaction (e.g., Stevens-Johnson syndrome, erythema multiforme, toxic skin eruption) to efavirenz;²³² concomitant use with voriconazole contraindicated (because of efavirenz component).²³²

• Emtricitabine/rilpivirine/tenofovir alafenamide (Odefsey) or emtricitabine/rilpivirine/tenofovir DF (Complera): Concomitant use with certain drugs that induce CYP3A or elevate gastric pH contraindicated (because of rilpivirine component);^{233 244} substantially decreased plasma concentrations of rilpivirine may occur and may result in loss of virologic response and development of resistance to rilpivirine and/or class resistance to HIV NNRTIs.^{233 244}

• Fixed combinations containing emtricitabine: Consider contraindications associated with each drug in the fixed combination.^{230 232 233 244 245}

Warnings/Precautions

Warnings

Lactic Acidosis and Severe Hepatomegaly with Steatosis

Lactic acidosis and severe hepatomegaly with steatosis (sometimes fatal) reported in patients receiving HIV NRTIs, including emtricitabine with or without a tenofovir prodrug, in conjunction with other antiretrovirals.^{1 230 232 233 244 245} Reported most frequently in women;^{1 230 232 233 244 245} obesity and long-term NRTI therapy also may be risk factors.^{1 230 232 233 244 245} Cases reported in patients with no known risk factors.^{1 230 232 233 244 245}

Use emtricitabine (single entity or fixed combinations) with caution in patients with known risk factors for liver disease.^{1 230 232 233 244 245}

Discontinue 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).^{1 230 232 233 244 245}

Individuals with HBV Infection

Test all HIV-infected patients for presence of HBV before initiating antiretroviral therapy.^{1 230 232 233 244 245}

Emtricitabine (single entity or fixed combinations) not indicated for treatment of chronic HBV infection.^{1 230 232 233 244 245}

Safety and efficacy not established for treatment of HIV infection in patients coinfected with HBV.^{1 230 232 233 244 245} (See Treatment of HIV Infection under Uses.)

Severe acute exacerbations of HBV reported following discontinuance of emtricitabine with or without a tenofovir prodrug.^{1 230 232 233 244 245} HBV exacerbations have been associated with hepatic decompensation and hepatic failure.^{1 230 232 233 244 245}

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.^{1 230 232 233 244 245} If appropriate, initiation of HBV treatment may be warranted.^{1 230 232 233 244 245}

Precautions Related to HIV-1 Preexposure Prophylaxis

Use emtricitabine/tenofovir DF (Truvada) for HIV-1 PrEP only in HIV-1-negative adults at high risk.²³⁰

Confirm a negative HIV-1 test immediately prior to initiating PrEP and screen for HIV-1 infection at least once every 3 months during PrEP.²³⁰ Also test for HBV prior to initiating PrEP.²³⁰ (See Individuals with HBV Infection under Cautions.)

Emtricitabine/tenofovir DF PrEP not always effective in preventing acquisition of HIV-1 infection.²³⁰

Must be used as part of a comprehensive HIV prevention strategy that includes other prevention measures (e.g., safer sex practices).²³⁰ (See REMS.) Counsel all uninfected individuals about safer sex practices that include consistent and correct use of condoms, knowledge of their own HIV-1 status and that of their partner(s), and regular testing for other sexually transmitted infections that can facilitate HIV-1 transmission (e.g., syphilis, gonorrhea).²³⁰ Inform and support uninfected individuals regarding efforts to reduce sexual risk behavior.²³⁰

Because emtricitabine/tenofovir DF alone does not constitute a complete antiretroviral regimen for treatment of HIV-1 infection, HIV-1 resistance-associated mutations may emerge if emtricitabine/tenofovir DF PrEP is used in individuals with undetected HIV-1 infection.²³⁰ Drug-resistant HIV-1 variants have been identified in such individuals.²³⁰

Many HIV-1 tests (e.g., rapid tests) detect anti-HIV antibodies and may not identify HIV-1 during the acute stage of infection.²³⁰ Prior to initiating PrEP, evaluate HIV-negative individuals for current or recent signs or symptoms consistent with acute viral infections (e.g., fever, fatigue, myalgia, rash) and ask about any potential exposure events within the last month (e.g., unprotected sex, condom broke during sex with HIV-infected partner).²³⁰

If clinical symptoms consistent with acute viral infection are present and recent (<1 month) exposures to HIV-1 are suspected, delay initiating PrEP for at least 1 month and reconfirm HIV-1 status or use a test approved by FDA as an aid in the diagnosis of HIV-1 infection, including acute or primary HIV-1 infection.²³⁰

During PrEP, if symptoms consistent with acute HIV-1 infection develop following a potential exposure event, discontinue the drugs until negative infection status is confirmed using a test approved by FDA as an aid in the diagnosis of HIV-1 infection, including acute or primary HIV-1 infection.²³⁰

Counsel uninfected individuals to strictly adhere to recommended emtricitabine/tenofovir DF dosage schedule.²³⁰ (See Preexposure Prophylaxis [PrEP] for Prevention of HIV-1 Infection under Dosage and Administration.) Effectiveness in reducing risk of acquiring HIV-1 is strongly correlated with adherence.²³⁰

Adverse effects similar to those reported in HIV-infected patients receiving the drugs for treatment of HIV-1 infection.²³⁰

Other Warnings/Precautions

Precautions Related to Use of Fixed Combinations

Emtricitabine/tenofovir alafenamide, emtricitabine/tenofovir DF, efavirenz/emtricitabine/tenofovir DF, emtricitabine/rilpivirine/tenofovir alafenamide, emtricitabine/rilpivirine/tenofovir DF: Consider cautions, precautions, contraindications, and interactions associated with each drug in the fixed combination.^{230 232 233 244 245} Consider cautionary information applicable to specific populations (e.g., pregnant or nursing women, individuals with hepatic or renal impairment, geriatric patients) for each drug.^{230 232 233 244 245}

Because the antiretrovirals contained in the fixed-combination preparations also may be available in single-entity or other fixed-combination preparations, take care to ensure that therapy is not duplicated if a fixed combination is used in conjunction with other antiretrovirals.^{230 232 233 244 245}

Do not use multiple emtricitabine-containing preparations concomitantly.^{1 230 232 233 244 245}

Because of similarities between emtricitabine and lamivudine, do not use emtricitabine (single entity or fixed combinations) concomitantly with any preparation containing lamivudine.^{1 200 232 233 244 245} In addition, do not use fixed combinations containing tenofovir DF concomitantly with adefovir.^{200 232 233}

Adipogenic Effects

Possible redistribution or accumulation of body fat, including central obesity, dorsocervical fat enlargement (“buffalo hump”), peripheral wasting, breast enlargement, and general cushingoid appearance.^{1 230 232 233 244 245}

Mechanisms and long-term consequences of adipogenic effects unknown; causal relationship not established.^{1 230 232 233 244 245}

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]);^{1 230 232 233 244 245} this may necessitate further evaluation and treatment.^{1 230 232 233 244 245}

Autoimmune disorders (e.g., Graves' disease, polymyositis, Guillain-Barré syndrome) also reported in the setting of immune reconstitution;^{1 230 232 233 244 245} time to onset is more variable and can occur many months after initiation of antiretroviral therapy.^{1 230 232 233 244 245}

Specific Populations

Pregnancy

Emtricitabine (Emtriva): Category B.^{1 230 233}

Emtricitabine/tenofovir alafenamide (Descovy): Insufficient human data to assess risk of birth defects and miscarriage if used in pregnant women.²⁴⁵

Emtricitabine/tenofovir DF (Truvada): Category B.^{230 233}

Efavirenz/emtricitabine/tenofovir DF (Atripla): Category D.²³²

Emtricitabine/rilpivirine/tenofovir alafenamide (Odefsey): Insufficient human data to assess risk of birth defects and miscarriage if used in pregnant women.²⁴⁴

Emtricitabine/rilpivirine/tenofovir DF (Complera): Category B.²³³

Antiretroviral Pregnancy Registry at 800-258-4263 or [Web].^{1 202 230 232 233 244 245}

Experts state that emtricitabine and tenofovir DF is a preferred dual NRTI option for use in conjunction with an INSTI, NNRTI, or PI for initial treatment of HIV-1 infection in antiretroviral-naive pregnant women, and is a preferred dual NRTI option in pregnant HIV-infected women coinfected with HBV.²⁰²

Experts state that the dual NRTI option of tenofovir DF and emtricitabine in conjunction with the fixed combination of lopinavir and ritonavir (lopinavir/ritonavir) is a preferred regimen for treatment of HIV type 2 (HIV-2) infection^{† [off-label]} in pregnant women.²⁰²

If HIV-negative woman receiving emtricitabine/tenofovir DF (Truvada) for HIV-1 PrEP becomes pregnant, carefully consider whether PrEP regimen should be continued, taking into account the potential increased risk of HIV-1 infection during pregnancy.²³⁰

Lactation

Emtricitabine distributed into human milk in low concentrations.^{1 34}

Instruct HIV-infected women not to breast-feed because of risk of HIV transmission and risk of adverse effects in the infant.^{1 202 230 232 233 244 245}

Pediatric Use

Emtricitabine (Emtriva): Safety and efficacy for treatment of HIV-1 infection in pediatric patients ≥3 months of age is supported by evidence from studies in pediatric patients.¹ Adverse effects reported in children similar to adults.¹ 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.^{1 20}

Emtricitabine/tenofovir alafenamide (Descovy): Should not be used in pediatric patients <12 years of age or weighing <35 kg.²⁴⁵

Emtricitabine/tenofovir DF (Truvada): Safety and efficacy for treatment of HIV-1 infection not established in pediatric patients weighing <17 kg;²³⁰ safety and efficacy for HIV-1 PrEP not established in pediatric patients.²³⁰

Efavirenz/emtricitabine/tenofovir DF (Atripla): Do not use in pediatric patients <12 years of age or weighing <40 kg.²³²

Emtricitabine/rilpivirine/tenofovir alafenamide (Odefsey): Safety and efficacy not established in pediatric patients <12 years of age or weighing <35 kg.²⁴⁴

Emtricitabine/rilpivirine/tenofovir DF (Complera): Safety and efficacy not established in pediatric patients <12 years of age or weighing <35 kg.²³³

Geriatric Use

Insufficient experience in those ≥65 years of age to determine whether they respond differently to emtricitabine (single-entity or fixed-combination preparations) than younger adults.^{1 230 232 233}

Hepatic Impairment

Emtricitabine not metabolized by liver enzymes; any impact of hepatic impairment expected to be limited.¹ (See Hepatic Impairment under Dosage and Administration.)

Emtricitabine/tenofovir alafenamide (Descovy): Not studied in patients with severe hepatic impairment (Child-Pugh class C).²⁴⁵

Emtricitabine/tenofovir DF (Truvada): Not studied in patients with hepatic impairment.²³⁰

Efavirenz/emtricitabine/tenofovir DF (Atripla): Not recommended in those with moderate or severe hepatic impairment.²³²

Emtricitabine/rilpivirine/tenofovir alafenamide (Odefsey): Not studied in patients with severe hepatic impairment (Child-Pugh class C).²⁴⁴

Emtricitabine/rilpivirine/tenofovir DF (Complera): Not studied in patients with severe hepatic impairment (Child-Pugh class C).²³³

Renal Impairment

Dosage adjustment of emtricitabine (Emtriva) necessary based on degree of renal impairment.¹ Monitor clinical response and renal function in patients with renal impairment.¹ (See Renal Impairment under Dosage and Administration.)

Emtricitabine/tenofovir alafenamide (Descovy): Not recommended in patients with severe renal impairment (estimated Cl_cr <30 mL/minute).²⁴⁵

Emtricitabine/tenofovir DF (Truvada): Do not use for treatment of HIV-1 in patients with Cl_cr <30 mL/minute or patients with end-stage renal disease requiring dialysis.²³⁰ Do not use for PrEP in HIV-1 uninfected adults with Cl_cr <60 mL.²³⁰ If Cl_cr decreases during emtricitabine/tenofovir DF (Truvada) PrEP, evaluate potential causes and reassess potential risks and benefits of continued use.²³⁰

Efavirenz/emtricitabine/tenofovir DF (Atripla): Do not use in those with estimated Cl_cr <50 mL/minute.²³²

Emtricitabine/rilpivirine/tenofovir alafenamide (Odefsey): Not recommended in those with severe renal impairment (estimated Cl_cr <30 mL/minute).²⁴⁴

Emtricitabine/rilpivirine/tenofovir DF (Complera): Do not use in those with moderate, severe, or end-stage renal impairment (estimated Cl_cr <50 mL/minute) or if dialysis required.²³³

Common Adverse Effects

Mild to moderate headache, GI effects (diarrhea, nausea), rash.¹

Drug Interactions

Emtricitabine does not inhibit CYP1A2, 2A6,2B6, 2C9, 2C19, 2D6, or 3A4.¹ Interactions with drugs metabolized by these CYP isoenzymes unlikely.¹

Emtricitabine does not inhibit glucuronosyltransferase (uridine diphosphoglucuronosyltransferase, UDP-glucuronate β-d-glucuronosyltransferase [acceptor-unspecific]), an enzyme responsible for glucuronidation.¹ Pharmacokinetic interactions unlikely.¹

The following drug interactions are based on studies using emtricitabine.¹ Interaction studies also have been performed using emtricitabine/tenofovir alafenamide, emtricitabine/tenofovir DF, efavirenz/emtricitabine/tenofovir DF, emtricitabine/rilpivirine/tenofovir alafenamide, or emtricitabine/rilpivirine/tenofovir DF.^{230 232 233 244 245} When a fixed combinations containing emtricitabine is used, consider interactions associated with each drug in the fixed combination.^{230 232 233 244 245}

Specific Drugs

Emtricitabine Pharmacokinetics

Absorption

Bioavailability

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

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

Emtricitabine capsules: Bioavailability is 93%.¹

Emtricitabine oral solution: Bioavailability is 75%.¹

Fixed-combination tablet containing efavirenz 600 mg, emtricitabine 200 mg, and tenofovir DF 300 mg (efavirenz/emtricitabine/tenofovir DF; Atripla) is bioequivalent to a 600-mg tablet of efavirenz, 200-mg capsule of emtricitabine, and 300-mg tablet of tenofovir DF taken simultaneously in fasting state.²³²

Fixed-combination tablet containing emtricitabine 200 mg, rilpivirine 25 mg, and tenofovir DF 300 mg (emtricitabine/rilpivirine/tenofovir DF; Complera) taken with a meal is bioequivalent to a 200-mg emtricitabine capsule, 25-mg rilpivirine tablet, and 300-mg tenofovir DF tablet taken simultaneously with a meal.²³³

Fixed-combination tablet containing emtricitabine 200 mg and tenofovir DF 300 mg (emtricitabine/tenofovir DF; Truvada) is bioequivalent to a 200-mg capsule of emtricitabine and 300-mg tablet of tenofovir DF.²³⁰

Food

Food does not have a clinically important effect on emtricitabine absorption.¹

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.¹ 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.¹

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.¹ Dosage adjustments needed.¹ (See Renal Impairment under Dosage and Administration.)

Distribution

Extent

Emtricitabine distributed into saliva³³ and into vaginal tissue and cervicovaginal fluid following oral administration.^{30 31 36}

Crosses human placenta.²⁰²

Distributed into human milk in low concentrations.^{1 34}

Plasma Protein Binding

<4 %.¹

Elimination

Metabolism

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

Elimination Route

Excreted in urine (86%) and feces (14%).¹ Eliminated by glomerular filtration and active tubular secretion.¹

Removed by hemodialysis;¹ not known whether removed by peritoneal dialysis.¹

Half-life

10 hours.¹

Special Populations

Renal impairment reduces renal clearance.¹

Stability

Storage

Oral

Capsules

Emtricitabine (Emtriva): 25°C (may be exposed to 15–30°C).¹

Solution

Emtricitabine (Emtriva): 2–8°C until dispensed.¹ For patient use, store at 25°C (may be exposed to 15–30°C); use within 3 months.¹

Tablets

Emtricitabine/tenofovir DF (Truvada), efavirenz/emtricitabine/tenofovir DF (Atripla), emtricitabine/rilpivirine/tenofovir DF (Complera): 25°C (may be exposed to 15–30°C).^{230 232 233 235} Store in original container; keep tightly closed.^{230 232 233 235}

Emtricitabine/tenofovir alafenamide, emtricitabine/rilpivirine/tenofovir alafenamide: <30°C.^{244 245} Dispense in original container; keep tightly closed.^{244 245}

Actions and Spectrum

• Emtricitabine is an HIV NRTI.^{1 26} Inactive until converted intracellularly to an active 5′-triphosphate metabolite.^{1 26}

• Active in vitro against HIV-1 and HIV-2.¹ Also has some activity against HBV.^{5 7}

• Inhibits replication of HIV by interfering with viral RNA-directed DNA polymerase (reverse transcriptase).¹

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

• HIV resistant to emtricitabine may be cross-resistant to some other NRTIs (e.g., lamivudine).¹

• Cross-resistance between emtricitabine and PIs is highly unlikely since the drugs have different target enzymes.²⁰⁰ Cross-resistance between emtricitabine and NNRTIs is considered to be low since the drugs bind at different sites on reverse transcriptase and have different mechanisms of action.²⁰⁰

Advice to Patients

• Critical nature of compliance with HIV therapy and importance of remaining under the care of a clinician.^{1 230 232 233 244 245} Importance of taking as prescribed; do not alter or discontinue antiretroviral regimen without consulting clinician.^{1 230 232 233 244 245}

• Importance of using emtricitabine (Emtriva),¹ emtricitabine/tenofovir alafenamide (Descovy),²⁴⁵ or emtricitabine/tenofovir DF (Truvada)²³⁰ in conjunction with other antiretrovirals for treatment of HIV-1 infection—not for monotherapy.

• Efavirenz/emtricitabine/tenofovir DF (Atripla),²³² emtricitabine/rilpivirine/tenofovir alafenamide (Odefsey),²⁴⁴ or emtricitabine/rilpivirine/tenofovir DF (Complera)²³³ can be used alone as a complete treatment regimen.

• Antiretroviral therapy is not a cure for HIV infection; opportunistic infections and other complications associated with HIV disease may still occur.^{1 230 232 233 244 245}

• Advise HIV-infected patients that effective antiretroviral treatment regimens can decrease HIV-1 concentrations in blood and genital secretions and strict adherence to such regimens in conjunction with risk-reduction measures may decrease, but cannot absolutely eliminate, the risk of secondary transmission of HIV to others.²⁰⁰ Importance of continuing to practice safer sex (e.g., using latex or polyurethane condoms to minimize sexual contact with body fluids), never sharing personal items that can have blood or body fluids on them (e.g., toothbrushes, razor blades), and never reusing or sharing needles.^{1 200 233 244 245}

• Emtricitabine/tenofovir DF (Truvada) medication guide must be provided to and reviewed with all HIV-negative individuals each time emtricitabine/tenofovir DF is dispensed for HIV-1 PrEP.^{37 230} (See REMS.) Advise such individuals of the importance of confirming that they are HIV-1-negative before starting PrEP, importance of regular HIV-1 testing (at least every 3 months) during PrEP, importance of strictly adhering to recommended dosage schedule and not missing any doses, and importance of using a complete prevention strategy that also includes other measures (e.g., consistent condom use, testing for other sexually transmitted infections such as syphilis and gonorrhea that may facilitate HIV-1 transmission, reducing sexual risk behavior).²³⁰ Advise uninfected individuals that PrEP does not protect all individuals from acquiring HIV-1 and to report any symptoms of acute HIV-1 infection (e.g., fever, headache, fatigue, arthralgia, vomiting, myalgia, diarrhea, pharyngitis, rash, night sweats, cervical and inguinal adenopathy) immediately to a clinician.²³⁰

• Importance of reading patient information provided by the manufacturer.^{1 230 232 233 244 245}

• 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.^{1 230 232 233 244 245} Importance of contacting clinician if symptoms suggestive of lactic acidosis or hepatotoxicity (e.g., nausea, vomiting, unusual/unexpected stomach discomfort, weakness) occur.^{1 230 232 233 244 245}

• Inform patients that testing for HBV infection recommended before antiretroviral therapy initiated.^{1 230 232 233 244 245} 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.^{1 230 232 233 244 245}

• Redistribution/accumulation of body fat may occur; cause and long-term health effects unknown.^{1 230 232 233 244 245}

• Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal products.^{1 230 232 233 244 245}

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.^{1 230 232 233 244 245} Advise HIV-infected women not to breast-feed.^{1 230 232 233 244 245}

• Importance of advising patients of other important precautionary information.^{1 230 232 233 244 245} (See Cautions.)

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.

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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