Emtriva

Generic Name: Emtricitabine
Class: 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

Warning(s)

  • Lactic Acidosis and Hepatomegaly with Steatosis
  • Lactic acidosis and severe hepatomegaly with steatosis, including fatalities, reported in patients receiving nucleoside reverse transcriptase inhibitors (NRTIs) in conjunction with other antiretrovirals.1 230 232 233 (See Hepatic Effects and Lactic Acidosis under Cautions.)

  • HBV Infection
  • Single entity and fixed combinations containing emtricitabine not approved for treatment of chronic HBV infection; safety and efficacy not established in HIV-infected patients coinfected with HBV.1 230 232 233

  • Severe, acute exacerbations of HBV reported following discontinuance of emtricitabine or tenofovir in patients coinfected with HIV-1 and HBV.1 230 232 233

  • Monitor hepatic function closely with both clinical and laboratory follow-up for at least several months after emtricitabine is discontinued in coinfected patients.1 230 232 233 If appropriate, initiation of HBV treatment may be warranted.1 230 232 233

  • HIV-1 Preexposure Prophylaxis (PrEP)
  • Prescribe emtricitabine/tenofovir (Truvada) for HIV-1 PrEP only for individuals confirmed to be HIV-1-negative immediately prior to initiation of PrEP; confirm HIV-1-negative status periodically (at least every 3 months) during PrEP.230

  • Drug-resistant HIV-1 variants have been identified when emtricitabine/tenofovir PrEP was used following undetected acute HIV-1 infection.230 Do not initiate PrEP if signs or symptoms of acute HIV-1 infection are present, unless negative infection status is confirmed.230 (See Precautions Related to HIV-1 Preexposure Prophylaxis [PrEP] under Cautions.)

REMS:

FDA approved a REMS for emtricitabine to ensure that the benefits outweigh the risk. The REMS may apply to one or more preparations of emtricitabine and consists of the following: medication guide and elements to assure safe use. See the FDA REMS page () or the ASHP REMS Resource Center ().

Introduction

Antiretroviral; nucleoside reverse transcriptase inhibitor (NRTI).1 200

Uses for Emtriva

Treatment of HIV Infection

Treatment of HIV-1 infection in conjunction with other antiretrovirals.1 2 3

Used with another NRTI (dual NRTIs) in conjunction with a nonnucleoside reverse transcriptase inhibitor (NNRTI) or HIV protease inhibitor (PI) in NNRTI- or PI-based regimens.200 201 Also used with another NRTI (dual NRTIs) in conjunction with an HIV integrase inhibitor or HIV entry inhibitor.200

For initial treatment in HIV-infected adults and adolescents, some experts state that tenofovir and either emtricitabine or lamivudine is the preferred dual NRTI option, especially in HIV-infected patients coinfected with HBV.200 Abacavir and either emtricitabine or lamivudine is an alternative NRTI option for initial treatment.200

In antiretroviral-experienced patients, base decision to use emtricitabine on laboratory testing and treatment history.1

Slideshow: Flashback: FDA Drug Approvals 2013

Emtricitabine/tenofovir fixed combination (Truvada) used in conjunction with other antiretrovirals.230 Can be used to decrease pill burden,200 but should not be used as a component of a triple NRTI regimen.230

Efavirenz/emtricitabine/tenofovir fixed combination (Atripla) used alone or in conjunction with other antiretrovirals.232 Used to decrease pill burden and improve compliance.232

Emtricitabine/rilpivirine/tenofovir fixed combination (Complera) can be used alone.233 Used to decrease pill burden and improve compliance.233

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

Emtricitabine/tenofovir used for PrEP in combination with safer sex practices to reduce the risk of sexually acquired HIV-1 in HIV-1-negative adults at high risk.230 450 451 457 463 467

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 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

Postexposure prophylaxis of HIV infection in health-care workers and others exposed occupationally via percutaneous injury or mucous membrane or nonintact skin contact with blood, tissues, or other body fluids associated with risk for transmission of the virus. Used in conjunction with other antiretrovirals.199

Postexposure Prophylaxis following Nonoccupational Exposure to HIV

Postexposure prophylaxis of HIV infection in individuals who have had nonoccupational exposure to blood, genital secretions, or other potentially infectious body fluids of a person known to be infected with HIV when that exposure represents a substantial risk for HIV transmission.198 Used in conjunction with other antiretrovirals.198

Emtriva Dosage and Administration

Administration

Oral Administration

Administer emtricitabine (Emtriva) or emtricitabine/tenofovir (Truvada) orally without regard to meals.1 230

Administer efavirenz/emtricitabine/tenofovir (Atripla) orally once daily on an empty stomach, preferably at bedtime.232

Administer emtricitabine/rilpivirine/tenofovir (Complera) orally with a meal.233

Dosage

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

Antiretroviral agents contained in Atripla, Truvada, or Complera also are available in other single-entity or fixed-combination preparations; ensure that therapy is not duplicated when Atripla, Truvada, or Complera is used in conjunction with other antiretrovirals.230 232 233 When selecting concomitant therapy, consider cautions and interactions for each drug in the fixed combination.230 232 233

Pediatric Patients

Treatment of HIV Infection
Oral

Infants 0–3 months of age: 3 mg/kg (as the oral solution) once daily.1

Children 3 months to 17 years of age: 6 mg/kg (up to a maximum of 240 mg as the oral solution) once daily.1

Children weighing >33 kg who can swallow an intact capsule: 200 mg (as the capsule) once daily.1

Emtricitabine/tenofovir (Truvada) in children ≥12 years of age weighing ≥35 kg: 1 tablet (emtricitabine 200 mg and tenofovir disoproxil fumarate 300 mg) once daily.230

Adults

Treatment of HIV Infection
Oral

200 mg (as the capsule) once daily.1 Alternatively, 240 mg (as the oral solution) once daily.1

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

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

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

Preexposure Prophylaxis (PrEP) for Prevention of HIV-1 Infection
HIV-1-negative Adults at High Risk
Oral

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

Use only in high-risk adults confirmed to be HIV-1-negative; 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
Oral

200 mg (as the capsule) once daily.199

Initiate postexposure prophylaxis as soon as possible following exposure (within hours rather than days) and continue for 4 weeks, if tolerated.199

Postexposure Prophylaxis following Nonoccupational Exposure to HIV
Oral

200 mg (as the capsule) once daily.198

Initiate postexposure prophylaxis as soon as possible following exposure (preferably ≤72 hours after exposure) and continue for 28 days.198

Prescribing Limits

Pediatric Patients

Treatment of HIV Infection
Oral

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

Efavirenz/emtricitabine/tenofovir (Atripla): Dosage adjustment not needed in adults with mild hepatic impairment; however, caution advised.232 Do not use in those with moderate or severe hepatic impairment.232

Emtricitabine/rilpivirine/tenofovir (Complera): Dosage adjustment not needed in adults 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

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

Renal Impairment

Treatment of HIV Infection
Oral

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

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

Table 1. Emtricitabine Dosage for Treatment of HIV-1 Infection in Adults with Renal Impairment1200

Clcr (mL/minute)

Dosage of Capsules

Dosage of Oral Solution

30–49

200 mg every 48 hours

120 mg every 24 hours

15–29

200 mg every 72 hours

80 mg every 24 hours

<15

200 mg every 96 hours

60 mg every 24 hours

Hemodialysis patients

200 mg every 96 hours; on day of dialysis, give dose after the procedure

60 mg every 24 hours; on day of dialysis, give dose after the procedure

Efavirenz/emtricitabine/tenofovir (Atripla): Dosage adjustment not needed in adults with Clcr ≥50 mL/minute;232 do not use in those with Clcr <50 mL/minute.232

Emtricitabine/rilpivirine/tenofovir (Complera): Do not use if Clcr <50 mL/minute or requires dialysis.233

Emtricitabine/tenofovir (Truvada): Dosage adjustment not needed in adults with Clcr 50–80 mL/minute; however, monitor calculated Clcr and serum phosphorus.230 In adults with Clcr 30–49 mL/minute, reduce dosage to 1 tablet (emtricitabine 200 mg and tenofovir disoproxil fumarate 300 mg) once every 48 hours; monitor clinical response and renal function since dosage not evaluated clinically.230 Do not use in adults with Clcr <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

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

Emtricitabine/tenofovir (Truvada): Dosage adjustment not needed in adults with Clcr ≥60 mL/minute; however, monitor calculated Clcr and serum phosphorus.230 If Clcr decreases, evaluate potential causes and reassess potential risks and benefits of continued use.230 Do not use if Clcr <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 Emtriva

Contraindications

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

  • When used in fixed combination with other antiretrovirals (e.g., efavirenz, rilpivirine, tenofovir), consider contraindications associated with each drug.230 232 233

  • Emtricitabine/tenofovir (Truvada): Do not use alone for treatment of HIV-1 infection; 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.)

Warnings/Precautions

Hepatic Effects and Lactic Acidosis

Lactic acidosis and severe hepatomegaly with steatosis (sometimes fatal) reported in patients receiving NRTIs, including emtricitabine, in conjunction with other antiretrovirals.1 230 232 233 Reported most frequently in women; obesity and long-term NRTI therapy also may be risk factors.1 230 232 233 Has been reported in patients with no known risk factors.1 230 232 233

Use with caution in patients with known risk factors for liver disease.1 230 232 233

Interrupt therapy 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

Individuals with HBV Infection

Test all HIV patients for presence of HBV before initiating antiretroviral therapy.1 230 232 233

Not indicated for treatment of chronic HBV infection.1 230 232 233

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

Severe acute exacerbations of HBV reported following discontinuance of emtricitabine.1 230 232 233 HBV exacerbations have been associated with hepatic decompensation and hepatic failure.1 230 232 233

If 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 If appropriate, initiation of HBV treatment may be warranted.1 230 232 233

Use of Fixed Combinations

Do not use multiple emtricitabine-containing preparations concomitantly.1 230 232 233

Emtricitabine should not be administered with lamivudine or fixed combinations containing lamivudine.1

When used in fixed combination with other antiretrovirals (e.g., efavirenz, rilpivirine, tenofovir), consider cautions, precautions, contraindications, and interactions associated with each drug.230 232 233 Consider cautionary information applicable to specific populations (e.g., pregnant or nursing women, individuals with hepatic or renal impairment, geriatric patients) considered for each drug in the fixed combination.230 232 233

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

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 jiroveci [formerly P. carinii]);1 this may necessitate further evaluation and treatment.1 230 232 233

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

Precautions Related to HIV-1 Preexposure Prophylaxis (PrEP)

Use emtricitabine/tenofovir (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 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 alone does not constitute a complete antiretroviral regimen for treatment of HIV-1 infection, HIV-1 resistance-associated mutations may emerge if emtricitabine/tenofovir PrEP 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 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

Specific Populations

Pregnancy

Emtricitabine: Category B.1 230 233

Antiretroviral Pregnancy Registry at 800-258-4263 or .1 202 230 232 233

Some experts state that emtricitabine is an alternative (not preferred) NRTI for use in multiple-drug antiretroviral treatment regimens in pregnant women.202 These experts state that tenofovir and either emtricitabine or lamivudine is the preferred dual NRTI option for treatment in pregnant HIV-infected women coinfected with HBV.202

If HIV-negative woman receiving emtricitabine/tenofovir 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

Pediatric Use

Safety and efficacy of emtricitabine 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

Safety and efficacy of emtricitabine in fixed combination with efavirenz and tenofovir (Atripla) or in fixed combination with rilpivirine and tenofovir (Complera) not established in pediatric patients <18 years of age.232 233

Safety and efficacy of emtricitabine in fixed combination with tenofovir (Truvada) for the treatment of HIV-1 infection not established in pediatric patients <12 years of age or weighing <35 kg; safety and efficacy for HIV-1 PrEP not established in pediatric patients.230

Geriatric Use

Insufficient experience in those ≥65 years of age to determine whether they respond differently 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.)

Renal Impairment

Dosage adjustment of emtricitabine 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.)

Common Adverse Effects

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

Interactions for Emtriva

Emtricitabine does not inhibit CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2C19, CYP2D6, or CYP3A4.1 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 Drug interaction studies have not been performed using fixed-combinations containing emtricitabine.230 232 233 When used in fixed combination with other antiretrovirals, consider interactions associated with each drug in the fixed combination.230 232 233

Specific Drugs

Drug

Interaction

Comments

Abacavir

In vitro evidence of additive or synergistic antiretroviral effects1

Atazanavir

No in vitro evidence of antagonistic antiretroviral effects203

Darunavir

Pharmacokinetic interaction unlikely204

No in vitro evidence of antagonistic antiretroviral effects204

Delavirdine

In vitro evidence of additive or synergistic antiretroviral effects1

Efavirenz

In vitro evidence of additive or synergistic antiretroviral effects1

Etravirine

No in vitro evidence of antagonistic antiretroviral effects214

Famciclovir

Pharmacokinetic interaction unlikely1

Indinavir

No effect on pharmacokinetics of either drug1

Lamivudine

In vitro evidence of additive antiretroviral effects1

Do not use concomitantly;1 200 201 no potential benefit since emtricitabine is an analog of lamivudine and has the same resistance profile and minimal additive antiretroviral effects200 201

Maraviroc

No in vitro evidence of antagonistic antiretroviral effects224

Nelfinavir

In vitro evidence of additive to synergistic antiretroviral effects1

Nevirapine

In vitro evidence of additive or synergistic antiretroviral effects1

Rilpivirine

Pharmacokinetic interactions unlikely226

No in vitro evidence of antagonistic antiretroviral effects226

Ritonavir

In vitro evidence of additive or synergistic antiretroviral effects1

Saquinavir

In vitro evidence of additive or synergistic antiretroviral effects1

Stavudine

Pharmacokinetic interaction unlikely1

In vitro evidence of additive or synergistic antiretroviral effects1

Tenofovir

Pharmacokinetic interaction unlikely1

In vitro evidence of additive to synergistic antiretroviral effects1

Tipranavir

In vitro evidence of additive antiretroviral effects211

Zidovudine

In vitro evidence of additive or synergistic antiretroviral effects1

Emtriva 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, tenofovir disoproxil fumarate 300 mg, and emtricitabine 200 mg (Atripla) is bioequivalent to a 600-mg tablet of efavirenz, a 300-mg tablet of tenofovir disoproxil fumarate, and a 200-mg capsule of emtricitabine given simultaneously.232

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

Fixed-combination tablet containing emtricitabine 200 mg and tenofovir disoproxil fumarate 300 mg (Truvada) is bioequivalent to a 200-mg capsule of emtricitabine and a 300-mg tablet of tenofovir disoproxil fumarate given simultaneously.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 (Clcr <50 mL/minute or end-stage renal disease requiring dialysis) due to reduced renal clearance of the drug.1 Dosage adjustment 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

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

Solution

Emtricitabine: 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 fixed combinations: 25°C (may be exposed to 15–30°C).230 232 233

Actions and Spectrum

  • Thio analog of cytidine.1

  • Pharmacologically related to other NRTIs (e.g., abacavir, didanosine, lamivudine, stavudine, zidovudine); differs structurally from these drugs; also differs pharmacologically and structurally from other currently available antiretroviral agents.1

  • 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 Importance of taking as prescribed; do not alter or discontinue antiretroviral regimen without consulting clinician.1 230 232 233

  • Importance of using emtricitabine or emtricitabine/tenofovir (Truvada) in conjunction with other antiretrovirals for treatment of HIV-1 infection—not for monotherapy.1 230 Efavirenz/emtricitabine/tenofovir (Atripla) or emtricitabine/rilpivirine/tenofovir (Complera) can be used alone for treatment of HIV-1 infection.232 233

  • 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

  • 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

  • Truvada medication guide must be provided to and reviewed with all HIV-negative individuals each time emtricitabine/tenofovir 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

  • Redistribution/accumulation of body fat may occur, with as yet unknown long-term health effects.1 230 232 233

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

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

  • Importance of advising patients of other important precautionary information.1 230 232 233 (See Cautions.)

Preparations

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

Emtricitabine

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Capsules

200 mg

Emtriva

Gilead

Solution

10 mg/mL

Emtriva

Gilead

Emtricitabine Combinations

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, film-coated

200 mg with Tenofovir Disoproxil Fumarate 300 mg

Truvada

Gilead

200 mg with Tenofovir Disoproxil Fumarate 300 mg and Efavirenz 600 mg

Atripla

Bristol-Myers Squibb and Gilead

200 mg with Tenofovir Disoproxil Fumarate 300 mg and Rilpivirine Hydrochloride 25 mg (of rilpivirine)

Complera

Gilead

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Atripla 600-200-300MG Tablets (BRISTOL-MYERS SQUIBB/GILEAD): 30/$1,878.96 or 90/$5,400.81

Complera 200-25-300MG Tablets (GILEAD SCIENCES): 30/$1,940.02 or 90/$5,720.03

Emtriva 200MG Capsules (GILEAD SCIENCES): 30/$475.97 or 60/$890.01

Truvada 200-300MG Tablets (GILEAD SCIENCES): 30/$1,149.01 or 90/$3,406.79

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions February 15, 2013. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

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203. Bristol-Myers Squibb. Reyataz (atazanavir sulfate) capsules prescribing information. Princeton, NJ; 2012 Mar.

204. Janssen. Prezista (darunavir) oral suspension and tablets prescribing information. Titusville, NJ; 2012 Jun.

211. Boehringer Ingelheim. Aptivus (tipranavir) capsules and oral solution prescribing information. Ridgefield, CT; 2012 Apr.

214. Janssen. Intelence (etravirine) tablets prescribing information. Raritan, NJ; 2012 Mar.

224. ViiV Healthcare. Selzentry (maraviroc) tablets prescribing information. Research Triangle Park, NC; 2011 Nov.

226. Tibotec Therapeutics. Edurant (rilpivirine) tablets prescribing information. Raritan, NJ; 2011 May.

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