Emtricitabine

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule, Oral:

Emtriva: 200 mg [contains fd&c blue #2 (indigotine)]

Solution, Oral:

Emtriva: 10 mg/mL (170 mL) [contains edetate disodium, fd&c yellow #6 (sunset yellow), methylparaben, propylene glycol, propylparaben; cotton candy flavor]

Pharmacology

Mechanism of Action

Nucleoside reverse transcriptase inhibitor; emtricitabine is a cytosine analogue which is phosphorylated intracellularly to emtricitabine 5'-triphosphate which interferes with HIV viral RNA dependent DNA polymerase resulting in inhibition of viral replication.

Pharmacokinetics/Pharmacodynamics

Absorption

Rapid, extensive

Metabolism

Converted intracellularly to the active triphosphate form; undergoes minimal biotransformation via oxidation and glucuronide conjugation

Excretion

Urine (86% primarily as unchanged drug, 13% as metabolites, 9% of dose as oxidative metabolite; 4% as glucuronide metabolite); feces (14%)

Clearance: Renal clearance is greater than creatinine clearance; thus, emtricitabine may be eliminated by both glomerular filtration and active tubular secretion

Time to Peak

Plasma: 1 to 2 hours

Half-Life Elimination

Normal renal function:

Infants, Children, and Adolescents: Elimination half-life (emtricitabine):

Single dose: 11 hours

Multiple dose: 7.9 to 9.5 hours

Infants 0 to 3 months (n=20; median age: 26 days): 12.1 ± 3.1 hours

Infants 3 to 24 months (n=14): 8.9 ± 3.2 hours

Children 25 months to 6 years (n=19): 11.3 ± 6.4 hours

Children 7 to 12 years (n=17): 8.2 ± 3.2 hours

Adolescents 13 to 17 years (n=27): 8.9 ± 3.3 hours

Adults: Emtricitabine: 10 hours; Intracellular half-life (emtricitabine 5'-triphosphate): 39 hours

Protein Binding

<4%

Use in Specific Populations

Special Populations: Renal Function Impairment

C_max and AUC are increased in patients with CrCl less than 50 mL/minute or ESRD requiring dialysis.

Special Populations: Children

Exposure is similar to adults. In neonates, the AUC was similar to the AUC observed in children at least 3 months to 17 years of age.

Use: Labeled Indications

HIV-1 infection, treatment: Treatment of HIV-1 infection in combination with other antiretroviral agents.

Use: Off Label

HIV-1 nonoccupational postexposure prophylaxisyes

Based on the Centers for Disease Control and Prevention, US Department of Health and Human Services updated guidelines for antiretroviral postexposure prophylaxis after sexual, injection drug use, or other nonoccupational exposure to HIV, emtricitabine (in conjunction with other antiretrovirals) is effective and recommended as postexposure prophylaxis of HIV-1 infection following nonoccupational exposure (nPEP) in individuals exposed to blood, genital secretions, or other potentially infectious body fluids that may contain HIV when that exposure represents a substantial risk for HIV transmission.

HIV-1 occupational postexposure prophylaxisyes

Based on the US Public Health Service updated guidelines for the management of occupational exposures to human immunodeficiency virus and recommendations for postexposure prophylaxis, emtricitabine (in combination with tenofovir disoproxil fumarate and raltegravir) is an effective and recommended treatment option for postexposure prophylaxis of HIV-1 infection in healthcare personnel following occupational exposure (oPEP) to blood and/or other body fluids that may contain HIV.

Contraindications

Hypersensitivity to emtricitabine or any component of the formulation

Dosage and Administration

Dosing: Adult

HIV-1 infection, treatment: Oral:

Capsule: 200 mg once daily

Solution: 240 mg once daily

HIV-1 nonoccupational postexposure prophylaxis (nPEP) (off-label use): Oral: Capsule: 200 mg once daily; initiate therapy within 72 hours of exposure and continue for 28 days in combination with other antiretrovirals (3-drug regimen) Note: The fixed-dose emtricitabine and tenofovir disoproxil fumarate combination product is recommended for these components of the 3-drug regimen (HHS [nPEP] 2016).

HIV-1 occupational postexposure prophylaxis (oPEP) (off-label use): Oral: Capsule: 200 mg once daily in combination with tenofovir disoproxil fumarate and raltegravir; initiate therapy as soon as possible after occupational exposure (and within 72 hours) and continue for 4 weeks; Note: The fixed-dose emtricitabine and tenofovir disoproxil fumarate combination product is recommended for these components of the regimen (Kuhar 2013).

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Note: Due to bioavailability differences, oral dosage forms are not bioequivalent; oral solution and capsules should not be interchanged on a mg:mg basis. Gene mutation and antiretroviral (ARV) resistance patterns should be evaluated (refer to https://www.iasusa.org/ for more information) when necessary.

HIV-1 infection, treatment: Note: Use in combination with other ARV agents. Oral:

Infants 1 to <3 months: Oral solution: 3 mg/kg/dose once daily.

Infants ≥3 months, Children, and Adolescents ≤17 years:

Oral solution: 6 mg/kg/dose once daily; maximum daily dose: 240 mg/day.

Capsules: Patient weight >33 kg and able to swallow capsule whole: 200 mg once daily.

Adolescents ≥18 years:

Capsules: 200 mg once daily.

Oral solution: 240 mg once daily.

HIV-1 nonoccupational postexposure prophylaxis (nPEP) (HHS [nPEP] 2016): Note: Initiate therapy within 72 hours of exposure and continue for 28 days in combination with other ARV agents. Oral:

Infants 1 to <3 months: Oral solution: 3 mg/kg/dose once daily.

Infants ≥3 months and Children:

Oral solution: 6 mg/kg/dose once daily; maximum daily dose: 240 mg/day.

Capsules: Patient weight >33 kg and able to swallow capsule whole: 200 mg once daily.

Adolescents: The combination product is recommended (see emtricitabine and tenofovir disoproxil fumarate monograph).

Administration

Administer with or without food.

Storage

Capsules: Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Dispense in original container.

Oral solution: Store at 2°C to 8°C (36°F to 46°F). Use within 3 months if stored at 25°C (77°F) with excursions permitted to 15°C to 30°C (59°F to 86°F).

Drug Interactions

Cladribine: Agents that Undergo Intracellular Phosphorylation may diminish the therapeutic effect of Cladribine. Avoid combination

LamiVUDine: May enhance the adverse/toxic effect of Emtricitabine. Avoid combination

Orlistat: May decrease the serum concentration of Antiretroviral Agents. Monitor therapy

Adverse Reactions

Clinical trials were conducted in patients receiving other antiretroviral agents, and it is not possible to correlate frequency of adverse events with emtricitabine alone. The range of frequencies of adverse events is generally comparable to comparator groups, with the exception of hyperpigmentation, which occurred more frequently in patients receiving emtricitabine. Unless otherwise noted, percentages are as reported in adults.

>10%:

Central nervous system: Dizziness (4% to 25%), headache (6% to 22%), insomnia (5% to 16%), abnormal dreams (2% to 11%)

Dermatologic: Hyperpigmentation (children: 32%; adults: 2% to 4%; primarily of palms and/or soles but may include tongue, arms, lip and nails; generally mild and nonprogressive without associated local reactions such as pruritus or rash), skin rash (17% to 30%; includes hypersensitivity reaction, maculopapular rash, pruritus, pustular rash, vesiculobullous rash)

Gastrointestinal: Diarrhea (children: 20%; adults: 9% to 23%), vomiting (children: 23%; adults: 9%), nausea (13% to 18%), abdominal pain (8% to 14%), gastroenteritis (children: 11%)

Infection: Infection (children: 44%)

Neuromuscular & skeletal: Weakness (12% to 16%), increased creatine phosphokinase (grades 3/4: 11% to 12%)

Otic: Otitis media (children: 23%)

Respiratory: Cough (children: 28%; adults; 14%), rhinitis (children: 20%; adults: 12% to 18%), pneumonia (children: 15%)

Miscellaneous: Fever (children: 18%)

1% to 10%:

Central nervous system: Depression (6% to 9%), paresthesia (5% to 6%), neuritis (≤4%), neuropathy (≤4%)

Endocrine & metabolic: Increased serum triglycerides (grades 3/4: 4% to 10%), increased amylase (grades 3/4: children: 9%; adults: 2% to 5%), hyperglycemia (grades 3/4: 2% to 3%)

Gastrointestinal: Dyspepsia (4% to 8%), increased serum lipase (grades 3/4: ≤1%)

Genitourinary: Hematuria (grades 3/4: 3%)

Hematologic & oncologic: Anemia (children: 7%), neutropenia (grades 3/4: children: 2%; adults: 5%)

Hepatic: Increased serum transaminases (grades 3/4: 2% to 6%), increased serum alkaline phosphatase (>550 units/L: 1%), increased serum bilirubin (grades 3/4: 1%)

Neuromuscular & skeletal: Myalgia (4% to 6%), arthralgia (3% to 5%)

Respiratory: Sinusitis (8%), upper respiratory tract infection (8%), pharyngitis (5%)

<1%, postmarketing, and/or case reports: Immune reconstitution syndrome

Warnings/Precautions

Concerns related to adverse effects:

• Immune reconstitution syndrome: Patients may develop immune reconstitution syndrome resulting in the occurrence of an inflammatory response to an indolent or residual opportunistic infection during initial HIV treatment or activation of autoimmune disorders (eg, Graves’ disease, polymyositis, Guillain-Barré syndrome) later in therapy; further evaluation and treatment may be required.
• Lactic acidosis/hepatomegaly: Lactic acidosis and severe hepatomegaly with steatosis, sometimes fatal, have been reported with use of nucleoside analogs, alone or in combination with other antiretrovirals. Suspend treatment in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity (marked transaminase elevation may/may not accompany hepatomegaly and steatosis).

Disease-related concerns:

• Chronic hepatitis B: Severe acute exacerbations of hepatitis B (HBV) have been reported in patients who are coinfected with HIV-1 and HBV and have discontinued emtricitabine. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who are coinfected with HIV-1 and HBV and discontinue emtricitabine. If appropriate, anti-hepatitis B therapy may be warranted, especially in patients with advanced hepatic disease or cirrhosis, because posttreatment exacerbation of hepatitis may lead to hepatic decompensation and liver failure. All patients with HIV should be tested for HBV prior to or when initiating treatment.
• Renal impairment: Use with caution in patients with renal impairment; dosage adjustment required.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Dosage form specific issues:

• Propylene glycol: Some dosage forms may contain propylene glycol; large amounts are potentially toxic and have been associated with hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution (AAP 1997; Zar 2007).

Monitoring Parameters

Viral load, CD4, liver function tests; serum creatinine; hepatitis B testing is recommended prior to or when initiating therapy.

Pregnancy

Pregnancy Considerations

Emtricitabine has a high level of transfer across the human placenta.

No increased risk of overall birth defects has been observed according to data collected by the antiretroviral pregnancy registry. Maternal antiretroviral therapy (ART) may be associated with adverse pregnancy outcomes including preterm delivery, stillbirth, low birth weight, and small for gestational age infants. Actual risks may be influenced by maternal factors, such as disease severity, gestational age at initiation of therapy, and specific ART regimen, therefore close fetal monitoring is recommended. Because there is clear benefit to appropriate treatment, maternal ART should not be withheld due to concerns for adverse neonatal outcomes. Long-term follow-up is recommended for all infants exposed to antiretroviral medications; children without HIV but who were exposed to ART in utero and develop significant organ system abnormalities of unknown etiology (particularly of the CNS or heart) should be evaluated for potential mitochondrial dysfunction. Cases of lactic acidosis and hepatic steatosis have been reported in pregnant women with use of nucleoside reverse transcriptase inhibitors (NRTIs).

The Health and Human Services (HHS) perinatal HIV guidelines consider emtricitabine a preferred NRTI for pregnant females living with HIV who are antiretroviral-naive, who have had ART therapy in the past but are restarting, who require a new ART regimen (due to poor tolerance or poor virologic response of current regimen), and who are not yet pregnant but are trying to conceive. In addition, females who become pregnant while taking emtricitabine may continue if viral suppression is effective and the regimen is well tolerated. The pharmacokinetics of emtricitabine are not significantly altered during pregnancy and dosing adjustments are not needed.

The HHS perinatal HIV guidelines consider emtricitabine with tenofovir disoproxil fumarate to be a preferred NRTI backbone for initial therapy in antiretroviral-naive pregnant females. The guidelines also consider emtricitabine plus tenofovir disoproxil fumarate a recommended dual NRTI backbone in regimens for HIV/hepatitis B virus-coinfected pregnant females. Use caution with hepatitis B coinfection; hepatitis B flare may occur if emtricitabine is discontinued. Emtricitabine is also a preferred component of an initial regimen when acute HIV infection is detected during pregnancy.

In general, ART is recommended for all pregnant females living with HIV to keep the viral load below the limit of detection and reduce the risk of perinatal transmission. Therapy should be individualized following a discussion of the potential risks and benefits of treatment during pregnancy. Monitoring of pregnant females is more frequent than in nonpregnant adults. ART should be continued postpartum for all females living with HIV and can be modified after delivery.

Emtricitabine is one of the agents recommended for preexposure prophylaxis in couples with discordant HIV status who are planning a pregnancy. The partner without HIV should begin therapy 1 month prior to attempting conception and continue therapy for 1 month after attempting conception.

Health care providers are encouraged to enroll pregnant females exposed to antiretroviral medications as early in pregnancy as possible in the Antiretroviral Pregnancy Registry (1-800-258-4263 or http://www.APRegistry.com). Health care providers caring for pregnant females living with HIV and their infants may contact the National Perinatal HIV Hotline (888-448-8765) for clinical consultation (HHS [perinatal] 2019).

Patient Education

What is this drug used for?

• It is used to treat HIV infection.

Frequently reported side effects of this drug

• Dizziness
• Nightmares
• Loss of strength and energy
• Headache
• Trouble sleeping
• Abdominal pain
• Nausea
• Vomiting
• Diarrhea
• Runny nose

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Lactic acidosis like fast breathing, fast heartbeat, abnormal heartbeat, vomiting, fatigue, shortness of breath, severe loss of strength and energy, severe dizziness, feeling cold, or muscle pain or cramps.
• Liver problems like dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin.
• Depression
• Skin discoloration
• Infection
• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.