Emtricitabine is a nucleoside reverse transcriptase inhibitor (NRTI) indicated for use with other antiretroviral medications to treat HIV-1 infections. Emtricitabine belongs to the same nucleoside series as lamivudine, and therefore, should not be used in individuals who display resistance to lamivudine. Before starting emtricitabine, all potential drug recipients should be tested for the presence of chronic hepatitis B virus (HBV). The package labeling contains a Black Box Warning that severe, acute HBV exacerbations have been reported in HIV and HBV coinfected patients who discontinue use of emtricitabine. Closely monitor any HIV and HBV coinfected patient who discontinues emtricitabine for several months for signs and symptoms of worsening hepatitis infection.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Oral Administration
-Administer with or without food.
Oral Liquid Formulations
-Administer oral solution using the supplied dosing cup.
Rash, including allergic reaction, maculopapular rash, pruritus, pustular rash, rash (unspecified), urticaria, vesicular rash, and bullous rash, was reported in 17-30% of adults receiving emtricitabine as part of combination therapy and was listed as a Grade 2-4 event (rash, exfoliative rash/exfoliative dermatitis, macular rash, maculopapular rash, pruritis, and vesicular rash) in 7% of patients. Rash was noted in 21% of pediatric patients.
Gastrointestinal related adverse events reported with emtricitabine as part of combination therapy include diarrhea (9-23% adults; 20% pediatrics), nausea (9-18% adults), abdominal pain (8-14% adults; 10% pediatrics), dyspepsia (4-8% adults), vomiting (2-9% adults; 23% pediatrics), and gastroenteritis (11% pediatrics).
Musculoskeletal reactions reported with emtricitabine as part of combination therapy consisted of arthralgia (3-5%), myalgia (4-6%), and paresthesias (5-6%).
Central nervous system or psychiatric adverse reactions, including depression (6-9%), dizziness (4-25%), peripheral neuropathy/neuritis (4%), abnormal dreams (2-11%), and insomnia (5-16%), were reported during clinical trials with emtricitabine as part of combination therapy.
Respiratory adverse events reported with emtricitabine during combination therapy include cough (14% adults; 28% pediatrics) and rhinitis (12-18% adults; 20% pediatrics).
Abnormal lab values were reported with emtricitabine when used as part of combination therapy and included elevated creatinine kinase levels (9-12%), hyperamylasemia (2-8%), hypertriglyceridemia (4-10%), hypercholesterolemia (22%), hyperglycemia or hypoglycemia (2-3%), and elevated serum lipase (<= 1%). Additionally, elevated hepatic enzymes were reported including ALT levels > 5 times the upper limits of normal (ULN) (2-5%), AST levels > 5xULN (3-6%), alkaline phosphatase > 550 units/L (1%), and hyperbilirubinemia > 2.5xULN (<= 1%). Grade 3/4 laboratory abnormalities were experienced by 9% of pediatric patients and included hyperamylasemia, elevated hepatic enzymes, elevated CPK, hyperbilirubinemia, elevated lipase, and decreased glucose.
In clinical trials, skin hyperpigmentation was reported in patients treated with emtricitabine. This discoloration manifested on the palms of the hands and/or soles of the feet, was generally mild and asymptomatic, and was predominantly reported in non-Caucasian patients. The mechanism and clinical significance are unknown. According to the manufacturer, the incidence of hyperpigmentation was higher in pediatric patients (32%) than in adults.
Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside reverse transcriptase inhibitors, including emtricitabine. Many of these cases have occurred in women, obese patients, and patients with prolonged nucleoside exposure. If a patient develops clinical or laboratory findings suggestive of lactic acidosis or hepatotoxicity while receiving emtricitabine, the drug should be discontinued.
Infectious adverse events reported with the use of emtricitabine in clinical trials include sinusitis (8%), upper respiratory tract infection (8%), naso-pharyngitis (5%), unspecified pediatric infection (44%), otitis media (23%), and pneumonia in pediatric patients (15%).
General adverse events reported with emtricitabine during combination therapy trials include asthenia (12-16%), headache (6-22%), and fatigue (9%). Fever was noted in 18% of pediatric patients during trials.
Neutropenia was reported in 3-5% of adults with the use of emtricitabine during combination therapy clinical trials. Anemia was noted in 7% of pediatric patients. Grade 3/4 laboratory abnormalities were experienced by 9% of pediatric patients and included neutropenia (2.6%) and decreased hemoglobin.
Abnormal urinary laboratory values reported during emtricitabine during combination therapy trials include hematuria (3%) and glycosuria (< 1%).
Severe acute hepatitis B exacerbation (i.e., hepatic decompensation and hepatic failure) has been reported in HBV and HIV coinfected patients who discontinue treatment with emtricitabine. If use of emtricitabine is stopped in a coinfected patient, closely monitor hepatic function with both clinical and laboratory follow-up for at least several months. If appropriate, treatment for hepatitis B infection may be warranted. Prior to initiating antiretroviral therapy for the treatment of HIV, it is recommended that all patients be tested for the presence of chronic HBV.
During baseline evaluation of people with HIV, discuss risk reduction measures and the need for status disclosure to sexual or needle-sharing partners, especially with untreated patients who are still at high risk of HIV transmission. Include the importance of adherence to therapy to achieve and maintain a plasma HIV RNA less than 200 copies/mL. Maintaining a plasma HIV RNA less than 200 copies/mL, including any measurable value below this threshold, with antiretroviral therapy prevents sexual transmission of HIV to their partners. Patients may recognize this concept as Undetectable = Untransmittable or U=U. Instruct patients to achieve sustained viral suppression (i.e., 2 recorded measurements of plasma viral loads that are below the limits of detection and taken at least 3 months apart) before attempting to conceive a child in order to maximize their health, prevent HIV sexual transmission, and minimize the risk of HIV transmission to the infant once conception occurs. For partners with different HIV status when the person with HIV is on antiretroviral therapy and has achieved sustained viral suppression, sexual intercourse without a condom allows conception without sexual HIV transmission to the person without HIV. Expert consultation is recommended.
Unplanned antiretroviral therapy interruption may be necessary for specific situations, such as serious drug toxicity, intercurrent illness or surgery precluding oral intake (e.g., gastroenteritis or pancreatitis), severe hyperemesis gravidarum unresponsive to antiemetics, or drug non-availability. If short-term treatment interruption (i.e., less than 1 to 2 days) is necessary, in general, it is recommended that all antiretroviral agents be discontinued simultaneously, especially if the interruption occurs in a pregnant patient or is because of a serious toxicity. However, if a short-term treatment interruption is anticipated in the case of elective surgery, the pharmacokinetic properties and food requirements of specific drugs should be considered; as stopping all simultaneously in a regimen containing drugs with differing half-lives may result in functional monotherapy of the drug with the longest half-life and may increase the risk for resistant mutations. Healthcare providers are advised to reinitiate a complete and effective antiretroviral regimen as soon as possible after an interruption of therapy. Planned long-term treatment interruptions are not recommended due to the potential for HIV disease progression (i.e., declining CD4 counts, viral rebound, acute viral syndrome), development of minor HIV-associated manifestations or serious non-AIDS complications, development of drug resistance, increased risk of HIV transmission, and increased risk for opportunistic infections. If therapy must be discontinued, counsel patient on the potential risks and closely monitor for any clinical or laboratory abnormalities.
Testing for human immunodeficiency virus (HIV) infection resistance is recommended in all antiretroviral treatment-naive patients at the time of HIV diagnosis, regardless of whether treatment will be initiated. Additionally, perform resistance testing prior to initiating or changing any HIV treatment regimen. Transmission of drug-resistant HIV strains has been both well documented and associated with suboptimal virologic response to initial antiretroviral therapy. The prevalence of transmitted drug resistance (TDR) in high-income countries ranges from 9% to 14% and varies by country. In most TDR surveys, non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance and nucleoside reverse transcriptase inhibitor (NRTI) resistance are the most common mutation class types detected, followed by protease inhibitor (PI) and integrase strand transfer inhibitor (INSTI) resistance mutations, respectively. Resistance testing at baseline can help optimize treatment and, thus, virologic response. In the absence of therapy, resistant viruses may decline over time to less than the detection limit of standard resistance tests, but may still increase the risk of treatment failure when therapy is eventually initiated. Thus, if therapy is deferred, resistance testing should still be performed during acute HIV infection with the genotypic resistance test result kept in the patient's medical record until it becomes clinically useful. Additionally, because of the possibility of acquisition of another drug-resistant virus before treatment initiation, repeat resistance testing at the time therapy is initiated would be prudent. Due to the similarities between the two drugs, emtricitabine will not likely be effective in individuals who display antimicrobial resistance to lamivudine. Clinicians should not expect patients with the M184 mutation associated with lamivudine to benefit from emtricitabine. The M184 mutation confers high-level resistance, and emtricitabine, like lamivudine, selects for the M184 mutation. It is important that persons with detectable viral load who plan to switch therapy from lamivudine to emtricitabine have genotypic testing performed to determine whether the M184V mutation is present. A patient's treatment history is also extremely important; if lamivudine has failed in the past, the 184 is archived, thus rendering emtricitabine ineffective in this patient population. In addition, as with all other antiretroviral agents, resistance can develop when emtricitabine is used either alone or in combination with other agents; monotherapy with emtricitabine is not recommended.
Emtricitabine is not indicated for the treatment of chronic hepatitis B virus (HBV) infection, and safety and efficacy of treatment have not been established in patients with hepatitis B and HIV coinfection. Perform hepatitis B virus (HBV) screening in any patient who presents with HIV-infection to assure appropriate treatment. Patients who are coinfected with HIV and HBV should be started on a fully suppressive antiretroviral (ARV) regimen with activity against both viruses (regardless of CD4 counts and HBV DNA concentrations). HIV treatment guidelines recommend these patients receive an ARV regimen that contains a dual NRTI backbone of tenofovir alafenamide or tenofovir disoproxil fumarate with either emtricitabine or lamivudine. If tenofovir cannot be used, entecavir should be used in combination with a fully suppressive ARV regimen (note: entecavir should not be considered part of the ARV regimen). Avoid using single-drug therapy to treat HBV (i.e., lamivudine, emtricitabine, tenofovir, or entecavir as the only active agent) as this may result in HIV resistant strains. Further, HBV treatment regimens that include adefovir or telbivudine should also be avoided, as these regimens are associated with a higher incidence of toxicities and increased rates of HBV treatment failure. Most coinfected patients should continue treatment indefinitely with the goal of maximal HIV suppression and prevention of HBV relapse. If considering treatment discontinuation, it is important to note that some patients with coexisting HIV and HBV infections have experienced severe acute hepatitis B exacerbation (e.g., hepatic decompensation or failure) following discontinuation of emtricitabine. Therefore, patients who discontinue emtricitabine should have transaminase concentrations monitored every 6 weeks for the first 3 months, and every 3 to 6 months thereafter. If appropriate, resumption of anti-hepatitis B treatment may be required, especially in patients with advanced liver disease or cirrhosis. For patients who refuse a fully suppressive ARV regimen, but still require treatment for HBV, consider 48 weeks of peginterferon alfa; do not administer HIV-active medications in the absence of a fully suppressive ARV regimen. Instruct patients to avoid consuming alcohol, and offer vaccinations against hepatitis A and hepatitis B as appropriate.
Safety and efficacy of emtricitabine capsules have not been established in neonates, infants, children, or adolescents weighing <= 33 kg. Consider administering emtricitabine solution in pediatric patients weighing <= 33 kg or who are unable to swallow an intact capsule.
Geriatric patients are more likely to have decreased renal function and may require dose reduction and special monitoring (see Dosage). Clinical trials of emtricitabine did not contain significant numbers of elderly patients to determine if they would respond differently from younger patients.
Lactic acidosis and hepatomegaly with steatosis, including fatal cases, have been reported following use of emtricitabine, both alone and in combination with other antiretroviral medications. Treatment with emtricitabine should be suspended in any patient who develops clinical or laboratory findings suggestive of hepatotoxicity or lactic acidosis, which may include hepatomegaly and steatosis even in the absence of marked elevated hepatic enzymes. Although these adverse events may occur in any drug recipient, some risk factors include hepatic disease (e.g., alcoholism), obesity, and prolonged nucleoside exposure. In addition, a majority of these cases have been in females; it is unknown if being pregnant augments the incidence of this syndrome in patients receiving nucleoside analogs. However, because being pregnant itself can mimic some of the early symptoms of the lactic acid and hepatic steatosis syndrome or be associated with other significant disorders of liver metabolism, clinicians need to be alert for early diagnosis of this syndrome. Pregnant women receiving nucleoside analogs should have LFTs and serum electrolytes assessed more frequently during the last trimester and any new symptoms should be evaluated thoroughly.
Antiretroviral therapy should be provided to all patients during pregnancy, regardless of HIV RNA concentrations or CD4 cell count. Using highly active antiretroviral combination therapy (HAART) to maximally suppress viral replication is the most effective strategy to prevent the development of resistance and to minimize the risk of perinatal transmission. Begin HAART as soon as pregnancy is recognized, or HIV is diagnosed. HIV guidelines recommend the use of emtricitabine with tenofovir alafenamide or tenofovir disoproxil fumarate as preferred 2-NRTI backbones in patients who are pregnant or trying to become pregnant. Available data from the Antiretroviral Pregnancy Registry, which includes more than 4,567 first trimester exposures to emtricitabine, have shown no difference in the risk of overall major birth defects when compared to the 2.7% background rate among pregnant women in the US. When emtricitabine exposure occurred in the first trimester, the prevalence of defects was 2.9% (95% CI: 2.5 to 3.5). Nucleoside reverse transcriptase inhibitors (NRTIs) are known to induce mitochondrial dysfunction. An association of mitochondrial dysfunction in infants and in utero antiretroviral exposure has been suggested, but not established. While the development of severe or fatal mitochondrial disease in exposed infants appears to be extremely rare, more intensive monitoring of hematologic and electrolyte parameters during the first few weeks of life is advised. Nucleoside analogs have been associated with the development of lactic acidosis, especially during pregnancy. It is unclear if pregnancy augments the incidence of lactic acidosis/hepatic steatosis in patients receiving nucleoside analogs. However, because pregnancy itself can mimic some early symptoms of the lactic acid/hepatic steatosis syndrome or be associated with other significant disorders of liver metabolism, clinicians need to be alert for early diagnosis of this syndrome. Pregnant patients receiving nucleoside analogs should have LFTs and serum electrolytes assessed more frequently during the last trimester of pregnancy, and any new symptoms should be evaluated thoroughly. Regular laboratory monitoring is recommended to determine antiretroviral efficacy. Monitor CD4 counts at the initial visit. Patients who have been on HAART for at least 2 years and have consistent viral suppression and CD4 counts consistently greater than or equal to 300 cells/mm3 do not need CD4 counts monitored after the initial visit during the pregnancy. However, CD4 counts should be monitored every 3 months during pregnancy for patients on HAART less than 2 years and have CD4 counts less than 300 cells/mm3, patients with inconsistent adherence, or patients with detectable viral loads. For patients on HAART less than 2 years but have CD4 counts greater than or equal to 300 cells/mm3, monitor CD4 counts every 6 months. Monitor plasma HIV RNA at the initial visit (with review of prior levels), 2 to 4 weeks after initiating or changing therapy, monthly until undetectable, and then at least every 3 months during pregnancy. Viral load should also be assessed at approximately 36 weeks gestation, or within 4 weeks of planned delivery, to inform decisions regarding mode of delivery and optimal treatment for newborns. Patients whose HIV RNA levels are above the threshold for resistance testing (usually greater than 500 copies/mL but may be possible for levels greater than 200 copies/mL in some laboratories) should undergo antiretroviral resistance testing (genotypic testing, and if indicated, phenotypic testing). Resistance testing should be conducted before starting therapy in treatment-naive patients who have not been previously tested, starting therapy in treatment-experienced patients (including those who have received pre-exposure prophylaxis), modifying therapy in patients who become pregnant while receiving treatment, or modifying therapy in patients who have suboptimal virologic response to treatment that was started during pregnancy. DO NOT delay initiation of antiretroviral therapy while waiting on the results of resistance testing; treatment regimens can be modified, if necessary, once the testing results are known. First trimester ultrasound is recommended to confirm gestational age and provide an accurate estimation of gestational age at delivery. A second trimester ultrasound can be used for both anatomical survey and determination of gestational age in those patients not seen until later in gestation. Perform standard glucose screening in patients receiving antiretroviral therapy at 24 to 28 weeks gestation, although it should be noted that some experts would perform earlier screening with ongoing chronic protease inhibitor-based therapy initiated prior to pregnancy, similar to recommendations for patients with high-risk factors for glucose intolerance. Liver function testing is recommended within 2 to 4 weeks after initiating or changing antiretroviral therapy, and approximately every 3 months thereafter during pregnancy (or as needed). All pregnant patients should be counseled about the importance of adherence to their antiretroviral regimen to reduce the potential for development of resistance and perinatal transmission. It is strongly recommended that antiretroviral therapy, once initiated, not be discontinued. If a patient decides to discontinue therapy, a consultation with an HIV specialist is recommended. There is a pregnancy exposure registry that monitors outcomes in pregnant patients exposed to emtricitabine; information about the registry can be obtained at www.apregistry.com or by calling 1-800-258-4263.
HIV treatment guidelines recommend clinicians provide mothers with evidence-based, patient-centered counseling to support shared decision-making regarding infant feeding. Inform patients that use of replacement feeding (i.e., formula or banked pasteurized donor human milk) eliminates the risk of HIV transmission. Advise patients who receive a diagnosis of HIV infection while breast-feeding (acute HIV) to immediately discontinue breast-feeding and switch to replacement feeding in order to reduce the risk of postnatal HIV transmission to the infant. Replacement feeding is also recommended for use when mothers with HIV are not on antiretroviral therapy (ART) or do not have suppressed viral load during pregnancy, as well as at delivery. For patients on ART who have achieved and maintained viral suppression during pregnancy (at minimum throughout the third trimester) and postpartum, the transmission risk from breast-feeding is less than 1%, but not zero. Virologically suppressed mothers who choose to breast-feed should be supported in this decision. If breast-feeding is chosen, counsel the patient about the importance of adherence to therapy and recommend that the infant be exclusively breast-fed for up to 6 months of age, as exclusive breast-feeding has been associated with a lower rate of HIV transmission as compared to mixed feeding (i.e., breast milk and formula). Promptly identify and treat mastitis, thrush, and cracked or bleeding nipples, as these conditions may increase the risk of HIV transmission through breast-feeding. Breast-fed infants should undergo immediate diagnostic and virologic HIV testing. Testing should continue throughout breast-feeding and up to 6 months after cessation of breast-feeding. For expert consultation, healthcare workers may contact the Perinatal HIV Hotline (888-448-8765). Limited data suggest small amounts of emtricitabine are excreted during breast-feeding. Exposure of an exclusively breast-fed infant is estimated at approximately 2% of the recommended infant dose, potentially placing the infant at risk of developing viral resistance or other associated adverse events. Other antiretroviral medications whose passage into human breast milk have been evaluated include nevirapine, zidovudine, lamivudine, and nelfinavir.
Emtricitabine is eliminated by the kidney. Emtricitabine should be used with caution in patients with renal impairment, including renal failure, and dosage adjustments are required.
Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy. During the initial phase of HIV treatment, patients whose immune system responds to emtricitabine therapy may develop an inflammatory response to indolent or residual opportunistic infections (such as progressive multifocal leukoencephalopathy (PML), mycobacterium avium complex (MAC), cytomegalovirus (CMV), Pneumocystis carinii pneumonia (PCP), or tuberculosis (TB)), which may necessitate further evaluation and treatment. In addition, autoimmune disease (including Graves' disease, Guillain-Barre syndrome, and polymyositis) may also develop; the time to onset is variable and may occur months after treatment initiation.
HIV treatment guidelines recommend all patients presenting with HIV infection undergo routine screening for hepatitis C virus (HCV). For HCV seronegative individuals who are at continued high risk of acquiring hepatitis C, specifically men who have sex with men (MSM) or persons who inject drugs, additional HCV screening is recommended annually or as indicated by clinical presentation (e.g., unexplained ALT elevation), risk activities, or exposure. Similarly, the AASLD/IDSA HCV guidelines and the CDC preexposure prophylaxis (PrEP) guidelines recommend HCV serologic testing at baseline and every 12 months for MSM, transgender women, and persons who inject drugs. Use an FDA-approved immunoassay licensed for detection of HCV antibodies (anti-HCV); in settings where acute HCV infection is suspected or in persons with known prior infection that cleared spontaneously or after treatment, use of nucleic acid testing for HCV RNA is recommended. If hepatitis C and HIV coinfection is identified, consider treating both viral infections concurrently. It is recommended to use a fully suppressive antiretroviral therapy and an HCV regimen in all patients with coinfection regardless of CD4 count, as lower CD4 counts do not appear to compromise the efficacy of HCV treatment. In most patients, a simplified pangenotypic HCV regimen (i.e., glecaprevir; pibrentasvir or sofosbuvir; velpatasvir) may be an appropriate choice; however, these regimens are NOT recommended for use in persons with HCV and HIV coinfection who: are treatment-experienced with HCV relapse (reinfection after successful therapy is not an exclusion); have decompensated cirrhosis; on a tenofovir disoproxil fumarate containing regimen with eGFR less than 60 mL/minute; on efavirenz, etravirine, nevirapine, or boosted protease inhibitor; have untreated chronic hepatitis B; are pregnant. Patients with HCV and HIV coinfection who meet these exclusion criteria should be treated for HCV following standard approaches as described in the AASLD/IDSA HCV guidelines. Treatment of HCV infection in children younger than 3 years is not usually recommended; however, treatment should be considered for all children 3 years and older with HCV and HIV coinfection who have no contraindications to treatment. Instruct patients with coinfection to avoid consuming alcohol, limit ingestion of potentially hepatotoxic medications, avoid iron supplementation in the absence of documented iron deficiency, and receive vaccinations against hepatitis A and hepatitis B as appropriate.
Initiation of therapy for HIV treatment:
-For adults, initiation of treatment immediately (or as soon as possible) after HIV diagnosis is recommended in all patients to reduce the risk of disease progression and to prevent the transmission of HIV, including perinatal transmission and transmission to sexual partners. Starting antiretroviral therapy early is particularly important for patients with AIDS-defining conditions, those with acute or recent HIV infection, and individuals who are pregnant; delaying therapy in these subpopulations has been associated with high risks of morbidity, mortality, and HIV transmission.
-Prior to initiating treatment, obtain baseline plasma HIV RNA (viral load) and CD4 count; results do not need to be available before starting therapy.
-Antiretroviral drug-resistance testing:-Genotypic drug-resistance testing is recommended prior to initiation of therapy and prior to changing therapy for treatment failure.
--Standard genotypic drug-resistance testing in treatment-naive people should focus on testing for mutations in reverse transcriptase (RT) and protease (PR) genes.
-Testing for mutations in the integrase gene should also be performed if integrase strand transfer inhibitor (INSTI) resistance is a concern (e.g., people who acquire HIV after pre-exposure prophylaxis with long-acting cabotegravir).
-Phenotypic resistance testing may be used in conjunction with the genotypic test for patients with known or suspected complex drug-resistance mutation patterns.
-HIV-1 proviral DNA resistance testing is available for use in patients with HIV RNA concentrations below the limits of detection or with low-level viremia (i.e., less than 1,000 copies/mL), where genotypic testing is unlikely to be successful; however, the clinical utility of this assay has not been fully determined.
-It is not necessary to delay treatment until resistance test results are available; however, subsequent modifications to the treatment regimen should be made, if needed, once the test results are available.
-Pediatric guidelines are also available.
Place in therapy for HIV treatment:
-For pregnant and non-pregnant adults and adolescents, emtricitabine plus tenofovir alafenamide or tenofovir disoproxil fumarate are preferred 2-NRTI backbones.
-Pediatric guidelines are also available.
Per the manufacturer, this drug has been shown to be active against most strains of the following microorganisms either in vitro and/or in clinical infections: human immunodeficiency virus (HIV)
NOTE: The safety and effectiveness in treating clinical infections due to organisms with in vitro data only have not been established in adequate and well-controlled clinical trials.
This drug may also have activity against the following microorganisms: hepatitis B virus
NOTE: Some organisms may not have been adequately studied during clinical trials; therefore, exclusion from this list does not necessarily negate the drug's activity against the organism.
For the treatment of human immunodeficiency virus (HIV) infection in combination with other antiretroviral agents:
Oral dosage (capsules):
Adults: 200 mg PO once daily.
Children and Adolescents weighing more than 33 kg: 200 mg PO once daily.
Oral dosage (solution):
Adults: 240 mg PO once daily.
Infants, Children, and Adolescents 3 months to 17 years: 6 mg/kg/dose (Max: 240 mg/dose) PO once daily.
Neonates and Infants younger than 3 months: 3 mg/kg/dose PO once daily.
For human immunodeficiency virus (HIV) prophylaxis*:
-for human immunodeficiency virus (HIV) prophylaxis* after occupational exposure:
Oral dosage (capsules):
Adults: 200 mg PO once daily plus tenofovir 300 mg PO once daily (generally given as single combination product), in combination with a third antiretroviral agent, is a preferred regimen for HIV post-exposure prophylaxis (PEP). According to PEP guidelines, individuals potentially exposed to HIV should receive a 3-drug regimen for a total of 28 days; however if tolerability is a concern, use of a 2-drug regimen may be considered and is preferred to prophylaxis discontinuation. The recommended third antiretroviral agent to be administered in combination with emtricitabine and tenofovir varies among published guidelines and includes one of the following: raltegravir, dolutegravir, lopinavir; ritonavir, or atazanavir boosted with ritonavir. Additionally, emtricitabine plus tenofovir may be used as part of alternative regimens in combination with other antiretroviral agents. Begin prophylaxis as soon as possible, ideally within 2 hours of exposure. If initiation of prophylaxis is delayed (beyond 36 hours or 72 hours after exposure), efficacy of the antiretroviral regimen may be diminished and treatment should be determined on a case-by-case basis. Exposures for which PEP is indicated include: skin puncture by a sharp object that has been contaminated with blood, body fluid, or other infectious material; bite from a patient with visible bleeding in the mouth which causes bleeding by the exposed worker; splash of blood, body fluid, or other infectious material onto the workers mouth, nose, or eyes; exposure of blood, body fluid, or other infectious material on a workers non-intact skin (i.e., open wound, chapped skin, abrasion, dermatitis).
-for human immunodeficiency virus (HIV) prophylaxis* after nonoccupational exposure, including sexual assault:
NOTE: Higher risk exposures for which prophylaxis is recommended include exposure of vagina, rectum, eye, mouth, or other mucous membrane, nonintact skin, or percutaneous contact with blood, semen, vaginal secretions, rectal secretions, breast milk, or any body fluid that is visibly contaminated with blood when the source is known to be HIV-positive. Exposures to a source patient with unknown HIV status should be assessed on a case-by-case basis.
Oral dosage (capsules):
Adults: 200 mg PO once daily in combination with tenofovir and raltegravir or dolutegravir for 28 days is a preferred HIV post-exposure prophylaxis (PEP) regimen in adults. Emtricitabine in combination with tenofovir and darunavir/ritonavir is an alternative HIV PEP regimen. A 3-drug regimen is recommended for all cases when PEP is indicated; however, the use of a 2-drug regimen (2 NRTIs or a combination of a PI and a NNRTI) may be considered if tolerability or adherence is a concern. Begin prophylaxis as soon as possible after exposure; prophylaxis initiated more than 72 hours after exposure is unlikely to be effective.
Adolescents weighing more than 33 kg: 200 mg PO once daily in combination with tenofovir and raltegravir or dolutegravir for 28 days is a preferred HIV post-exposure prophylaxis (PEP) regimen in adolescents of appropriate weight. Emtricitabine in combination with tenofovir and darunavir/ritonavir is an alternative HIV PEP regimen. A 3-drug regimen is recommended for all cases when PEP is indicated; however, the use of a 2-drug regimen (2 NRTIs or a combination of a PI and a NNRTI) may be considered if tolerability or adherence is a concern. Begin prophylaxis as soon as possible after exposure; prophylaxis initiated more than 72 hours after exposure is unlikely to be effective.
Children weighing more than 33 kg: 200 mg PO once daily in combination with tenofovir and raltegravir for 28 days is a preferred HIV post-exposure prophylaxis (PEP) regimen in children of appropriate weight. Emtricitabine in combination with tenofovir and lopinavir/ritonavir or darunavir/ritonavir is an alternative HIV PEP regimen. A 3-drug regimen is recommended for all cases when PEP is indicated; however, the use of a 2-drug regimen (2 NRTIs or a combination of a PI and a NNRTI) may be considered if tolerability or adherence is a concern. Begin prophylaxis as soon as possible after exposure; prophylaxis initiated more than 72 hours after exposure is unlikely to be effective.
Oral dosage (solution):
Adults: 240 mg PO once daily in combination with tenofovir plus raltegravir or dolutegravir for 28 days is a preferred HIV post-exposure prophylaxis (PEP) regimen in adults. Emtricitabine in combination with tenofovir and darunavir/ritonavir is an alternative HIV PEP regimen. A 3-drug regimen is recommended for all cases when PEP is indicated; however, the use of a 2-drug regimen (2 NRTIs or a combination of a PI and a NNRTI) may be considered if tolerability or adherence is a concern. Begin prophylaxis as soon as possible after exposure; prophylaxis initiated more than 72 hours after exposure is unlikely to be effective.
Adolescents: 6 mg/kg/dose PO once daily (Max: 240 mg/dose) in combination with tenofovir plus raltegravir or dolutegravir for 28 days is a preferred HIV post-exposure prophylaxis (PEP) regimen in adolescents. Emtricitabine in combination with tenofovir and darunavir/ritonavir is an alternative HIV PEP regimen. A 3-drug regimen is recommended for all cases when PEP is indicated; however, the use of a 2-drug regimen (2 NRTIs or a combination of a PI and a NNRTI) may be considered if tolerability or adherence is a concern. Begin prophylaxis as soon as possible after exposure; prophylaxis initiated more than 72 hours after exposure is unlikely to be effective.
Children 2 to 12 years: 6 mg/kg/dose PO once daily (Max: 240 mg/dose) in combination with tenofovir plus raltegravir for 28 days is a preferred HIV post-exposure prophylaxis (PEP) regimen in children 2 years and older. Emtricitabine in combination with tenofovir and lopinavir/ritonavir or darunavir/ritonavir (children 3 years and older) is an alternative HIV PEP regimen. A 3-drug regimen is recommended for all cases when PEP is indicated; however, the use of a 2-drug regimen (2 NRTIs or a combination of a PI and a NNRTI) may be considered if tolerability or adherence is a concern. Begin prophylaxis as soon as possible after exposure; prophylaxis initiated more than 72 hours after exposure is unlikely to be effective.
Infants and Children 3 months to 1 year: 6 mg/kg/dose PO once daily in combination with zidovudine plus raltegravir or lopinavir/ritonavir for 28 days is an alternative HIV post-exposure prophylaxis (PEP) regimen in infants and children younger than 2 years. A 3-drug regimen is recommended for all cases when PEP is indicated; however, the use of a 2-drug regimen (2 NRTIs or a combination of a PI and a NNRTI) may be considered if tolerability or adherence is a concern. Begin prophylaxis as soon as possible after exposure; prophylaxis initiated more than 72 hours after exposure is unlikely to be effective.
Infants 4 weeks to 2 months: 3 mg/kg/dose PO once daily in combination with zidovudine plus raltegravir or lopinavir/ritonavir for 28 days is an alternative HIV post-exposure prophylaxis (PEP) regimen in infants and children younger than 2 years. A 3-drug regimen is recommended for all cases when PEP is indicated; however, the use of a 2-drug regimen (2 NRTIs or a combination of a PI and a NNRTI) may be considered if tolerability or adherence is a concern. Begin prophylaxis as soon as possible after exposure; prophylaxis initiated more than 72 hours after exposure is unlikely to be effective.
For the treatment of chronic hepatitis B infection* in persons coinfected with HIV:
Oral dosage (capsules):
Adults: 200 mg PO once daily as part of a fully suppressive antiretroviral regimen as an alternative to lamivudine. When treating both HIV and HBV, tenofovir and lamivudine or tenofovir and emtricitabine (at appropriate HIV treatment doses and in combination with other antiretroviral agents) are appropriate first-line treatment options. Most persons on HAART should receive HBV therapy indefinitely.
Children and Adolescents weighing more than 33 kg: 200 mg PO once daily as part of a fully suppressive antiretroviral regimen as an alternative to lamivudine. When treating both HIV and HBV, tenofovir and lamivudine or tenofovir and emtricitabine (at appropriate HIV treatment doses and in combination with other antiretroviral agents) are appropriate first-line treatment options. Most persons on HAART should receive HBV therapy indefinitely.
Oral dosage (solution):
Adults: 200 mg PO once daily as part of a fully suppressive antiretroviral regimen as an alternative to lamivudine. When treating both HIV and HBV, tenofovir and lamivudine or tenofovir and emtricitabine (at appropriate HIV treatment doses and in combination with other antiretroviral agents) are appropriate first-line treatment options. Most persons on HAART should receive HBV therapy indefinitely.
Infants, Children, and Adolescents 3 months to 17 years: 6 mg/kg/dose (Max: 200 mg/dose) PO once daily as part of a fully suppressive antiretroviral regimen as an alternative to lamivudine. When treating both HIV and HBV, tenofovir and lamivudine or tenofovir and emtricitabine (at appropriate HIV treatment doses and in combination with other antiretroviral agents) are appropriate first-line treatment options. Most persons on HAART should receive HBV therapy indefinitely.
Infants 1 to 2 months: 3 mg/kg/dose PO once daily provides similar exposure as that observed with the recommended dosage in older children (6 mg/kg/day). In general, 6 mg/kg/dose PO once daily is the recommended dose for children as part of a fully suppressive antiretroviral regimen as an alternative to lamivudine; guidelines do not specifically address the dosage for infants younger than 3 months.
Maximum Dosage Limits:
-Adults
200 mg/day PO for capsules; 240 mg/day PO for oral solution.
-Geriatric
200 mg/day PO for capsules; 240 mg/day PO for oral solution.
-Adolescents
> 33 kg: 200 mg/day PO for capsules; 6 mg/kg/day, not to exceed 240 mg/day, PO for oral solution.
<= 33 kg: 6 mg/kg/day, not to exceed 240 mg/day, PO for oral solution; safety and efficacy of the capsule have not been established.
-Children
> 33 kg: 200 mg/day PO for capsules; 6 mg/kg/day, not to exceed 240 mg/day, PO for oral solution.
<= 33 kg: 6 mg/kg/day, not to exceed 240 mg/day, PO for oral solution; safety and efficacy of the capsule have not been established.
-Infants
>= 3 months: 6 mg/kg/day, not to exceed 240 mg/day, PO for oral solution; safety and efficacy of the capsule have not been established.
< 3 months: 3 mg/kg/day PO for oral solution; safety and efficacy of the capsule have not been established.
-Neonates
3 mg/kg/day PO for oral solution; safety and efficacy of the capsule have not been established.
Patients with Hepatic Impairment Dosing
The pharmacokinetics of emtricitabine have not been studied in patients with hepatic impairment; however, it is not metabolized by hepatic enzymes and, therefore, the impact of hepatic impairment should be limited.
Patients with Renal Impairment Dosing
The following dose adjustments are for adult patients with renal impairment. There are insufficient data to recommend a specific dosing adjustment of emtricitabine in pediatric patients with renal impairment.
CrCl >= 50 mL/min: No dosage adjustment needed.
CrCl 30 to 49 mL/min: 200 mg PO every 48 hours for capsules; 120 mg PO every 24 hours for oral solution.
CrCl 15 to 29 mL/min: 200 mg PO every 72 hours for capsules; 80 mg PO every 24 hours for oral solution.
CrCl < 15 mL/min: 200 mg PO every 96 hours for capsules; 60 mg PO every 24 hours for oral solution.
Intermittent hemodialysis
Adult patients requiring hemodialysis should receive emtricitabine 200 mg PO every 96 hours for capsules or 60 mg PO every 24 hours for oral solution with the dose administered after hemodialysis on dialysis days.
*non-FDA-approved indication
Abacavir; Dolutegravir; Lamivudine: (Major) Do not coadminister lamivudine, 3TC-containing products and emtricitabine-containing products due to similarities between emtricitabine and lamivudine.
Abacavir; Lamivudine, 3TC: (Major) Do not coadminister lamivudine, 3TC-containing products and emtricitabine-containing products due to similarities between emtricitabine and lamivudine.
Abacavir; Lamivudine, 3TC; Zidovudine, ZDV: (Major) Do not coadminister lamivudine, 3TC-containing products and emtricitabine-containing products due to similarities between emtricitabine and lamivudine.
Acetaminophen; Ibuprofen: (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions.
Acyclovir: (Moderate) Monitor for acyclovir or emtricitabine-related adverse events during concomitant use. Concomitant use may increase acyclovir or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as acyclovir and emtricitabine, may increase the risk of adverse reactions.
Adefovir: (Moderate) Patients who are concurrently taking adefovir with emtricitabine are at risk of developing lactic acidosis and severe hepatomegaly with steatosis. Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs alone or in combination with antiretrovirals. A majority of these cases have been in women; obesity and prolonged nucleoside exposure may also be risk factors. Particular caution should be exercised when administering nucleoside analogs to any patient with known risk factors for hepatic disease; however, cases have also been reported in patients with no known risk factors. Suspend adefovir in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity (which may include hepatomegaly and steatosis even in the absence of marked transaminase elevations).
Amikacin: (Moderate) Monitor for changes in serum creatinine and adverse reactions, such as lactic acidosis or hepatotoxicity if emtricitabine is administered in combination with nephrotoxic agents, such as aminoglycosides. Consider the potential for drug interaction prior to and during concurrent use of these medications. Both emtricitabine and aminoglycosides are excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. While no drug interactions due to competition for renal excretion have been observed, coadministration of these medications may increase concentrations of both drugs.
Aminoglycosides: (Moderate) Monitor for changes in serum creatinine and adverse reactions, such as lactic acidosis or hepatotoxicity if emtricitabine is administered in combination with nephrotoxic agents, such as aminoglycosides. Consider the potential for drug interaction prior to and during concurrent use of these medications. Both emtricitabine and aminoglycosides are excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. While no drug interactions due to competition for renal excretion have been observed, coadministration of these medications may increase concentrations of both drugs.
Amlodipine; Celecoxib: (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions.
Bupivacaine; Meloxicam: (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions.
Celecoxib: (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions.
Celecoxib; Tramadol: (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions.
Cidofovir: (Moderate) Monitor for changes in serum creatinine and adverse reactions, such as lactic acidosis or hepatotoxicity if emtricitabine is administered in combination with nephrotoxic agents, such as cidofovir. Consider the potential for drug interaction prior to and during concurrent use of these medications. Both emtricitabine and cidofovir are excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. While no drug interactions due to competition for renal excretion have been observed, coadministration of these medications may increase concentrations of both drugs.
Diclofenac: (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions.
Diclofenac; Misoprostol: (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions.
Diflunisal: (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions.
Diphenhydramine; Ibuprofen: (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions.
Diphenhydramine; Naproxen: (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions.
Dofetilide: (Moderate) Use caution when administering dofetilide concurrently with emtricitabine as both drugs are actively secreted via cationic secretion and could compete for common renal tubular transport systems. This results in a possible increase in plasma concentrations of either drug. Increased concentrations of dofetilide may increase the risk for side effects including proarrhythmia.
Dolutegravir; Lamivudine: (Major) Do not coadminister lamivudine, 3TC-containing products and emtricitabine-containing products due to similarities between emtricitabine and lamivudine.
Doravirine; Lamivudine; Tenofovir disoproxil fumarate: (Major) Do not coadminister lamivudine, 3TC-containing products and emtricitabine-containing products due to similarities between emtricitabine and lamivudine.
Echinacea: (Moderate) Use Echinacea sp. with caution in patients taking medications for human immunodeficiency virus (HIV) infection. Some experts have suggested that Echinacea's effects on the immune system might cause problems for patients with HIV infection, particularly with long-term use. There may be less risk with short-term use (less than 2 weeks). A few pharmacokinetic studies have shown reductions in blood levels of some antiretroviral medications when Echinacea was given, presumably due to CYP induction. However, more study is needed for various HIV treatment regimens. Of the agents studied, the interactions do not appear to be significant or to require dose adjustments at the time of use. Although no dose adjustments are required, monitoring drug concentrations may give reassurance during co-administration. Monitor viral load and other parameters carefully during therapy.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Major) Do not coadminister lamivudine, 3TC-containing products and emtricitabine-containing products due to similarities between emtricitabine and lamivudine.
Etodolac: (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions.
Fenoprofen: (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions.
Flurbiprofen: (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions.
Foscarnet: (Moderate) Monitor for changes in serum creatinine and adverse reactions, such as lactic acidosis or hepatotoxicity if emtricitabine is administered in combination with nephrotoxic agents, such as foscarnet. Consider the potential for drug interaction prior to and during concurrent use of these medications. Both emtricitabine and foscarnet are excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. While no drug interactions due to competition for renal excretion have been observed, coadministration of these medications may increase concentrations of both drugs.
Ganciclovir: (Moderate) Monitor for changes in serum creatinine and adverse reactions, such as lactic acidosis or hepatotoxicity if emtricitabine is administered in combination with nephrotoxic agents, such as ganciclovir. Consider the potential for drug interaction prior to and during concurrent use of these medications. Both emtricitabine and ganciclovir are excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. While no drug interactions due to competition for renal excretion have been observed, coadministration of these medications may increase concentrations of both drugs.
Gentamicin: (Moderate) Monitor for changes in serum creatinine and adverse reactions, such as lactic acidosis or hepatotoxicity if emtricitabine is administered in combination with nephrotoxic agents, such as aminoglycosides. Consider the potential for drug interaction prior to and during concurrent use of these medications. Both emtricitabine and aminoglycosides are excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. While no drug interactions due to competition for renal excretion have been observed, coadministration of these medications may increase concentrations of both drugs.
Hydrocodone; Ibuprofen: (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions.
Ibuprofen: (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions.
Ibuprofen; Famotidine: (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions.
Ibuprofen; Oxycodone: (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions.
Ibuprofen; Pseudoephedrine: (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions.
Indomethacin: (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions.
Interferon Alfa-2b: (Moderate) Use together with caution and monitor for hepatic decompensation. Interferons and anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs) can both cause hepatotoxicity. Patients with chronic, cirrhotic HCV co-infected with HIV receiving NRTIs and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART.
Interferon Alfa-n3: (Moderate) Use together with caution and monitor for hepatic decompensation. Interferons and anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs) can both cause hepatotoxicity. Patients with chronic, cirrhotic HCV co-infected with HIV receiving NRTIs and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART.
Interferon Beta-1a: (Moderate) Use together with caution and monitor for hepatic decompensation. Interferons and anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs) can both cause hepatotoxicity. Patients with chronic, cirrhotic HCV co-infected with HIV receiving NRTIs and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART.
Interferon Beta-1b: (Moderate) Use together with caution and monitor for hepatic decompensation. Interferons and anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs) can both cause hepatotoxicity. Patients with chronic, cirrhotic HCV co-infected with HIV receiving NRTIs and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART.
Interferon Gamma-1b: (Moderate) Use together with caution and monitor for hepatic decompensation. Interferons and anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs) can both cause hepatotoxicity. Patients with chronic, cirrhotic HCV co-infected with HIV receiving NRTIs and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART.
Interferons: (Moderate) Use together with caution and monitor for hepatic decompensation. Interferons and anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs) can both cause hepatotoxicity. Patients with chronic, cirrhotic HCV co-infected with HIV receiving NRTIs and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART.
Ketoprofen: (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions.
Ketorolac: (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions.
Lamivudine, 3TC: (Major) Do not coadminister lamivudine, 3TC-containing products and emtricitabine-containing products due to similarities between emtricitabine and lamivudine.
Lamivudine, 3TC; Zidovudine, ZDV: (Major) Do not coadminister lamivudine, 3TC-containing products and emtricitabine-containing products due to similarities between emtricitabine and lamivudine.
Lamivudine; Tenofovir Disoproxil Fumarate: (Major) Do not coadminister lamivudine, 3TC-containing products and emtricitabine-containing products due to similarities between emtricitabine and lamivudine.
Meclofenamate Sodium: (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions.
Mefenamic Acid: (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions.
Meloxicam: (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions.
Nabumetone: (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions.
Naproxen: (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions.
Naproxen; Esomeprazole: (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions.
Naproxen; Pseudoephedrine: (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions.
Nonsteroidal antiinflammatory drugs: (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions.
Orlistat: (Moderate) According to the manufacturer of orlistat, HIV RNA levels should be frequently monitored in patients receiving orlistat while being treated for HIV infection with anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs). Loss of virological control has been reported in HIV-infected patients taking orlistat with atazanavir, ritonavir, tenofovir disoproxil fumarate, emtricitabine, lopinavir; ritonavir, and emtricitabine; efavirenz; tenofovir disoproxil fumarate. The exact mechanism for this interaction is not known, but may involve inhibition of systemic absorption of the anti-retroviral agent. If an increased HIV viral load is confirmed, orlistat should be discontinued.
Oxaprozin: (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions.
Paromomycin: (Moderate) Monitor for changes in serum creatinine and adverse reactions, such as lactic acidosis or hepatotoxicity if emtricitabine is administered in combination with nephrotoxic agents, such as aminoglycosides. Consider the potential for drug interaction prior to and during concurrent use of these medications. Both emtricitabine and aminoglycosides are excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. While no drug interactions due to competition for renal excretion have been observed, coadministration of these medications may increase concentrations of both drugs.
Peginterferon Alfa-2a: (Moderate) Use together with caution and monitor for hepatic decompensation. Interferons and anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs) can both cause hepatotoxicity. Patients with chronic, cirrhotic HCV co-infected with HIV receiving NRTIs and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART.
Peginterferon Alfa-2b: (Moderate) Use together with caution and monitor for hepatic decompensation. Interferons and anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs) can both cause hepatotoxicity. Patients with chronic, cirrhotic HCV co-infected with HIV receiving NRTIs and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART.
Peginterferon beta-1a: (Moderate) Use together with caution and monitor for hepatic decompensation. Interferons and anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs) can both cause hepatotoxicity. Patients with chronic, cirrhotic HCV co-infected with HIV receiving NRTIs and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART.
Piroxicam: (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions.
Plazomicin: (Moderate) Monitor for changes in serum creatinine and adverse reactions, such as lactic acidosis or hepatotoxicity if emtricitabine is administered in combination with nephrotoxic agents, such as aminoglycosides. Consider the potential for drug interaction prior to and during concurrent use of these medications. Both emtricitabine and aminoglycosides are excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. While no drug interactions due to competition for renal excretion have been observed, coadministration of these medications may increase concentrations of both drugs.
Ribavirin: (Moderate) Use emtricitabine with ribavirin and interferon with caution and closely monitor for hepatic decompensation and anemia. Dose reduction or discontinuation of interferon, ribavirin, or both should be considered if worsening clinical toxicities are observed, including hepatic decompensation (e.g., Child-Pugh greater than 6). Hepatic decompensation (some fatal) has occurred in HCV/HIV coinfected patients who received both ribavirin/interferon and anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs) therapies.
Ropeginterferon alfa-2b: (Moderate) Use together with caution and monitor for hepatic decompensation. Interferons and anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs) can both cause hepatotoxicity. Patients with chronic, cirrhotic HCV co-infected with HIV receiving NRTIs and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART.
Streptomycin: (Moderate) Monitor for changes in serum creatinine and adverse reactions, such as lactic acidosis or hepatotoxicity if emtricitabine is administered in combination with nephrotoxic agents, such as aminoglycosides. Consider the potential for drug interaction prior to and during concurrent use of these medications. Both emtricitabine and aminoglycosides are excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. While no drug interactions due to competition for renal excretion have been observed, coadministration of these medications may increase concentrations of both drugs.
Sulindac: (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions.
Sumatriptan; Naproxen: (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions.
Tacrolimus: (Moderate) Monitor for changes in serum creatinine and adverse reactions, such as lactic acidosis or hepatotoxicity if emtricitabine is administered with tacrolimus. Consider the potential for drug interaction prior to and during concurrent use of these medications. Medications that decrease renal function, such as tacrolimus, may increase concentrations of emtricitabine; as emtricitabine is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion.
Tobramycin: (Moderate) Monitor for changes in serum creatinine and adverse reactions, such as lactic acidosis or hepatotoxicity if emtricitabine is administered in combination with nephrotoxic agents, such as aminoglycosides. Consider the potential for drug interaction prior to and during concurrent use of these medications. Both emtricitabine and aminoglycosides are excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. While no drug interactions due to competition for renal excretion have been observed, coadministration of these medications may increase concentrations of both drugs.
Tolmetin: (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions.
Valacyclovir: (Moderate) Monitor for valacyclovir or emtricitabine-related adverse events during concomitant use. Concomitant use may increase valacyclovir or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as valacyclovir and emtricitabine, may increase the risk of adverse reactions.
Valganciclovir: (Moderate) Monitor for changes in serum creatinine and adverse reactions, such as lactic acidosis or hepatotoxicity if emtricitabine is administered in combination with nephrotoxic agents, such as valganciclovir. Consider the potential for drug interaction prior to and during concurrent use of these medications. Both emtricitabine and valganciclovir are excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. While no drug interactions due to competition for renal excretion have been observed, coadministration of these medications may increase concentrations of both drugs.
Emtricitabine exhibits antiviral activity against both HIV-1 and HBV. Emtricitabine, a synthetic nucleoside analog of cytidine, is phosphorylated by cellular enzymes to form emtricitabine 5'-triphosphate. Emtricitabine 5'-triphosphate inhibits the activity of HIV-1 reverse transcriptase (RT) by competing with the natural substrate deoxycytidine 5'-triphosphate for incorporation into nascent viral DNA, resulting in chain termination. Emtricitabine 5'-triphosphate is a weak inhibitor of mammalian DNA polymerase alpha, beta, epsilon, and mitochondrial DNA polymerase-gamma.
The antiviral activity of emtricitabine against laboratory and clinical isolates of HIV-1 was assessed in lymphoblastoid cell lines, the MAGI-CCR5 cell line, and peripheral blood mononuclear cells (PBMC). The 50% effective concentration (EC50) values for emtricitabine were in the range of 1.3 to 640 nanomolar. Emtricitabine displayed antiviral activity in cell culture against HIV-1 clades A, B, C, D, E, F, and G (EC50 values ranged from 7 to 75 nanomolar) and showed strain-specific activity against HIV-2 (EC50 values ranged from 7 to 1,500 nanomolar in PBMCs and MAGI cells).
Emtricitabine-resistant isolates of HIV-1 have been selected in cell culture and in vivo. Genotypic analysis of these isolates showed that the reduced susceptibility to emtricitabine was associated with a valine or isoleucine (M184V/I) substitution in the HIV-1 RT. People with the M184V/I mutation are cross-resistant to lamivudine, but retain susceptibility to didanosine, stavudine, tenofovir, and zidovudine, and to non-nucleoside reverse transcriptase inhibitors (NNRTIs). HIV-1 isolates containing the K65R substitution, selected in vivo by abacavir, didanosine, and tenofovir, demonstrated reduced susceptibility to inhibition by emtricitabine. Viruses harboring substitutions conferring reduced susceptibility to zidovudine and stavudine (M41L, D67N, K70R, L210W, T215Y/F, K219Q/E) or didanosine (L74V) remained susceptible to emtricitabine. HIV-1 containing the K103N substitution associated with resistance to NNRTIs was susceptible to emtricitabine.
Emtricitabine is administered orally. Once in systemic circulation, the drug exhibits low plasma protein binding (less than 4%) that is independent of plasma concentration. At peak plasma concentration, the mean plasma-to-blood drug concentration ratio is approximately 1 and the mean semen-to-plasma drug concentration ratio is approximately 4. The plasma half-life is approximately 10 hours. Emtricitabine does not undergo hepatic enzyme metabolism. It is metabolized via oxidation to 3'-sulfoxide diastereomer (approximately 9% of dose) and via conjugation with glucuronic acid to 2'-O-glucuronide (approximately 4% of dose). It is excreted renally. Approximately 86% of the dose is recovered in the urine and 14% in the feces. About 13% of the dose found in the urine was recovered as 3 metabolites. The renal clearance is greater than the estimated creatinine clearance; elimination is presumed to be by both glomerular filtration and active tubular secretion, suggesting there may be competition for elimination with other compounds that are also renally eliminated.
Affected cytochrome P450 isoenzymes: none
-Route-Specific Pharmacokinetics
Oral Route
Emtricitabine is rapidly and extensively absorbed, with a mean absolute bioavailability of 93% for the capsules and 75% for the solution. Peak plasma drug concentrations occur approximately 1 to 2 hours post-dose. Food has no clinically significant effect on emtricitabine's systemic exposure, and the drug may be administered with or without food. The AUC and Cmax increase in proportion to oral dosage over the range of 25 to 200 mg.
-Special Populations
Hepatic Impairment
The pharmacokinetics of emtricitabine have not been studied in patients with hepatic impairment; however, it is not metabolized by hepatic enzymes and, therefore, the impact of hepatic impairment should be limited.
Renal Impairment
Emtricitabine is renally eliminated and clearance is reduced in patients with moderate to severe renal impairment; dosage adjustment is required. Emtricitabine is removed via hemodialysis; when initiated 1.5 hours after dosing, a 3-hour period of hemodialysis (at a dialysate flow rate of 600 mL/min) removes approximately 30% of an emtricitabine dose. It is not known if emtricitabine is removed by peritoneal dialysis. The effects of renal impairment on emtricitabine pharmacokinetic parameters in pediatric patients is not known.
Pediatrics
Infants older than 3 Months, Children, and Adolescents
Pediatric pharmacokinetic parameters in patients older than 3 months are similar to those seen in adults. The mean Cmax across the age bands (n = 77) ranged from 1.9 to 2.7 mcg/mL as compared to the adult mean Cmax of 1.8 mcg/mL. The mean AUC in pediatric patients ranged from 8.7 to 12.6 mcg x hour/mL compared to 10 mcg x hour/mL in adults. The mean half-life was 8.2 to 11.3 hours in pediatric patients as compared to approximately 10 hours in adults.
Neonates and Infants younger than 3 Months
Emtricitabine pharmacokinetics were studied in 20 neonates born to HIV-positive mothers who received prenatal and intrapartum combination antiretroviral therapy. After birth, the neonates received two short courses of emtricitabine oral solution (3 mg/kg daily x 4 days) during the first 3 months of life. The AUC observed after the daily 3 mg/kg dose was similar to the AUC observed in pediatric patients 3 months to 17 years of age who received the oral solution 6 mg/kg, up to 240 mg, daily or capsules 200 mg daily. In the neonates, the mean Cmax was 1.6 +/- 0.6 mcg/mL, while the mean AUC was 11 +/- 4.2 mcg x hour/mL; the mean half-life was 12.1 +/- 3.1 hours. Over the first 3 months of life, the AUC decreased with increasing age with an AUC of 13.44 mcg x hour/mL at 0 to 21 days old, 8.55 mcg x hour/mL at 22 to 42 days old, and 9.27 mcg x hour/mL at 43 to 90 days old. This correlates to an increase in total body clearance of the drug which started at 13 mL/min at 0 to 21 days old and increased to 29 mL/min by 43 to 90 days of age. In a study of 6 neonates who received a single 3 mg/kg dose after a single maternal dose of 600 mg during delivery, the median AUC (17.9 mcg x hour/mL) exceeded that of adults and older children; however, the median half-life was similar at 9.2 hours.
Gender Differences
Emtricitabine pharmacokinetic parameters are similar between male and female patients.
Ethnic Differences
Ethnic differences do not alter the pharmacokinetics of emtricitabine.
Other
Pregnancy
According to population pharmacokinetic modeling, clearance of emtricitabine is increased by 18% during pregnancy compared with non-pregnant patients. This increased clearance results in drug exposures (AUC) and peak concentrations (Cmax) that are reduced by 15% and 16.5%, respectively, during the second and third trimesters. All trough concentrations (Cmin) remain above therapeutic levels (IC50); thus dosage adjustments are not required. There is high placental transfer to the fetus.