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EMTRICITABINE

Hazardous Substances DataBank Number
7337
Related PubChem Records
Related CIDs

1 Human Health Effects

1.1 Human Toxicity Excerpts (Complete)

/SIGNS AND SYMPTOMS/ Lactic acidosis and severe hepatomegaly with steatosis, including fatalities, have been reported in patients receiving nucleoside reverse transcriptase inhibitors (NRTIs), including emtricitabine, in conjunction with other antiretroviral agents. Most reported cases have involved women; obesity and long-term therapy with a nucleoside analog also may be risk factors.
American Society of Health-System Pharmacists 2013; Drug Information 2013. Bethesda, MD. 2013, p. 702
American Society of Health-System Pharmacists 2013; Drug Information 2013. Bethesda, MD. 2013, p. 702

1.2 Body Burden (Complete)

Not known whether emtricitabine is distributed into human milk; ... .
McEvoy, G.K. (ed.). American Hospital Formulary Service- Drug Information 2005. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2005 (Plus Supplements)., p. 711

2 Emergency Medical Treatment

2.1 Antidote and Emergency Treatment (Complete)

There is no known antidote to emtricitabine. ... If overdose occurs the patient should be monitored for signs of toxicity, and standard supportive treatment applied as necessary.
Thomson.Micromedex. Drug Information for the Health Care Professional. 25th ed. Volume 1. Plus Updates. Content Reviewed by the United States Pharmacopeial Convention, Inc. Greenwood Village, CO. 2005., p. 1267
Hemodialysis treatment removes approximately 30% of the emtricitabine dose over a 3-hour dialysis period starting within 1.5 hours of emtricitabine dosing (blood flow rate of 400 mL/min and a dialysate flow rate of 600 mL/min). It is not known whether emtricitabine can be removed by peritoneal dialysis.
Physicians Desk Reference 65th ed. PDR Network, LLC, Montvale, NJ. 2011, p. 1155
/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/
Currance, P.L. Clements, B., Bronstein, A.C. (Eds).; Emergency Care For Hazardous Materials Exposure. 3Rd edition, Elsevier Mosby, St. Louis, MO 2005, p. 160
/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/
Currance, P.L. Clements, B., Bronstein, A.C. (Eds).; Emergency Care For Hazardous Materials Exposure. 3Rd edition, Elsevier Mosby, St. Louis, MO 2005, p. 160
/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/
Currance, P.L. Clements, B., Bronstein, A.C. (Eds).; Emergency Care For Hazardous Materials Exposure. 3Rd edition, Elsevier Mosby, St. Louis, MO 2005, p. 160-1
Emergency and supportive measures: Maintain an open airway and assist ventilation if needed. Treat coma, seizures, hypotension or anaphylaxis if they occur. Replace fluid losses resulting from gastroenteritis with intravenous crystalloids. Maintain steady urine flow with intravenous fluids to alleviate crystalluria and reverse renal dysfunction. Treat lactic acidosis with judicious doses of sodium bicarbonate and by withdrawal of the offending drug. /Antiviral and antiretroviral agents/
OLSON, K.R. (Ed). Poisoning and Drug Overdose, Sixth Edition. McGraw-Hill, New York, NY 2012, p. 126
Specific drugs and antidotes: There are no specific antidotes for these agents. Anecdotal cases of patients with severe lactic acidosis suggest that vitamin deficiency may be a contributor to the development of a life-threatening condition. Riboflavin ... and/or thiamine ... may be beneficial if levels are low. /Antiviral and antiretroviral agents/
OLSON, K.R. (Ed). Poisoning and Drug Overdose, Sixth Edition. McGraw-Hill, New York, NY 2012, p. 126
Decontamination: Administer activated charcoal orally if conditions are appropriate. Gastric lavage is not necessary after small to moderate ingestions if activated charcoal can be given promptly. /Antiviral and antiretroviral agents/
OLSON, K.R. (Ed). Poisoning and Drug Overdose, Sixth Edition. McGraw-Hill, New York, NY 2012, p. 126

3 Animal Toxicity Studies

3.1 Non-Human Toxicity Excerpts (Complete)

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Emtricitabine did not affect fertility in male rats at approximately 140-fold or in male and female mice at approximately 60-fold higher exposures (AUC) than in humans given the recommended daily dose. Fertility was normal in the offspring of mice exposed daily from before birth (in utero) through sexual maturity at daily exposures (AUC) of approximately 60-fold higher than human exposures at the recommended daily dose.
Physicians Desk Reference 65th ed. PDR Network, LLC, Montvale, NJ. 2011, p. 1156
/GENOTOXICITY/ Emtricitabine was not genotoxic in the reverse mutation bacterial test (Ames test), mouse lymphoma or mouse micronucleus assays.
Physicians Desk Reference 65th ed. PDR Network, LLC, Montvale, NJ. 2011, p. 1156

3.2 Ongoing Test Status

The following link will take the user to the National Toxicology Program (NTP) Test Agent Search Results page, which tabulates all of the "Standard Toxicology & Carcinogenesis Studies", "Developmental Studies", and "Genetic Toxicity Studies" performed with this chemical. Clicking on the "Testing Status" link will take the user to the status (i.e., in review, in progress, in preparation, on test, completed, etc.) and results of all the studies that the NTP has done on this chemical.[Available from, as of November 15, 2013: http://ntp-apps.niehs.nih.gov/ntp_tox/index.cfm?fuseaction=ntpsearch.searchresults&searchterm=143491-57-0]

4 Metabolism / Pharmacokinetics

4.1 Metabolism / Metabolites (Complete)

The biotransformation of emtricitabine includes oxidation of the thiol moiety to form the 3'-sulfoxide diastereomers (approximately 9% of dose) and conjugation with glucuronic acid to form 2'-O-glucuronide (approximately 4% of dose). No other metabolites were identifiable. Emtricitabine is not metabolized by liver enzymes.
Thomson.Micromedex. Drug Information for the Health Care Professional. 25th ed. Volume 1. Plus Updates. Content Reviewed by the United States Pharmacopeial Convention, Inc. Greenwood Village, CO. 2005., p. 1265

4.2 Absorption, Distribution and Excretion (Complete)

Emtricitabine is rapidly and extensively absorbed following oral administration with peak plasma concentrations occurring at 1 to 2 hours post-dose. Following multiple dose oral administration of emtriva to 20 HIV-infected subjects, the (mean + or - SD) steady state plasma emtricitabine peak concentration (Cmax) was 1.8 + or 0.7 ug/mL and the area under the plasma concentration-time curve over a 24-hour dosing interval (AUC) was 10.0 + or - 3.1 hr/ug/mL. The mean steady state plasma trough concentration at 24 hours post-dose was 0.09 ug/mL. The mean absolute bioavailability of emtriva was 93%.
Physicians Desk Reference 65th ed. PDR Network, LLC, Montvale, NJ. 2011, p. 1154
In vitro binding of emtricitabine to human plasma proteins was <4% and independent of concentration over the range of 0.02 to 200 ug/mL. At peak plasma concentration, the mean plasma to blood drug concentration ratio was approximately 1.0 and the mean semen to plasma drug concentration ratio was approximately 4.0.
Physicians Desk Reference 65th ed. PDR Network, LLC, Montvale, NJ. 2011, p. 1155
Time to peak concentration: 1 to 2 hours post dose
Thomson.Micromedex. Drug Information for the Health Care Professional. 25th ed. Volume 1. Plus Updates. Content Reviewed by the United States Pharmacopeial Convention, Inc. Greenwood Village, CO. 2005., p. 1265
Emtricitabine is distributed into human milk in low concentrations.
American Society of Health-System Pharmacists 2013; Drug Information 2013. Bethesda, MD. 2013, p. 703
The renal clearance is greater than the estimated creatinine clearance, suggesting elimination by both glomerular filtration and active tubular secretion. There may be competition for elimination with other compounds that are also renally eliminated. Fecal: 14%. Urine: 86%. 13% of the dose was recovered in the urine as three putative metabolites.
Thomson.Micromedex. Drug Information for the Health Care Professional. 25th ed. Volume 1. Plus Updates. Content Reviewed by the United States Pharmacopeial Convention, Inc. Greenwood Village, CO. 2005., p. 1266
The pharmacokinetics of emtricitabine are altered in patients with renal impairment. In patients with creatinine clearance less than 50 mL/min or with end-stage renal disease (ESRD) requiring dialysis, Cmax and AUC of emtricitabine were increased due to a reduction in renal clearance.
Physicians Desk Reference 65th ed. PDR Network, LLC, Montvale, NJ. 2011, p. 1155

4.3 Biological Half-Life (Complete)

The plasma emtricitabine half-life is approximately 10 hours.
Physicians Desk Reference 65th ed. PDR Network, LLC, Montvale, NJ. 2011, p. 1155

4.4 Mechanism of Action (Complete)

Emtricitabine, a synthetic nucleoside analog of cytosine, is phosphorylated by cellular enzymes to form emtricitabine 5'-triphosphate. Emtricitabine 5'-triphosphate inhibits the activity of the HIV-1 reverse transcriptase by competing with the natural substrate deoxycytidine 5'-triphosphate and by being incorporated into nascent viral DNA which results in chain termination. Emtricitabine 5'-triphosphate is a weak inhibitor of mammalian DNA polymerase alpha, beta, epsilon and mitochondrial DNA polymerase gamma.
Physicians Desk Reference 65th ed. PDR Network, LLC, Montvale, NJ. 2011, p. 1155

5 Pharmacology

5.1 Therapeutic Uses (Complete)

Antiviral Agents
National Library of Medicine's Medical Subject Headings. Emtricitabine. Online file (MeSH, 2014). Available from, as of November 19, 2013: https://www.nlm.nih.gov/mesh/2014/mesh_browser/MBrowser.html
Emtricitabine is used in conjunction with other antiretroviral agents for the treatment of HIV-1 infection in pediatric patients 12 years of age or older. The fixed combination containing emtricitabine and tenofovir (Truvada) can be used in conjunction with other antiretrovirals in children 12 years of age or older weighing at least 35 kg. For initial treatment of HIV-infected pediatric patients, the HHS Panel on Antiretroviral Therapy and Medical Management of HIV-infected Children recommends antiretroviral therapy with at least 3 drugs, including either a PI or NNRTI with 2 NRTIs. When PI-based or NNRTI-based regimens are used in pediatric patients, emtricitabine and (abacavir (for individuals 3 months of age or older who test negative for the HLA-B*5701 allele), tenofovir (for adolescents 12 years of age or older at Tanner stage 4 or 5), or zidovudine) are preferred dual NRTI options. A dual NRTI combination of emtricitabine and lamivudine is not recommended, because of similar resistance profiles and minimal additive antiretroviral activity. A triple NRTI regimen that includes abacavir, tenofovir, and either lamivudine or emtricitabine or a triple NRTI regimen that includes tenofovir, didanosine, and either lamivudine or emtricitabine should not be used at any time in pediatric patients because of the high rate of early virologic failure reported in antiretroviral-naive adults.
American Society of Health-System Pharmacists 2013; Drug Information 2013. Bethesda, MD. 2013, p. 700
Emtricitabine has been evaluated in a randomized, open-label, multicenter study (study 303) in 440 previously treated adults (mean age: 42 years; 86% male; 64% white; 13% Hispanic; 21% African American; median baseline plasma HIV-1 RNA level: 1.7 log10 copies/mL; mean baseline CD4+ T-cell count: 527 cells/mm3) who had received a lamivudine-containing regimen that also included 2 other antiretrovirals (background regimen) for at least 12 weeks prior to study entry and had plasma HIV-1 levels of 400 copies/mL or less. Patients in this study were randomized to receive emtricitabine in conjunction with stavudine or zidovudine and PI or NNRTI or to continue their lamivudine-containing background regimen (i.e., lamivudine in conjunction with stavudine or zidovudine and a PI or NNRTI). At week 48, 77 and 67% of adults receiving the regimen that included emtricitabine and 82 and 72% of those receiving the regimen that included lamivudine had plasma HIV-1 RNA levels less than 400 or 50 copies/mL, respectively. Virologic failure (i.e., individuals who failed to achieve virologic suppression or experienced rebound after achieving virologic suppression) was reported in 7% of those receiving the emtricitabine-containing regimen and in 8% of those receiving the lamivudine-containing regimen at week 48. Administration of the emtricitabine-containing regimen resulted in a mean increase in CD4+ T-cell counts of 29 cells/mm3; administration of the lamivudine-containing regimen resulted in a mean increase in CD4+ T-cell counts of 61 cells/cu mm.
American Society of Health-System Pharmacists 2013; Drug Information 2013. Bethesda, MD. 2013, p. 700
Safety and efficacy of emtricitabine used in conjunction with other antiretrovirals have been evaluated in a randomized multicenter study in treatment-naive adults (study 301A). In this study, 571 HIV-infected adults (mean age: 36 years; 85% male; 52% white; 26% Hispanic; 16% African American; median baseline plasma HIV-1 RNA level: 4.9 log10 copies/mL; mean baseline CD4+ T-cell count: 318 cells/mm3) were randomized to receive emtricitabine or stavudine in conjunction with didanosine (delayed-release capsules) and efavirenz. Results of this study indicated that an initial regimen that includes emtricitabine in conjunction with didanosine and efavirenz is as effective as an initial regimen of stavudine in conjunction with didanosine and efavirenz. At week 48, 81 and 78% of adults receiving the regimen that included emtricitabine and 68 and 59% of those receiving the regimen that included stavudine had plasma HIV-1 RNA levels less than 400 or 50 copies/mL, respectively. Virologic failure (i.e., individuals who failed to achieve virologic suppression or experienced rebound after achieving virologic suppression) at week 48 was reported in 3% of those receiving the emtricitabine-containing regimen and in 11% of those receiving the stavudine-containing regimen. At week 48, increases in CD4+ T-cell counts were greater in patients receiving the regimen that included emtricitabine (mean increase of 168 cells/mm3) than in those receiving the regimen that included stavudine (mean increase of 134 cells/mm3).
American Society of Health-System Pharmacists 2013; Drug Information 2013. Bethesda, MD. 2013, p. 700
For initial treatment regimens in HIV-infected adults and adolescents, the US Department of Health and Human Services (HHS) Panel on Antiretroviral Guidelines for Adults and Adolescents states that tenofovir and either emtricitabine or lamivudine is the preferred dual NRTI option for use in NNRTI-, PI-, HIV entry inhibitor-, or HIV integrase inhibitor-based regimens, especially in HIV-infected patients coinfected with hepatitis B virus (HBV). Regimens containing only 1 of these 3 antiretrovirals (tenofovir, emtricitabine, or lamivudine) are not recommended in HIV-infected patients coinfected with HBV because of the increased risk of HBV resistance.
American Society of Health-System Pharmacists 2013; Drug Information 2013. Bethesda, MD. 2013, p. 700
Emtricitabine is used in conjunction with other antiretroviral agents for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in adults, adolescents, and pediatric patients. Emtricitabine should always be used in conjunction with other antiretrovirals and should not be used alone in the treatment of HIV infection. Emtricitabine usually is used in multiple-drug regimens that include another nucleoside reverse transcriptase inhibitor (NRTI) (dual NRTIs) and either an HIV protease inhibitor (PI) or nonnucleoside reverse transcriptase inhibitor (NNRTI) (PI- or NNRTI-based regimens). Emtricitabine also is used with another NRTI (dual NRTIs) in conjunction with an HIV integrase inhibitor or HIV entry inhibitor.
American Society of Health-System Pharmacists 2013; Drug Information 2013. Bethesda, MD. 2013, p. 699
Emtricitabine is indicated, in combination with other antiretroviral agents, for the treatment of HIV-1 infection in adult patients. In antiretroviral-treatment-experienced patients, the use of emtricitabine may be considered for adults with HIV strains that are expected to be susceptible to emtricitabine as assessed by genotypic or phenotypic testing. /Included in US product labeling/
Thomson.Micromedex. Drug Information for the Health Care Professional. 25th ed. Volume 1. Plus Updates. Content Reviewed by the United States Pharmacopeial Convention, Inc. Greenwood Village, CO. 2005., p. 1265

5.2 Drug Warnings (Complete)

Safety and efficacy of emtricitabine have been established for treatment of HIV-1 infection in children 3 months of age and older. The pharmacokinetics and safety of emtricitabine were evaluated in a dose-finding study in 20 neonates born to HIV-infected mothers.20 1 These neonates received zidovudine prophylaxis for 6 weeks. In addition, these neonates received 2 short courses of emtricitabine (3 mg/kg daily for 4 days per course) during the first 12 weeks of life. This dose was well tolerated and was not associated with any safety issues. Systemic exposure (area under the plasma concentration-time curve [AUC]) in infants 0-3 months of age receiving emtricitabine 3 mg/kg daily was similar to that reported in children 3 months to 17 years of age receiving emtricitabine 6 mg/kg daily. All neonates were HIV-1 negative at the end of the study (6 months postpartum); efficacy of emtricitabine for the prevention or treatment of HIV was not determined.
American Society of Health-System Pharmacists 2013; Drug Information 2013. Bethesda, MD. 2013, p. 703
Lactic acidosis and severe hepatomegaly with steatosis, including fatalities, have been reported in patients receiving nucleoside reverse transcriptase inhibitors (NRTIs), including emtricitabine, in conjunction with other antiretroviral agents. Most reported cases have involved women; obesity and long-term therapy with a nucleoside analog also may be risk factors.
American Society of Health-System Pharmacists 2013; Drug Information 2013. Bethesda, MD. 2013, p. 702
Caution should be observed when nucleoside reverse transcriptase inhibitors are used in patients with known risk factors for liver disease; however, lactic acidosis and severe hepatomegaly with steatosis have been reported in patients with no known risk factors. Emtricitabine therapy should be interrupted in any patient with clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity (signs of hepatotoxicity include hepatomegaly and steatosis even in the absence of marked increases in serum aminotransferase concentrations).
American Society of Health-System Pharmacists 2013; Drug Information 2013. Bethesda, MD. 2013, p. 702
Prior to initiation of emtricitabine therapy for the treatment of HIV-1 infection, patients should be tested for chronic hepatitis B virus (HBV). Emtricitabine is not indicated for the treatment of chronic HBV infection; safety and efficacy of the drug have not been established in patients with coexisting HBV and HIV infections. Exacerbations of HBV infection have been reported in HIV-infected patients following discontinuance of emtricitabine. Patients with HBV infection and HIV infection should be closely monitored with clinical and laboratory follow-up for at least several months after stopping emtricitabine therapy.
American Society of Health-System Pharmacists 2013; Drug Information 2013. Bethesda, MD. 2013, p. 702
Redistribution or accumulation of body fat, including central obesity, dorsocervical fat enlargement ("buffalo hump"), peripheral wasting, breast enlargement, and general cushingoid appearance noted in patients receiving antiretroviral therapy.
American Society of Health-System Pharmacists 2013; Drug Information 2013. Bethesda, MD. 2013, p. 702
Emtricitabine is distributed into human milk in low concentrations. Because of the risk of adverse effects in the infant and the risk of HIV transmission, HIV-infected women should not breast-feed infants.
American Society of Health-System Pharmacists 2013; Drug Information 2013. Bethesda, MD. 2013, p. 703
Experience in those 65 years of age or older insufficient to determine whether they respond differently than younger adults. Use caution in dosage selection; the greater frequency of decreased hepatic, renal, and/or cardiac function and of concomitant disease or drug therapy observed in geriatric individuals should be considered.
American Society of Health-System Pharmacists 2013; Drug Information 2013. Bethesda, MD. 2013, p. 703
The most common adverse effects in adults receiving emtricitabine in conjunction with other antiretrovirals are mild to moderate headache, diarrhea, nausea, and rash. Adverse effects reported in children 3 months to 21 years of age receiving emtricitabine in clinical studies have been similar to those in adults, with the exception of a higher frequency of hyperpigmentation.
American Society of Health-System Pharmacists 2013; Drug Information 2013. Bethesda, MD. 2013, p. 703
FDA Pregnancy Risk Category: B /NO EVIDENCE OF RISK IN HUMANS. Adequate, well controlled studies in pregnant women have not shown increased risk of fetal abnormalities despite adverse findings in animals, or, in the absence of adequate human studies, animal studies show no fetal risk. The chance of fetal harm is remote but remains a possibility./
American Society of Health-System Pharmacists 2013; Drug Information 2013. Bethesda, MD. 2013, p. 703
Antiretroviral therapy is not a cure for HIV infection, and oppertunistic infection still may occur. HIV transmission durring sexual contact or sharing needles is not prevented by antiretrovirals.
American Society of Health-System Pharmacists 2013; Drug Information 2013. Bethesda, MD. 2013, p. 704
Obesity or prolonged nucleoside exposure may be risk factors for lactic acidosis/severe hepatomegaly with steatosis. Cases have been reported with the use of nucleoside analogues alone or in combination with other antiretrovirals; a majority of these cases have been in women and cases have been reported with no known risk factors.
Thomson.Micromedex. Drug Information for the Health Care Professional. 25th ed. Volume 1. Plus Updates. Content Reviewed by the United States Pharmacopeial Convention, Inc. Greenwood Village, CO. 2005., p. 1266
/Adverse effects occurring at an /incidence less frequent include: Abdominal pain; abnormal dreams; arthralgia (pain in the joints; muscle pain stiffness; difficulty in moving); depressive disorders; dizziness; dyspepsia (acid or sour stomach; belching; heartburn; indigestion; stomach discomfort, upset or pain); insomnia (sleeplessness; trouble sleeping; unable to sleep); myalgia (joint pain; swollen joints; muscle aching or cramping; muscle pains or stiffness); neuritis (numbness or tingling of hands, feet, or face); paresthesia (burning, crawling, itching, numbness, prickling, pins and needles, or tingling feelings); peripheral neuropathy; rash and vomiting.
Thomson.Micromedex. Drug Information for the Health Care Professional. 25th ed. Volume 1. Plus Updates. Content Reviewed by the United States Pharmacopeial Convention, Inc. Greenwood Village, CO. 2005., p. 1267
FDA approved a REMS for emtricitabine to ensure that the benefits outweigh the risk. The REMS may apply to one or more preparations of emtricitabine and consists of the following: medication guide and elements to assure safe use.
American Society of Health-System Pharmacists 2013; Drug Information 2013. Bethesda, MD. 2013, p. 699

5.3 Interactions (Complete)

Pharmacokinetic interactions with drugs metabolized by uridine diphosphate-glucuronosyltransferase are unlikely. Emtricitabine does not inhibit glucuronosyltransferase (uridine diphosphoglucuronosyltransferase, UDP-glucuronate B-d-glucuronosyltransferase (acceptor-unspecific)), an enzyme responsible for glucuronidation.
American Society of Health-System Pharmacists 2013; Drug Information 2013. Bethesda, MD. 2013, p. 703
Pharmacokinetic interactions with drugs metabolized by hepatic microsomal enzymes are unlikely. In vitro studies indicate that emtricitabine does not inhibit cytochrome P-450 (CYP) isoenzymes 1A2, 2A6, 2B6, 2C9, 2C19, 2D6, or 3A4.
American Society of Health-System Pharmacists 2013; Drug Information 2013. Bethesda, MD. 2013, p. 703
At concentrations up to 14 fold higher than those observed in vivo, emtricitabine did not inhibit in vitro drug metabolism mediated by any of the following human CYP 450 isoforms: CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2C19, CYP2D6 and CYP3A4. Emtricitabine did not inhibit the enzyme responsible for glucuronidation (uridine-5'-disphosphoglucuronyl transferase). Based on the results of these in vitro experiments and the known elimination pathways of emtricitabine, the potential for CYP450 mediated interactions involving emtricitabine with other medicinal products is low.
Physicians Desk Reference 65th ed. PDR Network, LLC, Montvale, NJ. 2011, p. 1155
The potential for drug interactions with emtricitabine has been studied in combination with indinavir, stavudine, famciclovir, and tenovir disoproxil fumarate. There were no clinically significant drug interactions for any of these drugs.
Physicians Desk Reference 65th ed. PDR Network, LLC, Montvale, NJ. 2011, p. 1155

6 Environmental Fate & Exposure

6.1 Environmental Fate / Exposure Summary

Emtricitabine's production and use as an antiviral and in the treatment of AIDS may result in its release to the environment through various waste streams. If released to air, an estimated vapor pressure of 1.7X10-8 mm Hg at 25 °C indicates emtricitabine will exist in both the vapor and particulate phases in the atmosphere. Vapor-phase emtricitabine will be degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals and ozone; the half-lives for these reactions in air are estimated to be 2.6 hours and 16 days. Particulate-phase emtricitabine will be removed from the atmosphere by wet or dry deposition. Emtricitabine does not absorb light at wavelengths >290 nm and, therefore, is not expected to be susceptible to direct photolysis by sunlight. If released to soil, emtricitabine is expected to have high mobility based upon an estimated Koc of 55. Volatilization from moist soil surfaces is not expected to be an important fate process based upon an estimated Henry's Law constant of 1.1X10-17 atm-cu m/mole. Emtricitabine is not expected to volatilize from dry soil surfaces based upon its estimated vapor pressure. If released into water, emtricitabine is not expected to adsorb to suspended solids and sediment based upon the estimated Koc. Volatilization from water surfaces is not expected to be an important fate process based upon this compound's estimated Henry's Law constant. An estimated BCF of 3 suggests the potential for bioconcentration in aquatic organisms is low. Hydrolysis is not expected to be an important environmental fate process since this compound lacks functional groups that hydrolyze under environmental conditions. Occupational exposure to emtricitabine may occur through inhalation of dust and dermal contact with this compound at workplaces where entecavir is produced or used. Use data indicate that the general population may be exposed to emtricitabine via medical administration of this compound for the treatment of viral infection. (SRC)

6.2 Probable Routes of Human Exposure (Complete)

Occupational exposure to emtricitabine may occur through inhalation of dust and dermal contact with this compound at workplaces where entecavir is produced or used. Use data indicate that the general population may be exposed to emtricitabine via medical administration of this compound for the treatment of viral infection. (SRC)

6.3 Artificial Pollution Sources (Complete)

Emtricitabine's production and use as an antiviral(1) and in the treatment of AIDS(2) may result in its release to the environment through various waste streams(SRC).
(1) O'Neil MJ, ed; The Merck Index. 15th ed., Cambridge, UK: Royal Society of Chemistry, p. 657 (2013)
(2) PDR; Physicians' Desk Reference 67th ed. Montvale, NJ: Medical Economics Co. p. 2646 (2013)

6.4 Environmental Fate (Complete)

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 55(SRC), determined from a structure estimation method(2), indicates that emtricitabine is expected to have high mobility in soil(SRC). Volatilization of emtricitabine from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 1.1X10-17 atm-cu m/mole(SRC), using a fragment constant estimation method(3). Emtricitabine is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.7X10-8 mm Hg at 25 °C(SRC), determined from a fragment constant method(4). Biodegradation data in soil were not available(SRC, 2013).
(1) Swann RL et al; Res Rev 85: 17-28 (1983)
(2) US EPA; Estimation Program Interface (EPI) Suite. Ver. 4.1. Jan, 2011. Available from, as of Nov 20, 2013: https://www.epa.gov/oppt/exposure/pubs/episuitedl.htm
(3) Meylan WM, Howard PH; Environ Toxicol Chem 10: 1283-93 (1991)
(4) Lyman WJ; p. 31 in Environmental Exposure From Chemicals Vol I, Neely WB, Blau GE, eds, Boca Raton, FL: CRC Press (1985)
AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 55(SRC), determined from a structure estimation method(2), indicates that emtricitabine is not expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 1.1X10-17 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). According to a classification scheme(5), an estimated BCF of 3(SRC), from its log Kow of -0.43(6) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Emtricitabine is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(3). Biodegradation data in water were not available(SRC, 2013).
(1) Swann RL et al; Res Rev 85: 17-28 (1983)
(2) US EPA; Estimation Program Interface (EPI) Suite. Ver. 4.1. Jan, 2011. Available from, as of Nov 20, 2013: https://www.epa.gov/oppt/exposure/pubs/episuitedl.htm
(3) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 7-4, 7-5, 15-1 to 15-29 (1990)
(4) Meylan WM, Howard PH; Environ Toxicol Chem 10: 1283-93 (1991)
(5) Franke C et al; Chemosphere 29: 1501-14 (1994)
(6) PDR; Physicians' Desk Reference 59nd ed. Montvale, NJ: Medical Economics Co. p. 1370 (2005)
ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), emtricitabine, which has an estimated vapor pressure of 1.7X10-8 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), will exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase emtricitabine is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 2.6 hours(SRC), calculated from its rate constant of 1.3X10-10 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). The rate constant for the vapor-phase reaction of emtricitabine with ozone has been estimated as 7.0X10-19 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). This corresponds to an atmospheric half-life of about 16 days at an atmospheric concentration of 7X10+11 ozone molecules per cu cm(4). Particulate-phase emtricitabine may be removed from the air by wet or dry deposition(SRC). Emtricitabine does not absorb UV light at wavelengths >290 nm(5) and, therefore, is not expected to be susceptible to direct photolysis by sunlight(SRC).
(1) Bidleman TF; Environ Sci Technol 22: 361-367 (1988)
(2) Lyman WJ; p. 31 in Environmental Exposure From Chemicals Vol I, Neely WB, Blau GE, eds, Boca Raton, FL: CRC Press (1985)
(3) Meylan WM, Howard PH; Chemosphere 26: 2293-99 (1993)
(4) Atkinson R, Carter WPL; Chem Rev 84: 437-70 (1984)
(5) O'Neil MJ, ed; The Merck Index. 15th ed., Cambridge, UK: Royal Society of Chemistry, p. 657 (2013)

6.5 Environmental Abiotic Degradation (Complete)

The rate constant for the vapor-phase reaction of emtricitabine with photochemically-produced hydroxyl radicals has been estimated as 1.3X10-10 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 2.6 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). The rate constant for the vapor-phase reaction of emtricitabine with ozone has been estimated as 7.0X10-19 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(1). This corresponds to an atmospheric half-life of about 16 days at an atmospheric concentration of 7X10+11 ozone molecules per cu cm(2). Emtricitabine is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(3). Emtricitabine does not absorb UV light at wavelengths >290 nm(4) and, therefore, is not expected to be susceptible to direct photolysis by sunlight(SRC).
(1) Meylan WM, Howard PH; Chemosphere 26: 2293-99 (1993)
(2) Atkinson R, Carter WPL; Chem Rev 84: 437-70 (1984)
(3) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 7-4, 7-5, 8-12 (1990)
(4) O'Neil MJ, ed; The Merck Index. 15th ed., Cambridge, UK: Royal Society of Chemistry, p. 657 (2013)

6.6 Environmental Bioconcentration (Complete)

An estimated BCF of 3 was calculated in fish for emtricitabine(SRC), using a log Kow of -0.43(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).
(1) PDR; Physicians' Desk Reference 59nd ed. Montvale, NJ: Medical Economics Co. p. 1370 (2005)
(2) US EPA; Estimation Program Interface (EPI) Suite. Ver. 4.1. Jan, 2011. Available from, as of Nov 20, 2013: https://www.epa.gov/oppt/exposure/pubs/episuitedl.htm
(3) Franke C et al; Chemosphere 29: 1501-14 (1994)

6.7 Soil Adsorption / Mobility (Complete)

Using a structure estimation method based on molecular connectivity indices(1), the Koc of emtricitabine can be estimated to be 55(SRC). According to a classification scheme(2), this estimated Koc value suggests that emtricitabine is expected to have high mobility in soil.
(1) US EPA; Estimation Program Interface (EPI) Suite. Ver. 4.1. Jan, 2011. Available from, as of Nov 20, 2013: https://www.epa.gov/oppt/exposure/pubs/episuitedl.htm
(2) Swann RL et al; Res Rev 85: 17-28 (1983)

6.8 Volatilization from Water / Soil (Complete)

The Henry's Law constant for emtricitabine is estimated as 1.1X10-17 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that emtricitabine is expected to be essentially nonvolatile from water and moist soil surfaces(2). Emtricitabine is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.7X10-8 mm Hg(SRC), determined from a fragment constant method(3).
(1) Meylan WM, Howard PH; Environ Toxicol Chem 10: 1283-93 (1991)
(2) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 15-1 to 15-29 (1990)
(3) Lyman WJ; p. 31 in Environmental Exposure From Chemicals Vol I, Neely WB, Blau GE, eds, Boca Raton, FL: CRC Press (1985)

6.9 Environmental Water Concentrations (Complete)

While data specific to emtricitabine were not located(2013, SRC), the literature suggests that some pharmaceutically active compounds originating from human and veterinary therapy are not eliminated completely in municipal sewage treatment plants and are therefore discharged into receiving waters(1). Wastewater treatment processes often were not designed to remove them from the effluent(2). Selected organic waste compounds may be degrading to new and more persistent compounds that may be released instead of or in addition to the parent compound(2).
(1) Heberer T; Tox Lett 131: 5-17 (2002)
(2) Koplin DW et al; Environ Sci Toxicol 36: 1202-211 (2002)

6.10 Milk Concentrations (Complete)

Emtricitabine is distributed into human milk in low concentrations.
American Society of Health-System Pharmacists 2013; Drug Information 2013. Bethesda, MD. 2013, p. 703
EXPERIMENTAL: The aim was to evaluate emtricitabine (FTC) and tenofovir (TFV) neonatal ingestion through breast milk. Median TFV and FTC breast milk doses represented 0.03% and 2%, respectively, of the proposed oral infant doses. Neonatal simulated plasma concentrations were extremely low for TFV but between the half-maximal inhibitory concentration and the adult minimal expected concentration for FTC. The rare children who will acquire HIV despite TDF-FTC therapy will need to be monitored for viral resistance acquisition.
Benaboud S et al; Antimicrob Agents Chemother 55(3): 1315-7 (2011)

7 Environmental Standards & Regulations

7.1 FDA Requirements (Complete)

The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including emtricitabine, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.
DHHS/FDA; Electronic Orange Book-Approved Drug Products with Therapeutic Equivalence Evaluations. Available from, as of November 15, 2013: https://www.fda.gov/cder/ob/

8 Chemical / Physical Properties

8.1 Molecular Formula

C8-H10-F-N3-O3-S
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Cambridge, UK: Royal Society of Chemistry, 2013., p. 657

8.2 Molecular Weight

247.24
Goldfrank, L.R., Goldfrank''s Toxicologic Emergencies 7th Ed. 2002., McGraw-Hill, New York, N.Y., p. 657

8.3 Color / Form (Complete)

White to off white powder
Physicians Desk Reference 67th ed. PDR Network, LLC, Montvale, NJ. p. 2646 (2013)
White solid from ether and methanol
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Cambridge, UK: Royal Society of Chemistry, 2013., p. 657

8.4 Melting Point

136-140 °C
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Cambridge, UK: Royal Society of Chemistry, 2013., p. 657

8.5 LogP

log Kow = -0.43
PDR; Physicians' Desk Reference. 59nd ed. Montvale, NJ: Medical Economics Co. pp. 1370 (2005)

8.6 Dissociation Constants

pKa = 2.65 (amine)
PDR; Physicians' Desk Reference. 59nd ed. Montvale, NJ: Medical Economics Co. pp. 1370 (2005)

8.7 Solubility (Complete)

About 1.12X10+6 mg/L in water at 25 °C
Physicians Desk Reference 67th ed. PDR Network, LLC, Montvale, NJ. p. 2646 (2013)

9 Spectral Information

9.1 UV Spectra

UV max = 287.8 at pH 2; 280.0 at pH 7; 279.8 at pH 11 (e 14210, 11090, 11810)
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Cambridge, UK: Royal Society of Chemistry, 2013., p. 657

10 Chemical Safety & Handling

10.1 Storage Conditions (Complete)

Store at 25 °C (77 °F); excursions permitted to 15 °C-30 °C (59 °F-86 °F)
Physicians Desk Reference 65th ed. PDR Network, LLC, Montvale, NJ. 2011, p. 1158

10.2 Disposal Methods (Complete)

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational exposure or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in soil or water; effects on animal, aquatic, and plant life; and conformance with environmental and public health regulations.

11 Manufacturing / Use Information

11.1 Uses (Complete)

MEDICATION
Antiviral Agents
National Library of Medicine's Medical Subject Headings. Emtricitabine. Online file (MeSH, 2014). Available from, as of November 19, 2013: https://www.nlm.nih.gov/mesh/2014/mesh_browser/MBrowser.html

11.2 Manufacturers

Bristol-Myers Squibb , P.O. Box 4500, Princeton, NJ 08543-4500
Physicians Desk Reference 67th ed. PDR Network, LLC, Montvale, NJ. p. 2646 (2013)
Bristol-Myers Squibb & Gillead Sciences, 333 Lakeside Drive, Foster City, CA 94404
Physicians Desk Reference 67th ed. PDR Network, LLC, Montvale, NJ. p. 720 (2013)

11.3 Methods of Manufacturing (Complete)

Preparation: D. C. Liotta et al., World Intellectual Property Organization 9214743 (1992 to Emory University); G. Dionne, United States of America patent 5538975 (1996 to BioChem Pharma, Inc.)
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Cambridge, UK: Royal Society of Chemistry, 2013., p. 657

11.4 Formulations / Preparations (Complete)

Oral: Solution 10 mg/mL, Emtriva (Gilead).
American Society of Health-System Pharmacists 2013; Drug Information 2013. Bethesda, MD. 2013, p. 704
Oral: Capsules: 200 mg Emtriva, (Gilead).
American Society of Health-System Pharmacists 2013; Drug Information 2013. Bethesda, MD. 2013, p. 704
Trade name (emtricitabine): ETruvada (co-formulation tablet of emtricitabine and tenofovir disoproxyl fumarate) (Gilead Sciences Inc.)
Bonneau PR, Simonean B; HIV and AIDS Therapeutics. Ullmann's Encyclopedia of Industrial Chemistry 7th ed. (1999-2013). NY, NY: John Wiley & Sons. Online Posting Date: January 15, 2007
Table: Emtricitabine Comination Preparations
Route of Administration
Oral
Dosage Form
Tablets, film-coated
Strength
200 mg with Tenofovir, Disoproxil fumarate 300 mg
Brand or Generic Name (Manufacturer)
Truvada (Gilead)
Route of Administration
Oral
Dosage Form
Tablets, film-coated
Strength
200 mg with Tenofovir, Disoproxil fumarate 300 mg and Efavirenz 600 mg
Brand or Generic Name (Manufacturer)
Atripla (Bristol-Myers Squibb and Gilead)
Route of Administration
Oral
Dosage Form
Tablets, film-coated
Strength
200 mg with Tenofovir, Disoproxil fumarate 300 mg and Ripivirine hydrochloride 25 mg (of ripivirine)
Brand or Generic Name (Manufacturer)
Complera (Gilead)
American Society of Health-System Pharmacists 2013; Drug Information 2013. Bethesda, MD. 2013, p. 704

12 Special References

12.1 Special Reports (Complete)

Bang LM, Scott LJ; Emtricitabine: An Antiretroviral Agent for HIV Infection; Drugs 63 (22): 2413-24 (2003)
Zapor MJ et al; Antiretrovirals, Part II: Focus on Non-protease Inhibitor Antiretrovirals (NRTIs, NNRTIs, and Fusion Inhibitors); Psychosomatics 45 (6): 524-35 (2004)
Mjodrzejewski KA, Herman RA; Emtricitabine: A Once-Daily Nucleoside Reverse Transcriptase Inhibitor; Ann Pharmacother 38 (6): 1006-14 (2004)

13 Synonyms and Identifiers

13.1 Substance Title

EMTRICITABINE

14 Administrative Information

14.1 Hazardous Substances DataBank Number

7337

14.2 Last Revision Date

20140630

14.3 Last Review Date

Reviewed by SRP on 1/16/2014

14.4 Update History

Complete Update on 2014-06-30, 35 fields added/edited/deleted

Complete Update on 2006-04-14, 40 fields added/edited/deleted

Created 20050407

CONTENTS