EMTRICITABINE (Generic for EMTRIVA)

General Administration Information
For storage information, see the specific product information within the How Supplied section.

Route-Specific Administration

Oral Administration
-Administer orally with or without food.
Oral Liquid Formulations
-Administer oral solution using a calibrated dosing syringe.

Rash was noted in 21% of pediatric patients during emtricitabine trials. Rash, further specified as 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.

Gastrointestinal related adverse events reported with emtricitabine in pediatric patients include diarrhea (20%), abdominal pain (10%), vomiting (23%), and gastroenteritis (11%). Vomiting tended to occur more frequently in pediatric patients than with adults. Other adverse events reported in adults include nausea (9-18%) and dyspepsia (4-8%).

The adverse event profile of emtricitabine in pediatric patients was generally comparable to that observed in clinical trials with adult patients. Musculoskeletal reactions reported with emtricitabine as part of combination therapy in adult patients consisted of arthralgia (3-5%), myalgia (4-6%), and paresthesias (5-6%).

The adverse event profile of emtricitabine in pediatric patients was generally comparable to that observed in clinical trials with adult patients. Central nervous system or psychiatric adverse reactions in adult patients, 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 were generally reported more frequently in pediatric patients as compared to adults and include cough (28%) and rhinitis (20%).

Grade 3/4 laboratory abnormalities were experienced by 9% of pediatric patients during emtricitabine clinical trials (n=116). Hyperamylasemia at > 2x upper limit of normal (ULN) was reported in 4 patients. Elevated hepatic enzymes were also noted and included 2 patients with an AST > 5x ULN and 1 patient with elevated GGT > 10x ULN. Two patients had elevated CPK > 4x ULN, while hyperbilirubinemia (> 3x ULN), elevated lipase (> 2.5x ULN), and decreased glucose/hypoglycemia (< 40 mg/dL) were reported in 1 patient each. Other abnormal lab values reported during adult trials included elevated creatinine kinase levels (9-12%), hypertriglyceridemia (4-10%), hypercholesterolemia (22%), and hyperglycemia.

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 pediatric clinical trials include unspecified infection (44%), otitis media (23%), and pneumonia (15%). Infections reported in adult patients include sinusitis (8%), upper respiratory tract infection (8%), and naso-pharyngitis (5%).

Fever was noted in 18% of pediatric patients during emtricitabine trials. General adverse events reported during adult trials include asthenia (12-16%), headache (6-22%), and fatigue (9%).

Anemia was noted in 7% of pediatric patients during emtricitabine trials. Grade 3/4 laboratory abnormalities were experienced by 9% of pediatric patients and included neutropenia with neutrophils < 750/mm3 (2.6%) and decreased hemoglobin of < 7 g/dL (< 1%).

The adverse event profile of emtricitabine in pediatric subjects was generally comparable to that observed during adult clinical trials. Abnormal urinary laboratory values reported during adult 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.

Unplanned antiretroviral therapy interruption may be necessary in specific situations, such as serious drug toxicity, intercurrent illness or surgery precluding oral intake (e.g., gastroenteritis or pancreatitis), or drug non-availability. If short-term treatment interruption is necessary (i.e., < 1-2 days), in general, it is recommended that all antiretroviral agents be discontinued simultaneously, especially if the interruption is because of 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. When the antiretroviral regimen contains drugs with differing half-lives, stopping all drugs simultaneously may result in functional monotherapy of the drug with the longest half-life. For example, after discontinuation, the duration of detectable drug concentrations of efavirenz and nevirapine ranges from < 1 week to > 3 weeks. Simultaneously stopping all drugs in a regimen containing these agents may result in functional monotherapy with the NNRTI and may increase the risk of NNRTI-resistant mutations. 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. Therefore, 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 results kept in the patient's medical record until they become 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 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 co-infected with HIV and HBV and require treatment for either infection should be started on a fully suppressive antiretroviral regimen that contains NRTIs with activity against both viruses. Avoid using single-drug therapy to treat HBV (i.e., lamivudine, emtricitabine, or tenofovir as the only active agent) due to the risk of developing resistant strains of HIV. The HIV guidelines recommend that coinfected pediatric patients 2 years and older receive an antiretroviral regimen that contains tenofovir in combination with either lamivudine or emtricitabine as the dual NRTI backbone. If tenofovir cannot be used, another agent with anti-HBV activity should be used in combination with lamivudine or emtricitabine to assure adequate treatment of HBV infection. Management of HIV should be continued with the goal of maximal suppression. In addition, after discontinuation of emtricitabine in patients with coexisting HBV and HIV infection, some patients have experienced severe acute hepatitis B exacerbation. In patients co-infected with HBV and HIV who discontinue emtricitabine, closely monitor hepatic function with both clinical and laboratory follow-up for at least several months. If appropriate, resumption of anti-hepatitis B treatment may be required, especially in patients with advanced liver disease or cirrhosis.

Lactic acidosis and hepatotoxicity with steatosis, including fatal cases, have been reported after use of emtricitabine, both alone and in combination with other antiretroviral medications. Suspend treatment with emtricitabine 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 reactions may occur in any drug recipient, some risk factors include hepatic disease (e.g., alcoholism), obesity, and prolonged nucleoside exposure. In addition, adult females appear to be at a higher risk for lactic acidosis; it is not clear whether this increased risk applies to pediatric females.

Emtricitabine is principally eliminated by the kidney and should be used with caution in patients with renal impairment, including renal failure; 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 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.

Perform hepatitis C virus (HCV) screening in any child whose mother is known to have HCV infection and all HIV-infected adolescents. Treatment of HCV infection in children < 3 years is not usually recommended; however, treatment should be considered for all children >= 3 years and adolescents with hepatitis C and HIV coinfection who have no contraindications to treatment. For antiretroviral-naive adolescent patients with CD4 counts > 500 cells/mm3, consideration may be given to deferring ARV therapy until the hepatitis C treatment regimen has been completed. Conversely, for adolescent patients with CD4 counts < 200 cells/mm3, consider delaying initiation of the hepatitis C treatment regimen until the patient is stable on a fully suppressive ARV regimen. All HIV-infected children and adolescents, regardless of HIV and HCV status, should receive standard vaccination with hepatitis A and B vaccines. Additionally, HIV/HCV-coinfected adolescents should be counseled to avoid alcohol.

Description: Emtricitabine (also referred to as FTC) is a nucleoside analog of cytosine. It is an anti-retroviral nucleoside reverse transcriptase inhibitor (NRTI) used as part of combination therapy to treat HIV infection. While it belongs to the same nucleoside series as lamivudine (3TC), emtricitabine has consistently been more potent against HIV in vitro than lamivudine. Due to the similarities between the two drugs, emtricitabine will not likely be effective in individuals who display antimicrobial resistance to lamivudine. There is a Black Box warning that states safety and efficacy have not been established for patients co-infected with HIV and HBV and that severe, acute exacerbations of hepatitis B have been reported in patients after discontinuation of emtricitabine. Emtricitabine is FDA approved for pediatric patients as young as neonates.

Initiation of HIV therapy
-Antiretroviral drug resistance testing (preferably genotypic testing) is recommended prior to initiation of therapy in antiretroviral treatment (ART)-naive patients and prior to changing therapy for treatment failure.
-Initiation of treatment immediately or within days after HIV diagnosis is recommended in all pediatric patients, except for patients with cryptococcal meningitis, disseminated Mycobacterium avium complex disease, or Mycobacterium tuberculosis disease. In these patients, initiate treatment for the opportunistic infection first, ahead of ART initiation. The urgency of rapid treatment initiation is especially critical for all patients younger than 1 year, who carry the highest risk of rapid disease progression and mortality. If therapy is deferred for certain circumstances, closely monitor the patient's virologic, immunologic, and clinical status at least every 3 to 4 months. If therapy is deferred, initiate treatment when HIV RNA concentrations increase, CD4 count or percentage values decline (i.e., approaching CDC Stage 2 or 3), the patient develops new HIV-related clinical symptoms, or the ability of the caregiver and patient to adhere to the prescribed regimen has improved.

Place in therapy for HIV
-Emtricitabine is one of the preferred nucleoside reverse transcriptase inhibitors (NRTIs) to be included as a part of a 2-NRTI backbone regimen for treatment-naive pediatric patients. The 2-NRTI backbone should be used in combination with a non-nucleoside reverse transcriptase inhibitor (NNRTI), protease inhibitor (PI), or integrase strand transfer inhibitor (INSTI). Specific recommendations vary depending on age.

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 (solution):
Neonates and Infants younger than 3 months: 3 mg/kg/dose PO once daily.
Infants, Children, and Adolescents 3 months to 17 years: 6 mg/kg/dose (Max: 240 mg/dose) PO once daily.
Oral dosage (capsules):
Children and Adolescents weighing more than 33 kg: 200 mg PO once daily.

For human immunodeficiency virus (HIV) prophylaxis* due to nonoccupational exposure:
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):
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.
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.
Oral dosage (solution):
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.
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.
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.
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.

For the treatment of chronic hepatitis B infection* in persons coinfected with HIV:
Oral dosage (solution):
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.
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.
Oral dosage (capsules):
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.

Maximum Dosage Limits:
-Neonates
3 mg/kg/day PO for oral solution; safety and efficacy of the capsule have not been established.
-Infants
>= 3 months: 6 mg/kg/day PO (Max: 240 mg/day) 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.
-Children
> 33 kg: 200 mg/day PO for capsules; 6 mg/kg/day PO (Max: 240 mg/day) for oral solution.
<= 33 kg: 6 mg/kg/day PO (Max: 240 mg/day) for oral solution; safety and efficacy of the capsule have not been established.
-Adolescents
> 33 kg: 200 mg/day PO for capsules; 6 mg/kg/day PO (Max: 240 mg/day) for oral solution.
<= 33 kg: 6 mg/kg/day PO (Max: 240 mg/day) for oral solution; safety and efficacy of the capsule have not been established.

Patients with Hepatic Impairment Dosing
Pharmacokinetics have not been studied in patients with hepatic impairment; however, emtricitabine is not metabolized by hepatic enzymes and, therefore, the impact of hepatic impairment should be limited.

Patients with Renal Impairment Dosing
There are insufficient data to recommend a specific dosage adjustment of emtricitabine in pediatric patients with renal impairment. The following dose adjustments are recommended for adult patients with renal impairment.
Oral Solution
CrCl 50 mL/minute or more: No dosage adjustment needed.
CrCl 30 to 49 mL/minute: 120 mg PO every 24 hours.
CrCl 15 to 29 mL/minute: 80 mg PO every 24 hours.
CrCl less than 15 mL/minute: 60 mg PO every 24 hours.

Capsules
CrCl 50 mL/minute or more: No dosage adjustment needed.
CrCl 30 to 49 mL/minute: 200 mg PO every 48 hours.
CrCl 15 to 29 mL/minute: 200 mg PO every 72 hours.
CrCl less than 15 mL/minute: 200 mg PO every 96 hours.

Intermittent hemodialysis
There are no data available in pediatric patients. For adults, the recommended dose is 200 mg PO every 96 hours for the capsules or 60 mg PO every 24 hours for the oral solution with the dose administered after hemodialysis on dialysis days.

*non-FDA-approved indication

Monograph content under development

Mechanism of Action: Emtricitabine inhibits viral reverse transcriptase and is active in vitro for both HIV-1 and HBV. It is similar in structure and activity to lamivudine, although its activity against HIV-1 is approximately 4-10 fold greater than that of lamivudine. This increased potency may be due to a greater binding affinity and more efficient incorporation into viral DNA. It is a synthetic nucleoside analog of cytosine and is phosphorylated by cellular enzymes to emtricitabine 5'-triphosphate. Emtricitabine 5'-triphosphate inhibits the activity of HIV-1 reverse transcriptase by competing with the deoxycytidine 5'-triphosphate and by being incorporated into nascent viral DNA, resulting in chain termination. Emtricitabine 5'-triphosphate is a weak inhibitor of polymerase alpha, beta, epsilon and mitochondrial DNA polymerase gamma. Combination therapy targets different points in the life cycle of HIV, reducing the ability of HIV to mutate to drug-resistant strains. In combination with another NRTI (e.g., zidovudine or stavudine) and efavirenz, emtricitabine has been shown to increase CD4 cell counts and reduce plasma HIV-1 RNA levels.

Pharmacokinetics: Emtricitabine is administered orally and exhibits low plasma protein binding (< 4%) that is independent of plasma concentration.

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). Emtricitabine 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
The results of in vitro studies, with concentrations up to 14-fold higher than those observed in vivo, indicate that CYP450 mediated interactions are not expected. Emtricitabine did not inhibit the enzyme responsible for glucuronidation (uridine-5'-disphosphoglucuronyl transferase).


-Route-Specific Pharmacokinetics
Oral Route
Emtricitabine is rapidly and extensively absorbed, with a mean absolute bioavailability of 93% for capsules and 75% for solution. Food has no clinically significant effect on systemic exposure, and the drug may be administered with or without food.


-Special Populations
Pediatrics
Neonates and Infants < 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 h/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 h/mL at 0-21 days old, 8.55 mcg x h/mL at 22-42 days old , and 9.27 mcg xh/mL at 43-90 days old. This correlates to an increase in total body clearance of the drug which started at 13 ml/min at 0-21 days old and increased to 29 ml/min by 43-90 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 h/mL) exceeded that of adults and older children; however the median half-life was similar at 9.2 hours.

Infants > 3 Months, Children, and Adolescents
Pediatric pharmacokinetic parameters in patients > 3 months are similar to those seen in adults. The mean Cmax across the age bands (n=77) ranged from 1.9-2.7 mcg/mL as compared to the adult mean Cmax of 1.8 mcg/mL. The mean AUC in pediatric patients ranged from 8.7-12.6 mcg x h/mL compared to 10 mcg x h/mL in adults. The mean half-life was 8.2-11.3 hours in pediatric patients as compared to approximately 10 hours in adults.

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 a dose. It is not known if emtricitabine is removed by peritoneal dialysis. The effects of renal impairment on the pharmacokinetic parameters in pediatric patients is not known.