英文药名：Emtriva Capsules（Emtricitabine）

中文药名：恩曲他滨胶囊

生产厂家：鸟居药业
给药说明：
商標名
Emtriva Capsules 200mg
一般名
エムトリシタビン　Emtricitabine
化学名
4-Amino-5-fluoro-1-［(2R,5S)-2-(hydroxymethyl)-1,3-oxathiolan-5-yl］pyrimidin-2(1H)-one
分子式
C8H10FN3O3S
分子量
247.25
化学構造式

性状
它是白色至淡黄色的粉末，并易溶于水和甲醇，微溶于乙腈中，极微溶于乙酸异丙酯。
熔点
约155℃
分配系数
-0.43（辛醇/水）
【批准的条件】
一、本药物，因为它是目前正在日本进行的临床试验和国外，正在使用中，它们继续被收集的有效性和安全性的数据进一步对这种药物的病人使其充分地描述，以获得知情同意，有可能请求医生。
二、药代动力学研究，以及，它可以定期汇报进展情况和结束后尽快提交分析结果和试验结果。此外，临床试验计划或正在进行海外，应结束后尽快提交分析结果和试验结果越好。
三、在复试阶段，直到最后，进行了国内所有病例治疗原则后，市场调查，对实际使用这种药物的信息（患者的背景，疗效和安全性（其他药合用它可以通过收集数据等）和药物相互作用定期报告），包括我们这个时代的有效性和安全性，在应用调查结果时需提交的申请附件复检。
药理作用 
本品是一种新型核苷类逆转录酶抑制剂，对HIV-1、HIV-2及HBV均有抗病毒活性。本品口服后被磷酸化为具有细胞活性的5′-三磷酸盐，5′-三磷酸盐通过进入病毒DNA主链，与主链结合，导致链终止，从而抑制HIV-1逆转录酶及HBV DNA聚合酶活性。
药动学
给雄性小鼠口服和静注单剂量本品10mg/kg、100mg/kg或600mg/kg，结果显示，本品吸收好，清除快，且在研究所使用的剂量范围内其药代动力学呈剂量依赖性，总清除速率快，接近于肾血流量。对HIV感染者单独给予本品100～1200mg，Tmax为1.25～1.61h。HIV感染者接受本品1天200mg，其血浆半衰期为7.5～8h，本品三磷酸盐的细胞内半衰期大约为39h。
适应证
与其他抗逆转录病毒药物联合用于成人HIV-1感染的治疗。
禁忌证
1.已知对本品或其中任一组分过敏者禁用。
2.禁用于晚期肾病及肝功能不全者。
3.孕妇服用本品可能对胎儿和新生儿有不利影响。本品可通过乳腺分泌也可影响受乳婴儿，一般不推荐孕妇和哺乳期妇女使用本品。
4.老年人选择剂量时应慎重，可根据其肝、肾、心功能的衰退、伴发的疾病以及其他药物治疗的影响，酌情减量服用。
注意事项
1.本品主要经肾排泄，故肾功能不全患者服用本品应减量。
2.儿童尚未建立安全有效的依据，故儿童不推荐使用。
3.尚无特效解救药，药物过量采用支持治疗。
不良反应
1.全身：腹痛、无力、头痛。
2.消化系统：腹泻、消化不良、恶心、呕吐。
3.骨骼肌肉：关节痛、肌痛。
4.神经系统：睡梦异常、抑郁、头晕、失眠、神经痛、外周神经炎、感觉异常。
5.呼吸系统：咳嗽加重、鼻炎。
6.皮肤：疹。
用法用量
18岁以上成人口服用药，每次200mg，1次/d。空腹服用，也可与食物同服。肾功能不良者应调整剂量，改为200mg，隔天1次或每3天1次。
药物相应作用
本品不影响肝微粒体酶P450酶系统，不产生由此介导的药物相互作用，与替诺氟韦、茚地那韦、泛昔洛韦、司坦夫定合用，药代动力学几乎无影响。
http://www.info.pmda.go.jp/go/pack/6250028M1029_1_06/

These highlights do not include all the information needed to use EMTRIVA safely and effectively. See full prescribing information for EMTRIVA.EMTRIVA (emtricitabine) capsule for oral useEMTRIVA (emtricitabine) solution for oral useInitial U.S. Approval:

Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs alone or in combination with other antiretrovirals [See Warnings and Precautions (5.1)].

EMTRIVA is not approved for the treatment of chronic hepatitis B virus (HBV) infection and the safety and efficacy of EMTRIVA have not been established in patients coinfected with HBV and HIV-1. Severe acute exacerbations of hepatitis B have been reported in patients who have discontinued EMTRIVA. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who are coinfected with HIV-1 and HBV and discontinue EMTRIVA. If appropriate, initiation of anti-hepatitis B therapy may be warranted [See Warnings and Precautions (5.2)].

EMTRIVA is indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection.

Additional important information regarding the use of EMTRIVA for the treatment of HIV-1 Infection:

EMTRIVA may be taken without regard to food.

Significantly increased drug exposures were seen when EMTRIVA was administered to patients with renal impairment [See Clinical Pharmacology (12.3)]. Therefore, the dosing interval or dose of EMTRIVA should be adjusted in patients with baseline creatinine clearance <50 mL/min using the following guidelines (see Table 1). The safety and effectiveness of these dose adjustment guidelines have not been clinically eva luated. Therefore, clinical response to treatment and renal function should be closely monitored in these patients.

Although there are insufficient data to recommend a specific dose adjustment of EMTRIVA in pediatric patients with renal impairment, a reduction in the dose and/or an increase in the dosing interval similar to adjustments for adults should be considered.

Table 1 Dose Adjustment in Adult Patients with Renal Impairment

	Creatinine Clearance (mL/min)
Formulation	≥50 mL/min	30–49 mL/min	15–29 mL/min	<15 mL/min or on hemodialysisHemodialysis Patients: If dosing on day of dialysis, give dose after dialysis
Capsule (200 mg)	200 mg every 24 hours	200 mg every 48 hours	200 mg every 72 hours	200 mg every 96 hours
Oral Solution (10 mg/mL)	240 mg every 24 hours (24 mL)	120 mg every 24 hours (12 mL)	80 mg every 24 hours (8 mL)	60 mg every 24 hours (6 mL)

EMTRIVA is available as capsules and oral solution.

EMTRIVA capsules, containing 200 mg of emtricitabine, are size 1 hard gelatin capsules with a blue cap and white body, printed with "200 mg" in black on the cap and "GILEAD" and the corporate logo in black on the body.

EMTRIVA oral solution is a clear, orange to dark orange liquid containing 10 mg of emtricitabine per mL.

EMTRIVA is contraindicated in patients with previously demonstrated hypersensitivity to any of the components of the products.

Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs alone or in combination, including emtricitabine and other antiretrovirals. A majority of these cases have been in women. Obesity and prolonged nucleoside exposure may be risk factors. Particular caution should be exercised when administering nucleoside analogs to any patient with known risk factors for liver diseases; however, cases have also been reported in patients with no known risk factors. Treatment with EMTRIVA should be suspended 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).

It is recommended that all patients with HIV-1 be tested for the presence of chronic Hepatitis B virus (HBV) before initiating antiretroviral therapy. EMTRIVA is not approved for the treatment of chronic HBV infection and the safety and efficacy of EMTRIVA have not been established in patients coinfected with HBV and HIV-1. Severe acute exacerbations of Hepatitis B have been reported in patients after the discontinuation of EMTRIVA. In some patients infected with HBV and treated with EMTRIVA, the exacerbations of hepatitis B were associated with liver decompensation and liver failure. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who are coinfected with HIV-1 and HBV and discontinue EMTRIVA. If appropriate, initiation of anti-Hepatitis B therapy may be warranted.

EMTRIVA is a component of TRUVADA (a fixed-dose combination of emtricitabine and tenofovir disoproxil fumarate) and ATRIPLA (a fixed-dose combination of efavirenz, emtricitabine, and tenofovir disoproxil fumarate). EMTRIVA should not be coadministered with TRUVADA or ATRIPLA. Due to similarities between emtricitabine and lamivudine, EMTRIVA should not be coadministered with other drugs containing lamivudine, including Combivir (lamivudine/zidovudine), Epivir or Epivir-HBV (lamivudine), Epzicom (abacavir sulfate/lamivudine), or Trizivir (abacavir sulfate/lamivudine/zidovudine).

Emtricitabine is principally eliminated by the kidney. Reduction of the dosage of EMTRIVA is recommended for patients with impaired renal function [See Dosage and Administration (2.5) and Clinical Pharmacology (12.3)].

Redistribution/accumulation of body fat including central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, facial wasting, breast enlargement, and "cushingoid appearance" have been observed in patients receiving antiretroviral therapy. The mechanism and long-term consequences of these events are currently unknown. A causal relationship has not been established.

Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy, including EMTRIVA. During the initial phase of combination antiretroviral treatment, patients whose immune system responds may develop an inflammatory response to indolent or residual opportunistic infections [such as Mycobacterium avium infection, cytomegalovirus, Pneumocystis jirovecii pneumonia (PCP), or tuberculosis], which may necessitate further eva luation and treatment.

The following adverse reactions are discussed in other sections of the labeling:

Adult Patients

More than 2,000 adult patients with HIV-1 infection have been treated with EMTRIVA alone or in combination with other antiretroviral agents for periods of 10 days to 200 weeks in clinical trials.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The most common adverse reactions (incidence ≥10%, any severity) identified from any of the 3 large controlled clinical trials include headache, diarrhea nausea, fatigue, dizziness, depression, insomnia, abnormal dreams, rash, abdominal pain, asthenia, increased cough, and rhinitis.

Studies 301A and 303 - Treatment Emergent Adverse Reactions: The most common adverse reactions that occurred in patients receiving EMTRIVA with other antiretroviral agents in clinical studies 301A and 303 were headache, diarrhea, nausea, and rash, which were generally of mild to moderate severity. Approximately 1% of patients discontinued participation in the clinical studies due to these events. All adverse reactions were reported with similar frequency in EMTRIVA and control treatment groups with the exception of skin discoloration which was reported with higher frequency in the EMTRIVA treated group.

Skin discoloration, manifested by hyperpigmentation on the palms and/or soles was generally mild and asymptomatic. The mechanism and clinical significance are unknown.

A summary of EMTRIVA treatment emergent clinical adverse reactions in studies 301A and 303 is provided in Table 2.

Table 2 Selected Treatment-Emergent Adverse Reactions (All Grades, Regardless of Causality) Reported in ≥3% of EMTRIVA-Treated Patients in Either Study 301A or 303 (0–48 Weeks)

	303		301A
	EMTRIVA + ZDV/d4T + NNRTI/PI (N=294)	Lamivudine + ZDV/d4T + NNRTI/PI (N=146)	EMTRIVA + didanosine + efavirenz (N=286)	Stavudine + didanosine + efavirenz (N=285)
Body as a Whole
Abdominal pain	8%	11%	14%	17%
Asthenia	16%	10%	12%	17%
Headache	13%	6%	22%	25%
Digestive System
Diarrhea	23%	18%	23%	32%
Dyspepsia	4%	5%	8%	12%
Nausea	18%	12%	13%	23%
Vomiting	9%	7%	9%	12%
Musculoskeletal
Arthralgia	3%	4%	5%	6%
Myalgia	4%	4%	6%	3%
Nervous System
Abnormal dreams	2%	<1%	11%	19%
Depressive disorders	6%	10%	9%	13%
Dizziness	4%	5%	25%	26%
Insomnia	7%	3%	16%	21%
Neuropathy/peripheral neuritis	4%	3%	4%	13%
Paresthesia	5%	7%	6%	12%
Respiratory
Increased cough	14%	11%	14%	8%
Rhinitis	18%	12%	12%	10%
Skin
Rash eventRash event includes rash, pruritus, maculopapular rash, urticaria, vesiculobullous rash, pustular rash, and allergic reaction.	17%	14%	30%	33%

Studies 301A and 303 - Laboratory Abnormalities:

Laboratory abnormalities in these studies occurred with similar frequency in the EMTRIVA and comparator groups. A summary of Grade 3 and 4 laboratory abnormalities is provided in Table 3 below.

Table 3 Treatment-Emergent Grade 3/4 Laboratory Abnormalities Reported in ≥1% of EMTRIVA-Treated Patients in Either Study 301A or 303

	303		301A
	EMTRIVA + ZDV/d4T + NNRTI/PI (N=294)	Lamivudine + ZDV/d4T + NNRTI/PI (N=146)	EMTRIVA + Didanosine + Efavirenz (N=286)	Stavudine + Didanosine + Efavirenz (N=285)
Percentage with grade 3 or grade 4 laboratory abnormality	31%	28%	34%	38%
ALT (>5.0 × ULNULN = Upper limit of normal)	2%	1%	5%	6%
AST (>5.0 × ULN)	3%	<1%	6%	9%
Bilirubin (>2.5 × ULN)	1%	2%	<1%	<1%
Creatine kinase (>4.0 × ULN)	11%	14%	12%	11%
Neutrophils (<750 mm3)	5%	3%	5%	7%
Pancreatic amylase (>2.0 × ULN)	2%	2%	<1%	1%
Serum amylase (>2.0 × ULN)	2%	2%	5%	10%
Serum glucose <40 or >250 mg/dL)	3%	3%	2%	3%
Serum lipase (>2.0 × ULN)	<1%	<1%	1%	2%
Triglycerides (>750 mg/dL)	10%	8%	9%	6%

Study 934 - Treatment Emergent Adverse Reactions: In Study 934, 511 antiretroviral-naïve patients received either VIREAD + EMTRIVA administered in combination with efavirenz (N=257) or zidovudine/lamivudine administered in combination with efavirenz (N=254). Adverse reactions observed in this study were generally consistent with those seen in previous studies in treatment-experienced or treatment-naïve patients (Table 4).

Table 4 Selected Treatment-Emergent Adverse ReactionsFrequencies of adverse reactions are based on all treatment-emergent adverse events, regardless of relationship to study drug. (Grades 2–4) Reported in ≥5% in Any Treatment Group in Study 934 (0–144 Weeks)

	TDFFrom Weeks 96 to 144 of the study, patients received TRUVADA with efavirenz in place of VIREAD + EMTRIVA with efavirenz. + EMTRIVA + EFV	AZT/3TC + EFV
	N=257	N=254
Gastrointestinal Disorder
Diarrhea	9%	5%
Nausea	9%	7%
Vomiting	2%	5%
General Disorders and Administration Site Condition
Fatigue	9%	8%
Infections and Infestations
Sinusitis	8%	4%
Upper respiratory tract infections	8%	5%
Nasopharyngitis	5%	3%
Nervous System Disorders
Headache	6%	5%
Dizziness	8%	7%
Psychiatric Disorders
Depression	9%	7%
Insomnia	5%	7%
Skin and Subcutaneous Tissue Disorders
Rash eventRash event includes rash, exfoliative rash, rash generalized, rash macular, rash maculo-papular, rash pruritic, and rash vesicular.	7%	9%

Study 934 – Laboratory Abnormalities: Significant laboratory abnormalities observed in this study are shown in Table 5.

Table 5 Significant Laboratory Abnormalities Reported in ≥1% of Patients in Any Treatment Group in Study 934 (0–144 Weeks)

	TDFFrom Weeks 96 to 144 of the study, patients received TRUVADA with efavirenz in place of VIREAD + EMTRIVA with efavirenz. + EMTRIVA + EFV	AZT/3TC + EFV
	N=257	N=254
Any ≥ Grade 3 Laboratory Abnormality	30%	26%
Fasting Cholesterol (>240 mg/dL)	22%	24%
Creatine Kinase (M: >990 U/L) (F: >845 U/L)	9%	7%
Serum Amylase (>175 U/L)	8%	4%
Alkaline Phosphatase (>550 U/L)	1%	0%
AST (M: >180 U/L) (F: >170 U/L)	3%	3%
ALT (M: >215 U/L) (F: >170 U/L)	2%	3%
Hemoglobin (<8.0 mg/dL)	0%	4%
Hyperglycemia (>250 mg/dL)	2%	1%
Hematuria (>75 RBC/HPF)	3%	2%
Glycosuria (3+)	<1%	1%
Neutrophils (<750/mm3)	3%	5%
Fasting Triglycerides (>750 mg/dL)	4%	2%

Pediatric Patients

Assessment of adverse reactions is based on data from Study 203, an open label, uncontrolled study of 116 HIV-1-infected pediatric patients who received emtricitabine through 48 weeks. The adverse reaction profile in pediatric patients was generally comparable to that observed in clinical studies of EMTRIVA in adult patients [See Adverse Reactions (6.1)]. Hyperpigmentation was more frequent in children. Additional adverse reactions identified from this study include anemia.

Selected treatment-emergent adverse events, regardless of causality, reported in patients during 48 weeks of treatment were the following: infection (44%), hyperpigmentation (32%), increased cough (28%), vomiting (23%), otitis media (23%), rash (21%), rhinitis (20%), diarrhea (20%), fever (18%), pneumonia (15%), gastroenteritis (11%), abdominal pain (10%), and anemia (7%). Treatment-emergent grade 3/4 laboratory abnormalities were experienced by 9% of pediatric patients, including amylase >2.0 × ULN (n=4), neutrophils <750/mm (n=3), ALT >5 × ULN (n=2), elevated CPK (>4 × ULN) (n=2) and one patient each with elevated bilirubin (>3.0 × ULN), elevated GGT (>10 × ULN), elevated lipase (>2.5 × ULN), decreased hemoglobin (<7 g/dL), and decreased glucose (<40 mg/dL).

The potential for drug interactions with EMTRIVA has been studied in combination with zidovudine, indinavir, stavudine, famciclovir, and tenofovir disoproxil fumarate. There were no clinically significant drug interactions for any of these drugs Drug interactions studies are described elsewhere in the labeling [See Clinical Pharmacology (12.3)]

Pregnancy Category B

The incidence of fetal variations and malformations was not increased in embryofetal toxicity studies performed with emtricitabine in mice at exposures (AUC) approximately 60-fold higher and in rabbits at approximately 120-fold higher than human exposures at the recommended daily dose. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, EMTRIVA should be used during pregnancy only if clearly needed.

Antiretroviral Pregnancy Registry: To monitor fetal outcomes of pregnant women exposed to EMTRIVA, an Antiretroviral Pregnancy Registry has been established. Healthcare providers are encouraged to register patients by calling 1–800–258–4263.

Nursing Mothers: The Centers for Disease Control and Prevention recommend that HIV-1-infected mothers not breast-feed their infants to avoid risking postnatal transmission of HIV-1. It is not known whether emtricitabine is excreted in human milk. Because of both the potential for HIV-1 transmission and the potential for serious adverse reactions in nursing infants, mothers should be instructed not to breast-feed if they are receiving EMTRIVA.

The safety and efficacy of emtricitabine in patients between 3 months and 21 years of age is supported by data from three open-label, non-randomized clinical studies in which emtricitabine was administered to 169 HIV-1 infected treatment-naive and experienced (defined as virologically suppressed on a lamivudine containing regimen for which emtricitabine was substituted for lamivudine) subjects [See Clinical Studies(14.3)].

The pharmacokinetics of emtricitabine were studied in 20 neonates born to HIV-1-positive mothers [See Clinical Studies (14.3)]. All neonates were HIV-1 negative at the end of the study; the efficacy of emtricitabine in preventing or treating HIV-1 could not be determined.

Clinical studies of EMTRIVA did not include sufficient numbers of subjects aged 65 years and over to determine whether they respond differently from younger subjects. In general, dose selection for the elderly patient should be cautious, keeping in mind the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

It is recommended that the dose or dosing interval for EMTRIVA be modified in patients with creatinine clearance <50 mL/min or in patients who require dialysis [See Dosage and Administration (2.5)].

There is no known antidote for EMTRIVA. Limited clinical experience is available at doses higher than the therapeutic dose of EMTRIVA. In one clinical pharmacology study single doses of emtricitabine 1200 mg were administered to 11 patients. No severe adverse reactions were reported.

The effects of higher doses are not known. If overdose occurs the patient should be monitored for signs of toxicity, and standard supportive treatment applied as necessary.

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.

EMTRIVA is the brand name of emtricitabine, a synthetic nucleoside analog with activity against human immunodeficiency virus type 1 (HIV-1) reverse transcriptase.

The chemical name of emtricitabine is 5-fluoro-1-(2R,5S)-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl]cytosine. Emtricitabine is the (-) enantiomer of a thio analog of cytidine, which differs from other cytidine analogs in that it has a fluorine in the 5-position.

It has a molecular formula of CHFNOS and a molecular weight of 247.24. It has the following structural formula:

Emtricitabine is a white to off-white powder with a solubility of approximately 112 mg/mL in water at 25 °C. The log P for emtricitabine is -0.43 and the pKa is 2.65.

EMTRIVA is available as capsules or as an oral solution.

EMTRIVA capsules are for oral administration. Each capsule contains 200 mg of emtricitabine and the inactive ingredients, crospovidone, magnesium stearate, microcrystalline cellulose, and povidone.

EMTRIVA oral solution is for oral administration. One milliliter (1 mL) of EMTRIVA oral solution contains 10 mg of emtricitabine in an aqueous solution with the following inactive ingredients: cotton candy flavor, FD&C yellow No. 6, edetate disodium, methylparaben, and propylparaben (added as preservatives), sodium phosphate (monobasic), propylene glycol, water, and xylitol (added as a sweetener). Sodium hydroxide and hydrochloric acid may be used to adjust pH.

Emtricitabine is an antiviral drug. [See Clinical Pharmacology (12.4)]

Adult Subjects

The pharmacokinetics of emtricitabine were eva luated in healthy volunteers and HIV-1-infected individuals. Emtricitabine pharmacokinetics are similar between these populations.

Figure 1 shows the mean steady-state plasma emtricitabine concentration-time profile in 20 HIV-1-infected subjects receiving EMTRIVA capsules.

Figure 1 Mean (± 95% CI) Steady-State Plasma Emtricitabine Concentrations in HIV-1-Infected Adults (N=20)

Absorption

Emtricitabine is rapidly and extensively absorbed following oral administration with peak plasma concentrations occurring at 1–2 hours post-dose. Following multiple dose oral administration of EMTRIVA capsules to 20 HIV-1-infected subjects, the (mean ± SD) steady-state plasma emtricitabine peak concentration (C) was 1.8 ± 0.7 µg/mL and the area-under the plasma concentration-time curve over a 24-hour dosing interval (AUC) was 10.0 ± 3.1 µg∙hr/mL. The mean steady state plasma trough concentration at 24 hours post-dose was 0.09 µg/mL. The mean absolute bioavailability of EMTRIVA capsules was 93% while the mean absolute bioavailability of EMTRIVA oral solution was 75%. The relative bioavailability of EMTRIVA oral solution was approximately 80% of EMTRIVA capsules.

The multiple dose pharmacokinetics of emtricitabine are dose proportional over a dose range of 25–200 mg.

Distribution

In vitro binding of emtricitabine to human plasma proteins was <4% and independent of concentration over the range of 0.02–200 µg/mL. At peak plasma concentration, the mean plasma to blood drug concentration ratio was ~1.0 and the mean semen to plasma drug concentration ratio was ~4.0.

Metabolism

In vitro studies indicate that emtricitabine is not an inhibitor of human CYP450 enzymes. Following administration of C-emtricitabine, complete recovery of the dose was achieved in urine (~86%) and feces (~14%). Thirteen percent (13%) of the dose was recovered in urine as three putative metabolites. The biotransformation of emtricitabine includes oxidation of the thiol moiety to form the 3'-sulfoxide diastereomers (~9% of dose) and conjugation with glucuronic acid to form 2'-O-glucuronide (~4% of dose). No other metabolites were identifiable.

Elimination

The plasma emtricitabine half-life is approximately 10 hours. The renal clearance of emtricitabine 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.

Effects of Food on Oral Absorption

EMTRIVA capsules and oral solution may be taken with or without food. Emtricitabine systemic exposure (AUC) was unaffected while C decreased by 29% when EMTRIVA capsules were administered with food (an approximately 1000 kcal high-fat meal). Emtricitabine systemic exposure (AUC) and C were unaffected when 200 mg EMTRIVA oral solution was administered with either a high-fat or low-fat meal.

Special Populations

Race, Gender

The pharmacokinetics of emtricitabine were similar in adult male and female patients and no pharmacokinetic differences due to race have been identified.

Pediatric Patients

The pharmacokinetics of emtricitabine at steady state were determined in 77 HIV-1-infected children, and the pharmacokinetic profile was characterized in four age groups (Table 6). The emtricitabine exposure achieved in children receiving a daily dose of 6 mg/kg up to a maximum of 240 mg oral solution or a 200 mg capsule is similar to exposures achieved in adults receiving a once-daily dose of 200 mg.

The pharmacokinetics of emtricitabine were studied in 20 neonates born to HIV-1-positive mothers. Each mother received prenatal and intrapartum combination antiretroviral therapy. Neonates received up to 6 weeks of zidovudine prophylactically after birth. The neonates were administered two short courses of emtricitabine oral solution (each 3 mg/kg once daily × 4 days) during the first 3 months of life. The AUC observed in neonates who received a daily dose of 3 mg/kg of emtricitabine was similar to the AUC observed in pediatric patients ≥3 months to 17 years who received a daily dose of emtricitabine as a 6 mg/kg oral solution up to 240 mg or as a 200 mg capsule (Table 6).
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产地国家：日本
原产地英文商品名:
EMTRIVA CAPSULE（エムトリバカプセル）200MG/CAP 30CAPS/BOTTLE
原产地英文药品名:
EMTRICITABINE
中文参考商品译名:
EMTRIVA胶囊剂（エムトリバカプセル）200毫克/胶囊 30胶囊/瓶
中文参考药品译名:
恩曲他滨
生产厂家中文参考译名:
鸟居药业有限公司
生产厂家英文名:
Torii Pharmaceutical Co., Ltd.