每日1次三联片剂Complera获准用于初治HIV-1成人感染 
2011年8月，美国FDA批准了Gilead科学有限公司开发的由利匹韦林(rilpivirine)25mg、恩曲他滨(emtricitabine)200mg和替诺福韦酯(tenofovir disoproxil fumarate)300mg组成的复合片剂Complera,用于治疗无既往治疗史的成人艾滋病毒(HIV-1)感染患者。
COMPLERA（恩曲他滨，rilpivirine，富马酸替诺福韦酯）片剂，口服使用
美国首次批准：2011
警告：乳酸性酸中毒/重度肝肿大伴脂肪变性和后处理急性发作期乙型肝炎查看完整处方信息了解完整的黑框警告。
乳酸性酸中毒和严重肝肿大伴脂肪变性，包括致命的情况下，有报道使用核苷类似物，包括富马酸替诺福韦酯，COMPLERA的一个组成部分。
COMPLERA没有被批准用于治疗慢性乙型肝炎病毒（HBV）感染的治疗。乙型肝炎的严重急性加重已经报道的患者的HIV-1和HBV谁已停止恩曲他滨或VIREAD，二COMPLERA的部件的共感染。肝功能应该在这些患者密切监测。如果适当的话，抗乙型肝炎治疗开始可以保证。
目前的主要变化
剂量和给药方法  06/2014
禁忌  06/2014
警告和注意事项  05/2015
警告和注意事项  06/2014
适应症和用法
COMPLERA，两种核苷类似物的HIV-1逆转录酶抑制剂（恩曲他滨和富马酸替诺福韦酯）和一个非核苷逆转录酶抑制剂（rilpivirine）的组合，被指示用作完整方案为HIV-1感染的治疗
（1）成人患者无抗逆转录病毒治疗的历史和与HIV-1 RNA的小于或等于10万拷贝/ml，在治疗开始。
（2）在某些病毒学抑制（HIV-1的RNA <50拷贝/毫升）成人患者在稳定的抗逆转录病毒疗法在治疗开始，以取代他们目前的抗逆转录病毒治疗方案（见下文）。
无抗逆转录病毒治疗史开始治疗时COMPLERA成人患者有以下几点值得考虑：
更多rilpivirine治疗的患者与HIV-1 RNA大于100,000拷贝/毫升在治疗经历病毒学失败的开始（HIV-1 RNA≥50拷贝/毫升）相比，rilpivirine治疗的患者与HIV-1 RNA小于或等于10万拷贝/毫升。
不管在治疗开始的HIV-1 RNA水平，更rilpivirine治疗的受试者与CD4+细胞在治疗经历病毒学失败的开始计数低于200个细胞/ mm3的相比受试者的CD4+细胞计数大于或等于200个细胞/立方毫米。
在rilpivirine治疗的受试者的观察病毒治疗失败率赋予更高的速率整体治疗抗性和交叉抗性的对NNRTI类相比依法韦仑。
与rilpivirine开发的替诺福韦和拉米夫定/恩曲他滨相关性相比，依非韦伦治疗的更多患者。
COMPLERA的功效成立于谁是病毒学抑制（HIV-1 RNA <50拷贝/毫升）的稳定利托那韦，提高蛋白酶抑制剂含-方案的患者。考虑与COMPLERA取代目前的方案在病毒学抑制（HIV-1 RNA<50拷贝/毫升），成年人时，以下几点应满足：
患者应当病毒学失败的历史。
患者应该被抑制（HIV-1 RNA <50拷贝/毫升）之前切换治疗至少6个月。
患者应目前是对前切换治疗他们的第一或第二抗逆转录病毒疗法。
患者应当电阻没有当前或过去的历史，以任何COMPLERA的三个组成部分。
对HIV-1 RNA和方案耐受性监测的其他替代疗法，以评估潜在的病毒学失败或反弹后建议。
COMPLERA是不建议患者小于18岁。
用法用量
推荐剂量：一个片剂（含有200mg恩曲他滨，rilpivirine 25毫克和300毫克的富马酸替诺福韦酯），每天一次与食物一起服用。
剂量肾功能损害：不应给予患者低于每分钟50毫升肌酐清除率。
与利福布汀合用，rilpivirine的额外的25毫克片剂（Edurant）每天一次，推荐采取与之同时COMPLERA和随餐的利福布汀共同给药的持续时间。
剂型和规格
片剂：200毫克的恩曲他滨，rilpivirine 25毫克和300毫克的富马酸替诺福韦酯。
禁忌
COMPLERA合用是禁忌用药物，其中在rilpivirine血浆浓度显著下跌可能会发生，这可能会导致病毒学应答和可能的阻力和交叉耐药性的损失。
警告和注意事项
皮肤及过敏反应：上市后的经验，包括药物反应的嗜酸粒细胞增多和全身症状（DRESS）的情况下，在严重的皮肤和过敏性反应的报道。立即停止治疗，如果过敏或皮疹伴肝血清生化指标的全身症状，或海拔开发，并密切监测临床状态，包括肝血清生化指标。
新发或加重肾功能损害：可包括急性肾功能衰竭和Fanconi综合征。与COMPLERA开始治疗前评估肌酐清除率。在危险的患者肾功能不全，治疗期间开始治疗COMPLERA并定期评估之前估计肌酐清除，血清磷，尿葡萄糖和尿蛋白。避免并发或近期使用肾毒性药物管理COMPLERA。
注意应给予处方COMPLERA与药物可降低rilpivirine的曝光。
注意应给予处方COMPLERA药物与尖端扭转型室中的一个已知危险。
抑郁症：严重抑郁症的报道。立即医疗评估，建议严重的抑郁症。
肝毒性：肝不良事件的报道对收到一个含有rilpivirine-方案的患者。显示器前，用COMPLERA治疗的患者有潜在肝脏疾病或肝脏相关的测试显着升高在肝相关的测试。也可以考虑无危险因素监测肝相关检查的患者。
骨密度（BMD）跌幅：考虑与病理性骨折或骨质疏松或骨质流失的其他危险因素的历史监测BMD患者。
合用与其他产品：不要与含恩曲他滨，rilpivirine或富马酸替诺福韦酯包括ATRIPLA，恩曲他滨，STRIBILD，TRUVADA，VIREAD，或含有拉米夫定药物的药物使用。不要管理与阿德福韦酯组合。不要在rilpivirine（Edurant）的组合共同使用，除非在与利福布丁合用需要调整剂量。
体内脂肪重新分配/积累：观察在接受抗逆转录病毒治疗的患者。
免疫重建综合征：可能需要进一步的评估和治疗。
不良反应
最常见的不良药物反应rilpivirine（发生率大于或等于2％，等级2-4）是抑郁症，失眠，头痛和。
最常见的不良反应为恩曲他滨和富马酸替诺福韦酯（发生率≥10％）有腹泻，恶心，乏力，头痛，头晕，抑郁，失眠，异梦，和皮疹。
药物相互作用
COMPLERA是一个完整的方案治疗的HIV-1感染的治疗;因此，COMPLERA不应施用其他抗逆转录病毒药物治疗HIV-1感染。
CYP3A4诱导剂或抑制剂：药物诱导或抑制CYP3A4的可能影响rilpivirine的血浆浓度。
药物，增加胃pH值：药物，增加胃pH值可能会降低rilpivirine的血药浓度。
特殊人群中使用
哺乳母亲：女性艾滋病病毒感染者应指示不进行母乳喂养，由于艾滋病毒传播的可能性。
儿科：不建议患者小于18岁。
COMPLERA(emtricitabine, rilpivirine, tenofovir disoproxil fumarate) tablets
INDICATION
COMPLERA is indicated as a complete regimen for the treatment of HIV-1 infection:
•In patients 12 years and older who have no antiretroviral (ARV) treatment history with HIV-1 RNA ≤100,000 copies/mL
•To replace the current ARV regimen in patients who are virologically suppressed (HIV-1 RNA <50 copies/mL) for ≥6 months on their first or second ARV regimen with no history of treatment failure and no known resistance to any component of COMPLERA. Efficacy was established in patients who were stable on a ritonavir-boosted, protease inhibitor-containing regimen. Additional monitoring of HIV-1 RNA and regimen tolerability is recommended after replacing therapy to assess for potential virologic failure or rebound.
Prescribing considerations in patients with no ARV treatment history: Virologic failure (HIV-1 RNA ≥50 copies/mL) was higher in subjects with baseline HIV-1 RNA >100,000 copies/mL and in subjects with baseline CD4 cell count <200 cells/mm3 (regardless of baseline HIV-1 RNA levels). Compared to efavirenz, virologic failure in rilpivirine-treated subjects conferred a higher rate of overall resistance and cross-resistance to the NNRTI class and more subjects developed tenofovir- and lamivudine/emtricitabine-associated resistance.
IMPORTANT SAFETY INFORMATION
BOXED WARNING: LACTIC ACIDOSIS/SEVERE HEPATOMEGALY WITH STEATOSIS and POST TREATMENT ACUTE EXACERBATION OF HEPATITIS B
•Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs, including tenofovir disoproxil fumarate (tenofovir DF), a component of COMPLERA, in combination with other antiretrovirals.
•COMPLERA is not approved for the treatment of chronic hepatitis B virus (HBV) infection, and the safety and efficacy of COMPLERA have not been established in patients coinfected with HBV and HIV-1. Severe acute exacerbations of hepatitis B have been reported in patients who are coinfected with HBV and HIV-1 and have discontinued emtricitabine or tenofovir DF, which are components of COMPLERA. 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 COMPLERA. If appropriate, initiation of anti-hepatitis B therapy may be warranted.
CONTRAINDICATIONS
•Coadministration: COMPLERA should not be coadministered with drugs that induce CYP3A or increase gastric pH as this may lead to loss of virologic response and possible resistance to COMPLERA or the NNRTI class. Use of the following drugs with COMPLERA is contraindicated: carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifampin, rifapentine, proton pump inhibitors (e.g., esomeprazole, lansoprazole, dexlansoprazole, omeprazole, pantoprazole, rabeprazole), systemic dexamethasone (>1 dose) and St. John's wort.
WARNINGS AND PRECAUTIONS
•Skin and hypersensitivity reactions: Severe skin and hypersensitivity reactions have been reported with the use of rilpivirine-containing regimens, including cases of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS). In clinical trials of rilpivirine &plus; FTC/TDF, most rashes were Grade 1 or 2 and occurred in the first 4-6 weeks of treatment; Grades 2-4 rash occurred in 1&percnt; of subjects. Discontinue COMPLERA immediately for severe skin or hypersensitivity reactions, including but not limited to, severe rash or rash accompanied by fever, blisters, mucosal involvement, conjunctivitis, facial edema, angioedema, hepatitis, or eosinophilia. Monitor clinical status and laboratory parameters, and initiate appropriate therapy.
•New onset or worsening renal impairment: Cases of acute renal failure and Fanconi syndrome have been reported with the use of tenofovir DF. In all patients, assess estimated creatinine clearance (CrCl) prior to initiating and during therapy. In patients at risk for renal dysfunction, additionally monitor serum phosphorus, urine glucose, and urine protein. Do not administer COMPLERA in patients with CrCl <50 mL/min. Avoid concurrent or recent use with a nephrotoxic agent. Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after initiation of high-dose or multiple NSAIDs in patients with risk factors for renal dysfunction; consider alternatives to NSAIDs in these patients. Persistent or worsening bone pain, pain in extremities, fractures and/or muscular pain or weakness may be manifestations of proximal renal tubulopathy and should prompt an eva luation of renal function.
New onset or worsening renal impairment: Cases of acute renal failure and Fanconi syndrome have been reported with the use of tenofovir DF. In all patients, assess estimated creatinine clearance (CrCl) prior to initiating and during therapy.In patients at risk for renal dysfunction, additionally monitor serum phosphorus, urine glucose, and urine protein.Do not administer COMPLERA in patients with CrCl <50 mL/min.Avoid concurrent or recent use with a nephrotoxic agent. Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after initiation of high dose or multiple NSAIDs in patients with risk factors for renal dysfunction; consider alternatives to NSAIDs in these patients.Persistent or worsening bone pain, pain in extremities, fractures and/or muscular pain or weakness may be manifestations of proximal renal tubulopathy and should prompt an eva luation of renal function.
•Drug interactions: Use COMPLERA with caution when given with drugs that may reduce the exposure of rilpivirine or when coadministered with a drug with known risk of Torsades de Pointes. Supratherapeutic doses of rilpivirine have been shown to prolong the QTc interval of the electrocardiogram in healthy subjects.
•Depressive disorders: eva luate patients with severe depressive symptoms to assess if symptoms are due to COMPLERA and if the risks of continued treatment outweigh the benefits. In adult clinical trials (N=686), the incidence of depressive disorders was 9%, Grades 3-4 depressive disorders was 1%, and discontinuation due to depressive disorders was 1%; and suicidal ideation and suicide attempt was reported in 4 and 2 subjects, respectively. In a pediatric (age 12 to <18 years) clinical trial (N=36), the incidence of depressive disorders was 19% and Grades 3-4 depressive disorders was 6%; suicidal ideation and suicide attempt were reported in 1 subject.
•Hepatotoxicity: Hepatic adverse events have been reported, including cases of hepatic toxicity in adults without pre-existing hepatic disease or other identifiable risk factors. Patients with underlying hepatitis B or C, or those with marked elevations in liver-associated tests may be at increased risk. Appropriate laboratory testing and monitoring before and during therapy is recommended in patients with underlying hepatic disease or in patients with marked elevations in liver-associated tests prior to treatment initiation; consider testing and monitoring in patients without pre-existing hepatic dysfunction or other risk factors.
•Bone effects: Decreases in bone mineral density (BMD) and mineralization defects, including osteomalacia, have been seen in adult and pediatric patients treated with tenofovir DF. In clinical trials conducted in pediatric subjects, the total body BMD gain was less in tenofovir DF-treated subjects as compared to the control group. Consider monitoring BMD in adult and pediatric patients with a history of pathologic fracture or risk factors for bone loss.
•Antiviral products: COMPLERA is a complete regimen for the treatment of HIV-1 infection. Do not coadminister with other antiretrovirals including products containing any of the same active components (unless needed for dose adjustment); products containing lamivudine; or with adefovir dipivoxil.
•Fat redistribution and accumulation has been observed in patients receiving ARV therapy.
•Immune reconstitution syndrome, including the occurrence of autoimmune disorders with variable times to onset, has been reported.
ADVERSE REACTIONS
•In adult clinical studies: Most common adverse reactions (incidence ≥2%, Grades 2-4) in adults with no ARV treatment history were depressive disorders (2%), insomnia (2%) and headache (2%). No new adverse reactions to COMPLERA were identified in stable, virologically suppressed patients switching to COMPLERA from a regimen containing a ritonavir-boosted protease inhibitor; however, the frequency of adverse reactions increased by 20% after switching to COMPLERA.
•In a pediatric clinical study: Most common adverse reactions (reported by ≥2 patients, all Grades) in patients 12 to <18 years with no ARV treatment history were headache (19%), depression (19%), somnolence (14%), nausea (11%), dizziness (8%), abdominal pain (8%), vomiting (6%), and rash (6%).
DRUG INTERACTIONS
•CYP3A inducers: Drugs that induce CYP3A may decrease rilpivirine plasma concentrations, which may lead to loss of virologic response and possible resistance to COMPLERA or the NNRTI class.
•CYP3A inhibitors: Drugs that inhibit CYP3A may increase rilpivirine plasma concentrations.
•Drugs increasing gastric pH may significantly decrease rilpivirine plasma concentrations and lead to loss of virologic response and possible resistance to COMPLERA or the NNRTI class.
•Use of proton pump inhibitors with COMPLERA is contraindicated.
•Antacids should be administered ≥2 hours before or ≥4 hours after COMPLERA.
•H2-receptor antagonists should be administered ≥12 hours before or ≥4 hours after COMPLERA.
•Drugs affecting renal function: Coadministration of COMPLERA with drugs that reduce renal function or compete for active tubular secretion may increase concentrations of emtricitabine and tenofovir.
•Prescribing information: Consult the full Prescribing Information for COMPLERA for more information on potentially significant drug interactions, including clinical comments.
PREGNANCY AND BREASTFEEDING
•Pregnancy Category B: There are no adequate and well-controlled studies in pregnant women. Use during pregnancy only if potential benefit justifies the potential risk. An Antiretroviral Pregnancy Registry has been established.
•Breastfeeding: Emtricitabine and tenofovir have been detected in human milk. Because of both the potential for HIV transmission and the potential for serious adverse reactions in nursing infants, mothers should be instructed not to breastfeed.
DOSAGE AND ADMINISTRATION
•Dosage: Patients 12 years and older (≥35 kg): 1 tablet taken orally once daily with food.
•Renal impairment: Do not use in patients requiring dose reduction, including patients with estimated CrCl <50 mL/min.
•Rifabutin coadministration: Additional rilpivirine 25 mg taken once daily with a meal is recommended. 
http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d637cfab-f1e8-4eb3-a1b3-f85ca3bec612