近日，美国食品和药物管理局（FDA）正式批准Truvada作为第一款能够对HIV感染高危（即与HIV感染者或者未知HIV感染状态的性伴侣发生无保护措施的性行为）个体起到减少感染几率的日常口服用药。来自旧金山地区的生物制药科技公司Gilead Sciences的新药Truvada是在经过两次临床试验后获得上市批准的。 Truvada可以起到阻止HIV在人体细胞内繁殖的作用。在对近2500名具有高危性行为的男性测试者研究后。医生发现，在测试者定期服用药物的情况下，药物对感染率的下降起到显著作用。测试结果显示Truvada有效地使HIV感染风险下降了42%。在另一项对近4800对一方感染另一方未感染的异性恋伴侣的试验中，Truvada减少感染风险高达75%。 “TRUVADA“特鲁瓦达”为日服一次的丸状药物，由位于美国加利福尼亚州的吉利德科技公司生产，适用人群为同性恋、双性恋和性伴侣为艾滋病病毒携带者的高危人群。 美国药管局要求“特鲁瓦达”服用者同时注意性行为安全如使用避孕套等，以期有效降低感染风险。他们每隔3个月还要接受一次艾滋病病毒检测，以保证一旦感染尽快接受治疗。 美国药管局局长马格丽特・汉伯格说，批准“特鲁瓦达”上市是抗击艾滋病的重要里程碑，美国每年新增约5万名艾滋病病毒感染者，新的预防和治疗方案对于美国抵御艾滋病非常重要。 TRUVADA（恩曲他滨/富马酸替诺福韦酯 emtricitabine/tenofovir disoproxil fumarate）片剂，口服使用 最初美国批准：2004年 警告： 乳酸性酸中毒/脂肪变性，乙型肝炎治疗后急性发作严重肝肿大及耐药性与IN的PrEP完整黑框警告确诊的HIV-1 INFECTIONSee完整的处方信息TRUVADA的使用风险。 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，已经报告了使用核苷类似物，包括VIREAD，TRUVADA的一个组成部分。 TRUVADA没有被批准用于治疗慢性乙型肝炎病毒（HBV）感染的治疗。乙肝严重的急性加重已报告患者的HIV-1和HBV谁已经停产TRUVADA合并感染。因此，肝功能应密切在谁停止TRUVADA HBV感染者进行监测。如果适当的话，抗乙肝治疗开始可能有必要。 用于PrEP的指示TRUVADA必须只规定个人确认为HIV阴性初次使用前，并定期在使用过程中。耐药的HIV-1的变种已确定与使用TRUVADA为以下未被发现急性HIV-1感染PrEP的指示。请不要对PrEP的指示启动TRUVADA如果除非负感染状态的确认标志或急性HIV感染症状都存在。 目前的主要变化 * 黑框警告  07/2012 适应证和用途 * 暴露前预防  07/2012 用法与用量  07/2012 禁忌  07/2012 警告和注意事项 * 新发或加重肾功能不全  07/2012 * 降低骨密度  07/2012 * 免疫重建综合征  07/2012 * 综合管理，以减少感染HIV-1的风险 07/2012 作用机理 TRUVADA是抗病毒药物恩曲他滨和富马酸替诺福韦酯的固定剂量组合[见微生物] 适应症和用法 TRUVADA是恩曲他滨和VIREAD，既核苷类似物的HIV-1逆转录酶抑制剂的组合。 TRUVADA是与用于成人和儿童患者12岁及以上的治疗HIV-1感染的其它抗逆转录病毒药物组合表示。 TRUVADA将结合表示与安全性行为的暴露前预防（PrEP的），以减少高风险性收购HIV-1在成人的风险。 用法用量 HIV-1感染的治疗 推荐剂量在成人和儿童患者（12岁及以上，体重大于或等于35公斤）：每日一次或与食物内服。 推荐剂量肾功能受损的HIV-1感染成年患者：肌酐清除率30-49毫升/分钟：1片，每48小时。 肌酐清除率低于30毫升/分或血液透析：不要使用TRUVADA。 提前预防 推荐剂量HIV-1感染的成年人：每日一次或与食物内服。 在肾功能受损的HIV感染个人推荐剂量：肌酐清除率如果低于60毫升/分钟不要在HIV感染的个体使用TRUVADA。如果肌酐清除率下降未感染的个人观察，同时使用TRUVADA的准备，评估潜在的原因，并重新评估潜在风险和继续​​使用的好处。 剂型和规格 片剂：200毫克的恩曲他滨和300毫克的富马酸替诺福韦酯。 禁忌症 不要使用TRUVADA用于暴露前预防与未知的或正HIV-1身份的人。TRUVADA应艾滋病毒感染者只有在与其他抗逆转录病毒药物联合使用。 警告和注意事项 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TRUVADA开始治疗前评估肌酐清除率（肌酐清除率）。监控肌酐清除率和血清磷病人慎用。避免并发或近期使用肾毒性药物服用Truvada的。 合用其他产品：不要使用含有恩曲他滨和富马酸替诺福韦酯包括药物ATRIPLA，COMPLERA，恩曲他滨，VIREAD;或用含有拉米夫定药物。不要与阿德福韦酯联合管理。 降低骨密度（BMD）：考虑患者骨密度的评估，病理性骨折或骨质疏松或骨质流失其他危险因素的历史。 体内脂肪重新分配/积累：在接受抗逆转录病毒治疗的患者中观察到。 免疫重建综合征：可能需要进一步的评估和治疗。 三重核苷只有服法：早期病毒学失败已经艾滋病毒感染者的报道。仔细监测和考虑治疗的修改。 综合治理，降低患病的风险HIV-1：使用作为综合预防策略包括其他防范措施的一部分;严格遵守给药方案。 管理，以减少感染HIV-1耐药的风险： 之前发起TRUVADA为PrEP的 - 如果急性病毒感染一致的临床症状是本和最近（<1月）曝光被怀疑，延迟开始的PrEP至少一个月，再次确认负HIV-1的状态，或使用由核准的测试FDA在HIV-1感染，包括急性或原发性HIV-1感染的辅助诊断。 同时使用TRUVADA为PrEP的-HIV-1的筛选试验应重复至少每3个月。 不良反应 在HIV1感染患者中，最常见的不良反应（发生率大于或等于10％）是腹泻，恶心，疲劳，头痛，眩晕，抑郁，失眠，异常的梦想，和皮疹。 在HIV-1感染个人PrEP试验，通过TRUVADA科目超过2％，比更频繁地服用安慰剂受试者被报道的不良反应为头痛，腹痛，体重下降。 药物相互作用 去羟肌苷：富马酸替诺福韦酯增加去羟肌苷的浓度。请小心使用和合用时，监测去羟肌苷的毒性（例如，胰腺炎，神经病变）的证据。考虑剂量减少或去羟肌苷停药如有必要。 阿扎那韦：合用降低阿扎那韦的浓度，增加替诺福韦的浓度。使用仅与利托那韦TRUVADA阿扎那韦;监视诺福韦毒性的证据。 洛匹那韦/利托那韦：合用会增加替诺福韦的浓度。监视诺福韦毒性的证据。 特殊人群中使用 哺乳期妇女：妇女感染HIV-1应不指示母乳喂养。 更新日期：2013年9月 制造商：GILEAD吉利德公司 详细资料：https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=044d9708-99f3-4a61-b314-dee76ae2e37f Truvada(emtricitabine/tenofovir disoproxil fumarate) BOXED WARNING Lactic acidosis and severe hepatomegaly w/ steatosis, including fatal cases, reported w/ the use of nucleoside analogues in combination w/ other antiretrovirals. Not approved for treatment of chronic hepatitis B virus (HBV) infection. Severe acute exacerbations of hepatitis B reported in patients coinfected w/ HBV and HIV-1 and who have discontinued therapy; closely monitor hepatic function w/ both clinical and lab follow-up for at least several months. If appropriate, initiation of anti-hepatitis B therapy may be warranted. Drug-resistant HIV-1 variants have been identified w/ use for preexposure prophylaxis (PrEP) indication following undetected acute HIV-1 infection. PrEP use must only be prescribed to individuals confirmed to be HIV-negative immediately prior to initiating and periodically (at least every 3 months) during use; do not initiate if signs/symptoms of acute HIV-1 infection are present unless negative infection status is confirmed. THERAPEUTIC CLASS Nucleoside reverse transcriptase inhibitor (NRTI) combination DEA CLASS RX ADULT DOSAGE & INDICATIONS HIV-1 Infection Combination w/ Other Antiretrovirals: 1 tab (200mg/300mg) qd HIV-1 Pre-Exposure Prophylaxis Combination w/ Safer Sex Practices for High-Risk Patients: 1 tab (200mg/300mg) qd PEDIATRIC DOSAGE & INDICATIONS HIV-1 Infection Combination w/ Other Antiretrovirals: 17 to <22kg: 1 tab (100mg/150mg) qd 22 to <28kg: 1 tab (133mg/200mg) qd 28 to <35kg: 1 tab (167mg/250mg) qd ≥35kg: 1 tab (200mg/300mg) qd Monitor weight periodically and adjust dose accordingly DOSING CONSIDERATIONS Renal Impairment HIV-1 Infection: CrCl 30-49mL/min: 1 tab q48h CrCl <30mL/min (Including Hemodialysis): Not recommended for use HIV-1 PrEP: CrCl <60mL/min: Not recommended for use ADMINISTRATION Oral route Take w/ or w/o food. Swallow tab whole. HOW SUPPLIED Tab: (Emtricitabine/Tenofovir Disoproxil Fumarate [TDF]) 100mg/150mg, 133mg/200mg, 167mg/250mg, 200mg/300mg CONTRAINDICATIONS Individuals w/ unknown or positive HIV-1 status when used for PrEP. Use in HIV-infected patients w/o other concomitant antiretroviral agents. WARNINGS/PRECAUTIONS Obesity and prolonged nucleoside exposure may be risk factors for lactic acidosis and severe hepatomegaly w/ steatosis. Caution w/ known risk factors for liver disease. D/C if findings suggestive of lactic acidosis or pronounced hepatotoxicity develop. Test for the presence of chronic HBV before initiating therapy; offer vaccination to HBV-uninfected individuals. Redistribution/accumulation of body fat and immune reconstitution syndrome reported. Autoimmune disorders (eg, Graves' disease, polymyositis, Guillain-Barre syndrome) reported in the setting of immune reconstitution and can occur many months after initiation of treatment. Early virological failure and high rates of resistance substitutions reported w/ certain regimens that only contain 3 nucleoside reverse transcriptase inhibitors; consider treatment modification in these patients. Use for PrEP only as part of a comprehensive prevention strategy that includes other prevention measures (eg, safer sex practices). Delay starting PrEP therapy for at least 1 month and reconfirm HIV-1 status or use an FDA-approved test to diagnose acute or primary HIV-1 infection if symptoms of acute viral infection are present and recent (<1 month) exposures are suspected. D/C PrEP therapy if symptoms of acute HIV-1 infection develop following potential exposure event until negative status is confirmed using an FDA-approved test. Caution in elderly. TDF: Renal impairment (eg, acute renal failure, Fanconi syndrome) reported; caution in patients at risk of renal dysfunction, including patients who have previously experienced renal events while receiving adefovir dipivoxil. Promptly evaluate renal function in at-risk patients w/ persistent/worsening bone pain, pain in extremities, fractures, and/or muscular pain/weakness. Decreased bone mineral density (BMD) and increased biochemical markers of bone metabolism reported. Osteomalacia associated w/ proximal renal tubulopathy reported; consider hypophosphatemia and osteomalacia secondary to proximal renal tubulopathy in patients at risk of renal dysfunction who present w/ persistent or worsening bone/muscle symptoms. ADVERSE REACTIONS HIV-1 Infected Patients: Diarrhea, nausea, fatigue, headache, dizziness, depression, insomnia, abnormal dreams, rash. HIV-1 Uninfected Patients: Headache, abdominal pain, decreased weight. DRUG INTERACTIONS Avoid w/ concurrent or recent use of nephrotoxic agents (eg, high-dose or multiple NSAIDs). Do not coadminister w/ emtricitabine-, TDF-, or tenofovir alafenamide-containing products, drugs containing lamivudine, or w/ adefovir dipivoxil. Coadministration w/ drugs eliminated by active tubular secretion (eg, acyclovir, cidofovir, ganciclovir, valacyclovir, aminoglycosides [eg, gentamicin], high-dose or multiple NSAIDs) may increase levels of emtricitabine, TDF, and/or the coadministered drug. Drugs that decrease renal function may increase levels of emtricitabine and/or TDF. Refer to PI for dosing modifications when used w/ concomitant therapies. TDF: May increase levels of didanosine; d/c didanosine if didanosine-associated adverse effects develop. Decreases atazanavir levels; do not coadminister w/ atazanavir w/o ritonavir (RTV). Lopinavir/RTV, atazanavir w/ RTV, and darunavir w/ RTV may increase TDF levels; d/c treatment if TDF-associated adverse reactions develop. P-gp and breast cancer resistance protein transporter inhibitors may increase absorption. Ledipasvir/sofosbuvir may increase exposure; monitor for adverse reactions in patients receiving concomitant therapy w/ ledipasvir/sofosbuvir w/o an HIV-1 protease inhibitor/RTV or an HIV-1 protease inhibitor/cobicistat combination. Consider an alternative hepatitis C virus or antiretroviral therapy in patients receiving concomitant therapy w/ ledipasvir/sofosbuvir and an HIV-1 protease inhibitor/RTV or an HIV-1 protease inhibitor/cobicistat combination. If coadministration is necessary, monitor for adverse reactions associated w/ TDF. Refer to PI for dosing modifications when used w/ concomitant therapies. PREGNANCY AND LACTATION Pregnancy: Category B. Physicians are encouraged to register pregnant patients in the Antiretroviral Pregnancy Registry. Lactation: Excreted in human milk; not for use in nursing. MECHANISM OF ACTION Emtricitabine: Nucleoside analogue of cytidine; inhibits activity of HIV-1 reverse transcriptase (RT) by competing w/ natural substrate deoxycytidine 5'-triphosphate and by being incorporated into nascent viral DNA, which results in chain termination. TDF: Acyclic nucleoside phosphonate diester analogue of adenosine monophosphate; inhibits activity of HIV-1 RT by competing w/ the natural substrate deoxyadenosine 5'-triphosphate and, after incorporation into DNA, by DNA chain termination. PHARMACOKINETICS Absorption: Emtricitabine: Rapid. (Fasted) Bioavailability (92%) (median); Cmax=1.8mcg/mL; Tmax=1-2 hrs; AUC=10mcg•hr/mL. TDF: (Fasted) Bioavailability (25%) (median); Cmax=0.3mcg/mL; Tmax=1 hr; AUC=2.29mcg•hr/mL. Distribution: Found in breast milk. Emtricitabine: Plasma protein binding (<4%). TDF: Plasma protein binding (<0.7%). Metabolism: Emtricitabine: 3'-sulfoxide diastereomers and their glucuronic acid conjugate (metabolites). Elimination: Emtricitabine: Urine (86%; 13% metabolites); T1/2=10 hrs (median). TDF: Urine (70-80%, unchanged) (IV); T1/2=17 hrs (median). ASSESSMENT Assess for risk factors for lactic acidosis or liver disease, renal dysfunction, HBV infection, pregnancy/nursing status, and possible drug interactions. Confirm a negative HIV-1 test immediately prior to initiating PrEP therapy. In patients at risk of renal dysfunction, assess CrCl, serum phosphorus (P), urine glucose, and urine protein. Assess BMD in patients w/ history of pathologic bone fracture or other risk factors for osteoporosis or bone loss. MONITORING Monitor for signs/symptoms of lactic acidosis, hepatomegaly w/ steatosis, hepatotoxicity, new onset or worsening renal impairment, bone effects, redistribution/accumulation of body fat, immune reconstitution syndrome, autoimmune disorders, and other adverse reactions. Closely monitor hepatic function w/ both clinical and laboratory follow-up for at least several months in patients coinfected w/ HBV and HIV-1 and who have discontinued therapy. Screen for HIV-1 infection at least once every 3 months when using for PrEP. In patients at risk of renal dysfunction or w/ mild renal impairment, monitor CrCl, serum P, urine glucose, and urine protein periodically. PATIENT COUNSELING Inform about the risks/benefits of therapy. Inform that medication is not a cure for HIV-1 and patients may continue to experience illness associated w/ HIV-1 infection (eg, opportunistic infections). Advise about the importance of adhering to recommended dosing schedule. Inform about safe sex practices. Instruct not to breastfeed, share needles or personal items that can have blood or body fluids on them, or d/c w/o informing physician. For PrEP, inform patients/partners about the importance of knowing their HIV-1 status, obtaining HIV-1 test at least every 3 months, getting tested for other sexually transmitted infections, and immediate reporting to physician if any symptoms of acute HIV-1 infection develop. Monitor weight periodically in pediatric patients. STORAGE 25°C (77°F); excursions permitted to 15-30°C (59-86°F).