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日前,美国食品药品管理局(FDA)批准了吉利德科学公司每天1次服用的艾滋病治疗药物Complera。
Complera是鲁瓦达(含有核苷类逆转录酶抑制剂恩曲他滨和替诺福韦)和非核甘类逆转录酶抑制剂利匹韦林的复合制剂。鲁瓦达于2004年上市,被称为是“艾滋病鸡尾酒疗法”,利匹韦林是今年5月份获批准上市的。
Complera是治疗以前未接受其他艾滋病药物治疗的成人艾滋病感染一线药物,每天一次用药从而,增加了患者使用的依从性。不过,与其他艾滋病药物一样,Complera同样具有严重的副作用,如乳酸酸中毒和严重肝损害。
Manufacturer:
Gilead Sciences, Inc.
Pharmacological Class:
Nucleoside analogue reverse transcriptase inhibitors + non-nucleoside reverse transcriptase inhibitor.
Active Ingredient(s):
Emtricitabine 200mg, tenofovir disoproxil fumarate 300mg, rilpivirine 25mg; tabs.
Indication(s):
HIV-1 infection.
Pharmacology:
Complera is a fixed-dose combination of antiviral drugs emtricitabine, rilpivirine and tenofovir disoproxil fumarate.
Clinical Trials:
The efficacy of rilpivirine is based on the analyses of 48-week data from two trials (ECHO and THRIVE) in antiretroviral treatment-naïve adults. In ECHO, the background regimen (BR) was tenofovir DF + emtricitabine. In THRIVE, the BR consisted of one of the following: tenofovir DF + emtricitabine or zidovudine + lamivudine or abacavir + lamivudine. Subjects were randomized to receive either rilpivirine 25mg once daily or efavirenz 600mg once daily in addition to a BR. Based on the pooled data from both trials at 48 weeks, the proportion of subjects with <50 HIV-1 RNA copies/mL receiving rilpivirine/tenofovir DF/emtricitabine (N=550) compared to subjects receiving efavirenz/tenofovir DF/emtricitabine (N=546) was 83% and 81%, respectively. The mean CD4+ cell count increase from baseline was 193 cells/mm3 for rilpivirine-treated subjects and 182 cells/mm3 for efavirenz-treated subjects.
Legal Classification:
Rx
Adults:
Take with a meal. 1 tablet once daily. Renal impairment (CrCl<50mL/min): not recommended.
Children:
<18 years: not recommended.
Contraindication(s):
Concomitant carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifampin, rifapentine, esomeprazole, lansoprazole, omeprazole, pantoprazole, rabeprazole, systemic dexamethasone (more than single dose), St. John’s wort.
Warnings/Precautions:
Suspend if lactic acidosis or hepatotoxicity occurs. Women, obesity, prolonged nucleoside exposure, other risk factors for hepatic dysfunction: increased risk of toxicity. Not for treating chronic hepatitis B; test for HBV before starting therapy and monitor patients coinfected with HIV-1 and HBV during and for several months after stopping treatment (discontinuing therapy may exacerbate HBV infection). Renal impairment: monitor CrCl and serum phosphorus. May prolong QTc interval with supratherapeutic doses. History or risk of fractures or osteopenia: monitor bone mineral density (BMD); consider Vitamin D and calcium supplementation. Pregnancy (Cat. B). Nursing mothers: not recommended.
Interaction(s):
Avoid concomitant drugs that contain emtricitabine, tenofovir, rilpivirine, lamivudine, or adefovir dipivoxil. Emtricitabine/tenofovir: Monitor drugs that reduce renal function or compete for renal tubular secretion (eg, adefovir dipivoxil, cidofovir, acyclovir, valacyclovir, ganciclovir, valganciclovir). Avoid concomitant or recent use of nephrotoxic agents. Rilpivirine: Potentiated by CYP3A inhibitors. Antagonized by CYP3A inducers (see Contraindications). May antagonize azole antifungals (monitor for breakthrough fungal infections), methadone (monitor). Separate antacids (by at least 2 hours before or at least 4 hours after) and H2-receptor antagonists (by at least 12 hours before or 4 hours after) rilpivirine; drugs that increase gastric pH may result in decreased plasma concentrations. Caution with drugs with a known risk for torsades de pointes.
Adverse Reaction(s):
Insomnia, headache, GI upset, fatigue, dizziness, depression, abnormal dreams, rash; fat redistribution, immune reconstitution syndrome, lactic acidosis, severe hepatomegaly with steatosis (may be fatal).
How Supplied:
Tabs—30
Last Updated:
9/22/2011
(FDA)宣布Complera获准用于治疗病毒1型(HIV-1)
2011年8月10日，吉利德科学公司和美国食品药品管理局(FDA)宣布Complera(恩曲他滨/利匹韦林/替诺福韦酯)获准用于治疗感染人类免疫缺陷病毒1型(HIV-1)的初治成人。Complera是三种抗逆转录病毒药的复方片剂，分别为吉利德公司生产的Truvada，即固定剂量的核苷类逆转录酶抑制剂恩曲他滨与替诺福韦酯的复方制剂，及蒂泊特克制药公司生产的非核苷类逆转录酶抑制剂(NNRTI)Edurant(利匹韦林)。Complera的用法为每日1次，与餐同服。
FDA批准Complera是基于由2项3期双盲、设有效药物对照的随机研究[TMC278(利匹韦林)与EFV(依法韦仑)治疗初治HIV感染者之疗效比较研究，即ECHO研究；以及TMC278每日1次给药方案与依法韦仑抗HIV疗效比较研究，即THRIVE研究)得出的48周安全性及疗效数据，这两项研究均由蒂泊特克制药公司完成。在ECHO研究中，研究者将TMC278(25 mg)每日1次与EFV(600mg)每日1次联合其选定的基础治疗方案(阿巴卡韦与拉米夫定联用，恩曲他滨与替诺福韦酯联用，或是齐多夫定与拉米夫定联用)进行了比较。除了基础治疗方案外，两项临床试验在设计上完全相同。
据蒂泊特克制药公司2010年7月的新闻发布会，这两项全球性试验均达到了主要目的，即证实在第48周时TMC278治疗组在病毒载量低于检测水平(如，<50拷贝数/ml)的患者百分比方面不劣于EFV(最大允许差异为12%)。
吉利德公司进行的一项生物等效性研究显示，接受单一复方片剂Complera治疗的患者所达到的血药浓度与接受恩曲他滨+利匹韦林+替诺福韦酯治疗的患者相同。
在开始Complera治疗时，应考虑以下几点：
开始治疗时HIV-1 RNA病毒载量>100,000拷贝/ml的利匹韦林治疗组发生病毒学失败的患者比例大于开始治疗时HIV-1 RNA病毒载量<100,000拷贝/ml的受试者。
利匹韦林治疗组患者的病毒学失败导致总治疗无效率，以及对NNRTI类药物的交叉耐药率，均高于依法韦仑治疗组。
利匹韦林治疗组发生拉米夫定/恩曲他滨相关性耐药的患者例数多于依法韦仑治疗组。
在研究中，使用利匹韦林的患者报告最多的不良药物反应是失眠和头痛，与使用恩曲他滨和替诺福韦酯相关的最常见不良药物反应为腹泻、恶心、疲乏、头痛、眩晕、抑郁、失眠、异常梦境以及皮疹。
Complera的处方信息中包含一个有关乳酸酸中毒和重度肝肿大伴脂肪变性风险的黑框警告。这则警告还声明，Complera尚未获准用于治疗慢性乙肝病毒(HBV)感染，Complera的安全性和疗效尚未在HBV和HIV-1共感染患者中得到证实。 |
