EDURANT (rilpivirine hydrochloride) tablet, film coated
[CENTOCOR ORTHO BIOTECH]
5月20日，美国FDA批准了Edurant（rilpivirine，利匹韦林）与其它抗逆转录病毒药物联用治疗HIV - 1感染的成人（初治）患者。
批准日期：2011年5月20日；Company: Tibotec Pharmaceuticals
一般描述
EDURANT(rilpivirine)是人类免疫缺陷病毒类型1(HIV-1)的一种非核苷逆转录酶抑制剂(NNRTI)。可得到白色至淡白色，薄膜包衣，圆形，双凸形，6.4 mm EDURANT片，为口服给药。每片含27.5 mg rilpivirine 盐酸盐，等同于25 mg rilpivirine。
rilpivirine盐酸盐化学名为4-[[4-[[4-[(E)-2-cyanoethenyl]-2,6-dimethylphenyl]amino]2- pyrimidinyl]amino]benzonitrile monohydrochloride。分子式为C22H18N6 • HCl
和分子量是402.88。盐酸Rilpivirine盐酸盐有下列结构式：
Rilpivirine盐酸盐是白色至几乎白粉。Rilpivirine盐酸盐跨越宽广pH范围实际上不溶于水。
每个EDURANT片还含无活性成分交联羧甲基纤维素钠，硬脂酸镁，乳糖一水化物，聚乙烯吡啶酮K30，聚山梨醇20和硅化微晶纤维素。片涂层含羟丙基纤维素2910 6 mPa.s，乳糖一水化物，PEG 3000, 二氧化钛和三醋精。
作用机制
Rilpivirine是一种抗病毒药[见临床药理学].
适应证和用途
EDURANT是一种人类免疫缺陷病毒类型1 (HIV-1)特异性，非核苷逆转录酶抑制剂(NNRTI)适用于：在未治疗过成年患者与其他抗病毒药联用为治疗HIV-1 感染。
用EDURANT初始治疗时应考虑以下几点：
（1）在开始治疗时有HIV-1 RNA大于100,000拷贝/mLEDURANT治疗受试者与在开始治疗时有 HIV-1 RNA低于100,000拷贝/mL受试者比较经历更多病毒学失败。
（2）在EDURANT治疗受试者与依法韦仑比较观察病毒学失败率总体治疗耐药性和对NNRTI类交叉耐药性率较高。
（3）与依法韦仑比较用EDURANT治疗受试者发生拉米夫定[lamivudine]/恩曲他滨[emtricitabine]伴耐药性更多。
剂量和给药方法
25 mg(25mg一片)每天1次随进餐服用.
剂型和规格
25 mg片
禁忌证
EDURANT禁忌与可能发生显著降低rilpivirine血浆浓度药物共同给药，这可能导致丧失病毒学反应和可能耐药性和交叉耐药性。
警告和注意事项
（1）EDURANT与可能减低rilpivirine暴露药物应谨慎开处方给药。
（2）EDURANT与一种已知有尖端扭转型室性心动过速[Torsade de Pointes]风险药物开处方应谨慎。
（3）抑郁疾患：曾报道严重抑郁病(心情抑郁，抑郁，烦躁不安，重症抑郁，情绪改变，消极想法，自杀意向，自杀观念)。对严重抑郁病建议立即医学评价。
（4）患者可能发生体脂肪再分布/积蓄或免疫重建综合征。
不良反应
对EDURANT最常见不良药物反应(发生率>2%)至少中度至严重强度≥2级)是抑郁，失眠，头痛和皮疹。
药物相互作用
（1） EDURANT不应与NNRTIs联用。
（2）EDURANT与诱导或抑制CYP3A4药物共同给药可能影响rilpivirine的血浆浓度。
（3）EDURANT与增加胃pH药物的共同给药可能减低rilpivirine的血浆浓度。
（4）参考不应与EDURANT共同给药其它药物的完整处方资料和对其它药物可能需要改变剂量或给药方案。
特殊人群中使用
（1）妊娠：只有如潜在效益正当地胜于潜在风险才在妊娠期间使用。可得到妊娠注册。
（2）哺乳母亲：由于l对HIV传播潜能母亲不应哺乳喂养。
如何供应/贮存和处置
EDURANT(rilpivirine)片以白至灰白色，膜衣，圆，双凸形6.4mm片供应。每片含27.5mg 盐酸rilpivirine，等同于25mg rilpivirine。每片一侧凹有“TMC”和另侧“25”。
EDURANT片被以下列规格包装在瓶中：25mg片-30片瓶(NDC 59676-278-01).
为了避光保护讲贮藏EDURANT片在原始瓶中。贮存EDURANT片在25°C(77°F)；外出允许至15°-30°C (59°-86°F)[见USP控制室温]。
Manufacturer:
Janssen Therapeutics
Pharmacological Class:
Non-nucleoside reverse transcriptase inhibitor (NNRTI)
Active Ingredient(s):
Rilpivirine 25mg; tablets.
Indication(s):
HIV-1 infection in antiretroviral treatment-naïve adult patients, in combination with other antiretroviral agents.
Pharmacology:
Rilpivirine is a diarylpyrimidine NNRTI of HIV-1 and inhibits HIV-1 replication by non-competitive inhibition of HIV-1 reverse transcriptase.
Clinical Trials:
The efficacy of rilpivirine is based on the analyses of 48-week data from two Phase 3 trials TMC278-C209 and TMC278-C215 and from a 96-week (with extension to 192 weeks) Phase 2b trial in antiretroviral treatment-naïve adults.
Antiretroviral treatment-naïve HIV-1 infected subjects enrolled in the Phase 3 trials had a plasma HIV-1 RNA ≥5000 copies/mL and were screened for susceptibility to N(t)RTI and for absence of specific NNRTI RAMs. In TMC278-C209, the background regimen (BR) was tenofovir disoproxil fumarate + emtricitabine. In TMC278-C215, the BR consisted of one of the following: tenofovir disoproxil fumarate + emtricitabine or zidovudine + lamivudine or abacavir + lamivudine. Based on the pooled data from both trials at 48 weeks, the proportion of subjects with <50 HIV-1 RNA copies/mL receiving rilpivirine 25 mg (N=686) compared to subjects receiving efavirenz (N=682) was 83% and 80%, respectively. The mean CD4+ cell count increase from baseline was 192 cells/mm3 for rilpivirine-treated subjects and 176 cells/mm3 for efavirenz-treated subjects.
Study TMC278-C204 enrolled 368 HIV-1-infected treatment-naïve adult subjects who had a plasma HIV-1 RNA ≥5000 copies/mL, previously received ≤2 weeks of treatment with an N(t)RTI or protease inhibitor, had no prior use of NNRTIs, and were screened for susceptibility to N(t)RTI and for absence of specific NNRTI RAMs. At 96 weeks, the proportion of subjects with <50 HIV-1 RNA copies/mL receiving rilpivirine 25 mg (N=93) compared to subjects receiving efavirenz (N=89) was 76% and 71%, respectively. The mean increase from baseline in CD4+ counts was 146 x 106 cells/mm3 in subjects receiving rilpivirine 25mg and 160 x 106 cells/mm3 in subjects receiving efavirenz. At 192 weeks, 63% of subjects who originally received 25mg once daily achieved HIV RNA <50 copies/mL compared to 61% of subjects in the control group.
Legal Classification:
Rx
Adults:
Take with a meal. 25mg once daily.
Children:
Not recommended.
Contraindication(s):
Concomitant carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifampin, rifapentine, esomeprazole, lansoprazole, omeprazole, pantoprazole, rabeprazole, dexamethasone (more than single dose), St. John’s wort.
Warnings/Precautions:
May prolong QTc interval with supratherapeutic doses. Severe renal or hepatic impairment. Pregnancy (Cat. B). Nursing mothers: not recommended.
Interaction(s):
Concomitant NNRTIs: not recommended. 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):
Depression, insomnia, headache, rash; fat redistribution, immune reconstitution syndrome.
How Supplied:
Tabs—30
2011年5月FDA批准HIV治疗新药利匹韦林 (rilpivirine)
2011年5月20日美国食品和药品监督管理局批准Edurant (rilpivirine)与其它抗病毒药联用为治疗未治疗过成年的HIV治疗成年的HIV-1 感染。
Edurant属于一类被称为非核苷逆转录酶抑制剂(NNRTI)HIV药物。通过阻断HIV病毒复制起作用。Edurant是用作高活性抗逆转录病毒治疗(HAART)方案的一部分，被设计成抑制血内HIV量(病毒负荷)。Edurant是每天1次与食物服用的药丸。
FDA药物评价和研究中心抗微生物产品室主任Edward Cox, M.D., M.P.H说“患者可能对各种HIV药不同地反应或经受不同副作用。FDA批准为开始HIV治疗患者提供另一种治疗选择”。
Edurant的安全性和有效性是根据来自两项3期临床试验有1,368例有HIV感染成年受试者48-周资料，和来自96-周(与延伸至192周)试验。.患者未曾接受既往HIV治疗和被选择接受用Edurant治疗或依法韦仑[efavirenz](被FDA-批准为HIV感染治疗另一个NNRTI)。两种药物都与其它抗病毒药联用。
Edurant与依法韦仑一样有效减低病毒负荷。在48周治疗后Edurant和依法韦仑组分别83%和80%受试者血液中有不可检测量HIV。在开始治疗时有较高病毒负荷的接受Edurant患者比开始治疗时较低病毒负荷患者更可能对药物不反应。此外，用 Edurant治疗失败人们比依法韦仑失败患者发生更多耐药性。
最常报道副作用in服用Edurant患者中包括抑郁，失眠，头痛和皮疹。与服用依法韦仑比较较少患者由于副作用停止服药。
Edurant不治愈HIV 感染。患者必须保持不断HIV治疗以控制HIV 感染和减低HIV-相关疾病。