美国食品药物管理局(US Food and Drug Administration)27日表示，一种治疗爱滋病毒(HIV)的新药丸已经获得准许，让成年的爱滋病毒感染者使用。名为Stribild的新药丸结合了先前已经批准的2项药物和2项新药物，每天使用一次。
新浪报道，美国食品药物管理局药物评估及研究中心(Center for Drug eva luation and Research)抗菌产品办公室(Office of Antimicrobial Products)主任寇克斯(Edward Cox)说，经过持续的研发，对爱滋病毒感染的治疗已经向前推进，从使用多种药丸到只使用一种药丸即可，简化治疗方法。
加州的吉利德生物技术公司(Gilead Sciences)就Stribild，对超过1,400名病人进行2次双盲临床试验(double-blind clinical trials)。
结果显示，Stribild的成效良好，历经48周实验，约有90%病人的病毒指数下降到侦测不到的水准。Stribild是以不曾接受爱滋病毒治疗的成年感染者为实验对象，美国食品暨药物管理局表示，这种新药丸还需要进行进一步研究，以确定它对妇女和儿童的安全性，以及它是否会和其他药物产生交互作用。
Gilead Sciences公司与美国食品药品管理局(FDA)联合宣布，Stribild(埃替拉韦150 mg/cobicistat 150 mg/恩曲他滨200 mg/富马酸替诺福韦酯300 mg)每日1次的单一片剂方案已获准用于从未接受过治疗的成年人类免疫缺陷病毒-1(HIV-1)感染患者。Stribild包含以前批准的2种HIV治疗药物和2种新药——埃替拉韦和cobicistat。埃替拉韦是一种HIV整合酶链转移抑制剂，cobicistat是一种药代动力学增强剂，可抑制代谢某些HIV药物的酶，以延长埃替拉韦的疗效。恩曲他滨和延胡索酸泰诺福韦酯的复合制剂已于2004年通过核准，商品名为Truvada，可阻断HIV复制所需的另一种酶。
Stribild通过核准是基于2项3期关键研究的48周数据的支持，在这些研究中，单一片剂方案相对于Atripla(依非韦伦600 mg/恩曲他滨200 mg/富马酸替诺福韦酯300 mg)和一种包含利托那韦强化的阿扎那韦加Truvada(恩曲他滨/富马酸替诺福韦酯)治疗方案达到了非劣效性标准。这些研究旨在评估治疗48周后血液中检测不出HIV水平的患者百分率。结果显示，Stribild、Atripla和Truvada+阿扎那韦+利托那韦治疗者中，血液中检测不出HIV水平的患者分别占88%~ 90%、84%和87%。
在所有关于Stribild的研究中，多数不良事件为轻至中度。临床试验中观察到的常见不良反应包括恶心和腹泻。严重不良反应包括新发肾功能受损或肾功能受损加重、骨密度降低、脂肪再分配和免疫重建综合征。Stribild产品说明书中包含关于乳酸酸中毒/严重肝肿大伴脂肪变性以及治疗后乙型肝炎急性加重的黑框警告。

Pharmacological Class:
Integrase strand transfer inhibitor + pharmacokinetic enhancer + nucleos(t)ide analog HIV-1 reverse transcriptase inhibitors.

Active Ingredient(s):
Elvitegravir 150mg, cobicistat 150mg, emtricitabine 200mg, tenofovir disoproxil fumarate (DF) 300mg; tablets.

Company
Gilead Sciences, Inc.

Indication(s):

Treatment of HIV-1 infection in adults who are antiretroviral treatment-naïve.

Pharmacology:

Stribild is a fixed-dose combination tablet containing elvitegravir, cobicistat, emtricit­abine, and tenofovir DF. Elvitegravir is a HIV-1 integrase strand transfer inhibitor. Cobicistat is a mechanism-based inhibitor of CYP450 enzymes of the CYP3A family. Tenofovir DF, an acyclic nucleoside phosphonate diester analog of adeno­sine monophosphate, is converted in vivo to ­tenofovir. Emtricitabine is a synthetic nucleoside analog of cytidine.

Clinical Trials:

The approval of Stribild is supported by 48-week data from two Phase 3 studies in which the single tablet regimen met its primary objective of non-inferiority compared to Atripla (efavirenz 600mg/emtricitabine 200mg/tenofovir disoproxil fumarate 300mg) (Study 102) and to a regimen containing ritonavir-boosted atazanavir plus Truvada (emtricitabine 200mg/tenofovir disoproxil fumarate 300mg) (Study 103).

Legal Classification:

Rx

Adults:

1 tablet once daily with food. Renal impairment (CrCl <70mL/min): do not initiate; if CrCl declines to <50mL/min during therapy discontinue. Severe hepatic impairment: not recommended.

Children:

<18 years: not established.

Contraindication(s):

Concomitant alfuzosin, rifampin, ergots, cisapride, St. John’s wort, lova­statin, simvastatin, pimozide, sildenafil (when dosed for PAH), triazolam, oral midazolam.

Warnings/Precautions:

Suspend therapy if lactic acidosis or hepatotoxicity (eg, hepatomegaly, steatosis) occurs. Not for treating chronic hepatitis B; test for HBV before starting therapy and closely monitor patients co-infected with HBV and HIV during and for several months after stopping treatment (discontinuing therapy may exacerbate HBV infection). Monitor creatinine clearance, urine glucose, urine protein, serum phosphorus (for patients at risk for renal impairment). History of pathologic fracture or risk factors of osteoporosis or bone loss: consider monitoring bone mineral density (BMD). Pregnancy (Cat. B). Nursing mothers: not recommended.

Interaction(s)

See Contraindications. Avoid with concurrent or recent use of nephrotoxic agents. Do not administer with other antiretroviral agents. May be potentiated by CYP3A inhibitors, antagonized by CYP3A inducers. May potentiate drugs metabolized by CYP3A or CYP2D6, or are substrates of P-gp, BCRP, OATP1B1 or OATP1B3. May antagonize CYP2C9 substrates. Separate antacids by at least 2 hours. May potentiate antiarrhythmics, digoxin, clarithromycin (reduce dose by 50% if CrCl 50–60mL/min), telithromycin, carbamaze­pine, clonazepam, ethosuximide, SSRIs, TCAs, trazodone, ketoconazole (max 200mg/day), itraconazole (max 200mg/day), voriconazole, beta-blockers, calcium channel blockers, fluticasone (use alternative corticosteroid), atorvastatin, immunosuppressants, (monitor), neuroleptics, sedatives/hypnotics, PDE5 inhibitors (see literature for dose adjustments). Antagonized by carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifapentine, systemic dexamethasone. Con­com­itant colchicine (see literature); do not coadminister to patients with renal or hepatic impairment. Dis­continue use of bosentan at least 36 hours prior to initiation of Stribild; after at least 10 days following initiation, resume bosentan. Concomitant salmet­erol: not recommended; increased risk of cardiovascular events. Use alternative non-hormonal methods of contraception. Monitor INR.

Adverse Reaction(s)

Nausea, diarrhea; decreased BMD, fat redistribution, immune reconstitution syndrome.

How Supplied:

Tabs—30

LAST UPDATED:

12/1/2012