抗艾滋病新型复方制剂Evotaz(ATAZANAVIR SULFATE; COBICISTAT)获FDA批准上市
2015年5月6日，艾滋病复方新药Evotaz获FDA批准上市， Evotaz 是atazanavir、cobicistat和其它抗病毒药的固定剂量复方制剂，用于治疗成人艾滋病。
Evotaz为片剂，用法是每日一次，由300mg的atazanavir(一种蛋白酶抑制剂，以商品名Reyataz 单独销售)、150mg的 cobicistat(据称是一种“增强药代动力学”的药物，目前由吉利德以商品名Tybost销售)组成。
Evotaz获批对HIV感染者而言是一个好消息。据悉每年约有50000人感染HIV而导致获得性免疫缺陷综合征(AIDS)。目前美国的HIV感染者约为110万人，而大多数患者对治疗有耐药性，因此需要新的治疗方法来抑制病毒。
FDA批准Evotaz是基于称为114号研究的3期临床试验的阳性结果。该双盲试验比较了300mg Reyataz+150mg cobicistat (即Evotaz)和300mg Reyataz+100mg ritonavir 的效果。48周治疗后，服用Evotaz的病人中85%的HIV-1 RNA水平低于50个拷贝/ml，与对照组Reyataz/ritonavir的87%消退率相比是不分伯仲。此外，Evotaz作为蛋白酶抑制剂单独使用时抗病毒的失效率低于6%，与cobicistat联用后，失效率就降到最低。
最重要的是，临床试验结果表明48周后病人的耐药性为零，单独用tenofovir无耐药性，而当用Evotaz 后病人表现出对 emtricitabine有耐药性。但是总体而言，3期临床结果表明了 Evotaz的有效性和安全性。
百时美施贵宝的全球市场总管Murdo Gordon表示， 百时美很高兴能为全球AIDS患者提供新的治疗方法，atazanavir与cobicistat 联用能维持48周以上安全、有效的治疗。
Pharmacological Class:
HIV-1 protease inhibitor + CYP3A inhibitor.
Active Ingredient(s):
Atazanavir 300mg, cobicistat 150mg; tablets.
Company
Bristol-Myers Squibb
Indication(s):
HIV-1 infection in combination with other antiretroviral agents. Limitations of use: guide use in treatment-experienced patients by number of baseline primary protease inhibitor resistance substitutions.
Pharmacology:
Atazanavir selectively inhibits the virus-specific processing of viral polyproteins in HIV-1 infected cells, preventing formation of mature virions. Cobicistat increases the systemic exposure of the CYP3A substrate atazanavir.
Clinical Trials:
The safety and efficacy of atazanavir coadministered with cobicistat were eva luated in a randomized, double-blind, active-controlled trial (Study 114) in HIV-1 infected treatment-naive patients (N = 692). Patients were randomized to either atazanavir 300mg with cobicistat 150mg or atazanavir 300mg with ritonavir 100mg; all received concomitant tenofovir DF 300mg and emtricitabine 200mg once daily. The mean increase from baseline in CD4+ cell count at Week 48 was 213 cells/mm3 in patients receiving atazanavir with cobicistat vs. 219 cells/mm3 in patients receiving atazanavir with ritonavir. HIV-1 RNA <50 copies/mL was seen in 85% of the atazanavir with cobicistat group vs. 87% of the atazanavir with ritonavir group (difference − 2.2%; 95% CI: −7.4%, 3.0%).
Legal Classification:
Rx
Adults:
Take with food. 1 tablet daily.
Children:
<18 years: not established.
Contraindication(s):
Concomitant alfuzosin, ranolazine, dronedarone, colchicine (in renal/hepatic impaired), rifampin, irinotecan, lurasidone, triazolam, oral midazolam, ergots, cisapride, St. John's wort, lovastatin, simvastatin, pimozide, nevirapine, sildenafil (for PAH), indinavir.
Warnings/Precautions:
Assess CrCl prior to initiation. When concomitant tenofovir DF: assess baseline CrCl, urine glucose, and urine protein; if CrCl <70mL/min: not recommended; monitor serum phosphorous if risk of renal impairment. ESRD with hemodialysis in treatment-experienced or hepatic impairment: not recommended. Cardiac conduction abnormalities; consider ECG monitoring if preexisting marked 1st -degree AV block or 2nd/3rd -degree AV block. Consider interruption or discontinuation if nephrolithiasis or cholelithiasis occurs. Hepatitis B and/or C or marked elevations in transaminases: monitor LFTs before and during therapy. Consider alternative if jaundice or scleral icterus occurs. Diabetes. Hyperbilirubinemia. Fat redistribution. Immune reconstitution syndrome. Hemophilia. Elderly. Pregnancy (Category B). Nursing mothers: not recommended.
Interaction(s)
See Contraindications. Separate dosing with concomitant H2 receptor antagonists, PPIs (not recommended in treatment-experienced), antacids, enteric-coated didanosine. Concomitant tenofovir DF with concomitant or recent nephrotoxic agents, other antiretrovirals that require CYP3A inhibition (eg, HIV protease inhibitors, elvitegravir), atazanavir- or cobicistat-containing products, ritonavir, CYP2C8 substrates with narrow therapeutic indices (eg, paclitaxel, repaglinide), efavirenz, etravirine, apixaban, rivaroxaban, dabigatran etexilate, avanafil, inhaled/nasal steroids, salmeterol, voriconazole: not recommended. May need to adjust dose of insulin, antidiabetics, dasatinib, nilotinib, sildenafil, tadalafil, vardenafil, perphenazine, risperidone, thioridazine, buprenorphine, naloxone, methadone, tramadol, bosentan, rifabutin, and sedatives/hypnotics. Concomitant maraviroc: give maraviroc 150mg twice daily. Monitor concomitant antiarrhythmics, digoxin, vincristine, vinblastine, warfarin, clonazepam, carbamazepine, lamotrigine, SSRIs, TCAs, trazodone, fentanyl, immunosuppressants, other statins, β-blockers, CCBs. Concomitant macrolide or ketolide antibiotics, CYP3A-inducing anticonvulsants, systemic corticosteroids: consider alternatives.
Adverse Reaction(s)
Jaundice, ocular icterus, nausea; rash (may be severe).
How Supplied:
Tabs—30
