Tybost(Cobicistat)作为HIV药增效剂，与阿扎那韦或达芦那韦联合用于治疗HIV-1感染获FDA批准用于治疗HIV-1感染
FDA已批准吉利德公司的Tybost(cobicistat)，一种CYP3A抑制剂，通过与阿扎那韦或达芦那韦联合用药治疗1型人类免疫缺陷病毒(HIV-1)感染。
cobicistat是一种药代动力学增强剂，通过抑制代谢阿扎那韦和达芦那韦的关键酶(CYP3A)来增加药物的全身暴露量，并延长其作用时间。cobicistat也是抗HIV复方药物Stribild的成分之一，Stribild于2012年8月获FDA批准。
Tybost是剂量为150mg的片剂，通过每日一次，与蛋白酶抑制剂阿扎那韦(Reyataz)或达芦那韦(Prezista)联合用药来治疗HIV-1感染。由于Tybost抑制CYP3A，这可能会导致由CYP3A代谢的其他药物的血浆浓度升高，并引发其潜在的、可能危及生命甚至致命的严重副作用。因此，相比于其他药物，Tybost更需要专业医护人员对其进行额外关注，以确保检查并监测药物血药浓度，尤其是启用新药物或改变剂量的时候。
Tybost的批准基于以下临床试验：
支持使用阿扎那韦和Tybost联合用药的数据来源于在初治成人患者中进行的II期和III期试验，该试验比较阿扎那韦/cobicistat 300/150mg和阿扎那韦/利托那韦300/100mg分别与Truvada组合，每日一次用药的疗效。结果表明，基于阿扎那韦/cobicistat方案不劣于基于阿扎那韦/利托那韦的方案。
支持cobicistat与达芦那韦联合用药的数据来源于在健康受试者中进行的多剂量试验，该试验比较达芦那韦/cobicistat 800/150mg与达芦那韦/利托那韦800/100mg的相对生物利用度。
在临床试验中观察到的Tybost(与阿扎那韦联合用药)最常见的不良反应为黄疸，眼黄疸，和恶心。
TYBOST Rx
Generic Name and Formulations:
Cobicistat 150mg; tabs.

Company:
Gilead Sciences, Inc.
Indications for TYBOST:
HIV-1 infection: to increase systemic exposure of atazanavir or darunavir (once-daily dosing) in combination with other antiretroviral agents.

Limitations Of use:
Not interchangeable with ritonavir to increase systemic exposure of darunavir 600mg twice daily, fosamprenavir, saquinavir, or tipranavir. Different drug interactions possible when cobicistat and ritonavir given with atazanavir or darunavir.

Adult:
Take with food. Must be co-administered at same time as atazanavir or darunavir. ≥18yrs: 150mg once daily with atazanavir 300mg once daily (if treatment-naïve or experienced) or with darunavir 800mg once daily (if treatment-naïve or experienced with no darunavir resistance associated substitutions).

Children:
<18yrs: not established.

Contraindications:
Concomitant alfuzosin, dronedarone, carbamazepine, phenobarbital, phenytoin, rifampin, irinotecan (with atazanavir only), ergot derivatives, cisapride, St. John’s wort, lovastatin, simvastatin, pimozide, nevirapine, sildenafil (as Revatio for PAH treatment), indinavir (with atazanavir only), triazolam, oral midazolam.

Warnings/Precautions:
Assess CrCl prior to initiation. Renal impairment: consider alternatives that do not require dose adjustments. When co-administering tenofovir disoproxil fumarate: obtain baseline CrCl, urine glucose, urine protein and monitor during treatment; not recommended if CrCl <70mL/min; measure serum phosphorus in patients with or at risk for renal impairment. Severe hepatic impairment. Pregnancy. Nursing mothers: not recommended.

Interactions:
See Contraindications. Concomitant nephrotoxic agent with cobicistat + tenofovir disoproxil fumarate: not recommended. Concomitant darunavir 600mg twice daily or darunavir in combination with efavirenz, nevirapine, etravirine; atazanavir in combination with etravirine or efavirenz (in treatment-experienced); more than 1 antiretroviral that requires PK enhancement, other HIV-1 protease inhibitors (eg, fosamprenavir, saquinavir, tipranavir): not recommended. Concomitant Stribild, lopinavir/ritonavir, other cobicistat- or ritonavir-containing drugs/regimens: not recommended. Potentiated by concomitant CYP3A inhibitors. May potentiate drugs metabolized by CYP3A or CYP2D6 or substrates of P-gp, BCRP, OATP1B1, or OATP1B3. Antagonized by concomitant CYP3A inducers (eg, anticonvulsants, corticosteroids); may reduce efficacy and develop resistance; monitor. See full labeling.

Pharmacological Class:
Pharmacokinetic enhancer.

Adverse Reactions:
Jaundice, rash, ocular icterus, nausea; serum creatinine increase.

How Supplied:
Tabs—30