Palm Beach Atlantic University Gregory School of Pharmacy, West Palm Beach, FL, USA.
Am J Health Syst Pharm. 2021 Feb 19;78(5):376-388. doi: 10.1093/ajhp/zxaa416.
The pharmacology, pharmacokinetics, and role in therapy of fostemsavir in management of HIV-1 infection are reviewed, with an emphasis on clinical efficacy and safety data from phase 2 and phase 3 clinical trials.
Fostemsavir (Rukobia, ViiV Healthcare), is a prodrug of temsavir, a novel pyridine compound with potent activity against HIV-1. Fostemsavir, the first oral attachment inhibitor, was approved and granted the breakthrough therapy designation by the Food and Drug Administration for use in combination with other antiretroviral agents for the treatment of HIV-1 infection in heavily treatment-experienced adults. As absorption of temsavir is not altered with increased gastric pH, patients may take acid suppressive agents such as famotidine during fostemsavir therapy.Temsavir is primarily metabolized through hydrolysis but also via cytochrome P-450 (CYP) oxidation; therefore, coadministration of fostemsavir with strong CYP3A inducers such as rifampin, carbamazepine, phenytoin, mitotane, enzalutamide, or St John's wort is contraindicated because it may result in significantly lower temsavir exposure, which can ultimately impair virologic response. The most common adverse reactions associated with fostemsavir use include nausea, diarrhea, headache, abdominal pain, dyspepsia, fatigue, rash, and sleep disturbance.
Fostemsavir may be an effective option for heavily treatment-experienced adults with multidrug-resistant HIV-1 infection. Fostemsavir is a particularly attractive treatment option for patients who are no longer able to achieve viral suppression with use of currently available antiretroviral therapies and who are able to adhere to a twice-daily oral regimen.
综述福替司韦在治疗 HIV-1 感染中的药理学、药代动力学和治疗作用，重点介绍 2 期和 3 期临床试验的临床疗效和安全性数据。
福替司韦（Rukobia，ViiV Healthcare）是替诺福韦的前药，是一种新型吡啶化合物，对 HIV-1 具有强大的活性。福替司韦是首个口服附着抑制剂，已获得美国食品和药物管理局（FDA）批准，并被授予突破性治疗药物认定，与其他抗逆转录病毒药物联合用于治疗接受过大量治疗的成人 HIV-1 感染。由于替诺福韦的吸收不受胃内 pH 值升高的影响，患者在接受福替司韦治疗期间可以服用法莫替丁等胃酸抑制药物。替诺福韦主要通过水解代谢，但也通过细胞色素 P-450（CYP）氧化代谢；因此，福替司韦与利福平、卡马西平、苯妥英、米托坦、恩杂鲁胺或贯叶连翘等强 CYP3A 诱导剂联合使用是禁忌的，因为这可能导致替诺福韦暴露显著降低，最终损害病毒学应答。与福替司韦使用相关的最常见不良反应包括恶心、腹泻、头痛、腹痛、消化不良、疲劳、皮疹和睡眠障碍。
福替司韦可能是多重耐药 HIV-1 感染的大量治疗经验成人的有效选择。对于那些由于使用现有抗逆转录病毒疗法无法实现病毒抑制且能够坚持每日两次口服治疗方案的患者，福替司韦是一种特别有吸引力的治疗选择。
