Adis, 41 Centorian Drive, Private Bag 65901, Mairangi Bay, North Shore, 0754 Auckland, New Zealand.
Drugs. 2013 Jul;73(10):1121-9. doi: 10.1007/s40265-013-0083-6.
Crofelemer (Fulyzaq) is a botanical drug substance (oligomeric proanthocyanidin) extracted from the stem bark latex of the Croton lechleri tree. Crofelemer undergoes minimal systemic absorption following oral administration; it acts locally within the gastrointestinal (GI) tract by inhibiting the two principal chloride ion channels in the luminal membrane of enterocytes. Crofelemer is the first (and so far only) agent to be approved by the US FDA specifically for the symptomatic relief of non-infectious (i.e. secretory) diarrhoea in adult patients with HIV/AIDS on antiretroviral therapy (ART). This approval was based on findings from the ADVENT study, a large (n = 376 randomized patients), multicentre, phase III trial in which the recommended dosage of oral crofelemer (125 mg twice daily) significantly reduced secretory diarrhoea in HIV-positive individuals on ART compared with placebo, as assessed over a 4-week period. Crofelemer was generally well tolerated in ADVENT (which included a 5-month placebo-free extension phase) and a 48-week, open-label, phase III safety study; infections and GI disorders were the most frequently reported treatment-emergent adverse events (TEAEs) in patients receiving the drug. Of note, the overall incidence of TEAEs was similar in the crofelemer and placebo groups during the 4-week placebo-controlled phase of ADVENT. Treatment with crofelemer had no appreciable effect on immune parameters, such as HIV viral load and CD4+ cell counts.
可来福美（Fulyzaq）是一种从三叶橡胶树茎干乳胶中提取的植物药（低聚原花青素）。可来福美经口服给药后，全身吸收极少；它在胃肠道（GI）腔内局部发挥作用，通过抑制肠上皮细胞腔内膜上的两种主要氯离子通道来发挥作用。可来福美是美国食品药品监督管理局（FDA）批准的首个（也是迄今为止唯一的）专门用于治疗接受抗逆转录病毒疗法（ART）的艾滋病毒/艾滋病（HIV/AIDS）成年患者非感染性（即分泌性）腹泻症状的药物。这一批准是基于 ADVENT 研究的结果，这是一项大型（n = 376 名随机患者）、多中心、III 期临床试验，结果显示，与安慰剂相比，推荐剂量的口服可来福美（每日两次 125mg）可显著减少接受 ART 的 HIV 阳性个体的分泌性腹泻，评估时间为 4 周。在 ADVENT 中（包括为期 5 个月的无安慰剂扩展阶段）和一项 48 周、开放标签、III 期安全性研究中，可来福美通常具有良好的耐受性；在接受药物治疗的患者中，感染和胃肠道疾病是最常报告的治疗中出现的不良事件（TEAEs）。值得注意的是，在 ADVENT 的 4 周安慰剂对照阶段，可来福美组和安慰剂组的 TEAEs 总发生率相似。可来福美治疗对免疫参数（如 HIV 病毒载量和 CD4+细胞计数）没有明显影响。
