腹泻是许多人类免疫缺陷病毒（HIV）携带者和艾滋病（AIDS）患者用药后常见的不良反应，也是患者停止使用抗逆转录病毒药物、改用其他治疗方案的原因之一。
近日，由Napo制药公司开发的crofelemer（商品名：Fulyzaq）获美国FDA批准，用于减轻正在接受抗逆转录病毒联合用药治疗的HIV携带者及AIDS患者的水样腹泻症状，每日服用2次。 
批准日期：2012年12月31日；公司：Salix Pharmaceuticals，Ltd.

FULYZAQ™ (crofelemer)缓释片，为口服使用 

美国初次批准：2012 

作用机制

Crofelemer是在肠上皮细胞的管腔膜环磷酸腺苷(cAMP)-刺激囊性纤维化跨膜电导调节物(CFTR)氯离子(Cl-)通道，和钙-激活Cl通道(CaCC)两者的抑制剂。通过肠上皮细胞CFTR Cl通道和CaCC调节Cl-和液体分泌。在腹泻中Crofelemer通过阻断Cl分泌和伴有高容积水丢失而起作用，使胃肠道Cl和水流动正常化。

适应证和用途

FULYZAQ是抗腹泻药适用于在用抗逆转录病毒治疗HIV/AIDS成年患者中对非感染性腹泻解除症状。

剂量和给药方法

每天2次每次口服1片125mg缓释片，有或无食物。

剂型和规格

缓释片：125mg

禁忌证

无。

警告和注意事项

开始用crofelemer前除外腹泻的传染性病因。如果不考虑传染性病因，有传染性病因患者将不能接受适宜治疗而其疾病可能恶化。(5.1) 

不良反应

最常见不良反应(发生率 ≥ 3%)是上呼吸道，支气管炎，咳嗽，胀气和胆红素增加。 

为报告怀疑不良反应，联系Salix Pharmaceuticals电话1-866-669-7597或FDA电话1-800¬FDA-1088或www.fda.gov/medwatch 

特殊人群中使用

（1）妊娠：根据动物数据，可能致胎儿危害。

（2）儿童使用：尚未确定小于18岁患者中FULYZAQ的安全性和有效性。

如何供应/贮存和处置

Crofelemer缓释片，125 mg，是白色，椭圆形肠溶片一侧印有125SLXP。可得到以下包装大小：

60片瓶: NDC 65649-802-02

保存在20°C-25°C(68°F-77°F)；外出允许15°C-30°C (59°F-86°F)间。. 见USP控制室温。

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Name       Generic Name   Manufacture         NDC

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FULYZAQ TAB 125MG 60   CROFELEMER    VALEANT (FORMERLY SALIX)    65649-0802-02   

FULYZAQ TAB 125MG 60   CROFELEMER    MISSION PHARMACAL COMPANY   70564-0802-02 

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Fulyzaq® (crofelemer) 125 mg Delayed-Release Tablets Significantly Improves Noninfectious Diarrhea in Adult Patients Living with HIV on ART Therapy 

Fulyzaq® (crofelemer) for the treatment of noninfectious diarrhea caused by anti-retroviral therapy (ART) in adult patients with HIV. The Antidiarrhea Therapy in HIV Disease−Emerging Treatment Concepts (ADVENT) trial concluded that Fulyzaq provides significant improvement in the symptomatic relief of noninfectious diarrhea with a safety profile similar to placebo and with no negative impact on clinical immune parameters (HIV viral load and CD4+ cell count). 

“Diarrhea can be an unfortunate and persistent occurrence for patients living with HIV who are on ART therapies,” said Rodger MacArthur, M.D., professor of medicine at Wayne State University, Division of Infectious Diseases and lead investigator. “The ADVENT trial showed that Fulyzaq (crofelemer) significantly improved diarrhea without negatively impacting ART. This is an important advancement in treatment, as Fulyzaq is the only FDA-approved option for relief of noninfectious diarrhea specifically for people living with HIV.” 

The ADVENT trial was a randomized, double-blind, phase 3 trial that used a two-stage design to determine optimal dose and eva luate Fulyzaq for the treatment of noninfectious diarrhea in HIV positive patients. Under the placebo-controlled method, the study eva luated 374 patients and revealed that patients achieved significant clinical response when treated with Fulyzaq 125 mg delayed-release tablets compared to the placebo (17.6% vs 8.0%, one-sided, P = .01). Additionally, Fulyzaq was minimally absorbed, well tolerated, did not negatively impact ART efficacy, and had a safety profile comparable to placebo. 

“We are excited that the leading peer-reviewed journal HIV Clinical Trials highlights the ADVENT trial that demonstrates the efficacy and safety of Fulyzaq,” said Bill Forbes, PharmD, Executive Vice President, Medical, Research and Development and Chief Development Officer, Salix. “It is our hope that increasing knowledge about diarrhea treatment options will enable patients living with HIV to start the dialogue with healthcare providers for managing this often under-discussed and, therefore, undertreated condition.” 

Fulyzaq acts as an anti-secretory, anti-diarrheal agent that works locally in the gastrointestinal (GI) lumen and exhibits minimal systemic absorption. It normalizes the flow of water in the GI tract to relieve diarrhea in people taking ART. Fulyzaq is derived on a sustainable basis from the Croton lechleri plant, native to northwestern South America. The ADVENT trial led to the Food and Drug Administration approval of Fulyzaq in December 2012. Visit www.fulyzaq.com for more information. For more details regarding the article, visit www.hivclinicaltrials.com. 

Indication for FULYZAQ® 

FULYZAQ® is an antidiarrheal indicated for the symptomatic relief of noninfectious diarrhea in adult patients with HIV/AIDS on antiretroviral therapy 

Important Safety Information about FULYZAQ® 

FULYZAQ® (crofelemer) delayed-release tablets should not be used for the treatment of infectious diarrhea. Rule out infectious etiologies of diarrhea before starting FULYZAQ. If infectious etiologies are not considered, and FULYZAQ is initiated based on a presumptive diagnosis of noninfectious diarrhea, then there is a risk that patients with infectious etiologies will not receive the appropriate treatments, and their disease may worsen. 

Based on animal data, FULYZAQ may cause fetal harm. Safety and effectiveness of FULYZAQ have not been established in patients less than 18 years of age. 

In clinical studies, the most common adverse reactions (occurring in ≥3% of patients and at a rate greater than placebo) were upper respiratory tract infection, bronchitis, cough, flatulence, and increased bilirubin. 

About FULYZAQ® 

FULYZAQ® is derived on a sustainable basis from the Croton lechleri plant, native to northwestern South America. FULYZAQ ™ acts as an anti-secretory, anti-diarrheal agent that works locally in the GI lumen and exhibits minimal systemic absorption. At the recommended dose of one 125 mg delayed-release tablet taken orally, twice daily, FULYZAQ ™ works to inhibit both the cyclic adenosine monophosphate (cAMP)-stimulated cystic fibrosis transmembrane conductance regulator (CFTR) chloride ion (C1-) channel, and the calcium-activated C1- channels (CaCC). 

Inhibiting CFTR and CaCC reduces the secretion of chloride ions, along with the water that enables their transport, out of the circulatory system and into the intestinal lumen. The secretion of chloride ions has been shown to cause diarrhea, with the associated symptoms of dehydration, electrolyte imbalance, abdominal cramping, urgency and increased frequency. 

Salix obtained rights to crofelemer under license from Napo Pharmaceuticals, Inc. 

About HIV/AIDS-Associated Diarrhea 

Diarrhea remains a common problem for patients with HIV/AIDS that may lead to discontinuation or premature switching of antiretroviral therapy (ART). Currently it is estimated that approximately 1.2 million persons are living with HIV infection in the United States. Additionally, it is estimated that approximately 135,000 – 270,000 persons on anti-retroviral therapy (ART) suffer from noninfectious diarrhea. 

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