部份中文利那洛肽处方资料（仅供参考）
商品名：Constella Hartkapseln
英文名：linaclotide
中文名：利那洛肽胶囊
生产商：ALLERGAN PHARMACEUTICALS
药品简介
2013年6月18日，新药Constella（linaclotide 利那洛肽 290mcg）胶囊获欧洲批准上市，为首个用于治疗中重度IBS-C成人患者新药，目前，Constella已在德国、英国以及北欧国家上市.
Constella（linaclotide 利那洛肽）是一种鸟苷酸环化酶-C受体激动剂（GCCA），同时具有内脏镇痛效应和内分泌活性。利那洛肽是一种含有14个氨基酸的合成肽类结构，与内源性鸟苷肽家族相关。
利那洛肽及其活性代谢产物都可以与小肠上皮管腔表面的鸟苷酸环化酶-C（GC-C）受体结合。在动物模型中，通过GC-C的活化，利那洛肽可以减轻内脏疼痛，提高胃肠道转运速度，在人类中，该药物也可以提高结肠的转运速度。GC-C活化的结果即细胞内外cGMP（环鸟苷酸）浓度升高。细胞外cGMP可以降低疼痛神经纤维的活性，可减轻模型动物的内脏疼痛。细胞内cGMP可通过激活CFTR（囊性纤维化跨膜传导调节因子），增加小肠腔内氯化物和碳酸氢盐的分泌量，最终导致小肠液分泌增多和小肠转运速度增快。
作用机理
利那洛肽是具有内脏止痛和分泌活性的鸟苷酸环化酶C受体激动剂（GCCA）。
利那洛肽是一种结构上与内源鸟苷肽家族有关的14个氨基酸的合成肽。利那洛肽及其活性代谢物均与肠上皮腔表面的GC-C受体结合。通过利那卡洛肽在GC-C上的作用，已证明在动物模型中可减轻内脏痛并增加胃肠道转运，并增加人类的结肠转运。GC-C的激活导致细胞外和细胞内环状鸟苷单磷酸（cGMP）浓度的增加。细胞外cGMP降低了疼痛纤维的活性，从而减少了动物模型的内脏疼痛。细胞内cGMP通过激活囊性纤维化跨膜电导调节剂（CFTR）导致氯化物和碳酸氢盐分泌到肠腔中，从而导致肠液增加和转运加快。
适应症
对于成人，便秘适用于对症治疗便秘（IBS-C）的中度至重度肠易激综合症。
用法与用量
建议剂量为每天一次一粒胶囊（290微克）。
医生应定期评估是否需要继续治疗。利那洛肽的功效已在双盲安慰剂对照研究中确立，长达6个月。如果患者在治疗4周后仍未出现症状改善，则应重新检查患者，并重新考虑继续治疗的益处和风险。
特殊人群
肾或肝功能不全的患者
肝或肾功能不全的患者无需调整剂量。
老年患者
对于老年患者，尽管不需要调整剂量，但应仔细监测治疗并定期重新评估。
小儿
尚未确定Constella在0至18岁儿童中的安全性和有效性。无可用数据。
该药物不应在儿童和青少年中使用（请参阅第4.4和5.1节）。
给药方法
口服使用。饭前至少30分钟应服用胶囊。
禁忌症
对利那洛肽或列出的任何赋形剂超敏反应。
患有已知或疑似机械性胃肠道梗阻的患者。
保质期
未开封的28瓶，90瓶和多包装的瓶子，内装112（4包28个）胶囊：3年。
未开封的瓶子10胶囊：2年。
首次开放后：18周。
特殊的储存注意事项
请勿在30°C以上的温度下存放。 保持瓶子密闭，以防潮气。
该瓶子装有一个或多个装有硅胶的密封罐，以保持胶囊干燥。 将罐子放在瓶子里。
容器的性质和内容
白色高密度聚乙烯（HDPE）瓶，带有防篡改密封和防儿童进入的瓶盖，以及一个或多个装有硅胶的干燥剂罐。
包装大小：10、28或90粒胶囊和多包装，每片含112（4包28粒）胶囊。 并非所有包装尺寸都可以销售。
完整说明资料附件：
https://www.medicines.org.uk/emc/medicine/31618
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包装规格：（2013年6月18日在欧洲上市,注：以下产品不同规格和不同价格，购买以咨询为准）
290ugx10片/瓶
290ugx28片/瓶
290ugx60片/瓶
290ugx90片/瓶
Linaclotide Given Positive CHMP Opinion For Irritable Bowel Syndrome With Constipation
Almirall, S.A. (ALM:MC) and Ironwood Pharmaceuticals, Inc. (NASDAQ: IRWD) have announced that the European Committee for Medicinal Products for Human Use (CHMP) has issued a positive opinion recommending the marketing approval for Constella® (linaclotide 290 micrograms), for the symptomatic treatment of moderate to severe irritable bowel syndrome with constipation (IBS-C) in adults.
The CHMP positive opinion is a recommendation to the European Commission (EC) and one of the final steps in the review of a marketing authorization application. The EC usually follows the recommendations of the CHMP. Once approved, it will be marketed under the brand name Constella®.
"Patients with IBS-C suffer from several very uncomfortable gastrointestinal symptoms for which there are currently very few available therapies", said Bertil Lindmark, Chief Scientific Officer at Almirall. "With linaclotide physicians will have one of the first specifically designed therapies with proven efficacy and tolerability over time. Therefore, we are very pleased at Almirall with this first IBS-C treatment recommended for approval by CHMP and are confident in linaclotide's benefits".
This positive recommendation is based on the efficacy and safety of linaclotide eva luated in two double-blind, placebo-controlled Phase III clinical studies. The clinical trials involved approximately 1,600 adult patients, of which more than 800 were treated with linaclotide 290 mcg. In both trials, treatment with linaclotide resulted in statistically significant improvements in both abdominal pain/discomfort and degree of relief of IBS-C symptoms (co-primary endpoints), as well as complete spontaneous bowel movement frequency, stool consistency and severity of straining and bloating (secondary endpoints). These improvements were maintained over the entire treatment period (12 and 26 weeks). The incidence of adverse events was similar in both studies, with diarrhoea being the most common adverse event in linaclotide-treated patients1,2.
"This positive opinion is a significant step toward helping these highly symptomatic adult patients; many of whom are searching for new treatment options," said Mark Currie, PhD, Senior Vice President, R&D and Chief Scientific Officer of Ironwood. "The discovery of linaclotide by Ironwood scientists and the work we have done to reach patients in Europe with our partner, Almirall, has been a collaborative effort with the goal of helping this underserved patient population."
Almirall holds exclusive marketing rights for linaclotide in Europe.
About linaclotide (Constella®)
Linaclotide is a guanylate cyclase-C (GCCA) agonist that is provided as an oral capsule intended for once-daily administration for the treatment of irritable bowel syndrome with constipation.
It binds to guanylate cyclase C locally in the intestine, with no measurable blood plasma concentrations, resulting in an increase in both intracellular and extracellular concentrations of cyclic guanosine monophosphate (cGMP). Elevations in intracellular cGMP are believed to stimulate secretion of intestinal fluid and accelerate gastrointestinal transit resulting in increased frequency of bowel movements. Elevations in extracellular cGMP are believed to decrease activity of pain-sensing nerves, which is thought to be responsible for a reduction in intestinal pain, according to nonclinical models.
Constella® is a trademark owned by Ironwood Pharmaceuticals, Inc. and its use in Europe is pending marketing approval from the European Commission.
About Irritable Bowel Syndrome with Constipation (IBS-C)
IBS is defined as a functional bowel disorder in which abdominal pain or discomfort is associated with defecation or a change in bowel habit and with features of disordered defecation.[i] IBS-C is one of four clinically different subtypes of IBS. One-third of patients with IBS are thought to have IBS-C[ii] and suffer chronically from both abdominal pain and constipation.
The Rome III Diagnostic Criteria for Functional Gastrointestinal Disorders includes criterion for the diagnosis of IBS3 as:
■Recurrent abdominal pain or discomfort at least three days/month, in the last three months with symptom onset at least 6 months prior to diagnosis, associated with two or more of the following:
■improvement with defecation
■onset associated with a change of frequency of stool
■onset associated with a change in form (or appearance) of stool
The estimated preva lence of IBS at 10-15% of the European population puts it in line with conditions such as migraine (12%) and asthma (11%).5 IBS can have a negative impact on daily living with considerable socio-economic and psychological consequences, and represents a major proportion of gastrointestinal workload in both primary and secondary care. Due to the complex, multimodal nature of the condition there is no cure for IBS and minimal therapeutic options.6