Müller-Lissner Stefan, Kamm Michael A, Musoglu Ahmet, Earnest David L, Dunger-Baldauf Cornelia, Shetzline Michael A
Park-Klinik Weissensee, Berlin, Germany.
Am J Gastroenterol. 2006 Nov;101(11):2558-69; quiz 2671. doi: 10.1111/j.1572-0241.2006.00789.x.
To assess the long-term safety and tolerability of tegaserod in patients with chronic constipation (CC).
This 13-month, uncontrolled extension study enrolled CC patients who completed a 12-wk randomized, double-blind, placebo-controlled core study. Patients receiving tegaserod 6 or 2 mg b.i.d. during the core study continued on the same dose; those receiving placebo were switched to tegaserod 6 mg b.i.d (placebo-to-tegaserod). Safety and tolerability were assessed by monitoring adverse events (AEs), laboratory parameters, vital signs, and electrocardiograms. Symptom evaluations included patient satisfaction with bowel habit and bothersomeness of constipation, abdominal distension/bloating, and abdominal discomfort/pain.
A total of 842 patients entered the extension study; 451 (54%) completed. AEs typically occurred within the first month of tegaserod treatment. Long-term treatment neither increased AE incidence nor revealed new safety risks. Headache (11.3%, 14.5%, and 16.1% in the tegaserod 6 mg b.i.d., 2 mg b.i.d., and placebo-to-tegaserod groups, respectively) and abdominal pain (8.8%, 8.8%, 10.9%) were the most common AEs. Diarrhea, the most common drug-related AE (4.9%, 2.5%, 8.0%), rarely led to discontinuation (0.7%, 0.0%, 2.2%). Diarrhea was transient, resolved without treatment interruption or rescue medication, and had no clinically significant consequences. Of 27 serious AEs, none were considered treatment related. No deaths or reports of ischemic colitis occurred in tegaserod-treated patients. No clinically relevant changes occurred in other safety parameters. Safety findings were similar in patients switched from placebo to tegaserod and those maintained on tegaserod.
Tegaserod has a favorable safety profile and is well tolerated during continuous long-term treatment in patients with CC.
评估替加色罗对慢性便秘（CC）患者的长期安全性和耐受性。
这项为期13个月的非对照扩展研究纳入了完成12周随机、双盲、安慰剂对照核心研究的CC患者。在核心研究期间接受6毫克或2毫克替加色罗每日两次治疗的患者继续使用相同剂量；接受安慰剂的患者改为每日两次6毫克替加色罗（从安慰剂改为替加色罗）。通过监测不良事件（AE）、实验室参数、生命体征和心电图来评估安全性和耐受性。症状评估包括患者对排便习惯的满意度以及便秘、腹胀/胃胀和腹部不适/疼痛的困扰程度。
共有842名患者进入扩展研究；451名（54%）完成研究。不良事件通常在替加色罗治疗的第一个月内出现。长期治疗既未增加不良事件发生率，也未发现新的安全风险。头痛（替加色罗6毫克每日两次组、2毫克每日两次组和从安慰剂改为替加色罗组分别为11.3%、14.5%和16.1%）和腹痛（8.8%、8.8%、10.9%）是最常见的不良事件。腹泻是最常见的与药物相关的不良事件（4.9%、2.5%、8.0%），很少导致停药（0.7%、0.0%、2.2%）。腹泻是短暂的，无需中断治疗或使用救援药物即可缓解，且没有临床显著后果。在27例严重不良事件中，无一例被认为与治疗相关。接受替加色罗治疗的患者未发生死亡或缺血性结肠炎报告。其他安全参数未出现临床相关变化。从安慰剂改为替加色罗的患者和继续使用替加色罗的患者的安全性结果相似。
替加色罗具有良好的安全性，在CC患者的持续长期治疗中耐受性良好。
