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【drug-news】替加色罗治疗慢性便秘的长期作用安
December 8, 2006 — Tegaserod (Zelnorm) used for up to 16 months is a safe, well tolerated, and effective treatment for patients with chronic constipation, according to a study conducted in Europe, Australia, and the Republic of South Africa.
Altered serotonin signaling is believed to be one mechanism involved in chronic constipation, according to Dr. Stefan Müller-Lissner, from Park-Klinik Weissensee, Berlin, and colleagues. Tegaserod is a serotonin receptor agonist that "stimulates GI motility, and to a lesser extent, increases intestinal chloride and water secretion."
As a result, they report in the November issue of the American Journal of Gastroenterology, treatment with tegaserod results in "net intraluminal water movement, softer stool, and enhanced aboral flow of luminal contents."
Tegaserod has already proved effective over 12 months in treating constipation related to irritable bowel syndrome, the authors note. Previous trials of tegaserod included more than 14,000 patients.
In their current report, the investigators explain that they already completed a 3-month, randomized, double-blind, placebo-controlled clinical trial of tegaserod for treatment of chronic constipation, which established the drug's short-term safety and efficacy. The current trial is a 13-month extension of that study.
Subjects who were originally dosed at 6 mg twice daily (n = 283), as well as participants originally assigned to placebo (n = 274), used the 6 mg b.i.d. dose during the extension trial. Those originally on tegaserod 2 mg twice daily (n = 283) continued at that dose. The only other medication they were permitted to use was bisacodyl 15 mg/day if they had gone for more than 4 days without a bowel movement.
None of the participants were older than 65 years. Mean age of the whole group was 45.8 years, and median duration of chronic constipation symptoms was 10 years.
The patients reported that symptoms, such as abdominal pain, bloating, and constipation, were less bothersome throughout the 13 month extension study compared with baseline. The improvements in symptoms were greatest during the first 6 months, then sustained for the next 7 months.
"The continued improvement in bloating is particularly noteworthy, as this symptom is difficult to treat and there is currently no specific treatment shown to be effective against this common complaint," the investigators write.
The most common adverse events included headache (11.3% to 16.1%) and abdominal pain (8.8% to 16.1%). Others included diarrhea, nausea, back pain, constipation, flatulence. The authors note that the adverse event rate decreased over time in all three treatment groups who completed the extension study.
Dr. Müller-Lissner and associates point out that 92.7% of patients did not experience episodes of diarrhea. Among those who did have a bout, diarrhea was transient and usually required no other treatment or study drug interruption. None required treatment for hypokalemia, dehydration, syncope, hypotension or cardiac effects; and no cases of ischemic colitis occurred.
Laboratory testing showed no clinically relevant changes in vital signs or urinalysis, hematology, or prolongation of the QTc interval or other ECG abnormalities. There were some cases of transiently elevated liver enzymes, but they were not considered clinically significant.
All of the 27 serious adverse events documented were attributed to conditions other than the constipation or tegaserod. Overall, 19.3% withdrew from the study because of lack of efficacy, and 6.3% because of adverse effects.
"In summary," the team writes, "these data suggest that tegaserod is a well-tolerated long-term treatment option for patients with chronic constipation."
This study was funded by Novartis Pharma AG, manufacturer of tegaserod.
Am J Gastroenterol. 2006;101:2558-2569.
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作者:admin@医学,生命科学 2011-02-14 18:15
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