LAS VEGAS -- For treating patients with chronic constipation, a recently approved chloride channel activator compares well with other medications in efficacy and tolerability, according to a review of published data presented here.
LAS VEGAS, Oct. 31 -- For treating patients with chronic constipation, a recently approved chloride channel activator compares well with other medications in efficacy and tolerability, according to a review of published data presented here.
Amitiza ((lubiprostone), approved by the FDA last January, is the newest treatment option for chronic constipation, said Lin Chang, M.D., of the University of California, Los Angeles, at an industry-sponsored symposium held in conjunction with the American College of Gastroenterology meeting.
Amitiza selectively activates CLC-2 chloride channels, enhancing intestinal fluid secretion, Dr. Chang said.
This method of action differs from that of other drugs for treating constipation. Lactulose and PEG 3350, both approved for short-term constipation treatment and sold under a variety of brand names, are osmotic laxatives. Zelnorm (tegaserod), is a 5-HT4 agonist, Dr. Chang said.
Both Zelnorm and Amitiza are FDA-approved for long-term treatment of constipation, Dr. Chang noted.
When doctors prescribe a drug for constipation, patients are usually anxious to know is how soon they will have a bowel movement, Dr. Chang said. Clinicians should be prepared for the question.
In a study of 237 patients published in the American Journal of Gastroenterology last year, 61.3% of patients who received Amitiza had a spontaneous bowel movement within 24 hours, compared with 31.4% of patients in the placebo group, Dr. Chang said.
In a study published in the same journal this year, 73.2% of patients who received Zelnorm had a spontaneous bowel movement within 24 hours, compared with 52% of the placebo group, Dr. Chang noted.
In terms of adverse event profiles, the most common adverse events associated with lactulose and PEG 3350 are flatulence, intestinal cramps, diarrhea, nausea, and vomiting, Dr. Chang said.
For Zelnorm, the most common adverse events are headache, diarrhea, and abdominal pain, Dr. Chang said. For Amitiza, adverse effects were nearly identical: nausea, diarrhea, and headache, she said.
Both Amitiza and Zelnorm have proven well tolerated in short-term use (four to 12 weeks) and long-term use (six to 16 months), Dr. Chang said. Amitiza is classed as pregnancy category C, while Zelnorm is classed as pregnancy category B.
After Dr. Chang's presentation, a panel discussion ensued on whether laxatives approved for short-term use might also be useful for long-term treatment of constipation. The panelists also discussed whether combining laxative treatments might be beneficial.
Panelists were Dr. Satish S.C. Rao, M.D., Ph.D, of the University of Iowa in Iowa City, and David A. Peura, M.D., of the University of Virginia in Charlottesville.
Dr. Peura said that, according to his clinical experience, lactulose is not well tolerated for long periods of time because of the side effects of bloating and gas. It is difficult to get patients to comply with taking this drug for extended periods, he said.
Dr. Rao agreed. For managing long-term constipation, lactulose "has a very limited role to play in today's management," he said.
PEG 3350, on the other hand, is often well-tolerated in adults for up to three months, and there is data to suggest the drug is well-tolerated for up to a year in pediatric populations, Dr. Rao added.
As far as combining constipation treatments, there is a theoretical benefit to combining two mechanisms of action, but clinical experience has not borne that out, both Drs. Roa and Peura said.
In addition, there have been no studies examining combined constipation treatments, they said. "We have no clinical data on that," Dr. Peura said.
Finally, combination treatment for constipation would likely be prohibitively expensive, both doctors agreed. "It is going to break the bank," Dr. Peura said. "When you start adding up a lot of different medications it gets really expensive."
The symposium was sponsored by Sucampo Pharmaceuticals Inc., of Bethesda, Md., and Takeda Pharmaceuticals of North America, l in Deerfield, Ill.. They co-market Amitiza.