FORT LAUDERDALE, FLA. — About 10% of patients with ulcerative colitis who are taking 5-aminosalicylic acid medications develop worsening diarrhea that may be linked to these drugs.
“Continued treatment with a salicylate in a patient who isn't responding can be worse than useless, because 5-ASA [5-aminosalicylic acid] can trigger diarrhea in some patients,” Dr. Raymond Sandler said in an interview at an international colorectal disease symposium sponsored by the Cleveland Clinic Florida.
Many patients with ulcerative colitis who are receiving ineffective treatment with a salicylate also take an antidiarrheal drug, as well as other motility-inhibiting drugs such as antiemetics or even narcotics. These additional drugs may well exacerbate the adverse effects of 5-ASA by prolonging its presence in the gut.
Instead, physicians should withdraw patients who are nonresponders to 5-ASA from the drug if the patients require “step-up” therapy with steroids or immunomodulator drugs, Dr. Sandler said.
Salicylates are for patients with mild to moderate disease. “Once a patient remains symptomatic despite treatment with a 5-ASA drug, such as mesalamine, [he or she] can no longer be considered to have mild disease,” said Dr. Sandler, a gastroenterologist at the Cleveland Clinic Florida in Weston.
“The first thing I do is stop the salicylate” and see how the patient responds. “I've seen no refractory [ulcerative colitis] patient get worse when taken off a 5-ASA drug,” he said.
Dr. Sandler recommended starting patients with mild ulcerative colitis on a low-dose salicylate regimen and monitoring them for 1–2 months. If a patient's condition worsens, he or she should be taken off the drug rather than increasing the dosage.
If the patient's condition remains the same or improves slightly, doubling the dose is reasonable. But the higher dosage should be continued only if the patient improves. If the patient fails to improve, the salicylate should be stopped and treatment with another drug should be started.
For immunomodulator treatment of ulcerative colitis, Dr. Sandler prefers either 6-mercaptopurine or azathioprine. But he cautioned that patients who start one of these drugs should be tested to see if they have an adequate level of thiopurine methyltransferase, an enzyme necessary for the safe metabolism of these drugs.
Patients with inadequate enzyme levels can develop leukopenia and life-threatening agranulocytosis. In addition, bridge therapy with steroids or other drugs is usually necessary because of the relatively long delay before 6-mercaptopurine and azathioprine start to work.
A promising alternate immunomodulating drug is tacrolimus, which appears safe and effective in retrospective studies. However, the safety and efficacy of systemic tacrolimus for ulcerative colitis still needs to be confirmed in prospective studies, Dr. Sandler said.