Diphenoxylate

A few short years ago, even gastroenterologists cringed when a patient with irritable bowel syndrome walked in. Today, thanks in large part to a public relations push and a better understanding of the disorder, primary care physicians can manage irritable bowel syndrome (IBS) patients with more confidence.

Last fall, an American College of Gastroenterology task force issued a position statement (Am. J. Gastroenterol. 97[11, suppl.]:S1-5, 2002). Some agents used in the past, even bulking agents, were judged to have little or no evidence of efficacy, although most gastroenterologists continue to advise patients to eat high-fiber foods.

The past year also saw the introduction of tegaserod, a new drug specifically labeled for IBS, and the reintroduction of alosetron. These are the first two agents specifically approved to treat IBS, and some experts say that their efficacy is impressive. In trials, about 60% of patients had a positive response to each drug. Other experts, however, note that about 40% of patients had no benefit and placebo response was high, so the impact of these agents was modest. Some gastroenterologists are reluctant to prescribe the two drugs because of cost and concern about alosetron's safety, even though the Food and Drug Administration carefully reviewed safety data before its reintroduction. Alosetron was first approved in 2000 but was withdrawn 8 months later because of 84 cases of ischemic colitis and 113 cases of serious constipation that led to several hospitalizations and 2 deaths. The May 2002 reintroduction requires that physicians who prescribe it have special training, be competent in managing ischemic colitis, and be registered with the manufacturer.

Patient education, reassurance, and dietary advice are considered the first steps for treating IBS, and these alone will relieve or improve symptoms in many patients. Drug treatment for patients with diarrheal symptoms usually starts with either an anti-spasmodic or an antidiarrheal agent; in some cases, the two classes are used together. Tricyclic antidepressants tend to be reserved for refractory patients, with alosetron and tegaserod currently viewed as last resorts for diarrhea and constipation, respectively. The task force also determined that various behavioral therapies are effective.

Alosetron and tegaserod have not been evaluated in the elderly. Other IBS drugs are used in the elderly with caution. However, IBS is uncommon in the elderly, particularly new-onset IBS, and physicians should rule out other conditions.

Because of limited clinical experience, avoid alosetron and tegaserod during the first trimester of pregnancy. Both drugs or their metabolites probably are secreted in breast milk, and because severe adverse effects have been associated with alosetron, it probably should be avoided during breast-feeding. Imipramine has not been shown to be teratogenic in animals, but long-term use during pregnancy may be associated with withdrawal in newborns. Desipramine, the active metabolite of imipramine, has not been studied in animals. Amitriptyline has shown dose-related teratogenicity in animals, but human risk appears to be low. The risks of using tricyclic antidepressants while nursing are not known. Surveillance studies with dicyclomine have noted an increased incidence of birth defects, but because there is no clustering of specific defects, there may be no association, and the risk is considered low. Dicyclomine should not be used while breast-feeding. Hyoscyamine has not been studied during pregnancy or breast-feeding, but it is considered probably compatible with breast-feeding. Loperamide has no evidence of impaired fertility or fetal harm in animals or humans; only small, probably acceptable, amounts are secreted in breast milk. Diphenoxylate and atropine combination has not been associated with impaired fertility or fetal harm in animals and humans; infrequent dosing is probably compatible with nursing.

COPYRIGHT 2003 International Medical News Group
COPYRIGHT 2003 Gale Group