Date Published: March 27, 2007
Publisher: Public Library of Science
Author(s): Su-Ting T Li, David C Grossman, Peter Cummings, David Candy
Abstract: BackgroundLoperamide is widely used in adults for acute diarrhea. However, its use in children has been discouraged by the World Health Organization and the American Academy of Pediatrics owing to concerns over safety and efficacy in young children.Methods and FindingsTo assess the efficacy and adverse effects of loperamide compared with placebo for acute diarrhea in children, we reviewed Medline, EMBase, the Cochrane Central Register of Controlled Trials, and bibliographies of known clinical trials and of review articles, and we also interviewed key investigators in the field. We undertook a systematic review and meta-analysis of randomized controlled trials of children younger than 12 y of age with acute diarrhea, comparing loperamide with placebo. Included trials reported data on diarrhea duration or severity, or provided data on adverse effects. Compared with patients who received placebo, patients allocated to loperamide were less likely to continue to have diarrhea at 24 h (prevalence ratio 0.66, 95% confidence interval [CI]: 0.57 to 0.78), had a shorter duration of diarrhea by 0.8 d (95% CI: 0.7 to 0.9 d), and had a lower count of stools at 24 h (0.84, 95% CI: 0.77 to 0.92). Results were similar when random-effects summaries were estimated. Serious adverse events, defined as ileus, lethargy, or death, were reported in eight out of 927 children allocated to loperamide (0.9%, 95% CI: 0.4% to 1.7%). Serious adverse events were not reported in any of the 764 children allocated to placebo (0%, 95% CI: 0% to 0.5%). Among the children allocated to loperamide, serious adverse events were reported only among children younger than 3 y.ConclusionsIn children who are younger than 3 y, malnourished, moderately or severely dehydrated, systemically ill, or have bloody diarrhea, adverse events outweigh benefits even at doses ≤0.25 mg/kg/d. In children who are older than 3 y with no/minimal dehydration, loperamide may be a useful adjunct to oral rehydration and early refeeding.
Partial Text: Worldwide, children younger than 5 y of age have approximately three cases of diarrhea annually and 1.6–2.5 million children younger than 5 y die each year from diarrhea, as estimated from studies published between 1992 and 2000 . The national health-care cost for diarrhea-associated disease in the United States was estimated to be US$1.55 billion in 2002 . In a 1997 survey, an estimated 34% of persons with a diarrheal illness in the United States reported taking anti-diarrheal medications . Some review papers on the treatment of acute diarrhea in adults suggest loperamide as a first-line agent [4,5]. Although loperamide is widely used in adults, the World Health Organization and the American Academy of Pediatrics are concerned about its use in young children because of concerns over its efficacy and safety [6,7]. In the United States, loperamide is approved by the Food and Drug Administration for use in children older than 2 y of age.
Loperamide appears to decrease diarrhea duration and frequency in children when used as an adjunct to oral or intravenous rehydration. Compared with patients given placebo, patients who were randomized to loperamide were 34% less likely to have had diarrhea 24 after initiation of therapy and 41% less likely to have had diarrhea 48 h after initiation of therapy, had 0.8 fewer days of diarrhea, and had a 16% reduction in diarrheal stools within the first 24 h of treatment. Serious adverse events of death, ileus, or lethargy were reported only in children younger than 3 y of age.