Loperamide Therapy for Acute Diarrhea in Children: Systematic Review and Meta-Analysis

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.

Evaluation of the use of oral rehydration therapy in the management of diarrhoea among children under 5: knowledge attitudes and practices of mothers/caregivers

“…2,7 Some studies have shown clearly that caregivers' responses and the use of ORT is aligned to their knowledge and attitudes towards this therapy, 7,8 and that is why some resort to traditional remedies or prescriptions instead of giving rehydrating ORT to their children during episodes of diarrhoea. For example, despite concerns regarding their safety, 9,10 there is strong evidence that unconventional remedies are still being used to treat diarrhoea in some parts of South Africa, 11,12 and this is consistent with reports from other similar contexts across countries. 7,[13][14][15][16][17][18][19] These misconceptions in the ORT attitudes of caregivers is compounded by their apparent poor knowledge and awareness.…”

Rotavirus Infection Increases Intestinal Motility but Not Permeability at the Onset of Diarrhea

“…Regarding RV infections, Yamashiro and coworkers (26) found a significant effect of the stool score on days 3 to 5 of treatment. Meta-analyses confirmed that patients treated with loperamide are less likely to have diarrhea 24 h after treatment and present with a shorter duration of diarrhea and fewer stools than patients in the placebo group (27).…”

Infectious diarrhea: when to test and when to treat

“…13,15 Bismuth subsalicylate is not routinely recommended for use in children, because the salicylate component could predispose them to Reye syndrome.…”