Loperamide Therap as an adjunct to oral hydration vs. oral hydration and placebo. Specifically in Acute Diarrhea and Dehydration

1. Loperamide Therapy for Acute
Diarrhea
Loperamide as an adjunct to oral rehydration vs.
oral rehydration & Placebo
Elie Geara & Joseph A. Di Como

2. Question
 What is the efficacy of Loperamide in
the treatment of acute diarrheal
illness in children?

3. Loperamide in acute diarrhea in childhood: results of a double
blind, placebo controlled multicenter clinical trial Evans et al.
1984, British Medical Journal
 Randomized double blind 4 hospital study
 315 patients (Age: 3 months- 3 years) with hospital admission for acute
diarrhea of less than 2 weeks
 0.8 mg/kg body weight loperamide syrup + rehydration, 0.4 mg/kg body weight
loperamide syrup + rehydration, rehydration + placebo alone
 Drug Administration was continued until diarrhea resolved or for 7 days
 Assessment Criteria: Diarrhea was deemed to resolve when: a) at the
passage of the first formed stool, b) at the passage of the second semisolid
stool, c)no stool had passed for 24 hours
• In the Placebo group, there was a
probability of 55% of diarrhea
continuing beyond 24 hrs as
compared with 36% in the 2
loperamide groups
• The differences among these 3
groups persisted for about 3 days
• Differences in recovery time were
stratified based on several variables.
The presence of absence of
pathogens was the only variable that
appeared to influence recovery rates.

4. Loperamide in acute diarrhea in childhood: results of a double
blind, placebo controlled multicenter clinical trial Evans et al.
1984, British Medical Journal
• Relative Recovery Rate calculated by dividing the observed
number of resolutions of diarrhea in a treatment group by the
expected number
• RR < 1.0 indicates disadvantage

5. Li S-TT, Grossman DC, Cummings P (2007) Loperamide Therapy for Acute
Diarrhea in Children: Systematic Review and Meta-Analysis. PLoS Med 4(3):
e98. doi:10.1371/journal.pmed.0040098
 Systematic review and meta-analysis of randomized controlled trials of children younger than 12 years of age
with acute diarrhea, comparing loperamide with placebo.
 13 studies met the four criteria for selection: Study design (randomized controlled trial), study population
(children younger than 12 years of age with acute diarrhea), intervention (loperamide versus control), and
availability of outcome data on diarrhea duration and severity.
 Compared with patients who received placebo, patients allocated to loperamide were less likely to continue to
have diarrhea at 24h (prevalence ratio 0.66, 95% confidence interval [CI]: 0.7 to 0.9 d), and had a lower count
of stools at 24h (0.84, 95% CI 0.77 to 0.92).
 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% d ).
 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 years.
Treatment Loperamide Placebo
Number of patients 927 764
Adverse outcomes 8 0

6. Comparison:
Strength Weakness
Evans et al (1984)
Loperamide in acute
diarrhea in childhood:
results of a double
blind, placebo
controlled multicenter
clinical trial
• double blind, randomized treatment
• multiple study centers: variability
•Consistency in management of data: general form,
follow up chart, and stool chart
•Data was stratified based on recruitment center as
well as variations such as age, state of hydration,
duration of diarrhea, drugs before admission, and
stool pathogens
• study was done in 1984
•Inconsistency in stool pathogen
measurements
•Unclear where in coarse of diarrheal
illness drug was initiated
•No unified protocol for management of
patients across centers other than study
treatment
Li S-TT, Grossman
DC, Cummings P
(2007) Loperamide
Therapy for Acute
Diarrhea in Children:
Systematic Review and
Meta-Analysis.
• Extensive search not limited by language
• Studies had to fulfill four indicators of
methodological quality.
•All studies had the same dose of more or equal to
0.25 mg/kg/d
•Relatively large sample size
• Lack of consistency in outcome
measures.
• Unclear how representative the children
recruited in the studies compared with all
children worldwide with diarrhea.
•Serveral studies did not report hydration
status, or specifically excluded children
with moderate or severe dehydration.
•No study reported nutritional status.

7. Conclusion
 Loperamide may prove useful in the management of
acute diarrhea when response to oral hydration alone
is slow or unsatisfactory.
 0.8 mg/kg of loperamide speeded recovery by ~24
hours
 if a child is less than 3 years of age, malnourished,
moderately or severely dehydrated or has bloody
diarrhea, the risk of adverse events from lioperamide
treatment outweigh the benefits, even at low doses.
 Further research is needed to clarify how treatment
can provide maximum benefit for the patient.

8. Bibliography
 Evans et al. 1984. Loperamide in acute
diarrhoea in childhood: results of a double blind,
placebo controlled multicentre clinical trial British
Medical Journal 289: 1263-66
 Li S-TT, Grossman DC, Cummings P. 2007.
Loperamide Therapy for Acute Diarrhea in
Children: Systematic Review and Meta-Analysis.
PLoS Med 4(3): e98.
doi:10.1371/journal.pmed.0040098