Original article
Treatment of Travelers’ Diarrhea: Randomized Trial Comparing Rifaximin, Rifaximin Plus Loperamide, and Loperamide Alone

Presented at Digestive Disease Week, Los Angeles, California, May 20–25, 2006.
https://doi.org/10.1016/j.cgh.2007.02.004Get rights and content

Background & Aims: Antimotility agents provide rapid temporary relief of acute diarrhea, whereas antibiotics slowly cure the illness. Thus, the combination of an antimotility agent and an antibiotic may provide greater therapeutic benefit than either drug alone. This study evaluated the efficacy and safety of rifaximin-loperamide in the treatment of travelers’ diarrhea. Methods: Consenting adults with acute diarrhea (≥3 unformed stools in 24 hours with ≥1 symptom of enteric infection) were randomized to receive rifaximin 200 mg 3 times daily for 3 days; loperamide 4 mg initially followed by 2 mg after each unformed stool; or a combination of both drugs using the same dosing regimen. The primary end point was the median time from beginning therapy until passing the last unformed stool. Results: A total of 310 patients completed treatment with rifaximin (n = 102), loperamide (n = 104), or rifaximin-loperamide combination therapy (n = 104). The groups showed demographic similarity. Rifaximin and rifaximin-loperamide significantly reduced the median time until passage of the last unformed stool (32.5 ± 4.14 h and 27.3 ± 4.13 h, respectively) vs loperamide (69 ± 4.11 h; P = .0019). The mean number of unformed stools passed during illness was lower with rifaximin-loperamide (3.99 ± 4.28) compared with rifaximin (6.23 ± 6.90; P = .004) or loperamide alone (6.72 ± 6.93; P = .002). All treatments were well tolerated with a low incidence of adverse events. Conclusions: Rifaximin-loperamide therapy provided rapid symptomatic improvement and greater overall wellness compared with either agent alone.

Section snippets

Study Population

Eligible patients included otherwise healthy US students age 18 years or older attending school in Mexico (Guadalajara and Cuernavaca) for 2–5 weeks during June through August of 2004 or June through August of 2005 and suffering from TD (defined as the passage of ≥3 unformed stools in 24 hours with ≥1 symptom of enteric infection, including abdominal cramps and pain, nausea, vomiting, fever, tenesmus, and moderate to severe intestinal gas-related symptoms, lasting ≤72 hours). All individuals

Results

A total of 311 patients were included in the intention-to-treat population and safety analysis during the summers of 2004 and 2005. One patient in the rifaximin-loperamide treatment group discontinued the study after 1 day for nonmedical reasons. Therefore, 310 patients with acute diarrhea completed treatment with rifaximin (n = 102), loperamide (n = 104), or rifaximin-loperamide combination therapy (n = 104). The groups were comparable in terms of age, duration of diarrhea, race, sex, and

Discussion

Current guidelines for the treatment of TD suggest administration of symptomatic drugs for mild illness and antibacterial agents for moderate to severe illness.6 Loperamide is considered the most effective therapy for rapid symptomatic relief of TD,9, 10 but antibiotic treatment often is necessary to cure the intestinal illness.6, 26 To this end, clinical studies have evaluated the effects of combining loperamide with systemic antibiotics for the treatment of TD and have reported conflicting

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  • Cited by (0)

    Supported by Salix Pharmaceuticals, Inc. Also supported in part by grants from the Public Health Service (DK 56338), which funds the Texas Gulf Coast Digestive Diseases Center, and the National Institutes of Health National Center for Research Resources to the University of Texas General Clinical Research Center (M01-RR 02558 and NIH NIAID R01 AI54948). In addition, H.L.D., P.C.O., and C.D.E. have received honoraria for speaking for Salix Pharmaceuticals, Inc., and H.L.D. and Z.-D.J. have received grants administered through the University of Texas for research from Salix Pharmaceuticals, Inc.

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