A Rifaximin Review From The Medical Letter

Abstract & Commentary

Synopsis: The Medical Letter describes rifaximin as one alternative to a quinolone antibiotic for treatment of travelers diarrhea, while noting that for severe diarrhea a fluoroquinolone is preferred.

Source: The Medical Letter. Rifaximin (Xifaxan)for Travellers’ Diarrhea. Vol.46 (Issue 1191) Sept 13, 2004. www.medicalletter.org

By Michele Barry, MD

Rifaximin (xifaxan®) is a non-systemic rifamycin antibiotic similar to rifampin. This agent has been approved by the FDA for the oral treatment of travellers’ diarrhea (TD), in patients 12 years of age or older, which is caused by enterotoxigenic E coli. It has been available in parts of Europe since 1987, but recently it has become more widely available in both Latin America and Asia.

Rifaximin works by binding to the beta subunit of bacterial DNA-dependent RNA polymerase, and inhibiting its action. Following oral administration, almost 97% of a dose is excreted in the feces unchanged. High concentrations are achieved within the intestinal tract that are effective against a broad range of enteropathogens, including enterotoxigenic and enteroaggregative strains of E. coli causing TD. It is much less active against Campylobacterjejuni, and there have been failures in the treatment of Shigella flexneri dysentery.

The agent is well-tolerated, with only a few hypersensitivity reactions that have been described, including rashes, allergic dermatitis, urticaria, and angioneurotic edema. Rifaximin is contraindicated in patients with known sensitivity to rifamycins. Although it can induce CYP3A4, there have been no significant drug interactions described, perhaps due to low systemic absorption. Rifaximin has not been studied in pregnant women, but is known to be teratogenic when injected into animals at high dose, and thus, is not recommended during pregnancy.

The dose of rifamixin suggested for TD is 200 mg TID for 3 days, and at this date, costs approximately $32.76 for 200 mg 3 times a day for the 3-day course. Only 2 relevant studies are reported in The Medical Letter, and one was a placebo comparison to rifaximin in 380 college students and tourists with TD in Guatemala, Mexico, and Kenya. Although microbiologic eradication rates of pathogens were similar with either rifaximin or placebo, median time to last unformed stool was statistically shorter with rifaxamin than with placebo. In a head-to-head study of rifaximin and ciprofloxacin in 187 students and tourists in Mexico and Jamaica who presented largely with enterotoxigenic E. coli, there was no statistical difference seen between these agents. The Medical Letter describes rifaximin as one alternative to a quinolone antibiotic for treatment of travelers diarrhea, while noting that for severe diarrhea a fluoroquinolone is preferred.

Comment by Michele Barry, MD

Rifaximin is a rifamycin antibacterial which has the desirable trait of not being absorbed from the gastrointestinal tract. It has been employed for prevention of surgical infection as prophylaxis during bowel surgery, for diverticular disease, and to reduce hyperammonemia in hepatic encephalopathy. The efficacy of rifaximin has been demonstrated in only a limited number of controlled clinical trials, and clearly it does not work for Campylobacter induced TD, nor is it very effective in the treatment of Shigella flexneri dysentery. However, when rifaximin is given for 3 days (total 1.8 grams), the fecal concentration of drug reach 8000µg/g, or more than 125 times the MIC90 for enterotoxigenic strains of E. coli ( ETEC). Since this antibiotic will be largely excreted into the environment, E. coli resistance should be monitored with future use. Rifaximin is an exciting new option for the treatment of ETEC travellers’ diarrhea, but probably should not be used for travelers with bloody diarrhea or systemic symptoms, nor should it be taken during pregnancy.

References

1. Dupont, et al. Clin Infect Dis. 2001;33(11):1087-1015.

2. Steffen, et al. Am Jl Gastro. 2003;98(5):1073-1078

3. Infante, et al. Clinical Gastro & Hepatology. 2004;2(2): 135-138.

4. Ericsson, et al. Travelers Diarrhea. Hamilton, London: BC Decker, Inc, 2003.

Michele Barry, MD, FACP, Professor of Medicine; Co-Director, Tropical Medicine and International Travelers’ Clinic, Yale University School of Medicine, is Associate Editor for Travel Medicine Advisor.