Pharmacology Update

Rifaximin Tablets (XifaxanTM)

By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD

The first nonabsorbable, gastrointestinal-selective antibiotic has been approved for the treatment of travelers’ diarrhea caused by noninvasive strains of Escherichia coli. Rifaximin, a derivative of rifampin, is currently available in 17 countries worldwide. It is marketed in this country as XifaxanTM by Salix Pharmaceuticals.

Indications

Rifaximin is indicated for the treatment of patients, 12 years or older, with travelers’ diarrhea caused by noninvasive strains of E. coli. It should not be used for diarrhea complicated by fever, blood in the stool, or diarrhea caused by pathogens other than E. coli.1

Dosage

The recommended dose is 200 mg taken 3 times a day for 3 days. It may be taken without regard to meals. If the diarrhea persists more than 24-48 hours or if fever or blood in the stool occurs, rifaximin should be discontinued and medical attention should be sought.1

Rifaximin is supplied as 200 mg tablets.

Potential Advantages

Rifaximin is essentially not absorbed after oral administration as less than 0.4% is excreted in the urine. Adverse events during clinical studies were similar to placebo and rifaximin has been shown not to significantly affect intestinal or hepatic CYP3A4 activity.1

Potential Disadvantages

Rifaximin is only indicated for uncomplicated travelers’ diarrhea caused by E. coli. Activity against other pathogens such as Campylobactor jejuni, Shigella spp., or Salmonella spp. has not been demonstrated.1 Hypersensitivity reactions (eg, allergic dermatitis, angioneurotic edema, urticaria) have been reported in postmarketing studies outside the United States. Development of resistant strains of E. coli has been shown in vitro.1 Common side effects are flatulence, headache, abdominal pain, rectal tenesmus, defecation urgency, nausea, constipation, pyrexia, and vomiting. However the frequencies of these were not different compared to placebo.1

Comments

Rifaximin is a virtually nonabsorbable semi-synthetic antibiotic. Its efficacy was studied primarily in Mexico, Central America, Africa, and India. The primary efficacy end point was time to last unformed stool (TLUS). Clinical cure was defined as absence of unformed stools. TLUS for rifaximin (600 mg daily for 3 days) was about 33 hours compared to about 60 hours for placebo.1,2 Clinical cure was 79.2% and 60.5% respectively (P = .001).1 In a comparative study, rifaximin (400 mg twice daily for 3 days) was comparable to ciprofloxacin (500 mg twice daily for 3 days).3

The median TLUS were 25.7 hours and 25.0 hours respectively. Rifaximin also appeared to shorten the duration of unformed stools compared to trimethoprim/sulfamethoxazole.4 The cost of rifaximin was not available at the time of this review.

Clinical Implications

Travelers’ diarrhea is characterized by a twofold or greater increase in the frequency of unformed bowel movement and associated abdominal cramps, nausea, bloating, urgency, fever, and malaise.5 It is generally acquired by ingestion of fecal contaminated food or water. An effective antibiotic treatment is ciprofloxacin (500 mg twice daily for 3 days). Treatment generally will shorten the duration of illness from 3-5 days to 1-1.5 days. Rifaximin provides an alternative for uncomplicated travelers’ diarrhea caused by E. coli (enterotoxigenic and enteroaggregative strains). It may be less effective against enteroaggregative-negative strains.6 It is not recommended for use in diarrhea caused by other pathogens such as Campylobactor jejuni, Salmonella spp., and Shigella spp. or in more severe diarrhea (ie, fever or blood in the stool).

Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente, and Assistant Clinical Professor of Medicine, University of California, San Francisco. Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA. Both are Associate Editors of Internal Medicine Alert.

References

1. Xifaxan Product Information. May 2004. Salix Pharmaceutical Inc.

2. Steffen R, et al. Am J Gastroenterol. 2003;98(5):1073-1078.

3. DuPoint HL, et al. Clin Infect Dis. 2001;33(11):1807-1815.

4. DuPoint HL, et al. Digestion. 1998;59(6):708-714.

5. National Center for Infectious Diseases Travelers’ Health 2003-2004. www.cdc.gov/travel/diarrhea.htm

6. Infante RM, et al. Clin Gastroenterol Hepatol. 2004;2(2):135-8.