By William Elliott, MD, FACP, and James Chan, PharmD, PhD
Dr. Elliott is Assistant Clinical Professor of Medicine, University of California, San Francisco.
Dr. Chan is Associate Clinical Professor, School of Pharmacy, University of California, San Francisco.
Drs. Elliott and Chan report no financial relationships relevant to this field of study.
The FDA has approved a new drug for the treatment of traveler’s diarrhea (TD). Rifamycin sodium is the second in the class of rifamycin antibacterials (rifamixin) to be approved for this indication. The FDA granted qualified infectious disease product, priority review, and fast track designations. Rifamycin will be marketed as Aemcolo.
Rifamycin is indicated for the treatment of TD caused by noninvasive strains of Escherichia coli in adults.1
The recommended dose is 388 mg (two tablets) orally twice daily for three days.1 It should be taken with a glass of fluid (not alcohol) and can be taken with or without food. Rifamycin is available as 194 mg of rifamycin in a delayed-release formulation.
Rifamycin is formulated using a Multi Matrix (MMX) technology. The enteric-coated, pH-dependent polymer film allows the drug to be released in the distal small bowel and colon.2 In addition to minimal systemic absorption, this targeted release reduces the risk of disturbing the microflora in the upper gastrointestinal tract.3
It is not recommended for use in patients with diarrhea complicated by fever and/or bloody stool or caused by other (e.g., invasive) bacteria.1
The approval of rifamycin was based on two randomized, Phase III trials. The authors of one trial compared the drug to placebo. In the second trial, the authors compared rifamycin to ciprofloxacin in subjects with TD.1,4,5,6 In trial 1, subjects were randomized to rifamycin (two tablets twice daily for three days; n = 199) or matching placebo (n = 65). The primary endpoint was time to last unformed stool (TLUS) between the first dose of the study drug and the last unformed stool passed before the start of clinical cure.5 Clinical cure was defined as passage of two or fewer soft stools or no watery stools, no fever, and no sign or symptoms of enteric infection during a 24-hour interval or no stools or only formed stools during a 48-hour interval. The median TLUS was 46 hours for rifamycin vs. 68 hours for placebo. Percent clinical cures were 81.4% compared to 56.9%, respectively.
In trial 2, the authors compared rifamycin (n = 420) to ciprofloxacin (500 mg twice daily) for three days (n = 415).4,6 TLUS was 44.3 hours for rifamycin compared to 40.3 hours for ciprofloxacin, demonstrating noninferiority. Clinical cure rates were 85.0% compared to 84.8%. The risk of colonization by extended spectrum beta-lactamase-producing E. coli was more likely with ciprofloxacin than rifamycin. Adverse reactions associated with rifamycin in these trials were constipation (3.5%) and headache (3.3%).1
TD is the most common travel-related illness, affecting 10-40% of travelers.7 High-risk areas are Asia, Africa, the Middle East, Mexico, and Central and South America. The most common bacterial pathogens are enterotoxigenic and enteroaggregative E. coli. Less common pathogens include mucosa-invasive Campylobacter jejuni, Shigella spp, and Salmonella spp.8 The International Society of Travel Medicine recommends azithromycin, ciprofloxacin, and rifaximin as options for moderate to severe TD, with azithromycin as the preferred agent to treat severe TD.9 A fluoroquinolone (e.g., ciprofloxacin) and rifaximin are options if fluoroquinolone-resistant E. coli or invasive bacteria are not suspected.9
Rifamycin provides another potential option for noninvasive TD due to E. coli. Rifamycin has been shown to be noninferior to ciprofloxacin, but comparative efficacy to rifaximin has not been published. Azithromycin and ciprofloxacin can be given as a single dose (unless symptoms have not resolved in 24 hours) compared to a three-day course for rifaximin and rifamyin.9 Rifamycin is expected to be available the first quarter of 2019.
- Aries Pharmaceuticals, Inc. Aemcolo Prescribing Information, November 2018. Available at: . Accessed Dec. 20, 2019.
- Nardelli S, Pisani LF, Tontini, GE et al. MMX® technology and its applications in gastrointestinal diseases. Therap Adv Gastroenterol 2017;10:545-552.
- Lin SW, Lin CJ, Yang JC. Rifamycin SV MMX for the treatment of traveler’s diarrhea. Expert Opin Pharmacother 2017;18:1269-1277.
- Steffen R, Jiang ZD, Gracias Garcia ML, et al. Rifamycin SV-MMX® for treatment of travelers’ diarrhea: Equally effective as ciprofloxacin and not associated with the acquisition of multi-drug resistant bacteria. J Travel Med 2018; Nov 20. doi: 10.1093/jtm/tay116. [Epub ahead of print].
- ClinicalTrials.gov. Study to evaluate safety and efficacy of rifamycin SV Multi-Matrix system (MMX) for the treatment of traveler’s diarrhea (TD). Available at: . Accessed Dec. 20, 2018.
- ClinicalTrials.gov. Rifamycin SV-MMX® tablets versus ciprofloxacin capsules in acute traveller’s diarrhoea (ERASE). Available at: . Accessed Dec. 20, 2018.
- U.S. Food & Drug Administration. FDA approves new drug to treat travelers’ diarrhea. Nov. 16, 2018. Available at: . Accessed Dec. 20, 2018.
- Diptyanusa A, Ngamprasertchai T, Piyaphanee W. A review of antibiotic prophylaxis for traveler’s diarrhea: Past to present. Trop Dis Travel Med Vaccines 2018; Nov 7;4:14. doi: 10.1186/s40794-018-0074-4. eCollection 2018.
- Riddle MS, Connor BA, Beeching NJ, et al. Guidelines for the prevention and treatment of travelers’ diarrhea: A graded expert panel report. J Travel Med 2017;24(suppl_1):S57-S74.