1.1. Adults
Rifaximin is not indicated for treatment of systemic infections as the drug is minimally absorbed after oral administration [1, 2].
Rifaximin, a derivative of rifampin, is as antibiotic with minimal systemic absorption with bactericidal activity against aerobic and anaerobic gram-positive and gram-negative microorganisms. Rifaximin is FDA-approved for use in managing travelers’ diarrhea due to noninvasive strains of Escherichia coli (E. coli) in adults and children 12 years of age and older and should not be used in diarrhea due to pathogens other than E. coli or complicated by fever or blood in the stool [1-9].
Rifaximin is also FDA-approved for reducing risk of overt hepatic encephalopathy (HE) recurrence in patients 18 years of age and older [1, 2]. In a randomized, double-blind, placebo-controlled trial over a six-month time period, Bass and cohorts evaluated rifaximin safety and efficacy to maintain remission from HE episodes in 299 adult outpatients receiving concurrent lactulose therapy with a recent history of recurrent, overt HE. Results showed that the risk of a breakthrough HE episode was significantly lower with rifaximin therapy compared to placebo [hazard ratio (HR), 0.42; 95% confidence interval (CI), 0.28 to 0.64; P less than 0.001]. The risk of hospitalization was also significantly lower in rifaximin-treated patients compared to those receiving placebo (HR, 0.50; 95% CI, 0.29 to 0.87; P = 0.01) [10].
In May 2015, rifaximin gained FDA approval for treating irritable bowel syndrome with diarrhea (IBS-D) in adults [1, 2]. Pimentel and cohorts compared rifaximin efficacy to placebo in two separate trials involving 1260 patients with IBS without constipation. Patients were randomly administered rifaximin 550 mg three times daily or placebo for 14 days, and then followed for 10 weeks. Results showed that rifaximin was significantly better than placebo in relieving IBS symptoms (e.g., bloating; abdominal pain; loose, watery stools) [11]. Data have also shown that rifaximin-treated patients respond better than those receiving placebo with a first recurrence of IBS-D [12]. A few small studies have evaluated rifaximin use in irritable bowel syndrome/Crohn’s disease. Gionchetti and cohorts assessed rifaximin efficacy compared to placebo in 26 ulcerative colitis patients unresponsive to steroid therapy and found that while overall clinical response was not significantly better than placebo, rifaximin-treated patients showed a significant reduction in stool frequency and rectal bleeding [13]. Prantera and colleagues evaluated rifaximin dosing and efficacy compared to placebo in 83 Crohn’s disease patients and found no statistical difference in clinical response or clinical remission but observed a significantly reduced number of treatment failures in rifaximin-treated patients [14].
Although not FDA-approved, rifaximin has shown some efficacy in treatment of hepatic encephalopathy and infectious diarrhea due to Salmonella and noninvasive Shigella [15-25]. Use of rifaximin for the treatment of infectious diarrhea due to Campylobacter spp. is extremely limited, and generally not recommended as a first or second line agent [18, 26, 27]. One small, open-label, randomized trial in 54 Korean patients with liver cirrhosis evaluated rifaximin therapy in hepatic encephalopathy and found rifaximin comparable to lactulose in improving blood ammonia, flapping tremor and mental status [21]. Similarly, Mas et al, in a randomized, double-blind, double-dummy trial, compared rifaximin to lactitol in 103 acute hepatic encephalopathy patients and found rifaximin as effective as lactitol in managing hepatic encephalopathy episodes. Investigators found rifaximin significantly better than lactitol in improving ammonia levels and EEG grade, which led to better portal-systemic encephalopathy scores in rifaximin-treated patients [22]. Miglio and cohorts assessed rifaximin benefit and tolerability when compared to neomycin in 49 cirrhosis patients with hepatic encephalopathy and found rifaximin as effective as neomycin in improving neuropsychiatric signs and blood ammonia levels [23].
Table 1 summarizes adult oral recommended maximum rifaximin dosages for FDA-approved uses. Dosages exceeding these recommendations will be reviewed.
| Drug Name | Dosage Form/Strength | Treatment Indication | Maximum Recommended Dosage |
|---|---|---|---|
| rifaximin (Xifaxan) | 200 mg tablets | travelers’ diarrhea (due to noninvasive E. coli strains) | 200 mg three times daily (600 mg/day) x 3 days |
| rifaximin (Xifaxan) | 550 mg tablets | reduce the risk of HE recurrence | 550 mg twice daily (1100 mg/day) |
| 550 mg tablets | IBS-D | 550 mg 3 times daily for 14 days; retreatment for patients with symptom recurrence may occur up to 2 times with same dosage regimen |
Legend:
- HE = hepatic encephalopathy
- IBS-D = irritable bowel syndrome with diarrhea