XIFAXAN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for XIFAXAN (XIFAXAN).
Rifaximin is a non-systemic, gut-selective antibiotic that inhibits bacterial RNA synthesis by binding to the beta-subunit of bacterial DNA-dependent RNA polymerase, thereby reducing bacterial overgrowth and altering gut microbiota composition.
| Metabolism | Rifaximin is minimally absorbed (<0.4%) following oral administration; the small absorbed fraction undergoes hepatic metabolism via CYP3A4 and is excreted in feces. It is not significantly metabolized systemically. |
| Excretion | Rifaximin is primarily eliminated unchanged in feces via biliary excretion (approximately 97% of an oral dose). Renal excretion of unchanged drug accounts for <0.4% of the dose. Fecal elimination is the major route. |
| Half-life | The terminal elimination half-life for rifaximin after oral administration ranges from 1.8 to 10 hours, with a mean of approximately 6 hours. The half-life is extended in hepatic impairment due to reduced clearance, and no dosage adjustment is recommended for renal impairment. |
| Protein binding | Rifaximin is highly protein bound (approximately 67-71%) in human plasma, primarily to albumin. Binding is independent of concentration. |
| Volume of Distribution | The apparent volume of distribution (Vd/F) after oral administration ranges from 15 to 60 L (approximately 0.2-0.9 L/kg), with a mean of about 30 L. This relatively low Vd indicates limited extravascular distribution, consistent with its gut-selective action and minimal systemic absorption. |
| Bioavailability | Oral bioavailability is very low, approximately 0.4% due to poor absorption and extensive first-pass metabolism. Systemic absorption is negligible, with rifaximin largely confined to the gastrointestinal tract. |
| Onset of Action | For traveler's diarrhea, clinical response (resolution of loose stools) can be seen within 24-48 hours. For hepatic encephalopathy reduction, onset of reduction in overt HE episodes is typically observed within 7-14 days. Onset of action is dependent on the indication and route (oral only). |
| Duration of Action | Duration of action for treatment of traveler's diarrhea is the course of therapy (3 days). For hepatic encephalopathy prevention, rifaximin is dosed continuously (400 mg twice daily) to maintain remission; the duration of action per dose is approximately 12 hours, supporting twice-daily administration. |
550 mg orally twice daily for traveler's diarrhea; 550 mg orally three times daily for hepatic encephalopathy.
| Dosage form | TABLET |
| Renal impairment | No dosage adjustment required for renal impairment. Caution in severe renal impairment (CrCl <30 mL/min) due to limited data. |
| Liver impairment | No dosage adjustment recommended for Child-Pugh classes A, B, or C. Monitor for adverse effects in severe hepatic impairment. |
| Pediatric use | Not approved for use in pediatric patients; safety and efficacy not established. |
| Geriatric use | No specific dosage adjustment; use with caution due to potential age-related renal and hepatic function decline. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for XIFAXAN (XIFAXAN).
| Breastfeeding | Rifaximin is excreted in human breast milk in very low amounts (M/P ratio not established; estimated <0.1% of maternal dose). Due to minimal absorption, risk to the nursing infant is likely low. Caution is advised; use only if clearly needed. |
| Teratogenic Risk | Rifaximin (XIFAXAN) is minimally absorbed orally (<0.4%), resulting in negligible systemic exposure. Animal studies show no evidence of teratogenicity at clinically relevant doses. Human data are limited; however, due to minimal absorption, the risk of fetal harm is considered low across all trimesters. No specific trimester risks have been identified. |
■ FDA Black Box Warning
None
| Serious Effects |
["Hypersensitivity to rifaximin or any rifamycin antimicrobial agent","Travelers' diarrhea complicated by fever or bloody stools"]
| Precautions | ["Hypersensitivity reactions (e.g., angioedema, anaphylaxis)","Clostridium difficile-associated diarrhea (CDAD) reported with nearly all antibacterial agents","Use with caution in patients with severe hepatic impairment (Child-Pugh C) due to limited data","Potential for development of bacterial resistance with prolonged use"] |
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| Fetal Monitoring | No specific maternal or fetal monitoring is required beyond routine prenatal care. Monitor for gastrointestinal effects (e.g., diarrhea) in the mother. |
| Fertility Effects | Animal studies at doses up to 300 mg/kg/day (approximately 120 times the human dose) showed no impairment of fertility. No human data on fertility effects are available; based on minimal systemic absorption, significant impact on fertility is unlikely. |