RIFAXIMIN
Clinical safety rating: safe
Animal studies have demonstrated safety
Rifaximin is a non-aminoglycoside, semi-synthetic antibiotic derived from rifamycin that inhibits bacterial RNA synthesis by binding to the beta-subunit of bacterial DNA-dependent RNA polymerase, thereby blocking transcription.
| Metabolism | Rifaximin is minimally absorbed (<0.4%) and undergoes extensive metabolism in the liver via CYP3A4 to inactive metabolites (primarily desacetylrifaximin and rifaximin hydrolase products). It is not significantly metabolized by other CYP isoforms. |
| Excretion | Rifaximin is primarily eliminated in feces as unchanged drug (>96% of an oral dose). Renal excretion is negligible (<0.4%). Biliary excretion is minimal due to poor systemic absorption. |
| Half-life | The terminal elimination half-life is approximately 1.8 to 2.5 hours in patients with normal hepatic function. Due to negligible systemic absorption, the half-life has limited clinical relevance; drug action is largely confined to the gastrointestinal tract. |
| Protein binding | 67% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | The apparent volume of distribution (Vd) is approximately 1.2 L/kg. This large value reflects extensive tissue binding or distribution in the gastrointestinal tract; however, due to poor oral absorption, systemic distribution is minimal and the Vd parameter has limited clinical significance. |
| Bioavailability | Oral bioavailability is extremely low (<0.4%) due to minimal systemic absorption. The drug acts locally in the gastrointestinal tract. |
| Onset of Action | For traveler's diarrhea: onset of clinical improvement within 24 hours of the first dose. For hepatic encephalopathy: reduction in symptoms typically within 2–4 days of continuous dosing. |
| Duration of Action | The intraluminal antimicrobial activity persists for the duration of dosing (typically 3 days for traveler's diarrhea or 14 days for hepatic encephalopathy). Systemic effects are negligible; duration of action is limited by drug presence in the gut lumen. |
550 mg orally three times daily for 14 days for travelers' diarrhea; 200 mg orally three times daily for 3 days for irritable bowel syndrome with diarrhea; 400 mg orally three times daily for 7 days for hepatic encephalopathy.
| Dosage form | TABLET |
| Renal impairment | No adjustment required for any degree of renal impairment as rifaximin is minimally absorbed (<0.4%) and undergoes extensive fecal excretion. |
| Liver impairment | No adjustment recommended for Child-Pugh A or B; for Child-Pugh C, use with caution due to limited data, but no specific dose reduction is established. |
| Pediatric use | For travelers' diarrhea in children ≥12 years: 200 mg orally three times daily for 3 days; for hepatic encephalopathy in children ≥12 years: 400 mg orally three times daily; for infants and younger children, safety and efficacy not established. |
| Geriatric use | No specific dose adjustment required; use standard adult dosing. Monitor for adverse effects due to potential age-related decline in hepatic/renal function, though no significant accumulation expected. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
No significant drug interactions For travelers' diarrhea and hepatic encephalopathy not systemic infections.
| Breastfeeding | Excretion in human milk unknown; due to low systemic absorption, exposure to infant is likely minimal. Caution advised; no M/P ratio available. |
| Teratogenic Risk | Animal studies show no evidence of teratogenicity; no adequate human studies in pregnant women. Minimal systemic absorption (<0.4%) suggests low fetal exposure. Risk cannot be ruled out. |
| Fetal Monitoring |
■ FDA Black Box Warning
None.
| Common Effects | hepatic encephalopathy |
| Serious Effects |
["Hypersensitivity to rifaximin, any rifamycin (e.g., rifampin, rifabutin), or any component of the formulation."]
| Precautions | ["Clostridioides difficile-associated diarrhea: Antibiotic use may promote overgrowth of C. difficile.","Systemic absorption: Minimal, but caution in severe hepatic impairment due to increased exposure.","Hypersensitivity reactions: Rash, urticaria, and anaphylaxis have been reported.","Superinfection: Prolonged use may result in overgrowth of nonsusceptible organisms."] |
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| No specific fetal monitoring required. Monitor for maternal adverse effects (e.g., Clostridioides difficile-associated diarrhea) as with other antibiotics. |
| Fertility Effects | No studies on human fertility; animal studies show no impairment of fertility. |