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. |
| Molecular Weight | 785.9 |
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 | Limited human data; animal studies show no evidence of teratogenicity at clinically relevant doses. Use only if clearly needed. |
| 2nd trimester | No known fetal risk based on systemic absorption <0.4% and lack of placental transfer data; avoid if possible due to limited data. |
| 3rd trimester | Not expected to cause fetal harm due to minimal systemic absorption; consider risk-benefit. |
Clinical note
No significant drug interactions For travelers' diarrhea and hepatic encephalopathy not systemic infections.
| Placental transfer | Negligible due to minimal systemic absorption (<0.4%); no direct evidence of placental transfer. |
| Breastfeeding | Minimal systemic absorption (<0.4%) suggests negligible excretion into breast milk; caution with diarrhea-associated dehydration in infant. |
■ FDA Black Box Warning
None.
| Common Effects | hepatic encephalopathy |
| Serious Effects |
Hypersensitivity to rifaximin or any rifamycinBowel obstructionActive intestinal perforation
| 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. |
| Food/Dietary | No clinically significant food interactions. Take with or without food. Avoid alcohol as it may worsen hepatic encephalopathy in liver disease patients. |
Loading safety data…
| Lactation Rating |
| L2 (Probably Compatible) |
| 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 | 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. |
| Clinical Pearls | Rifaximin is a non-absorbable (<0.4%) rifamycin antibiotic used for traveler's diarrhea, irritable bowel syndrome with diarrhea (IBS-D), and hepatic encephalopathy. For IBS-D, treat for 14 days; retreatment is allowed if symptoms recur. For hepatic encephalopathy, maintain dose (550 mg BID) during remission. Monitor for Clostridioides difficile colitis despite minimal systemic absorption. Avoid in patients with inflammatory bowel disease (risk of pseudomembranous colitis). Not effective for diarrhea caused by invasive pathogens (e.g., Campylobacter, Shigella, Salmonella). |
| Patient Advice | Take rifaximin exactly as prescribed; for traveler's diarrhea, it shortens duration but not fill the course if symptoms resolve. · Do not use for diarrhea with fever or bloody stools – seek medical care. · For IBS-D, retreatment may be needed if symptoms recur. · For hepatic encephalopathy, continue maintenance dose even if feeling well to prevent recurrence. · Common side effects include nausea, flatulence, and headache; rare allergic reactions. · Report severe or persistent diarrhea during or after treatment. · Rifaximin may cause urine discoloration (reddish) – harmless. |