Generic Name

Xifaxan

Mechanism

• Selective ribosomal binding: Rifaximin binds to the β‑subunit of bacterial DNA‑dependent RNA polymerase, inhibiting transcription of essential bacterial genes.
• Minimal systemic absorption: < 0.4 % bioavailability ensures the drug remains confined to the gut lumen.
• Activity spectrum: Potent against gram‑positive and gram‑negative anaerobes, *Clostridioides difficile*, *Helicobacter pylori*, and enteric viruses (e.g., norovirus).

Pharmacokinetics

• Absorption: Virtually none systemically; <1 % plasma levels.
• Distribution: High concentration in intestinal mucosa; negligible tissue penetration.
• Metabolism: Occurs primarily in the gut via bacterial enzymes; no hepatic first‑pass metabolism.
• Elimination: Fecal excretion of unchanged drug; 98‑99 % recovered in stool.
• Half‑life: Terminal plasma half‑life ~2 h; luminal half‑life 3–5 h.
• Drug interactions: Minimal CYP modulation; no clinically significant interactions with most systemic drugs.

Indications

• Recurrent hepatic encephalopathy (HE): 10 mg IV or oral 550 mg PO, 3 times daily for 2‑4 weeks, then 550 mg PO daily for 6–12 months.
• Irritable bowel syndrome – diarrhea predominant (IBS‑D): 550 mg PO twice daily for 14 days.
• Traveler’s diarrhea: 550 mg PO every 12 h for 3 days (pre‑travel or at onset).
• Norovirus gastroenteritis: 550 mg PO twice daily for 2‑3 days (off‑label, early evidence).
• Weakened or immunocompromised patients with *C. difficile* colitis (off‑label, adjunctive).
• Post‑operative ileus (off‑label): 550 mg PO daily (clinical judgment).

Contraindications

• Allergy to rifamycins (e.g., rash, urticaria, anaphylaxis).
• Severe hepatic impairment (CYP‑enzyme limited; minimal hepatic metabolism, but caution if cirrhosis).
• Concurrent rifampin therapy: Antagonistic effect, avoid.
• Pregnancy: Category C; use only if no alternatives, counsel on potential fetal risk.
• Neutropenia: Reduced bacterial clearance, monitor counts.
• Drug‑drug interactions: Rare; monitor if concomitant cyclosporine, gemfibrozil, or carbamazepine.

Dosing

• Mixing: Tablet should be taken whole; crushing increases systemic absorption risk.
• Food: No food restriction; can take with meals.

Adverse Effects

Common (≤10 %)
• Flatulence, abdominal discomfort, cramping
• Nausea, mild GI upset
• Headache, dizziness

Serious (≤1 %)
• Hypersensitivity rash, anaphylaxis (rare)
• Esophagitis (high oral dose)
• Increase in serum alkaline phosphatase in HE (monitor).

Medication‑induced nephrotoxicity not reported; drug remains gut‑localized.

Monitoring

• Hepatic encephalopathy: Neurocognitive tests (PHES, Cochin), ammonia levels, serum albumin, bilirubin.
• IBS‑D: Symptom diary, stool frequency & consistency.
• Adverse effects: Physical exam for rash or GI distress; CBC/creatinine every 4 weeks (if concurrent nephrotoxic drugs).
• Drug levels: Not clinically required due to negligible systemic exposure.

Clinical Pearls

• Gut‑centric therapy: Because rifaximin remains in the lumen, dosing once or twice daily suffices, reducing systemic side effects common to other antibiotics.
• Synergy with lactulose: In HE, rifaximin plus lactulose significantly lowers recurrence versus lactulose alone.
• Rapid onset: Patients often report symptom relief within 12–24 h for IBS‑D, a key differentiator from other agents (e.g., linaclotide).
• Resistance profile: Up to 10 % of *E. coli* isolates show inducible resistance; retreatment is limited but LI‑ricaximin has no cross‑resistance with other rifamycins.
• Off‑label nitroimidazole‑resistant *C. difficile*: Rifaximin may eradicate low‑level vegetative forms; pair with vancomycin or fidaxomicin if needed.
• Paediatric use: Approx. 300 mg PO BID may be effective for IBS‑D; robust adult data support dosing equivalence.
• Pregnancy + breastfeeding: Data sparse; drug is not excreted into breast milk in significant amounts; decision should weigh benefits versus unknown risks.

Take‑home: Xifaxan’s minimal systemic absorption, gut‑specific action, and favorable tolerability make it first‑line for both infectious and functional GI disorders, with excellent patient adherence due to concise dosing regimens.