Generic Name

Rifaximin

Mechanism

• Bacteriostatic inhibition of bacterial RNA synthesis
• Binds reversible to the β‑subunit of DNA‑dependent RNA polymerase
• Blocks transcription of essential bacterial genes → ↓ protein synthesis
• Intestinal‑centric activity
• Extremely low systemic absorption (<0.4 %); concentrates in the gut lumen
• Target colon and small‑bowel microbiota, causing minimal systemic exposure

Pharmacokinetics

• Absorption: < 0.4 % systemic uptake; plasma levels < 0.0004 mg/L
• Distribution: Lymph:plasma ratio ~ 1:3 (high intestinal concentrations)
• Metabolism & Elimination: Primarily conjugated by UDP‑glucuronosyltransferase (UGT) (hepatic); excreted in feces (≈ 80 %) and bile (≈ 20 %)
• Half‑life: ~ 8 h (lumen); ~ 4 h in plasma
• Drug–drug interactions:
• Minor CYP3A4 induction; few clinically significant interactions
• Contraindicated with rifampin‑based therapy (competitive inhibition of UGT).

Indications

• IBS‑D – short‑course therapy (2–4 weeks) to reduce stool frequency & abdominal pain
• Recurrent hepatic encephalopathy – prevent recurrence in cirrhotic patients
• Travel‑associated travelers’ diarrhea (off‑label) – 400 mg BID for 7–10 days
• Other uses (off‑label):
• Small intestinal bacterial overgrowth (SIBO)
• Cytomegalovirus colitis (in conjunction with antivirals)

Contraindications

• Allergy to rifamycins or related compounds
• Severe hepatic impairment or cirrhosis with active liver failure (risk of hepatotoxicity)
• Pregnancy: Category B – limited data; use only if benefits outweigh risks
• Breastfeeding: excretion in milk, avoid if possible
• Caution: avoid in patients with antibiotic‑resistant bacterial flora (e.g., MRSA) on the gastrointestinal tract – resistance may develop

Dosing

• Administer with a full glass of water; may be taken on an empty stomach.
• Tolerate well in patients with renal impairment; no dose adjustment needed.

Adverse Effects

Common (≥ 5 %)
• GI upset: nausea, abdominal pain, bloating
• Headache, dizziness
• Flatulence, constipation

Serious (≤ 1 %)
• Hepatotoxicity: elevated ALT/AST, cholestatic jaundice (monitor LFTs)
• Hypersensitivity: rash, anaphylaxis (rare)
• Bacterial dysbiosis → overgrowth of resistant organisms (e.g., Clostridioides difficile)

Monitoring

• Baseline & periodic liver function tests (ALT, AST, bilirubin) while on HE therapy
• CBC only if concern for neutropenia (rare)
• Renal function: not required; no dose adjustment in CKD
• Symptom diary (IBS-D): stool frequency, consistency, pain score

Clinical Pearls

• Non‑absorbable strength: minimizes systemic side effects – ideal for patients with multiple comorbidities.
• Rapid onset: benefits visible within 48 h – useful for acute HE precipitating events.
• Add‑on therapy: with lactulose or probiotics for HE improves outcomes vs. monotherapy.
• Resistance caution: avoid routine use for uncomplicated travel diarrhea; risk of selecting resistant enteric flora.
• Patient education: advise to take on an empty stomach for optimal gut concentration; do not exceed prescribed duration to limit resistance.
• Drug safety: safe dose in pregnancy (Category B) but only if benefits justify use; discontinue breastfeeding.

Key Takeaway: Rifaximin’s localized activity, excellent safety profile, and proven efficacy make it a first‑line oral therapy for IBS‑D and a cornerstone agent for hepatic encephalopathy prevention.