What are the possible side effects of Xifaxin (rifaximin)?

Possible Side Effects of Rifaximin (Xifaxin)

Rifaximin (Xifaxin) is generally well-tolerated with a favorable safety profile due to its minimal systemic absorption, with headache being the most common side effect in most indications.

Common Side Effects by Indication

Travelers' Diarrhea (200 mg three times daily for 3 days)

• Headache (10% vs 9% with placebo) 1

Irritable Bowel Syndrome with Diarrhea (550 mg three times daily for 14 days)

• Nausea (3% vs 2% with placebo) 1
• Elevated ALT (2% vs 1% with placebo) in retreatment studies 1
• Constipation (most common side effect with 5-HT3 receptor antagonists used for IBS-D) 2

Hepatic Encephalopathy (550 mg twice daily)

More common side effects (≥5%) include:

• Peripheral edema (15% vs 8% with placebo) 1
• Nausea (14% vs 13% with placebo) 1
• Dizziness (13% vs 8% with placebo) 1
• Fatigue (12% vs 11% with placebo) 1
• Ascites (11% vs 9% with placebo) 1
• Muscle spasms (9% vs 7% with placebo) 1
• Pruritus (9% vs 6% with placebo) 1
• Abdominal pain (9% vs 8% with placebo) 1
• Anemia (8% vs 4% with placebo) 1

Rare but Serious Side Effects

• Clostridium difficile-associated colitis (reported in post-marketing surveillance) 1, 2

• Hypersensitivity reactions including:

  • Exfoliative dermatitis
  • Rash
  • Angioneurotic edema (swelling of face and tongue, difficulty swallowing)
  • Urticaria
  • Flushing
  • Pruritus
  • Anaphylaxis (can occur within 15 minutes of administration) 1

• Severe cutaneous adverse reactions in patients with cirrhosis:

  • Stevens-Johnson syndrome (SJS)
  • Toxic epidermal necrolysis (TEN) 1

• Musculoskeletal disorders:

  • Rhabdomyolysis (reported in patients with cirrhosis, with or without concomitant statin use) 1
  • Myalgia 1

Drug Interactions

1. P-glycoprotein inhibitors (e.g., cyclosporine):

   • May significantly increase systemic exposure to rifaximin
   • Use with caution, especially in patients with hepatic impairment 1

2. Warfarin:

   • Changes in INR have been reported
   • Monitor INR and prothrombin time
   • Dose adjustment of warfarin may be needed 1

3. CYP3A4 substrates:

   • In vitro studies suggest rifaximin may induce CYP3A4
   • Clinical significance unclear, especially in patients with reduced liver function 1

Safety Advantages

Rifaximin has several safety advantages compared to other antibiotics:

• Minimal systemic absorption (less than 0.4%) 3
• Low risk of developing bacterial resistance 4, 5
• Limited cross-resistance with other antimicrobials 4
• Safety profile generally comparable to placebo in clinical trials 6
• Suitable for long-term use in hepatic encephalopathy with continued effectiveness and good safety profile over 24+ months 7

Special Considerations

• Hepatic impairment: Use with caution in patients with severe hepatic impairment (Child-Pugh Class C) 7
• Cost: High cost may impact long-term adherence 7
• Monitoring: For long-term use, monitoring for development of resistance may be appropriate 5

When to Discontinue

Discontinue rifaximin at the first signs or symptoms of:

• Severe cutaneous adverse reactions
• Other signs of hypersensitivity 1

Rifaximin's unique pharmacokinetic properties (poor absorption, bile solubility, low water solubility) contribute to its favorable safety profile and targeted action in the gastrointestinal tract, making it generally well-tolerated for both short-term and long-term use 3, 5.