Side Effects of Xifaxan (Rifaximin)
Rifaximin (Xifaxan) has a favorable safety profile with adverse events similar to placebo, with the most common side effects being peripheral edema, nausea, dizziness, fatigue, and ascites in hepatic encephalopathy patients, and headache, ALT elevation, and nausea in IBS-D patients. 1, 2
Common Side Effects by Indication
Hepatic Encephalopathy (550 mg twice daily)
- Most common (≥10%): 2
- Peripheral edema
- Nausea
- Dizziness
- Fatigue
- Ascites
Irritable Bowel Syndrome with Diarrhea (550 mg three times daily)
- Most common (≥2%): 2
- ALT elevation (liver enzyme)
- Nausea
Travelers' Diarrhea (200 mg three times daily)
- Most common (≥2%): 2
- Headache
Serious Side Effects
Hypersensitivity Reactions
- Rifaximin is contraindicated in patients with hypersensitivity to rifaximin, any rifamycin antimicrobial agents, or any components of the formulation 2
- Severe hypersensitivity reactions may include:
- Exfoliative dermatitis
- Angioneurotic edema
- Anaphylaxis 2
Clostridium difficile-Associated Diarrhea
- Like all antibiotics, rifaximin can potentially cause Clostridium difficile-associated diarrhea (CDAD)
- Severity ranges from mild diarrhea to fatal colitis
- Evaluate if diarrhea occurs after therapy or does not improve/worsens during therapy 2
Safety Profile
Rifaximin has a particularly favorable safety profile compared to many other medications due to its minimal systemic absorption (<0.4%), making it especially suitable for patients with liver disease 3. Clinical trials have demonstrated:
- Adverse event profile similar to placebo 1
- No significant increase in drug-related adverse events, serious adverse events, or drug-related adverse events resulting in study discontinuation compared to placebo 1
- No increased risk of Clostridium difficile infection with long-term use compared to control groups 3
Special Precautions
Hepatic Impairment
- Use with caution in patients with severe hepatic impairment (Child-Pugh Class C)
- Increased systemic exposure may occur in severe liver disease
- Clinical trials were limited to patients with MELD scores <25 2
Drug Interactions
- P-glycoprotein (P-gp) inhibitors: Caution with concomitant use of P-gp inhibitors like cyclosporine, which can substantially increase systemic exposure to rifaximin 2
- Warfarin: Monitor INR and prothrombin time; dose adjustment of warfarin may be needed to maintain target INR range 2
Limitations of Use
- Not effective for travelers' diarrhea complicated by fever or blood in stool
- Not effective against Campylobacter jejuni infections
- Effectiveness against Shigella spp. and Salmonella spp. has not been proven 2
Pregnancy Considerations
- May cause fetal harm; use during pregnancy only if potential benefit justifies potential risk to the fetus 2
Despite being an antibiotic, rifaximin's minimal systemic absorption contributes to its excellent safety profile, making it well-tolerated in most patients across its approved indications.