Potential Complications of Xifaxan (Rifaximin)
Xifaxan is generally well-tolerated with minimal systemic absorption, but clinicians must monitor for Clostridium difficile-associated diarrhea (CDAD), hypersensitivity reactions, and increased systemic exposure in patients with severe hepatic impairment. 1
Serious Complications Requiring Immediate Attention
Clostridium difficile-Associated Diarrhea (CDAD)
- CDAD can occur with rifaximin use and may range from mild diarrhea to fatal colitis, similar to other antibacterial agents 1
- This complication can develop even up to 2 months after rifaximin administration has been discontinued 1
- If CDAD is suspected, discontinue rifaximin immediately and initiate appropriate fluid/electrolyte management, protein supplementation, and C. difficile-directed antibiotic therapy 1
- Recent studies in hepatic encephalopathy patients found that C. difficile infection rates were not increased with long-term rifaximin compared to controls 2
Hypersensitivity Reactions
- Rifaximin is contraindicated in patients with hypersensitivity to rifaximin, any rifamycin antimicrobial agents, or components of the formulation 1
- Serious reactions include:
- These reactions can occur as early as 15 minutes after drug administration 1
Complications in Special Populations
Severe Hepatic Impairment (Child-Pugh Class C)
- Patients with severe hepatic impairment have significantly increased systemic rifaximin exposure 1
- Clinical trials were limited to patients with MELD scores <25, with only 8.6% having MELD scores >19 1
- Exercise caution when administering rifaximin to Child-Pugh Class C patients due to increased systemic absorption 1
Drug Interactions with P-glycoprotein Inhibitors
- Concomitant use of P-glycoprotein (P-gp) inhibitors like cyclosporine can substantially increase systemic rifaximin exposure 1
- In patients with hepatic impairment, the combination of reduced metabolism and P-gp inhibition creates an additive effect that further increases systemic exposure 1
- Exercise caution when combining rifaximin with P-gp inhibitors 1
Common Adverse Events (Not Life-Threatening)
Hepatic Encephalopathy Treatment (550 mg twice daily)
The most common adverse reactions occurring in ≥5% of patients include: 1
- Peripheral edema (15%)
- Nausea (14%)
- Dizziness (13%)
- Fatigue (12%)
- Ascites (11%)
- Muscle spasms (9%)
- Pruritus (9%)
Long-Term Safety Profile
- Long-term rifaximin use (≥24 months) does not increase the rate of adverse events compared to short-term use 3
- No increase in infection rates, including C. difficile, or development of bacterial antibiotic resistance was observed with prolonged exposure (median 427 days) 3
- The safety profile remains consistent with long-term administration 3
Clinical Pitfalls to Avoid
Inappropriate Use Leading to Treatment Failure
- Do not use rifaximin for diarrhea complicated by fever or bloody stools 1
- Rifaximin is not effective against invasive pathogens including Campylobacter jejuni, Shigella spp., and Salmonella spp. 1
- Discontinue rifaximin if diarrhea worsens or persists beyond 24-48 hours and consider alternative antibiotics 1
Development of Drug-Resistant Bacteria
- Prescribing rifaximin without proven or strongly suspected bacterial infection increases the risk of drug-resistant bacteria 1
- This is particularly relevant when using rifaximin for travelers' diarrhea prophylaxis 1
Monitoring Recommendations
- Assess for signs of CDAD in any patient presenting with diarrhea during or after rifaximin therapy 1
- Monitor for hypersensitivity reactions, especially during initial doses 1
- In hepatic encephalopathy patients, monitor clinical laboratory parameters regularly during long-term therapy 3
- Evaluate hepatic function (MELD score, Child-Pugh class) before initiating therapy in cirrhotic patients 1