Side Effects of Rifaximin
Rifaximin has a favorable safety profile with adverse events occurring at rates similar to placebo in clinical trials, making it one of the safest antibiotics for gastrointestinal conditions. 1, 2
Common Side Effects by Indication
Hepatic Encephalopathy (550 mg twice daily)
The most frequently reported adverse events occurring in ≥5% of patients include: 2
- Peripheral edema (15% vs 8% placebo)
- Nausea (14% vs 13% placebo)
- Dizziness (13% vs 8% placebo)
- Fatigue (12% vs 11% placebo)
- Ascites (11% vs 9% placebo)
- Muscle spasms (9% vs 7% placebo)
- Pruritus (9% vs 6% placebo)
- Abdominal pain (9% vs 8% placebo)
- Anemia (8% vs 4% placebo)
- Depression (7% vs 5% placebo)
Irritable Bowel Syndrome with Diarrhea (550 mg three times daily)
The adverse event profile is minimal, with only the following occurring at ≥2% and higher than placebo: 2
- Nausea (3% vs 2% placebo)
- ALT increased (2% vs 1% placebo)
Travelers' Diarrhea (200 mg three times daily)
The most common adverse event was: 2
- Headache (10% vs 9% placebo) - this was the most common adverse event across all indications 1
Serious but Rare Adverse Events
Clostridium difficile Infection
While theoretically concerning with any antibiotic, recent studies demonstrate that C. difficile infection rates are not increased with rifaximin compared to placebo. 1 The FDA label includes a warning about C. difficile-associated diarrhea (CDAD), but this appears to be a class effect warning rather than a specific rifaximin concern. 2
Hypersensitivity Reactions
Rifaximin is contraindicated in patients with hypersensitivity to rifamycin agents. Reported reactions include: 2
- Exfoliative dermatitis
- Angioneurotic edema (swelling of face and tongue, difficulty swallowing)
- Urticaria
- Anaphylaxis (occurring as early as 15 minutes after administration)
Severe Cutaneous Adverse Reactions
Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported in patients with cirrhosis. 2 Discontinue rifaximin immediately at the first signs of severe cutaneous reactions.
Rhabdomyolysis
Cases have been reported in patients with cirrhosis, both with and without concomitant statin use. 2
Long-Term Safety Profile
Long-term treatment (up to 24 months) with rifaximin shows no increase in adverse event rates compared to short-term use. 3 In a study with 510.5 person-years of exposure, the safety profile remained consistent with the original 6-month trial, with no increase in infection rates or development of bacterial antibiotic resistance. 3
Important Safety Considerations
Drug Interactions
Concomitant use with P-glycoprotein inhibitors (such as cyclosporine) can substantially increase systemic rifaximin exposure. 2 Exercise caution when combining these medications, particularly in patients with hepatic impairment where the effect may be additive. 2
Hepatic Impairment
Caution is warranted in patients with severe hepatic impairment (Child-Pugh Class C) due to increased systemic exposure. 2 Clinical trials were limited to patients with MELD scores <25. 2
Discontinuation Rates
Discontinuation due to adverse events is extremely low: 2
- 0.4% in travelers' diarrhea trials
- Minimal discontinuations in hepatic encephalopathy and IBS-D trials
Clinical Context
The side effect profile of rifaximin is remarkably benign compared to other antibiotics, with most adverse events occurring at rates similar to placebo. 1, 4 This favorable safety profile, combined with minimal systemic absorption, makes rifaximin suitable for long-term maintenance therapy without the typical concerns associated with prolonged antibiotic use. 4, 3