From the Guidelines
Rifaximin is generally well-tolerated, with the most common side effects being headache, nausea, bloating, gas, and abdominal discomfort, as reported in a 2022 study 1.
Side Effects of Rifaximin
The side effects of rifaximin can be categorized into common and rare but serious side effects.
- Common side effects include:
- Headache
- Nausea
- Bloating
- Gas
- Abdominal discomfort
- Rare but serious side effects include:
- Allergic reactions (rash, itching, swelling, severe dizziness, trouble breathing)
- Clostridium difficile infection (severe diarrhea, abdominal pain, fever)
- Peripheral edema (swelling in extremities) According to a 2021 study, rifaximin has a favorable safety profile compared to other antibiotics, as it primarily targets bacteria in the intestines without significantly affecting beneficial gut flora throughout the body 1.
Special Considerations
Patients with severe liver impairment should use rifaximin cautiously, as blood levels may increase 1. The typical dosage for IBS-D is 550 mg three times daily, while for hepatic encephalopathy it's 550 mg twice daily.
Evidence Quality
The evidence for the side effects of rifaximin is based on moderate to high-quality studies, including a 2022 study published in Gastroenterology 1 and a 2021 study published in Gut 1.
Clinical Implications
In clinical practice, rifaximin can be a useful treatment option for patients with IBS-D, given its favorable safety profile and efficacy in improving symptoms. However, patients should be monitored for potential side effects, and the drug should be used cautiously in patients with severe liver impairment.
From the FDA Drug Label
The following clinically significant adverse reactions are described elsewhere in labeling: • Clostridium difficile-associated diarrhea [see Warnings and Precautions (5.2)]
The adverse reactions that occurred at a frequency ≥2% in XIFAXAN-treated patients (n=320) at a higher rate than placebo (n=228) in the two placebo-controlled trials of TD was: • headache (10% XIFAXAN, 9% placebo)
The most common adverse reactions that occurred at an incidence ≥5% and at a higher incidence in XIFAXAN-treated subjects than in the placebo group in the 6-month trial are provided in Table 1 (%) eferred Term XIFAXAN Tablets 550 mg TWICE DAILY n=140 Placebo n=159 Peripheral edema 21 (15%) 13 (8%) Nausea 20 (14%) 21 (13%) Dizziness 18 (13%) 13 (8%) Fatigue 17 (12%) 18 (11%) Ascites 16 (11%) 15 (9%) Muscle spasms 13 (9%) 11 (7%) Pruritus 13 (9%) 10 (6%) Abdominal pain 12 (9%) 13 (8%) Anemia 11 (8%) 6 (4%) Depression 10 (7%) 8 (5%) Nasopharyngitis 10 (7%) 10 (6%) Abdominal pain upper 9 (6%) 8 (5%) Arthralgia 9 (6%) 4 (3%) Dyspnea 9 (6%) 7 (4%) Pyrexia 9 (6%) 5 (3%) Rash 7 (5%) 6 (4%)
The adverse reactions that occurred at a frequency ≥2% in XIFAXAN-treated patients (n=328) at a higher rate than placebo (n=308) in Trial 3 for IBS-D during the double-blind treatment phase were: • ALT increased (XIFAXAN 2%, placebo 1%) • nausea (XIFAXAN 2%, placebo 1%)
The following adverse reactions have been identified during post-approval use of XIFAXAN. Because these reactions are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. These reactions have been chosen for inclusion due to either their seriousness, frequency of reporting, or causal connection to XIFAXAN Infections and Infestations Cases of C. difficile-associated colitis have been reported [see Warnings and Precautions (5. 2)]. Hypersensitivity Reactions Exfoliative dermatitis, rash, angioneurotic edema (swelling of face and tongue and difficulty swallowing), urticaria, flushing, pruritus and anaphylaxis have been reported. These events occurred as early as within 15 minutes of drug administration Musculoskeletal and Connective Tissue Disorders Cases of rhabdomyolysis have been reported in patients with cirrhosis, with and without concomitant statin use. Severe Cutaneous Adverse Reactions Severe cutaneous adverse reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), have been reported in association with the use of rifaximin in patients with cirrhosis
The side effects of Rifaximin include:
- Gastrointestinal:
- Nausea
- Abdominal pain
- Abdominal pain upper
- Diarrhea
- Clostridium difficile-associated diarrhea
- Nervous system:
- Headache
- Dizziness
- Fatigue
- Musculoskeletal:
- Muscle spasms
- Arthralgia
- Rhabdomyolysis
- Dermatologic:
- Rash
- Pruritus
- Exfoliative dermatitis
- Angioneurotic edema
- Urticaria
- Anaphylaxis
- Stevens-Johnson syndrome
- Toxic epidermal necrolysis
- Hepatic:
- ALT increased
- Respiratory:
- Dyspnea
- Cardiovascular:
- Peripheral edema
- Hematologic:
- Anemia
- Infections:
- C. difficile-associated colitis
- Metabolic:
- Ascites
- Psychiatric:
From the Research
Side Effects of Rifaximin
- The studies 3, 4, 5, 6, 7 do not provide a comprehensive list of side effects of Rifaximin.
- However, it is mentioned that Rifaximin has "few side effects" 3 and is associated with "fewer systemic adverse effects" compared to systemically absorbed antibiotics 4.
- One study notes that Rifaximin is "not systemically absorbed", which suggests that it may have fewer side effects compared to other antibiotics 4.
- Another study mentions that Rifaximin can be used without "side effects" for the prevention of travelers' diarrhea 5.
- The studies also mention that there were "no differences in adverse events" between Rifaximin and placebo in clinical trials 7.
- Overall, the available evidence suggests that Rifaximin is generally well-tolerated and has a low risk of side effects, but the specific side effects are not clearly documented in the provided studies.
Comparison to Other Treatments
- Rifaximin is compared to other treatments such as trimethoprim/sulfamethoxazole and ciprofloxacin, and is found to be equivalent or superior in terms of efficacy 4.
- Rifaximin is also compared to bismuth subsalicylate, and is found to be more effective for the prevention of travelers' diarrhea 5.
- The studies suggest that Rifaximin is a viable alternative to other treatments for certain conditions, but the side effect profiles of these treatments are not directly compared.