Usage
Rifaximin is a non-absorbable, gut-selective antibiotic primarily used for the treatment of gastrointestinal conditions. It is prescribed for:
- Traveler’s diarrhea: Caused by noninvasive strains of Escherichia coli (E. coli). Not effective against diarrhea with fever, bloody stool, or caused by other pathogens.
- Hepatic encephalopathy (HE): Reduces the risk of recurrent episodes of overt HE in adults.
- Irritable bowel syndrome with diarrhea (IBS-D): Treats IBS-D in adults.
- Small intestinal bacterial overgrowth (SIBO): Though not FDA-approved for this indication, it’s sometimes used off-label for SIBO treatment.
Pharmacological Classification: Rifaximin is classified as a rifamycin antibiotic.
Mechanism of Action: Rifaximin inhibits bacterial RNA synthesis by binding to the beta-subunit of bacterial DNA-dependent RNA polymerase. Its minimal systemic absorption limits its effects to the gut. This gut-selectivity minimizes the impact on the normal gut flora and reduces the risk of systemic side effects.
Alternate Names
Rifaximin is the generic name. A popular brand name is Xifaxan.
How It Works
Pharmacodynamics: Rifaximin exerts its antibacterial effects locally within the gut lumen. It alters gut flora composition and reduces bacterial production of toxins implicated in HE.
Pharmacokinetics: Rifaximin is minimally absorbed (<1%) after oral administration, resulting in high fecal concentrations. It is primarily eliminated unchanged in feces, with negligible renal or hepatic excretion. A high-fat meal can slightly delay absorption but doesn’t significantly affect peak concentration. It’s moderately bound to plasma proteins (67.5%). In patients with hepatic encephalopathy, systemic exposure is higher but still clinically irrelevant.
Mode of Action: Rifaximin binds to the beta-subunit of bacterial DNA-dependent RNA polymerase, thereby inhibiting bacterial RNA synthesis.
Receptor Binding, Enzyme Inhibition, or Neurotransmitter Modulation: Rifaximin primarily acts through enzyme inhibition (bacterial RNA polymerase).
Elimination Pathways: Primarily fecal excretion (>96% unchanged).
Dosage
Standard Dosage
Adults:
- Traveler’s diarrhea: 200 mg orally three times a day for 3 days.
- Hepatic encephalopathy: 550 mg orally twice a day. Long-term treatment is usually recommended.
- IBS-D: 550 mg orally three times a day for 14 days. Repeat treatment (up to two times) is possible if symptoms recur.
Children:
- Traveler’s diarrhea: 200 mg three times a day for 3 days (12 years and older). Dosing in children younger than 12 should be determined by a doctor.
- Hepatic encephalopathy and IBS-D: Safety and efficacy not established in children younger than 18.
- SIBO: 200-550 mg three times a day for 7-14 days (expert opinion and limited studies).
Special Cases:
- Elderly Patients: No dosage adjustment typically required.
- Patients with Renal Impairment: Caution advised. Dosage modification usually not needed due to minimal systemic absorption.
- Patients with Hepatic Dysfunction: No dosage adjustment necessary for mild to moderate impairment. Caution with severe impairment.
- Patients with Comorbid Conditions: Individualized dosing based on specific comorbidities.
Clinical Use Cases
Rifaximin is not indicated for use in clinical scenarios requiring systemic antibiotics, like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations. Its use is restricted to the gastrointestinal tract.
Dosage Adjustments
Dose adjustments are typically not needed based on renal or hepatic dysfunction, metabolic disorders, or genetic polymorphisms due to Rifaximin’s minimal systemic absorption. However, caution is recommended in severe hepatic impairment.
Side Effects
Common Side Effects
Nausea, dizziness, headache, fatigue, abdominal pain, bloating, flatulence, constipation, peripheral edema.
Rare but Serious Side Effects
- Clostridium difficile-associated diarrhea (CDAD)
- Angioedema, anaphylaxis (hypersensitivity reactions)
- Severe skin reactions (SJS, TEN)
Long-Term Effects
Peripheral edema, ascites, muscle spasms, arthralgia, low mood.
Adverse Drug Reactions (ADR)
Severe skin reactions (SJS/TEN), anaphylaxis, angioedema, C. difficile infection.
Contraindications
- Hypersensitivity to rifaximin, rifamycin antibiotics, or any component of the formulation.
- Intestinal obstruction.
- Diarrhea with fever and/or blood in the stool.
- Diarrhea caused by pathogens other than E. coli (for traveler’s diarrhea).
Drug Interactions
Rifaximin has limited drug interactions due to its poor systemic absorption. However, moderate interactions may occur with cyclosporine and warfarin. Concomitant use of other rifamycin antibiotics for systemic infections is not recommended.
Pregnancy and Breastfeeding
- Pregnancy: Limited human data. Animal studies show potential fetal harm. Not recommended during pregnancy.
- Breastfeeding: Unknown if rifaximin is excreted in human milk. Minimal systemic absorption suggests low risk to the infant. An alternate drug may be preferred, particularly when nursing a newborn or preterm infant.
Drug Profile Summary
- Mechanism of Action: Inhibits bacterial RNA synthesis by binding to bacterial DNA-dependent RNA polymerase.
- Side Effects: Nausea, dizziness, headache, fatigue, abdominal pain, bloating; rarely C. difficile infection, severe skin reactions.
- Contraindications: Hypersensitivity to rifaximin, rifamycins, intestinal obstruction.
- Drug Interactions: Limited, moderate interactions with cyclosporine and warfarin.
- Pregnancy & Breastfeeding: Not recommended during pregnancy; caution during breastfeeding.
- Dosage: See detailed dosage guidelines above.
- Monitoring Parameters: Monitor for signs of C. difficile infection and allergic reactions. Liver function tests may be monitored in patients with HE.
Popular Combinations
- Hepatic encephalopathy: Often used in combination with lactulose.
Precautions
- General Precautions: Assess for hypersensitivity, intestinal obstruction, and dehydration.
- Specific Populations: See pregnancy and breastfeeding information. Not recommended for children under 12 (traveler’s diarrhea) and under 18 (IBS-D/HE).
- Lifestyle Considerations: May cause dizziness; advise caution when driving or operating machinery.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Rifaximin?
A: See detailed dosage guidelines above for specific indications and patient populations.
Q2: Can Rifaximin be used in pregnant or breastfeeding women?
A: It is not recommended during pregnancy due to potential fetal risk based on animal data. While it’s likely low risk during breastfeeding due to minimal systemic absorption, an alternate drug may be preferred.
Q3: How does Rifaximin differ from other antibiotics?
A: Its minimal systemic absorption allows it to act selectively within the gut, minimizing disruption of normal gut flora and reducing systemic side effects.
Q4: What are the most serious side effects of Rifaximin?
A: Clostridium difficile infection, severe skin reactions (SJS/TEN), and allergic reactions (angioedema, anaphylaxis).
Q5: Can Rifaximin be used to treat all types of diarrhea?
A: No. It is only effective against traveler’s diarrhea caused by noninvasive E. coli. It’s not effective against diarrhea caused by other pathogens, or diarrhea complicated by fever or bloody stool.
Q6: How long should Rifaximin be taken for hepatic encephalopathy?
A: Long-term treatment is usually recommended to reduce the risk of recurrent episodes.
Q7: Are there any dietary restrictions while taking Rifaximin?
A: Generally, no specific dietary restrictions are required. It can be taken with or without food.
Q8: Can Rifaximin be used in patients with liver disease?
A: Yes, it is used to treat hepatic encephalopathy. No dosage adjustment is needed for mild to moderate liver impairment. Caution is advised in severe liver disease.
Q9: Can Rifaximin be crushed or chewed?
A: The tablets can be swallowed whole or crushed and mixed with applesauce, other soft foods, or liquids for easier administration if needed.
Q10: How should I advise patients about potential drug interactions?
A: Inform patients about the potential for interactions with certain medications, particularly cyclosporine and warfarin. Encourage them to disclose all medications and supplements they are taking.
