Rifaximin - Drug Monograph

Introduction

Rifaximin is a semi-synthetic, non-systemic antibiotic derived from rifamycin. It is classified as a rifamycin antibacterial agent with minimal systemic absorption, making it particularly useful for gastrointestinal conditions. First approved by the FDA in 2004, rifaximin has become an important therapeutic option for various gastrointestinal disorders due to its targeted action within the intestinal lumen.

Mechanism of Action

Rifaximin acts by inhibiting bacterial RNA synthesis through binding to the beta subunit of bacterial DNA-dependent RNA polymerase. This interaction blocks the initiation chain formation in RNA transcription, ultimately leading to bacterial cell death. Unlike systemic rifamycins, rifaximin's minimal systemic absorption allows for high concentrations in the gastrointestinal tract while minimizing systemic exposure and associated side effects.

Indications

• Travelers' diarrhea caused by non-invasive strains of Escherichia coli
• Hepatic encephalopathy reduction in recurrence
• Irritable bowel syndrome with diarrhea (IBS-D) in adults
• Off-label uses: Small intestinal bacterial overgrowth (SIBO), Clostridioides difficile infection, inflammatory bowel disease, diverticulitis

Dosage and Administration

• Renal impairment: No dosage adjustment required
• Hepatic impairment: No dosage adjustment required
• Pediatrics: Safety and effectiveness not established
• Geriatrics: No specific dosage adjustment recommended

Pharmacokinetics

Contraindications

• Hypersensitivity to rifaximin, other rifamycin derivatives, or any component of the formulation
• Patients with complicated diarrhea (bloody diarrhea, fever, or systemic illness)

Warnings and Precautions

• Clostridioides difficile-associated diarrhea may occur
• Development of drug-resistant bacteria with prolonged use
• Use caution in patients with severe hepatic impairment
• Not effective for patients with diarrhea complicated by fever or bloody stool
• Superinfections may occur with prolonged use

Drug Interactions

• Minimal systemic interactions due to low bioavailability
• Potential interaction with warfarin (monitor INR)
• May reduce efficacy of oral contraceptives (use additional contraception)
• Theoretical interaction with cyclosporine (monitor levels)

Adverse Effects

• Nausea (10-15%)
• Flatulence (6-12%)
• Headache (6-10%)
• Abdominal pain (5-8%)
• Constipation (5-7%)
• Pyrexia (3-5%)

• Clostridioides difficile infection
• Severe cutaneous adverse reactions
• Anaphylaxis and hypersensitivity reactions
• Stevens-Johnson syndrome

Monitoring Parameters

• Clinical response to therapy
• Signs of superinfection or C. difficile infection
• Hepatic function in patients with pre-existing liver disease
• Electrolyte balance in patients with prolonged diarrhea
• Signs of hypersensitivity reactions

Patient Education

• Complete the full course of therapy even if symptoms improve
• Report any bloody diarrhea, fever, or worsening symptoms
• Notify healthcare provider if pregnancy is suspected
• Inform provider of all medications being taken
• Store at room temperature away from moisture and heat
• Do not use for viral infections
• Maintain adequate hydration during treatment for diarrhea

References

1. FDA Prescribing Information: Xifaxan (rifaximin) 2. DuPont HL. Rifaximin: a novel nonabsorbed rifamycin for gastrointestinal disorders. Clin Infect Dis. 2005;41 Suppl 7:S541-7. 3. Bass NM et al. Rifaximin treatment in hepatic encephalopathy. N Engl J Med. 2010;362(12):1071-81. 4. Pimentel M et al. Rifaximin therapy for patients with irritable bowel syndrome without constipation. N Engl J Med. 2011;364(1):22-32. 5. Scarpignato C et al. Rifaximin: more than a gut-selective antimicrobial. Therap Adv Gastroenterol. 2018;11:1756284818783885. 6. Clinical Pharmacology [Internet]. Tampa (FL): Elsevier. Rifaximin. Available from: https://www.clinicalpharmacology.com 7. Micromedex Solutions [Internet]. Truven Health Analytics. Rifaximin. Available from: https://www.micromedexsolutions.com