Rifacol

Approved Indications:

• Hepatic Encephalopathy (HE): To reduce the risk of overt HE recurrence in adults.
• Traveler’s Diarrhea: Caused by noninvasive strains of Escherichia coli in patients ≥12 years old.
• Irritable Bowel Syndrome with Diarrhea (IBS-D): In adults.

Off-Label / Clinically Accepted Uses:

• Small Intestinal Bacterial Overgrowth (SIBO): Used in combination therapy for symptom relief.
• Clostridioides difficile infection (CDI): Used as part of salvage or adjunctive therapy.
• Crohn’s Disease and Ulcerative Colitis: Investigational use in select patients to reduce bacterial load.

Adults:

• Hepatic Encephalopathy: 550 mg orally twice daily.
• IBS-D: 550 mg orally three times daily for 14 days. Can be repeated up to 2 times if symptoms recur.
• Traveler’s Diarrhea: 200 mg orally three times daily for 3 days.

Pediatrics (≥12 years):

• Traveler’s Diarrhea: 200 mg orally three times daily for 3 days.

Geriatrics:

• No dosage adjustment required; monitor for hepatic function and response.

Renal Impairment:

• No dose adjustment necessary.

Hepatic Impairment:

• Mild to moderate (Child-Pugh A or B): No adjustment needed.
• Severe (Child-Pugh C): Use with caution due to potential systemic accumulation.

Administration:

• Oral route only.
• May be taken with or without food.
• Tablets should not be crushed or chewed.

Rifaximin is a non-systemic, broad-spectrum antibacterial agent that binds irreversibly to the β-subunit of bacterial DNA-dependent RNA polymerase. This action inhibits bacterial RNA synthesis and leads to cell death. Rifaximin acts primarily in the gastrointestinal tract with minimal systemic absorption, making it effective for gut-related infections and conditions like hepatic encephalopathy by modulating the gut microbiota and reducing ammonia-producing bacteria.

• Absorption: Poorly absorbed; systemic bioavailability <1%.
• Distribution: Primarily remains in the gastrointestinal tract; minimal systemic distribution.
• Metabolism: Minimal; undergoes limited hepatic metabolism via CYP3A4.
• Elimination: Primarily via feces (>96% unchanged); negligible renal elimination.
• Half-Life: ~6 hours (varies slightly by indication).
• Peak Plasma Concentration: Occurs within 1–2 hours post-dose.

• Pregnancy: Category C (based on prior classification). No adequate human studies. Use only if benefits outweigh potential risks.
• Lactation: Unknown if excreted in human milk. Due to poor absorption, minimal risk is expected; use caution, especially with prolonged use.

• Primary Class: Gastrointestinal Antibiotic
• Subclass: Non-systemic Rifamycin Derivative

• Known hypersensitivity to rifaximin, rifamycin derivatives, or any excipients.
• Diarrhea complicated by fever or blood in stool.
• Known or suspected cases of invasive enteric pathogens.

• Severe Hepatic Impairment: Use cautiously; risk of systemic absorption and toxicity.
• C. difficile-Associated Diarrhea (CDAD): Consider in differential diagnosis if diarrhea develops during or after treatment.
• Antibiotic Resistance: Risk of bacterial overgrowth or resistance with prolonged use.
• Allergic Reactions: Cross-sensitivity with other rifamycin antibiotics (e.g., rifampin).
• Monitoring: Monitor mental status in HE; repeat IBS-D treatment only if needed.

Common:

• GI System: Flatulence, abdominal pain, nausea, constipation.
• CNS: Headache, dizziness.
• Hepatic Encephalopathy Use: Peripheral edema, fatigue.

Serious:

• Allergic Reactions: Anaphylaxis, angioedema.
• Liver: Elevated liver enzymes, especially in HE patients.
• Rare: C. difficile-associated diarrhea, superinfection.

Onset: Typically within first week of therapy. Most side effects are mild and self-limiting.

• Cyclosporine: May increase rifaximin levels; monitor.
• P-glycoprotein inhibitors (e.g., verapamil): Can increase systemic exposure.
• CYP3A4 inhibitors/inducers: Limited systemic effect, but caution advised in hepatic impairment.
• Oral contraceptives: No known interaction, but theoretical concern in hepatic impairment.

Rifaximin is a substrate of P-glycoprotein (P-gp) and partially metabolized by CYP3A4, though clinical impact is minimal due to low systemic absorption.

• FDA: Rifaximin approved for repeat use in IBS-D up to two times if symptoms recur (revised in recent years).
• NICE/EMA: Supports use in HE and IBS-D; evidence base strengthened by real-world studies showing efficacy and safety.
• Updated HE management guidelines (AASLD): Include rifaximin as standard adjunctive therapy to lactulose in recurrent episodes.

• Temperature: Store below 25°C (77°F).
• Humidity/Light: Store in a dry place; protect from moisture.
• Handling: Keep in original container tightly closed.
• Reconstitution/Refrigeration: Not required; ready-to-use oral tablet form.