Makindo Medical Notes

💡 Key Point: Rifaximin is a rifamycin derivative that acts only within the gut. It is minimally absorbed and should never be used for systemic infections. It has revolutionised the management of hepatic encephalopathy by reducing ammonia-producing gut bacteria with minimal toxicity.

🧠 About

• Rifaximin is a semi-synthetic rifamycin antibiotic that acts locally in the gastrointestinal tract.
• It is poorly absorbed orally — systemic levels are negligible, reducing toxicity risk.
• Widely used in hepatic encephalopathy to prevent recurrence of episodes by reducing gut-derived ammonia.
• 💷 Approximate cost: £1689.65 per 6-month course (NHS reference cost, 2024).

⚙️ Mechanism of Action

• Rifaximin binds to the β-subunit of bacterial DNA-dependent RNA polymerase.
• Inhibits RNA synthesis, leading to suppression of bacterial growth in the gut lumen.
• Because of poor absorption, it exerts its effect locally — sparing systemic flora and reducing resistance pressure.

🎯 Indications & Typical Doses

• 🌍 Traveller’s diarrhoea: 200 mg three times daily for 3 days (only when not associated with fever, blood, or >8 loose stools/24 h).
• 🧠 Hepatic encephalopathy: 550 mg twice daily to reduce recurrence (used with lactulose). Proven to decrease hospitalisations and mortality.
• 🦠 Clostridioides difficile (recurrent): 400 mg three times daily for 20 days, started immediately after standard CDI therapy — reduces relapse risk.

🔗 Interactions

• Few systemic interactions due to poor absorption.
• May slightly alter exposure to CYP3A4-metabolised drugs (e.g. warfarin, cyclosporin) — monitor INR or levels if co-administered.
• Always cross-check with the BNF.

⚠️ Cautions

• ❗ Not suitable for systemic infections — blood levels are negligible.
• Use with caution if intestinal obstruction or severe hepatic impairment.
• Although resistance is uncommon, avoid overuse to preserve activity against gut flora.

🚫 Contraindications

• 🔴 Hypersensitivity to rifamycins (e.g. rifampicin, rifabutin).
• 🔴 Intestinal obstruction or severe ulceration preventing drug transit.
• 🔴 Systemic infections — ineffective due to lack of absorption.

💥 Adverse Effects

• 🧠 Neurological: Headache, dizziness, depression.
• 🫁 Respiratory: Dyspnoea.
• 🦠 Gastrointestinal: Diarrhoea, nausea, vomiting, abdominal pain, distension, ascites (especially in cirrhotics).
• 🦵 Musculoskeletal: Arthralgia, muscle spasms, peripheral oedema.
• 🌿 Dermatological: Rash, pruritus.

🧾 Monitoring

💡 Teaching Tip

• Rifaximin replaced neomycin as the safer gut-selective antimicrobial in hepatic encephalopathy.
• Illustrates the concept of “luminal antibiotic therapy” — local gut action, minimal systemic toxicity.
• Remind students that although it’s a rifamycin, it does not stain secretions orange (unlike rifampicin).
• Perfect case for discussing antibiotic stewardship: use only when recurrence risk justifies cost.

📚 References

• BNF: Rifaximin
• European Association for the Study of the Liver (EASL) Guidelines, 2023 – Hepatic Encephalopathy
• Sidhu SS et al. Hepatology 2019;70:1691–1700 – Rifaximin in recurrent HE.
• MHRA Drug Safety Update (2022): Rifaximin safety profile.