A 58-year-old man with cirrhosis has had three episodes of overt hepatic encephalopathy in the past year. He takes lactulose regularly with two soft stools per day but continues to break through into encephalopathy. What is the most appropriate addition to his regimen?

• A Neomycin 500 mg twice daily long term
• B Flumazenil infusion weekly
• C Protein restriction to 20 g per day
• D Rifaximin 550 mg twice daily ✓

Explanation

Rifaximin, a minimally absorbed oral antibiotic acting on gut ammonia-producing flora, reduces recurrence of overt encephalopathy when added to lactulose in patients with repeated breakthrough episodes, and is approved for secondary prophylaxis. Long-term neomycin risks ototoxicity and nephrotoxicity, protein restriction worsens sarcopenia since adequate protein including branched chain amino acids is now recommended, and flumazenil is only a short-term diagnostic or emergency agent.

Reference: Katzung's Basic and Clinical Pharmacology, 16th ed.

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