Can neomycin be used to treat hyperammonemia?

Can Neomycin Be Used to Treat Hyperammonemia?

Yes, neomycin can be used to treat hyperammonemia, particularly in the context of hepatic encephalopathy, but it is relegated to an alternative choice due to significant toxicity concerns including ototoxicity, nephrotoxicity, and neurotoxicity that make it unattractive for long-term use. 1

Clinical Context and Positioning

Neomycin is FDA-approved as adjunctive therapy for hepatic coma (portal-systemic encephalopathy) by reducing ammonia-forming bacteria in the intestinal tract, with subsequent reduction in blood ammonia resulting in neurologic improvement 2. However, its role has been significantly downgraded in modern practice.

Guideline Recommendations

• The AASLD/EASL 2014 guidelines classify neomycin as an alternative choice for treatment of overt hepatic encephalopathy (GRADE II-1, B, 2) 1
• This recommendation places neomycin well below first-line agents (lactulose) and second-line agents (rifaximin) in the treatment hierarchy 1
• The Korean Association for the Study of the Liver (2020) explicitly states that neomycin is not recommended for management of hepatic encephalopathy due to side effects including intestinal malabsorption, nephrotoxicity, and ototoxicity 1

Mechanism and Efficacy

Neomycin works through two mechanisms:

• Reduces ammonia-producing bacteria in the gut through its antimicrobial action 2
• Acts as a glutaminase inhibitor, reducing ammonia production from glutamine metabolism 1

Evidence of Effectiveness

• A 1991 randomized trial demonstrated that neomycin (1g every 8 hours) significantly decreased blood ammonia levels in cirrhotic patients with chronic portal-systemic encephalopathy over 21 days 3
• When combined with lactulose, neomycin showed an additive effect in reducing gut ammonia production by inhibiting bacterial ureolysis, causing a 17% reduction in urea production rate and 70% reduction in urea degradation rate 4

Critical Safety Concerns

The major limitation preventing routine use of neomycin is its toxicity profile, particularly with long-term administration: 1

• Ototoxicity: Can cause permanent hearing loss, even when used as an irrigant solution 5
• Nephrotoxicity: Can produce acute renal failure, including "high output" renal failure that may be unsuspected 5
• Neurotoxicity: Additional central nervous system effects 1
• Intestinal malabsorption: Affects nutrient absorption 1

A case report documented total permanent deafness and acute renal failure from neomycin absorption following surgical cavity irrigation, with renal function recovering after peritoneal dialysis but hearing loss remaining permanent 5.

Clinical Algorithm for Use

When to consider neomycin:

1. Patient has overt hepatic encephalopathy with hyperammonemia 1
2. First-line therapy (lactulose) has failed or is contraindicated 1
3. Rifaximin is unavailable or unaffordable 1
4. Short-term use only is anticipated (not for continuous long-term therapy) 1
5. Patient has normal baseline renal function and hearing 5

Preferred alternatives before neomycin:

• Lactulose (first choice, GRADE II-1, B, 1) 1
• Rifaximin added to lactulose (GRADE I, A, 1) 1
• Oral BCAAs (GRADE I, B, 2) 1
• IV L-ornithine L-aspartate (GRADE I, B, 2) 1

Important Caveats

• Neomycin was "widely used in the past" but has fallen out of favor due to its toxicity profile 1
• The drug "still has its advocates" but this represents a minority opinion in modern hepatology 1
• Metronidazole is similarly positioned as an alternative with comparable concerns (peripheral neuropathy with long-term use) 1
• For hyperammonemia in other contexts (urea cycle disorders, pediatric patients), neomycin is not mentioned in current guidelines, which favor nitrogen scavengers and kidney replacement therapy 1, 6, 7

In summary, while neomycin can reduce ammonia levels and is FDA-approved for this indication, modern practice reserves it as a last-resort alternative due to serious toxicity risks, particularly for any use beyond short-term therapy. 1, 2