Neomycin for Hyperammonemia
Neomycin is NOT recommended as a primary treatment for hyperammonemia and should only be considered as a second-line alternative agent specifically for hepatic encephalopathy-related hyperammonemia when first-line therapies (lactulose and rifaximin) have failed or are contraindicated, and only for short-term use due to significant toxicity concerns including nephrotoxicity, ototoxicity, and intestinal malabsorption. 1
Clinical Context and Current Position in Treatment Guidelines
Neomycin has been relegated to alternative status in modern treatment algorithms for hyperammonemia. The Korean Association for the Study of the Liver explicitly states that neomycin is not recommended for management of hepatic encephalopathy due to side effects including intestinal malabsorption, nephrotoxicity, and ototoxicity. 1 The American Association for the Study of Liver Diseases and European Association for the Study of the Liver classify neomycin only as an alternative choice (GRADE II-1, B, 2) for overt hepatic encephalopathy, far below preferred agents. 1
FDA-Approved Indication
The FDA label indicates neomycin sulfate tablets are approved as adjunctive therapy in 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, this approval predates modern evidence favoring safer alternatives.
Treatment Algorithm for Hyperammonemia
For Hepatic Encephalopathy-Related Hyperammonemia:
- First-line: Lactulose monotherapy (GRADE II-1, B, 1) 1
- Second-line: Add rifaximin to lactulose for patients who have experienced one or more episodes of overt hepatic encephalopathy (GRADE I, A, 1) - this combination has the highest quality evidence 1
- Third-line: Consider neomycin only when rifaximin and lactulose have failed or are contraindicated, and limit to short-term use 1
For Acute Severe Hyperammonemia (Non-Hepatic Encephalopathy):
Neomycin has no role in the management of acute severe hyperammonemia from urea cycle disorders or other metabolic causes. 3, 4 The appropriate treatment hierarchy is:
- Immediate: Stop protein intake, provide IV glucose (8-10 mg/kg/min) and lipids (0.5-3 g/kg daily), ensure ≥100 kcal/kg daily 3, 4
- Pharmacologic: Nitrogen-scavenging agents (sodium benzoate, sodium phenylacetate) and L-arginine hydrochloride at weight-based dosing 3, 4
- Dialysis: High-dose continuous venovenous hemodialysis (CVVHD) for ammonia >300-400 μmol/L or moderate-to-severe encephalopathy 4, 5
Mechanism and Efficacy Evidence
Neomycin acts as a glutaminase inhibitor, reducing ammonia production from glutamine metabolism in the intestinal tract. 1 A 1992 study demonstrated neomycin (700 mg every 8 hours for 4 days) produced a mean reduction of 38.2 μmol/L in blood ammonia (P = 0.01), which was statistically significant. 6 However, a 1991 comparative trial showed rifaximin was at least as effective as neomycin and produced an earlier reduction in blood ammonia levels. 7
Critical Safety Concerns and Toxicity Profile
The major limitation preventing routine use of neomycin is its toxicity profile, particularly with long-term administration:
- Nephrotoxicity - can cause acute kidney injury 1
- Ototoxicity - risk of irreversible hearing loss 1
- Intestinal malabsorption - affects nutrient absorption 1
- Neurotoxicity - particularly concerning with prolonged use 1
These toxicities make neomycin substantially inferior to rifaximin, which has superior safety and efficacy profiles. 1
Important Clinical Caveats
- Never use as monotherapy: Antibiotics should never replace lactulose as the foundation of therapy for hepatic encephalopathy - they are add-on or alternative agents only 1
- Wrong context: For severe hyperammonemia with encephalopathy from metabolic causes, nitrogen scavengers and kidney replacement therapy are appropriate, not antibiotics 1, 4
- Duration limits: If neomycin must be used, limit to short-term therapy only due to cumulative toxicity risk 1
- Monitoring required: The duration of hyperammonemic coma prior to dialysis is the most important prognostic factor for neurological outcomes, not the rate of ammonia clearance 4, 5
When Neomycin Might Be Considered
The only scenario where neomycin has a potential role is in hepatic encephalopathy when:
- Patient has failed lactulose therapy 1
- Rifaximin is unavailable, contraindicated, or unaffordable 1
- Short-term use only is anticipated 1
- Patient has no contraindications (renal dysfunction, hearing impairment) 1
Even in this narrow scenario, metronidazole (despite its own peripheral neuropathy risk with long-term use) may be preferable to neomycin. 1