What is the risk of ototoxicity with oral neomycin use?

Oral Neomycin Carries Significant Ototoxicity Risk and Should Be Avoided for Long-Term Use

Oral neomycin can cause permanent bilateral hearing loss and vestibular toxicity, even at recommended doses in patients with normal renal function, making it an unattractive choice for continuous therapy. 1

FDA Black Box Warning on Systemic Absorption

The FDA explicitly warns that systemic absorption occurs following oral administration, with potential for:

• Permanent bilateral auditory ototoxicity 2
• Vestibular toxicity in patients with normal renal function when treated with higher doses or for longer periods than recommended 2
• Delayed onset of ototoxicity, where patients may not have symptoms during therapy, and total or partial deafness may occur long after discontinuation 2

Clinical Context: Hepatic Encephalopathy Guidelines

While neomycin remains listed as an alternative treatment option for overt hepatic encephalopathy, major hepatology guidelines explicitly state that long-term ototoxicity, nephrotoxicity, and neurotoxicity make neomycin unattractive for continuous long-term use. 1 The American Association for the Study of Liver Diseases and European Association for the Study of the Liver both grade neomycin as GRADE II-1, B, 2—a notably weaker recommendation compared to lactulose (GRADE II-1, B, 1) or rifaximin (GRADE I, A, 1). 1

Actual Incidence from Prospective Studies

The true risk appears lower than historical case reports suggested, but remains clinically significant:

• A prospective study of 30 adults on long-term oral neomycin found ototoxicity in 2 of 30 subjects (6.7%) 3
• A pediatric study demonstrated significant hearing loss in the 2-8 kHz range in 9 of 17 children (53%) 3
• The wide variation reflects differences in dosing, duration, and patient populations 3, 4

High-Risk Populations Requiring Extreme Caution

Renal impairment is the single most critical risk factor because neomycin clearance is almost exclusively renal, leading to drug accumulation. 2 Additional high-risk groups include:

• Advanced age (increases risk substantially) 1, 5
• Prolonged treatment duration >2 weeks 5
• Concurrent use of loop diuretics (furosemide, ethacrynic acid), which potentiate ototoxicity 1, 2
• Gastrointestinal inflammation, which increases systemic absorption 4
• Concurrent nephrotoxic drugs (vancomycin, amphotericin B, cisplatin) 2

Monitoring Requirements If Neomycin Must Be Used

Baseline and serial monitoring is mandatory but does not prevent toxicity—it only detects it earlier:

• Baseline audiometry with vestibular testing and Romberg testing 1, 5
• Serial high-frequency audiometry (extending to 20 kHz if possible, as damage begins at high frequencies) 3, 6
• Monthly renal function assessment 1, 5
• Serum neomycin concentrations in high-risk patients 5, 2
• Monthly questioning about auditory or vestibular symptoms 1

Critical Clinical Pitfall

Ototoxicity is often delayed in onset—patients may not develop symptoms during therapy, and total deafness can occur long after neomycin discontinuation. 2 This means normal hearing during treatment does not guarantee safety. The damage is typically permanent and irreversible, even with dialysis. 7, 8

Absolute Contraindications

• Pregnancy: Risk of fetal auditory/vestibular nerve damage 1, 5
• Myasthenia gravis: Impairs neuromuscular transmission and can cause respiratory paralysis 5, 2

Safer Alternatives for Hepatic Encephalopathy

When treating hepatic encephalopathy, rifaximin added to lactulose is the best-documented regimen (GRADE I, A, 1) with no ototoxicity risk. 1 Other alternatives include oral BCAAs, IV L-ornithine L-aspartate, or short-term metronidazole (though metronidazole carries peripheral neuropathy risk with prolonged use). 1

Topical Neomycin Ototoxicity Risk

Aminoglycoside-containing eardrops (including neomycin) should never be used when tympanostomy tubes are present due to direct middle ear exposure and ototoxicity risk. 1 Only quinolone drops (ofloxacin, ciprofloxacin) are approved for use with tubes. 1 However, topical neomycin for intact eardrums in otitis externa carries minimal systemic absorption and is generally safe. 9

Bottom Line for Clinical Practice

Use oral neomycin only as a last resort for short-term therapy (<2 weeks) when safer alternatives have failed, and never in patients with renal impairment, advanced age, or concurrent ototoxic drug exposure. 1, 5 The risk-benefit ratio strongly favors rifaximin, lactulose, or other alternatives for any condition requiring prolonged aminoglycoside exposure. 1