Which medications can cause sensorineural hearing loss (ototoxicity)?

Medications That Cause Hearing Loss (Ototoxicity)

Primary Ototoxic Drug Classes

The most important ototoxic medications are aminoglycoside antibiotics, platinum-based chemotherapy agents (especially cisplatin), loop diuretics, and to a lesser extent macrolide antibiotics and NSAIDs. 1, 2, 3

Aminoglycosides (Highest Risk - Permanent Damage)

Aminoglycosides cause dose-dependent, irreversible sensorineural hearing loss that destroys cochlear outer hair cells, initially affecting high frequencies (>8000 Hz) before progressing to speech-critical frequencies. 2, 3, 4

Risk hierarchy among aminoglycosides:

• Streptomycin: Primarily vestibulotoxic (balance problems) > cochleotoxic (hearing loss) 2
• Amikacin: Most effective with lower ototoxicity than kanamycin/capreomycin 1
• Tobramycin: Both auditory and vestibular damage, irreversible and usually bilateral 3
• Gentamicin: Substantial ototoxicity risk 5
• Kanamycin and Capreomycin: Significantly inferior safety profiles compared to amikacin 1

Critical risk factors for aminoglycoside ototoxicity:

• Cumulative dose and prolonged duration (>7-10 days) 2, 3
• Peak levels >12 mcg/mL or trough levels >2 mcg/mL 3
• Concurrent loop diuretics (furosemide, ethacrynic acid) or other ototoxic drugs 1, 2
• Renal insufficiency 1
• Advanced age 3
• Mitochondrial DNA variants (MT-RNR1 gene, especially m.1555A>G variant) - ototoxicity can occur even with therapeutic drug levels 2, 3

Platinum-Based Chemotherapy (High Risk - Permanent Damage)

Cisplatin is one of the most ototoxic agents, causing irreversible bilateral sensorineural hearing loss in 20-75% of patients by destroying cochlear outer hair cells from the basal turn. 1

Platinum agent ototoxicity ranking:

• Cisplatin: 20-75% incidence, irreversible, high-frequency loss progressing to speech frequencies 1
• Carboplatin: ~5% incidence when used alone; significant risk at cumulative doses >1500 mg/m² 1
• Oxaliplatin: Very rarely causes ototoxicity 1

Cisplatin-specific risk factors:

• Cumulative dose (higher total exposure) 1
• Administration schedule: 100 mg/m² over 3 days is worse than over 5 days 1
• Young age (children at higher risk) 1
• Concurrent aminoglycosides or loop diuretics 1
• Cranial radiotherapy ≥30 Gy to cochlea or cranial nerve VIII 1
• Pre-existing hearing impairment 1
• Renal insufficiency 1
• Genetic variants (glutathione S-transferase genotypes, WFS1 variants) 1

Tinnitus: 40% of cisplatin-treated survivors report persistent tinnitus 4-10 years post-treatment. 1

Loop Diuretics (Moderate Risk - Usually Reversible)

Loop diuretics (furosemide, ethacrynic acid) cause acute, typically transient hearing impairment, though high-dose or prolonged therapy can cause permanent damage. 1, 6

Synergistic toxicity: Loop diuretics dramatically potentiate aminoglycoside ototoxicity when co-administered. 1, 2

Macrolide Antibiotics (Moderate Risk - Usually Reversible)

Macrolides (erythromycin, azithromycin, clarithromycin) cause dose-dependent, reversible sensorineural hearing loss that typically resolves within 6-14 days after discontinuation. 7, 8

• Azithromycin caused hearing decrements in 25% of COPD patients versus 20% with placebo in randomized trials 7
• Patients with pre-existing hearing impairment should be counseled about potential transient worsening 7

Vancomycin (Low-Moderate Risk)

Vancomycin-associated ototoxicity is significantly increased when combined with aminoglycosides; the American Heart Association recommends avoiding this combination. 9

Management for patients with pre-existing hearing loss:

• Baseline audiometry before initiating therapy 9
• Target trough levels 5-10 mg/L to minimize risk 9
• Weekly audiometry for prolonged therapy (>2-4 weeks), especially in patients >53 years 9
• Immediate reporting of tinnitus, vertigo, or hearing changes 9

NSAIDs and Aspirin (Low Risk - Usually Reversible)

High-dose NSAIDs and aspirin cause acute, transient tinnitus and hearing impairment that resolves with dose reduction or discontinuation. 6, 10

Paradoxically, aspirin showed protective effects against gentamicin ototoxicity in one double-blind placebo-controlled trial conducted in China. 5

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Monitoring and Prevention Strategies

Baseline and Serial Audiometry

For cisplatin-treated patients:

• Baseline pure tone audiometry (500-8000 Hz) before chemotherapy 1
• Repeat at completion of therapy (minimum) 1
• Annual surveillance for children <6 years; every other year for older patients 1
• Survivors treated with cisplatin ± high-dose carboplatin (>1500 mg/m²) or cranial radiotherapy ≥30 Gy require lifelong surveillance 1

For aminoglycoside-treated patients:

• Baseline audiometry before therapy 2, 3
• Monthly high-quality audiometry during treatment 1
• Serial audiograms in high-risk patients (renal impairment, prolonged therapy, concurrent ototoxic drugs) 3

Drug Level Monitoring

Aminoglycosides:

• Monitor serum concentrations in all patients 3
• Avoid peak levels >12 mcg/mL and trough levels >2 mcg/mL 3
• Single daily dosing preferred over divided doses to minimize toxicity 1

Vancomycin:

• Target trough levels 5-10 mg/L in patients with pre-existing hearing loss 9

Genetic Screening Considerations

Screen for mitochondrial DNA variants (MT-RNR1, m.1555A>G) if there is known maternal history of aminoglycoside-induced ototoxicity; consider alternative antibiotics unless infection severity outweighs permanent hearing loss risk. 2, 3

Otoprotective Agents

Sodium thiosulfate for cisplatin in children with localized hepatoblastoma reduced hearing loss without compromising survival, but showed lower survival in disseminated disease (suggesting tumor protection). 1

No otoprotective agents are currently recommended for routine clinical use due to concerns about interfering with antimicrobial or antineoplastic efficacy. 11

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Medications That Do NOT Cause Hearing Loss

Tetracyclines (doxycycline, minocycline) are NOT ototoxic and are not listed among hearing loss-causing antibiotics by the American Thoracic Society, Infectious Diseases Society of America, or British Thoracic Society. 7

• Minocycline may cause dizziness/vertigo from CNS effects (not true ototoxicity) 7
• Doxycycline can be used safely as an alternative in patients with pre-existing hearing loss 7

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Critical Clinical Pitfalls

Avoid these high-risk combinations:

• Aminoglycosides + loop diuretics (synergistic permanent damage) 1, 2
• Aminoglycosides + vancomycin (additive nephrotoxicity and ototoxicity) 9
• Cisplatin + aminoglycosides or loop diuretics 1

Immediate discontinuation required if:

• Patient reports tinnitus, vertigo, dizziness, or subjective hearing decline 9, 2, 3
• Audiometry shows high-frequency hearing loss 1
• Rising trough aminoglycoside levels >2 mcg/mL 3

Patient counseling priorities:

• Instruct patients to report tinnitus or hearing changes immediately 9, 3
• Discuss occupational impact before cisplatin therapy (e.g., musicians, pilots) 1
• Warn about telephone use difficulties and multi-speaker conversation challenges as early signs 1