What are the ototoxic and vestibulotoxic drugs?

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Ototoxic and Vestibulotoxic Drugs

The most clinically significant ototoxic and vestibulotoxic drugs are aminoglycosides (particularly gentamicin, amikacin, and streptomycin), platinum-based chemotherapy agents (especially cisplatin), and loop diuretics, with aminoglycosides causing irreversible vestibular damage and cisplatin causing irreversible bilateral sensorineural hearing loss in 20-75% of patients. 1

Major Drug Classes and Specific Agents

Platinum-Based Chemotherapy Agents (Primarily Ototoxic)

  • Cisplatin: The most ototoxic agent, causing irreversible damage to outer hair cells of the cochlea, resulting in bilateral sensorineural hearing loss in 20-75% of patients. Initially affects high frequencies but can progress to speech-critical lower frequencies. Approximately 40% of long-term survivors report persistent tinnitus 4-10 years post-treatment. 1

  • Carboplatin: Causes ototoxicity in approximately 5% of patients—significantly less than cisplatin but still clinically relevant. 1

  • Vinca alkaloids: Can cause ototoxicity to a much lesser extent than platinum agents. 1

  • Oxaliplatin: Very rarely causes ototoxicity. 1

Aminoglycosides (Both Ototoxic and Vestibulotoxic)

These antibiotics cause irreversible vestibulocochlear nerve damage with both auditory and vestibular toxicity: 2, 3

  • Amikacin: Causes ototoxicity with auditory effects predominating over vestibular effects, though both occur. Risk increases with prolonged use and older age. 3

  • Streptomycin: Among aminoglycosides, streptomycin is least associated with hearing loss but still causes significant vestibular toxicity. Patients should be instructed to watch for unsteady gait, tinnitus, and diminished hearing. 2, 3

  • Gentamicin: Well-documented vestibulotoxicity that profoundly affects quality of life, physical activities, and independence. Bilateral vestibular loss presents with ataxia, disequilibrium, and oscillopsia rather than vertigo or hearing loss. 4

  • Kanamycin and Capreomycin: Also cause ototoxicity and vestibulotoxicity. 3

Critical clinical point: Aminoglycoside ototoxicity and vestibular toxicity are usually irreversible. Ototoxicity on audiogram is defined as a 20 dB loss from baseline at any one test frequency or a 10 dB loss at any two adjacent test frequencies. 3

Loop Diuretics (Ototoxic)

Loop diuretics are identified as ototoxic agents, particularly when used concomitantly with other ototoxic drugs like aminoglycosides or cisplatin. 1 High-dose therapy is primarily associated with acute and transient hearing impairment or tinnitus. 5

Additional Ototoxic Agents

Based on comprehensive reviews, other drug classes include: 6, 7

  • Antimicrobials (53 medications identified as ototoxic)
  • Psychotropics (21 medications)
  • Antihypertensive/Antiarrhythmics (19 medications)
  • NSAIDs (18 medications) - high-dose therapy associated with acute, transient hearing impairment
  • Anti-malarial drugs
  • Industrial chemicals including solvents and nitriles 8

Risk Factors for Ototoxicity

For cisplatin specifically: 1

  • Increasing cumulative dose
  • Application schedule (100 mg/m² over 5 days is better than over 3 days)
  • Young age
  • Concomitant use of other ototoxic drugs (aminoglycosides and loop diuretics)
  • Preceding/concomitant radiotherapy to cochlea or cranial nerve VIII
  • Impaired pre-exposure hearing ability
  • Renal insufficiency
  • Specific genetic variants (glutathione S-transferase genotypes, WFS1 variants)

For aminoglycosides: 3

  • Older age
  • Duration of treatment
  • Cumulative dose
  • Prolonged use
  • Concomitant loop diuretics

Clinical Presentation Patterns

Ototoxicity (Hearing Loss)

  • Cisplatin: Bilateral sensorineural hearing loss starting at high frequencies, progressing to speech frequencies
  • Aminoglycosides: Hearing loss detected by audiometric testing; tinnitus and auditory disturbances

Vestibulotoxicity

  • Key presenting symptoms: Ataxia, disequilibrium, and oscillopsia (NOT vertigo or hearing loss as primary complaints) 4
  • Vertigo, loss of balance, unsteady gait
  • Bilateral vestibular loss profoundly affects quality of life and independence 4

Important Clinical Caveats

Synergistic toxicity occurs: The simultaneous administration of multiple ototoxic agents (e.g., cisplatin + aminoglycosides, aminoglycosides + loop diuretics) leads to synergistic hearing loss. 1, 5

Irreversibility: Both aminoglycoside and cisplatin-induced damage are typically irreversible and permanent. 1, 2, 3

Delayed presentation: Ototoxicity from antineoplastic agents or aminoglycosides is typically associated with delayed and irreversible loss, unlike the acute transient effects of diuretics or NSAIDs. 5

References

4
Research

Aminoglycoside Vestibulotoxicity.

Advances in oto-rhino-laryngology, 2019

5
Research

Drug-induced ototoxicity. Pathogenesis and prevention.

Medical toxicology and adverse drug experience, 1989

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