What are examples of ototoxic drugs and how can their effects be minimized?

Ototoxic Drugs and Strategies to Minimize Their Effects

Cisplatin and aminoglycoside antibiotics are the most potent ototoxic medications, requiring careful monitoring and preventive strategies to minimize permanent hearing damage and tinnitus. 1, 2

Common Ototoxic Medications

High-Risk Medications

• Platinum-based chemotherapy agents

  • Cisplatin (highest risk: 20-75% of patients develop hearing loss) 1
  • Carboplatin (lower risk: ~5% of patients) 1
  • Oxaliplatin (very rare ototoxicity) 1

• Aminoglycoside antibiotics 3, 4

  • Gentamicin
  • Tobramycin
  • Amikacin

• Loop diuretics 3, 5

  • Furosemide
  • Ethacrynic acid

Moderate-Risk Medications

• NSAIDs (typically reversible) 3

  • Aspirin/salicylates
  • Ibuprofen

• Other medications 3

  • Macrolide antibiotics (erythromycin)
  • Vancomycin
  • Anti-arrhythmics
  • Calcium channel blockers
  • ACE inhibitors
  • Antimalarials
  • Phosphodiesterase-5 inhibitors

Risk Factors for Ototoxicity

• Treatment-related factors

  • Cumulative dose (especially for cisplatin) 1
  • Rapid infusion rates
  • Concomitant use of multiple ototoxic drugs 3, 5

• Patient-related factors

  • Young age (children more susceptible) 1, 2
  • Pre-existing hearing loss 3
  • Renal insufficiency 2
  • Genetic variants (e.g., glutathione S-transferase genotypes, WFS1 variants) 1
  • Prior/concurrent cranial radiation 1, 2

Mechanisms of Ototoxicity

• Cisplatin: Damages outer hair cells of the cochlea, starting with the basal region (high frequencies) 1
• Aminoglycosides: Increase cell membrane permeability in the inner ear 5
• Loop diuretics: Can cause acute and transient hearing impairment, especially when combined with aminoglycosides 5

Prevention and Monitoring Strategies

Before Treatment

1. Baseline assessment

   • Pure tone audiometry (including frequencies 500-8000 Hz) before starting platinum agents 1
   • Document pre-existing hearing conditions

2. Risk evaluation

   • Consider patient's profession and hearing-dependent activities 1
   • Identify concurrent ototoxic medications
   • Assess renal function (especially for cisplatin and aminoglycosides) 2

During Treatment

1. Monitoring

   • Regular audiometric testing during treatment with high-risk medications 1
   • Encourage patients to report early signs of hearing impairment (difficulty with telephone conversations, trouble understanding speech in noisy environments) 1

2. Dose modifications

   • Consider spreading cisplatin doses over more days (better tolerance than concentrated doses) 1
   • Use the lowest effective dose of ototoxic medications 3
   • Monitor renal function regularly 2

3. Preventive agents

   • Sodium thiosulfate: Shows promise in children with localized hepatoblastoma, but concerns exist about possible tumor protection in metastatic disease 1
   • Not recommended: Amifostine, sodium diethyldithiocarbamate, intratympanic therapies (dexamethasone, acetylcysteine) 1

After Treatment

• Continue audiometric monitoring after completion of therapy 1
• Early intervention for hearing loss (hearing aids, assistive devices) 1
• For tinnitus: Consider cognitive behavioral therapy (CBT) 1

Special Considerations

Children

• Higher susceptibility to ototoxicity (40-60% hearing loss with cisplatin) 2
• More significant impact on speech, language development, and education 1
• Require more vigilant monitoring and consideration of preventive strategies 1

Elderly Patients

• May have pre-existing hearing loss
• Often have decreased renal function, increasing risk 2
• May require dose adjustments based on renal function 2

Management of Established Ototoxicity

• Hearing aids for hearing loss 1
• Cochlear implants for profound hearing loss 1
• Assistive devices (telephone amplifiers, auditory trainers) 1
• Cognitive behavioral therapy for tinnitus management 1

Pitfalls to Avoid

• Combining multiple ototoxic medications (particularly aminoglycosides with loop diuretics) 5
• Failing to monitor renal function during treatment with cisplatin or aminoglycosides 2
• Overlooking early signs of hearing impairment during treatment 1
• Inadequate follow-up after completion of ototoxic therapy 1
• Using ASHA criteria for grading hearing loss (may overestimate the problem) 1

By implementing these strategies, healthcare providers can minimize the risk and impact of medication-induced ototoxicity while still providing necessary treatment for serious conditions.