How to manage patients on ototoxic medications, such as gentamicin, to minimize the risk of hearing loss?

Management of Patients on Ototoxic Medications

Patients receiving aminoglycosides (gentamicin, amikacin) require mandatory baseline audiometry, monthly audiometric monitoring during treatment, serum drug level monitoring, and immediate drug discontinuation if ototoxicity develops, as aminoglycoside-induced hearing loss is often irreversible. 1, 2

Pre-Treatment Assessment

Baseline Evaluation

• Obtain baseline audiometry before initiating aminoglycoside therapy in all patients who can be tested 1
• Screen for hearing or balance difficulties through direct patient questioning 1
• Check renal function (serum creatinine, BUN, or creatinine clearance) as impaired renal function increases ototoxicity risk 1, 2
• Identify high-risk patients: elderly, those with pre-existing renal impairment, diabetes, immunocompromised state, or previous exposure to ototoxic drugs 1, 2, 3
• Review medication history for concomitant ototoxic agents (loop diuretics, cisplatin, vancomycin) which should be avoided 1, 2

During Treatment Monitoring

Aminoglycoside-Specific Protocols

Serum Drug Level Monitoring:

• Measure peak and trough levels to ensure therapeutic efficacy while avoiding toxic accumulation 1, 2
• Target trough levels <5 mg/L for amikacin 1
• Target peak levels: 25-35 mg/L for daily dosing or 65-80 mg/L for three-times-weekly dosing of amikacin 1
• For gentamicin: avoid prolonged peak levels >12 mcg/mL and trough levels >2 mcg/mL 2
• Timing: Check trough levels weekly for first 4 weeks, then can reduce to fortnightly when stable 1
• Peak levels: Measure in first week, repeat if poor response 1

Audiometric Monitoring:

• Perform monthly audiometry until aminoglycoside treatment ceases 1
• Define ototoxicity as 20 dB loss from baseline at any one test frequency OR 10 dB loss at any two adjacent test frequencies 1
• Final audiometry should be offered 2 months after the final dose 1
• For nebulized amikacin: Perform intermittent audiometry during treatment based on perceived risk and symptoms 1

Renal Function Monitoring:

• Monitor twice weekly during month 1, weekly during month 2, then fortnightly thereafter 1
• Increase monitoring frequency if evidence of renal impairment develops 1

Other Ototoxic Medications

Macrolides (Azithromycin, Clarithromycin):

• Screen for hearing/balance difficulties before initiating therapy 1
• Inform patients that ototoxicity is rare and almost always reversible with macrolides 1
• Instruct patients to report any hearing or balance changes promptly 1

Cisplatin:

• Administer sodium thiosulfate (15-minute infusion starting 6 hours after cisplatin completion) for non-metastatic cancers to prevent ototoxicity 1
• Strong recommendation for sodium thiosulfate in non-metastatic hepatoblastoma 1
• Weak recommendation against sodium thiosulfate in metastatic cancers due to uncertain survival effects 1

Action Upon Detection of Ototoxicity

Immediate Interventions

• Discontinue the aminoglycoside immediately if ototoxicity is detected on audiogram 1
• Alternative: Reduce dosing frequency if discontinuation is not feasible, though hearing loss already occurred is likely permanent 1
• Seek expert advice to consider regimen change 1

Patient Instructions

• Instruct patients to stop treatment immediately and inform prescriber if they develop:
  • Tinnitus (ringing in ears) 1
  • Vertigo or loss of balance 1
  • Hearing loss 1
  • Auditory disturbances 1

Dose Adjustments in Renal Impairment

For Aminoglycosides:

• Reduce dose and/or extend dosing interval when GFR <60 mL/min/1.73m² 1
• Base dosing on ideal body weight in obese patients, not actual weight 1, 2
• Monitor serum levels closely as accumulation risk increases with renal dysfunction 1, 2
• Use creatinine clearance to guide interval adjustments: multiply serum creatinine (mg/100 mL) by 8 to approximate dosing interval in hours 2

Special Populations

Elderly Patients:

• Higher risk for both nephrotoxicity and ototoxicity 1
• Monitor more closely and consider dose reduction 1
• Accurate renal assessment critical as serum creatinine may underestimate renal insufficiency due to decreased muscle mass 4

Patients with Pre-existing Hearing Loss:

• Inform about potential for further, almost always reversible deterioration with macrolides 1
• Unknown efficacy of sodium thiosulfate in preventing further deterioration in those with pre-existing cisplatin-induced hearing loss 1

Pregnancy:

• Avoid aminoglycosides in second or third trimester due to risk of vestibular or auditory nerve damage to fetus 1

Critical Pitfalls to Avoid

• Never combine multiple aminoglycosides (amikacin with capreomycin, kanamycin, or streptomycin) as there is no clinical benefit and increased toxicity risk 1
• Avoid concurrent loop diuretics (furosemide, ethacrynic acid) as they potentiate ototoxicity 1, 2
• Do not delay audiometry until symptoms appear, as damage may already be irreversible 1, 2
• Do not rely on patient-reported symptoms alone for monitoring, as objective audiometry is essential 1
• Aminoglycoside-induced hearing loss is usually irreversible, unlike macrolide-associated ototoxicity which typically reverses upon discontinuation 1, 5, 2