What are the ototoxic drugs that pose a significant risk to patients?

From the Guidelines

Ototoxic drugs that pose a significant risk to patients include aminoglycoside antibiotics, platinum-based chemotherapy agents, loop diuretics, macrolide antibiotics, antimalarials, and certain NSAIDs. These medications can damage the inner ear structures, leading to hearing loss, tinnitus, or balance disorders. The risk increases with higher doses, longer treatment durations, concurrent use of multiple ototoxic medications, pre-existing hearing problems, renal impairment, advanced age, and genetic susceptibility 1. Aminoglycosides primarily damage cochlear hair cells, while platinum compounds can cause permanent bilateral hearing loss, particularly affecting high frequencies 1. Some key points to consider when managing patients on these medications include:

• Using the lowest effective dose for the shortest duration necessary
• Maintaining proper hydration to reduce risk
• Considering alternative medications for high-risk patients
• Implementing regular monitoring during therapy, including baseline hearing tests before treatment and follow-up evaluations after treatment completion 1
• Being aware of the potential for increased risk with certain patient factors, such as young age, concomitant applications of other ototoxic drugs, preceding/concomitant radiotherapy to cochlea or cranial nerve VIII, impaired pre-exposure hearing ability, renal insufficiency, and specific genetic variants 1. It is essential to weigh the benefits of these medications against the potential risks and to take steps to minimize the risk of ototoxicity whenever possible.

From the FDA Drug Label

Ototoxicity with use of Tobramycin for Injection Tobramycin for Injection can cause both auditory and vestibular eighth nerve damage. Ototoxicity has been observed in up to 31% of patients treated with a single dose of cisplatin 50 mg/m 2, and is manifested by tinnitus and/or hearing loss in the high frequency range (4,000 to 8,000 Hz).

The ototoxic drugs that pose a significant risk to patients are:

• Tobramycin: can cause both auditory and vestibular eighth nerve damage, with symptoms including dizziness, vertigo, tinnitus, roaring in the ears, and hearing loss 2
• Cisplatin: can cause ototoxicity, manifested by tinnitus and/or hearing loss in the high frequency range, with a prevalence of up to 31% in patients treated with a single dose of 50 mg/m 2 3

From the Research

Ototoxic Drugs

The following are some of the ototoxic drugs that pose a significant risk to patients:

• Aminoglycosides, such as gentamicin 4, 5, 6, 7, streptomycin 5, amikacin 5, 8, neomycin 5, dihydrostreptomycin 5, and kanamycin 5
• Loop diuretics, such as furosemide 4, 7
• Cisplatin 6, 7
• Salicylates 5, 7

Mechanism of Ototoxicity

These drugs can cause ototoxicity by:

• Generating free radicals within the inner ear, leading to permanent damage to sensory cells and neurons 5, 6
• Interacting with cell membranes in the inner ear, increasing their permeability and allowing other ototoxic medications to penetrate and cause damage 4
• Targeting the outer hair cells in the basal turn of the cochlea, leading to high-frequency sensorineural hearing loss 6

Risk Factors

Several risk factors can predispose a patient to developing ototoxicity, including:

• Preexisting disorders of hearing and balance 4
• Hypovolemia, bacteremia, liver and renal dysfunction 4
• Simultaneous administration of other ototoxic medications 4, 5, 6, 7
• Cumulative dose and duration of aminoglycoside therapy 4
• Genetic mutations, such as the 1555 chromosomal mutation 4