What drugs cause ototoxicity (oto-toxicity)?

From the Guidelines

Ototoxic drugs, including aminoglycosides, platinum-based chemotherapy drugs, loop diuretics, salicylates, and antimalarials, can cause hearing loss, tinnitus, or balance problems, and patients taking these medications should be monitored with baseline and follow-up hearing tests, especially those receiving long-term therapy or high doses, as recommended by the most recent study 1. The risk of ototoxicity increases with higher doses, longer treatment duration, concurrent use of multiple ototoxic drugs, pre-existing hearing problems, kidney dysfunction, and advanced age. These medications typically cause damage by generating free radicals that destroy the delicate hair cells in the cochlea or by interfering with fluid balance in the inner ear. Symptoms may develop gradually or suddenly and can be temporary or permanent. Some key points to consider include:

• Aminoglycosides, such as gentamicin, tobramycin, and amikacin, can cause ototoxicity, with the risk increasing with higher doses and longer treatment duration 1.
• Platinum-based chemotherapy drugs, such as cisplatin and carboplatin, can also cause ototoxicity, especially with high cumulative doses 1.
• Loop diuretics, such as furosemide, can cause ototoxicity, especially when used in combination with other ototoxic medications 1.
• Salicylates, such as aspirin, can cause ototoxicity in high doses, and antimalarials, such as quinine and chloroquine, can also cause ototoxicity.
• Patients with pre-existing hearing problems, kidney dysfunction, or advanced age are at higher risk of ototoxicity.
• Monitoring for ototoxicity should include baseline and follow-up hearing tests, and alternative medications should be considered for patients with existing hearing impairment when possible. In terms of specific recommendations, the most recent study 1 recommends that patients taking ototoxic medications should be monitored with baseline and follow-up hearing tests, especially those receiving long-term therapy or high doses. Additionally, alternative medications should be considered for patients with existing hearing impairment when possible, and patients should be educated about the risks of ototoxicity and the importance of monitoring their hearing. Overall, the key to preventing ototoxicity is to monitor patients closely and adjust their treatment regimens as needed to minimize the risk of hearing loss and other complications.

From the FDA Drug Label

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 prevalence of hearing loss in children is particularly high and is estimated to be 40 to 60%. Decreased ability to hear normal conversational tones may occur Deafness after the initial dose of cisplatin has been reported. Ototoxic effects may be more severe in children receiving cisplatin. Hearing loss can be unilateral or bilateral and tends to become more frequent and severe with repeated cisplatin doses.

Ototoxicity is a known side effect of cisplatin, with up to 31% of patients experiencing it after a single dose. The risk of ototoxicity may be increased by prior or simultaneous cranial irradiation, and may be more severe in patients less than 5 years of age, patients being treated with other ototoxic drugs, and in patients with renal impairment 2.

• Key factors that increase the risk of ototoxicity:
  • Prior or simultaneous cranial irradiation
  • Age less than 5 years
  • Treatment with other ototoxic drugs
  • Renal impairment
• Monitoring for ototoxicity is recommended prior to initiation of therapy, prior to each subsequent dose, and for several years post therapy.

From the Research

Definition and Causes of Ototoxicity

• Ototoxicity refers to damage to the inner ear that leads to functional hearing loss or vestibular disorders caused by certain medications or environmental exposures 3, 4, 5.
• Ototoxic drugs include aminoglycoside and macrolide antibiotics, loop diuretics, platinum-based chemotherapeutic agents, some NSAIDs, and antimalarial medications 3.
• Exposure to these drugs can cause damage to the cochlea and vestibule, leading to hearing loss and balance problems 4, 5.

Mechanisms of Ototoxicity

• The mechanisms underlying ototoxicity involve damage to the hair cells and other structures in the inner ear 4, 5.
• Aminoglycoside antibiotics and cisplatin are known to induce ototoxicity by generating reactive oxygen species and disrupting the normal function of the inner ear 4, 5.
• Understanding the mechanisms of ototoxicity is crucial for developing strategies to prevent and treat drug-induced hearing loss 3, 4, 5.

Diagnosis and Monitoring of Ototoxicity

• Baseline audiometry is essential for monitoring ototoxicity in patients receiving cisplatin-based chemotherapy 6.
• Regular audiometric testing can help detect hearing loss and other ototoxic effects early on 6, 7.
• Validated survey instruments can be used to detect and monitor ototoxicity, including drug-induced tinnitus and dizziness 7.

Prevention and Management of Ototoxicity

• Strategies to prevent ototoxicity include using alternative medications, reducing dosage, and monitoring hearing function regularly 3, 4, 5.
• Otoprotective agents and other interventions are being developed to prevent and treat drug-induced hearing loss 4, 5.
• Clinical guidelines and protocols are available for diagnosing and managing ototoxicity in clinical practice and clinical trials 7.