What is the risk of ototoxicity associated with Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)?

From the Guidelines

Ototoxicity from NSAIDs is a rare but potentially serious side effect that can cause temporary or permanent hearing loss, tinnitus, or balance problems. The most commonly implicated NSAIDs include aspirin (especially at high doses exceeding 2.4g daily), ibuprofen, naproxen, and indomethacin.

Key Points to Consider

• The risk increases with higher doses, longer duration of use, and in patients with pre-existing hearing problems or kidney dysfunction.
• The mechanism involves reduced cochlear blood flow, inhibition of prostaglandin synthesis in the inner ear, and direct damage to cochlear hair cells.
• Symptoms typically develop gradually and may be reversible if the medication is stopped promptly.
• Patients taking high-dose NSAIDs should be monitored for early signs of hearing changes or tinnitus.
• Those with risk factors should consider using the lowest effective dose for the shortest duration possible.
• Alternative pain management strategies may be appropriate for patients with existing hearing impairment.
• If ototoxicity is suspected, the NSAID should be discontinued immediately and audiological evaluation should be performed to assess hearing function. However, the provided evidence does not directly address the risk of ototoxicity associated with NSAIDs, as the studies focus on other topics, such as the management of non-tuberculous mycobacterial pulmonary disease 1 and the use of nonsteroidal anti-inflammatory agents, including cyclooxygenase-2 enzyme inhibitors and aspirin 1.

Clinical Decision Making

In clinical practice, it is essential to prioritize the patient's safety and well-being, and consider the potential risks and benefits of NSAID use.

• Based on the available evidence, it is recommended to use the lowest effective dose of NSAIDs for the shortest duration possible to minimize the risk of ototoxicity.
• Patients with pre-existing hearing problems or kidney dysfunction should be closely monitored for signs of ototoxicity.
• Alternative pain management strategies should be considered for patients with existing hearing impairment.
• If ototoxicity is suspected, the NSAID should be discontinued immediately, and audiological evaluation should be performed to assess hearing function.

From the FDA Drug Label

In patients taking naproxen in clinical trials, the most frequently reported adverse experiences in approximately 1% to 10% of patients are: ... Special Senses: tinnitus*, visual disturbances, hearing disturbances The following are additional adverse experiences reported in < 1% of patients taking naproxen during clinical trials and through postmarketing reports ... Special Senses: hearing impairment, corneal opacity, papillitis, retrobulbar opticneuritis, papilledema

The risk of ototoxicity associated with Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) includes:

• Tinnitus (reported in approximately 1% to 10% of patients)
• Hearing disturbances (reported in approximately 1% to 10% of patients)
• Hearing impairment (reported in less than 1% of patients) 2

From the Research

Risk of Ototoxicity Associated with NSAIDs

• The risk of ototoxicity associated with Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) has been studied in various research papers 3, 4, 5, 6, 7.
• A study published in 2010 found that regular use of NSAIDs was independently associated with an increased risk of hearing loss, with a multivariate-adjusted hazard ratio of 1.21 (95% CI, 1.11-1.33) 3.
• Another study published in 2006 discussed the molecular insights for prevention and clinical management of drug ototoxicity, including NSAIDs, and suggested that understanding the mechanisms of drug ototoxicity may lead to new strategies for preventing and curing drug-induced hearing loss 4.
• A review published in 1993 discussed the ototoxicity associated with salicylates, including NSAIDs, and found that tinnitus and hearing loss, usually reversible, are associated with acute intoxication and long-term administration of salicylates 5.
• A case report published in 2010 described a rare but serious side effect of NSAIDs, irreversible sensorineural deafness, and highlighted the importance of monitoring patients for signs of ototoxicity, such as tinnitus 6.
• A study published in 1996 discussed drug-induced tinnitus and other hearing disorders, including those associated with NSAIDs, and emphasized the importance of prevention and monitoring to minimize the risk of ototoxicity 7.

Key Findings

• Regular use of NSAIDs increases the risk of hearing loss, particularly in younger individuals 3.
• The risk of ototoxicity associated with NSAIDs may be related to biochemical and electrophysiological changes in the inner ear and eighth cranial nerve impulse transmission 5, 7.
• Monitoring patients for signs of ototoxicity, such as tinnitus, is crucial to prevent permanent damage 6.
• Understanding the mechanisms of drug ototoxicity may lead to new strategies for preventing and curing drug-induced hearing loss 4.