Over the Counter Pain Relievers and Ototoxicity

Nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen are the two most commonly used medications, with up to 24% of adults taking ibuprofen (an NSAID) and 28% taking acetaminophen in any week (Kyle et al., 2015). Salicylate, the active ingredient in aspirin, is also widely used for pain control and reduction of inflammation. With such ubiquitous use, a causal relationship with ototoxicity would have enormous public health impact, yet conclusions vary related to the impact of these over the counter (OTC) medications on hearing and tinnitus. Nevertheless, as many patients unfortunately conclude that all OTC medications are safe because they require no prescription, the potential of OTC pain relievers to harm auditory function illustrates the need for drug developers, regulators, and clinicians to be aware of ototoxic risks.

Studies of the impact of OTC pain relievers on humans have generally shown a deleterious effect on auditory function overall, but the specific harm of different medications and doses varies by study and sample details. Increased risk of hearing loss is correlated with long-term use of acetaminophen and ibuprofen individually (Kyle et al., 2015) and together (Curhan et al., 2012). When considered as a group, NSAIDs in general have been linked to a 20% increased risk of self-reported hearing loss (Kyle et al., 2015). An epidemiological survey of over 62,000 nurses showed that ibuprofen and acetaminophen use in men and women, and salicylate use in men, 2 or more days per week was correlated with an increased risk of hearing loss, but such a relationship was not demonstrated for salicylate use in women (Curhan et al., 2012). It is possible, however, that different hearing loss measurement techniques between men and women contributed to this inconsistency. Other studies have demonstrated a 15-40 dB hearing loss and reduced or abolished DPOAEs (indicated impaired outer hair cell function) with moderate use of salicylate (Jiang et al., 2017; Sheppard et al., 2014).

The hearing loss and tinnitus that result from NSAID and acetaminophen might be reversible, at least in some cases. For example, salicylate affects auditory function in several ways, such as causing temporary cochlear vascular changes, impairing outer hair cell electromotility and amplification, and reducing neural output by limiting the compound action potential of the cochlea (Curhan et al., 2012). These mechanisms are usually temporary, but salicylate can also lead to permanent outer hair cell damage and spiral ganglion neuron apoptosis if chronically administered (Sheppard et al., 2014).

There may be some controversy about the specific relationships to hearing loss of individual OTC pain relievers, but in many cases this is due to inconsistencies of study design. For example, studies may use self-reporting of hearing loss which is unconfirmed by audiometric data, may contain no information about the confounding effect of lifetime noise exposure, and may have small sample sizes that reduce statistical power (Curhan et al., 2012; Kyle et al., 2015). However, few auditory scientists and clinicians doubt that a significant ototoxic potential of OTC pain relievers exists. Since OTC medications are often considered to be safe by users because no prescription is needed, the risks of toxicity to the ears and other organ systems should be considered by clinicians, scientists, regulators, and drug developers.

References Curhan, S.G., Shargorodsky, J. Eavey, R., & Curhan, G.C. (2012). Analgesic use and the risk of hearing loss in women. Am J Epidemiol, 176(6), 544-554.

Jiang, C., Luo, B., Senthilvelan, M., Chen, G.-D., & Salvi, R. (2017). Plastic changes along auditory pathway during salicylate-induced ototoxicity: hyperactivity and CF shifts. Hear Res, 347, 28-40.

Kyle, M.E., Wang, J.C., & Shin, J.J. (2015). Impact of nonaspirin nonsteroidal anti-inflammatory agents and acetaminophen on sensorineural hearing loss: a systematic review. Otolaryngol Head Neck Surg, 152(3), 393-409.

Sheppard, A., Hayes, S.H., Chen, G.-D., Ralli, M., & Salvi, R. (2014). Review of salicylate-induced hearing loss, neurotoxicity, tinnitus and neuropathophysiology. Acta Oto Italica, 34, 79-93.

Authors David Hicks, M.D.: Dr. Hicks directs business development at Turner Scientific, and has significant training and experience in clinical treatment of ear disorders. Contact: dhicks@turnerscientific.com

Jeremy Turner, Ph.D.: Dr. Turner is the founder and Chief Scientific Officer at Turner Scientific. He completed his Ph.D. in auditory neuroscience, and has more than 22 years’ experience in preclinical hearing loss, tinnitus, and ototoxicity research. Contact: jturner@turnerscientific.com

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