Case report: Naproxen-associated sudden sensorineural hearing loss

McKinnon, Brian J

LCDR Brian J. McKinnon, MC USN*

CAPT Lorenz F. Lassen, MC USN*

Naproxen is a commonly used nonsteroidal anti-inflammatory drug (NSAID) whose side effects include tinnitus and transient hearing loss. Sudden sensorineural hearing loss has rarely been reported as a result of NSAID use. This usually occurs in patients taking other ototoxic medications, with poor renal function, or with autoimmune disease. This article reports the case of an otherwise healthy patient who experienced permanent sensorineural hearing loss after a brief course of naproxen and reviews the literature on NSAID-related permanent sensorineural hearing loss.

Introduction

Naproxen is a commonly used nonsteroidal anti-inflammatory drug (NSAID) that is generally considered effective, safe, and well tolerated. It is available both by prescription and as an over-the-counter medication. A propionic acid derivative related to ibuprofen, its anti-inflammatory effects are thought to be from the inhibition of cyclooxygenase and the resultant decrease of prostaglandin synthesis. Naproxen is completely absorbed from the gastrointestinal tract and is 99% bound to the serum. Although temporary ototoxic side effects (tinnitus with occasional transient hearing loss and/or vertigo) have been reported to occur in 1 to 9% of patients,' sensorineural hearing loss from the use of naproxen is rare.2-5

Case Report

An otherwise healthy 35-year-old African-American woman was prescribed naproxen (500 mg by mouth twice a day) for low-back pain. Forty-eight hours after the first naproxen dose, she experienced bilateral hearing loss, tinnitus, otalgia, intolerance to loud noise, and dizziness. She was seen by a primary care physician and referred to an otolaryngologist.

Head and neck examination was normal. Audiometric evaluation showed moderate, bilateral sensorineural hearing loss (Fig. 1). A military reference audiogram, done several years earlier, was normal. Rotational chair vestibular examination was normal, and electronystagmography showed left-sided vestibular nerve weakness. Magnetic resonance imaging of the brain and internal auditory canals was normal. There was a slightly elevated erythrocyte sedimentation rate (23 mm/h) and a weakly positive anti-nuclear antibody test (1:40). Raji cell assay was negative. Other laboratory studies (complete blood count, electrolytes, complement profile, microhemagglutination-treponema pallidum, and thyroid and liver function tests) were normal.

The patient was given a 2-week course of prednisone (60 mg/d) without resolution of her symptoms. Follow-up 6 months later showed no significant improvement in hearing, tinnitus, or noise intolerance. At present, she uses bilateral hearing aides, but these are uncomfortable because of her poor dynamic range and hyperacusis.

Discussion

Although salicylates have been used since the 4th century BC, it was Miller in 1877 who recognized the ototoxic effects of salicylates in high doses.3 Typically, the hearing loss is a temporary 20- to 40-dB threshold shift that is bilateral, symmetric, and sensorineural. Tinnitus usually accompanies hearing loss and is a result of this auditory distortion caused by alterations of cochlear neuron activity. Tinnitus may precede the development of sensorineural hearing loss.3

The mechanisms of naproxen's ototoxic effects have been suggested to be similar to those described for salicylates.35 Ototoxicity appears to be multifactorial.3 Salicylates and NSAIDs have been shown to increase levels of norepinephrine, decrease concentrations of prostaglandins, and increase leukotrienes in the perilymph.6 Decreased blood flow and cochlear hemorrhage (which may be influenced by catecholamines and arachidonic metabolites) have been suggested as occurring in salicylate and NSAID ototoxicity.3-6 Reversible morphologic changes to cochlear outer hair cells have been observed that may result from changes in cellular permeability.3 Physiologic evidence of cochlear outer hair cell injury is strongly supported by diminished otoacoustic emission activity during salicylate toxicity.3

Several reports of permanent sensorineural hearing loss associated with either salicylates or NSAIDs describe individuals who had underlying renal dysfunction, rheumatoid arthritis, polyarteritis nodosa, advanced age, or the use of NSAIDs with other potentially ototoxic medications.2'8 In 1982, Chapman2 reported five patients who developed sensorineural hearing loss while taking naproxen; only two patients completely recovered after stopping the medication. Chapman implicated impaired renal function as a cofactor in one patient with permanent hearing loss. Similar adverse reactions have been reported with piroxicam7 and ketoralac.1

The patient described here had a slightly elevated erythrocyte sedimentation rate and a weakly positive anti-nuclear antibody test. Although there were no other signs or symptoms of autoimmune disease, she could have had a subclinical early autoimmune problem. Kastanioudakis et al. evaluated 45 patients with rheumatoid arthritis and observed a 35.5% incidence of mild symmetric bilateral sensorineural hearing loss.9 There was no correlation of hearing loss with drug therapy (which included NSAIDs, D-penicillamine, plaquenil, and methotrexate), age, sex, disease duration, articular and extra-articular manifestation, or the presence of autoantibodies. Hence, the significance of the minimally abnormal anti-nuclear antibody test and erythrocyte sedimentation rate in an otherwise healthy individual to the development of sudden hearing loss is difficult to interpret.

Conclusions

That salicylates and NSAIDs can cause reversible sensorineural hearing loss is well known to most health care providers. What is not as well appreciated is that NSAID-induced sensorineural hearing loss can be permanent. Cofactors may include renal disease and autoimmune disorders. Clearly, the prescribing health care provider should ask the patient about such conditions and warn of hearing loss as a potential side effect.

That the first symptom of sensorineural hearing loss from NSAIDs is tinnitus should be communicated to the patient. The patient should be told to immediately discontinue NSAIDs and seek help should tinnitus or distorted hearing develop.

References

1. Clinical Pharmacology. Gold Standard Multimedia, 1997. 2. Chapman P: Naproxen and sudden hearing loss. J Laryngol Otol 1982; 96: 163-6. 3. Jung TI, Choi DC, Park YS, Lee CS, Rhee CK: Ototoxicity of salicylate, nonsteroldal antiinflammatory drugs, and quinine. Otolaryngol Clin North Am 1993; 26: 791-810.

4. Brien JA: Ototoxicity associated with salicylates: a brief review. Drug Saf 1993; 9: 143-8.

Seligmann H, Goldsher M, Fradis M, Ben-David J, Podoshin L: Drug-induced tinnitus and other hearing disorders. Drug Saf 1996; 14: 198-212. Jung IT, Baer W, Park YM, Woo HY, Rozehnal S, Miller SK: Effect of round window membrane application of salicylate and indomethacin on hearing and levels of arachidonic acid metabolites in perilymph. Acta Oto-Laryngol Suppl 1992; 493: 81-7.

Vernick DM, Kelly JH: Sudden hearing loss associated with piroxicam. Am J Otol 1986; 7: 97-8.

Schaab KC, Setzen G, Dickinson ET: Acute sensorineural hearing loss following intravenous ketoralac administration. J Emerg Med 1995;13: 509-13. Kastanioudakis I, Moustopoulos MH, Drosos AA, Tsiakou E, Danielidis V, Skevas A: Inner ear involvement in rheumatoid arthritis: a prospective clinical study. J laryngol Otol 1995; 109: 713-8.

*Department of Otolaryngology-Head and Neck Surgery, Naval Medical Center, Portsmouth, VA 23708-2197.

t Department of Otolaryngology-Head and Neck Surgery. Eastern Virginia Medical School, Norfolk, VA 23507-1912.

The views expressed in this article are those of the authors and do not reflect the official policy or position of the Department of the Navy, the Department of Defense, or the U.S. Government.

Reprint requests: LCDR Brian J. McKinnon, MC USN, Naval Medical Center, Portsmouth, Department of Otolaryngology-Head and Neck Surgery (Code 0609), 630 John Paul Jones Circle, Portsmouth, VA 23708-2197.

This manuscript was received for review in December 1997 and was accepted for publication in March 1998.

Copyright Association of Military Surgeons of the U.S. Nov 1998
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