July/August 2023

Hearing Loss: Medication-Related Hearing Loss
By Mark Coggins, PharmD, BCGP, FASCP
Today’s Geriatric Medicine
Vol. 16 No. 4 P. 5

Awareness and Education Can Preserve Hearing

It’s well known that hearing loss—a common problem that can be caused by loud noise, disease, genetic variations, and medications—increases as people age. However, older adults may be at a heightened risk of medication-related hearing loss, which can be easily overlooked since hearing impairment is viewed as a normal part of the aging process. And because hearing loss can have a significant impact on a person’s quality of life and well-being, affecting their ability to communicate, social interactions, education, work performance, and mental health, it’s important for health care professionals to take an active role in helping older adults identify and minimize and impairment caused by medications.

Ototoxicity
Medications and other substances that cause hearing loss are called ototoxic, which means “poisonous to the ear.” Hundreds of medications, both prescription and over-the-counter, have been identified as being ototoxic and can damage structures within the inner ear or vestibule-cochlear nerve, resulting in symptoms of ototoxicity.1

Symptoms of Ototoxicity
Hearing loss can be unilateral (occurring in one ear) or bilateral (occurring in both ears) and may be complete or partial, depending on the severity of damage to the hair cells lining the cochlea. Tinnitus is often one of the first symptoms of damage and may be described as ringing in the ears, buzzing, hissing, roaring, humming, or clicking sounds. The sound may be soft or loud, high or low pitched, and may occur in one or both ears.

Other common symptoms of ototoxicity may include the following:2

• difficulty hearing speech or sounds;
• hearing muffled or distorted sounds;
• dizziness or vertigo (bouncing vision);
• nausea or vomiting;
• loss of balance or coordination; and
• unsteady gait.

Risk Factors for Ototoxicity
Factors that increase the risk for ototoxicity include the following:3

• impaired renal function;
• prolonged treatment course;
• advanced age (older than 65);
• previous aminoglycoside therapy;
• sensorineural hearing loss; and
• occupational noise exposure while taking ototoxic medications.
• The risk of ototoxicity is also increased when multiple ototoxic medications are used at the same time.

Common Ototoxic Medications
Ototoxic medications may cause permanent hearing loss or temporary or reversible hearing loss. Common classes of medications that can cause permanent hearing loss include aminoglycoside antibiotics and platinum-based chemotherapy agents, while loop diuretics, salicylates, and NSAIDs are more likely to cause temporary or reversible hearing loss.

Aminoglycoside Antibiotics
Aminoglycoside antibiotics, including streptomycin, amikacin, kanamycin, tobramycin, and gentamicin, are powerful medications used to treat serious bacterial infections such as meningitis and sepsis. Because these are known to cause permanent hearing damage, they should be reserved to treat serious life-threatening diseases—situations in which saving a patient’s life outweighs the possibility of damage to hearing.4 The risk of hearing loss increases with higher doses and longer courses of treatment. These antibiotics also tend to be slowly cleared from the fluid in the inner ear and can sometimes be detected in the inner ear fluid months after the final dose is given. As a result, hearing loss can be delayed in onset and may occur long after the antibiotic was used. Patients with eardrum perforation should not be prescribed topical aminoglycoside agents such as neomycin otic drops because these medications could be absorbed in the inner ear, resulting in damage and hearing loss.5

Chemotherapeutic Agents
Some medications used to treat cancer can cause hearing loss. For example, platinum-based therapeutic agents, including cisplatin, carboplatin, and oxaliplatin, as well as other chemotherapeutic agents such as bleomycin, and cyclophosphamide, increase risk for permanent hearing loss. In the case of cisplatin, hearing loss may occur in 40% to 80% of patients given the drug.6 The risk of hearing loss depends on the type and dose of chemotherapy as well as other factors such as age, kidney function, and genetic susceptibility. Ototoxic effects can be minimized, though not always prevented, by close blood level monitoring.

Loop Diuretics
Loop diuretics such as furosemide, bumetanide, chlorthalidone, and torsemide are used to treat fluid retention (edema) caused by conditions such as heart failure, kidney disease, or liver disease. They can cause temporary or reversible hearing loss by altering the fluid balance in the inner ear.7 Hearing loss may occur when these drugs are given intravenously for acute kidney failure, acute hypertensive crisis, or acute pulmonary edema/congestive heart failure. It may begin within minutes or hours of taking the medication and resolve within hours or days after stopping it. However, the repeated or prolonged use of loop diuretics increases the risk of permanent hearing loss. Rare cases of ototoxicity have occurred in patients with chronic kidney disease taking these medications orally in high doses.

Quinine
Quinine is a drug used to treat malaria, a parasitic infection transmitted by mosquitoes. It’s also become increasingly popular in the treatment of nocturnal leg cramps. Quinine medications can cause a variety of adverse effects at usual therapeutic doses, including cinchonism (marked by tinnitus, high-tone hearing loss, and other symptoms).8 Hearing loss usually occurs within hours or days of taking quinine and resolves within days or weeks after stopping it. However, high doses or long-term use of quinine may increase the risk of permanent hearing loss.

Salicylates
Salicylates, which include aspirin, can cause reversible hearing loss by interfering with the function of the cochlea.9 The hearing loss usually occurs within hours or days of taking salicylates and resolves within hours or days after stopping them. However, high doses or long-term use of salicylates may increase the risk of permanent hearing loss.

NSAIDs
NSAIDs are a class of medications used to treat pain, inflammation, and fever. Common NSAIDs include naproxen, ibuprofen, meloxicam, and many others. Several mechanisms may affect hearing loss through a number of different mechanisms.10 NSAIDs can reduce blood flow to the inner ear, which can impair its function and lead to cell death. They can also interfere with the balance of chemicals in the inner ear, such as glutamate and potassium, which are important for transmitting sound signals to the brain. Further, they can increase oxidative stress and inflammation in the inner ear, which can damage its structures and cells. NSAIDs also can cause kidney injury and reduce renal function, which may increase the risk of ototoxicity when given with other ototoxic medications. Most can cause temporary tinnitus and hearing loss, but the toxic effects typically can be reversed once the medications are discontinued.

Recommendations to Minimize Ototoxicity
Drug accumulation of an ototoxic medication can increase the exposure of the inner ear to toxic effects. Drug accumulation can be influenced by factors such as dose, frequency, duration of use, metabolism, excretion, and interactions with other drugs. As drug concentrations increase in the blood and tissues, so does the risk of adverse effects. It is essential to use the lowest effective dose possible and closely monitor blood levels of known ototoxic medications. Older adults are at greater risk of ototoxicity because of several factors that can contribute to drug accumulation in the body, including reduced renal and hepatic function, increased potential for polypharmacy and drug interactions, increased sensitivity to adverse drug reactions, and decreased metabolism of medications.2 In addition, remember that combination therapy using ototoxic medications significantly increases the risk of hearing loss.

The Provider’s Role in Prevention
Health care professionals should increase patient awareness about ototoxic medications and their associated risks. Because it’s not always apparent which drugs may be ototoxic, it’s important to educate patients that almost any medication could cause hearing loss, make them aware of potential symptoms of ototoxicity, and encourage them to contact their doctors immediately if symptoms occur. Recognizing symptoms early can allow prompt identification and possibly help prevent permanent damage.

Providers should refer patients for hearing evaluations. Symptoms alone may not always be reliable. When possible, it may be appropriate to refer patients to see an audiologist for a baseline assessment prior to treatment and regularly during treatment. Although monitoring alone won’t prevent ototoxic hearing loss, it can help identify problems earlier and may help prevent permanent hearing loss.

To help patients minimize the risk of hearing loss from ototoxic medications, health care providers should recommend that their patients do the following:

• Avoid ototoxic drugs if possible.

• Remember that over-the-counter medications such as NSAIDS (eg, ibuprofen, naproxen) and aspirin can be ototoxic.

• Only use ototoxic drugs when other effective and safer alternatives are unavailable.

For patients who take ototoxic medications, the following recommendations may be helpful. Advise patients to do the following:

• Avoid exposure to loud noises and use hearing protection since loud noise can worsen the damage to the inner ear and increase the risk of permanent hearing loss.

• Stay hydrated and eat a balanced diet, as dehydration and malnutrition can affect blood circulation and increase the toxicity of the drugs. There’s also evidence that the consumption of antioxidants may help reduce ototoxicity.

— Mark D. Coggins, PharmD, BCGP, FASCP, is vice president of pharmacy services and medication management for skilled nursing centers operated by Diversicare in nine states and is a past director on the board of the American Society of Consultant Pharmacists. He was nationally recognized by the Commission for Certification in Geriatric Pharmacy with the 2010 Excellence in Geriatric Pharmacy Practice Award.

References
1. Bauman N. Drugs and tinnitus: put yourself in the driver’s seat. Tinnitus Today. 2009:34(1):21-23.

2. Cianfrone G, Pentangelo D, Cianfrone F, et al. Pharmacological drugs inducing ototoxicity, vestibular symptoms and tinnitus: a reasoned and updated guide. Eur Rev Med Pharmacol Sci. 2011;15(6):601-636.

3. Academy of Doctors of Audiology. Ototoxic and vestbulotoxic drugs. https://static1.squarespace.
com/static/5b7deefb1aef1dc9d406b2e8/t/5b898644898583982679a66f/1535739464862/
Ototoxic+and+Vestibulotoxic+Drugs+-+ADA.pdf

4. American Speech-Language-Hearing Association. Evidence-based systematic review (EBSR): drug-induced hearing loss-aminoglycosides. https://www.asha.org/siteassets/uploadedFiles/EBSRAminoglycosides.pdf. Published April 2010.

5. Marais J, Rutka JA. Ototoxicity and topical ear drops. Clin Otolaryngol Allied Sci. 1998;23:360-367.

6. Scientists have found out why the cancer drug Cisplatin cause hearing loss. Hear-it.org website. https://www.hear-it.org/scientists-have-found-out-why-cancer-drug-cisplatin-cause-hearing-loss. Published September 4, 2018.

7. Ding D, Liu H, Qi W, et al. Ototoxic effects and mechanisms of loop diuretics. J Otol. 2016;11(4):145-156.

8. Hogan DB. Quinine: not a safe drug for treating nocturnal leg cramps. CMAJ. 2015;187(4):237-238.

9. Sheppard A, Hayes SH, Chen GD, Ralli M, Salvi R. Review of salicylate-induced hearing loss, neurotoxicity, tinnitus and neuropathophysiology. Acta Otorhinolaryngol Ital. 2014;34(2):79-93.

10. Tabuchi K, Nishimura B, Nakamagoe M, Hayashi K, Nakayama M, Hara A. Ototoxicity: mechanisms of cochlear impairment and its prevention. Curr Med Chem. 2011;18(31):4866-4871.