May/June 2014

Medication-Related Ototoxicity

By Mark D. Coggins, PharmD, CGP, FASCP
Today’s Geriatric Medicine
Vol. 7 No. 3 P. 6

Older adults’ hearing loss frequently is attributed to the aging process, but some medications also can cause damage that can lead to hearing loss. Because of the increased incidence of medication use among older adults, physicians should be aware of medications that may be considered ototoxic.

Causes and Symptoms
Medications and environmental substances that damage structures within the inner ear or vestibule-cochlear nerve are considered ototoxic, with at least 300 medications identified as such.1 The damage they cause to hair cells prevents the transmission of sound and motion into electrical impulses the brain can understand.

Symptoms of ototoxicity include tinnitus (ringing in the ears), hearing loss (bi- or unilateral), dizziness, lack of movement coordination, unsteady gait, and oscillating or bouncing vision (vertigo).2 Hearing loss may be complete or partial, depending on the severity of damage to the hair cells lining the cochlea. Tinnitus, which often is one of the first symptoms of damage, also may be described as roaring, clicking, hissing, or buzzing and may be soft or loud and high or low pitched. Additionally, fall risk can increase for patients who experience dizziness, poor coordination, unsteady gait, or vertigo.3,4

The progression of ototoxicity may be rapid or appear months following medication use. In the early stages, otoxicity may go undiagnosed if hearing loss is minimal or restricted to high-pitched sounds. As exposure to ototoxic medications increases, resulting damage can initially affect the ear’s ability to comprehend high-pitched sounds and then subsequently affect lower-pitched sounds.4 It is usually when hearing loss affects the lower speech frequencies that patients notice the changes, but often this also is the stage by which permanent damage has occurred.4

Monitoring
In addition to being aware of symptoms associated with ototoxicity, clinicians should consider utilizing audiologists, who can perform hearing tests before, during, and after the administration of medications to detect the progression of ototoxic hearing loss.

The progression from the loss of high frequency, high-pitched sounds to low frequency, low-pitched sounds is important in evaluating hearing loss. Whereas typical hearing tests involve frequencies only as high as 6,000 to 8,000 Hz, audiologists can perform testing that evaluates hearing in very high frequencies such as 9,000 to 20,000 Hz, possibly allowing for earlier detection of ototoxic effects.5

Drug Accumulation
It is essential for health care providers to understand the risk factors for ototoxicity, which often lead to drug accumulation and an increased potential for permanent hearing loss. These risk factors include medication dose, therapy duration, cumulative lifetime dose, impaired kidney function, infusion rate of certain medications (eg, IV furosemide, aminoglycosides), coadministration of multiple ototoxic medications (eg, aminoglycosides with loop diuretics), age, previous exposure to head and neck radiation (chemotherapeutic agents), genetic susceptibility, and family history of ototoxicity.2

Since most ototoxic drugs are eliminated through the kidneys, the risk of toxicity is increased by renal failure. When renal function is diminished, doses of ototoxic medications must be corrected to ensure blood levels remain therapeutic. Routine monitoring of blood levels is essential to ensure that ototoxic medications, such as the aminoglycosides, are kept below maximum therapeutic levels. Keeping these medications within suggested limits often can preserve hearing.2

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.4

Risk vs. Benefit
Before starting patients on a medication known to be ototoxic, it is important for the health care team to consider the possible effects hearing and/or balance problems may have on a patient’s quality of life after drug therapy. In cases where alternatives are possible, it is best to avoid ototoxic medications, especially in the elderly and patients with preexisting hearing loss or additional risk factors for increased ototoxicity.

Common Ototoxic Medications1-4,6

Aminoglycosides
Aminoglycoside antibiotics, including streptomycin, amikacin, kanamycin, gentamicin, and neomycin are just a few of the aminoglycoside antibiotics known to cause permanent hearing damage and should be reserved for serious life-threatening diseases where saving a patient’s life outweighs the possibility of damage to hearing.

Patients with eardrum perforation should not be prescribed topical ototoxic agents such as neomycin otic drops because these medications could be absorbed in the inner ear, resulting in damage and hearing loss.

Chemotherapeutic Agents
Medications such as cisplatin, bleomycin, carboplatin, and cyclophosphamide are used to treat cancer but can cause permanent hearing damage. Ototoxic effects can be minimized, though not always prevented, by close blood level monitoring. In these cases, hearing loss often presents as a sensation of hearing muffled voices, though vestibular effects also are common.

Hearing loss usually occurs after one to two weeks of treatment, although it often can be delayed up to six months posttreatment.

NSAIDs
Most NSAIDs can potentially cause temporary tinnitus and hearing loss, but the toxic effects typically can be reversed once the medication is discontinued. It is important to keep in mind that NSAIDs also can cause kidney injury and reduce renal function, which may increase the risk of ototoxicity when given with other ototoxic medications.

Salicylates
Salicylates, including aspirin and aspirin-containing products, are known to cause tinnitus and hearing loss, with the effects being dose dependent (ie, 2,700 mg or more per day). Topical salicylates containing methyl salicylate also can cause tinnitus. As with NSAIDS, the effects generally can be reversed once the medication is discontinued.

Loop Diuretics
Common loop diuretics, including bumetadine, chlorthalidone, ethacrynic acid, and furosemide, usually are ototoxic when given intravenously for acute kidney failure, acute hypertensive crisis, or acute pulmonary edema/congestive heart failure. Rare cases of ototoxicity have been found when patients with chronic kidney disease take these medications orally in high doses.

Other Ototoxic Medications
Other categories of medications known to be ototoxic include quinine, erythromycin antibiotics, anesthetics, cardiac medications, glucocorticosteroids, and mood-altering drugs.

Need for Greater Ototoxicity Testing
When evaluating a medication for ototoxicity, it is important to consider the fact that the FDA does not have Good Clinical Practice guidelines for monitoring ototoxicity in the clinical trials of new drugs. Testing of inner ear function typically is not required unless the new investigational pharmacological agent is within a drug class known to cause ototoxicity as a side effect. As a result, the issue of ototoxicity usually is discovered only after enough people have suffered the consequences of ototoxicity, and health care professionals make the correlation.7

Because of the uncertainty about medications that may cause ototoxicity, it is important to advise patients to report any issues such as the emergence or worsening of tinnitus when new medications are started or doses are increased. The sidebar below provides a summary of reminders that can help to minimize the risk of ototoxicity.

— Mark D. Coggins, PharmD, CGP, FASCP, is director of pharmacy services for more than 300 skilled nursing centers operated by Golden Living and a director on the board of the American Society of Consultant Pharmacists. He was recognized by the Commission for Certification in Geriatric Pharmacy with the 2010 Excellence in Geriatric Pharmacy Practice Award.

Tips to Reduce Ototoxicity Risk

• Familiarize yourself with ototoxic medications and their associated risks.

• Recognizing ototoxicity early on can lead to earlier identification and possibly prevent permanent damage.

• Do not treat the elderly and others with preexisting hearing loss with ototoxic drugs if other effective alternatives are available.

• Recognize that combination therapy of ototoxic medications increases the risk of hearing loss.

• Discuss with patients the potential for ototoxicity of any drugs.

• Use the lowest effective dose possible, and closely monitor blood levels of known ototoxic medications.

• Remind patients to minimize their exposure to loud noises when taking ototoxic medications and to immediately report any hearing changes when new medications are added or doses change as part of their treatment regimen.

• Inform patients that over-the-counter medications such as aspirin and NSAIDs can be ototoxic.

• Encourage patients to report any changes in hearing immediately, especially when new medications are added or doses increased.

• When possible, assess patients’ hearing before starting ototoxic medications and monitor during treatment as symptoms alone are not always reliable.

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. 2011;15(6):601-636.

3. Ototoxicity. Vestibular Disorders Association website. http://www.vestibular.org/ototoxicity. Accessed March 23, 2014.

4. Ototoxicity. Virtual Medical Centre website. http://www.myvmc.com/diseases/ototoxicity. Last updated March 13, 2014. Accessed March 21, 2014.

5. American Speech-Language-Hearing Association Audiology Information Series. Medication effects on hearing. http://www.asha.org/uploadedFiles/aud/InfoSeriesHearingMedicationEffects.pdf. Accessed March 21, 2014.

6. League for the Hard of Hearing. Ototoxic medications: drugs that can cause hearing loss and tinnitus. http://www.ata.org/sites/ata.org/files/pdf/Ototoxic_Brochure_by_League_for_Hard_of_Hearing
2012_Jul_12.pdf. Published 2000. Accessed March 21, 2014.

7. American Academy of Audiology. American Academy of Audiology position statement and clinical practice guidelines: ototoxicity monitoring. http://www.audiology.org/resources/documentlibrary/documents/otomonpositionguideline.pdf. Published October 2009. Accessed March 21, 2014.