What Is Ototoxicity?

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Ototoxicity is a term used to describe a drug side effect that causes damage to the inner ear or auditory nerve, resulting in hearing loss, a loss of balance, and sometimes deafness. There is an ever-increasing number of drugs known to cause ototoxicity to varying degrees, including chemotherapy drugs, aspirin, and erythromycin.

Because ototoxic hearing loss can sometimes be irreversible, every effort should be made to prevent an inner ear injury before the hearing is significantly impaired. Some doctors are making a greater effort to monitor for hearing loss in people exposed to high-risk ototoxic agents.

Ototoxicity Symptoms

The symptoms of ototoxicity can vary based on which part of the ear is affected. The inner ear consists of the cochlea (which translates sound into electrical signals), the auditory nerve (which carries the signals to the brain), and the vestibular nerve (which helps orient your position in space and maintain equilibrium).

Depending on which parts of the inner ear are affected, symptoms of ototoxicity may include:

  • Dizziness
  • Unsteady gait
  • Loss of coordination with movement
  • Vertigo (dizziness)
  • Oscillating vision (in which objects appear to jump or vibrate)
  • Aural fullness (a feeling that something is stuffed in your ear)
  • Tinnitus (ringing in the ear)
  • Hyperacusis (increased sensitivity to sound at different volumes or frequencies)
  • Hearing loss in one or both ears

Symptoms of ototoxicity may develop rapidly or over the course of months, depending on the drug involved and other factors.

Causes

Among the drugs of greatest concern are those used in chemotherapy, such as Eloxitan (oxaliplatin), nitrogen mustard, Paraplantin (carboplatin), and Platinol (cisplatin).

Drugs like Platinol may cause symptomatic ototoxicity in 50% of users. Because the drugs attack fast-replicating cells, they primarily target cancer cells, but they also can damage other fast-replicating cells—including auditory hair cells that amplify sound waves.

Exposure to chemotherapy drugs, aminoglycoside, and loop diuretics during pregnancy may not only affect the mother but may also cause hearing impairment in a fetus.

But there are more than 600 drugs known to have ototoxic effects. Aside from chemotherapies, those more likely to be ototoxic include:

  • Aminoglycoside antibiotics like amikacin, dihydrostreptomycin, Gentak (gentamicin), kanamycin A, netilmicin, ribostamycin, streptomycin, and Tobrex (tobramycin)
  • Non-aminoglycoside antibiotics like erythromycin and Vanocin (vancomycin)
  • Loop diuretics like bumetanide, Demadex (torsemide), Edecrin (ethacrynic acid), and Lasix (furosemide)
  • Salicylates like aspirin, chloroquine, and quinine

Aminoglycoside and non-aminoglycoside antibiotics may cause ototoxic hearing impairment in up to 25% of users and vestibular dysfunction in up to 10% of users.

Loop diuretics and salicylates affect roughly 1% of users, most often the elderly.

Environmental chemicals and substances like arsenic, carbon monoxide, hexane, lead, mercury, tin, and toluene can also cause ototoxicity, particularly in industrial or occupational settings where there is ongoing exposure.

Risk Factors

There are other factors beyond the drugs or exposures themselves that may contribute to the risk of ototoxicity, including:

  • Age (children and the elderly are at greatest risk)
  • Family history of ototoxicity
  • Drug dose and duration of therapy
  • Cumulative lifetime dose
  • Rate of infusion (for antibiotics and chemotherapy)
  • Using multiple ototoxic drugs
  • Impaired kidney function (causing drug accumulation)
  • Previous head and neck radiation (for chemotherapy drugs)
  • Pre-existing hearing loss (especially sensorineural hearing loss)

Genetics are also believed to play a part, given that ototoxicity to antibiotics like Gentak (gentamicin) often runs in families.

There are also gene mutations loosely associated with ototoxicity which appear to slow the rate in which certain drugs, especially chemotherapy drugs, are metabolized.

Diagnosis

Ototoxicity is often missed in the early stages because it can be confused for other conditions. A "stuffed" sensation in the ear may be mistaken for an allergy, while sudden dizziness or vertigo can be attributed to any number of conditions from labyrinthitis (inner ear inflammation) to hypotension (low blood pressure).

Because older people are at an increased risk, in part because they have higher rates of pre-existing hearing loss, the symptoms of ototoxicity may be missed or simply attributed to aging.

The same is likely in babies and toddlers in whom progressive hearing loss may go unnoticed until it becomes severe.

Because high-pitched sounds are usually affected first, people may not even notice that their hearing is impaired until the lower frequencies are also affected.

Audiologic Testing

Audiologic (hearing) tests are the only way to make an ototoxicity diagnosis. These are conducted by an audiologist, a healthcare professional trained in the evaluation of hearing and related disorders.

Audiologic tests commonly used include:

  • Pure-tone air conduction: Likely the most sensitive hearing test in the earliest stages of ototoxicity)
  • Pure-tone bone conduction: Used to detect sensorineural hearing loss affecting the inner ear)
  • Otoacoustic emission: Used to measure reflected sounds from the inner ear
  • Auditory brainstem response: Measures auditory nerve response; ideal for infants and bed-bound patients
  • Romberg test: Used to detect neurological causes of dizziness and vertigo

These may be done if symptoms of ototoxicity are present. Hearing testing may also be done periodically if a highly ototoxic drug is used—ideally at the onset of therapy, during treatment, and after treatment has been completed. Such routine testing may help catch ototoxic effects before you notice them.

For example, the American Speech-Language-Hearing Association (ASHA) recommends that pure-tone air conduction testing be performed:

  • Within 24 hours of starting chemotherapy or 72 hours of starting aminoglycosides
  • One month later and every three months thereafter until treatment is stopped or completed
  • Six months after the completion of therapy

Despite evidence that doing so can detect ototoxicity before a person's hearing is significantly impaired, the ASHA recommendations have not been implemented in most clinical settings.

Treatment

Stopping the offending drug or exposure can lead to symptom improvement in some cases, but not all. Prevention, therefore, is the only way to reduce the risk of hearing loss.

Currently, there are no drugs approved by the U.S. Food and Drug Administration (FDA) for the prevention or treatment of drug-induced ototoxicity. A few otoprotective agents, such as sodium thiosulfate, amifostine, and N-acetylcysteine, have been investigated in people undergoing Platinol chemotherapy.

Although the drugs seemed promising in reducing the risk of hearing loss, they also appeared to reduce the efficacy of the chemotherapy.

If ototoxic hearing loss occurs, rehabilitation efforts may include hearing aids, assistive listening devices, and cochlear implants along with communication skills training for those with significant hearing impairment. Younger children may require the help of a speech-language pathologist.

To improve balance, physical therapy can help retrain the brain to compensate for the impaired equilibrium.

Drugs like Valium (diazepam), Hyoscine (scopolamine), or Phenergan (promethazine) may also be prescribed if there is significant vestibular injury, particularly if it occurs in both ears. Only in the most severe cases is surgery indicated, and even then, it remains very controversial.

Prognosis

The likelihood of recovery from ototoxicity is dependent on:

  • The drug used
  • Duration of use
  • Any pre-existing risk factors you may have had prior to treatment

There are no hard-and-fast rules as to who might be affected or to what degree hearing may be altered.

With that said, and generally speaking:

  • Platinum-based chemotherapy drugs like Platinol are most likely to cause severe and permanent hearing loss, usually in both ears and at all hearing frequencies.
  • Children undergoing chemotherapy or adults who have had previous head and neck radiation often fare worse. Hearing loss may start to develop as early as one to two weeks after the start of therapy.
  • Aminoglycoside and non-aminoglycoside antibiotics can also cause permanent hearing loss, albeit less commonly, and mainly affect high frequencies in one or both ears. Chronic dizziness caused by vestibular damage is also common. Children are more affected than adults.
  • Ototoxicity from salicylates and loop diuretics are generally reversible once treatment is stopped. It is only in newborns exposed during pregnancy that permanent hearing impairment may occur.
  • Hearing loss caused by environmental, occupational, or industrial ototoxins is almost always permanent.

A Word From Verywell

Ototoxicity is an under-recognized drug side effect that doctors and patients often miss until one's hearing or balance has been significantly impaired.

Because ototoxicity is not frequently monitored according to ASHA standards, the onus is placed on you, the patient, to be proactive and request audiological testing if you going to be (or are being treated) with chemotherapy or aminoglycoside drugs. The sooner symptoms are detected, the better.

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