Ototoxicity

Understanding Ototoxicity and Vestibulotoxicity

The inner ear contains two major components:

• The cochlea, responsible for hearing
• The vestibular system, responsible for balance

Ototoxicity means “ear poisoning.” It refers to damage to the cochlea (hearing) and/or the vestibular system (balance) caused by medications or toxic substances.

When the balance organs are primarily affected, we use the more specific term vestibulotoxicity.

These conditions occur because certain drugs can damage delicate inner ear cells called hair cells. These are microscopic sensory cells that convert sound waves and head movements into electrical signals for the brain. Once hair cells are destroyed, they do not regenerate in humans.

Clinical Manifestations

The symptoms depend on which part of the inner ear is affected.

Hearing-Related Symptoms (Cochlear Toxicity)

• High-frequency (high pitched) hearing loss (difficulty hearing birds, alarms, consonants like “s” or “f”)
• Tinnitus (ringing or buzzing in the ears). Learn more about tinnitus here.
• Difficulty understanding speech in noisy environments
• Progressive hearing loss over days to weeks

Importantly, hearing loss usually begins in the highest frequencies, which patients may not initially notice. To learn more about hearing loss, read this article.

Balance-Related Symptoms (Vestibulotoxicity)

• Chronic imbalance
• Oscillopsia (a sensation that the world is bouncing when walking)
• Difficulty walking in the dark
• Increased risk of falls

Unlike vertigo from conditions such as Ménière's disease, vestibulotoxicity often causes constant imbalance rather than spinning attacks. To learn more about vertigo read this article.

When both hearing and balance are affected, symptoms can be particularly disabling.

Medications Known to Cause Ototoxicity

Different drug categories affect the ear in different ways.

Chemotherapy Agents (Platinum-Based)

This is the #1 cause of ototoxicity in North America.

The most common chemotherapy-related ototoxicity is associated with “platinum agents,” and the two most commonly used forms are:

• Cisplatin
• Carboplatin

How they damage the ear:
Cisplatin causes direct toxicity to outer hair cells in the cochlea and may damage the hearing nerve. It also produces oxidative stress and inflammation inside the cochlea.

Cisplatin ototoxicity is often permanent and cumulative.

Aminoglycoside Antibiotics

This is the #1 cause of ototoxicity in developing world.

Examples:

• Gentamicin
• Tobramycin
• Amikacin

These are powerful antibiotics used for severe infections.

How they damage the ear:
Aminoglycosides accumulate in the inner ear fluids and generate reactive oxygen species (harmful oxygen molecules) that damage hair cells. Some preferentially damage balance organs (gentamicin), others hearing (amikacin).

Damage may continue even after the drug is stopped.

Loop Diuretics

These medications treat heart issues, high blood pressure and fluid overload. They act primarily at the level of the kidney to evacuate excess water and salt in the body.

Examples:

• Furosemide

How they damage the ear:
They disrupt the ion (salt) balance inside the inner ear by affecting the stria vascularis (a structure that maintains the chemical environment needed for hearing).

* Fortunately, when given alone to a reasonably healthy individual, loop diuretics have a low risk of causing ear damage. In addition, most cases are reversible. However, they are more likely to cause harm when given in high doses to a seriously ill patient (for example, in the hospital) with kidney and liver disease.

Salicylates

Example:

• Aspirin

Salicylates are a class of medication known for their anti-inflammatory, pain-relieving (analgesic), and fever-reducing (antipyretic) properties. Aspirin, the most familiar salicylate, is used not only for pain and fever but also in low doses to reduce blood clotting and lower the risk of heart attacks and strokes

How they damage the ear:
Salicylates temporarily change outer hair cell function and reduce cochlear amplification. High doses can cause hearing loss and tinnitus, both of which are most commonly reversible once the medication is stopped.

* Fortunately, when given alone to a reasonably healthy individual, aspirin has a very low risk of causing ear damage (even less so than loop diuretics). In addition, most cases are reversible.

Other Agents

• Vancomycin (a type of antibiotic)
• Other combination of chemotherapies

The mechanisms vary but often involve stress to ear cells or disruption of their metabolism.

Risk Factors for Ototoxicity

Thankfully, not everyone exposed to these drugs develops ear damage. We don’t really understand why some individuals do, and other don’t.

Important risk factors that have been identified include (the first two are the most important):

• High cumulative dose
• Simultaneous use of multiple ototoxic drugs
• Intravenous administration
• Existent kidney or liver disease (reduced drug clearance)
• Prior hearing loss
• Very young age (especially children receiving chemotherapy)

Genetic Risk

Certain individuals carry mitochondrial DNA mutations (such as the A1555G mutation) that make them extremely sensitive to aminoglycosides. Even a single dose can cause profound hearing loss.

Genetic testing may be considered in high-risk families.

How to detect toxicity: workup and diagnosis

When ototoxicity is suspected, early evaluation is critical. This is because the earlier it is discovered, the quicker the medication can be stopped, and hearing has a chance to recover before permanent damage settles in. The workup typically includes:

Clinical evaluation

Includes detailed medical history (drug exposure, timing of symptoms)

Audiograms

Evaluation of hearing should be done at baseline (before starting chemotherapy for example), and then before every cycle (these are called “serial audiogram”). A final hearing test should be done at the end of the treatment. Additionally, an urgent audiogram is recommended for any patient taking medication known to cause ototoxicity and experiencing hearing changes. To learn more about audiograms, read this article.

In cancer patients receiving cisplatin, routine hearing monitoring is strongly recommended.

High-frequency audiometry (above 8,000 Hz)

This special type of audiogram evaluates very high-pitched sounds, as they’re the first to be affected by ototoxicity. Therefore, high-frequency audiometry detects early signs of ear damage even before the patient notices any problems. To learn more about high-frequency audiometry, read this article.

Otoacoustic emissions (test of outer hair cell function)

This objective test measures ototoxicity without requiring patient collaboration. It detects a sound produced by a healthy ear. For more information on otoacoustic emissions, see this article.

Vestibular testing (VNG, vHIT)

These tests are done when balance symptoms are present. You can learn more about VNGs in this article, and more about vHIT in this article.

Blood levels

Certain drugs (like aminoglycosides and vancomycin) may be monitored to reduce toxicity.

Treatment and Prevention : Is it possible?

Unfortunately, there is no proven medication that reverses established hair cell loss in humans.

Management focuses on:

Immediate Steps

• Stopping or reducing the offending drug (when medically feasible)
• Substituting safer alternatives

Proven Preventive Measures

• Therapeutic drug monitoring (especially aminoglycosides)
• Using the lowest effective dose
• Avoiding combination ototoxic therapies when possible
• Hydration and renal monitoring
• Injections of cortisone in the ear is sometimes given, but efficacy remains to be confirmed.

For cisplatin, sodium thiosulfate has shown benefit in selected pediatric oncology protocols, but its use depends on cancer type and oncologic considerations.

Rehabilitation

If permanent damage occurs:

• Hearing aids
• Cochlear implantation for severe cases
• Vestibular rehabilitation therapy (physical therapy for balance)

Long-Term Outcomes: Does hearing loss recover?

The prognosis really depends on the drug involved.

Aminoglycosides

Damage is usually permanent, which may slowly worsen even after therapy ends.. Vestibular toxicity can lead to lifelong imbalance, though patients often compensate over time.

Cisplatin

Typically causes permanent high-frequency hearing loss, which may slowly worsen even after therapy ends.

Loop Diuretics and Salicylates

Usually reversible once the drug is discontinued.

Combined Toxicity

When multiple ototoxic drugs are used, hearing loss can be more severe and permanent.

Final Thoughts

Ototoxicity is a serious but often predictable complication of certain medications. As physicians, we balance the life-saving benefits of these drugs against their potential risks.

Early detection, careful monitoring, and patient awareness are the most powerful tools we have today.

If you or a loved one are receiving medications known to affect the ear and notice changes in hearing or balance, prompt evaluation by an ENT specialist is essential.

Protecting hearing begins with awareness.