What Is Ototoxicity?

Overview

Ototoxicity is damage to the ear as a whole, which includes the hearing and the balance organs, caused by exposure to certain drugs or chemicals. It can be temporary or permanent, and it can affect either one or both ears, which can cause a wide range of symptoms like hearing loss, tinnitus, dizziness, nausea, imbalance, or blurry vision.^1,6

Ototoxicity is usually diagnosed when a person develops hearing issues or balance problems after the use of a high dose of certain medicines. As is the case with many conditions, early diagnosis of the underlying cause and speedy treatment can prevent the condition from worsening.  However, the symptoms are often reversible if the patient stops taking the medication that has caused it straightaway. But unfortunately, there is a chance of permanent ear damage if the condition is not treated immediately.^1,2

Causes of ototoxicity

Ototoxicity is caused by exposure to drugs or chemicals that have the potential of being toxic to the ear (oto-), specifically the cochlea (the hearing apparatus), the vestibular system (the balance organs), or the vestibulocochlear nerve (the nerve sending balance and hearing information from the inner ear to the brain).^1,4

Ototoxicity can be caused by common medications since there are many substances that have ototoxic potential, including over-the-counter drugs, prescription medications, and environmental chemicals. Some of the most common ototoxic agents are:

• Antibiotics: such as gentamicin, streptomycin, tobramycin, erythromycin, vancomycin, neomycin
• Loop diuretics: such as furosemide, bumetanide, ethacrynic acid
• Chemotherapeutic agents: such as cisplatin, carboplatin, oxaliplatin
• Antiseptics and disinfectants, such as hydrogen peroxide
• Other medicinal ototoxic drugs, such as salicylates (aspirin), quinine
• Ototoxicants in the environment and workplace: such as solvents (toluene), metals (mercury), pesticides (organophosphates)

Fortunately, occurrence and the degree of ototoxicity are dependent on several factors such as the type and dose of the drug or chemical, duration and/or frequency of exposure and the route of administration (oral, intravenous, intratympanic). Individual susceptibility, genetic factors, mixed drug interaction and the presence of other ear diseases or conditions can also play a factor in the emergence of ototoxicity.

Signs and symptoms of ototoxicity

As discussed above, the ear is made of different areas, which are in charge of different aspects, so the signs and symptoms of ototoxicity could vary depending on which part of the ear is affected. Ototoxicity can affect:^1,4

• The cochlea: causing sensorineural hearing loss (SNHL) or tinnitus (ringing in the ears)
• The vestibular system: causing vertigo (spinning sensation), dizziness, nausea, imbalance, or nystagmus (involuntary eye movements)
• The vestibulocochlear nerve: causing both SNHL and vestibular symptoms

The onset of ototoxicity can be sudden or gradual, which means some symptoms may appear immediately after exposure to a drug or chemical, while others may develop over time or even after discontinuation of the drug or chemical. These symptoms may be temporary or reversible, while others may be permanent or progressive.¹

Variables surrounding ototoxicity are very diverse, meaning the severity of it can range from mild to profound; depending on the cause, personal factors and which part of the ear is affected, some people may experience only a slight decrease in hearing sensitivity or mild tinnitus which will not interfere with their daily activities while others may experience a severe hearing loss that requires hearing aids or cochlear implants, or in extreme cases, disabling vertigo that prevents them from performing normal tasks.^1,5

Management and treatment for ototoxicity

The management and treatment for ototoxicity will differ between individuals as it is dependent on the cause and type of ototoxicity, but the general principles can be summarised in 3 steps.^7.8 

Prevention: 

• Avoid exposure to known ototoxic agents whenever possible
• Use protective measures such as earplugs or muffs when exposed to loud noise
• Monitor blood levels of ototoxic drugs
• Following the prescribed dosage and duration of ototoxic drugs
• Informing your doctor about any history of ear problems or family history of hearing loss
• Informing your doctor about any other medications or supplements you are taking
• Reporting any signs or symptoms of ototoxicity to your doctor as soon as possible

Diagnosis: 

This step will involve undergoing a thorough medical history and physical examination as well as some tests as mentioned below.^9,10

• Hearing test (audiogram) to measure your hearing sensitivity
• Balance test (vestibular function tests) to assess your balance function
• Imaging (CT scan or MRI) to rule out other causes of hearing loss or balance problems 
• Genetic test, if indicated, to identify any genetic predisposition to ototoxicity.

Treatment: 

The treatment step may include one or more of the following:¹

• Stopping or reducing the dose of the ototoxic drug or chemical (this should be done if possible and under medical supervision)
• Switching to a less ototoxic alternative (if available and appropriate)
• Using medications to treat the symptoms of ototoxicity (such as anti-nausea drugs for vertigo or steroids for inflammation)
• Undergoing rehabilitation to improve your hearing or balance function (such as hearing aids, cochlear implants, vestibular therapy, or balance exercises)
• Undergoing surgery to correct any structural problems in the ear (such as a cholesteatoma or a perilymph fistula)
• Seeking psychological support or counselling to cope with the emotional impact of ototoxicity

Diagnosis

As discussed above, diagnosis of ototoxicity will be done by a medical professional and will involve undergoing a thorough medical history, physical examination as well as some tests. The diagnosis of ototoxicity is based on the following criteria:¹

• A history of exposure to a known or suspected ototoxic agent
• A temporal relationship between the exposure and the onset of symptoms
• A characteristic pattern of hearing loss or balance dysfunction
• The exclusion of other possible causes of hearing loss or balance dysfunction

The diagnosis of ototoxicity can be challenging, as there is no definitive test or biomarker to confirm it. Moreover, the symptoms of ototoxicity can be vague, variable, or delayed. Therefore, a high index of suspicion and a multidisciplinary approach may be required to diagnose ototoxicity.

Risk factors

There are several risk factors that could contribute to developing cytotoxicity, like age, gender, genetics, renal & liver functions, dehydration, noise exposure and drug interactions.^3,6 

• Older people are more susceptible to ototoxicity due to a reduced ability to metabolise and excrete drugs, and they may have pre-existing hearing loss or balance impairment
• Women are also shown to be more prone to ototoxicity than men, as they have higher levels of oestrogen, which may increase the sensitivity of the inner ear to certain drugs
• Some people have a genetic mutation that makes them more vulnerable to ototoxicity, such as those with mitochondrial DNA mutations or connexin 26 mutations
• People with impaired kidney and/or liver functions are more likely to develop ototoxicity, as they have a reduced ability to eliminate (metabolise) drugs from their system
• Dehydration also plays a role in ototoxicity as it causes a lower volume of blood and body fluids, which increases the drug concentration in one's system
• Some drugs can interact with each other and increase the risk of ototoxicity, such as loop diuretics and aminoglycosides or salicylates and quinine
• People exposed to loud noises are more likely to develop ototoxicity, as noise can damage the hair cells in the cochlea and potentiate the effects of ototoxic drugs

Complications

• Hearing impairment: ototoxicity can cause mild to profound hearing loss that can affect one’s ability to communicate, socialise, work, learn, and enjoy life. Hearing loss can also lead to isolation, depression, anxiety, cognitive decline, and dementia
• Balance impairment: ototoxicity can cause vertigo, dizziness, imbalance, and falls that can affect one’s ability to perform daily activities, drive, exercise, and travel. Balance impairment can also lead to injuries, fractures, disability, and reduced quality of life
• Tinnitus: ototoxicity can cause tinnitus that can interfere with concentration, sleep, relaxation, and well-being. Tinnitus can also cause distress, frustration, irritability, and depression

FAQs

Can ototoxicity be prevented?

Ototoxicity is a condition that’s very dependent on risk factors and thus can be prevented by avoiding exposure to known or suspected ototoxic agents wherever possible. 

If, for some reason, you need to take an ototoxic drug for a medical condition, you should inform your doctor about any history of ear problems or family history of hearing loss and any other medications or supplements you are taking. You should also follow the prescribed dosage and duration of the ototoxic drug carefully and report any signs or symptoms to your doctor as soon as possible. It is also beneficial to use protective measures such as ear plugs or muffs when exposed to loud noises.

How common is ototoxicity?

The exact prevalence of ototoxicity is unknown, as there is no standardised definition or reporting system for it. It is worth noting that ototoxicity is more common among older people, people with kidney or liver problems, people who are dehydrated, and people who are exposed to loud noise in par with the risk factors for ototoxicity.

When should I see a doctor?

You should see a doctor if you experience any of the following signs or symptoms of ototoxicity:

• Hearing loss or difficulty hearing
• Tinnitus or ringing in the ears
• Vertigo or spinning sensation
• Dizziness or lightheadedness
• Nausea or vomiting
• Imbalance or difficulty walking
• Nystagmus or involuntary eye movements
• Blurry vision or double vision

You should also see a doctor if you are taking a drug that is known to cause ototoxicity in you and notice any changes in your hearing or balance function. You should not reduce your dose or stop taking the medication without consulting your doctor first.

Summary

Ototoxicity is the damage to the ear caused by exposure to certain drugs or chemicals. It can affect the hearing and balance organs or the nerve that connects them to the brain. Ototoxicity can cause hearing loss, tinnitus, vertigo, dizziness, nausea, imbalance, or blurry vision. Ototoxicity can be both temporary or permanent, and it can affect one or both ears.

Ototoxicity is diagnosed based on the history of exposure, the onset and pattern of symptoms, and the exclusion of other causes. The treatment for ototoxicity depends on the cause and type of ototoxicity. 

The treatment may include stopping or reducing the dose of the ototoxic drug, switching to a less ototoxic alternative, using medications to treat the symptoms, undergoing rehabilitation to improve the hearing or balance function, undergoing surgery to correct any structural problems in the ear, or seeking psychological support or counselling. Ototoxicity can be prevented by avoiding exposure to known or suspected ototoxic agents whenever possible. 

Ototoxicity is a serious condition that can affect your quality of life and well-being. If you suspect that you have ototoxicity, it is advisable to seek medical attention as soon as possible.