Anti tuberculosis: Ototoxicity

Risk Factors

• high aminoglycoside serum concentrations
• concomitant ototoxins (e.g. loop diuretics, amphotericin B, cefa­losporins, cyclosporin, cisplatin, furosemide and vancomycin)
• prior aminoglycoside use
• increasing age (>60)
• pre-existing hearing loss
• Impaired renal function

Vestibular Toxicity

• Observe the patient closely for tinnitus and unsteadiness
• Assess vestibular toxicity at least monthly
• Fullness in the ears and intermittent ringing in the ears are early symptoms of vestibular toxicity.
• Toxicity is related to the total dose and is cumulative.
• It is impossible to predict for an individual patient what dose is tolerated

Causative Agents

• aminoglycosides and capreomycin are toxic to the eighth cranial nerve and can cause both vestibular and auditory toxicity
• vestibular: streptomycin > kanamycin > amikacin 
• A degree of disequilibrium can be caused by Mild disequilibrium can also be caused by cycloserine, fluoroquinolones, ethionamide/prothionamide, isoniazid, or linezolid

Management

• Prior to stopping the injectable agent, evaluate whether these and/or other medications are causing the symptoms.
• When these are reported, it is sometimes possible to change the dosing to 2 or 3 times a week and continue the injectable agent for another month or more.
• Stopping the injectable should be done after carefully excluding other causes of the symptoms.
• Other drugs or all drugs can be held for several days to see if the symptoms improve.
• Symptoms of vestibular toxicity generally do not improve with holding medication
• If tinnitus and unsteadiness develop and these are attributed to vestibular toxicity, stop the injectable agent. This is one of the few adverse reactions that cause permanent intolerable toxicity and necessitate discontinuation of a class of agents.
• If the injectable agent is continued or an attempt is made to substitute one injectable for another, persistent vertigo, unsteadiness, tinnitus, and ataxia will develop.
• Drug induced vestibular toxicity is not reversible

Auditory Toxicity

• Hearing loss is a direct effect of injectable medication toxicity to the eighth cranial nerve.
• Some degree of loss occurs in nearly all patients treated for drug-resistant TB.
• High-frequency loss usually occurs first.
• The effects are cumulative.
• Hearing loss may be reversible or permanent.
• dam­age usually occurs in the first 2 months of treatment and is reversible if the dosage is reduced or the drug is stopped

Causative

• Streptomycin has less auditory toxicity, but has more vestibular toxicity.
• cochlear: kanamycin ³ amikacin > streptomycin
• ESRF-HD patients who developed ototoxicity during the course of antituberculosis therapy, isoniazid was probably the responsible agent either alone or it added to the side effects of other drugs

Management

• Consider change of the injectable to 3 times a week, after 3 to 4 months, when the cultures are negative.
• Avoid loop diuretics because they increase eighth nerve toxicity.
• Resistance to streptomycin is common and should be excluded before substituting it for another injectable.
• Some patients must tolerate significant hearing loss in order to achieve a cure of their drug-resistant TB.
• The decision to continue therapy with an injectable when significant hearing loss occurs should be discussed with an expert in the management of drug-resistant TB and also with the patient.

References:

1. DRUG-RESISTANT TUBERCULOSIS | A SURVIVAL GUIDE FOR CLINICIANS
2. Ototoxic Medications Drugs that can cause hearing loss and tinnitus. American Tinnitus Association
3. Tuberculosis Drug Toxicities & Approaches to Management. Mayo Clinic Center for Tuberculosis
4. Neurological: Ototoxicity (hearing loss or vestibulopathy). https://drtbnetwork.org/913-neurological-ototoxicity-hearing-loss-or-vestibulopathy
5. Is isoniazid ototoxic in patients undergoing hemodialysis? http://www.ncbi.nlm.nih.gov/pubmed/12218336