Published: 2 June 2016

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Medicine-induced Hearing Loss

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Prescriber Update 37(2): 30-31
June 2016

The Centre for Adverse Reactions Monitoring (CARM) received 76 reports of hearing loss from 1 January 2006 to 31 December 2015. The five most frequently reported medicines were:

• gentamicin (six reports)
• erythromycin (six reports)
• thyroxine (five reports, all associated with a formulation change)
• cisplatin (four reports)
• influenza vaccine (four reports).

Medicine-induced ototoxicity is the functional impairment of the inner ear (cochlea and/or vestibular system) or eighth cranial nerve secondary to a pharmaceutical agent¹. Ototoxic medicines that may cause hearing loss include aminoglycosides, macrolide antibiotics, antimalarials, platinum-based antineoplastic agents, anti-inflammatory medicines and loop diuretics (Table 1)².

The mechanisms by which ototoxic medicines cause hearing loss are poorly understood³. Cisplatin and the aminoglycosides are believed to cause sensory hair cell apoptosis via a process involving the production of reactive oxygen species^4,5. Loop diuretics may alter the potassium gradient between the chambers of the cochlear, affecting its function⁶. Topical preparations instilled into the auditory canal can lead to damage to middle ear structures if the ear drum has been perforated or tympanostomy tubes have been inserted⁷. Medicines that cause peripheral neuropathy may also affect hearing through damage to the auditory nerve.

Hearing loss can occur at any time during or after treatment with an ototoxic medicine and may be gradual or sudden in onset. Hearing loss may be unilateral or bilateral and may fluctuate in severity. Medicine-induced damage to the cochlea usually affects the ability to hear high frequencies initially, but may progress to lower frequencies. Cochlear damage may also manifest as tinnitus.

Risk factors for medicine-induced hearing loss include:^2,3,6

• the patient's age (greater risk in children and older people)
• dehydration
• reduced medicine elimination (particularly due to renal failure)
• co-administration of two or more ototoxic medicines
• perforated ear drum (for medicines administered topically into the external auditory canal)
• genetic predisposition (eg, aminoglycoside and cisplatin ototoxicity).

When prescribing potentially ototoxic medicines, patients should be advised of the possibility of hearing loss and to report any hearing difficulties to their healthcare provider. Audiological monitoring is recommended for potent ototoxic medicines such as cisplatin¹.

Please continue to report any cases of medicine-induced hearing loss to CARM. Reports can be submitted on paper or electronically (https://nzphvc.otago.ac.nz/reporting/).

Table 1: Ototoxic medicines associated with hearing loss (adapted from Drug-induced hearing loss, Prescrire International²; this is not an exhaustive list)

Medicine Class	Examples
Medicines recognised as causing hearing loss
Antibiotics	Aminoglycosides, macrolides, tetracyclines, vancomycin
Antifungals	Itraconazole, terbinafine
Anti-inflammatory medicines	Aspirin, COX-2 inhibitors, non-steroidal anti-inflammatory drugs (NSAIDs)
Antimalarials	Chloroquine, mefloquine, quinine
Antineoplastics	Bortezomib, carboplatin, cisplatin, docetaxel, nilotinib, vinblastine, vincristine
Iron chelating medicines	Deferasirox, deferoxamine
Loop diuretics	Bumetanide, furosemide
Phosphodiesterase type-5 inhibitors	Sildenafil, tadalafil, vardenafil
Other medicines	Bromocriptine, febuxostat, hydroxychloroquine, interferon alfa, isotretinoin, sodium valproate, tacrolimus
Medicines that have been reported to cause hearing loss
Amphotericin B, artemether, bisphosphonates (eg, alendronic acid, zoledronic acid), boceprevir, chlormethine, deferiprone, enalapril, flumazenil, nitrous oxide gas, thalidomide, verteporfin

References

1. Steffens L, Venter K, O'Beirne GA, et al. 2014. The current state of ototoxicity monitoring in New Zealand. New Zealand Medical Journal 127(1398): 84-97.
2. Anonymous. 2014. Drug-induced hearing loss. Prescrire International 23(155): 290-294.
3. Yorgason JG, Luxford W, Kalinec F. 2011. In vitro and in vivo models of drug ototoxicity: studying the mechanisms of a clinical problem. Expert Opinion on Drug Metabolism & Toxicology 7(12): 1521-1534.
4. Mukherjea D, Rybak LP. 2011. Pharmacogenomics of cisplatin-induced ototoxicity. Pharmacogenomics 12(7): 1039-1050.
5. Huth ME, Ricci AJ, Cheng AG. 2011. Mechanisms of Aminoglycoside Ototoxicity and Targets of Hair Cell Protection. International Journal of Otolaryngology 2011: 19.
6. Yorgason JG, Fayad JN, Kalinec F. 2006. Understanding drug ototoxicity: molecular insights for prevention and clinical management. Expert Opinion on Drug Safety 5(3): 383-399.
7. Medsafe. 2007. Ototoxicity with aminoglycoside eardrops. Prescriber Update 28(1): 2-6. URL: www.medsafe.govt.nz/profs/PUArticles/watchingbriefsNov07.htm#Ototoxicity (accessed 22 April 2016).