REVIEW PAPER
OTOTOXICITY OF DRUGS USED IN THE TREATMENT OF COVID-19
Magdalena Beata Skarzynska 1, 2, A-E  
,   Bartłomiej Krol 3, F  
,   Natalia Czajka 3, E-F  
,   Łukasz Czajka 2, 1, E-F  
 
More details
Hide details
1
Otorhinolaryngology, Institute of Sensory Organs, Poland
2
Otorhinolaryngology, Center of Hearing and Speech, Poland
3
Otorhinolaryngology, Institute of Physiology and Pathology of Hearing, Poland
A - Research concept and design; B - Collection and/or assembly of data; C - Data analysis and interpretation; D - Writing the article; E - Critical revision of the article; F - Final approval of article;
CORRESPONDING AUTHOR
Magdalena Beata Skarzynska   

Institute of Sensory Organs, Center of Hearing and Speech, 05-830 Kajetany, 7 Mokra St., Poland; email: m.skarzynska@csim.pl, phone: + 48 22 4635346
Publication date: 2020-03-31
 
J Hear Sci 2020;10(1):9–20
 
KEYWORDS
TOPICS
ABSTRACT
Background:
Actual level of knowledge of treatment of COVID-19 disease caused by a type of coronavirus is that the disease cannot at present be cured by targeted therapy. Worldwide research is aiming to find a specific treatment, such as a vaccine or drug, for this type of coronavirus; this may help improve the situation, but it is highly expensive and time-consuming. The purpose of this paper is to review drug therapies approved in different parts of the world to treat COVID-19 and draw attention to ototoxicity as one of the adverse side-effects.

Material and Methods:
eview of current literature was done in the scientific databases PubMed, ResearchGate, GoogleScholar, and Science-Direct. Studies were reviewed with reference to the inclusion criteria, then graded to assess the internal and external validity, leaving 50 studies for review.

Results:
According to scientific reports, possible antiviral pharmacological agents to treat COVID-19 consist of chloroquine, hydroxychloro-quine, azitromycine, oseltamivir, and tocilizumab. In some cases, certain combinations may lead to additive ototoxicity as an adverse effect. Ototoxicity may be manifested by sensory and nervous hearing loss, tinnitus, imbalance, and cochlear-mandibular symptoms, which are sometimes temporary but sometimes permanent.

Conclusions:
Drug ototoxicity is well known as a cause of cochlear hearing loss, and so the use of new pharmacotherapy methods and drug combinations in the fight against the new coronavirus may have harmful effects. Ototoxicity needs to be taken into account.

 
REFERENCES (136)
1.
McGahey R. Will small business survive the COVID recession? [Internet]. Forbes. [cited 2020 Apr 14]. Available from: https://www.forbes.com/sites/r....
 
2.
Chen L, Liu W, Zhang Q, et al. RNA based mNGS approach identifies a novel human coronavirus from two individual pneumonia cases in 2019 Wuhan outbreak. Emerg Microbes Infect, 2020; 9(1): 313–9.
 
3.
Wu F, Zhao S, Yu B, et al. A new coronavirus associated with human respiratory disease in China. Nature, 2020; 579: 265–9.
 
4.
Lu R, Zhao X, Li J, et al. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet, 2020; 395(10224): 565–74.
 
5.
Tan W, Zhao X, Ma X, et al. A novel coronavirus genome identified in a cluster of pneumonia cases: Wuhan, China 2019−2020. China CDC Weekly; 2020; 2: 61–2.
 
6.
Zu ZY, Jiang MD, Xu PP, et al. Coronavirus disease 2019 (COVID-19): a perspective from China. Radiology, 2020; 200490.
 
7.
Chan JF-W, Yuan S, Kok K-H, et al. A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster. Lancet 2020; 395(10223): 514–23.
 
8.
General Office of National Health Committee. Office of State Administration of Traditional Chinese Medicine. Notice on the issuance of a programme for the diagnosis and treatment of novel coronavirus (2019-nCoV) infected pneumonia (trial fifth edition) [EB/OL] [Internet]. [cited 2020 May 25]. Available from: http://bgs.satcm.gov.cn/zhengc....
 
9.
Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet, 2020; 395(10223): 497–506.
 
10.
WHO Director-General’s remarks at the media briefing on 2019-nCoV on 11 February 2020 [Internet]. [cited 2020 May 25]. Available from: https://www.who.int/dg/speeche....
 
11.
Singhal T. A review of coronavirus disease-2019 (COVID-19). Indian J Pediatr, 2020; 87(4): 281–6.
 
12.
Cui J, Li F, Shi Z-L. Origin and evolution of pathogenic coronaviruses. Nat Rev Microbiol, 2019; 17(3): 181–92.
 
13.
Coronaviridae Study Group of the International Committee on Taxonomy of Viruses. The species. Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2. Nat Microbiol, 2020; 5(4): 536–44.
 
14.
WHO Director-General’s opening remarks at the media briefing on COVID-19: 11 March 2020 [Internet]. [cited 2020 May 25]. Available from: https://www.who.int/dg/speeche....
 
15.
Coronavirus disease 2019 [Internet]. [cited 2020 May 25]. Available from: https://www.who.int/emergencie....
 
16.
Li Q, Guan X, Wu P, et al. Early transmission dynamics in Wuhan, China, of novel coronavirus-infected pneumonia. N Engl J Med, 2020; 382(13): 1199–207.
 
17.
Deng S-Q, Peng H-J. Characteristics of and public health responses to the coronavirus disease 2019 outbreak in China. J Clin Med, 2020; 9(2): 575.
 
18.
Jiang F, Deng L, Zhang L, Cai Y, Cheung CW, Xia Z. Review of the clinical characteristics of coronavirus disease 2019 (COVID-19). J Gen Intern Med, 2020; 35: 1545–9.
 
19.
Xu X, Chen P, Wang J, et al. Evolution of the novel coronavirus from the ongoing Wuhan outbreak and modeling of its spike protein for risk of human transmission. Sci China Life Sci, 2020; 63(3): 457–60.
 
20.
Wong A, Li X, Lau S, Woo P. Global epidemiology of bat coronaviruses. Viruses, 2019; 11(2): 174.
 
21.
Han Q, Lin Q, Jin S, You L. Coronavirus 2019-nCoV: a brief perspective from the front line. J Infect, 2020; 80(4): 373–7.
 
22.
Drosten C, Günther S, Preiser W, et al. Identification of a novel coronavirus in patients with severe acute respiratory syndrome. N Engl J Med, 2003; 348(20): 1967–76.
 
23.
WHO Middle East respiratory syndrome coronavirus (MERS-CoV): The Kingdom of Saudi Arabia [Internet]. WHO. World Health Organization [cited 2020 May 25]. Available from: http://www.who.int/csr/don/24-....
 
24.
Zhou P, Yang X-L, Wang X-G, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature, 2020; 579(7798): 270–3.
 
25.
Li W, Shi Z, Yu M, et al. Bats are natural reservoirs of SARS-like coronaviruses. Science, 2005; 310(5748): 676–9.
 
26.
Rothe C, Schunk M, Sothmann P, et al. Transmission of 2019-nCoV infection from an asymptomatic contact in Germany. N Engl J Med, 2020; 382(10): 970–1.
 
27.
Wang D, Hu B, Hu C, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA, 2020; 323(11): 1061–9.
 
28.
Chen N, Zhou M, Dong X, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet, 2020; 395(10223): 507–13.
 
29.
Xu X-W, Wu X-X, Jiang X-G, et al. Clinical findings in a group of patients infected with the 2019 novel coronavirus (SARS-Cov-2) outside of Wuhan, China: retrospective case series. Br Med J, 2020; m606.
 
30.
Guan W, Ni Z, Hu Y, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med, 2020; 382(18): 1708–20.
 
31.
Jin Y-H, Cai L, Cheng Z-S, et al. A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version). Mil Med Res, 2020; 7(1): 4.
 
32.
Hellewell J, Abbott S, Gimma A, et al. Feasibility of controlling COVID-19 outbreaks by isolation of cases and contacts. Lancet Glob Health, 2020; 8(4): e488–96.
 
33.
Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet, 2020; 395(10229): 1054–62.
 
34.
Wang M, Cao R, Zhang L, et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res, 2020; 30(3): 269–71.
 
35.
Wujtewicz M, Dylczyk-Sommer A, Aszkiełowicz A, Zdanowski S, Piwowarczyk S, Owczuk R. COVID-19: what should anaethesiologists and intensivists know about it? Anaesthesiol Intensive Ther [Internet], [cited 2020 Mar 26]; Available from: https://www.termedia.pl/doi/10....
 
36.
Mitjà O, Clotet B. Use of antiviral drugs to reduce COVID-19 transmission. Lancet Glob Health, 2020; S2214109X20301145.
 
37.
Multicenter collaboration group of Department of Science and Technology of Guangdong Province and Health Commission of Guangdong Province for chloroquine in the treatment of novel coronavirus pneumonia. [Expert consensus on chloroquine phosphate for the treatment of novel coronavirus pneumonia]. Chin J Tuberc Respir Dis, 2020; 43(3): 185–8.
 
38.
Arechin Charakterystyka Produktu Leczniczego [Internet]. [cited 2020 May 25]. Available from: http://www.urpl.gov.pl/sites/d....
 
39.
Yao X, Ye F, Zhang M, et al. In vitro antiviral activity and projection of optimized dosing design of hydroxychloroquine for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Clin Infect Dis, 2020; ciaa237.
 
40.
Ganesan P, Schmiedge J, Manchaiah V, Swapna S, Dhandayutham S, Kothandaraman PP. Ototoxicity: a challenge in diagnosis and treatment. J Audiol Otol, 2018; 22(2): 59–68.
 
41.
Palomar García V, Abdulghani Martínez F, Bodet Agustí E, Andreu Mencía L, Palomar Asenjo V. Drug-induced otoxicity: current status. Acta Otolaryngol (Stockh), 2001; 121: 569–72.
 
42.
Humes HD. Insights into ototoxicity. Analogies to nephrotoxicity. Ann N Y Acad Sci, 1999; 884: 15–8.
 
43.
Echeverria P, Fina D, Norton S, Smith AL. Ototoxicity of gentamicin: clinical experience in a children’s hospital. Chemotherapy, 1978; 24(4): 267–71.
 
44.
Lord SG. Monitoring protocols for cochlear toxicity. Semin Hear, 2019; 40(2): 122–43.
 
45.
Fligor BJ. Pediatric ototoxicity: current trends and management. Semin Hear, 2019; 40(2): 154–61.
 
46.
Ototoxicity Monitoring: Position statement and practice guidelines [Internet]. American Academy of Audiology, 2014 [cited 2020 May 25]. Available from: https://www.audiology.org/publ....
 
47.
Sahraei Z, Shabani M, Shokouhi S, Saffaei A. Aminoquinolines against coronavirus disease 2019 (COVID-19): chloroquine or hydroxychloroquine. Int J Antimicrob Agents, 2020; 55(4):105945.
 
48.
Devaux CA, Rolain J-M, Colson P, Raoult D. New insights on the antiviral effects of chloroquine against coronavirus: what to expect for COVID-19? Int J Antimicrob Agents, 2020; 105938.
 
49.
Touret F, de Lamballerie X. Of chloroquine and COVID-19. Antiviral Res, 2020; 177: 104762.
 
50.
Gao J, Tian Z, Yang X. Breakthrough: chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies. Biosci Trends, 2020; 14(1): 72–3.
 
51.
Winzeler EA. Malaria research in the post-genomic era. Nature, 2008; 455(7214): 751–6.
 
52.
Bortoli R, Santiago M. Chloroquine ototoxicity. Clin Rheumatol, 2007; 26(11): 1809–10.
 
53.
Savarino A, Boelaert JR, Cassone A, Majori G, Cauda R. Effects of chloroquine on viral infections: an old drug against today’s diseases? Lancet Infect Dis, 2003; 3(11): 722–7.
 
54.
Baron S, editor. Medical Microbiology [Internet]. 4th ed. Galveston (TX): University of Texas Medical Branch at Galveston; 1996 [cited 2020 Mar 30]. Available from: http://www.ncbi.nlm.nih.gov/bo....
 
55.
Fitch CD. Ferriprotoporphyrin IX, phospholipids, and the antimalarial actions of quinoline drugs. Life Sci, 2004; 74(16): 1957–72.
 
56.
Huang Z, Srinivasan S, Zhang J, et al. Discovering thiamine transporters as targets of chloroquine using a novel functional genomics strategy. PLOS Genet, 2012; 8(11): e1003083.
 
57.
Vijayalakshmi Subramaniam RNV. Assessment of short term chloroquine-induced ototoxicity in malaria patients. Glob J Med Res [Internet], 2015. Available from: https://www.medicalresearchjou....
 
58.
Bondeson J, Sundler R. Antimalarial drugs inhibit phospholipase A2 activation and induction of interleukin 1beta and tumor necrosis factor alpha in macrophages: implications for their mode of action in rheumatoid arthritis. Gen Pharmacol, 1998; 30(3): 357–66.
 
59.
Krishna S, White NJ. Pharmacokinetics of quinine, chloroquine and amodiaquine. Clinical implications. Clin Pharmacokinet, 1996; 30(4): 263–99.
 
60.
Hu TY, Frieman M, Wolfram J. Insights from nanomedicine into chloroquine efficacy against COVID-19. Nat Nanotechnol, 2020; 15(4): 247–49.
 
61.
Burkard C, Verheije MH, Wicht O, et al. Coronavirus cell entry occurs through the endo-lysosomal pathway in a proteolysis-dependent manner. PLOS Pathog, 2014; 10(11): e1004502.
 
62.
Vincent MJ, Bergeron E, Benjannet S, et al. Chloroquine is a potent inhibitor of SARS coronavirus infection and spread. Virol J, 2005; 2: 69.
 
63.
Legssyer R, Josse C, Piette J, Ward RJ, Crichton RR. Changes in function of iron-loaded alveolar macrophages after in vivo administration of desferrioxamine and/or chloroquine. J Inorg Biochem, 2003; 94(1-2): 36–42.
 
64.
Seçkin U, Ozoran K, Ikinciogullari A, Borman P, Bostan EE. Hydroxychloroquine ototoxicity in a patient with rheumatoid arthritis. Rheumatol Int, 2000; 19(5): 203–4.
 
65.
Coronavirus (COVID-19) Update: Daily Roundup, March 24, 2020 [Internet]. FDA; 2020 [cited 2020 May 25]. Available from: https://www.fda.gov/news-event....
 
66.
Rynes RI. Antimalarial drugs in the treatment of rheumatological diseases. Br J Rheumatol, 1997; 36(7): 799–805.
 
67.
Fernandes MR de N, Soares DBR, Thien CI, Carneiro S. Hydroxychloroquine ototoxicity in a patient with systemic lupus erythematosus. An Bras Dermatol, 2018; 93(3): 469–70.
 
68.
Hadi U, Nuwayhid N, Hasbini AS. Chloroquine ototoxicity: an idiosyncratic phenomenon. Otolaryngol Head Neck Surg, 1996; 114(3): 491–3.
 
69.
Figueiredo MC, Atherino CCCT, Monteiro CV, Levy RA. Antimaláricos e ototoxicidade. Rev Bras Reumatol, 2004; 44(3): 212–4.
 
70.
Sotelo J, Briceño E, López-González MA. Adding chloroquine to conventional treatment for glioblastoma multiforme: a randomized, double-blind, placebo-controlled trial. Ann Intern Med, 2006; 144(5): 337–43.
 
71.
Mukherjee DK. Chloroquine ototoxicity: a reversible phenomenon? J Laryngol Otol, 1979; 93(8): 809–15.
 
72.
Bernard P. Alterations of auditory evoked potentials during the course of chloroquine treatment. Acta Otolaryngol (Stockh), 1985; 99(3-4): 387–92.
 
73.
Norris CH. Drugs affecting the inner ear. A review of their clinical efficacy, mechanisms of action, toxicity, and place in therapy. Drugs, 1988; 36(6): 754–72.
 
74.
Singh AK, Singh A, Shaikh A, Singh R, Misra A. Chloroquine and hydroxychloroquine in the treatment of COVID-19 with or without diabetes: a systematic search and a narrative review with a special reference to India and other developing countries. Diabetes Metab Syndr Clin Res Rev, 2020; 14(3): 241–6.
 
75.
Handbook of COVID-19 Prevention and Treatment [Internet]. [cited 2020 Apr 14]. Available from: https://video-intl.alicdn.com/....
 
76.
Gautret P, Lagier J-C, Parola P, et al. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int J Antimicrob Agents, 2020; 105949.
 
77.
Retallack H, Di Lullo E, Arias C, et al. Zika virus cell tropism in the developing human brain and inhibition by azithromycin. Proc Natl Acad Sci U S A, 2016; 113(50): 14408–13.
 
78.
Madrid PB, Panchal RG, Warren TK, et al. Evaluation of ebola virus inhibitors for drug repurposing. ACS Infect Dis, 2015; 1(7): 317–26.
 
79.
Wallace MR, Miller LK, Nguyen MT, Shields AR. Ototoxicity with azithromycin. Lancet, 1994; 343: 24.
 
80.
Lo SH, Kotabe S, Mitsunaga L. Azithromycin-induced hearing loss. Am J Health-Syst Pharm, 1999; 56: 380–3.
 
81.
Ress BD, Gross EM. Irreversible sensorineural hearing loss as a result of azithromycin ototoxicity. A case report. Ann Otol Rhinol Laryngol, 2000; 109(4): 435–7.
 
82.
Nishimoto N, Kishimoto T, Yoshizaki K. Anti-interleukin 6 receptor antibody treatment in rheumatic disease. Ann Rheum Dis, 2000; 59 Suppl 1: i21–7.
 
83.
Xu X, Han M, Li T, et al. Effective treatment of severe COVID-19 patients with tocilizumab. Proc Natl Acad Sci U S A, 2020; 117(20): 10970–5.
 
84.
Chinese Clinical Trial Registry (ChiCTR). The World Health Organization international clinical trials registered organization registered platform [Internet]. [cited 2020 May 25]. Available from: http://www.chictr.org.cn/showp....
 
85.
Bennardo F, Buffone C, Giudice A. New therapeutic opportunities for COVID-19 patients with tocilizumab: possible correlation of interleukin-6 receptor inhibitors with osteonecrosis of the jaws. Oral Oncol, 2020; 104659.
 
86.
Harrison C. Coronavirus puts drug repurposing on the fast track. Nat Biotechnol, 2020; 38, 379–81.
 
87.
Sanofi and Regeneron begin global Kevzara (sarilumab) clinical trial program in patients with severe COVID-19, Mar 16, 2020 [Internet]. [cited 2020 May 25]. Available from: http://www.news.sanofi.us/2020....
 
88.
Actemra side effects: common, severe, long term [Internet]. Drugs.com. [cited 2020 May 25]. Available from: https://www.drugs.com/sfx/acte....
 
89.
Actemra and dizziness - suspected cause - reports of side effects [Internet]. [cited 2020 May 25]. Available from: http://www.druglib.com/reporte....
 
90.
Sato T, Minakuchi S, Mochizuki M, Takeuchi M. Acute anterior uveitis after discontinuation of tocilizumab in a patient with rheumatoid arthritis. Clin Ophthalmol, 2014; 8: 187–90.
 
91.
Lu H. Drug treatment options for the 2019-new coronavirus (2019-nCoV). Biosci Trends, 2020; 14(1): 69–71.
 
92.
Li H, Wang YM, Xu JY, Cao B. [Potential antiviral therapeutics for 2019 Novel Coronavirus]. Chin J Tuberc Respir Dis, 2020; 43(0): E002.
 
93.
Li L, Cai B, Wang M, Zhu Y. [A multicenter study of efficacy and safety of oseltamivir in treatment of naturally acquired influenza]. Zhonghua Nei Ke Za Zhi, 2001; 40(12): 838–42.
 
94.
Cianfrone G, Pentangelo D, Cianfrone F, et al. Pharmacological drugs inducing ototoxicity, vestibular symptoms and tinnitus: a reasoned and updated guide. Eur Rev Med Pharmacol Sci, 2011; 15(6): 601–36.
 
95.
Tamiflu [Internet]. European Medicines Agency, 2018 [cited 2020 May 26]. Available from: https://www.ema.europa.eu/en/m....
 
96.
Choo D, Hossain M, Liew P, Chowdhury S, Tan J. Side effects of oseltamivir in end-stage renal failure patients. Nephrol Dial Transplant, 2011; 26(7): 2339–44.
 
97.
Sheahan TP, Sims AC, Graham RL, et al. Broad-spectrum antiviral GS-5734 inhibits both epidemic and zoonotic coronaviruses. Sci Transl Med, 2017; 9(396): eaal3653.
 
98.
Sheahan TP, Sims AC, Leist SR, et al. Comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against MERS-CoV. Nat Commun, 2020; 11(1): 222.
 
99.
de Wit E, Feldmann F, Cronin J, et al. Prophylactic and therapeutic remdesivir (GS-5734) treatment in the rhesus macaque model of MERS-CoV infection. Proc Natl Acad Sci U S A, 2020; 117(12): 6771–6.
 
100.
Remdesivir: Coronavirus Disease COVID-19 [Internet]. COVID-19 Treatment Guidelines [cited 2020 May 20]. Available from: https://www.covid19treatmentgu....
 
101.
Williamson BN et al. Clinical benefit of remdesivir in rhesus macaques infected with SARS-CoV-2. Preprint [Internet]. [cited 2020 May 20]. Available from: https://www.biorxiv.org/conten....
 
102.
Wang Y, Zhang D, Du G, et al. Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial. Lancet, 2020; 395(10236): 1569–78.
 
103.
Grein J, Ohmagari N, Shin D, et al. Compassionate use of remdesivir for patients with severe Covid-19. N Engl J Med, 2020.
 
104.
Information on COVID-19 treatment, prevention and research [Internet]. COVID-19 Treatment Guidelines [cited 2020 May 20]. Available from: https://www.covid19treatmentgu....
 
105.
Wu R, Wang L, Kuo H-CD, et al. An update on current therapeutic drugs treating COVID-19. Curr Pharmacol Rep, 2020; 1–15.
 
106.
Yousefi B, Valizadeh S, Ghaffari H, Vahedi A, Karbalaei M, Eslami M. A global treatments for coronaviruses including COVID-19. J Cell Physiol, 2020.
 
107.
McKee DL, Sternberg A, Stange U, Laufer S, Naujokat C. Candidate drugs against SARS-CoV-2 and COVID-19. Pharmacol Res, 2020; 157:104859.
 
108.
Xu X, Ong YK, Wang DY. Role of adjunctive treatment strategies in COVID-19 and a review of international and national clinical guidelines. Mil Med Res, 2020; 7(1): 22.
 
109.
Duggal P, Sarkar M. Audiologic monitoring of multi-drug resistant tuberculosis patients on aminoglycoside treatment with long term follow-up. BMC Ear Nose Throat Disord, 2007; 7: 5.
 
110.
Campbell KCM. Pharmacology and Ototoxicity for Audiologists [Internet]. Clifton Park, NY: Thomson/Delmar Learning; 2007.
 
111.
Campbell KC, Durrant J. Audiologic monitoring for ototoxicity. Otolaryngol Clin North Am, 1993; 26(5): 903–14.
 
112.
Fee WE. Aminoglycoside ototoxicity in the human. Laryngoscope, 1980; 90: 1–19.
 
113.
Wright CG, Schaefer SD. Inner ear histopathology in patients treated with cis-platinum. Laryngoscope, 1982; 92(12): 1408–13.
 
114.
Schuknecht HF. Pathology of the Ear. 2nd ed. Philadelphia: Lea & Febiger; 1993.
 
115.
Dreschler WA, van der Hulst RJ, Tange RA, Urbanus NA. The role of high-frequency audiometry in early detection of ototoxicity. Audiol, 1985(6); 24: 387–95.
 
116.
Dreschler WA, van der Hulst RJ, Tange RA, Urbanus NA. Role of high-frequency audiometry in the early detection of ototoxicity. II. Clinical aspects. Audiol, 1989; 28: 211–20.
 
117.
Fausti SA, Frey RH, Henry JA, Olson DJ, Schaffer HI. Early detection of ototoxicity using high-frequency, tone-burst-evoked auditory brainstem responses. J Am Acad Audiol, 1992; 3(6): 397–404.
 
118.
Frank T. High-frequency hearing thresholds in young adults using a commercially available audiometer. Ear Hear, 1990; 11(6): 450–4.
 
119.
Osterhammel D. High frequency audiometry clinical aspects. Scand Audiol, 1980; 9(4): 249–56.
 
120.
Kujansuu E, Rahko T, Punnonen R, Karma P. Evaluation of the hearing loss associated with cis-platinum treatment by high-frequency audiometry. Gynecol Oncol, 1989; 33(3): 321–2.
 
121.
Wiley TL, Cruickshanks KJ, Nondahl DM, et al. Aging and high-frequency hearing sensitivity. J Speech Lang Hear Res, 1998; 41(5): 1061–72.
 
122.
Beck A, Maurer J, Welkoborsky HJ, Mann W. [Changes in transitory evoked otoacoustic emissions in chemotherapy with cisplatin and 5FU]. HNO, 1992; 40(4): 123–7.
 
123.
Zorowka PG, Schmitt HJ, Gutjahr P. Evoked otoacoustic emissions and pure tone threshold audiometry in patients receiving cisplatinum therapy. Int J Pediatr Otorhinolaryngol, 1993; 25(1-3): 73–80.
 
124.
Ress BD, Sridhar KS, Balkany TJ, Waxman GM, Stagner BB, Lonsbury-Martin BL. Effects of cis-platinum chemotherapy on otoacoustic emissions: the development of an objective screening protocol. Otolaryngol Head Neck Surg, 1999; 121(6): 693–701.
 
125.
Norton S. Cochlear function and otoacoustic emissions. Semin Hear, 1992; 13: 1–14.
 
126.
Probst R, Lonsbury-Martin BL, Martin GK. A review of otoacoustic emissions. J Acoust Soc Am, 1991; 89(5): 2027–67.
 
127.
Rybak LP. Ototoxicity of loop diuretics. Otolaryngol Clin North Am, 1993; 26(5): 829–44.
 
128.
Board on Population Health and Public Health Practice, Health and Medicine Division, National Academies of Sciences, Engineering, and Medicine. Assessment of long-term health effects of antimalarial drugs when used for prophylaxis [Internet]. Savitz DA, Styka AN, editors. Washington, DC: National Academies Press; 2020 [cited 2020 Mar 30]. p. 25688. Available from: https://www.nap.edu/catalog/25....
 
129.
Lee N, Hui D, Wu A, et al. A major outbreak of severe acute respiratory syndrome in Hong Kong. N Engl J Med, 2003; 348(20): 1986–94.
 
130.
Colson P, Rolain J-M, Raoult D. Chloroquine for the 2019 novel coronavirus SARS-CoV-2. Int J Antimicrob Agents, 2020; 55(3): 105923.
 
131.
Mackenzie AH. Dose refinements in long-term therapy of rheumatoid arthritis with antimalarials. Am J Med, 1983; 75: 40–5.
 
132.
Lim SC, Tang SP. Hydroxychloroquine-induced ototoxicity in a child with systemic lupus erythematosus. Int J Rheum Dis, 2011; 14(1): e1–2.
 
133.
Coutinho MB, Duarte I. Hydroxychloroquine ototoxicity in a child with idiopathic pulmonary haemosiderosis. Int J Pediatr Otorhinolaryngol, 2002; 62(1): 53–7.
 
134.
Nielsen-Abbring FW, Perenboom RM, van der Hulst RJ. Quinine-induced hearing loss. ORL J Oto-Rhino-Laryngol Relat Spec, 1990; 52(1): 65–8.
 
135.
Scherbel AL, Harrison JW, Atdjian M. Further observations on the use of 4-aminoquinoline compounds in patients with rheumatoid arthritis or related diseases. Cleve Clin Q, 1958; 25(2): 95–111.
 
136.
Oliveira KRHM, Dos Anjos LM, Araújo APS, et al. Ascorbic acid prevents chloroquine-induced toxicity in inner glial cells. Toxicol Vitro Int J Publ Assoc BIBRA, 2019; 56: 150–5.
 
eISSN:2084-3127
ISSN:2083-389X