Ototoxic effects of hydroxychloroquine

Gonçalves, Laura Faustino; Patatt, Fernanda Soares Aurélio; de Paiva, Karina Mary; Haas, Patrícia

doi:10.1590/1806-9282.67.Suppl1.20200677

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Sumário

Review Article • Rev. Assoc. Med. Bras. 67 (Suppl 1) • 2021 • https://doi.org/10.1590/1806-9282.67.Suppl1.20200677 copy

Ototoxic effects of hydroxychloroquine

Authorship SCIMAGO INSTITUTIONS RANKINGS

SUMMARY

OBJECTIVE

To present scientific evidence based on a systematic review of the literature (PRISMA), aiming to systematize evidence of the ototoxic effects of hydroxychloroquine (HCQ).

METHODS

The studies were selected using a combination based on the Medical Subject Headings (MeSH). The databases searched were MEDLINE (PubMed), LILACS, SciELO, and BIREME, encompassing articles from January 2010 to May 2020, with no restrictions of language and place of publication.

RESULTS

A total of 148 articles with the potential to be included were retrieved. Of these, two answered the research question, which consisted of seeking evidence of the ototoxic effects of hydroxychloroquine. These studies scored 11 in their quality assessment with the modified protocol by Pithon et al.¹³13. Pithon MM, Sant’Anna LI, Baião FC, Santos RL, Coqueiro RS, Maia LC. Assessment of the effectiveness of mouthwashes in reducing cariogenic biofilm in orthodontic patients: a systematic review. J Dent. 2015;43(3):297-308. https://doi.org/10.1016/j.jdent.2014.12.010
https://doi.org/10.1016/j.jdent.2014.12.... .

CONCLUSIONS

The studies reported possible ototoxicity of HCQ. Audiovestibular changes, such as hearing loss, peripheral vestibular syndrome, and tinnitus were evidenced in patients submitted to HCQ. The improvement in the audiological examinations and the regression in the vestibular syndrome after stopping the treatment with HCQ are strong arguments in favor of the ototoxicity caused by this medication. However, there are still divergences about the relationship between ototoxic effects and the use of HCQ.

KEYWORDS:
Hydroxychloroquine; Hearing; Ototoxicity; Medication errors

Acronyms	Definitions
P	Patients
I	Hydroxychloroquine
C	Ototoxicity
O	Medication
S	Descriptive study Cross-sectional study Observational study

Author(s)/Year/Place of publication	Objective(s)	Examinations	History of medications	Results	Conclusion(s)
Chatelet et al.¹⁴14. Chatelet JN, Auffret M, Combret S, Bondon-Guitton E, Lambert M, Gautier S. Hydroxychloroquine-induced hearing loss: first case of positive rechallenge and analysis of the French pharmacovigilance database. Rev Med Interne. 2017;38(5):340-3. https://doi.org/10.1016/j.revmed.2016.07.008 https://doi.org/10.1016/j.revmed.2016.07... , 2017 France	To report the case of a patient treated with HCQ. She presented hearing loss, which improved when the medication was discontinued.	Auditory assessment with pure-tone threshold audiometry (PTA); diagnosed with sudden bilateral hearing loss. Brain MRI revealed the absence of lesions in the brainstem. A new visit to the otorhinolaryngologist, 4 months after discontinuation of HCQ for the second time, when the stabilization of the hearing loss was evidenced.	Use of 400 mg/day of HCQ. Ototoxicity was treated with three 1000-mg doses of methylprednisolone. Use of methotrexate (15 mg/week) in combination with glucocorticoids, for 15 years. Reintroduction of HCQ, 400 mg/day, 5 days a week, posteriorly removed	After using methylprednisolone, the hearing loss was partially solved, with an improvement in the audiometry. The hypothesis of hearing loss related to HCQ was considered, and the treatment was stopped. After 15 years of treating with methotrexate in combination with glucocorticoids, it was necessary to reintroduce HCQ. The patient presented peripheral vestibular syndrome 3 months after resuming the drug and was shortly after diagnosed with a mild bilateral hearing loss. After final discontinuation, there was neither recurrence of the vestibular syndrome nor worsening of the hearing loss.	Possible ototoxicity related to the use of HCQ.
Patil et al.²2. Patil A, Jerang Y, Mathew J. Hydroxychloroquine-induced auditory toxicity. Indian J Rheumatol. 2020;15(1):53-5. https://doi.org/10.4103/injr.injr_130_19 https://doi.org/10.4103/injr.injr_130_19... , 2020 India	To report the case of a middle-aged woman who developed auditory toxicity in relation to the use of HCQ	Audiological follow-up with PTA, in which the patient was diagnosed with a mild idiopathic sensorineural hearing loss. The thresholds worsened 6 months after beginning the treatment with HCQ. However, these symptoms improved after intervention.	Treated with HCQ (400 mg/day) and steroids (40 mg/day of prednisolone gradually reduced to 5 mg/day and maintained) for 1 year. After intervention, the patient was treated with mycophenolate mofetil and with increased the dosage of prednisolone to 10 mg/day	During therapy, the patient complained of tinnitus and gradual worsening of hearing. There was no history of vertigo, vomit, or other characteristics of involvement of the vestibular system. Diagnosed with mild idiopathic sensorineural hearing loss. The patient did not use any medication with the potential for auditory toxicity other than HCQ. A new audiogram obtained after stopping the use of HCQ showed auditory stabilization, with an improvement in the auditory thresholds, bilaterally.	Ototoxicity related to the use of HCQ was demonstrated.

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[1] *Corresponding author: patrícia.haas@ufsc.br