Can Hydroxychloroquine Cause Tinnitus?
Yes, hydroxychloroquine can cause tinnitus, and this ototoxic effect can be either reversible or irreversible depending on dose, duration, and individual patient factors.
Mechanism and Clinical Evidence
Hydroxychloroquine causes ototoxicity through binding to melanin in inner ear structures, similar to its retinal toxicity mechanism. 1 The drug can damage cochlear and vestibular structures, resulting in audiovestibular changes including tinnitus, hearing loss, and peripheral vestibular syndrome. 2
Documented Tinnitus Cases
- Tinnitus has been reported in multiple case series and systematic reviews as a recognized adverse effect of hydroxychloroquine. 2, 3, 4
- In one systematic review analyzing ototoxicity, tinnitus was documented in 2 cases, with outcomes ranging from reversible to irreversible. 4
- An overdose case report documented acute bilateral tinnitus that became permanent despite discontinuation of the medication. 5
- Tinnitus was identified as the most frequent auditory symptom in an integrative review of auditory and vestibular changes. 6
Reversibility and Prognosis
The key clinical distinction is that some patients experience improvement in audiological symptoms after stopping hydroxychloroquine, while others develop permanent changes. 2
- Improvement in audiological examinations and regression of vestibular symptoms after discontinuation provides strong evidence for drug-induced ototoxicity. 2
- However, irreversible ototoxicity can develop, particularly when oral doses exceed 250 mg/day. 7
- The characteristics of sensorineural hearing loss and tinnitus can be temporary, but persistent auditory dysfunction is well-documented. 3
Dose-Related Risk
Daily doses exceeding 250 mg/day significantly increase the risk of irreversible ototoxicity. 7
- Standard dosing for malaria treatment (as shown in guidelines) includes hydroxychloroquine at 800 mg initially, then 400 mg at 6,24, and 48 hours. 1
- Higher doses proposed for other indications carry substantially greater ototoxic risk than standard antimalarial dosing. 3
Clinical Monitoring Recommendations
While guidelines emphasize mandatory ophthalmologic monitoring every 6-12 months for retinal toxicity 7, audiological monitoring is not routinely mandated but should be considered, especially for patients reporting auditory symptoms.
Red Flags Requiring Attention:
- New onset tinnitus during treatment 2, 5, 6
- Bilateral or unilateral hearing changes 4
- Vertigo or imbalance 2, 6
- Headache with auditory symptoms 5
Common Pitfall
The most critical error is dismissing patient reports of tinnitus or hearing changes as unrelated to hydroxychloroquine therapy. Given that improvement after discontinuation is possible in some cases, early recognition and drug cessation may prevent permanent damage. 2 However, clinicians must balance this against the therapeutic benefits for conditions like systemic lupus erythematosus, where hydroxychloroquine provides substantial disease control. 7
Special Populations at Higher Risk:
- Patients with renal impairment (decreased drug excretion increases systemic levels and toxicity risk) 7
- Those on prolonged therapy 7, 3
- Patients receiving doses above recommended thresholds 7, 3
Practical Management Algorithm
- Before initiating therapy: Document baseline hearing status if feasible, particularly for patients requiring long-term treatment
- During therapy: Instruct patients to report any new tinnitus, hearing changes, or balance problems immediately 3
- If symptoms develop: Consider audiological evaluation and weigh risks versus benefits of continuation 3
- For persistent symptoms: Refer for formal hearing evaluation once patient is stable 3
The evidence clearly establishes hydroxychloroquine as an ototoxic medication capable of causing tinnitus, though the frequency is not precisely quantified and individual susceptibility varies. 2, 3, 4