Risk of Tinnitus with Hydroxychloroquine
Tinnitus is a recognized adverse effect of hydroxychloroquine therapy, though the precise incidence remains uncertain due to lack of systematic prevalence data. 1
Mechanism of Ototoxicity
- Hydroxychloroquine accumulates extensively in melanin-bearing tissues throughout the body, with particularly high concentrations in inner-ear structures such as the stria vascularis, which underlies its ototoxic potential. 1
- The drug concentrates within intracellular vesicles (endosomes and lysosomes) where it becomes trapped in melanin-rich cells, leading to potential damage. 1
Clinical Manifestations
- Tinnitus is documented as an adverse effect in the FDA drug label and has been reported in multiple case series and reviews. 2
- Sensorineural hearing loss frequently co-occurs with tinnitus in affected individuals, reflecting secondary damage to cochlear hair cells. 1
- In systematic reviews, tinnitus was found to be either reversible or irreversible after hydroxychloroquine discontinuation. 3
- One case series reported tinnitus in 2 of 19 documented cases of hydroxychloroquine ototoxicity. 3
- A case report documented bilateral tinnitus as part of acute neurotoxic vestibulopathy following accidental hydroxychloroquine overdose, with permanent persistence despite drug discontinuation. 4
Risk Factors for Ototoxicity
The primary risk factors that increase likelihood of auditory toxicity include:
- Daily doses exceeding approximately 250 mg (chloroquine-equivalent) are linked to higher likelihood of auditory toxicity. 5, 1
- Longer duration of hydroxychloroquine use is associated with increased risk of ototoxic events. 1
- Renal impairment increases systemic drug levels and toxicity risk, as hydroxychloroquine is cleared by the kidneys. 6, 7
- Concomitant tamoxifen use increases the risk of toxicity. 6
Comparison to Retinal Toxicity
A critical distinction exists between monitoring practices for different organ systems:
- While retinal toxicity has well-established screening protocols with baseline examination and annual screening after 5 years of use, there are currently no standardized audiological screening protocols for patients receiving long-term hydroxychloroquine. 1
- The American Academy of Ophthalmology recommends keeping daily dosage <5.0 mg/kg real weight to minimize retinal toxicity risk, with <2% risk up to 10 years at this dose. 7, 6
- Some older guidelines suggested routine ocular screening every 6-12 months, but similar recommendations for audiological monitoring are absent from current major guidelines. 5
Clinical Recommendations
Clinicians should remain vigilant for patient-reported hearing changes, tinnitus, or balance disturbances and consider prompt audiologic evaluation when symptoms arise. 1
- Patients should be counseled about the potential for auditory side effects when initiating hydroxychloroquine therapy. 8, 9
- Any new-onset tinnitus, hearing loss, or imbalance in patients taking hydroxychloroquine warrants consideration of drug-related ototoxicity. 9
- The improvement in audiological examinations and regression of vestibular symptoms after stopping hydroxychloroquine treatment provides strong evidence for drug-induced ototoxicity. 10
Common Pitfalls
- Do not dismiss tinnitus complaints as unrelated to hydroxychloroquine simply because audiological screening is not routinely performed like ophthalmologic screening. 1
- Do not assume ototoxicity only occurs with overdose—therapeutic doses maintained over long duration can cause auditory effects. 3
- Do not overlook the potential for permanent auditory dysfunction—while some cases are reversible, persistent tinnitus and hearing loss have been documented. 3, 4