Can Natalizumab Cause Tinnitus?
Tinnitus is not a recognized or documented adverse effect of natalizumab based on available clinical evidence, including large-scale trials, post-marketing surveillance, and comprehensive safety reviews.
Evidence from Clinical Trials and Safety Data
The most comprehensive evidence comes from systematic reviews and clinical trials involving thousands of patients:
Large-scale RCTs involving 3,255 patients treated with natalizumab 300 mg IV did not identify tinnitus as an adverse event in their safety profiles 1
Post-marketing surveillance data from the FDA Adverse Event Reporting System (FAERS) database analyzed 29,460 patients with drug-related tinnitus across multiple medications, and natalizumab was not among the top 25 tinnitus-associated drugs 2
Multiple sclerosis was identified as a relevant indication in tinnitus reports (n=914), but this reflects the underlying disease rather than natalizumab treatment 2
Documented Adverse Effects of Natalizumab
The established adverse effect profile of natalizumab includes 1, 3:
- Progressive multifocal leukoencephalopathy (PML) - the most serious risk, with incidence of 3.4/1000 patients (95% CI 3.08-3.74)
- Infections: nasopharyngitis, urinary tract infections, recurrent vaginitis 4, 3
- Systemic effects: headache, fatigue, nausea, fever, rigidity 4, 3
- Hypersensitivity reactions: urticaria 3
- Neuropsychiatric: anxiety, dizziness 4, 3
- Gastrointestinal: gastroenteritis 3
Clinical Context and Differential Diagnosis
If a patient on natalizumab reports tinnitus, consider alternative explanations:
Multiple sclerosis itself can cause auditory symptoms including tinnitus, hearing loss, and vertigo as part of brainstem or eighth cranial nerve involvement 5
Concomitant medications should be evaluated, as many drugs commonly used in MS patients can cause tinnitus, including antidepressants (duloxetine showed ROR 11.99), fluoroquinolones (ciprofloxacin ROR 9.96), and other immunomodulators 2
Disease progression affecting auditory pathways should be assessed with appropriate neuroimaging 5
Monitoring Recommendations
While tinnitus is not an expected natalizumab adverse effect, standard safety monitoring for natalizumab-treated patients should continue 5, 6, 7:
- JCV antibody testing every 6 months for seronegative patients 7
- MRI surveillance frequency based on JCV status and index values 5, 7
- Clinical vigilance for any new neurological symptoms, which should prompt immediate evaluation regardless of whether they are recognized adverse effects 7
Bottom line: Tinnitus should not be attributed to natalizumab without thorough investigation of other causes, including MS disease activity, concomitant medications, and other medical conditions.