Which medications can cause ear pain (otalgia)?

Medications That Can Cause Ear Pain

Ear pain (otalgia) is rarely a direct effect of systemic medications, but certain drugs can cause it indirectly through ototoxicity, inflammation, or allergic reactions.

Direct Ototoxic Medications That May Present With Ear Pain

Aminoglycoside Antibiotics

• Aminoglycosides (gentamicin, tobramycin, amikacin, streptomycin) are the most notorious ototoxic drugs, causing irreversible damage to auditory sensory cells in the organ of Corti, which can manifest as ear discomfort, tinnitus, and hearing loss 1, 2, 3.
• The risk increases with prolonged therapy, high doses, renal impairment, dehydration, and co-administration of other ototoxic agents 1, 4.
• Ototoxicity is dose-dependent and can worsen even after drug discontinuation 1.

Loop Diuretics

• Furosemide and other loop diuretics can cause acute, typically transient hearing impairment and tinnitus, especially with high-dose intravenous administration 1, 2, 3.
• The ototoxicity is usually reversible but can become permanent with repeated exposure or when combined with aminoglycosides 4, 5.

Antineoplastic Agents

• Cisplatin is particularly associated with delayed, irreversible hearing loss and tinnitus that may present with ear discomfort 1, 2, 3.
• Long-term treatment with chemotherapy agents typically causes destruction of auditory sensory cells 3.

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)

• High-dose or prolonged NSAID therapy (aspirin, ibuprofen, naproxen) can cause acute, usually transient tinnitus and hearing impairment that patients may describe as ear discomfort 2, 3, 4.
• At least 18 different NSAIDs have been associated with ototoxicity 5.

Antimalarial Drugs

• Chloroquine and related antimalarials are recognized causes of drug-induced tinnitus and hearing disorders 4, 5.

Phosphodiesterase-5 Inhibitors

• Tadalafil and related medications (sildenafil, vardenafil) have been reported to cause hearing loss and ear-related symptoms 1.

Topical Otic Preparations That Can Cause Ear Pain

Aminoglycoside-Containing Ear Drops

• Neomycin-containing otic preparations cause allergic contact dermatitis in 13–30% of patients with chronic otitis externa, presenting as persistent ear pain, erythema, pruritus, edema, and otorrhea despite treatment 6, 7.
• When a perforated eardrum is present, ototoxic ear drops (neomycin, polymyxin B, gentamicin) can pass into the inner ear and cause irreversible hearing loss 1.
• The American Academy of Otolaryngology-Head and Neck Surgery recommends avoiding aminoglycoside-containing drops when tympanic membrane integrity is uncertain or compromised 6.

Hydrocortisone-Containing Preparations

• Hydrocortisone in otic drops can cause contact sensitivity in 13–30% of patients with chronic otitis externa, manifesting as persistent ear pain and inflammation 6.

Benzocaine Topical Anesthetics

• Benzocaine otic drops are not FDA-approved for active ear infections and should be avoided, as they may mask disease progression and cause allergic reactions 7.

Medications That Cause Ear Pain Through Allergic or Inflammatory Mechanisms

Contact Allergens in Topical Preparations

• Neomycin is the most common substance causing allergic reactions in patients with ear conditions, and neomycin-containing preparations should be avoided in patients with treatment failure 7.
• Other common sensitizers include bacitracin, polymyxin B sulfate, triamcinolone, propylene glycol, and thimerosal 6.

Nickel (in Ear Jewelry)

• Nickel affects approximately 10% of women with pierced ears, causing allergic contact dermatitis with erythema, edema, and pain in the auricular area 8.

Critical Risk Factors That Increase Drug-Induced Ear Pain

• Age, dehydration, renal failure, and co-administration of multiple ototoxic drugs significantly increase the risk of drug-related hearing loss and associated ear discomfort 1, 4.
• Exposure to loud noise may potentiate hearing loss and ear symptoms from cochleotoxic drugs 3.
• Diabetes and immunocompromised states increase susceptibility to medication-related ear complications 6, 7.

Common Pitfalls to Avoid

• Never use ototoxic ear drops (aminoglycosides) when tympanic membrane integrity is uncertain, as this can cause irreversible inner ear damage 6, 1.
• Avoid neomycin-containing preparations in patients with eczema, chronic otitis externa, or history of contact dermatitis 6, 7.
• Do not dismiss ear pain in patients on aminoglycosides, loop diuretics, or chemotherapy—early recognition and drug discontinuation may prevent permanent damage 1, 3, 4.
• Ototoxicity can worsen even after the drug is withdrawn, so monitoring should continue beyond treatment cessation 1.