10Medication-Induced Tinnitus and Polypharmacy

FWhy a drug history comes first

Before imaging or bloods, ask what the patient swallows. Drug-induced tinnitus is common, frequently overlooked, and — unlike most other causes — sometimes fully reversible. More than two hundred agents have been linked to tinnitus or hearing change, and the comprehensive reference guides catalogue the main offenders by class [2011].

Two questions reframe the consultation. When did the noise start relative to a new prescription or a dose increase? And does it ease when a drug is paused? A temporal link to a recent medication change, with relief on withdrawal, is far more useful than any blood test for confirming a drug cause.

The clinically important distinction is reversibility. Salicylates, quinine and loop diuretics usually cause a temporary tinnitus that fades when the drug clears. Aminoglycosides and platinum chemotherapy destroy hair cells and tend to leave permanent tinnitus and hearing loss [2011].

TThe classic reversible offenders: salicylates, quinine, loop diuretics

High-dose aspirin is the textbook example. At doses above roughly 2.7 g per day, salicylate produces a characteristic high-pitched, often bilateral tinnitus accompanied by a mild flat hearing loss. The mechanism is elegant: salicylate reversibly interferes with prestin, the motor protein of the outer hair cell, blunting cochlear amplification rather than killing the cell [2000]. Stop the drug and the ear recovers within one to three days.

Quinine and its relatives chloroquine and hydroxychloroquine produce a similar reversible cinchonism — tinnitus, hearing loss and visual blur — though high cumulative antimalarial exposure can leave permanent damage.

Loop diuretics (furosemide, bumetanide, ethacrynic acid) disturb the ionic pump of the stria vascularis, collapsing the endocochlear potential. Tinnitus from a loop diuretic is usually transient and dose-related, seen most with rapid intravenous boluses or in renal failure — but the effect becomes dangerous when stacked with an aminoglycoside.

CThe permanent offenders: aminoglycosides and platinum chemotherapy

Aminoglycosides (gentamicin, tobramycin, amikacin, streptomycin, neomycin) are taken up by hair cells and generate reactive oxygen species that trigger apoptosis, beginning in the high-frequency basal turn. The loss is cumulative, can progress after the drug is stopped, and is permanent [2011]. Susceptibility is partly genetic — the mitochondrial m.1555A>G variant predisposes to profound deafness from even a single dose, which is why a family history of antibiotic-related deafness must be sought.

Cisplatin is the other great irreversible offender, producing dose-dependent high-frequency hearing loss and tinnitus in a majority of treated patients; carboplatin and oxaliplatin are less ototoxic. Audiometric monitoring during platinum chemotherapy is standard, and sodium thiosulfate now offers some otoprotection in paediatric solid tumours.

For these drugs the goal is prevention: weigh the indication, monitor hearing, avoid combining ototoxins, and counsel the patient that any tinnitus may be the first audible sign of permanent cochlear injury.

TThe everyday culprits and polypharmacy

Beyond the dramatic classes lie the drugs millions take daily. NSAIDs — ibuprofen, naproxen, diclofenac — and even paracetamol with frequent use are associated with tinnitus, generally mild and reversible. Some SSRIs and tricyclics can provoke tinnitus, and, paradoxically, so can their withdrawal; the same is true of benzodiazepines [2007]. PDE5 inhibitors (sildenafil, tadalafil) carry a recognised, usually transient, association with sudden hearing change and tinnitus.

The harder problem is polypharmacy. An elderly patient on a loop diuretic, an NSAID, an SSRI and an aminoglycoside course carries an additive ototoxic burden that no single agent would predict. Renal impairment compounds this by impairing clearance and raising drug levels. Always reconcile the full list, including over-the-counter analgesics and herbal products, rather than blaming one tablet.