Ototoxic Drug

Aka: Ototoxic Drug, Ototoxic Medication, Ototoxicity, Ototoxic Hearing Loss, Drug Induced Hearing Loss, Medication Causes of Hearing Loss, Medication Causes of Tinnitus

1. See Also
   1. Hearing Loss
   2. Sensorineural Hearing Loss
2. Causes: Medications
   1. Analgesics
      1. Aspirin (>2.7 g/day) and other Salicylates
      2. NSAIDs
      3. Acetaminophen
      4. Sulfasalazine (Azulfidine)
      5. Hydrocodone
   2. Antimicrobials
      1. Aminoglycosides (Gentamicin, Streptomycin, Amikacin, Kanamycin, Neomycin, Tobramycin)
         1. Starts with Tinnitus and rapidly progresses to Hearing Loss
         2. Ototoxicity symptoms are permanent if last >2-3 weeks after stopping the Aminoglycoside
      2. Vancomycin
         1. Rare, except in combination with other Ototoxic Drugs
      3. Macrolides
         1. Erythromycin (dose >2 g/day)
         2. Azithromycin
      4. Other antibiotics
         1. Chloramphenicol
         2. Tetracyclines (transient vestibular toxicity)
            1. Doxycycline
            2. Minocycline
         3. Imipenem-Cilastin (Primaxin)
         4. Linezolid (Zyvox)
         5. Sulfonamide
         6. Fluoroquinolones
      5. Antifungals
         1. Voriconazole
         2. Amphoteracin B
      6. Antivirals
         1. Ganciclovir
         2. Ribavirin
         3. Sofosbuvir (Solvaldil)
         4. Telaprevir (Incivek)
      7. Antimalarial Agents
         1. Quinine
         2. Chloroquine
         3. Mefloquine
   3. Loop Diuretics (especially at high dose with rapid infusion)
      1. Ethacrynic Acid (Demadex)
      2. Furosemide (Lasix)
   4. Antineoplastic
      1. Platinum agents (most common)
         1. Cisplatin
         2. Carboplatin
      2. Bleomycin
      3. Vincristine and other Vinca Alkaloids
      4. Nitrogen Mustard
      5. Methotrexate
      6. Etoposide
      7. Protein kinase inhibitors (e.g. Axitinib, Dasatinib, Imatinib, lapatinib, Osimertinib, Ruxolitinib)
   5. Other medications
      1. PDE5 Inhibitors
         1. Sildenafil (Viagra)
         2. Tadalafil (Cialis)
      2. Caffeine
      3. Atorvastatin (Lipitor)
      4. Bupropion (Wellbutrin)
      5. Risedronate (Actonel)
      6. Verenicline (Chantix)
      7. Misoprostol (Cytotec)
3. Causes: Industrial and Home Poisonings
   1. Background: Exposure Settings
      1. Automotive repair
      2. Boat building
      3. Manufacturing (leather, metal, battery, petroleum)
      4. Painting
      5. Pesticide spraying
      6. Fueling vehicles including aircraft
   2. Asphyxiants
      1. Carbon Monoxide Poisoning
      2. Tobacco Smoke
   3. Heavy Metal Poisoning
      1. Mercury Poisoning
      2. Lead Poisoning
      3. Organic Tin Compounds
   4. Nitriles
      1. Acrylonitrile (Hydrogen cyanide with a replaced ethenyl group)
      2. 3-Butenenitrile (Allyl Cyanide)
   5. Solvents
      1. Toluene
      2. Styrene
      3. P-Xylene
      4. Trichloroethylene
4. Causes: Ilicit Drugs and Poisonings
   1. Ilicit Drugs
      1. Ecstasy
5. Causes: Tinnitus
   1. All Ototoxic Medications listed above may cause Tinnitus
      1. Meds listed here are additional medications that have been associated with Tinnitus
   2. Common Causes of Tinnitus (includes medications above)
      1. Aspirin (high dose>2-3 g/day)
      2. NSAIDs
      3. Loop Diuretics
      4. PDE5 Inhibitors (e.g. Sildenafil)
      5. Quinine
      6. Mefloquine
   3. Neurologic
      1. Carbamazepine (Tegretol)
         1. Carbamazepine dampens cortical responses to sound (may alter hearing)
      2. Pregabalin (Lyrica)
      3. Anesthetics (Lidocaine, Bupivacaine)
   4. Antineoplastics
      1. Capecitabine (Xeloda)
      2. Taxanes (e.g. Paclitaxel) - uncommon
   5. Immunosuppressants
      1. Cyclosporine
      2. Interferon
      3. Monoclonal Antibody (e.g. Ipilimumab, Nivolumab, Trastuzumab)
   6. Vaccinations
      1. HPV Vaccine
      2. Pneumovax
   7. Miscellaneous
      1. Proton Pump Inhibitors
      2. Vecuronium
6. Symptoms
   1. Tinnitus may be present
   2. Sensorineural Hearing Loss from Ototoxic Drugs typically develops over weeks after exposure
   3. Hearing Loss be transient for some agents used at therapeutic levels (e.g. Erythromycin, Tetracyclines, Analgesics)
      1. Hearing Loss is often reversible after decreasing or stopping the offending agent
7. Evaluation
   1. See Sensorineural Hearing Loss
8. Resources
   1. Preventing Hearing Loss Caused by Chemical (Ototoxicity) and Noise Exposure (CDC NIOSH)
      1. https://www.cdc.gov/niosh/docs/2018-124/
9. References
   1. Cianfrone (2011) Eur Rev Med Pharmacol Sci 15(6): 601-36 [PubMed]
   2. Dalrymple (2021) Am Fam Physician 103(11):663-71 [PubMed]
   3. Ganesan (2018) J Audiol Otol 22(2): 59-68 [PubMed]
   4. Seligmann (1996) Drug Saf 14(3): 198-212 [PubMed]