 YOUR HEALTH

Ototoxicity: as a Drug Side Effect What Healthcare Providers (and Patients) Should Know

By Robert M. DiSogra, AuD the pathophysiology of tinnitus is buzzing, whistling, disturbance, beyond the scope of this article. Most auditory dysfunction, etc.). Determining the cause of tinnitus physicians and audiologists working It is essential for healthcare in most cases remains elusive to the with tinnitus patients would agree providers to understand the risk medical and audiology communities. that damage to the outer cells of the factors for ototoxicity, which often True, on the basis of the patient’s or changes in the biochemistry to drug accumulation and an medical, social, or occupational history, within the cochlea would explain the increased potential for permanent some causes, such as blast explosion, cause of the tinnitus. . These risk factors include concert noise, recreational noise, and medication dose, therapy duration, head trauma, can be readily linked (but Ototoxicity: Tinnitus as a cumulative lifetime dose, impaired not limited) to tinnitus. Drug Side Effect kidney function, infusion rate of certain When the cause of tinnitus The major classes of drugs known medications (e.g., IV , is unknown, exploration of the to be ototoxic are antimicrobials, ), co-administration patient’s drug regimen is the next antimalarial drugs, organic and of multiple ototoxic medications (e.g., step in the differential diagnosis. The industrial , and some topically aminoglycosides with loop diuretics), mechanism causing drug-induced administered agents. Added to the age, previous exposure to head and ototoxicity remains unclear. It may list are salicylates, nonsteroidal neck radiation (chemotherapeutic involve biochemical and consequent anti-inflammatory drugs (NSAIDs), agents), genetic susceptibility, and electrophysiological changes in the , loop family history of ototoxicity.3 inner ear and eighth cranial nerve diuretics, and agents impulse transmission.1 But exploring (e.g., platins and vincristine).2 Websites for Drug Side The Side Effect Resource Database Effects Information — (SIDER 2; http://sideeffects.embl.de) Especially Tinnitus “… there is no reported a total of 996 drugs with a No one knows every drug’s combined side effects total of 4,192. indication dosaging and side effects. common language Of these, 275, or 6.5 percent, listed However, the internet can be a tinnitus as a reported side effect using tremendous resource, even though for reporting tinnitus synonyms such as “ringing in ” and anyone can put up a website (e.g., “ear noise.” www.howicuredmytinnitus.com). during a drug’s Keep in mind that there is no Winker et al. proposed a list of pre-FDA-approval common language for reporting tinnitus guidelines for using websites that during a drug’s pre-FDA-approval offer medical information.4 One clinical trials.” clinical trials. Therefore, coinvestigators recommendation is that consumers might report tinnitus using descriptors and professionals look only at websites provided by the subject (humming,

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that have established credibility, operate under an advisory board, and are updated regularly. Websites should “One recommendation is that consumers and also include appropriate disclaimers that the information on the site is not a professionals look only at websites that have substitute for proper medical care. Consumers and professionals can established credibility, operate under an visit several excellent websites to determine whether any medication has advisory board, and are updated regularly.” tinnitus as a reported side effect. These include (but are not limited to) the condition and is clearly established temporary, as in the case of , following sites: as the cause of the tinnitus, the nonsteroidal anti-inflammatory www.drugs.com management strategy changes. drugs, and diuretics. Although the www.rxlist.com ototoxicity of many drugs resolves When you visit a drug information Onset of Tinnitus after treatment discontinuation, website, simply type in the name of The onset of tinnitus as a result of the use of derivatives and the drug (generic or brand name) and a drug is usually immediate (within 15 aminoglycosides is associated with go the “Side Effects” tab. Next, look to 20 minutes for oral medications). permanent hearing loss.5 under “Special Senses” or “Central When a drug enters the bloodstream, Nervous System.” If tinnitus is listed, it is considered systemic, and The Role of the then the next step is to confirm the therefore both ears would experience Pharmacist start date of the drug (or date a drug tinnitus. If there is a preexisting In pursuing a drug as the cause of dosage was increased) with the hearing loss without tinnitus, the tinnitus, the patient’s pharmacist can pharmacist. If the start date of the poorer ear may be more susceptible provide exact start dates and dates drug is established and the patient is to tinnitus. However, if there is of increased dosaging. Once a time sure of the start date of the tinnitus, it preexisting hearing loss with tinnitus, line has been established of when the can be concluded whether the tinnitus the tinnitus could get louder. drug was dispensed (or increased) and is truly an adverse drug reaction. tinnitus reported, the audiologist and The prescribing physician should Temporary or pharmacist are in a unique position be made aware of this discovery and Permanent? to work together, helping the patient correlation. The medication dosage Most tinnitus patients report that understand and manage the tinnitus. might be decreased or the medication their drug-related tinnitus lasts for as The prescribing physician is also discontinued or changed altogether. long as they are taking the medication. included for medical management. However, if the prescribed medication In other words, the tinnitus can be is the best one for a particular medical

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“What medications do “Should I stop my medi- Salus University and has lectured and published on this and other topics related to ototoxicity you take and why?” cation if I get tinnitus?” and pharmaceuticals and nutraceuticals for hear- This is a typical case history ques- No! Patients should consult their ing loss and tinnitus. His website, www.drbob- tion a physician or audiologist asks. prescribing physician before cutting disogra.com, lists his lecture topics and other information for professionals and consumers, The clinician does additional work to back or discontinuing any medica- including his Guide to Over-the-Counter Tinnitus pursue the possibility or probability tion. According to noted auditory Relief Products. that the patient’s tinnitus complaint researcher Kathleen C. M. Campbell: To read DiSogra’s article, “Over-the-Counter may be a drug side effect. With over “The health benefits of the drug far Dietary Supplements for Tinnitus: Do They Really 220 drugs listing tinnitus as a report- outweigh the risk of tinnitus (or hear- Help?” see Tinnitus Today (Winter issue, 2014.) ed side effect or adverse drug reac- ing loss).” (K. C. M. Campbell, PhD, tion (ADRs)6, more detective work is personal communication, 2012). 1 Seligmann, H., Podoshin, L., Ben-David, J., Fradis, M., & Goldsher, M. (1996). Drug-induced tinnitus needed to establish whether the tin- and other hearing disorders. Drug Safety, 14, nitus is truly pathological or not. The Summary 198–212. 2 Byung, I. H., Lee, H. W., Kim, T. Y., Lim, J. S., & terms “side effect” and “adverse drug Despite being a side effect or Shin, K. S. (2009). Tinnitus: Characteristics, causes, reaction” are used interchangeably. adverse drug reaction, drug-relat- mechanisms, and treatments. Journal of Clinical Neurology, 5, 11–19. ed tinnitus is manageable and in 3 Coggins, M. D. (2014). Medication-related ototoxici- Audiometric Testing most cases, is usually temporary ty. Today’s Geriatric Medicine, 7, 6. 4 Winker, M. A., Flanagin, A., Chi-Lum, B., White, J., When tinnitus is a symptom of and limited to the time the drug is Andrews, K., Kennett, R. L., . . . Musacchio, R. A. a drug side effect or other medical taken. For chemotherapy patients or (2000). Guidelines for medical and health informa- tion sites on the internet — principles governing problem, an audiological evaluation patients with chronic medical condi- AMA web sites. Journal of the American Medical Association, 283,1600–1606. should be scheduled to rule out tions, the health benefits of the drug 5 Lanvers-Kaminsky, C., Zehnhoff-Dinnesen, A. A., hearing loss as a cause. An audiol- outweigh the risk of tinnitus. There- Parfitt, R., & Ciarimboli, G. (2017). Drug-induced ototoxicity: Mechanisms, pharmacogenetics, and ogist will evaluate hearing and help fore, counseling is a critical compo- protective strategies. Clinical Pharmacology and differentiate between certain types nent of tinnitus management. Therapeutics, 101, 491–500. 6 DiSogra, RM Adverse drug reactions and audiology of losses — some of which could be practice, 3rd edition Audiology Today, American medically or surgically correctable. Robert M. DiSogra, Academy of Audiology, September, 2008. If there is preexisting hearing loss, AuD, is a consult- ing audiologist in the medication could aggravate the Millstone, New condition and the tinnitus could Jersey, and past emerge. This is why the information contributor to from the pharmacist is critical to de- Tinnitus Today (December 2014). termine whether the tinnitus is an He has been an adverse event or a sign that hearing audiologist for over 40 years. He developed and loss is getting worse. taught the Pharmacology/Ototoxcity course at

“Thank you for the kindness you have done for me tonight, calling me on a Friday night.” — Nanette L., daughter of someone with tinnitus

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