The Fluoroquinolone Toxicity Research Foundation

 
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Fluoroquinolones and hearing loss


As printed in Hearing Health, volume 17:4, Winter 2001


By Donna Anderson
Everyday hearing-robbing culprits range from noise and smoking to a variety of environmental chemicals. And in the healthcare arena, mainstays and marvels of modern medicine, although less predictably linked to auditory effects, can inflict damage.

Take Cipro (the common name for Ciprofloxacin), for example. This powerful antibiotic has been in the news a lot lately as Americans rush to seek protection against anthrax. Cipro is a known ototoxic villain.

Ototoxins are substances that harm or poison the ear. Some cause toxicity in the vestibular

organ where our sense of balance, position, motion and orientation in space is controlled. Nausea, vomiting and dizziness are signs of this kind of poisoning. Others, such as Cipro, can cause cochlear toxicity characterized by hearing loss or tinnitus (ringing in the ears). This is reason for concern considering the potential for widespread use of the powerful antibiotic among frightened Americans.

Since the anthrax scare began, Rosie O'Donnell says she has been to her doctor twice to find out if she had it; each time it was just a pimple. Though Rosie is by virtue of her celebrity a more likely target than the average Joe, millions of people are visiting their doctors in hopes of stocking up on Cipro.

An Internet search for information on the drug yields more than a hundred websites that have popped up in the last couple of months to market Cipro to the terrorized masses. The federal government is leading the shopping spree. The U.S. Department of Health and Human Services recently purchased 100 million Cipro tablets from Bayer. The supply, which would treat approximately 12 million people, cost $95 million and was purchased with monies from the $1.6 billion emergency funds proposed by President Bush on October 17.

Despite the government's recently garnered stockpile, the FDA strongly recommends that the antibiotic not be given out simply to have on hand, nor should it be taken as a preventative measure against anthrax. The foremost danger in using Cipro as a preventative is that anthrax could become drug-resistant. Beyond that, the drug has its share of side effects and adverse reactions; among them are ringing in the ears and/or hearing loss. Although these auditory effects are rare among people who have taken Cipro, when used in combination with other ototoxins, it is capable of doing much more damage than it might alone.

Even worse than Cipro
Aminoglycoside antibiotics are much heavier hitters than Cipro. This is common knowledge among healthcare professionals. Doctors usually reserve this class of antibiotics for bacterial infections which have not responded well to less ototoxic antibiotics.

Aminoglycosides, which are known under the generic names of gentamicin, streptomycin, amikacin, neomycin and tobramycin, can cause either vestibular or cochlear toxicity. They make their way quickly into the otic fluid in the inner ear but leave slowly. While the aminoglycoside-laced otic fluid bathes the nerve cells, more and more damage is done.

The first symptom of ototoxicity from this category of antibiotics is typically a high-pitched ringing in the ears or hearing loss in higher frequencies. If the medication is stopped immediately, the tinnitus may go away within a couple of weeks. However, in some cases, a permanent and total loss of hearing can occur within a month or two.

Other antibiotics are also ototoxic although to lesser degrees than the aminoglycosides. Erythromycin, from the class called macrolides, comes under many brand names and is known to damage hearing. Most often ototoxicity occurred when the drug was given in very high doses for more than one week. Fortunately, the hearing loss is usually temporary. Other macrolides, such as azithromycin, clarithromycin and troleandomycin, seem to be less ototoxic.

Vancomycin, another antibiotic, is typically prescribed with caution, usually for patients who are allergic to penicillin. High doses are often the culprit if hearing loss occurs; the loss is usually irreversible. Patients who are using both vancomycin and an aminoglycoside, a course of treatment for certain types of the heart-related condition endocarditis, should pay particular attention to signs of ototoxicity.

Two other members of the antibiotic family pose some concern. Capreomycin causes hearing loss in about 10 percent of those who take it. The drug, often combined with other medications to treat tuberculosis, also causes vestibular toxicity. In most cases, however, once the drug is stopped, the cochlear and vestibular symptoms stop and are reversible.

Minocycline, the only member of the tetracycline class that is a known ototoxin, is most often used to treat sexually transmitted diseases. It causes vestibular symptoms which may be noticeable after only one or two doses and will fade once the drug has been stopped.


Other culprits
Aspirin and compounds containing aspirin: Tinnitus caused by high doses of aspirin is one symptom of a syndrome called salicylism or aspirin toxicity. Fortunately, it is almost always reversible, except in the case of a near-lethal overdose. Patients who may be at higher risk for auditory symptoms are those with conditions that require ongoing treatment with high doses of aspirin, such as rheumatoid arthritis.


Most all other nonsteroidal anti-inflammatory drugs, comparable alternatives to aspirin, do not exhibit ototoxic effects. Acetaminophen has none at all. However, its effects are analgesic, not anti-inflammatory.

Anti-Cancer Drugs: Several anti-neoplastics cause either vestibular or cochlear toxicity or both. They include cisplatin, bleomycin, carboplatin, vincristine, nitrogen mustard and vinblastine. It may, however, be difficult to determine which drug is causing ototoxicity because anti-cancer drugs are often used in combinations. Depending on the type of cancer present, there may be alternatives that can be used but many respond most successfully to a particular drug.

Diuretics: Diuretics aid the body in eliminating water. Some of the most common, used to treat swelling or edema accompanying congestive heart failure, are known as high-ceiling or loop diuretics. Among them are furosemide, bumetanide and torsemide. With these, as with antibiotics, the higher the level of medication in the blood, the greater the risk of auditory effects. In some cases, cochlear toxicity leads to total and permanent hearing loss. Usually, though, once the dosage has been lowered or the medication stopped, hearing returns. Pre-existing hearing loss often puts a patient at higher risk of ototoxicity by a high ceiling diuretic.

Non-ototoxic alternatives exist. Thiazides, of which hydrochlorothiazide is the most frequently prescribed, are used to treat high blood pressure, reduce the risk of bone fracture in post-menopausal women, and aid in the management of Meniere's disease. Potassium-sparing diuretics also do not adversely affect the auditory and vestibular systems. Common names in this group are triamterene, spironolactone and amiloride.

Beware the chemicals
There are some notable chemical ototoxins that sometimes exist in work settings or in the environment, primarily through contamination. They are: trichloroethylene, xylene, styrene, butyl nitrite, toluene, hexane, carbon disulfide, mercury, manganese, tin, lead and carbon monoxide. Individuals who are exposed to any of them are at risk for auditory damage, a risk that is even higher if they are also taking an ototoxic medication.

Assessing your risk
Almost all medications have side effects. However, when a medication is prescribed to treat an illness, the goal often overrides the risk of possible side effects. Nonetheless, individuals with some degree of hearing loss should be especially vigilant and consider the potential outcome before using a medication that might incur more damage.
For instance, as things currently stand on the anthrax front, the vast majority of Americans have a negligible likelihood of exposure and if you already are experiencing tinnitus or deterioration in hearing, it is especially prudent to heed the FDA recommendation against preventative use of Cipro.

Whereas there is no substantial evidence that aspirin will exacerbate pre-existing hearing loss or tinnitus, in the cases of the aminoglycosides and high-ceiling diuretics, a greater risk of damage does exist. Anti-cancer drugs may also have a negative effect.

Many other factors can be considered in determining one's risk, such as the dosage and length of time for which the drug is prescribed. Also, ototoxic medications introduced intravenously are more likely to cause damage than those taken orally.

Self-defense strategies
Always inform or remind your physician of any auditory conditions when receiving a new prescription. Tell the doctor if you have experienced symptoms of vestibular or cochlear toxicity to a drug before, however minor. When being prescribed a new antibiotic or diuretic, reiterate any medications you take regularly. And if you are exposed to environmental ototoxins, including noise, report this increased risk.

Don't be afraid to ask your physician about alternatives, especially for antibiotics (e.g., penicillin and tetracycline) and diuretics (e.g., thiazides and potassium-sparing types).

Using these tactics, you can help protect your hearing and defend against tinnitus and vestibular problems which could arise from well-meaning efforts to protect your well-being. Diligence may pay off with lasting hearing health.

ADR Watch

Of the thousands of medications available today, many are available only through prescription while consumers can purchase countless others "over the counter." Each and every one has received FDA approval after extensive clinical testing. During that process, certain "adverse drug reactions" (ADRs) are identified and even side effects with an incidence as low as 1 in 5,000 are documented.

Over 300 auditory and/or vestibular symptoms are included in current ADR reference sources, according to a review released in September '01 by the American Academy of Audiology (AAA). The list is a literal A to Z, including everything from deafness to decreased hearing, ear infections, loss of balance, roaring in the ears, tinnitus, vertigo and many more. Author Robert M. DiSogra also carefully researched the ADR references to determine what drugs display one or more of these symptoms, ending up with nearly 2,000!

Among them are the many ototoxic products already mentioned plus some more familiar names: Claritin, Clomid, Cortisporin, Doan's products, Imitrex, Levaquin, Lithium, Motrin, Pepcid, Prozac, Tegretol and Xanax. It is important to remember, though, that none of these or the countless others on AAA's comprehensive list are unsafe or will cause auditory symptoms in most users. It does reinforce the point, though, that individuals taking any medication should monitor their hearing, sense of balance, etc., as closely as all other side effects and report them to their physicians.

For a complete copy of the AAA review, mail a check for $20 (postage included) to:

Adverse Drug Reactions
c/o American Academy of Audiology
8300 Greensboro Drive, #750
McLean, VA 22102

For more information on medications and ADRs, the following websites may prove helpful:

Center for Drug Evaluation and Research
www.fda.gov/cder


MedWatch
www.fda.gov/medwatch


Pharmaceutical Research and Manufacturers Association
www.phrma.org


MedScape Today
www.medscape.com