Ototoxic
Medications That Cause Tinnitus
by
Barry Keate
Ototoxic
medications are those that are toxic to the cochlea
or vestibular (balance) structures in the ear. These
medications have the potential to cause hearing loss,
tinnitus and/or dysequilibrium such as dizziness and
vertigo.
Ototoxicity
came to the forefront of clinical attention with the
discovery of streptomycin in 1944. Streptomycin was
successfully used in the treatment of tuberculosis;
however, a large number of patients were found to
develop irreversible cochlear and vestibular dysfunction.
Ototoxicity was also shown with the later development
of other aminoglycoside antibiotics. Today, many well
known pharmaceutical agents have been shown to have
toxic effects on the cochleovestibular system. The
list includes aminoglycosides and other antibiotics,
platinum-based chemotherapy medications, salicylates,
quinine and loop diuretics.
The
method of action of ototoxic medications differs somewhat
among the various drugs. Aminoglycosides seem to potentiate
glutamate receptors in the cochlea that promote degeneration
of hair cells and cochlear neurons.1
This, in turn, generates a cascade of free radical
damage which leads to the destruction of hair cells
and neurons.2
The
damage typically begins with the inner row of outer
hair cells and progresses through the other rows,
then to the inner hair cells. Patients frequently
develop symptoms following the cessation of therapy.
Ototoxicity-induced hearing loss tends to first manifest
in the high frequencies and often causes tinnitus.
It then progressively involves the lower frequencies
and eventually affects speech recognition.3
Since
free radical damage is central to lost hearing and
vestibular disturbances, it makes sense that taking
antioxidants before being exposed to ototoxic medications
will reduce the potential damage. A related article
on antioxidants and tinnitus can be seen in our
Tinnitus Information Center.
Ototoxicity
may be reversible or may be permanent, depending on
the type of medication used, dosage and duration of
treatment. There are many other medications that have
been listed as potentially ototoxic.
In
his excellent article, “What you should know
about ototoxic medications,” published in Tinnitus
Today, September 1996, Stephen Epstein, MD, lists
the six categories of medications that can be ototoxic
and the signs of ototoxicity:
"1
– Salicylates – Aspirin and aspirin containing
products
Toxic effects usually appear after consuming an average
of 6-8 pills per day. Toxic effects are almost always
reversible once medications are discontinued.
2
– Non-Steroidal Anti-Inflammatory Drugs (NSAIDS)
– Advil, Aleve, Anaprox, Clinoril, Feldene,
Indocin, Lodine, Motrin, Nalfon, Naprosyn, Nuprin,
Poradol, Voltarin. Toxic effects usually appear after
consuming an average of 6-8 pills per day. Toxic effects
are usually reversible once medications are discontinued.
3
– Antibiotics – Aminoglycosides, Erythromycin,
Vancomycin
a. Aminoglycosides – Streptomycin, Kanamycin,
Neomycin, Gantamycin, Tobramysin, Amikacin, Netilmicin.
These medications are ototoxic when used intravenously
in serious life-threatening situations. The blood
levels of these medications are usually monitored
to prevent ototoxicity. Topical preparations and eardrops
containing Neomycin and Gentamycin have not been demonstrated
to be ototoxic in humans.
b. Erythromycin – EES, Eryc, E-mycin, Ilosone,
Pediazole and new derivatives of Erythromycin, Biaxin,
Zithromax. Erythromycin is usually ototoxic when given
intravenously in dosages of 2-4 grams per 24 hours,
especially if there is underlying kidney insufficiency.
The usual oral dosage of Erythromycin averaging one
gram per 24 hours is not ototoxic. There are no significant
reports of ototoxicity with the new Erythromycin derivatives
since they are given orally and in lower dosages.
c. Vancomycin – Vincocin. This antibiotic is
used in a similar manner as the aminoglycosides; when
given intravenously in serious life-threatening infections,
it is potentially ototoxic. It is usually used in
conjunction with the aminoglycosides, which enhances
the possibility of ototoxicity.
4
– Loop Diuretics – Lasix, Endecrin, Bumex
These medications are usually ototoxic when given
intravenously for acute kidney failure or acute hypertension.
Rare cases of ototoxicity have been reported when
these medications are taken orally in high doses in
people with chronic kidney disease.
5
– Chemotherapy Agents – Cisplatin, Nitrogen
Mustard, Vincristine
These medications are ototoxic when given for treatment
of cancer. Maintaining blood levels of the medications
and performing serial audiograms can minimize their
toxic effects. The ototoxic effects of these medications
are enhanced in patients who are already taking other
ototoxic medications such as the aminoglycoside antibiotics
or loop diuretics.
6
– Quinine – Aralen, Atabrine (for treatment
of malaria), Legatrin, Q-Vel Muscle Relaxant (for
treatment of night cramps)
The ototoxic effects of quinine are very similar to
aspirin and the toxic effects are usually reversible
once medication is discontinued.
The
signs of ototoxicity, in order of frequency, are:
1 – Development of tinnitus in one or both ears.
2 – Intensification of existing tinnitus or
the appearance of a new sound.
3 – Fullness or pressure in the ears other than
being caused by infection.
4 – Awareness of hearing loss in an unaffected
ear or the progression of an existing loss.
5 – Development of vertigo or a spinning sensation
usually aggravated by motion which may or may not
be accompanied by nausea."4
Dr.
Epstein advises that if any of these symptoms develop
while taking any medication, stop the medication immediately
and call your doctor.
Just
as each of us is ultimately responsible for our own
health, those of us with tinnitus must be particularly
careful of medications that may cause our condition
to worsen. Please read all medication labels and information
carefully and review possible side-effects with your
doctor before using.
Antidepressants
It should also be noted that, while not strictly ototoxic,
prescription antidepressants can cause or worsen tinnitus
for some people. Both the older, tricyclic, and the
newer, SSRI, antidepressants have this capability.
Among the tricyclics, Clomipramine and Amitriptyline
are among the most frequent offenders. The SSRI antidepressants
include Prozac, Zoloft, Paxil, Celexa and Luvox. These
are listed in the Physician’s Desk Reference
as frequently causing tinnitus. One good choice for
many people with both tinnitus and depression is the
older medication Remeron, which has not been reported
to cause tinnitus.
If
you must take ototoxic medications, you should also
be taking antioxidants and have your hearing monitored
with periodic audiological evaluations.
List
of Ototoxic Medications
Here is a complete and updated listing of all ototoxic
medications, derived from the 2006 Physician’s
Desk Reference.
FOOTNOTES:
1-Pol Merkuriusz Lek (2001)9:713-5; Bienkowski, P;
Scinsake, A; Kostowski, W; Koros, E; Kukwa, A; Ototoxic
mechanism of aminoglycoside antibiotics-role of glutaminergic
NMDA receptors.
2 -Baylor College of Medicine; August 20, 1992; Andrew
T. Lyos, MD; Ototoxicity.
3 - Ear, Nose & Throat Journal; Sept. 2004; Peter
S. Rowland; New developments in our understanding
of ototoxicity.
4 - Tinnitus Today; Sept. 1996; Stephen Epstein, MD;
What you should know about ototoxic medications
|