The Fluoroquinolone Toxicity Research Foundation

 
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MJA Vol 178 7 April 2003 343
The Medical Journal of Australia ISSN:
0025-729X 7 April 2003 178 7 343-343
Eardrop attacks: seizures triggered by ciprofloxacin eardrops
.
Clinical record
A 65-year-old woman had recurrent generalised tonic–clonic
seizures. She was being treated with peritoneal dialysis for chronic
renal failure caused by a combination of agenesis of the left kidney
and focal sclerosing glomerulonephritis. Other medical problems
included mixed connective tissue disease, ischaemic heart disease,
Raynaud’s phenomenon, anaemia of chronic disease, asthma,
hypertension and chronic bilateral serous otitis media (treated
with tympanostomy tubes). Her regular medications included
atorvastatin, alendronate, perindopril, aspirin, allopurinol, ranitidine,
doxepin, controlled release morphine sulfate, ferrous sulfate, calcium
carbonate, frusemide, prednisolone, and diltiazem. Intermittently
she had been given erythropoietin (a seizure precipitant)1 for her
anaemia. She developed a rash when taking cephalosporins, and
had a sister who had primary generalised epilepsy.
The seizures continued despite cessation of the erythropoietin
therapy and administration of sodium valproate. Magnetic resonance
imaging of the brain and electroencephalography gave normal
results.
Meticulous medication review eventually revealed the coincidence of
seizures with the intermittent prescription of ciprofloxacin eardrops.
Eight of the nine seizures occurred while taking Ciproxin HC Ear
Drops (ciprofloxacin 2 mg, hydrocortisone 10 mg; Alcon
Laboratories, Sydney) for otitis media (Box). The ciprofloxacin
eardrops were neither recorded on admission nor listed by the
patient on direct questioning about medications she was taking.
She has had a seizure-free period of 9 months after cessation of the
eardrops, despite tapering of the dose of sodium valproate. The
ciprofloxacin eardrops are considered the probable cause of the
seizures in this case, according to the Naranjo algorithm for
estimating causality of an adverse drug reaction (score, 8).2

POLYPHARMACY in complex medical patients frequently
causes adverse effects.3 Up to 26% of prescription drugs are
not recorded at the time of hospital admission,4 and eardrops
are a common omission from medication lists. Ciprofloxacin
is a fluoroquinolone antibiotic that inhibits bacterial replica-tion.
It is thought to lower seizure threshold by reducing -aminobutyric
acid (GABA) transmission. Ciprofloxacin is
excreted renally and has a half-life of 2.9–4.3 hours, which
doubles in end-stage renal failure. Dose reduction is advised
when patients not receiving dialysis have a creatinine clear-
ance of less than 30 mL/min.5 There are reports of seizures
after enteral and intravenous administration of ciprofloxacin,6
but, to our knowledge, this is the first report of seizures with
ciprofloxacin eardrops. The recurrent seizures were believed
to be due to the combination of an epileptogenic predisposi-tion,
renal failure, and intermittent ciprofloxacin use, with
absorption facilitated by the bilateral tympanostomy tubes.
Topical medications can produce systemic effects and this
should be considered, particularly when other factors favour
systemic absorption. A thorough drug history is necessary in
assessing patients with complex medical problems taking
multiple medications.

Carolyn F Orr,* Dominic B Rowe †
*Research Registrar, †Neurologist
Department of Neurology, Royal North Shore Hospital
St Leonards, NSW
drowe@med.usyd.edu.au
Competing interests:None identified

1. Beccari M. Seizures in dialysis patients treated with recombinant erythropoie-tin.
Review of the literature and guidelines for prevention. Int J Artif Organs
1994; 17: 5-13.

2. Naranjo CA, Bust U, Sellers EM, et al. A method for estimating the probability of
adverse drug reactions. Clin Pharmacol Ther 1981; 30: 239-241.

3. Colley CA, Lucas LM. Polypharmacy: the cure becomes the disease. J Gen
Intern Med 1993; 8: 278-283.

4. Lau HS, Florax C, Porsius AJ, De Boer A. The completeness of medication
histories in hospital medical records of patients admitted to general internal
medicine wards. Br J Clin Pharmacol 2000; 49: 597-603.

5. Davis R, Markham A, Balfour JA. Ciprofloxacin. An updated review of its pharma-cology,
therapeutic efficacy and tolerability. Drugs 1996; 51: 1019-1074.

6. Kushner JM, Peckman HJ, Snyder CR. Seizures associated with fluoroquino-lones.
Ann Pharmacother 2001; 35: 1194-1198.
(Received 16 Oct 2002, accepted 6 Feb 2003) ❏
Lessons from practice
Topical medications can produce systemic effects.
Fluoroquinolones may trigger seizures by any route of
administration.
A thorough drug history is necessary in assessing patients
with complex medical problems.
Eardrops are a frequent omission from medication histories

http://www.mja.com.au/public/issues/178_07_070403/orr10717_fm.pdf