FDA approves topical fluoroquinolone for use in children

January 1998

BETHESDA, Md. - The Food and Drug Administration (FDA) recently approved the first new prescription eardrop in 20 years.

Ofloxacin otic solution (Floxin Otic, Daiichi Pharmaceutical Corp.) was approved in December for the treatment of otitis externa in children 1 year and older; acute otitis media (AOM) in children 1-12 years with tympanostomy tubes; and chronic suppurative otitis media in patients 12 years and older with perforated tympanic membranes.

"The large-scale studies demonstrated clinical efficacy and safety for each indication," said Jerome Klein, MD, director of pediatric infectious diseases, Boston University Medical Center. "I'm impressed with the extent of studies that have been performed. I think they probably are the largest studies for each indication available."

According to Elyane Lombardy, MD, executive director, research and development division of Daiichi Pharmaceuticals Corp., local treatment allows for minimal exposure, which reduces the risk of systemic toxicity in children.

"If a quinolone is justified, it allows the use of that quinolone in children without having the worry of systemic side effects and particularly arthropathies," she said.

Lombardy also stressed that ofloxacin otic solution demonstrated efficacy against methicillin-resistant Staphylococcus aureus, and penicillin-resistant Streptococcus pneumoniae.

Otitis externa

Based on studies of otitis externa in children 1 to 12 years, ofloxacin otic solution successfully eradicated all pathogens tested: Pseudomonas aeruginosa, S. aureus, Proteus mirabilis, Enterococcus faecalis, Klebsiella pneumoniae and Enterobacter cloacae, said FDA medical officer Cheryl L. McDonald, MD.

Of the 143 children who received ofloxacin otic solution, the most commonly reported adverse events were of mild to moderate intensity and included earache (8%), otitis media (8%), fever (6%), rhinitis (6%) and coughing (4%).

The comparison treatment, Cortisporin (neomycin and polymyxin B sulfates and hydrocortisone otic suspension, Glaxo Wellcome), had the same pathogen eradication rates and similar adverse events; 35% (50/143) Floxin Otic subjects and 26% (37/144) Cortisporin subjects.

The 287 study participants received either Floxin Otic 0.25 mL twice daily or Cortisporin 0.15 mL four times daily for 10 days.

Acute otitis media

Studies presented to the FDA using ofloxacin otic solution to treat AOM in children 1 to 12 years with tympanostomy tubes showed slightly lower pathogenic eradication rates than in studies for otitis externa. However, the lowest rate observed was 93% - for Haemophilus influenzae and M. catarrhalis - and all rates were higher for ofloxacin otic solution than for the comparison drug, amoxicillin/clavulanate (Augmentin, SmithKline Beecham), McDonald said.

A total of 474 children were given either ofloxacin otic solution 0.25 mL twice daily or amoxicillin/clavulanate 40 mg/kg/day for 10 days.

The overall adverse events rate was 42% (96/228) for ofloxacin otic solution vs. 52% (127/246) for amoxicillin/clavulanate. Diarrhea and rash were more common in the amoxicillin/clavulanate group, said McDonald.

CSOM

The open-label multicenter study of chronic suppurated OM was conducted in participants with perforated tympanic membranes 12 years and older. ofloxacin otic solution was given at 0.5 mL twice daily for 14 days.

The overall clinical/microbiological success rates were again lower than the studies for otitis externa, but the lowest rate observed was 86% for E. faecalis, McDonald said.

Most adverse events reported include "taste perversion" (17%), earache (6%), headache (5%) and dizziness (3%). Most adverse events were of mild to moderate intensity.

"Topical treatment is a very logical alternative for the treatment of localized infections, particularly when the site of infection is fairly easily accessible ... [and high concentrations acheived at the site of infections] and it could prevent the emergence of resistance," Lombardy said.

Editor's note: Until oral fluoroquinolones are approved for treatment of otitis media, it would be prudent not to use these drugs. I would not like to have to defend you in court if a child for whom you had prescribed one of these drugs developed any joint complaints in the future. The widespread use of these drugs for otitis would result in resistance to a class of drugs which is very useful for other indications without appreciably increasing our armamentarium for treating otitis. - P. Brunell