January 1998
BETHESDA, Md. - The Food and Drug Administration (FDA) recently approved ceftriaxone (Rocephin, Roche) for the treatment of acute otitis media (AOM) in children.
Based on safety and efficacy data presented by Hoffman-La Roche Inc., the FDA Anti-Infective Drugs Advisory Committee committee unanimously recommended ceftriaxone be approved to treat AOM caused by penicillin-susceptible strains of Streptococcus pneumoniae. In addition, studies showed the drug eradicated Haemophilus influenzae and Moraxella catarrhalis, and the panel agreed the drug can also be used to treat AOM caused by those organisms.
The committee could not recommend approval of ceftriaxone for AOM caused by penicillin-resistant strains of S. pneumoniae. None of the drugs currently approved for AOM are approved for penicillin-resistant S. pneumoniae.
"I believe the data are sufficient to show both bacteriological/clinical efficacy of single-dose Rocephin for the penicillin-susceptible organisms. I'm a little concerned about the penicillin-resistant pneumococci," said committee consultant G. Scott Giebink, MD, professor of pediatrics, University of Minnesota Medical School.
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Rocephin will be the first single-dose injectable antimicrobial drug available for the treatment of AOM. A single-dose intramuscular injection of 50 mg/kg (not to exceed 1 g) of the drug would be the recommended dosage.
The single dose also offers less potential for the emergence of resistance because of rapid, high and sustained concentration of the drug, which results in bactericidal activity in the middle ear. The single-dose injection ensures 100% compliance with treatment, according to Jonathan Solsky, MD, Roche director of clinical medicine.
"I work in an inner-city hospital where many families are dysfunctional, homeless, live in shelters and are not able to comply with a 10-day oral regimen ... For me, it is availability of a parenteral agent for AOM and I feel comfortable giving these patients the drug in a single dose," said Jerome O. Klein, MD, director of pediatric infectious diseases, Boston Medical Center.
"There is currently no alternative for children who cannot tolerate oral therapy or whose families cannot complete a course of oral antibiotics," said Jeffrey Blumer, MD, PhD, chief of the division of pediatric pharmacology and critical care, Rainbow Babies and Children's Hospital, Cleveland.
Clinical, pharmacokinetic and bacteriologic studies were conducted in the United States, France and Iceland. A total of 2,450 children 3 months to 6 years of age with AOM were enrolled in the studies; 1,350 received ceftriaxone. Among the 1,048 patients who reported adverse events, the most common included diarrhea (14.1%), diaper rash (5.2%), rash (4.9%), injection site pain (1.4%) and vomiting (1.4%).
Six serious adverse events were reported in patients who received ceftriaxone, but five were unrelated; one adverse event was classified as "remotely related." In the comparator agents, seven adverse events were observed; one was classified as "probably related." All patients recovered and no deaths were reported.
In addition, studies of parental preference conducted by Roche concluded that the majority of parents (67%) prefer the single-dose injection over multidose oral treatment (11.8%).
Committee chairman William Craig, MD, said the drug appears to have excellent bactericidal activity against the various pathogens associated with AOM. However, in comparative studies, ceftriaxone appeared to be less effective than standard-dose amoxicillin/clavulanate (Augmentin, SmithKline Beecham) but equally effective to high-dose Augmentin. It also looked to be equally effective with trimethoprim- sulfamethoxazole (TMP-SMX).
"There seems to be some equivalence with TMP-SMX, also with high-dose amoxicillin, based on the French study. The drug appeared less effective than amoxicillin in the U.S. study," Craig added.
Rocephin has been on the market since 1984 and is currently approved for 10 indications in patients, including lower respiratory tract infections, skin and skin structure infection, urinary tract infections, uncomplicated gonorrhea, pelvic inflammatory disease, bacterial septicemia and meningitis.
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