The Food and Drug Administration has expanded the approval of oseltamivir to include prophylaxis in children as young as 1 year who have had close contact with someone infected with influenza A or B.
Oseltamivir (Tamiflu) has until now only been approved for the treatment of children older than 1 year who were themselves infected.
The FDA reported that the data used for this expanded indication came from a study of the spread of influenza in households, which enrolled 1,100 subjects, of whom 222 were children 1–12 years old.
That study found that 17% of family contacts in the placebo group became ill with confirmed flu, compared with only 3% of those treated with oseltamivir within 48 hours after exposure. That benefit mirrored the one seen in adults. Prophylactic treatment in the study was a single dosing of the drug (30–60 mg, depending on patient weight) taken every day for 10 days.
Side effects seen in the prevention study were similar to side effects seen in treatment studies, with vomiting the most common.
Dr. Kathryn M. Edwards, an influenza-vaccine and infectious-disease expert, said she was pleased by the FDA action and thought this new indication was important—not just in the event that the avian flu hits the United States, but for seasonal flu as well.
“I think this drug can be very helpful,” Dr. Edwards, a professor of pediatrics at Vanderbilt, University, Nashville, Tenn., said in an interview. “Influenza is a serious illness. When my [patients] have the flu, and I confirm it, I treat them.”
This new approval does not obviate the need for yearly flu vaccination, the FDA noted. It is still recommended that pediatric patients get vaccinated.
In November, the FDA's Pediatric Advisory Committee reviewed safety data on oseltamivir and concluded there were no new safety concerns regarding the drug and no cause for concern about any neuropsychiatric events.
Possible neuropsychiatric events had been reported to the Roche Pharmaceuticals Inc. safety database. Through June 2005, a total of 67 neuropsychiatric events had been reported in 59 patients, with 19 cases of convulsion/encephalitis/encephalopathy, 15 cases of depressed consciousness, and 13 cases of hallucination/delirium, according to information provided by Roche to the FDA. However, in 51 of the patients, there was an alternative explanation for the event, and in 6 cases there was incomplete information, leaving only two cases—both described as cases of “abnormal behavior”—that could not be ruled out as possibly vaccine-associated.
The vast majority of these cases were reported from Japan, where the drug is used much more frequently than anywhere else in the world, and only one of the 59 cases occurred in the United States. To date, more than 13 million doses of oseltamivir have been administered to children less than 16 years of age, and, in the United States, oseltamivir is the most prescribed antiviral medication, according to Roche.
Roche has been asked by the FDA to update the labeling of oseltamivir to warn of the rare possibility of skin rash and other hypersensitivity reactions (anaphylaxis).
In other recent oseltamivir news, Vietnamese officials have reported that in four of eight avian flu cases treated with oseltamivir, the drug was not effective. In two of those cases, the patients had or developed resistant disease. One of those cases was in a 13-year-old girl, who was definitely known to have been treated early with adequate doses (N. Engl. J. Med. 2005;353:2667–72). In the other two cases, the drug probably was started too late, reported Dr. Menno de Jong of the Hospital for Tropical Diseases, Ho Chi Minh City.
Dr. Anne Moscona, professor of pediatrics and microbiology and immunology at Weill Medical College of Cornell University, New York, said in an accompanying editorial that this confirmation of resistant avian flu highlighted the need to discourage the general population from stockpiling the medication, since nonphysicians would be more likely to misuse the drug, which would favor the development of more resistance (N. Engl. J. Med. 2005;353:2633–6).
Misuse of oseltamivir in children would be particularly worrisome, since children are usually a main source of the spread of influenza in a community, have higher viral loads, and excrete virus for a longer period of time.
