The reports of death and neuropsychiatric adverse events from Japan most likely reflect greater use of the drug and more reporting of influenza-associated adverse events; they may partly reflect unknown pathophysiologic differences, Dr. Lewis said. Dosing, she noted, is similar in the United States and Japan.
It is possible, she said, “that similar events might be reported in the United States if Tamiflu use increases substantially or, especially, if awareness of neuropsychiatric complications [of influenza] increases.”
Of the 12 reports of skin hypersensitivity reactions that were filed during Tamiflu's postexclusivity period, four cases were “notable cases” that “could have possibly been caused by Tamiflu,” Ms. Truffa told the committee.
These and other cases identified from a review of adverse events from the 2004–2005 flu season prompted the FDA to further investigate all reports of serious skin and hypersensitivity reactions. Officials found 16 reports of serious skin reactions, 18 reports of anaphylaxis, and 1 associated death in children from the time of Tamiflu's approval to April 2005.
Additional data are currently under review, and the FDA will propose additional information in the Tamiflu labeling regarding serious skin reactions, FDA officials told the committee.
Current labeling lists dermatitis, rash, swelling of the face or tongue, and toxic epidermal necrolysis as observed and adverse reactions of the drug.
A reanalysis of data from the pediatric clinical trials of Tamiflu, as well as a literature review, failed to identify any differences in both skin and neuropsychiatric adverse events between children with influenza who received Tamiflu and those who received placebo or no treatment, Dr. Lewis said.
FDA Panel Clears Two Other Drugs
Sumatriptan and fluconazole were among the drugs that received a green light for routine adverse event monitoring by the Food and Drug Administration's Pediatric Advisory Committee.
The committee gave the thumbs-up after the FDA reported that there were no new unlabeled safety concerns identified in the pediatric adverse events that were reported during the drugs' 1-year postexclusivity periods.
There were six unduplicated pediatric adverse events reports associated with the sumatriptan (Imitrex) nasal spray for treatment of migraine, and none of the reports were serious or life threatening, reported Susan McCune, M.D., a medical officer in the FDA's division of pediatric drug development, Rockville, Md.
For the antifungal fluconazole (Diflucan), there were 19 unduplicated reports of adverse events in children, including four deaths. Most reports were “highly confounded” by underlying illness and concomitant medications, and “although serious adverse events occurred, most were expected or addressed in the drug's labeling,” said Larry Grylack, M.D., also of the FDA's division of pediatric drug development.
The 15 nonfatal adverse events reported in patients taking Diflucan involved the following: congenital anomalies in three reports, cardiac events in three, metabolic problems in two, hepatic problems in two, nonfatal fungemia in two, dosing errors in two, and hypersensitivity in one.
Dr. Grylack also reported that there were no new safety concerns identified for the NSAID rofecoxib (Vioxx). During a 7-month exclusivity period, there were 19 pediatric reports, including three foreign deaths, associated with the drug. No further monitoring is necessary, he said, since the drug has been withdrawn from the market.
The other drugs reviewed that also had no new safety concerns were antineoplastic agent irinotecan (Camptosar), antineoplastic agent carboplatin (Paraplatin), platelet-reducing agent anagrelide (Agrylin), and hematinic agent sodium ferric gluconate complex (Ferrlecit).