FDA considers Tamiflu safety in children

Safety information revealing deaths in Japanese children taking the influenza medication Tamiflu is being discussed by the US Food and Drug Administration on Friday. A safety committee of the European Medicines Evaluation Agency (EMEA) has also requested information from the drug’s manufacturer Roche.

However, the meeting of the FDA paediatric advisory committee is a routine assessment of safety, performed for relatively new drugs prescribed to children. Seven others, including the controversial Vioxx (rofecoxib), are being considered. The FDA notes: “Based on the information available to us, we cannot conclude that there is a causal relationship between Tamiflu and the reported paediatric deaths.” It adds that the “increased reports of neuropsychiatric events in Japanese children are most likely related to an increased awareness of influenza-associated encephalopathy”, increased use of Tamiflu in Japan, and greater monitoring of adverse events.The examination by the FDA and EMEA of Tamiflu has drawn attention because of the current outbreak of highly pathogenic bird flu in east Asia. This has increased fears of a human pandemic, for which Tamiflu would be the frontline treatment.Frightening hallucinationsSince Tamiflu (oseltamivir) was approved in 1999, 12 children under 16 years of age and taking the drug have died, and 32 have suffered “neuropsychiatric events” such as hallucinations, confusion, convulsions and brain inflammation. All the deaths and the vast majority of adverse events in children, also including skin rashes and sensitivity, have been reported in Japan, where Tamiflu has been widely prescribed.Many of the children died in their sleep, but one committed suicide an hour after taking the flu pill. Alarming behaviour has also been recorded. For example, there are two reports of boys jumping out of upper floor windows of their homes after two doses of Tamiflu. And in another case, an 8-year-old boy fled his house onto the street after having frightening hallucinations, three hours after his first dose.Intensive monitoringThe submission from Hoffman La-Roche – Roche’s US division – to the FDA states that the adverse events reported could be the result flu itself: “Neurological complications are not uncommon during influenza infections, the symptoms of which occur concurrently with the usage of Tamiflu, making any causal relationship of these events to Tamiflu difficult to assess in the absence of a controlled trial.”The FDA notes that the evidence that flu can cause brain inflammation, or encephalitis, was first reported by Japanese paediatricians in the 1990s, and the increased awareness of this rare flu complication may mean that Japanese doctors are more likely to report it than elsewhere.Japan also uses the majority of the world’s Tamiflu supply for seasonal flu. It has used 24 million prescriptions – four times more than the US, says Hoffman La-Roche. The country has also had intensive monitoring of the drug in its first six months after launch and again in the very active flu season of 2004 to 2005.The FDA said on Thursday that it anticipated it would continue monitoring adverse events linked with Tamiflu and report back to its paediatric advisory committee within two years. Friday’s meeting will not address pandemic flu preparations, it adds: “But indirectly, a better understanding of Tamiflu safety in children will be useful should a pandemic occur and there is widespread use of Tamiflu.”(Source: New Scientist: November 2005.)