Tamiflu linked to deaths of 12 children

The safety of the anti-flu drug Tamiflu was under question for the second time in a week yesterday following reports that it was linked to the deaths of 12 children in Japan.

Tamiflu, which is being stockpiled by governments around the world preparing for a threatened flu pandemic, is to be reviewed by US drug regulators today.

On Monday, European regulators said they were closely monitoring the psychological effects of the drug after it was linked to the suicides of two Japanese teenagers.

Yesterday in a report posted online, the US Food and Drug Administration said that 12 children had died in Japan from a range of causes including heart attack, suicide, pneumonia, and acute pancreatitis.

Four had suffered a "sudden death" which was "an unusual phenomenon in otherwise healthy children". All had taken Tamiflu.

"Deaths from influenza are uncommon among both children with and without high-risk conditions, but do occur," the FDA report said.

"Attribution of causality for the reports of sudden death and cardio-pulmonary arrest are extremely difficult to interpret because there is limited information leading up to the event." It added that it was "concerning" that 32 psychiatric events, such as hallucinations and abnormal behaviour, had been reported in children who took Tamiflu.

A panel of the FDA is examining reports of adverse reactions to Tamiflu as part of a wider review of how medicines work in children.

One question they will have to address is how to distinguish the effects of the drug from the effects of the flu.

In a separate summary posted on the FDA website, Roche, the manufacturer of Tamiflu, said: "There is no increase in deaths and neuropsychiatric events in patients on Tamiflu versus influenza patients in general." Officials from the FDA and Roche will present information about the cases to a meeting of an FDA advisory panel today.

Demand for Tamiflu has soared in recent months as avian flu, which has killed at least 64 people in the Far East, has spread to Europe.

At least 50 countries including the US, UK and Japan have placed orders worth $1.4 billion to prepare for a flu pandemic that experts say is inevitable.

The UK government has ordered 14.6 million courses of Tamiflu at a cost of £200 million. Three million courses have been delivered and the remainder is due by September 2006.

Japan is the only country in the world with extensive experience of Tamiflu.

The drug is routinely used by all sectors of the country's population during the winter flu season to shorten the duration of the illness, reduce complications and slow its spread.

The Japanese health ministry issued a warning in June 2004 about psychological and neurological disorders linked with Tamiflu.

The European Medicines Evaluation Agency, which licenses drugs in the European Union including the UK , said it had asked Roche to closely follow reports of psychological disorders, delusional states and abnormal behaviour linked with the drug.

In the UK, Tamiflu has been little used since its launch in 2003 and there have been only 41 "yellow card" reports of adverse reactions involving 161 separate side effects linked with it.

One case was of agitation and two were of "confusional state." Under the yellow card system doctors record any symptoms that could be linked with a drug.

The reports are intended to provide early warning of possible problems with a drug and do not show a causal link.

In the UK, the side effects listed for Tamiflu include nausea, fatigue, insomnia, dizziness, rash and - very rarely - hepatitis and Stevens-Johnson syndrome, a life threatening condition in which the skin blisters and sloughs off.

- INDEPENDENT