The Japanese government has warned doctors that Tamiflu, the drug being stockpiled around the world as a defence against a bird flu pandemic, should not be prescribed to teenagers for fear that it can lead to bizarre and self-destructive behaviour.

Tokyo’s Ministry of Health and Welfare today instructed the Japanese distributor of the drug to include a warning not to give the drug to patients aged between 10 and 19, after reports that at least 18 Japanese children taking Tamiflu have died as a result of irrational behaviour.

Concern over Tamiflu will complicate international preparations for a catastrophic bird flu pandemic, against which it is seen as the final line of defence. A

However, the European Medicine Agency (EMEA), which licences the drug in Europe, said that there was no equivalent warning in Europe as they had not found any link between the drug and any deaths.

Japan consumes 60 per cent of the world’s Tamiflu, the drug also known as oseltamivir, and manufactured by the Swiss pharmaceutical company Roche. Britain has purchased enough courses of the drug to treat 25 per cent of the population if there was an outbreak of a bird flu pandemic.

Despite scores of deaths in south-east Asia, there have been no cases of human bird flu in Japan, and the 8.6 million people who receive the drug every year are suffering from the common form of human influenza.

But for the past three years, there have been alarming stories of young people succumbing to fits of self-destructive behaviour while receiving Tamiflu.

Relatives who believe that their children were adversely affected by the drug have formed a lobby group to demand its withdrawal from sale.

One of the most disturbing cases was in February 2004 when a 17-year old boy took one capsule of Tamiflu at his home in Gifu prefecture, central Japan. No one was at home to witness what happened next, but he appears to have left the house in his pyjamas, walked barefoot through a snowstorm, climbed over two fences and stepped in front of an oncoming truck. The driver told police that he was smiling at the moment of impact.

At the end of last month, a fourteen year old boy in the city of Sendai told his mother that he was going to the toilet, but then walked out of the front door of his eleven storey apartment. His mother ran out to see him straddling the four foot guard rail and despite her cries of warning he fell to his death in the car park below. He had taken two Tamiflu capsules, the first day of a five day prescribed course for influenza.

According to Japan’s health ministry, most of the 54 Japanese who died after taking Tamiflu by October last year, succumbed to liver or other organ failure, most likely caused by influenza. But 16 of them were children aged 16 or under, several of whom had exhibited “abnormal” behaviour.

The drug is already sold in Japan with a general warning that users may have psychological side effects including abnormal behaviour and hallucinations.

Proponents of the drug, however, argue that this is more likely to be caused by the flu itself, than by Tamiflu, and that there is no scientific evidence of any link between the drug and the violent deaths.

“Tamiflu has now been used in over 45 million influenza patients worldwide and treatment with Tamiflu has proven successful in reducing the duration and severity of the disease,” Roche said in statement today.

“Reports of such events leading to death are extremely rare, occurring in around 1 out of every 5 million influenza patients treated. No causal link between such events and Tamiflu has been established."

The statement said that US health insurance records in 1999-2006 indicated that psychiatric symptoms were lower in influenza patients taking Tamiflu than those not taking Tamiflu.

Eduard Holdener, Roche's Chief Medical Officer, said: "Patient safety is a primary concern for Roche and since the introduction of Tamiflu, Roche has continuously monitored and reviewed post-marketing safety information and provides regular updates to the regulatory agencies."

Anti-Tamiflu campaigners criticised today's decision to provide “safety information”, but not remove the drug from sale for being an inadequate and irresolute step.

“The government has kept saying there is no link between Tamiflu and the deaths,” said Ryuko Hatano, whose son died after taking the drug. “I cannot understand the ministry’s attitude in which they cannot move a step nor a half step until they see the next victim.”

Last month the European Agency for the EMEA, which licences the drug in Europe, including Britain, recommended that advice be given to doctors stating that psychological disorders have been reported in users of Tamiflu in Japan.

However, a spokesman for the EMEA said: “There is no warning equivalent in Europe for Tamiflu. The current situation is that we see there is no causal relationship between Tamiflu and these events.”