According to Health Ministry and other medical sources, it appears that the drug induced hallucinations and dramatic shifts in behaviour in the boys, which led them to commit suicide.

Rokuro Hama, the doctor who made the connection, is the head of the Japan Institute for Pharmacovigilance and gave details of the incidents at a medical conference at the weekend. Dr Hama believes that Tamiflu was linked to a third case in which a teenage girl was narrowly prevented from jumping from a window two days after starting a course of the drug.

The revelations of possible dangerous side-effects came as Japan announced a draconian action plan to counter a bird flu outbreak or new strain of the disease. It includes measures for preventing social collapse and imposing bans on public gatherings, school attendance and work. It will also give the Government power to force people to go to hospital. The Health Ministry has put the number of Japanese deaths in such an outbreak at between 170,000 and 640,000.

The boys, who died during the 2004 and 2005 flu seasons, appear to have suffered severe side-effects within hours of taking a single capsule. Chugai Pharmaceutical, which distributes the drug in Japan, has told the ministry that a link between Tamiflu and the boys’ deaths could not be ruled out.

Japan has used more Tamiflu than any other country and has, accordingly, experienced the widest range of side-effects. Before the worldwide stockpiling began, the Japanese market accounted for 80 per cent of global sales of Tamiflu, which is used in about 10 million cases of flu a year in Japan.

A Tokyo doctor said that even though the drug would be an essential tool in fighting a bird flu pandemic, the incidents should send a message of caution around the world.

One of the boys, a 17-year-old from Gifu prefecture, walked out of his house barefoot and in pyjamas during a snowstorm. He crossed a building site and a railway line before jumping in front of a lorry on a busy road.

The other, a 14-year-old from Aichi prefecture, apparently jumped from the balcony of the ninth-floor flat. Neither boy had previously experienced any suicidal tendencies.

In Japan, Tamiflu is sold with a note warning users that it may have psychological sideeffects including abnormal behaviour and hallucinations. The British National Formulary, the drugs guide for British doctors, does not mention the possibility of patients on Tamiflu suffering any psychological disorders. Side effects recorded include nausea, vomiting, headache, fatigue and insomnia.

Roche, the maker of Tamiflu, said that it continued to monitor the drug’s safety. “Tamiflu has been used by over 30 million people worldwide,” it said.

Analysts played down the concerns, saying that the side-effects had not been observed before and more evidence was needed before a direct link could be established.

WILL IT WORK?

• Tamiflu, made by Roche Holding AG, does not cure a flu infection but can prevent illness from developing after exposure
  
  
• Unknown how effective it will be against the H5N1 bird flu virus; tests suggest that higher doses should have some effect
  
  
• About 40 countries have ordered the drug; Britain has ordered enough to protect up to a quarter of the population
  
  
• Bird flu has killed more than 60 people in Asia

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