Tamiflu (oseltamivir phos-phate)-the first-line pre-ventative against influenza and avian (bird) flu-can be a killer, its manufacturer Roche has finally been forced to admit. This has been known for at least four years since the deaths of eight young Japanese while taking the drug.
In spite of this, health authorities around the world have been buying and storing millions of doses of Tamiflu as protection against avian flu. The UK government has bought 14.6 million doses, while the US has ordered 20 million doses.
The latest warning is the third forced upon Roche by the US Food and Drug Administration (FDA). In 2003, the drug giant had to tell doctors to stop prescribing the drug to children under one year of age and, in 2006, it was forced to reveal that patients could harm themselves while taking the drug.
Then, in March this year, Roche had to announce that the hallucina-tions and abnormal behaviours seen with the drug could be so extreme that the patient might even commit suicide, as has already happened in Japan.
The FDA told Roche to issue the latest warning after it had received numerous reports from worried doctors across the country.
Japan's health ministry issued similar warnings in 2007 when it told doctors to stop prescribing the drug to children aged 10-19 years. In 2004, the drug's safety datasheet was altered to include neurological and psychological disorders as possible side-effects.
This action was taken following the eight deaths and seven serious injuries in Japan among adolescents taking the drug. One was a 14-year-old boy who leapt to his death after taking just one Tamiflu capsule, and aother was a 17-year-old boy who threw himself in front of a truck (N Engl J Med, 2005; 353: 2667-72).
By 2007, the Japanese health authorities had received 128 reports of psychological disorders in users, including 43 cases in children under 10, and 57 in adolescents between 10 and 19 years of age.
South Korean health authorities issued a similar warning against the use of Tamiflu in 2007, and has completely banned its use among teenagers.
Yet, no such warning has been issued in the UK or any other European country. The European Medicines Agency believes that the benefits of the drug still outweigh the risks, although the agency says it will closely monitor the safety reports from Japan.
Roche has always maintained that the drug is "well tolerated", provided that the patient doesn't have kidney or liver disease, or any other chronic condition. It says that self-injury, confusion and delirium are "uncommon" and the reaction could be as much the result of the illness as of the drug itself.
This was also the conclusion of researchers at Yokahama City University in Japan, who found no differences in the behaviour of 2800 children, around half of whom were taking the drug. However, this piece of research was later discredited when journalists discovered that the university had received $85,000 of research funding from the drug's Japanese manufacturer, Chugai Pharmaceutical.
In addition to hallucinations and abnormal behaviour that could end in suicide, Tamiflu can also cause anaphylactic shock, serious skin reactions, nausea, vomiting, bronch-itis, insomnia and vertigo.
Most reactions occur because the drug is prescribed 'off-label' to pop-ulations such as children, for whom drug safety trials have never been done, or because of an unlicensed use, where it is given for a condition for which it has never been tested, such as avian flu.
In fact, Tamiflu has been licensed as a preventative and treatment only for influenza types A and B, and Roche has admitted that there is no evidence that Tamiflu can protect against avian flu.
This same conclusion was arrived at after a review of 52 trials with the drug, although the researchers still concluded that it could be used against bird flu, albeit only as an emergency measure (Lancet, 2006; 367: 303-13). The World Health Organiza-tion came to a similar conclusion that same year when it described Tamiflu as our best defence against avian flu-possibly because it is, so far, our only defence against it.
This is not very surprising as the H5N1 virus responsible for bird flu has yet to be successfully transferred between humans. Also, biologists know that a virus such as the one that causes avian flu mutates one million times more frequently than DNA does, so the best we could hope for with any vaccine is that it will serve as a protective agent against last year's virus.
Despite the scientific evidence that ought to help in the decision-making process, governments are, in fact, driven more by fear. In 2006, the UK's chief medical officer Sir Liam Donaldson announced to the British public that 750,000 Britons could die from avian flu that year or the year after. Yet, according to the latest World Health Organization figures for the past five years, only 235 people have died because of bird flu worldwide.