Tamiflu? Effective for what's coming or not?

I am a doctor, and I don't prescribe Tamiflu or Relenza.
They are expensive and only shorten the duration of the illness by 1/2 of one day if started within the first 24 hours after symptoms present.

The trouble with Tamiflu

The companies behind the two leading anti-flu drugs are making millions out of the crisis. But just how effective are their products? Sarah Boseley reports
Sarah Boseley
The Guardian, Thursday 7 May 2009

It was a sight that would have gladdened the heart of Dr Severin Shwan, chief executive of Roche, one of the biggest drug companies in the world. A long line of well-heeled parents assembled on a bank holiday weekend at a British private school, Alleyn's in south London, patiently waiting their turn to receive a packet of Roche's drug Tamiflu from staff. Five pupils had been diagnosed with swine flu and the school had been closed. The pills were intended to stave off infection among the children who had been sent home.

The board of Roche, a Swiss-based company which has globalised the name it inherited from its founder, Fritz Hoffmann-La Roche in 1896, must be laughing. It has a drug which has become a household name and been stockpiled by the millions of boxes all over the world, against a potential pandemic that the World Health Organisation (WHO) warns is almost upon us. Roche has supplied governments with 220m courses worldwide. The UK has stored enough to treat half the population. And yet Tamiflu is of limited use.

There are two drug contenders to reduce the impact of a flu pandemic - Tamiflu (oseltamivir) and the GlaxoSmithKline (GSK) drug Relenza (zanamivir), which is similar but more complicated to use because it must be inhaled - not easy if people have breathing problems. But Relenza, too, is being stockpiled around the world, to the delight of a small Australian company called Biota Holdings - the company that developed Relenza and licensed it to GSK. Biota's share price leapt 16% last week when GSK announced it had sold $46m-worth of the flu drug, giving Biota $32.3m in licensing fees.

Relenza and Tamiflu are known as neuraminidase inhibitors (NIs). Two other, older flu drugs, amantadine and rimantadine, are now of little use because flu viruses have become resistant to them over the years. Nobody claims Tamiflu and Relenza cure flu, but they were licensed after trials that showed they mitigated its severity and reduced the length of the illness by about a day. Unfortunately, you have to take them within 48 hours of symptoms starting.

To Jefferson's horror, however, the WHO has recommended that the drugs should be used against seasonal flu - the usual forms of flu that hit us every winter - so that doctors get used to giving them, and patients to taking them, ahead of a pandemic. "Wide-scale use of antivirals and vaccines during a pandemic will depend on familiarity with their effective application during the inter-pandemic period," it reasons.

"It is more than madness," says Jefferson. "Especially as we don't know what the real reasons for that recommendation are." Doctors who work for the drug companies, carrying out their studies or sometimes simply allowing their name to be attached to the paper, also advise the WHO, he points out.

He argues that there is a very real possibility of resistance developing to the drugs if they are handed out like Smarties. Viruses are clever organisms, and evolve super-fast and efficiently. Treat a virus with drugs and you must hit it hard enough and for long enough to eliminate it. If the dose is not strong enough, or the patient stops taking the drugs mid-course, the virus will evolve into a form that can overcome the drug. It is then a resistant strain. This is a major problem with the Aids virus, HIV, for which many new drugs have had to be developed. Bacteria behave the same way - penicillin, once a wonder drug, is now of little use.

Jefferson points out that although Tamiflu is only eight years old, resistance has already set in. Last year a strain of winter flu was circulating in the US that was found to be resistant to Tamiflu. In the South East Asia bird flu outbreak, there was resistance among 16% of children given the drug and among two out of eight Vietnamese people aged between 8 and 35, according to the Cochrane review.

This resistance is inevitable, says Jefferson, if you believe in the theory of natural selection, in which organisms evolve to overcome threats to their survival. "We know that has already happened with Tamiflu. It has happened with amantadine, which has been around since the 60s." Of course, governments and the public want magic bullets. There is a belief that where there is an illness, there must be a cure. Handing out drugs reduces panic. People are more likely to stay put at home where they cannot infect too many people if they feel they are being treated.

And there is is a role for Tamiflu in severe and complicated cases caught early. But Jefferson balks at the idea of drug hand-outs at schools. "The spread will stop, but only because the children have been sent home," he says.

The most important trial in disease prevention of the last 50 years was carried out in 2005 by a US doctor called Stephen Luby. "For that he should receive a Nobel prize," says Jefferson. Luby carried out a randomised trial in squatter settlements in Karachi, promoting hand-washing in half the families. Children under five who regularly washed their hands had half as many episodes of diarrhoea, impetigo and acute respiratory infection. It saved lives. If the big pandemic hits, washing hands will save more lives than Tamiflu, he predicts.

Full:

http://www.guardian.co.uk/world/2009/may/07/tamiflu-swine-fl...