Oseltamivir (Tamiflu) + zanamivir (Relenza) combo a better strategy against swine flu

Using both oseltamivir and Zanamivir drugs cuts resistance to just 2 per cent.

At least two anti-viral drugs are necessary to effectively attack the swine-flu causing H1N1 virus, suggest studies.

Two anti-flu drugs will provide a better strategy than just one of the two commonly used flu drugs for countries stockpiling the anti-virals to control a major outbreak of swine flu.

Because the flu virus is very tricky by nature, a resistant strain of the virus can emerge faster if we are depending on a single drug. So, countries can fight it out in better way with more than one option.

Studies showed that using both Roche’s Tamiflu (oseltamivir) and GlaxoSmithKline’s Relenza (zanamivir) cut the proportion of flu-infected patients to 58 percent from 68 percent–and perhaps more importantly, slashed the chance of resistance emerging to just 2 percent from 38 percent.

“If you can hold off using your primary drug until the cumulative number of cases reaches a sufficiently high number, you reduce the spread of resistance and the final number of cases,” says team member Joseph Wu at the University of Hong Kong.

The key is to make sure the source population has good control of antiviral drugs, then all countries downstream benefit. If the source loses control then these strategies won’t work, he said.

Resistance risk

The two anti-flu drugs, which are being commonly stockpiled for use in a flu pandemic, are oseltamivir, which is sold as Tamiflu, and zanamivir, which is sold as Relenza.

Both oseltamivir and zanamivir work by inhibiting an enzyme called neuraminidase that the virus needs to replicate, but they act on different parts of the enzyme and resistance to one drug does not confer resistance to the other.

The current H1N1 strain is sensitive to both drugs. However, it is not sure how long that will last.

The researchers conducted their study after noticing that despite concerns about resistance, many countries stockpile just one drug, usually oseltamivir. There are some exceptions, however, including Australia and the UK, which stockpile both drugs.

Last year, an H1N1 flu strain that caused some seasonal flu rapidly developed resistance to oseltamivir. By December, “close to 100 per cent of H1N1 in Australia and the US, and many other parts of the world, were resistant to Tamiflu”.

To find out the efficacy of the two-drug strategy doctors either prescribed just one drug, both drugs in combination, or prescribed one, then switched to the other when supplies of the first drug ran out.

The two strategies that used more than one drug decreased the number of people who finally became infected from 68 to 58 per cent. It also reduced the chance of resistance emerging from 38 to just two per cent, which would translate into a significant number of lives saved, said Wu.

However, the safety of using two drugs together has not been assessed.

“Cross-resistance to both drugs at the same time is highly unlikely, so using the two drugs cleverly might be able to delay the emergence of resistance,” says epidemiologist Jodie McVernon at Melbourne University, Victoria, Australia, who was not involved in the study.

In a scenario where lots of drugs are being used over a short period of time, drug resistance will probably emerge, and efficacy would be substantially weakened, according Wu.

The study was carried with researchers from Harvard University and the Health Protection Agency in London, as well as the University of Hong Kong.

If the swine flu continues to spread, it will probably lead to “unprecedented levels of use” of Tamiflu, the antiviral drug most developed countries have stockpiled, said Marc Lipsitch, an epidemiologist at the Harvard School of Public Health in Boston. That is likely to lead to the emergence of a new strain of the H1N1 flu virus that is resistant to Tamiflu, he said.

“Ideally we’d like to delay the appearance of those resistant strains as long as we can,” he said. “If a country has a second drug and could use it for as little as 1 percent to 1.5 percent of cases, it could make a major difference.”