Antiviral treatment of influenza

Expert opinion on neuraminidase inhibitors for the prevention and treatment of influenza

Questions and answers about antivirals

Although vaccination is the preferred option for preventing influenza, antivirals can be useful when the vaccine fails, for example, due to:

• antigenic mismatch with circulating virus,

• waning immunity in elderly,

• patient being immunocompromised,

• the vaccine not yet available, or

• during an outbreak of ‘avian’ influenza or an emerging pandemic.

At least one EU country (the UK) makes specific recommendations on when to use antivirals according to the levels of circulating influenza viruses as determined by surveillance.

To date there have been few instances of resistance to the neuraminidase inhibitors and resistant viruses that transmit on are very rare. Resistant mutants to the M2 inhibitors have been detected in a number of countries and all current circulating influenza viruses are resistant to M2 inhibitors. Therefore, the use of M2 inhibitors in treatment of influenza is not recommended.  Antiviral resistance in Europe is monitored by ECDC and EuroFlu based on the reports sent by influenza reference laboratories to TESSy.

ECDC routinely collects, analyses and disseminates information on antiviral resistance from influenza viruses isolated from all EEA/EFTA countries.

The analysis of resistance against neuraminidase inhibitors and adamantanes is performed by measuring IC50 values and/or by genotyping of viruses for detection of known drug resistance mutations.

What are the uses of antivirals against seasonal influenza?

The policy and practice on the use of antivirals varies between European countries. In some countries, using evidence-based policies, antivirals are only recommended for adults who are at increased risk of the complications of flu. They are generally not recommended for otherwise healthy adults with ordinary influenza. Like all medicines they can have side effects in some people.

For people in a risk group the most important way of preventing the serious complications of flu is still the flu vaccine and taking general precautions. However, if you are in a risk group and have contracted the flu, you should seek advice early from your doctor, nurse or pharmacist who can advise you on whether you need to take antivirals as they can shorten the illness or reduce the severity of the symptoms.

When are antivirals effective? If I need them how quickly should I take them?

This is one of the major difficulties with antivirals. The scientific evidence suggests that antivirals are only effective if they are taken early on in the illness and the earlier the better. After someone has been unwell with influenza for 48 hours antivirals are not thought to help much at all. If antivirals can be given within 12 hours of the illness starting the benefit seems to be greater than if they are not given for 24 hours, which in turn is better than 48 hours.

Which are the antivirals we use in Europe against seasonal influenza and who should get them?

Currently two drugs are mostly recommended for the treatment of influenza, in Europe these are Oseltamivir (the trade name is Tamiflu) and Zanamivir (Relenza). Adamantane class of antivirals against influenza should not be used any more as all circulating influenza viruses are resistant to this class of drugs. None of these can be obtained except through a doctor or sometimes a nurse working under the supervision of a doctor. They are often only recommended as treatment for influenza in those considered to be ‘at risk’ of developing more serious complications from flu infection, such as the elderly or those with underlying conditions like asthma or heart disease. It is recommended for ‘at risk’ patients who present and who can start treatment within 48 hours of the onset of symptoms of influenza-like illness .These drugs are usually only recommended for use in this way during the period when flu is known to be circulating. Zanamivir and oseltamivir belong to neuraminidase inhibitor family of drugs that attack the flu virus replication cycle and prevent its spreading within the body. Their introduction is therefore an important addition to the tools we have to manage flu infection.

If antivirals are so good why don’t doctors give them out more often?

There are good reasons for this. If doctors use antivirals a lot then the influenza that is circulating may develop resistance to them. Also, like all medicines they have side effects and so should not be given without serious thought as to whether persons actually need them. Then not only are antivirals expensive some (notably oseltamivir – also called Tamiflu) are in short supply. If we use them now they may not be available when we really need them e.g. during a pandemic. Some European countries have scientific policies that they only allow or recommend doctors to use antivirals for flu when it has been shown that influenza is circulating in the population at a certain level.

Would it not be best if we all had antivirals at home to use when we need them?

No! Antivirals like zanamivir and oseltamivir should only be used under medical supervision. Also experience with other medicines is that when they are stored away at home ‘just in case’ they are usually never used, or not used properly or when they are used they have gone past their expiry date and no longer work.

I heard that sometimes everyone exposed to influenza has been given antivirals – why is that?

This is in special circumstances where people in a risk group have been exposed to influenza. The most common time this happens is when there is a proven influenza outbreak in an old people’s home, a nursing home or a hospital ward. Then antivirals may be given to all the people at risk as early treatment or prophylaxis.

Do people who have been immunized against influenza need antivirals?

Yes – even though the immunization gives some protection it is thought that antivirals add to this.