Antivirals for Influenza

Amantadine was the first specific therapy effective against the influenza A virus but has been superseded by the newer drugs oseltamivir and zanamivir. Antiviral drugs now form one part, but an important part, of plans to prevent and contain epidemics of influenza infection. However, it is important to consider that use of antivirals in the management of influenza infection (for individuals and in populations) should be selective and appropriate. Effective use of antivirals should be consistent with the efficacy of the drugs currently available and with coordinated disease control strategies.

Antivirals for influenza are currently recommended for:^1,2

• The treatment of influenza infection in at-risk adults (oseltamivir and zanamivir) and children (oseltamivir)
• Post-exposure prophylaxis in at-risk adults and adolescents over age 13 years who are not protected by vaccination and can commence treatment (oseltamivir) within 48 hours of exposure to influenza infection.

Amantadine

• Ineffective against influenza B
• Prevents penetration of the cell wall by the virus, but no direct action on the virus
• Licensed for prophylaxis and treatment of influenza A but not now recommended¹ because of a high rate of unacceptable adverse effects (such as nausea insomnia and hallucinations) ³
• Has a use in parkinsonism.

Oseltamivir

• Well tolerated
• Effective against influenza type A and B
• Inhibits neuramidase enzyme (which promotes release and spread of virus from infected cells)
• Taken orally (capsules or suspension, once daily dosage for up to 6 weeks during an epidemic for post-exposure prophylaxis in at-risk groups or at twice daily dosage for 5 days in the treatment of infection)
• Recommended for post-exposure prophylaxis in at-risk adults and adolescents over age 13 years not protected by influenza vaccination
• Should be started within 48 hours of close contact with someone suffering from influenza-like symptoms in post-exposure prophylaxis
• Should be started within 48 hours of the onset of symptoms in the treatment of influenza infection in at risk children over age 1 year and adults
• Not recommended for treatment of influenza infection, seasonal prophylaxis or post-exposure prophylaxis in otherwise healthy individuals
• Only for NHS prescription according to the notes above and NICE guidance.¹ The prescription should be endorsed “ SLS ” (selected list scheme).

Zanamivir

• Effective against influenza type A and B
• Inhibits neuramidase enzyme
• Taken by inhalation of powder twice daily (disks contain 4 blisters, 5 disks per pack of Relenza) There is a risk of bronchospasm in asthma and relieving inhalers should be kept available. It is best avoided in severe asthma.
• Licensed for use in influenza infection affecting at-risk adults and adolescents over 12 years
• Should be started within 48 hours of the onset of symptoms
• Not recommended for post exposure prophylaxis even in at-risk groups (unlike oseltamivir)
• Not recommended for treatment of influenza infection or seasonal prophylaxis in otherwise healthy individuals.

Influenza infection in at-risk patients

Oseltamivir and zanamivir can be used in adults, and oseltamivir in children. It must be started within 48 hours of the onset of flu symptoms.

Post-exposure prophylaxis in at-risk patients

Oseltamivir is recommended in adults and adolescents over age 13 for up to 6 weeks. It must be started within 48 hours of close contact with patients suffering from influenza symptoms. Included in the at-risk category are over 65 year olds and individuals with one or more of the following:

• Chronic respiratory disease
• Significant cardiovascular disease (not hypertension)
• Chronic renal disease
• Immunosuppression
• Diabetes mellitus.

Pandemic flu

Antiviral drugs are likely to be important in the event of another flu pandemic both for treatment and prevention of infection. Vaccines may not be available or supply limited.^4,5 However:

• Effectiveness at reducing mortality has not been established
• Current recommendations for use may change during a pandemic. For example the UK plan has identified groups likely to be a priority, but which are to be reviewed and possibly changed according to expert advice about the epidemiology and other information of an emerging pandemic. Priority groups are likely to be:
  • Health care workers (to maintain the health service response)
  • Essential service workers (to maintain key services)
  • Un-immunised high-risk groups (to reduce complications, hospital admissions and deaths)
  • Immunised people if it emerges that the vaccine is ineffective.
• Resistance to drugs may become significant.

Influenza infection in the otherwise healthy

Evidence for the efficacy of antivirals comes mainly from studies on otherwise healthy subjects. These studies have shown:

• Zanamivir reduces the duration of symptoms in influenza by 1.26 days.⁶
• Zanamivir reduces the rate of some complications compared with placebo and reduces antibiotic prescribing.⁶
• There is no evidence to show a reduction in serious complications requiring hospital admission or death.⁶
• Similar results have been shown for oseltamivir with a reduction in duration of symptoms of just over a day for healthy patients but no statistically significant reduction in the at-risk group of patients.⁶
• Oseltamivir has also been shown to reduce incidence of some complications such as otitis media in children and of lower respiratory complications requiring antibiotics in adults.⁶
• Again no trials clearly show a reduction in serious complications in either at-risk or healthy patients with use of oseltamivir.

It remains an unproven hypothesis that antiviral drugs will reduce the rate of serious complications in either at-risk or healthy subjects in the event of another flu pandemic or indeed a flu epidemic. There is consensus about the strategy for use of antivirals outlined above.⁷, ^8,9

The diagnosis of flu is made on clinical grounds. Influenza surveillance data can aid clinical diagnosis¹⁰. Surveillance of flu is a year-round global activity. The UK is part of an international network of flu surveillance involving 112 laboratories in 83 countries. In the UK the Health Protection Agency co-ordinates flu surveillance and will inform decisions about antiviral strategy across the UK.