Oseltamivir and Zanamivir licensed for treatment and the former also for post-exposure prophylaxis.
Cochrane review 2014 found little evidence of benefit. But this was based on community studies in healthy populations.
“Use of neuraminidase inhibitors in influenza” [October 2015, Academy of Medical Sciences] indicates that the use of antivirals can be beneficial in certain situations, but of limited use in others. Additionally, a recent review “Expert opinion on neuraminidase inhibitors for the prevention and treatment of influenza – review of recent systematic reviews and meta-analyses” August 2017, European Centre for Disease] supports use as treatment and prophylaxis.
UKHSA therefore recommends:
“Complicated” influenza defined as
- requiring hospital admission,
- signs of LRTI eg resp distress, chest signs
- CNS signs
- Worsening of underlying medical condition
Risk factors include:
- infants under 6 months;
- neurological, hepatic, renal, pulmonary and chronic cardiac disease ; diabetes mellitus;
- severe immunosuppression (includes prednisolone r≥2mg/kg/day for ≥1 week);
- morbid obesity (Z score BMI 3.33 or higher).
Oseltamivir (Tamiflu) PO or NG is first line, unless severe immunosuppression and A(H1N1) variant prone to resistance dominant – then zanamavir.
- Start treatment within 48hrs, do not wait on lab confirmation of diagnosis. May still be benefit in life threatening illness when started up to 5 days after onset. Rule is within 36hrs if child and zanamavir.
- should NOT be used in otherwise healthy patients but can be considered if felt to be “at serious risk of developing complications”.
- Test for resistance if no response after 5 days of treatment.
Presumes flu-like illness and circulating influenza, CMO publishes advice when surveillance levels cross threshold. Highly virulent strain would change things, of course. Further details including use of anti-virals at HPS.
Oseltamavir dose is twice daily for 5 days. Oral only, capsules can be opened and added to something sugary (very bitter). Liquid preparation available but limited supply, prioritise for infants. Give by NG if necessary. Licensed for treatment at all ages now, prophylaxis only over 1 yr. Diarrhoea and vomiting are the only significant side effects.
The earlier it is started the better: starting within 12 hours reduced duration of illness by 3 days, start within 48 hours and only 1 day benefit. 5% of childhood infections will become resistant whereas this is unusual in adults, probably due to kids having higher viral loads in primary infection. Consider resistance if no benefit after 5 days treatment.
Zanamivir used for adolescents 12 years and older – taken again twice daily for 5 days by diskhaler (age less important than ability to use device!). No resistance, very low rate of side effects (wheeze!). Zanamavir is preferred in severely immunocompromised AND (probable) A(H1N1)pdm09 disease, as resistance is higher . Unlicensed IV form of zanamavir is available on compassionate named patient basis.
Prophylaxis
For prophylaxis, vaccination best! But consider using anti-virals (NICE recommendations) for post-exposure prophylaxis with Oseltamivir where:
- 13yrs or older
- Have a risk factor, as above
- Influenza A or B is circulating, as above
- Present within 48hrs of close contact exposure
- Have not had flu vaccine for this season, or too recently for it to have been effective (within 14 days), or the wrong type, or have a condition that means vaccine may not be fully effective, or localised outbreak eg care home
Dose is once daily for 10 days. Treatment for up to 6 weeks might be required during an epidemic.
Other comments
Amantadine not recommended – targets M2 protein, only effective against type A influenza, rapid resistance and side effects common.
2 adolescents in Japan have committed suicide while on oseltamavir, plus there have been a number of other neuropsychiatric reports.
Peramivir is IV preparation with marketing authorization in EU, not yet available in UK.