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In this summary

 

This Guidelines summary covers Public Health England (PHE) guidance on the use of antiviral agents for the treatment of suspected or confirmed cases of seasonal influenza. You can see our summary of PHE advice on prophylactic treatment of people who may have been exposed to seasonal influenza here and 10 frequently asked questions can be found here.

Treatment of suspected or confirmed influenza

Summary algorithm for prescribing antiviral treatment for influenza

Summary algorithm for prescribing antiviral treatment for influenza

p.o.=by mouth; NG=nasogastric (administration via a nasogastric tube); INH=inhaled; NEB=nebulised; i.v.=intravenous.
Note: Commencing oseltamivir and zanamivir treatment more than 48 hours after symptom onset (36 hours for zanamivir use in children) is an off-label use. For other licensed and unlicensed treatments, see the full guideline.
* for treatment of suspected or confirmed oseltamivir-resistant influenza, see section 1.3.3 in the full guideline
clinical follow-up—advise patient to seek medical attention if illness worsens. Patient may need to be reswabbed for influenza testing if this occurs, noting on the form that they are already on antiviral treatment. The circulating influenza strain can be checked via the National Flu Report.
‡  The following hospitalised patients may be considered for IV zanamivir: patients who have already failed to respond to nebulised zanamivir; patients who have developed respiratory conditions affecting nebuliser delivery (e.g. airways disease, pulmonary oedema); patients who have multi-organ involvement or who require intensive care. 

  • The selection of first line antivirals in severely immunosuppressed individuals should take account of the subtype of influenza causing infection, or if not yet known, the dominant strain of influenza that is circulating during the current influenza season (obtainable from the PHE weekly influenza reports). Table 1 (below) provides guidance on the selection of antivirals for severely immunosuppressed patients, taking into account the dominant circulating strain of influenza, and the risk of developing oseltamivir resistance
  • In general, influenza A (H1N1) is considered to be a higher risk for the development of oseltamivir resistance, whilst influenza A(H3N2) and influenza B are considered lower risk. Further advice on the risk of individual subtypes can be obtained from a Consultant Microbiologist or Consultant Virologist
Table 1: Selection of antivirals for severely immunosuppressed patients
 Dominant circulating strain has a lower risk of oseltamivir resistance, eg A(H3N2), influenza B§Dominant circulating strain has a higher risk of oseltamivir resistance, e.g. A(H1N1)§

Uncomplicated influenza

Oseltamivir p.o.  and clinical follow up. 
Commence therapy within 48 hours of onset (or later at clinical discretion)

Zanamivir INH (Diskhaler®

Commence therapy within 36 hours of onset (or later at clinical discretion)

or if unable to take inhaled preparation use oseltamivir p.o.  and clinical follow up

Commence therapy within 48 hours of onset (or later at clinical discretion)

Complicated influenza

First line: oseltamivir p.o./NG
Second line: zanamivir INH, NEB, or i.v.
Consider switching to zanamivir if:

  • poor clinical response
  • subtype testing confirms a strain with potential oseltamivir resistance, e.g. A(H1N1)

Zanamivir INH, NEB, or i.v.

Commence therapy within 48 hours of onset (36 hours for children) or later at clinical discretion

(if there are delays in obtaining aqueous zanamivir, use oseltamivir as a bridging treatment until zanamivir is available)

p.o.=by mouth; INH=inhaled; NG=nasogastric (administration by nasogastric tube); NEB=nebulised; i.v.=intravenous
§
Also applicable if this is the strain known to be infecting patient; treatment however, should not be delayed while waiting for test results

Treatment of adults and children in community/A&E with uncomplicated influenza

  • All patients should be advised of the symptoms of complicated influenza and told to seek medical help should their condition worsen. The following recommendations for adults refer to dosages in Table 2, which also includes paediatric dosing. See table 3 for dosing in patients with hepatic dysfunction and table 4 for dosing in patients with renal dysfunction
    • previously healthy people (excluding pregnant women): no antiviral treatment, or if physician feels patient is at serious risk of developing serious complications from influenza, then oseltamivir by mouth (p.o.)
    • at risk population, including pregnant women (but excluding the severely immunosuppressed): oseltamivir (p.o.). Do not wait for laboratory confirmation. Treatment should be started as soon as possible, ideally within 48 hours of onset. There is evidence that treatment may reduce the risk of mortality even if started up to five days after onset. Treatment after 48 hours is an off-label use of oseltamivir and clinical judgement should be exercised. See 
    • severely immunosuppressed patients: Some influenza subtypes are associated with a greater risk of developing oseltamivir resistance, and the selection of first line antivirals in severely immunosuppressed individuals should take account of the dominant circulating strain of influenza (Table 1). The risk of resistance is highest in people who are severely immunosuppressed and have complicated influenza, who are given antivirals. Oseltamivir p.o. is the first line treatment, unless the dominant circulating strain is influenza A(H1N1) which has a higher risk for developing oseltamivir resistance, in which case use inhaled zanamivir (INH) (Table 1). Treatment should start as soon as possible. If clinical condition does not improve, continue with Zanamivir, take a specimen for resistance testing and consider other possible causes for a failure to improve
    • suspected or confirmed oseltamivir resistant influenza in a patient who requires treatment: zanamivir (INH). Treatment should be started as soon as possible
    • management of patients for whom zanamivir is indicated, who are unable to self-administer inhaled zanamivir: Some patients who would normally receive inhaled zanamivir are unable to use it, either due to underlying severe respiratory disease or inability to effectively self-administer the Diskhaler® (this includes children under 5, for whom zanamivir is unlicensed). Patients who are severely immunosuppressed and cannot take inhaled zanamivir should receive oseltamivir p.o. As they are at increased risk of developing oseltamivir resistant influenza, they should be reviewed clinically to assess response to therapy. Patients who have suspected or confirmed oseltamivir resistant infection and cannot take inhaled zanamivir should be considered for nebulised aqueous zanamivir. This is an unlicensed medication and the dose is provided on the manufacturer’s guidance supplied with the drug (see full guideline)
Table 2: Treatment dosage
TreatmentPremature (less than 36 weeks post conceptual age)0–12 months (36 weeks post conceptual age or greater)>1–12 years: dose according to weight below   Adults (13 years and over)
≤15 kg>15–23 kg>23–40 kg>40 kg 

Oseltamivir p.o. (treatment course: 5 days)

1 mg/kg per dose b.d. Unlicensed|

3 mg/kg/dose b.d.

30 mg b.d.

45 mg b.d.

60 mg b.d.

75 mg b.d.

75 mg b.d.

Zanamivir INH (treatment course: 5 days)

Not licensed for children <5 years old.

Children >5 years: 10 mg b.d.

10 mg b.d.

p.o.=by mouth; b.d.=twice daily; INH=inhaled
|
This is an unlicensed use of oseltamivir, and is based on evidence from the literature, and expert opinion
If a person in this age group weighs 40 kg or less, it is suggested that the >23–40 kg dose for those aged >1–12 years, is used

Use of antivirals in pregnancy, breastfeeding, and hepatic dysfunction

Use in pregnant women

  • Oseltamivir remains the first line option for the vast majority of pregnant women with influenza, including during seasons that are dominated by influenza A(H1N1)
  • For pregnant women who meet additional criteria for requiring zanamivir first line, further assessment (i.e. rapid diagnostics) and antiviral treatment should be discussed with a local infection specialist
  • Oseltamivir is generally well tolerated in patients with influenza, but side effects can occur. There are no data suggesting tolerability differs between pregnant and non-pregnant adults
  • Recent studies suggest there is no evidence of harm in pregnant women treated with oseltamivir or zanamivir
  • See the summaries of product characteristics for oseltamivir and zanamivir for more guidance regarding safety of use in pregnancy

Use during breastfeeding (new 2018)

Table 3: Recommended dosage for hepatic dysfunction
 Liver dysfunction
Oseltamivir p.o.. Standard dosing 
Zanamivir INH (Diskhaler® Standard dosing 
Zanamivir solution i.v./NEB  Refer to physician’s guidance document supplied by the manufacturer with the medication 
p.o.=by mouth; INH=inhaled; i.v.=intravenous; NEB=nebulised

Dosing in patients with renal dysfunction (amended 2018)

  • The information provided here on dosing in renal impairment and renal failure is intended specifically for consideration when patients have an existing history of chronic kidney disease (CKD) and renal failure results have been previously documented for the purpose of managing CKD. As with other groups, it is essential to give the first dose as soon as possible 
  • Clinical judgement will be required where renal function is unstable (i.e. in acute renal failure)
  • For full recommendations about using creatinine clearance (CrCl) and estimated glomular filtration rate (eGFR) to guide treatment in patients with stable renal function, please see the full guideline
Table 4: Recommended oseltamivir treatment dosing in relation to renal function (adults and those aged 13 years or over)
CrCl (ml/min)Oseltamivir p.o. treatment for 5 Days

>60 ml/min

75 mg b.d.

31–60 ml/min**

30 mg b.d.

11–30ml/min**

30 mg o.d.

≤10 ml/min††

30 mg once

Haemo-dialysis (HD)**

30 mg once and then 30 mg after every HD session

Peritoneal dialysis**

30 mg once

Haemo(dia)filtration**††
1–1.8 l/hr exchange rate

30 mg o.d.

Haemo(dia)filtration**††
1.9–3.6 l/hr exchange rate

30 mg b.d.

Haemo(dia)filtration**††
>3.6 l/hr exchange rate

75 mg b.d.

CrCl=creatinine clearance; p.o.=by mouth; b.d.=twice daily; o.d.=once daily
** Based on summary of product characteristics updated as of January 2017.

†† Based on expert opinion.

  • Note: it is acknowledged that the some of the advice for dosing in renal impairment presented here may differ to the renal drug handbook; however, the dosage information presented above is consistent with the summary of product characteristics provided by the manufacturer, at the time of writing
  • For adult zanamivir i.v. dosing in relation to renal function, see full guideline

Treatment of adults and children with complicated influenza

  • All patients with complicated influenza should receive treatment, often in hospital. Rapid testing for respiratory viruses including influenza virus is recommended for all patients fulfilling the clinical criteria for complicated infection. Treatment should be started as early as possible; do not wait for laboratory confirmation of influenza virus infection
  • See full guideline for recommendations on the treatment of complicated influenza in secondary care

Prescribing in primary care 

  • GPs may only prescribe antiviral medicines for the prophylaxis and treatment of influenza under the General Medical Services (GMS) regulations when the Chief Medical Officer (CMO) has confirmed that influenza is circulating in the community. The CMO announcement is issued to the NHS through the DH Central Alerting System (CAS)
  • GPs have the discretion to prescribe antiviral medicines for people who are not in the specified at-risk groups but who are considered to be at risk of complications if not treated with an antiviral medicine

Definitions

  • Uncomplicated influenza:  influenza presenting with fever, coryza, generalised symptoms (headache, malaise, myalgia, arthralgia) and sometimes gastrointestinal symptoms, but without any features of complicated influenza
  • Complicated influenza:  influenza requiring hospital admission and/or with symptoms and signs of lower respiratory tract infection (hypoxaemia, dyspnoea, lung infiltrate), central nervous system involvement and/or a significant exacerbation of an underlying medical condition.

Risk factors for complicated influenza:

  • neurological, hepatic, renal, pulmonary and chronic cardiac disease
  • diabetes mellitus
  • severe immunosuppression
  • age over 65 years
  • pregnancy (including up to two weeks post partum)
  • children under 6 months of age
  • morbid obesity (BMI ≥40)

For full details refer to Immunisation against infectious disease, known as the Green Book

Severe immunosuppression:  Examples of severe immunosuppression relevant to this guidance are given below. Degrees of immunosuppression are difficult to quantify and individual variation exists, therefore this list is not comprehensive:

  • severe primary immunodeficiency
  • current or recent (within 6 months) chemotherapy or radiotherapy for malignancy
  • solid organ transplant recipients on immunosuppressive therapy
  • bone marrow transplant recipients currently receiving immunosuppressive treatment, or within 12 months of receiving immunosuppression
  • patients with current graft-versus-host disease
  • patients currently receiving high dose systemic corticosteroids (equivalent to ≥40 mg prednisolone per day for >1 week in an adult, or ≥2 mg/kg/day for ≥1 week in a child), and for at least 3 months after treatment has stopped
  • HIV infected patients with severe immunosuppression (CD4 <200/μl or <15% of total lymphocytes in an adult or child over 5; CD4 <500/μl or <15% of total lymphocytes in a child aged 1–5; expert clinical opinion in a child aged under 1)
  • patients currently or recently (within 6 months) on other types of highly immunosuppressive therapy or where the patient’s specialist regards them as severely immunosuppressed

full guideline available from…

www.gov.uk/government/publications/influenza-treatment-and-prophylaxis-using-anti-viral-agents

Public Health England. PHE guidance on use of antiviral agents for the treatment and prophylaxis of seasonal influenza. October 2018.
Contains public sector information licensed under the Open Government Licence v3.0.

First included: November 2017, updated January 2019. 

PHE influenza antiviral treatment guideline