Download The use of antiviral drugs for influenza: Guidance for practitioners

PRACTICE POINT
The use of antiviral drugs for
influenza: Guidance for practitioners, 2012/2013;
Paediatric summary
Upton D Allen; Canadian Paediatric Society
Infectious Diseases and Immunization Committee
Paediatr Child Health 2013;18(3):155-8
Posted: Mar 1 2013 Reaffirmed: Feb 1 2016
Abstract
This practice point summarizes the use of antiviral
drugs to manage influenza illness in children and
youth for the 2012/2013 season. It excerpts a re­
cently published, full-length update of Canadian
recommendations for clinicians on the use of antivi­
ral drugs for the prevention and treatment of in­
fluenza, with a focus on paediatric antiviral therapy.
Detailed information on the selective use of chemo­
prophylaxis can be found in the source document,
which also highlights the importance of secondary
bacterial infections (Streptococcus pneumoniae,
methicillin-sensitive Staphylococcus aureus and
methicillin-resistant S aureus) in cases of severe in­
fluenza illness.
Key Words: Antiviral therapy; Children; Influenza;
Neuraminidase inhibitors
Citation for the full-length source document: Aoki FY,
Allen UD, Stiver HG, Evans GA. The use of antiviral
drugs for influenza: Guidance for practitioners
2012-2013. Can J Infect Dis Med Microbiol
2012;23(4):e79-e92. Available at: www.ammi.ca/me­
dia/48038/14791_aoki_final.pdf.pdf.
Antiviral use in children
There are fewer data to guide the management of in­
fluenza illness in children generally, and especially in
infants, than for adults. Background information on this
illness in children, provided in the full-length guidance
document, was based on data derived from paediatric
populations.[1]-[5] More on the strengths and weakness­
es of current evidence relating to antiviral use can be
found
at:
http://onlinelibrary.wiley.com/doi/
10.1002/14651858.CD008965.pub3/abstract. Signifi­
cant issues include high influenza attack rates in
school-aged children,[1]-[2] the atypical, non-specific na­
ture of influenza illness in young children,[3] and the
high risk of adverse outcomes from influenza illness
among children younger than five years of age.[5] Hos­
pitalizations occur more frequently among children
younger than two years of age compared with older
children, with the highest hospitalization rates being
among infants younger than six months of age.[3]
These statistics do not necessarily translate into deci­
sions to use antiviral therapy in patients younger than
two years of age; children of any age with mild influen­
za illness do not usually require treatment.
Three currently available antiviral agents are approved
for use for children in Canada. Amantadine, for sea­
sonal influenza A, is not currently useful because of re­
sistance. Oseltamivir (Tamiflu, Hoffman-La Roche Ltd,
Canada) and zanamivir (Relenza, GlaxoSmithKline
Inc, United Kingdom) are used for influenza A and B.
More recent studies on the neuraminidase inhibitors
(NAIs) have been reported or are in progress, and ex­
perience with their use is increasing.[6]-[9] However,
there is a notable paucity of current data from random­
ized trials in infants and young children. Two recent
studies provided valuable safety data[10] and data on
oseltamivir use in premature newborns.[11] However,
oseltamivir use for 2012/2013 seasonal influenza in
children younger than one year of age should be han­
dled on a case-by-case basis based on severity of ill­
ness. Oseltamivir is not approved for this indication in
Canada, though it was temporarily approved for use in
infants under one year on the basis of a favourable
risk-to-benefit ratio during the 2009 H1N1 pandemic.
INFECTIOUS DISEASES AND IMMUNIZATION COMMITTEE, CANADIAN PAEDIATRIC SOCIETY |
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Published recommendations for oseltamivir dosing for
babies younger than one year of age vary within a rea­
sonably narrow range.[12]-[14]
Treatment recommendations
Risk factors and drug doses are summarized in Table
1 and Table 2. A treatment algorithm is included as
Figure 1. For explanation of levels of evidence, see the
full guidance document.
TABLE 1
At-risk groups and comorbid medical conditions that predispose to severe influenza illness
• Asthma or other chronic pulmonary diseases, including bronchopulmonary dysplasia, cystic fibrosis, chronic bronchitis and emphysema
• Cardiovascular disease (excluding isolated hypertension; including congenital and acquired heart disease, such as congestive heart failure and symptomatic
coronary artery disease)
• Malignancy
• Chronic renal insufficiency
• Chronic liver disease
• Diabetes mellitus and other metabolic diseases
• Hemoglobinopathies such as sickle cell disease
• Immunosuppression or immunodeficiency due to disease (eg, HIV infection, especially if CD4 is <200×106/L), or iatrogenic, due to medication
• Certain rheumatological diseases, such as rheumatoid arthritis, systemic lupus erythematosus, psoriatic arthritis, antiphospholipid syndrome, scleroderma,
spondyloarthropathies, Sjogren’s syndrome, dermatomyositis, vasculitis, sarcoidosis and polyarteritis nodosa
• Neurological disease and neurodevelopmental disorders that compromise handling of respiratory secretions (cognitive dysfunction, spinal cord injury, seizure
disorders, neuromuscular disorders, cerebral palsy, metabolic disorders)
• Children younger than five years of age*
• Children or youth who reside in homes or other chronic care facilities
• Pregnant women and women up to two weeks postpartum regardless of how the pregnancy ended
• Individuals <18 years of age who are on chronic acetylsalicyclic acid therapy
• Obesity with a BMI ≥40 kg/m2, OR a BMI ≥3 z-scores above the mean for age and gender
• First Nations, Inuit and Métis children and youth
Adapted from references 15 and 16.
* Children who are two years through four years of age have a higher rate of complications compared with older children; however, the risk for these children is lower
than the risk for children younger than two years of age.
BMI: Body mass index
General principles:
• If the decision is made to start an antiviral drug,
treatment should be initiated as soon as possible
after onset of illness. The benefits of treatment are
much greater with initiation at <12 h than at 48 h.
(Strong recommendation, Grade B evidence)
• Otherwise healthy patients of any age with relative­
ly mild, self-limited influenza are not likely to benefit
from neuraminidase inhibitor (NAI) therapy initiated
>48 h after illness onset. Clinical judgment should
be used. (Option, Grade D evidence) However, an­
tiviral therapy should be initiated even if the interval
between illness onset and administration of antiviral
medication exceeds 48 h if:
2 | THE USE OF ANTIVIRAL DRUGS FOR INFLUENZA: GUIDANCE FOR PRACTITIONERS, 2012/2013; PAEDIATRIC SUMMARY
– The illness is severe enough to require hospital­
ization; (Strong recommendation, Grade X evi­
dence)
– The illness is progressive, severe or complicat­
ed, regardless of previous health status; (Strong
recommendation, Grade X evidence) or
– The individual belongs to a group, other than
age, at high risk for severe disease. (Strong rec­
ommendation, Grade X evidence)
• Parents of children for whom antiviral therapy is not
recommended should be advised of symptoms and
signs of worsening illness that might warrant re­
assessment. (Recommendation, Grade D evi­
dence)
• Treatment duration should routinely be five days
(Strong Recommendation, Grade A evidence), but
may be continued longer than five days if clinically
indicated. (Option, Grade D evidence) Intubated
patients with influenza illness should receive os­
eltamivir through a nasogastric tube. (Recommen­
dation, Grade C evidence)
• For patients unable to tolerate or receive oral os­
eltamivir, inhaled or intravenous zanamivir is a suit­
able option. However, children younger than seven
years of age are unlikely to be able to use the deliv­
ery device for zanamivir effectively. (Option, Grade
D evidence)
• Zanamivir may be preferred to oseltamivir in the fol­
lowing situations:
– Patients not responding to oseltamivir therapy
(Recommendation, Grade C evidence); or
– Patients with illness despite oseltamivir prophy­
laxis (Recommendation, Grade C evidence).
• For severely ill patients, zanamivir administered in­
travenously is preferred to inhaled drug. (Recom­
mendation, Grade D evidence)
• In ventilated patients, zanamivir should only be ad­
ministered intravenously. (Strong Recommenda­
tion, Grade X evidence)
• If patients are not responding to oseltamivir thera­
py, their virus should be tested for oseltamivir resis­
tance and the possibility of co-infection with anoth­
er pathogen considered. (Option, Grade D evi­
dence)
Treating infants, children and youth with mild or
uncomplicated influenza illness (Figure 1):
• For those with mild disease and no risk factors
other than age:
– Younger than one year of age: NAIs are current­
ly not approved for the routine treatment of sea­
sonal influenza illness. Given that infants
younger than six months of age are not eligible
for influenza vaccination, immunization of their
household and other close contacts is important
in protecting them against influenza, thereby po­
tentially leading to reduced need for antiviral
therapy. Influenza immunization of the pregnant
woman may also provide protection for her in­
fant during the first six months of life. (Option,
Grade D evidence)
– One to less than five years of age: Although
children under five years of age are classified
as ‘high risk’ (with those younger than two years
of age having the highest risk), those who are
otherwise healthy and have mild disease not re­
quiring hospitalization do not routinely require
antiviral therapy. For these children, treatment is
optional. (Option, Grade D evidence)
– Five or more years of age: Antiviral therapy is
not routinely recommended for children and
youth who are otherwise healthy and have mild
disease not requiring hospitalization. (Option,
Grade D evidence)
• For those with mild disease and risk factors other
than age:
– Younger than one year of age: NAIs are cur­
rently not approved for the routine treatment of
seasonal influenza illness.
– One or more years of age: For illness of ≤48 h
duration, treat with oseltamivir or, if age-appro­
priate, inhaled zanamivir. (Recommendation,
Grade B evidence)
– One or more years of age: For illness of >48 h
duration, treat with oseltamivir or, if age-appro­
priate, inhaled zanamivir may be considered on
a case-by-case basis. (Option, Grade D evi­
dence)
Note: Grade X evidence denotes situations where vali­
dating studies cannot be performed and there is a
clear preponderance of benefit or harm.
INFECTIOUS DISEASES AND IMMUNIZATION COMMITTEE, CANADIAN PAEDIATRIC SOCIETY |
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Treating infants, children and youth with moderate,
progressive, severe or complicated influenza ill­
ness with or without risk factors:
• Consider hospitalization and admission to the in­
tensive care unit. (Recommendation, Grade C evi­
dence)
• Start antivirals immediately. (Strong recommenda­
tion, Grade B evidence) Treat with oseltamivir or
zanamivir in appropriate doses. (Table 2)
• Oseltamivir or zanamivir should be started even
when the window between symptom onset and ini­
tial administration of the antiviral is >48 h. (Recom­
mendation, Grade C evidence)
• Treatment with zanamivir instead of oseltamivir
should be considered for:
– Patients not responding to oseltamivir therapy:
(Recommendation, Grade C evidence) or
– Patients with illness despite oseltamivir prophy­
laxis. (Recommendation, Grade C evidence)
• Although oseltamivir was approved temporarily for
use in infants younger than one year of age on the
basis of a favourable risk-to-benefit ratio during the
2009 H1N1 pandemic, its use in this population for
seasonal influenza should be handled on a caseby-case basis, based on severity of illness. (Option,
Grade D evidence)
4 | THE USE OF ANTIVIRAL DRUGS FOR INFLUENZA: GUIDANCE FOR PRACTITIONERS, 2012/2013; PAEDIATRIC SUMMARY
TABLE 2 Oseltamivir and zanamivir treatment of influenza in children and youth (<18 years of age) – October 2012
Medication
Treatment (five days)
Chemoprophylaxis (10 days)
75 mg twice daily
75 mg once daily
Oseltamivir*
Adults
Children ≥12 months
Body weight, kg
Body weight, lbs
≤15
≤33
30 mg twice daily
30 mg once daily
>15 to 23
>33 to 51
45 mg twice daily
45 mg once daily
>23 to 40
>51 to 88
60 mg twice daily
60 mg once daily
>40
>88
75 mg twice daily
75 mg once daily
Children 3 months to <12 months†
3 mg/kg/dose twice daily
3 mg/kg/dose once per day
Children <3 months‡
3 mg/kg/dose twice daily
Not recommended unless situation
judged critical due to limited data on
use in this age group
Zanamivir§
Adults
10 mg (two 5 mg inhalations) 10 mg (two 5 mg inhalations) once
twice daily
daily
Children (≥7 years)
10 mg (two 5 mg inhalations) 10 mg (two 5 mg inhalations) once
twice daily
daily
Treatment regimens adapted from reference 17. Please note that in Canada antivirals are not authorized for the routine treatment of seasonal influenza illness in babies
younger than one year of age. Such use may be considered on a case-by-case basis.*Oseltamivir is administered orally without regard to meals, although adminis­
tration with meals may improve gastrointestinal tolerability. Oseltamivir is available in 30 mg, 45 mg, and 75 mg capsules, and as a powder for oral suspension that is
reconstituted to provide a final concentration of either 6 mg/mL or 12 mg/mL. If the commercially manufactured oral suspension is not available, the capsules may be
opened and the contents mixed with a sweetened liquid to mask the bitter taste or a suspension can be compounded by retail pharmacies (final concentration 6 mg/
mL). When dispensing commercially manufactured oseltamivir (Tamiflu Powder for Oral Suspension [6 mg/mL or 12 mg/mL] Hoffman-La Roche Ltd, Canada), phar­
macists should ensure the units of measure on the prescription instructions match the dosing device; †Weight-based dosing is preferred. However, if weight is not
known, dosing by age for treatment of influenza (give two doses per day) or prophylaxis (give one dose per day) in full-term infants younger than one year of age may
be necessary: 0 to 3 months = 12 mg per dose for treatment (not for prophylaxis); 3 to 5 months = 20 mg per dose; 6 to 11 months = 25 mg per dose; ‡Current
weight-based dosing recommendations are not intended for premature infants. Premature infants may have slower clearance of oseltamivir due to immature renal
function, and doses recommended for full-term infants may lead to very high drug concentrations in this age group. Very limited data from a cohort of premature in­
fants demonstrated that oseltamivir concentrations among premature infants given 1 mg/kg body weight twice daily were similar to those observed with the recom­
mended treatment doses in term infants (3 mg/kg body weight twice daily). Observed drug concentrations were highly variable among premature infants. The Infec­
tious Diseases Society of America’s 2011 recommendations for paediatric pneumonia suggest 2 mg/kg/day divided twice daily. Currently available data are insuffi­
cient to recommend a specific dose of oseltamivir for premature infants; it is strongly suggested that an infectious disease physician or clinical pharmacist should be
consulted; §Zanamivir is administered by inhalation using a proprietary ‘Diskhaler’ device (Relenza, GlaxoSmithKline Inc, United Kingdom) distributed together with
the medication. Zanamivir is a dry powder, not an aerosol, and should not be administered using nebulizers, ventilators or other devices typically used for administer­
ing medications in aerosolized solutions. Zanamivir is not recommended for persons with chronic respiratory diseases, such as asthma or chronic obstructive pul­
monary disease, which increase the risk of bronchospasm.
INFECTIOUS DISEASES AND IMMUNIZATION COMMITTEE, CANADIAN PAEDIATRIC SOCIETY |
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CPS INFECTIOUS DISEASES AND IMMUNIZATION
COMMITTEE
Members: Robert Bortolussi MD (Past Chair); Natalie
A Bridger MD; Jane C Finlay MD; Susanna Martin MD
(Board Representative); Jane C McDonald MD;
Heather Onyett MD; Joan L Robinson MD (Chair)
Liaisons: Upton D Allen MD, Canadian Pediatric AIDS
Research Group; Michael Brady MD, Committee on Infectious Diseases, American Academy of Pediatrics;
Janet Dollin MD, College of Family Physicians of
Canada; Charles PS Hui MD, Committee to Advise on
Tropical Medicine and Travel, Public Health Agency of
Canada; Nicole Le Saux MD, IMPACT (Immunization
Monitoring Program, ACTive); Dorothy L Moore MD,
National Advisory Committee on Immunization (NACI);
John S Spika MD, Public Health Agency of Canada
Consultant: Noni E MacDonald MD
Principal author: Upton D Allen MD
Also available at www.cps.ca/en
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THE USE toOFreprint
ANTIVIRAL
DRUGS
FOR
INFLUENZA:
GUIDANCE
FOR PRACTITIONERS, 2012/2013; PAEDIATRIC SUMMARY
Disclaimer: The recommendations in this position statement do not indicate an
exclusive course of treatment or procedure to be followed. Variations, taking in­
to account individual circumstances, may be appropriate. Internet addresses
are current at time of publication.