The use of antiviral drugs for influenza: Guidance for practitioners, 2012/2013; Paediatric summary

Question 1

What antiviral agents are approved for use in Canada?

Answer 1

1. Amantadine for seasonal influenza A (resistance high)
2. Oseltamivir for influenza A and B
3. Zanamivir for influenza A and B

Question 2

What at-risk groups and comorbid medical conditions predispose children to severe influenza illness?

Answer 2

1. Asthma or other chronic pulmonary diseases, including bronchopulmonary dysplasia, cystic fibrosis, chronic bronchitis and emphysema
2. Cardiovascular disease (excluding isolated hypertension; including congenital and acquired heart disease, such as congestive heart failure and symptomatic coronary artery disease)
3. Malignancy
4. Chronic renal insufficiency
5. Chronic liver disease
6. Diabetes mellitus and other metabolic diseases
7. Hemoglobinopathies such as sickle cell disease
8. Immunosuppression or immunodeficiency due to disease (eg, HIV infection, especially if CD4 is <200×106/L), or iatrogenic, due to medication
9. 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
10. Neurological disease and neurodevelopmental disorders that compromise handling of respiratory secretions (cognitive dysfunction, spinal cord injury, seizure disorders, neuromuscular disorders, cerebral palsy, metabolic disorders)
11. Children younger than five years of age*
12. Children or youth who reside in homes or other chronic care facilities
13. Pregnant women and women up to two weeks postpartum regardless of how the pregnancy ended
14. Individuals <18 years of age who are on chronic acetylsalicyclic acid therapy
15. Obesity with a BMI ≥40 kg/m2, OR a BMI ≥3 z-scores above the mean for age and gender
16. First Nations, Inuit and Métis children and youth

Question 3

What are the general principles for treatment of influenza with antivirals?

Answer 3

1. 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.
2. Otherwise healthy patients of any age with relatively 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. However, antiviral therapy should be initiated even if the interval between illness onset and administration of antiviral medication exceeds 48 h if:
   a) The illness is severe enough to require hospitalization;
   b) The illness is progressive, severe or complicated, regardless of previous health status; or
   c) The individual belongs to a group, other than age, at high risk for severe disease.
3. Parents of children for whom antiviral therapy is not recommended should be advised of symptoms and signs of worsening illness that might warrant reassessment.
4. Treatment duration should routinely be five days, but may be continued longer than five days if clinically indicated. Intubated patients with influenza illness should receive oseltamivir through a nasogastric tube.
5. For patients unable to tolerate or receive oral oseltamivir, inhaled or intravenous zanamivir is a suitable option. However, children younger than seven years of age are unlikely to be able to use the delivery device for zanamivir effectively.
6. Zanamivir may be preferred to oseltamivir in the following situations:
   a) Patients not responding to oseltamivir therapy or
   b) Patients with illness despite oseltamivir prophylaxis.
7. For severely ill patients, zanamivir administered intravenously is preferred to inhaled drug.
8. In ventilated patients, zanamivir should only be administered intravenously.
9. If patients are not responding to oseltamivir therapy, their virus should be tested for oseltamivir resistance and the possibility of co-infection with another pathogen considered.

Question 4

What are the treatment recommendations for infants, children and youth with mild disease and no risk factors other than age?

Answer 4

1. <1yo: No NAI. No immunization if <6mo. Influenza vaccine for household and other close contacts and for pregnant women.
2. 1-5yo: No hospitalization. Treatment is optional
3. > 5yo: Antiviral therapy is not routinely recommended

Question 5

What are the treatment recommendations for infants, children and youth with mild disease and risk factors other than age?

Answer 5

1. <1yo: NAI are not approved
2. > 1yo: For illness <48h treat with oseltamivir or, if age-appropriate, inhaled zanamivir
3. > 1yo for illness >48h: treat w/ oseltamivir or, if age-appropriate, inhaled zanamivir maybe considered on a case-by-case basis

Question 6

What are the treatment recommendations for infants, children and youth with moderate, progressive, severe, or complicated influenza with or without risk factors other than age?

Answer 6

1. Consider hospitalization and admission to the intensive care unit.
2. Start antivirals immediately. Treat with oseltamivir or zanamivir in appropriate doses. (Table 2)
3. Oseltamivir or zanamivir should be started even when the window between symptom onset and initial administration of the antiviral is >48 h.
4. Treatment with zanamivir instead of oseltamivir should be considered for:
   a) Patients not responding to oseltamivir therapy or
   b) Patients with illness despite oseltamivir prophylaxis.
5. 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 case-by-case basis, based on severity of illness

Question 7

What is the recommended zanamivir dose?

Answer 7

Treatment: 10mg (5mg x 2) inhaled BID x 5d

Chemoprophylaxis: 10mg (5mg x 2) inhaled daily x 10d

Question 8

What is the recommended treatment oseltamivir dose for five day course?

Answer 8

Adult: 75mg PO BID

Children: >12mo:

a) <15kg 30mg PO BID
b) 15-23kg 45mg PO BID
c) 23-40kg 60mg PO BID
d) >40kg 75mg PO BID

3-12mo: 3mg/kg/dose PO BID

<3mo: 3mg/kg/dose BID

Question 9

What is the recommended chemoprophylaxis oseltamivir dose for ten day course?

Answer 9

Adult: 75mg PO daily

Children: >12mo:

a) <15kg 30mg PO daily
b) 15-23kg 45mg PO daily
c) 23-40kg 60mg PO daily
d) >40kg 75mg PO daily

3-12mo: 3mg/kg/dose PO daily

<3mo: Not recommended, use clinical judgment