The following guidance should be read in conjunction with relevant provincial and territorial guidance documents. The Public Health Agency of Canada will be posting regular updates and related documents at www.phac-aspc.gc.ca.
ntroduction
This guidance document has been prepared by the Public Health Agency of Canada to assist clinicians in the management of children under one year of age presenting with influenza-like-illness (ILI) in the context of the pandemic (H1N1) 2009 (pH1N1). This guidance has been updated based on current scientific evidence, expert opinion and the Interim Order, issued by the Federal Minister of Health, permitting the expanded use of oseltamivir for the influenza A H1N1 virus in children under 1 year of age.Although there are limited data regarding the use of Tamiflu® in children under one, there continues to be a need for recommendations to treat this population, given their increased risk for morbidity and mortality from influenza. Similar actions have also been taken internationally by the US FDA and the EMEA . This guidance is subject to review and change as new information becomes available. These guidelines should be used in conjunction with guidance contained in the Clinical recommendations for patients presenting with respiratory symptoms during the 2009-2010 influenza season, H1N1 PHAC Guidelines for health professionals, Annex E and Annex G of the Canadian Pandemic Influenza Plan. Influenza and children
Healthy children under 24 months and children with certain chronic health conditions are at increased risk of influenza-related complications and hospitalization from seasonal influenza6 . Recent Canadian epidemiological data for pH1N1 indicates higher rates of hospitalization and ICU admissions in children under 1 year of age compared with all pH1N1 cases in Canada. In children under the age of 2 years, greater than 90% have presented with fever when infected with pH1N1. Children may have higher fevers and may have febrile seizures. Atypical presentations are most common in infants, the elderly and immunocompromised persons. Unexplained fever may be the only manifestation of the disease in infants. In infants less than 2 months old, the condition can progress rapidly to severe illness. Younger children may experience nausea, vomiting, diarrhea and abdominal pain7 . Infants may also present with neurologic symptoms suggestive of meningitis or encephalitis, although the data for pH1N1 indicates these symptoms have occurred in < 5% of cases. ** Public Health Agency of Canada. Unpublished data.
CLINICAL MANAGEMENT of children under 1 year of age
Antivirals can reduce complications and mortality from influenza. Currently, the pH1N1 virus is susceptible to oseltamivir (Tamiflu®) and zanamivir (Relenza®), but resistant to amantadine. Relenza® is indicated only in children 7 years or older. The Interim Order issued by the Federal Minister of Health, pursuant to her authority under the Food and Drugs Act, permits the expanded use of oseltamivir as a treatment or prophylaxis for children under 1 year of age, for infection caused by the pH1N1 virus1. Adverse event data regarding use in children over 1 year of age is available in the Product Monograph8Clinical recommendations for the management of children under 1 year of age presenting with suspected, probable or confirmed pH1N1 infection, include early antiviral treatment (within 48 hours of symptom onset) and close follow-up, as they are at high risk for complications of influenza. When pH1N1 is known to be circulating in the community, clinicians should not wait for laboratory confirmation prior to initiating treatment. The parents or guardian should be informed that this is exceptional use. A recent review of the available clinical safety data indicates that there are no new safety signals for this age group and that the safety profile remains similar to that seen in children over one year of age. Currently available pharmacokinetic data supports updating Canadian recommendations for oseltamivir dosing. If oseltamivir is prescribed, the following dosing is recommended:
A) Treatment
| Age | Recommended Dose (weight-based), 1, 2 |
| 1 month to < 12 months | 3mg/kg/dose twice daily for 5 days |
| < 1 month | 2 mg/kg/dose twice daily for 5 days |
| 1 Not to exceed 30 mg twice daily, in accord with recommended dosing for patients > 1 year of age 2 Weight-based dosing is preferred, however, if weight is not known, dosing by age for full-term infants may be necessary as follows: 0-<3 months = 12 mg twice daily; 3-<6 months = 20 mg twice daily; 6 -<12 months = 25 mg twice daily | |
The Health Canada recommended dosing for infants under the age of 1 year is not intended for premature infants (those < 37 weeks gestational age at birth who have not reached their expected due date), and may result in high drug concentrations in this age group. Very limited data from a cohort of premature infants receiving a mean dose of 1.7 mg/kg BID demonstrated drug concentrations higher than those observed in term infants given a dose of 3 mg/kg BID. Insufficient data is available at this time to make specific recommendations for premature infants. It is recommended that clinicians consult with an infectious disease specialist and/or pharmacist when considering antiviral treatment of pre-term infants. In addition, an important consideration in the treatment of infants with lower body weight is the significant difference between weight-based dosing and age-based dosing; therefore it is important to get an accurate weight and use weight-based dosages as soon as possible.
Commercially manufactured Tamiflu for Oral Suspension should be used if available; if not, refer to the instructions found in “Emergency Compounding of an oral suspension from Tamiflu® capsules” on page 16 of the Tamiflu®
product monograph8 .Children under 1 year of age with influenza should be treated in hospital. If during the H1N1 pandemic demands on hospital resources become too great, hospitalization is still indicated in children less than 3 months, due to their increased risk of progressing rapidly to severe disease. Treatment should be started as soon as possible as the benefit wanes if treatment is initiated after 48 hours of the onset of symptoms.
B) Prophylaxis
At phase 6 of the pandemic, prophylactic use of antivirals is recommended only for outbreak control in closed health care settings or other closed facilities where high risk persons reside. If after a careful risk/benefit assessment this is thought to be clinically indicated for a particular patient, the following dosing with oseltamivir is recommended:
| Age | Recommended Dose (weight-based), 1, 2 |
| 3 month to < 12 months | 3mg/kg/dose twice daily for 10 days 3 |
| < 3 month | Not recommended at this time4 |
| 1 Not to exceed 30 mg once daily, in accord with recommended dosing for patients > 1 year of age 2 Weight-based dosing is preferred, however, if weight is not known, dosing by age for full-term infants may be necessary as follows: 3-<6 months = 20 mg once daily; 6-<12 months = 25 mg once daily 3 In children and the elderly, viral shedding may continue for up to 14 days after the onset of influenza illness. Therefore, if the index case is a child or an elderly person, prophylaxis with TAMIFLU may continue for up to 14 days. 4 Based on the available data, prevention of influenza in infants under 3 months of age is not recommended at this time unless there has been significant exposure and/or the risk of severe illness is considered to be high. | |
Adverse Reaction Reporting
Reports of adverse reactions to antiviral medications are important as this information will be used to guide their safe and effective use, particularly in certain populations where there may only be limited safety data available, for example pregnant women and children .
The Interim Order regarding the expanded use of Tamiflu® for children under one year of age applies to all strengths and formulations:
DIN#02304848, 30mg capsule
DIN#02304856, 45mg capsule
DIN#02241472, 75mg capsule
DIN#02245549, 12mg/ml (reconstituted) oral suspension
DIN#02304856, 45mg capsule
DIN#02241472, 75mg capsule
DIN#02245549, 12mg/ml (reconstituted) oral suspension
