National Guidelines for the Use of Antivirals for Control of Facility* Outbreaks Caused by Influenza A (H1N1), 2008-09 season

Preface

The following Public Health Agency of Canada (PHAC) guidelines are based on expert scientific advice from the Seasonal Influenza Antiviral Advisory Group (SIAAG). The SIAAG provides technical, scientific and public health expert advice to the Center for Immunization and Respiratory Infectious Diseases (CIRID) and the Influenza Section of the National Microbiology Laboratory (NML).

These guidelines are based on evolving knowledge and surveillance data for the 2008-09 influenza season that show a high rate of oseltamivir resistance (OsR) in A/H1N1 viruses and a continued high rate of amantadine resistance in A/H3N2 viruses (1). These guidelines provide recommendations for the prophylaxis of residents and staff in facilities in order to control outbreaks of laboratory-confirmed influenza caused by influenza A/H1. They do not supersede clinical judgment or provide guidance on the management of individual patient care. Product monographs (2-4) and other references should be consulted for detailed prescribing information. For National Interim Options for Clinicians Considering Influenza Antivirals in the Context of Changing Patterns of Resistance, 2008-09 season, please follow the link:
http://phac-aspc.gc.ca/influenza/vac_antiv/nitg_ldni-eng.php

These guidelines should supplement recommendations outlined in local or provincial policies. In the event of a facility outbreak of influenza-like illness (ILI), final recommendations for control are at the discretion of the local Medical Health Officer (MHO).

* Facility includes long-term care facilities, retirement homes, and any residential care facilities in which a number of children and adults are housed (e.g. facilities for severely handicapped children, prisons).

Guidelines for Antiviral Use

Characterization of influenza specimens detected during these outbreaks to the level of subtype (H1 or H3) for influenza A is essential in order to guide the selection of appropriate antiviral therapy. If laboratory capacity for subtyping is not available, virus specimens/isolates should be forwarded to a reference laboratory such as the NML. If H1 is detected, testing for antiviral resistance should be undertaken at the designated laboratory, either the provincial laboratory or the NML.

Ongoing community surveillance, for example sentinel site collection of nasopharyngeal (NP) swabs, ensures continuous community sampling for antiviral resistance. This provides epidemiological information to help interpret results from facility outbreaks.

As patterns of antiviral resistance evolve, public health partners should remain informed of local surveillance results and possible changes in recommendations, and should monitor facility ILI outbreaks more closely for the possible introduction or emergence of resistant influenza viruses. When lab results are not yet available, signals of possible OsR in a facility influenza outbreak include failure to control the outbreak promptly despite proper oseltamivir use (for example, within 48-72 hours) and/or predominance of influenza A/H1 virus circulating in the community. Identification of possible OsR influenza outbreak requires close monitoring and may warrant consideration of alternatives to oseltamivir (5).

1. In laboratory-confirmed influenza A or B outbreaks, where influenza antiviral prophylaxis and/or treatment are considered warranted, the recommended choice for prophylaxis/treatment is oseltamivir (6), unless influenza A/H1 has been confirmed. To date, outbreaks due to influenza A/H1N1 have been uncommon among facilities housing elderly persons in Canada.
2. When oseltamivir-resistance occurs in a facility outbreak, the selection of appropriate antivirals is based on the drug’s effectiveness (especially if influenza B is also circulating), side effect profile, ease of administration and risk of resistance, together with the age and underlying health of the residents.
3. Zanamivir is effective against influenza A (H1N1) (including current OsR viruses), A (H3N2) and influenza B. It may be used in persons ≥ 7 years of age but DISKHALER^® administration may be difficult in persons with poor muscle coordination, or cognitively impaired persons. A Canadian study has shown that nearly 80% of the residents of a long-term care facility had no difficulty complying with Zanamivir inhalations. Difficulty was associated with decreased functional and mental status (7). Use of zanamivir may be facilitated by nursing assistance. This may be feasible if a limited number of individuals require treatment/prophylaxis. Supervised zanamivir administration may be less feasible for large numbers requiring prophylaxis in which case amantadine is the preferred alternative.
   
   Zanamivir should be used with caution in patients with underlying asthma/chronic obstructive pulmonary disease (COPD) as there have been reports of bronchospasm in patients with severe asthma/COPD taking zanamivir (7). However, a few clinical trials have shown no difference in rates of bronchospasm when compared to placebo (8).
   
   When zanamivir is used for facility outbreak control, the opportunity for evaluation should be taken, given the limited experience with zanamivir in this context. Evaluation may include process (ease of administration, acceptability) and/or outcome (efficacy in outbreak control, serious outcomes and resistance).
4. Amantadine remains effective against influenza A (H1N1) but is no longer an option for influenza A (H3N2) due to high rates of amantadine resistance. Amantadine is not effective against influenza B. It may be used in persons ≥ 1 year of age but careful dosing requirements apply for elderly persons and those with renal dysfunction. Side effects, which include central nervous system (CNS) reactions such as agitation, confusion and hallucinations, could be experienced in up to 15% of patients. Those can be reduced with careful dose titration. Resistance to amantadine emerges readily within days of treatment onset. Amantadine prophylaxis is not effective in the household setting when it is also used to treat the index case. If institutionalized persons are treated with amantadine, they should be isolated from others for up to 2 days following completion of the treatment course (10).
5. In general, when influenza A/H1 has been laboratory-confirmed in one or many individual(s) in a facility setting:
   • In adults and children ≥7 years in Canada, zanamivir is recommended for use as prophylaxis or treatment, if administration can be well managed. If ease of administration is a concern, facilitated or supervised administration for treatment purposes should be considered. Exceptions include history of severe asthma/COPD (4). In the United States, zanamivir is also approved for prophylaxis in persons ≥ 5 years (9).
   • Amantadine is the only approved alternative for children 1-6 years of age. When amantadine is used for treatment, the case should be isolated from others until 2 days after treatment has ended (10).
   Table 1 outlines the recommended choices for particular settings if oseltamivir resistance is detected or suspected. Special considerations apply in prison settings.
   
   Table 1- Antiviral Guidelines for Facility Outbreaks caused by influenza A/H1
   
   

   SCENARIO I. Residential care settings housing elderly persons

   	Treatment	Prophylaxis	Rationale/Comments
   Elderly	Zanamivir	Zanamivir or Amantadine*	DISKHALER® administration of zanamivir may be difficult in persons with poor muscle coordination or cognitively disabled persons. Nurse-supervised zanamivir administration may be less feasible for large numbers of individuals requiring prophylaxis in which case amantadine may be preferable. *If amantadine is also used for treatment, cases should be isolated. In a mixed outbreak (H1 +H3/B), the MHO should be consulted if considering amantadine.
   Staff	Zanamivir	Zanamivir	Zanamivir should be used with caution in persons with underlying COPD/asthma

   
   

   SCENARIO II. Residential care settings housing children (e.g. Ronald McDonald House, group homes)

   	Treatment	Prophylaxis	Rationale/Comments
   Children 1-6 yrs of age	Amantadine#	Amantadine†	# Cases treated with amantadine should be isolated. † In the United States, zanamivir is approved for prophylaxis (but not treatment) for persons ≥5 years. In a mixed outbreak (H1 +H3/B), the MHO should be consulted if considering amantadine.
   Children ≥ 7 yrs of age	Zanamivir	Zanamivir or Amantadine*	DISKHALER® administration of zanamivir may be difficult in persons with poor muscle coordination or cognitively disabled persons.  Nurse-supervised zanamivir administration may be less feasible for large numbers of individuals requiring prophylaxis in which case amantadine may be preferable. *If amantadine is also used for treatment, cases should be isolated. In a mixed outbreak (H1 +H3/B), the MHO should be consulted if considering amantadine
   Staff	Zanamivir	Zanamivir	Zanamivir should be used with caution in persons with underlying COPD/asthma

   
   

   SCENARIO III. Residential care settings housing adults (e.g. prisons, transitional housing)

   	Treatment	Prophylaxis	Rationale/Comments
   Residents	Zanamivir	Zanamivir or Amantadine*	In prison settings, at the discretion of the Medical Director of the facility and in consultation with the MHO, issues related to DISKHALER® use should be balanced against amantadine side effects. In the event of OsR, zanamivir is recommended for treatment if manageable. *If amantadine is also used for treatment, cases should be isolated. In a mixed outbreak (H1 +H3/B), the MHO should be consulted if considering amantadine.
   Staff	Zanamivir	Zanamivir	Zanamivir should be used with caution in persons with underlying COPD/asthma

Acknowledgements:

These guidelines were adapted with permission from the document developed by the BC Centre for Disease Control entitled “Facility Influenza Outbreak Control – BC Guidelines for Antiviral Use in the Event of H1N1 Oseltamivir Resistance”.

The following current and past members of the Seasonal Influenza Antiviral Advisory Group (SIAAG) have contributed to the development of these guidelines: Upton Allen, Fred Aoki, Samina Aziz, Nathalie Bastien, Tim Booth, Michel Couillard, Shalini Desai, Gaston deSerres, Kathleen Dunn, Myrna Dyck, Travis Hottes, Naveed Janjua, Yan Li, Allison McGeer, Jennifer.McTaggart, Louise Pelletier, George Samuel, Shelly Sarwal, Claire Sevenhuysen, Tammy Simpson, Danuta Skowronski, Grant Stiver, Susan Tamblyn, Anne-Luise Winter.

References:

1. Public Health Agency of Canada. FluWatch weekly report. 2008-09 season [updated 2009 Mar 14, cited 2009 Mar 20]. Available from: http://www.phac-aspc.gc.ca/fluwatch/
2. Health Canada Drug Product Database. Amantadine product monograph, Pharmel. 2004 [updated 2009 Mar 04, cited 2009 Mar 20]. Available from: http://webprod.hc-sc.gc.ca/dpd-bdpp/index-eng.jsp
3. Health Canada Drug Product Database. Oseltamivir product monograph, Hoffman-La Roche. 2008 [updated 2009 Mar 04, cited 2009 Mar 20]. Available from: http://webprod.hc-sc.gc.ca/dpd-bdpp/index-eng.jsp
4. Health Canada Drug Product Database. Zanamivir product monograph, GlaxoSmithKline. 2008 [updated 2009 Mar 04, cited 2009 Mar 20]. Available from:
   http://webprod.hc-sc.gc.ca/dpd-bdpp/index-eng.jsp
5. Centers for Disease Control and Prevention. Interim Recommendations for the Use of Influenza Antiviral Medications in the Setting of Oseltamivir Resistance among Circulating Influenza A (H1N1) Viruses, 2008-09 Influenza Season. 2008 Dec 19 [cited 2009 Mar 20].  Available at: http://www.cdc.gov/flu/professionals/antivirals/index.htm
6. Statement on influenza vaccination for the 2008-2009 season. An Advisory Committee Statement (ACS). Can Commun Dis Rep 2008 Jul 15;34(ACS-3):1-46. Available at: http://www.phac-aspc.gc.ca/publicat/ccdr-rmtc/08pdf/acs-3.pdf
7. Lee C, Loeb M, Phillips A, Nesbitt J, Smith K, Fearon M, McArthur MA, Mazzulli T, Li Y, McGeer A. Zanamivir use during transmission of amantadine-resistant influenza A in a nursing home. Infect Control Hosp Epidemiol. 2000 Nov;21(11):700-4. Available at: http://www.journals.uchicago.edu/doi/pdf/10.1086/501727
8. Allen UD, Aoki F, Stiver HG et al. The use of antiviral drugs for influenza: Recommended guidelines for practitioners. Can J Infect Dis Med Microbiol 2006;17:273-79. Available at: http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=18382639
9. Prevention and Control of Influenza: Recommendations of the Advisory Committee on Immunization. MMWR Morb Mortal Wkly Rep. 2008 July 17;57:1-60. Available at: http://www.cdc.gov/mmwr/preview/mmwrhtml/rr57e717a1.htm
10. Statement on influenza vaccination for the 2005-2006 season. An Advisory Committee Statement (ACS). Can Commun Dis Rep 2006 Jun 15;31(ACS-6):1-32. Available at: http://www.phac-aspc.gc.ca/publicat/ccdr-rmtc/05pdf/acs-dcc3106.pdf