Re: Management of influenza with Tamiflu: Authors reply

We thank Dr Brown for his interest in our article, “Management of influenza infection in children and pregnant women in BC, an update.”[1] His comment raises important distinctions between the use of oseltamivir for severe influenza infection versus issues related to more permissive treatment and policies related to drug stockpiling. Dr Brown’s concerns about government stockpiling of oseltamivir are valid, and we agree that there is a great deal of controversy around these decisions.[2-4] Although several studies have reported that oseltamivir is cost effective for the treatment of influenza in most scenarios,[5-9] cost effectiveness and policy decisions regarding the stockpiling of oseltamivir are outside the scope of our article.

Our article provides practical local guidance for the diagnosis and treatment of influenza in children and pregnant women.[1] As described in the article, we agree that the absolute clinical benefit of oseltamivir for treatment of mild influenza infection in healthy outpatients with influenza is small, based on several randomized controlled trials.[10,11] Unfortunately, placebo-controlled, randomized treatment studies of severe influenza are not available and are unlikely to be performed. Nevertheless, a large number of well-conducted observational studies indicate that oseltamivir has substantial benefits for severe influenza, including improved survival.[12-15]

Our algorithm recommends testing or treating only those patients who are hospitalized for respiratory illness, who have risk factors for severe influenza disease, or both. These evidence-based recommendations are slightly more restrictive than—but otherwise consistent with—those of expert pediatric and infectious disease committees in North America (Canadian Paediatric Society, Association of Medical Microbiology and Infectious Disease Canada, American Academy of Pediatrics, Infectious Diseases Society of America, Centers for Disease Control and Prevention) as well as in the UK, Europe, and Australia.[9,16-19] We hope that more effective antivirals become available but, in the meantime, we continue to recommend oseltamivir for selected patients as the best available treatment for influenza.
—Ashley Roberts, MD, FRCPC
—Soren Gantt, MD, PhD, FRCPC
—Karen Ng, BScPharm, PharmD, BCPS
—Vanessa Paquette, BScPharm, PharmD
—Kristopher Kang, MD

References

1.    Ng K, Paquette V, Kang KT, et al. Management of influenza infection in children and pregnant women in BC, an update. BCMJ 2015;57:402-406.
2.    Cole A. Experts question wisdom of stockpiling oseltamivir. BMJ 2005;331:1041.
3.    Smith JR, Dutkowski R. Stockpiling oseltamivir: Roche clarifies data for improved mortality with oseltamivir. BMJ 2005;331:1203.
4.    Rouse A. Stockpiling oseltamivir: What is the number needed to treat with oseltamivir to prevent one flu death? BMJ 2005;331:1203.
5.    Lavelle TA, Uyeki TM, Prosser LA. Cost-effectiveness of oseltamivir treatment for children with uncomplicated seasonal influenza. J Pediatr 2012;160: 67-73.
6.    Talbird SE, Brogan AJ, Winiarski AP, et al. Cost-effectiveness of treating influenzalike illness with oseltamivir in the United States. Am J Health Syst Pharm 2009;66:469-480. 
7.    Postma MJ, Novak A, Scheilbeler HW, et al. Cost effectiveness of oseltamivir treatment for patients with influenza-like illness who are at increased risk for serious complications of influenza: Illustration for the Netherlands. Pharmacoeconomics 2007;25:497-501.
8.    Postma MJ, Beardsworth P, Wilschut JC. Cost effectiveness of oseltamivir treatment of influenza: A critique of published methods and outcomes. J Med Econ 2008;11:743-768. 
9.    National Institute for Health and Care Excellence. NICE technology appraisal guidance [TA168]: Amantadine, oseltamivir and zanamivir for the treatment of influenza. Accessed 8 December 2015. www.nice.org.uk/guidance/ta168.
10.    Wang K, Shun-Shin M, Gill P, et al. Neuraminidase inhibitors for preventing and treating influenza in children. Cochrane Database Syst Rev 2012;1:CD002744.
11.    Jefferson T, Jones M, Doshi P, et al. Oseltamivir for influenza in adults and children: Systematic review of clinical study reports and summary of regulatory comments. BMJ 2014;348:g2545.
12.    Farias JA, Fernández A, Monteverde E, et al. Critically ill infants and children with influenza A (H1N1) in pediatric intensive care units in Argentina. Intensive Care Med 2010;36:1015-1022.
13.    Centers for Disease Control and Prevention (CDC). Maternal and infant outcomes among severely ill pregnant and postpartum women with 2009 pandemic influenza A (H1N1)—United States, April 2009–August 2010. MMWR Morb Mortal Wkly Rep 2011;60:1193-1196.
14.    Biondi E, Krysan D. Treatment with oseltamivir decreases the length of hospital stay in critically ill children with influenza. J Pediatr 2012;160:528-529.
15.    Whitley RJ, Hayden FG, Reisinger KS, et al. Oral oseltamivir treatment of influenza in children. Pediatr Infect Dis J 2001;20:421.
16.    Allen UD, Canadian Paediatric Society, Infectious Diseases and Immunization Committee. The use of antiviral drugs for influenza: Guidance for practitioners, 2012/2013; Paediatric summary. Paediatr Child Health 2013;18:155-158.
17.    Harper SA, Bradley JS, Englund JA, et al. Seasonal influenza in adults and children—diagnosis, treatment, chemoprophylaxis, and institutional outbreak management: Clinical practice guidelines of the Infectious Diseases Society of America. Clin Infect Dis 2009;48:1003-1032.
18.    Fiore AE, Fry A, Shay D, et al. Antiviral agents for the treatment and chemoprophylaxis of influenza—recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2011;60:1-24.
19.    Australian Government, Department of Health. Influenza infection: CDNA national guidelines for public health units. Last modified 31 August 2011. www.health.gov.au/internet/main/publishing.nsf/Content/cdna-song-influenza.htm.