Employee Protection >Antivirals for Pandemic Influenza
Last reviewed Aug 1, 2011
Overview
Recent Additions
NEW: H1N1 Lessons Learned
Articles from Weekly Briefing/Osterholm Briefing
Resources from Others
Background
Antiviral Resistance
Economics
Ethics
Guidelines
Usage
Overview
Antiviral medications are used mainly to treat influenza, lessening the impact of a flu virus after a person has been infected. Under certain circumstances, these drugs can also reduce transmission of the virus or even prevent infection.
Two groups of antiviral drugs help treat or prevent influenza:
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The adamantanes (amantadine and rimantadine)
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The neuraminidase inhibitors, oseltamivir (brand name Tamiflu, made by Roche Laboratories) and zanamivir (Relenza, by GlaxoSmithKline).
Of these, only osteltamivir and zanamivir have been shown effective against the H5N1 virus in laboratory testing and are therefore considered the major class to use during a pandemic. Also, viruses are considered less likely to develop a resistance to these two drugs compared with the others. For these reasons, they have become part of many countries' antiviral stockpile plans.
Both agents work by blocking the ability of the virus to multiply beyond the infected host cell. Oseltamivir is taken by mouth as a capsule or liquid. Zanamivir is administered via an inhaler.
These drugs are generally considered to be capable of reducing the length of both influenza A and B by 1 to 2 days if given within 2 days of the start of symptoms. (The deadly H5N1 avian flu is a type of influenza A, and seasonal influenza can be either A or B.) Limited anecdotal evidence suggests they may be effective if given beyond this time frame as well. They can also prevent influenza in 70% to 90% of patients.
During an influenza pandemic, a combination of vaccines and antivirals will likely be used.
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Recent Additions
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 2011 Jan 21;60(RR1):1-24 [Full text]
NACCHO. Public health use and distribution of antivirals: NACCHO think tank meeting report. Released Jan 28, 2011 (but dated Dec 2010) [Full text]
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H1N1 Lessons Learned
van Boven M, Donker T, van der Lubben M, et al. Transmission of novel influenza A(H1N1) in households with post-exposure antiviral prophylaxis. PLoS ONE 2010 Jul 7;5(7):e11442 [Full text]
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Articles from Weekly Briefing/Osterholm Briefing
Antiviral drugs and pandemic preparedness: What you need to know to make informed decisions
First in a 4-part series. This article demystifies the scientific aspects of antivirals and what the federal government is doing.
Adamantanes: What role will these antivirals have in a pandemic?
Sidebar to above article. These older drugs will not be the first line of defense in a pandemic, but the federal government has not ruled out a role for them.
Antiviral drugs and pandemic preparedness: How government plans to build and distribute stockpiles
Part 2 of 4-part series. States and the fed are stocking antivirals, but businesses that plan to use such drugs to prevent illness will have to rely largely on their own stockpiles.
Chicago's antiviral stockpile: How a major metro area plans to distribute drugs
Sidebar to above article. Chicago's allocation from the federal stockpile will be distributed to the public for treatment at triage centers.
Antiviral drugs and pandemic preparedness: How some companies formulated their antiviral policies
Part 3 of 4-part series. Three companies detail dramatically different policies on antivirals.
Poll: Antivirals not part of most business pandemic preparedness plans
Sidebar to above story that reports results of a poll of more than 100 businesspeople.
Antiviral drugs and pandemic preparedness: What should your company offer employees?
Last in a 4-part series. How do you make a choice on antivirals that you can live with and protect employees? A cross-section of experts explores the issues.
Antivirals and legal considerations: A look at 4 scenarios
Sidebar to above article. Steven Gravely, partner and head of the healthcare practice group of law firm Troutman Sanders, highlights the potential risk to businesses of certain stockpiling and distribution scenarios.
Antivirals: The 'next Cipro'? Push past pandemic fatigue and consider your alternatives
Commentary on 4-part antiviral series in which Editor-in-Chief Michael Osterholm explains that antivirals likely represent our best chance to make a real clinical difference in reducing the health impact of the next pandemic.
Antivirals: Key components of pandemic plans
All companies need to consider now the role that influenza antiviral drugs will play in their developing pandemic preparedness plans.
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Resources from Others
Background
Buchholz U, Altmann D, Sagebiel D, et al. Stockpiling of anti-influenza drugs in private households: a survey in Germany. Eurosurveillance Weekly 2007 Jan 25;12(1):E070125.4 [Full text]
Cooper B. Influenza pandemic scenario analysis report: could a pandemic be contained using antiviral agents? Eurosurveillance Weekly 2004 May 6;8(19) [Full text]
De Clercq E. Antiviral agents active against influenza A viruses. Nature Rev Drug Disc 2006 Dec;5(12):1015-25 [Abstract]
Duerr HP, Brockmann SO, Piechotowski I, et al. Influenza pandemic intervention planning using InfluSim: pharmaceutical and non-pharmaceutical interventions. BMC Infect Dis 2007;7:76 (published online Jul 13) [Full text - PDF]
FDA. FDA update on the H1N1 flu vaccine and antiviral medications. [PDF]
GAO (US Government Accountability Office). Influenza pandemic: efforts under way to address constraints on using antivirals and vaccines to forestall a pandemic. GAO-08-92. Released Jan 22, 2008 (but dated Dec 21, 2007) [Full text - PDF]
GAO (US Government Accountability Office). Influenza pandemic: HHS needs to continue its actions and finalize guidance for pharmaceutical interventions. GAO-08-671. Sep 30, 2008 [Full text]
Garcia-Sastre A. Antiviral response in pandemic influenza viruses. Emerg Infec Dis 2006 Jan;12(1):44-7 [Full text]
Guralnik M, Rosenbloom RA, Petteruti MP, et al. Limitations of current prophylaxis against influenza virus infection. Am J Ther 2007 Sep-Oct;14(5):449-54 [Abstract]
Harrod ME, Emery S and DE Dwyer. Antivirals in the management of an influenza pandemic. MJA 2006 Nov 185 (10): (suppl) 58-61 [Full text]
Hota S, McGeer A. Antivirals and the control of influenza outbreaks. Clin Infect Dis 2007 Nov 15;45(10) (published online Oct 11) [Abstract]
Jones JC, Turpin EA, Bultmann H, et al. Inhibition of influenza virus infection by a novel antiviral peptide that targets viral attachment to cells. J Virol 2006 Dec;80(24):11960-7 [Abstract]
Khazeni N, Bravata DM, Holty JEC, et al. Safety and efficacy of extended-duration antiviral chemoprophylaxis against pandemic and seasonal influenza. Ann Intern Med 2009 Oct 6 (published online Aug 4) [Full text]
Longini IM Jr, Halloran ME, Nizam A, et al. Containing pandemic influenza with antiviral agents. Am J Epidemiol 2004 Apr 1;159(7):623-33 [Abstract]
Maurer-Stroh S, Ma J, Lee RTC, et al. Mapping the sequence mutations of the 2009 H1N1 influenza A virus neuraminidase relative to drug and antibody binding sites. Biology Direct 2009 May 20;4:18 [Abstract]
Monto AS. Vaccines and antiviral drugs in pandemic preparedness. Emerg Infec Dis 2006 Jan;12(1):55-60 [Full text]
NACCHO. Public health use and distribution of antivirals: NACCHO think tank meeting report. Released Jan 28, 2011 (but dated Dec 2010) [Full text]
Ortiz JR, Kamimoto L, Aubert RE, et al. Oseltamivir prescribing in pharmacy-benefits database, United States, 2004-2005. Emerg Infect Dis 2008 Aug (published online Jul 23) [Full text - PDF]
Russell RJ, Haire LF, Stevens DJ, et al. The structure of H5N1 avian influenza neuraminidase suggests new opportunities for drug design. Nature 2006 Sep 7;443(7107):45-9 [Abstract]
Shi D, Yang J, Yang D, et al. Anti-influenza viral prodrug oseltamivir is activated by carboxylesterase HCE1 and the activation is inhibited by anti-platelet agent clopidogrel. J Pharmacol Exp Ther 2006 (published online Sep 11) [Abstract]
Singer AC, Nunn MA, Gould EA, et al. Potential risks associated with the proposed widespread use of Tamiflu. Environ Health Perspect 2006 (published online Oct 11) [Links to abstract and full text]
Sugrue RJ, Tan BH, Yeo DSY, et al. Antiviral drugs for the control of pandemic influenza virus. Ann Acad Med Singapore 2008 Jun;37(6):518-24 [Full text - PDF]
Swaminathan A, Martin R, Gamon S, et al. Personal protective equipment and antiviral drug use during hospitalization for suspected avian or pandemic influenza. Emerg Infect Dis 2007 Oct;13(10) (published online Sep 5) [Full text]
Tambyah PA. Update on influenza antivirals. Respirology 2008 Mar;13(s1):S19-21 [Full text]
Trust for America's Health. Pandemic flu: lessons from the frontlines. Jun 4, 2009 [Links to press release and full report]
WHO. Antiviral drugs: their role during a pandemic Nov 2005 [Webpage]
WHO. Use of antiviral drugs against influenza A(H1N1). May 5, 2009 [Full text]
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Antiviral Resistance
Arino J, Bowman CS, Moghadas SM. Antiviral resistance during pandemic influenza: implications for stockpiling and drug use. BMC Infect Dis 2009 Jan 22;9:8 [Abstract]
CDC. Oseltamivir-resistant 2009 pandemic influenza A (H1N1) virus infection in two summer campers receiving prophylaxis--North Carolina, 2009. MMWR 2009 Sep 11;58(35):969-72 [Full text]
CDC. Update: drug susceptibility of swine-origin influenza A (H1N1) viruses, April 2009. MMWR 2009 Apr 28;58(Dispatch):1-3 [Full text]
Cheung C-L, Rayner JM, Smith GJD, et al. Distribution of amantadine-resistant H5N1 avian influenza variants in Asia. J Infect Dis Jun 15 2006;193(12) [Abstract]
Dharan NJ, Gubareva LV, Meyer JJ, et al. Infections with oseltamivir-resistant influenza A(H1N1) virus in the United States. JAMA 2009;301(10) (published online Mar 2) [Full text]
De Jong MD, Thanh TT, Khank TH, et al. Oseltamivir resistance during treatment of influenza A (H5N1) infection. N Engl J Med 2005 Dec 22;353(24):2667-72 [Full text]
Ilyushina NA, Govorkova EA, Russell CJ, et al. Contribution of H7 haemagglutinin to amantadine resistance and infectivity of influenza virus. J Gen Virol 2007 Apr;88(4):1266-74 [Abstract]
Mandelboim M, Hindyieh M, Segman-Meningher T, et al. Possible transmission of pandemic (HIN1) 2009 virus with oseltamivir resistance. (Letter) Emerg Infect Dis 2010 May (published online Mar 26) [Full text]
McKimm-Breschkin JL, Selleck PW, Usman TB, et al. Reduced sensitivity of influenza A (H5N1) to oseltamivir. Emerg Infect Dis 2007 Sep;13(9) [Full text]
McKimm-Breschkin J, Trivedi T, et al. Neuraminidase sequence analysis and susceptibilities of influenza virus clinical isolates to zanamivir and oseltamivir. Antimicrob Agents Chemother. 2003 Jul;47(7):2264-72 [Full text]
Meijer A, Lackenby A, Hungnes O, et al. Oseltamivir-resistant influenza A (H1N1) virus, Europe, 2007-08 season. Emerg Infect Dis 2009 Apr (published online Feb 26) [Full text]
Mishin VP, Hayden FG, Gubareva LV. Susceptibilities of antiviral-resistant influenza viruses to novel neuraminidase inhibitors. Antimicrob Agents Chemother 2005 Nov;49(11):4515-20 [Abstract]
Moscona A. Oseltamivir resistance: disabling our influenza defenses. (Perspective) N Engl J Med 2005 Dec 22;353(24):2633-6 [Full text]
Pachucki CT, Khurshid MA, Nawrocki J. Utility of reverse transcriptase PCR for rapid diagnosis of influenza a virus infection and detection of amantadine-resistant influenza a virus isolates. J Clin Microbiol. 2004 Jun;42(6):2796-8 [Full text]
Rameix-Welti MA, Agou F, Buchy P, et al. Natural variation can significantly alter the sensitivity of influenza A (H5N1) viruses to oseltamivir. Antimicrob Agents Chemother 2006 Nov;50(11):3809-15 [Abstract]
Reece PA. Neuraminidase inhibitor resistance in influenza viruses. J Med Virol 2007 Aug 17;79(10):1577-86 [Abstract]
Tumpey TM, Garcia-Sastre A, Mikulasova A, et al. Existing antivirals are effective against influenza viruses with genes from the 1918 pandemic virus. Proc Natl Acad Sci 2002 Oct 15;99(21):13849-54 [Abstract]
van der Vries E, Stelma FF, Boucher CAB. Emergence of a multidrug-resistant pandemic influenza A (H1N1) virus. (Letter) N Engl J Med 2010 Sep 30;363:1381-2 [Full text]
Wetherall NT, Trivedi T, Zeller J, et al. Evaluation of neuraminidase enzyme assays using different substrates to measure susceptibility of influenza virus clinical isolates to neuraminidase inhibitors: report of the neuraminidase inhibitor susceptibility network. J Clin Microbiol 2003 Feb;41(2): [Full text]
WHO. Antiviral use and the risk of drug resistance: pandemic (H1N1) 2009 briefing note 12. Sep 25, 2009 [Full text]
WHO. WHO/ECDC frequently asked questions for oseltamivir resistance. Epidemic and Pandemic Alert Response (EPR). Feb 15, 2008 [Full text]
Wu JT, Leung GM, Lipsitch M, et al. Hedging against antiviral resistance during the next influenza pandemic using small stockpiles of an alternative chemotherapy. PLoS Med 2009 May 19;6(5):e1000085 [Full text]
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Economics
CDC. Increased antiviral medication sales before the 2005-06 influenza season: New York City. MMWR 2006 Mar 17;55(10):277-9 [Full text]
Lee VJ, Phua KJ, Chen MI, et al. Economics of neuraminidase inhibitor stockpiling for pandemic influenza, Singapore. Emerg Infect Dis 2006 Jan;12(1) [Full text]
Li Y, Hsu EB, Links JM. Healthcare system cost evaluation of antiviral stockpiling for pandemic influenza preparedness . Biosecurity and Bioterrorism: Biodefense Strategy, Practice, and Science. June 2010, 8(2): 119-128. [Full text - PDF]
Siddiqui MR, Edmunds WJ. Cost-effectiveness of antiviral stockpiling and near-patient testing for potential influenza pandemic. Emerg Infect Dis 2008 Feb;14(2):267-75 [Full text]
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Ethics
Brett AS, Zuger A. The run on Tamiflu: should physicians prescribe on demand? (Perspective) N Engl J Med 2005 Dec 22;353(24):2636-7 [Full text]
CDC. Increased antiviral medication sales before the 2005-06 influenza season: New York City. MMWR 2006 Mar 17;55(10):277-9 [Full text]
WHO. Equitable access to therapeutic and prophylactic measures. Project on addressing ethical issues in pandemic influenza planning, working group one. Oct 20, 2006 [Full text - PDF]
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Guidelines
CDC. Antiviral drugs for the 2009-2010 influenza season. Oct 19, 2009 [Podcast]
CDC. Interim guidance on antiviral recommendations for patients with confirmed or suspected swine influenza A (H1N1) virus infection and close contacts. Dec 7, 2009 [Full text]
CDC. Questions & answers: Antiviral drugs, 2009-2010 flu season. Nov 17, 2009 [Full text]
CDC. Updated interim recommendations for the use of antiviral medications in the treatment and prevention of influenza for the 2009-2010 season. Dec 7, 2009 [Full text]
DOD. Pandemic influenza: clinical and public health guidelines for the military health system. May 17, 2007 [Full text - PDF]
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 2011 Jan 21;60(RR1):1-24 [Full text]
FDA. Dear Health Care Professionals: 2009 H1N1 flu virus. (Letter) (published online May 7) [Full text]
FDA. Stockpiled antivirals at or nearing expiration. News and Events. Oct 14, 2009. [Web page]
HHS. Considerations for antiviral drug stockpiling by employers in preparation for an influenza pandemic. Dec 15, 2008 [Full text]
HHS. Guidance on antiviral drug use during an influenza pandemic. Dec 15, 2008 [Full text]
IOM (Institute of Medicine). Antivirals for pandemic influenza: guidance on developing a distribution and dispensing program. Released Apr 25, 2008 [Link to full text]
WHO. Advice on use of oseltamivir. Mar 17, 2006 [Full text]
WHO. Clinical management of human infection with avian influenza A (H5N1) virus. Aug 15, 2007 [Full text]
WHO. Interim protocol: rapid operations to contain the initial emergence of pandemic influenza. May 2007 [Full text]
WHO. Pandemic (H1N1) 2009 briefing note 8. Recommended use of antivirals. Aug 21 [Full text]
WHO. Summary of the second WHO consultation on clinical aspects of human infection with avian influenza A(H5N1) virus, 19-21 March, 2007, Antalya, Turkey. Released Apr 19, 2007 [Full text]
WHO. WHO rapid advice guidelines on pharmacological management of humans infected with avian influenza A (H5N1) virus. May 2006 [Summary with link to full text]
Writing Committee of the Second World Health Organization Consultation on Clinical Aspects of Human Infection with Avian Influenza A (H5N1) Virus. Update on avian influenza A (H5N1) virus infection in humans. N Engl J Med 2008 Jan 17;358(3) [Full text]
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Usage
Apisarnthanarak A, Mundy LM. Antiviral therapy for avian influenza virus (H5N1) infection at 2 Thai medical centers: survey findings and implications for pandemic preparedness. Infect Control Hosp Epidemiol 2008;29 (published online Oct 30) [Abstract]
CDC. Antiviral safety information. Dec 24, 2009 (updated regularly) [Full text]
CDC. Questions & answers: Antiviral drugs, 2009-2010 flu season. Nov 17, 2009 [Full text]
Couch RB, Davis BR. Has oseltamivir been shown to be effective for treatment of H5N1 influenza? (Editorial) J Infect Dis 2010 (published online Sep 10) [Abstract]
Democratis J, Pareek M, Stephenson I. Use of neuraminidase inhibitors to combat pandemic influenza. J Antimicrob Chemother 2006 (published online Sep 6) [Abstract]
Gani R, Hughes H, Fleming D, et al. Potential impact of antiviral use on hospitalizations during influenza pandemic. Emerg Infect Dis 2005 Sep;11(9) [Full text]
Govorkova EA, Ilyushina NA, Boltz DA, et al. Efficacy of oseltamivir therapy in ferrets inoculated with different clades of H5N1 influenza virus. Antimicrob Agents Chemother 2007 Apr;51(4);1414-24 [Abstract]
Hanshaoworakul W, Simmerman JM, Narueponjirakul U, et al. Severe human influenza infections in Thailand: oseltamivir treatment and risk factors for fatal outcome. PLoS ONE 2009 Jun 25;4(6):e6051 [Full text]
Hayden FG, Pavia AT. Antiviral management of seasonal and pandemic influenza. J Infect Dis 2006 Nov 1;194(suppl 2):S119-26 [Abstract]
HHS. Proposed considerations for antiviral drug stockpiling by employers in preparation for an influenza pandemic. May 28, 2008 [Full text]
Jefferson T, Demicheli V, Rivetti D, et al. Antivirals for influenza in healthy adults: systematic review. Lancet 2006 Jan 28;367(9507):303-13 [Abstract]
Khazeni N, Bravata DM, Holty JEC, et al. Safety and efficacy of extended-duration antiviral chemoprophylaxis against pandemic and seasonal influenza. Ann Intern Med 2009 Oct 6 (published online Aug 4) [Full text]
Lee VJ, Yap J, Cook AR, et al. Oseltamivir ring prophylaxis for containment of 2009 H1N1 influenza outbreaks. N Engl J Med 2010 Jun 10;362(23):2166-74 [Full text]
Lee VJ, Chen MI. Effectiveness of neuraminidase inhibitors for preventing staff absenteeism during pandemic influenza. Emerg Infect Dis 2007 Mar;13(3) (published online Feb 5) [Full text]
Meijer A, Lackenby A, Hay A, et al. Influenza antiviral susceptibility monitoring activities in relation to national antiviral stockpiles in Europe during the winter 2006/2007 season. Eurosurveillance Monthly 2007 Apr;12(4) [Full text]
NICE (UK National Institute for Health and Clinical Excellence). Influenza (prophylaxis): amantadine, oseltamivir and zanamivir. Sep 24, 2008 [Full text of several guidance documents]
Ortiz JR, Shay DK, Liedtke LA, et al. A national survey of the Infectious Diseases Society of America Emerging Infections Network concerning neuraminidase inhibitor prescription practices and pandemic influenza preparations. Clin Infect Dis 2006 Aug 15;43(4):494-7 [Abstract]
Tanaka T, Nakajima K, Murashima A, et al. Safety of neuraminidase inhibitors against novel influenza A (H1N1) in pregnant and breastfeeding women. CMAJ 2009 Jul 15;181(1-2):55-8 (published online Jun 15) [Full text]
Tsiodras S, Mooney JD, Hatzakis A. Role of combination antiviral therapy in pandemic influenza and stockpiling implications. BMJ 2007 Feb 10;334(7588):293-4 [Abstract]
Ward P, Small I, Smith J, et al. Oseltamivir (Tamiflu) and its potential for use in the event of an influenza pandemic. J Antimicrob Chemother 2005 Feb;55(Suppl 1):i5-i21 [Abstract]
White NJ, Webster RG, Govorkova EA, et al. What is the optimal therapy for patients with H5N1 influenza? PLoS Med 2009 Jun 23;6(6):e1000091 [Full text]
WHO. Antiviral drugs: their role during a pandemic [Webpage]
Yen HL, Monto AS, Webster RG, et al. Virulence may determine the necessary duration and dosage of oseltamivir treatment for highly pathogenic A/Vietnam/1203/04 influenza virus in mice. J Infect Dis 2005 Aug 15;192(4) [Abstract]
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