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. 2011 Nov 1;28(11):927–959. doi: 10.1007/s12325-011-0072-7

Oseltamivir in seasonal, pandemic, and avian influenza: a comprehensive review of 10-years clinical experience

James R Smith 1,✉, Craig R Rayner 2,3, Barbara Donner 1, Martina Wollenhaupt 1, Klaus Klumpp 4, Regina Dutkowski 4
PMCID: PMC7101998  PMID: 22057727

Abstract

Oseltamivir (Tamiflu®; F. Hoffmann-La Roche Ltd, Basel, Switzerland) is an orally administered antiviral for the treatment and prevention of influenza A and B infections that is registered in more than 100 countries worldwide. More than 83 million patients have been exposed to the product since its introduction. Oseltamivir is recommended by the World Health Organization (WHO) for use in the clinical management of pandemic and seasonal influenza of varying severity, and as the primary antiviral agent for treatment of avian H5N1 influenza infection in humans. This article is a nonsystematic review of the experience gained from the first 10 years of using oseltamivir for influenza infections since its launch in early 2000, emphasizing recent advances in our understanding of the product and its clinical utility in five main areas. The article reviews the pharmacokinetics of oseltamivir and its active metabolite, oseltamivir carboxylate, including information on special populations such as children and elderly adults, and the co-administration of oseltamivir with other agents. This is followed by a summary of data on the effectiveness of oseltamivir treatment and prophylaxis in patients with all types of influenza, including pandemic (H1N1) 2009 and avian H5N1 influenza. The implications of changes in susceptibility of circulating influenza viruses to oseltamivir and other antiviral agents are also described, as is the emergence of antiviral resistance during and after the 2009 pandemic. The fourth main section deals with the safety profile of oseltamivir in standard and special patient populations, and reviews spontaneously reported adverse event data from the pandemic and pre-pandemic periods and the topical issue of neuropsychiatric adverse events. Finally, the article considers the pharmacoeconomics of oseltamivir in comparison with vaccination and usual care regimens, and as a component of pandemic influenza mitigation strategies.

Keywords: avian, efficacy, influenza, oseltamivir, pandemic, pharmacoeconomics, pharmacokinetics, resistance, safety, seasonal

Footnotes

This article is published with open access at Springerlink.com

References

  • 1.Centers for Disease Control and Prevention (CDC). Key facts about influenza (flu) and flu vaccine. Revised 3 June 2010. Available at: http://www.cdc.gov/flu/keyfacts.htm. Last accessed September 2, 2010.
  • 2.Thompson W.W., Shay D.K., Weintraub E., et al. Mortality associated with influenza and respiratory syncytial virus in the United States. JAMA. 2003;289:179–186. doi: 10.1001/jama.289.2.179. [DOI] [PubMed] [Google Scholar]
  • 3.Thompson W.W., Shay D.K., Weintraub E., et al. Influenza-associated hospitalizations in the United States. JAMA. 2004;292:1333–1340. doi: 10.1001/jama.292.11.1333. [DOI] [PubMed] [Google Scholar]
  • 4.Writing Committee of the WHO Consultation on Clinical Aspects of Pandemic. Bautista E., Chotpitayasunondh T., et al. Clinical aspects of pandemic 2009 influenza A (H1N1) virus infection. N Engl J Med. 2010;362:1708–1719. doi: 10.1056/NEJMra1000449. [DOI] [PubMed] [Google Scholar]
  • 5.World Health Organization (WHO). Cumulative number of confirmed human cases of avian influenza A/(H5N1) reported to WHO: 19 November 2010. Available at: http://www.who.int/csr/disease/avian_influenza/country/cases_table_2010_11_19/en/index.html. Last accessed September 1, 2010.
  • 6.Tamiflu SmPC. Tamiflu Summary of Product Characteristics. 2011. Available at: http://www.medicines.org.uk/emc/. Last accessed September 2, 2010.
  • 7.Tamiflu PI. Tamiflu Prescribing Information. 2011. Available at: http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search. Search_Drug_Name. Last accessed September 2, 2010.
  • 8.Moscona A. Neuraminidase inhibitors for influenza. N Engl J Med. 2005;353:1363–1373. doi: 10.1056/NEJMra050740. [DOI] [PubMed] [Google Scholar]
  • 9.World Health Organization (WHO). WHO guidelines for pharmacological management of pandemic influenza A(H1N1) 2009 and other influenza viruses. Revised February 2010. Available at: http://www.who.int/csr/resources/publications/swineflu/h1n1_use_antivirals_20090820/en/index. html. Last accessed September 1, 2010. [PubMed]
  • 10.Health Protection Agency. Pharmacologicial treatment and prophylaxis of influenza. Version 1.7. Available at: http://www.hpa.org.uk/web/HPAwebFile/HPAweb_C/1287147812045. Last accessed January 12, 2011.
  • 11.World Health Organization (WHO). Clinical management of human infection with avian influenza A (H5N1) virus. 15 August 2007. Available at: http://www.who.int/csr/disease/avian_influenza/guidelines/ClinicalManagement07.pdf. Last accessed September 1, 2010.
  • 12.Adisasmito W., Chan P.K., Lee N., et al. Effectiveness of antiviral treatment in human influenza A(H5N1) infections: analysis of a Global Patient Registry. J Infect Dis. 2010;202:1154–1160. doi: 10.1086/656316. [DOI] [PubMed] [Google Scholar]
  • 13.He G., Massarella J., Ward P. Clinical pharmacokinetics of the prodrug oseltamivir and its active metabolite Ro 64-0802. Clin Pharmacokinet. 1999;37:471–484. doi: 10.2165/00003088-199937060-00003. [DOI] [PubMed] [Google Scholar]
  • 14.Roberts NA, Wiltshire HR, Mendel DB, Webster RG. Oseltamivir carboxylate is effective against all subtypes of influenza neuraminidase. ASM Biodefense Research Meeting. Baltimore, Maryland, USA. March 9–12, 2003. Abstract.
  • 15.World Health Organization Update on oseltamivir-resistant pandemic (H1N1) 2009 influenza virus: January 2010. Wkly Epidemiol Rec. 2010;85:37–48. [PubMed] [Google Scholar]
  • 16.Stoner T.D., Krauss S., DuBois R.M., et al. Antiviral susceptibility of avian and swine influenza virus of the N1 neuraminidase subtype. J Virol. 2010;84:9800–9809. doi: 10.1128/JVI.00296-10. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17.Kurowski M., Oo C., Wiltshire H., Barrett J. Oseltamivir distributes to influenza virus replication sites in the middle ear and sinuses. Clin Drug Invest. 2004;24:49–53. doi: 10.2165/00044011-200424010-00006. [DOI] [PubMed] [Google Scholar]
  • 18.Jhee S.S., Yen M., Ereshefsky L., et al. Low penetration of oseltamivir and its carboxylate into cerebrospinal fluid in healthy Japanese and Caucasian volunteers. Antimicrob Agents Chemother. 2008;52:3687–3693. doi: 10.1128/AAC.00327-08. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19.Abe M., Smith J., Urae A., et al. Pharmacokinetics of oseltamivir in young and very elderly subjects. Ann Pharmacother. 2006;40:1724–1730. doi: 10.1345/aph.1H174. [DOI] [PubMed] [Google Scholar]
  • 20.Schentag J.J., Hill G., Chu T., Rayner C.R. Similarity in pharmacokinetics of oseltamivir and oseltamivir carboxylate in Japanese and Caucasian subjects. J Clin Pharmacol. 2007;47:689–696. doi: 10.1177/0091270007299761. [DOI] [PubMed] [Google Scholar]
  • 21.Oo C., Barrett J., Hill G., et al. Pharmacokinetics and dosage recommendations for an oseltamivir oral suspension for the treatment of influenza in children. Paediatr Drugs. 2001;3:229–236. doi: 10.2165/00128072-200103030-00005. [DOI] [PubMed] [Google Scholar]
  • 22.Strolin Benedetti M., Whomsley R., Baltes E.L. Differences in absorption, distribution, metabolism and excretion of xenobiotics between the paediatric and adult populations. Expert Opin Drug Metab Toxicol. 2005;1:447–471. doi: 10.1517/17425255.1.3.447. [DOI] [PubMed] [Google Scholar]
  • 23.Vogt B.A., Davis I.D., Avner E.D. The kidney. In: Klaus M.H., Fanaroff A.A., editors. Care of the highrisk neonate. 5th Edition. Pennsylvania: Saunders; 2001. pp. 426–427. [Google Scholar]
  • 24.Acosta E.P., Kimberlin D.W. Determination of appropriate dosing of influenza drugs in pediatric patients. Clin Pharmacol Ther. 2010;88:704–707. doi: 10.1038/clpt.2010.173. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25.Acosta E.P., Jester P., Gal P., et al. Oseltamivir dosing for influenza infection in premature neonates. J Infect Dis. 2010;202:563–566. doi: 10.1086/654930. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 26.Worley K.C., Roberts S.W., Bawdon R.E. The metabolism and transplacental transfer of oseltamivir in the ex vivo human model. Infect Dis Obstet Gynecol. 2008;2008:927574. doi: 10.1155/2008/927574. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 27.Wentges-van H.N., van Eijkeren M., van der Laan J.W. Oseltamivir and breastfeeding. Int J Infect Dis. 2008;12:451. doi: 10.1016/j.ijid.2007.11.009. [DOI] [PubMed] [Google Scholar]
  • 28.Robson R., Buttimore A., Lynn K., Brewster M., Ward P. The pharmacokinetics and tolerability of oseltamivir suspension in patients on haemodialysis and continuous ambulatory peritoneal dialysis. Nephrol Dial Transplant. 2006;21:2556–2562. doi: 10.1093/ndt/gfl267. [DOI] [PubMed] [Google Scholar]
  • 29.Snell P., Dave N., Wilson K., et al. Lack of effect of moderate hepatic impairment on the pharmacokinetics of oral oseltamivir and its metabolite oseltamivir carboxylate. Br J Clin Pharmacol. 2005;59:598–601. doi: 10.1111/j.1365-2125.2005.02340.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 30.Morrison D., Roy S., Rayner C., et al. A randomized, crossover study to evaluate the pharmacokinetics of amantadine and oseltamivir administered alone and in combination. PLoS ONE. 2007;2:e1305. doi: 10.1371/journal.pone.0001305. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 31.Davies BE, Cirrincione-Dall G, Ballester-Sanchis RM, Navarro MT, Brennen B. Pharmacokinetics and safety of co-administered oseltamivir and rimantadine in healthy subjects: an open-label, multiple-dose, randomised, crossover study. XII International Symposium on Respiratory Viral Infections. Taipei, Taiwan. March 11–14, 2010. Abstract.
  • 32.Oo C., Barrett J., Dorr A., Liu B., Ward P. Lack of pharmacokinetic interaction between the oral anti-influenza prodrug oseltamivir and aspirin. Antimicrob Agents Chemother. 2002;46:1993–1995. doi: 10.1128/AAC.46.6.1993-1995.2002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 33.Snell P., Oo C., Dorr A., Barrett J. Lack of pharmacokinetic interaction between the oral anti-influenza neuraminidase inhibitor prodrug oseltamivir and antacids. Br J Clin Pharmacol. 2002;54:372–377. doi: 10.1046/j.1365-2125.2002.01678.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 34.Hill G., Cihlar T., Oo C., et al. The anti-influenza drug oseltamivir exhibits low potential to induce pharmacokinetic drug interactions via renal secretion-correlation of in vivo and in vitro studies. Drug Metab Dispos. 2002;30:13–19. doi: 10.1124/dmd.30.1.13. [DOI] [PubMed] [Google Scholar]
  • 35.Davies BE, Aceves Baldo P, Brewster M. Effect of oseltamivir on anticoagulation: a crossover study in patients stabilized on warfarin. 49th Interscience Conference on Antimicrobial Agents and Chemotherapy. San Francisco, CA. September 12–15, 2009. Abstract.
  • 36.Aoki F, Lam H, Jeffrey JR, Sitar DS. Oseltamivir does not interact pharmacokinetically with cyclosporine, mycophenolate or tacrolimus in renal transplant patients. Annual Meeting of the Infectious Disease Society of America. San Francisco, CA, USA. October 6–9, 2005. Abstract.
  • 37.Holodniy M., Penzak S.R., Straight T.M., et al. Pharmacokinetics and tolerability of oseltamivir combined with probenecid. Antimicrob Agents Chemother. 2008;52:3013–3021. doi: 10.1128/AAC.00047-08. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 38.Rayner C.R., Chanu P., Gieschke R., Boak L.M., Jonsson E.N. Population pharmacokinetics of oseltamivir when coadministered with probenecid. J Clin Pharmacol. 2008;48:935–947. doi: 10.1177/0091270008320317. [DOI] [PubMed] [Google Scholar]
  • 39.Treanor J.J., Hayden F.G., Vrooman P.S., et al. Efficacy and safety of the oral neuraminidase inhibitor oseltamivir in treating acute influenza: a randomized controlled trial. US Oral Neuraminidase Study Group. JAMA. 2000;283:1016–1024. doi: 10.1001/jama.283.8.1016. [DOI] [PubMed] [Google Scholar]
  • 40.Nicholson K.G., Aoki F.Y., Osterhaus A.D., et al. Efficacy and safety of oseltamivir in treatment of acute influenza: a randomised controlled trial. Neuraminidase Inhibitor Flu Treatment Investigator Group. Lancet. 2000;355:1845–1850. doi: 10.1016/S0140-6736(00)02288-1. [DOI] [PubMed] [Google Scholar]
  • 41.Kaiser L., Wat C., Mills T., et al. Impact of oseltamivir treatment on influenza-related lower respiratory tract complications and hospitalizations. Arch Intern Med. 2003;163:1667–1672. doi: 10.1001/archinte.163.14.1667. [DOI] [PubMed] [Google Scholar]
  • 42.Welliver R., Monto A.S., Carewicz O., et al. Effectiveness of oseltamivir in preventing influenza in household contacts: a randomized controlled trial. JAMA. 2001;285:748–754. doi: 10.1001/jama.285.6.748. [DOI] [PubMed] [Google Scholar]
  • 43.Hayden F.G., Belshe R., Villanueva C., et al. Management of influenza in households: a prospective, randomized comparison of oseltamivir treatment with or without postexposure prophylaxis. J Infect Dis. 2004;189:440–449. doi: 10.1086/381128. [DOI] [PubMed] [Google Scholar]
  • 44.Hayden F.G., Atmar R.L., Schilling M., et al. Use of the selective oral neuraminidase inhibitor oseltamivir to prevent influenza. N Engl J Med. 1999;341:1336–1343. doi: 10.1056/NEJM199910283411802. [DOI] [PubMed] [Google Scholar]
  • 45.Peters P.H., Jr., Gravenstein S., Norwood P., et al. Long-term use of oseltamivir for the prophylaxis of influenza in a vaccinated frail older population. J Am Geriatr Soc. 2001;49:1025–1031. doi: 10.1046/j.1532-5415.2001.49204.x. [DOI] [PubMed] [Google Scholar]
  • 46.Whitley R.J., Hayden F.G., Reisinger K.S., et al. Oral oseltamivir treatment of influenza in children. Pediatr Infect Dis J. 2001;20:127–133. doi: 10.1097/00006454-200102000-00002. [DOI] [PubMed] [Google Scholar]
  • 47.Winther B., Block S.L., Reisinger K., Dutkowski R. Impact of oseltamivir treatment on the incidence and course of acute otitis media in children with influenza. Int J Pediatr Otorhinolaryngol. 2010;74:684–688. doi: 10.1016/j.ijporl.2010.03.024. [DOI] [PubMed] [Google Scholar]
  • 48.Reisinger K, Marcadis I, Cupelli LA, Shu D. Oseltamivir for prevention of seasonal influenza in children. Options for the Control of Influenza VI. Toronto, Canada. June 17–23, 2007. Abstract.
  • 49.Sugaya N., Mitamura K., Yamazaki M., et al. Lower clinical effectiveness of oseltamivir against influenza B contrasted with influenza A infection in children. Clin Infect Dis. 2007;44:197–202. doi: 10.1086/509925. [DOI] [PubMed] [Google Scholar]
  • 50.Sugaya N., Tamura D., Yamazaki M., et al. Comparison of the clinical effectiveness of oseltamivir and zanamivir against influenza virus infection in children. Clin Infect Dis. 2008;47:339–345. doi: 10.1086/589748. [DOI] [PubMed] [Google Scholar]
  • 51.Barr C.E., Schulman K., Iacuzio D., Bradley J.S. Effect of oseltamivir on the risk of pneumonia and use of health care services in children with clinically diagnosed influenza. Curr Med Res Opin. 2007;23:523–531. doi: 10.1185/030079906X167499. [DOI] [PubMed] [Google Scholar]
  • 52.Piedra P.A., Schulman K.L., Blumentals W.A. Effects of oseltamivir on influenza-related complications in children with chronic medical conditions. Pediatrics. 2009;124:170–178. doi: 10.1542/peds.2008-0977. [DOI] [PubMed] [Google Scholar]
  • 53.Johnston S.L., Ferrero F., Garcia M.L., Dutkowski R. Oral oseltamivir improves pulmonary function and reduces exacerbation frequency for influenzainfected children with asthma. Pediatr Infect Dis J. 2005;24:225–232. doi: 10.1097/01.inf.0000154322.38267.ce. [DOI] [PubMed] [Google Scholar]
  • 54.Lin J.T., Yu X.Z., Cui D.J., et al. A multicentre, randomized, controlled trial of oseltamivir in the treatment of influenza in a high-risk Chinese population. Curr Med Res Opin. 2006;22:75–82. doi: 10.1185/030079906X80297. [DOI] [PubMed] [Google Scholar]
  • 55.Chemaly R.F., Ghosh S., Bodey G.P., et al. Respiratory viral infections in adults with hematologic malignancies and human stem cell transplantation recipients: a retrospective study at a major cancer center. Medicine (Baltimore) 2006;85:278–287. doi: 10.1097/01.md.0000232560.22098.4e. [DOI] [PubMed] [Google Scholar]
  • 56.Peters P.H., Moscona A., Schulman K.L., Barr C.E. Study of the impact of oseltamivir on the risk for pneumonia and other outcomes of influenza, 2000–2005. Medscape J Med. 2008;10:131. [PMC free article] [PubMed] [Google Scholar]
  • 57.McGeer A., Green K.A., Plevneshi A., et al. Antiviral therapy and outcomes of influenza requiring hospitalization in Ontario, Canada. Clin Infect Dis. 2007;45:1568–1575. doi: 10.1086/523584. [DOI] [PubMed] [Google Scholar]
  • 58.Lee N., Choi K.W., Chan P.K., et al. Outcomes of adults hospitalised with severe influenza. Thorax. 2010;65:510–515. doi: 10.1136/thx.2009.130799. [DOI] [PubMed] [Google Scholar]
  • 59.Dutkowski R. Oseltamivir in seasonal influenza: cumulative experience in low- and high-risk patients. J Antimicrob Chemother. 2010;65(Suppl.2):ii11–ii24. doi: 10.1093/jac/dkq012. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 60.Ward P., Small I., Smith J., Suter P., Dutkowski R. Oseltamivir (Tamiflu) and its potential for use in the event of an influenza pandemic. J Antimicrob Chemother. 2005;55(Suppl.1):i5–i21. doi: 10.1093/jac/dki018. [DOI] [PubMed] [Google Scholar]
  • 61.Matheson NJ, Harnden AR, Perera R, Sheikh A, Symmonds-Abrahams M. Neuraminidase inhibitors for preventing and treating influenza in children. Cochrane Database Syst Rev. 2007;CD002744. [DOI] [PubMed]
  • 62.Jefferson T., Jones M., Doshi P., Del Mar C. Neuraminidase inhibitors for preventing and treating influenza in healthy adults: systematic review and meta-analysis. BMJ. 2009;339:b5106. doi: 10.1136/bmj.b5106. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 63.Ruf B.R., Szucs T. Reducing the burden of influenzaassociated complications with antiviral therapy. Infection. 2009;37:186–196. doi: 10.1007/s15010-009-8241-1. [DOI] [PubMed] [Google Scholar]
  • 64.Hernan M.A., Lipsitch M. Oseltamivir and risk of lower respiratory tract complications in patients with flu symptoms: a meta-analysis of eleven randomized clinical trials. Clin Infect Dis. 2011;53:277–279. doi: 10.1093/cid/cir400. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 65.Aoki F.Y., Macleod M.D., Paggiaro P., et al. Early administration of oral oseltamivir increases the benefits of influenza treatment. J Antimicrob Chemother. 2003;51:123–129. doi: 10.1093/jac/dkg007. [DOI] [PubMed] [Google Scholar]
  • 66.Kawai N., Ikematsu H., Iwaki N., et al. A comparison of the effectiveness of oseltamivir for the treatment of influenza A and influenza B: a Japanese multicenter study of the 2003–2004 and 2004–2005 influenza seasons. Clin Infect Dis. 2006;43:439–444. doi: 10.1086/505868. [DOI] [PubMed] [Google Scholar]
  • 67.Heinonen S., Silvennoinen H., Lehtinen P., et al. Early oseltamivir treatment of influenza in children 1–3 years of age: a randomized controlled trial. Clin Infect Dis. 2010;51:887–894. doi: 10.1086/656408. [DOI] [PubMed] [Google Scholar]
  • 68.Writing Committee of the Second World Health Organization Consultationon Clinical Aspects of Human Infection with Avian Influenza A Update on avian influenza A (H5N1) virus infection in humans. N Engl J Med. 2008;358:261–273. doi: 10.1056/NEJMra0707279. [DOI] [PubMed] [Google Scholar]
  • 69.Gambotto A., Barratt-Boyes S.M., de Jong M.D., Neumann G., Kawaoka Y. Human infection with highly pathogenic H5N1 influenza virus. Lancet. 2008;371:1464–1475. doi: 10.1016/S0140-6736(08)60627-3. [DOI] [PubMed] [Google Scholar]
  • 70.Kandun I.N., Tresnaningsih E., Purba W.H., et al. Factors associated with case fatality of human H5N1 virus infections in Indonesia: a case series. Lancet. 2008;372:744–749. doi: 10.1016/S0140-6736(08)61125-3. [DOI] [PubMed] [Google Scholar]
  • 71.Liem N.T., Tung C.V., Hien N.D., et al. Clinical features of human influenza A (H5N1) infection in Vietnam: 2004–2006. Clin Infect Dis. 2009;48:1639–1646. doi: 10.1086/599031. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 72.Hien N.D., Ha N.H., Van N.T., et al. Human infection with highly pathogenic avian influenza virus (H5N1) in northern Vietnam, 2004–2005. Emerg Infect Dis. 2009;15:19–23. doi: 10.3201/eid1501.080073. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 73.Smith J.R. Oseltamivir in human avian influenza infection. J Antimicrob Chemother. 2010;65(Suppl.2):ii25–ii33. doi: 10.1093/jac/dkq013. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 74.World Health Organization (WHO). Pandemic (H1N1) 2009 — update 112. 6 August 2010. Available at: http://www.who.int/csr/don/2010_08_06/en/index.html. Last accessed September 1, 2010.
  • 75.Li I.W., Hung I.F., To K.K., et al. The natural viral load profile of patients with pandemic swine-origin influenza A H1N1 2009 (pH1N1) and the effect of oseltamivir treatment. Chest. 2010;137:759–768. doi: 10.1378/chest.09-3072. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 76.Cao B., Li X.W., Mao Y., et al. Clinical features of the initial cases of 2009 pandemic influenza A (H1N1) virus infection in China. N Engl J Med. 2009;361:2507–2517. doi: 10.1056/NEJMoa0906612. [DOI] [PubMed] [Google Scholar]
  • 77.Ling L.M., Chow A.L., Lye D.C., et al. Effects of early oseltamivir therapy on viral shedding in 2009 pandemic influenza A (H1N1) virus infection. Clin Infect Dis. 2010;50:963–969. doi: 10.1086/651083. [DOI] [PubMed] [Google Scholar]
  • 78.Hien T.T., Boni M.F., Bryant J.E., et al. Early pandemic influenza (2009 H1N1) in Ho Chi Minh City, Vietnam: a clinical virological and epidemiological analysis. PLoS Med. 2010;7:e1000277. doi: 10.1371/journal.pmed.1000277. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 79.Lee N., Chan P.K., Hui D.S., et al. Viral loads and duration of viral shedding in adult patients hospitalized with influenza. J Infect Dis. 2009;200:492–500. doi: 10.1086/600383. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 80.Jain S., Kamimoto L., Bramley A.M., et al. Hospitalized Patients with 2009 H1N1 Influenza in the United States, April–June 2009. N Engl J Med. 2009;361:1935–1944. doi: 10.1056/NEJMoa0906695. [DOI] [PubMed] [Google Scholar]
  • 81.Farias J.A., Fernandez 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. doi: 10.1007/s00134-010-1853-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 82.Dominguez-Cherit G., Lapinsky S.E., Macias A.E., et al. Critically ill patients with 2009 influenza A(H1N1) in Mexico. JAMA. 2009;302:1880–1887. doi: 10.1001/jama.2009.1536. [DOI] [PubMed] [Google Scholar]
  • 83.Chien Y.S., Su C.P., Tsai H.T., et al. Predictors and outcomes of respiratory failure among hospitalized pneumonia patients with 2009 H1N1 influenza in Taiwan. J Infect. 2010;60:168–174. doi: 10.1016/j.jinf.2009.12.012. [DOI] [PubMed] [Google Scholar]
  • 84.Centers for Disease ControlPrevention. Patients hospitalized with 2009 pandemic influenza A (H1N1) — New York City, May 2009. MMWR Morb Mortal Wkly Rep. 2010;58:1436–1440. [PubMed] [Google Scholar]
  • 85.Campbell C.N., Mytton O.T., McLean E.M., et al. Hospitalization in two waves of pandemic influenza A(H1N1) in England. Epidemiol Infect. 2011;139:1560–1569. doi: 10.1017/S0950268810002657. [DOI] [PubMed] [Google Scholar]
  • 86.Lee E.H., Wu C., Lee E.U., et al. Fatalities associated with the 2009 H1N1 influenza A virus in New York city. Clin Infect Dis. 2010;50:1498–1504. doi: 10.1086/652446. [DOI] [PubMed] [Google Scholar]
  • 87.Louie J.K., Acosta M., Jamieson D.J., Honein M.A. Severe 2009 H1N1 influenza in pregnant and postpartum women in California. N Engl J Med. 2010;362:27–35. doi: 10.1056/NEJMoa0910444. [DOI] [PubMed] [Google Scholar]
  • 88.Siston A.M., Rasmussen S.A., Honein M.A., et al. Pandemic 2009 influenza A(H1N1) virus illness among pregnant women in the United States. JAMA. 2010;303:1517–1525. doi: 10.1001/jama.2010.479. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 89.Creanga A.A., Johnson T.F., Graitcer S.B., et al. Severity of 2009 pandemic influenza A (H1N1) virus infection in pregnant women. Obstet Gynecol. 2010;115:717–726. doi: 10.1097/AOG.0b013e3181d57947. [DOI] [PubMed] [Google Scholar]
  • 90.Kumar D., Michaels M.G., Morris M.I., et al. Outcomes from pandemic influenza A H1N1 infection in recipients of solid-organ transplants: a multicentre cohort study. Lancet Infect Dis. 2010;10:521–526. doi: 10.1016/S1473-3099(10)70133-X. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 91.Louie J.K., Acosta M., Winter K., et al. Factors associated with death or hospitalization due to pandemic 2009 influenza A(H1N1) infection in California. JAMA. 2009;302:1896–1902. doi: 10.1001/jama.2009.1583. [DOI] [PubMed] [Google Scholar]
  • 92.Torres J.P., O’Ryan M., Herve B., et al. Impact of the novel influenza A (H1N1) during the 2009 autumn-winter season in a large hospital setting in Santiago, Chile. Clin Infect Dis. 2010;50:860–868. doi: 10.1086/650750. [DOI] [PubMed] [Google Scholar]
  • 93.Institut de Veille Sanitaire (InVS). Benefit of early antiviral therapy in reducing the severity and mortality of influenza A (H1N1) 2009: data obtained from serious infection monitoring [French]. Available at: http://www.invs.sante.fr/surveillance/grippe_dossier/docs_professionnels/antiviraux_grippe_a_h1n1_211209.pdf. Last accessed February 19, 2010.
  • 94.Zarychanski R., Stuart T.L., Kumar A., et al. Correlates of severe disease in patients with 2009 pandemic influenza (H1N1) virus infection. CMAJ. 2010;182:257–264. doi: 10.1503/cmaj.091884. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 95.Lee V.J., Yap J., Cook A.R., et al. Oseltamivir ring prophylaxis for containment of 2009 H1N1 influenza outbreaks. N Engl J Med. 2010;362:2166–2174. doi: 10.1056/NEJMoa0908482. [DOI] [PubMed] [Google Scholar]
  • 96.Komiya N., Gu Y., Kamiya H., et al. Household transmission of pandemic 2009 influenza a (H1N1) virus in Osaka, Japan in May 2009. J Infect. 2010;61:284–288. doi: 10.1016/j.jinf.2010.06.019. [DOI] [PubMed] [Google Scholar]
  • 97.Leung Y.H., Li M.P., Chuang S.K. A school outbreak of pandemic (H1N1) 2009 infection: assessment of secondary household transmission and the protective role of oseltamivir. Epidemiol Infect. 2011;139:41–44. doi: 10.1017/S0950268810001445. [DOI] [PubMed] [Google Scholar]
  • 98.Aoki F.Y., Boivin G., Roberts N. Influenza virus susceptibility and resistance to oseltamivir. Antivir Ther. 2007;12:603–616. [PubMed] [Google Scholar]
  • 99.Dharan N.J., Gubareva L.V., Meyer J.J., et al. Infections with oseltamivir-resistant influenza A(H1N1) virus in the United States. JAMA. 2009;301:1034–1041. doi: 10.1001/jama.2009.294. [DOI] [PubMed] [Google Scholar]
  • 100.Hauge S.H., Dudman S., Borgen K., Lackenby A., Hungnes O. Oseltamivir-resistant influenza viruses A (H1N1), Norway, 2007–08. Emerg Infect Dis. 2009;15:155–162. doi: 10.3201/eid1502.081031. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 101.Kiso M., Mitamura K., Sakai-Tagawa Y., et al. Resistant influenza A viruses in children treated with oseltamivir: descriptive study. Lancet. 2004;364:759–765. doi: 10.1016/S0140-6736(04)16934-1. [DOI] [PubMed] [Google Scholar]
  • 102.Stephenson I., Democratis J., Lackenby A., et al. Neuraminidase inhibitor resistance after oseltamivir treatment of acute influenza A and B in children. Clin Infect Dis. 2009;48:389–396. doi: 10.1086/596311. [DOI] [PubMed] [Google Scholar]
  • 103.Toovey S., Rayner C., Prinssen E., et al. Assessment of neuropsychiatric adverse events in influenza patients treated with oseltamivir: a comprehensive review. Drug Saf. 2008;31:1097–1114. doi: 10.2165/0002018-200831120-00006. [DOI] [PubMed] [Google Scholar]
  • 104.NISN. Monitoring of neuraminidase inhibitor resistance among clinical influenza virus isolates in Japan during the 2003–2006 influenza seasons. Wkly Epidemiol Rec. 2007;82:149–150. [PubMed] [Google Scholar]
  • 105.Monto A.S., McKimm-Breschkin J.L., Macken C., et al. Detection of influenza viruses resistant to neuraminidase inhibitors in global surveillance during the first 3 years of their use. Antimicrob Agents Chemother. 2006;50:2395–2402. doi: 10.1128/AAC.01339-05. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 106.Sheu T.G., Deyde V.M., Okomo-Adhiambo M., et al. Surveillance for neuraminidase inhibitor resistance among human influenza A and B viruses circulating worldwide from 2004 to 2008. Antimicrob Agents Chemother. 2008;52:3284–3292. doi: 10.1128/AAC.00555-08. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 107.Meijer A., Lackenby A., Hungnes O., et al. Oseltamivirresistant influenza virus A (H1N1), Europe, 2007–08 Season. Emerg Infect Dis. 2009;15:552–560. doi: 10.3201/eid1504.081280. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 108.Kramarz P., Monnet D., Nicoll A., Yilmaz C., Ciancio B. Use of oseltamivir in 12 European countries between 2002 and 2007 — lack of association with the appearance of oseltamivir-resistant influenza A(H1N1) viruses. Euro Surveill. 2009;14:pii19112. doi: 10.2807/ese.14.05.19112-en. [DOI] [PubMed] [Google Scholar]
  • 109.Goddard N., Zucs P., Ciancio B., et al. Start of the influenza season 2008–9 in Europe — increasing influenza activity moving from West to East dominated by A(H3N2) Euro Surveill. 2009;14(ii):19097. [PubMed] [Google Scholar]
  • 110.Centers for Disease ControlPrevention Update: influenza activity — United States, September 28, 2008–April 4, 2009, and composition of the 2009/10 influenza vaccine. MMWR Morb Mortal Wkly Rep. 2009;58:369–374. [PubMed] [Google Scholar]
  • 111.Rameix-Welti M.A., Enouf V., Cuvelier F., Jeannin P., van der Werf S. Enzymatic properties of the neuraminidase of seasonal H1N1 influenza viruses provide insights for the emergence of natural resistance to oseltamivir. PLoS Pathog. 2008;4:e1000103. doi: 10.1371/journal.ppat.1000103. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 112.Bloom J.D., Gong L.I., Baltimore D. Permissive secondary mutations enable the evolution of influenza oseltamivir resistance. Science. 2010;328:1272–1275. doi: 10.1126/science.1187816. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 113.Hurt A.C., Selleck P., Komadina N., et al. Susceptibility of highly pathogenic A (H5N1) avian influenza viruses to the neuraminidase inhibitors and adamantanes. Antiviral Res. 2007;73:228–231. doi: 10.1016/j.antiviral.2006.10.004. [DOI] [PubMed] [Google Scholar]
  • 114.Hill A.W., Guralnick R.P., Wilson M.J., Habib F., Janies D. Evolution of drug resistance in multiple distinct lineages of H5N1 avian influenza. Infect Genet Evol. 2009;9:169–178. doi: 10.1016/j.meegid.2008.10.006. [DOI] [PubMed] [Google Scholar]
  • 115.de Jong M.D., Tran T.T., Truong H.K., et al. Oseltamivir resistance during treatment of influenza A (H5N1) infection. N Engl J Med. 2005;353:2667–2672. doi: 10.1056/NEJMoa054512. [DOI] [PubMed] [Google Scholar]
  • 116.Le Q.M., Kiso M., Someya K., et al. Avian flu: isolation of drug-resistant H5N1 virus. Nature. 2005;437:1108. doi: 10.1038/4371108a. [DOI] [PubMed] [Google Scholar]
  • 117.Earhart K.C., Elsayed N.M., Saad M.D., et al. Oseltamivir resistance mutation N294S in human influenza A (H5N1) virus in Egypt. J Infect Public Health. 2009;2:74–80. doi: 10.1016/j.jiph.2009.04.004. [DOI] [PubMed] [Google Scholar]
  • 118.World Health Organization (WHO). Weekly virological update. 26 August 2010. Available at: http://www.who.int/csr/disease/swineflu/notes/briefing_20091202/en/index.html. Last accessed September 2, 2010.
  • 119.Garten R.J., Davis C.T., Russell C.A., et al. Antigenic and genetic characteristics of swine-origin 2009 A(H1N1) influenza viruses circulating in humans. Science. 2009;325:197–201. doi: 10.1126/science.1176225. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 120.World Health Organization (WHO). Update on oseltamivir resistance in influenza A(H1N1)2009 viruses. 10 August 2011. Available at: http://www.who.int/influenza/surveillance_monitoring/updates/2011_08_12_weekly_web_update_oseltamivir_resistance.pdf. Last accessed January 12, 2011.
  • 121.Hayden F.G. Antiviral resistance in influenza viruses: clinical and epidemiological aspects. In: Mayers D.L., editor. Antimicrobial Drug Resistance. New York: Humana Press; 2009. pp. 1011–1034. [Google Scholar]
  • 122.Harvala H., Gunson R., Simmonds P., et al. The emergence of oseltamivir-resistant pandemic influenza A(H1N1) 2009 virus amongst hospitalised immunocompromised patients in Scotland, November–December, 2009. Euro Surveill. 2010;15:pii19536. [PubMed] [Google Scholar]
  • 123.Tramontana A.R., George B., Hurt A.C., et al. Oseltamivir resistance in adult oncology and hematology patients infected with pandemic (H1N1) 2009 virus, Australia. Emerg Infect Dis. 2010;16:1068–1075. doi: 10.3201/eid1607.091691. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 124.Rousset D, Le Goff J, Abou-Jaoude G. Emergence of successive mutations in the neuraminidase of the pandemic H1N1 virus respectively associated with oseltamivir resistance and reduced susceptibility to both oseltamivir and zanamivir under treatment with neuraminidase inhibitors. Options for the Control of Influenza. Hong Kong. September 3–7, 2010. Abstract.
  • 125.van der Vries E., Stelma F.F., Boucher C.A. Emergence of a multidrug-resistant pandemic influenza A (H1N1) virus. N Engl J Med. 2010;363:1381–1382. doi: 10.1056/NEJMc1003749. [DOI] [PubMed] [Google Scholar]
  • 126.World Health Organization. Weekly update on oseltamivir resistance to influenza A (H1N1) 2009 viruses. Available at: http://www.who.int/csr/disease/swineflu/oseltamivirresistant20100820.pdf. Last accessed September 1, 2010.
  • 127.Baz M., Abed Y., Papenburg J., et al. Emergence of oseltamivir-resistant pandemic H1N1 virus during prophylaxis. N Engl J Med. 2009;361:2296–2297. doi: 10.1056/NEJMc0910060. [DOI] [PubMed] [Google Scholar]
  • 128.Centers for Disease ControlPrevention. Oseltamivir-resistant 2009 pandemic influenza A (H1N1) virus infection in two summer campers receiving prophylaxis — North Carolina, 2009. MMWR Morb Mortal Wkly Rep. 2009;58:969–972. [PubMed] [Google Scholar]
  • 129.World Health Organization Oseltamivirresistant pandemic (H1N1) 2009 influenza virus, October 2009. Wkly Epidemiol Rec. 2009;84:453–459. [Google Scholar]
  • 130.Hamelin M.E., Baz M., Abed Y., et al. Oseltamivirresistant pandemic A/H1N1 virus is as virulent as its wild-type counterpart in mice and ferrets. PLoS Pathog. 2010;6:e1001015. doi: 10.1371/journal.ppat.1001015. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 131.Duan S., Boltz D.A., Seiler P., et al. Oseltamivirresistant pandemic H1N1/2009 influenza virus possesses lower transmissibility and fitness in ferrets. PLoS Pathog. 2010;6:e1001022. doi: 10.1371/journal.ppat.1001022. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 132.Kiso M., Shinya K., Shimojima M., et al. Characterization of oseltamivir-resistant 2009 H1N1 pandemic influenza A viruses. PLoS Pathog. 2010;6:e1001079. doi: 10.1371/journal.ppat.1001079. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 133.Smith E.V., Pynn M.C., Blackford S., Leopold D.J. Stevens-Johnson syndrome secondary to oseltamivir (Tamiflu) Br J Gen Pract. 2010;60:133–134. doi: 10.3399/bjgp10X483292. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 134.Wells Q., Hardin B., Raj S.R., Darbar D. Sotalolinduced torsades de pointes precipitated during treatment with oseltamivir for H1N1 influenza. Heart Rhythm. 2010;7:1454–1457. doi: 10.1016/j.hrthm.2010.07.025. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 135.Karplus R., Sanset S., Zaidenstein R., Schneider D., Berkovitch M. Suspected oseltamivir-induced bradycardia. Int J Infect Dis. 2010;14(Suppl.3):e374–e375. doi: 10.1016/j.ijid.2010.03.009. [DOI] [PubMed] [Google Scholar]
  • 136.Casscells S.W., Granger E., Kress A.M., Linton A., Madjid M. Use of oseltamivir after influenza infection is associated with reduced incidence of recurrent adverse cardiovascular outcomes among military health system beneficiaries with prior cardiovascular disease. Circulation. 2009;2:108–115. doi: 10.1161/CIRCOUTCOMES.108.820357. [DOI] [PubMed] [Google Scholar]
  • 137.Madjid M., Curkendall S., Blumentals W.A. The influence of oseltamivir on the risk of stroke after influenza infection. Cardiology. 2009;113:98–107. doi: 10.1159/000172796. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 138.Okabe N., Yamashita K., Taniguchi K., Inouye S. Influenza surveillance system of Japan and acute encephalitis and encephalopathy in the influenza season. Pediatr Int. 2000;42:187–191. doi: 10.1046/j.1442-200x.2000.01206.x. [DOI] [PubMed] [Google Scholar]
  • 139.Kasai T., Togashi T., Morishima T. Encephalopathy associated with influenza epidemics. Lancet. 2000;355:1558–1559. doi: 10.1016/S0140-6736(05)74614-6. [DOI] [PubMed] [Google Scholar]
  • 140.Morishima T., Togashi T., Yokota S., et al. Encephalitis and encephalopathy associated with an influenza epidemic in Japan. Clin Infect Dis. 2002;35:512–517. doi: 10.1086/341407. [DOI] [PubMed] [Google Scholar]
  • 141.United States Food and Drug Administration (FDA). Meeting of the FDA Pediatric Advisory Committee, 16 November 2006. Available at: http://www.fda.gov/OHRMS/DOCKETS/ac/oc06.htm. Last accessed July 3, 2008.
  • 142.Casscells S.W., Granger E., Kress A.M., Linton A. The association between oseltamivir use and adverse neuropsychiatric outcomes among TRICARE beneficiaries, ages 1 through 21 years diagnosed with influenza. Int J Adolesc Med Health. 2009;21:79–89. doi: 10.1515/IJAMH.2009.21.1.79. [DOI] [PubMed] [Google Scholar]
  • 143.Donner B, Bader-Weder S, Schwarz R, et al. Safety profile of oseltamivir during the 2009 influenza pandemic. Options for the Control of Influenza, Hong Kong SAR, China. September 3–7, 2010. Abstract.
  • 144.Dutkowski R., Thakrar B., Froehlich E., et al. Safety and pharmacology of oseltamivir in clinical use. Drug Saf. 2003;26:787–801. doi: 10.2165/00002018-200326110-00004. [DOI] [PubMed] [Google Scholar]
  • 145.Reisinger K, Cupelli LA, and Shu D. Seasonal prophylaxis of influenza with oseltamivir in children. 5th Annual Meeting of the World Society for Paediatric Infectious Diseases (WSPID). Bangkok, Thailand. November 15–18, 2007. Abstract.
  • 146.European Medicines Evaluation Agency (EMEA). Assessment report for Tamiflu. London, 24 September 2009. Available at: http://www.emea.europa.eu/docs/en_GB/document_library/EPAR_-_Assessment_Report_-_Variation/human/000402/WC500033109.pdf. Last accessed September 2, 2010.
  • 147.Centers for Disease Control and Prevention (CDC). Interim guidance on antiviral recommendations for patients with novel influenza A (H1N1) virus infection and their close contacts. Updated 7 December 2009. Available at: http://www.cdc.gov/h1n1flu/recommendations.htm. Last accessed September 1, 2010.
  • 148.Siedler K., Skopnik H. Oseltamivir for treatment of influenza in infants less than one year: a retrospective analysis. Pediatr Infect Dis J. 2010;29:495–498. doi: 10.1097/INF.0b013e3181cc4d01. [DOI] [PubMed] [Google Scholar]
  • 149.European Medicines Evaluation Agency (EMEA). Opinion of the Committee for Medicinal Products for Human Use pursuant to Article 5(3) of Regulation (EC) No.726/2004, on novel influenza (H1N1) outbreak; Tamiflu (oseltamivir), Relenza (zanamivir). Available at: http://www.emea.europa.eu/docs/en_GB/document_library/Other/2009/12/WC500018446.pdf. Last accessed September 1, 2010.
  • 150.Donner B., Niranhan V., Hoffmann G. Safety of oseltamivir in pregnancy: a review of preclinical and clinical data. Drug Saf. 2010;33:631–642. doi: 10.2165/11536370-000000000-00000. [DOI] [PubMed] [Google Scholar]
  • 151.Greer L.G., Sheffield J.S., Rogers V.L., et al. Maternal and neonatal outcomes after antepartum treatment of influenza with antiviral medications. Obstet Gynecol. 2010;115:711–716. doi: 10.1097/AOG.0b013e3181d44752. [DOI] [PubMed] [Google Scholar]
  • 152.Vu D., Peck A.J., Nichols W.G., et al. Safety and tolerability of oseltamivir prophylaxis in hematopoietic stem cell transplant recipients: a retrospective case-control study. Clin Infect Dis. 2007;45:187–193. doi: 10.1086/518985. [DOI] [PubMed] [Google Scholar]
  • 153.Ison MG, Szakaly P, Shapira MY, et al. Oseltamivir prophylaxis reduces the occurrence of influenza infection in transplant recipients. 14th Annual Congress of the European Society for Organ Transplantation. Paris, France. August 30–September 2, 2009. Abstract.
  • 154.Redelman-Sidi G. Influenza in patients with hematologic disease: an ounce of prevention is worth a pound of cure. Leuk Lymphoma. 2010;51:1954–1956. doi: 10.3109/10428194.2010.510226. [DOI] [PubMed] [Google Scholar]
  • 155.Watcharananan S.P., Suwatanapongched T., Wacharawanichkul P., et al. Influenza A/H 1N1 2009 pneumonia in kidney transplant recipients: characteristics and outcomes following highdose oseltamivir exposure. Transpl Infect Dis. 2010;12:127–131. doi: 10.1111/j.1399-3062.2010.00493.x. [DOI] [PubMed] [Google Scholar]
  • 156.Dutkowski R., Smith J.R., Davies B.E. Safety and pharmacokinetics of oseltamivir at standard and high dosages. Int J Antimicrob Agents. 2010;35:461–467. doi: 10.1016/j.ijantimicag.2009.12.023. [DOI] [PubMed] [Google Scholar]
  • 157.Schmidt A.C. Antiviral therapy for influenza: a clinical and economic comparative review. Drugs. 2004;64:2031–2046. doi: 10.2165/00003495-200464180-00003. [DOI] [PubMed] [Google Scholar]
  • 158.Lynd L.D., Goeree R., O’Brien B.J. Antiviral agents for influenza: a comparison of cost-effectiveness data. Pharmacoeconomics. 2005;23:1083–1106. doi: 10.2165/00019053-200523110-00003. [DOI] [PubMed] [Google Scholar]
  • 159.Postma M.J., Beardsworth P., Wilschut J.C. Cost effectiveness of oseltamivir treatment of influenza: a critique of published methods and outcomes. J Med Econ. 2008;11:743–768. doi: 10.3111/13696990802505557. [DOI] [PubMed] [Google Scholar]
  • 160.Sander B., Hayden F.G., Gyldmark M., Garrison L.P., Jr. Post-exposure influenza prophylaxis with oseltamivir: cost effectiveness and cost utility in families in the UK. Pharmacoeconomics. 2006;24:373–386. doi: 10.2165/00019053-200624040-00007. [DOI] [PubMed] [Google Scholar]
  • 161.Postma M.J., Novak A., Scheijbeler H.W., 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;25:497–509. doi: 10.2165/00019053-200725060-00005. [DOI] [PubMed] [Google Scholar]
  • 162.Talbird S.E., Brogan A.J., Winiarski A.P., Sander B. Costeffectiveness of treating influenzalike illness with oseltamivir in the United States. Am J Health Syst Pharm. 2009;66:469–480. doi: 10.2146/ajhp080296. [DOI] [PubMed] [Google Scholar]
  • 163.Nagase H., Moriwaki K., Kamae M., Yanagisawa S., Kamae I. Cost-effectiveness analysis of oseltamivir for influenza treatment considering the virus emerging resistant to the drug in Japan. Value Health. 2009;12(Suppl.3):S62–S65. doi: 10.1111/j.1524-4733.2009.00629.x. [DOI] [PubMed] [Google Scholar]
  • 164.Lugner A.K., Postma M.J. Mitigation of pandemic influenza: review of cost-effectiveness studies. Expert Rev Pharmacoecon Outcomes Res. 2009;9:547–558. doi: 10.1586/erp.09.56. [DOI] [PubMed] [Google Scholar]
  • 165.Sander B., Nizam A., Garrison L.P., Jr, et al. Economic evaluation of influenza pandemic mitigation strategies in the United States using a stochastic microsimulation transmission model. Value Health. 2009;12:226–233. doi: 10.1111/j.1524-4733.2008.00437.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

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