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Neuraminidase Inhibitors in Patients with Underlying Airways Disease

  • Current Opinion
  • Published:
American Journal of Respiratory Medicine

Abstract

Influenza virus infection accounts for significant morbidity, mortality, and healthcare expenditures among persons worldwide. Approximately 20 000 to 40 000 people in the US die each year as a result of influenza. Individuals most susceptible to adverse outcomes include the elderly and those with asthma, chronic obstructive pulmonary disease (COPD), heart disease, renal failure, malignancy, or immunosuppression. Prior to the AIDS epidemic, underlying respiratory disease was the greatest risk factor for influenza-related hospitalization ranking third to heart disease and malignancy for risk of mortality. Although the influenza vaccine can help prevent pneumonia and hospitalization, it is limited by less than ideal immunization rates and the possibility of viral antigenic shifts that render the vaccine ineffective. Pharmacologic interventions play an important role in the management of influenza virus infection by shortening the duration of symptoms.

The advent of the neuraminidase inhibitors (NAIs) zanamivir and oseltamivir has significantly affected the treatment of influenza. Unlike NAIs, the older therapeutic options amantadine and rimantadine may cause significant central nervous system adverse effects. In addition, amantadine and rimantadine are not active against influenza B viruses, whereas NAIs are active against both influenza A and B. Post-marketing surveillance of the NAIs has revealed that bronchospasm may occur in patients with underlying respiratory disease treated with the NAI zanamivir. Recent data suggest zanamivir is effective in patients with underlying respiratory disease, but the data are insufficient to elucidate the true risk of bronchospasm. Based on post-marketing reports, zanamivir should be used with caution in patients with asthma or COPD. Although oseltamivir has not been associated with any significant respiratory adverse effects, no data exist on the safety and efficacy of this NAI in patients with underlying respiratory disease.

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References

  1. WHO urges influenza vaccination for northern hemisphere [online]. Available from URL: http://www.who.int/inf/en/pr-2002-08.htm [Accessed 2002 Feb 2]

  2. Centers for Disease Control and Prevention. Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep 2001; 50: 1–46

    Google Scholar 

  3. Glezen WP, Decker M, Perrotta DM. Survey of underlying conditions of persons hospitalized with acute respiratory disease during influenza epidemics in Houston, 1978–1981. Am Rev Respir Dis 1987; 136: 550–5

    Article  PubMed  CAS  Google Scholar 

  4. Neuzil KM, Reed GW, Mitchel EF, et al. Influenza-associated morbidity and mortality in young and middle-aged women. JAMA 1999; 281: 901–7

    Article  PubMed  CAS  Google Scholar 

  5. Izurieta HS, Thompson WW, Kramarz P, et al. Influenza and the rates of hospitalization for respiratory disease among infants and young children. N Engl J Med 2000; 342: 232–9

    Article  PubMed  CAS  Google Scholar 

  6. Carrat F, Valleron A. Influenza mortality among the elderly in France, 1980–90: how many deaths may have been avoided through vaccination? J Epidemiol Community Health 1995; 49: 419–25

    Article  PubMed  CAS  Google Scholar 

  7. Dreitlein WB, Maratos J, Brocavich J. Zanamivir and oseltamivir: two new options for the treatment and prevention of influenza. Clin Ther 2001; 23: 327–55

    Article  PubMed  CAS  Google Scholar 

  8. Clementsen P, Jensen CB, Hannoun C, et al. Influenza A virus potentiates basophil histamine release caused by endotoxin-induced complement activation. Allergy 1988; 43: 93–9

    Article  PubMed  CAS  Google Scholar 

  9. Utell MJ, Aquilina AT, Hall WJ, et al. Development of airway reactivity to nitrates in subjects with influenza. Am Rev Respir Dis 1980; 121: 233–41

    PubMed  CAS  Google Scholar 

  10. Kondo S, Abe K. The effects of influenza virus infection on FEV1 in asthmatic children. Chest 1991; 100: 1235–8

    Article  PubMed  CAS  Google Scholar 

  11. Smith CB, Kanner RE, Golden CA, et al. Effect of viral infections on pulmonary function in patients with chronic obstructive pulmonary diseases. J Infect Dis 1980; 141: 271–80

    Article  PubMed  CAS  Google Scholar 

  12. Camner P, Jarstrand C, Philipson K. Tracheobronchial clearance in patients with influenza. Am Rev Resp Dis 1973; 108: 131–5

    PubMed  CAS  Google Scholar 

  13. Levandowski RA, Gerrity TR, Garrard CS. Modifications of lung clearance mechanisms by acute influenza A infection. J Lab Clin Med 1985; 106: 428–32

    PubMed  CAS  Google Scholar 

  14. The MIST Study Group. Randomised trial of efficacy and safety of inhaled zanamivir in treatment of influenza A and B virus infections. Lancet 1998; 352: 1877–81

    Article  Google Scholar 

  15. Hayden FG, Osterhaus ADME, Treanor JJ, et al. Efficacy and safety of the neuraminidase inhibitor zanamivir in the treatment of influenzavirus infections. N Engl J Med 1997; 337: 874–80

    Article  PubMed  CAS  Google Scholar 

  16. Monto AS, Fleming DM, Henry D, et al. Efficacy and safety of the neuraminidase inhibitor zanamivir in the treatment of influenza A and B virus infections. J Infect Dis 1999; 180: 254–61

    Article  PubMed  CAS  Google Scholar 

  17. Makela MJ, Pauksens K, Rostila T, et al. Clinical efficacy and safety of the orally inhaled neuraminidase inhibitor zanamivir in the treatment of influenza: a randomized, double-blind, placebo-controlled European study. J Infection 2000; 40: 42–8

    Article  CAS  Google Scholar 

  18. Treanor JJ, Hayden FG, Vrooman PS, et al. Efficacy and safety of the oral neuraminidase inhibitor oseltamivir in treating acute influenza: a randomized controlled trial. JAMA 2000; 283: 1016–24

    Article  PubMed  CAS  Google Scholar 

  19. Nicholson KG, Aoki FY, Osterhaus ADME, et al. Efficacy and safety of oseltamivir in treatment of acute influenza: a randomised controlled trial. Lancet 2000; 355: 1845–50

    Article  PubMed  CAS  Google Scholar 

  20. Aoki FY, Fleming DM, Griffin AD, et al. Impact of zanamivir treatment on productivity, health status and healthcare resource use in patients with influenza. Pharmacoeconomics 2000; 17: 187–95

    Article  PubMed  CAS  Google Scholar 

  21. Mauskopf JA, Cates SC, Griffin AD, et al. Cost effectiveness of zanamivir for the treatment of influenza in a high risk population in Australia. Pharmacoeconomics 2000; 17: 611–20

    Article  PubMed  CAS  Google Scholar 

  22. Kucers A, Crowe S, Grayson ML, et al. The use of antibiotics: a clinical review of antibacterial, antifungal and antiviral drugs. Oxford: Butterworth-Heinemann; 1997

    Google Scholar 

  23. Hayden FG, Hoffman HE, Spyker DA. Differences in side effects of amantadine hydrochloride and rimantadine hydrochloride relate to differences in pharmacokinetics. Antimicrob Agents Chemother 1983; 23: 458–64

    Article  PubMed  CAS  Google Scholar 

  24. Gubareva LV, Kaiser L, Hayden FG. Influenza virus neuraminidase inhibitors. Lancet 2000; 355: 827–35

    Article  PubMed  CAS  Google Scholar 

  25. Centers for Disease Control and Prevention. 2000–2001 influenza season summary [online]. Available from URL: http://www.cdc.gov/ncidod/diseases/flu/weeklyarchives2000-2001/00-01summary.htm [Accessed 2001 Sep 28]

  26. Daniel MJ, Barnett JM, Pearson BA. The low potential for drug interactions with zanamivir. Clin Pharmacokinet 1999; 36Suppl. 1: 41–50

    Article  PubMed  CAS  Google Scholar 

  27. Cass LMR, Brown J, Pickford M, et al. Pharmacoscintigraphic evaluation of lung disposition of inhaled zanamivir in healthy volunteers. Clin Pharmacokinet 1999; 36Suppl. 1:21–31

    Article  PubMed  CAS  Google Scholar 

  28. Lumpkin MM. Food and Drug Administration public health advisory, subject: safe and appropriate use of influenza drugs [online]. Available from URL: http://www.fda.gov/cder/drug/advisory/influenza.htm [Accessed 2001 Sep 28]

  29. Williamson JC, Pegram PS. Respiratory distress associated with zanamivir. N Engl J Med 2000; 342: 661–2

    Article  PubMed  CAS  Google Scholar 

  30. Relenza [package insert]. Research Triangle Park (NC): Glaxo Wellcome, 2001

  31. Cass LMR, Gunawardena KA, Macmahon MM, et al. Pulmonary function and airway responsiveness in mild to moderate asthmatics given repeated inhaled doses of zanamivir. Respir Med 2000; 94: 166–73

    Article  PubMed  CAS  Google Scholar 

  32. Data on file, GlaxoSmithKline, 2001

  33. Murphy KR, Eivindson A, Pauksens K, et al. Efficacy and safety of inhaled zanamivir for the treatment of influenza in patients with asthma or chronic obstructive pulmonary disease. Clin Drug Invest 2000; 20: 337–49

    Article  CAS  Google Scholar 

  34. Lalezari J, Campion K, Keene O, et al. Zanamivir for the treatment of influenza A and B infection in high-risk patients. Arch Intern Med 2001; 161: 212–7

    Article  PubMed  CAS  Google Scholar 

  35. Gravenstein S, Johnston SL, Loeschel E, et al. Zanamivir: a review of clinical safety in individuals at high risk of developing influenza-related complications. Drug Saf 2001; 24: 1113–25

    Article  PubMed  CAS  Google Scholar 

  36. Hayden FG, Treanor JJ, Fritz RS, et al. Use of the oral neuraminidase inhibitor oseltamivir in experimental human influenza: randomized controlled trials for prevention and treatment. JAMA 1999; 282: 1240–6

    Article  PubMed  CAS  Google Scholar 

  37. Hayden FG, Atmar RL, Schilling M, et al. Use of the selective oral neuraminidase inhibitor oseltamivir to prevent influenza. N Engl J Med 1999; 341: 1336–43

    Article  PubMed  CAS  Google Scholar 

  38. Welliver R, Monto AS, Carewicz O, et al. Effectiveness of oseltamivir in preventing influenza in household contacts. JAMA 2001; 285: 748–54

    Article  PubMed  CAS  Google Scholar 

  39. Tamiflu [package insert]. Nutley (NJ): Roche Laboratories, 2000

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The authors received no funding for the preparation of this manuscript. Furthermore, no known conflicts of interest exist related to the content of this manuscript.

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Correspondence to John C. Williamson.

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Williamson, J.C., Pegram, P.S. Neuraminidase Inhibitors in Patients with Underlying Airways Disease. Am J Respir Med 1, 85–90 (2002). https://doi.org/10.1007/BF03256597

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