Elsevier Health Sciences

Topics

« Back to Resource Center

Antivirals: Treatment, Prophylaxis and Pandemic Control

References

Label Authors Title Source Year
1

References in context

  • Amantadine and rimantadine were the first generation of influenza antiviral agents.1 These compounds specifically block the ion channel function of the M2 protein of influenza A virus (see Chapter 2), thus interfering with corresponding specific steps in the viral life cycle.
    Go to context

  • Particularly in the elderly or those with renal failure, serious CNS side effects due to amantadine (and less often rimantadine) include confusion, disorientation, mood alterations, memory disturbances, delusions, nightmares, ataxia, tremors, seizures, coma, acute psychosis, slurred speech, visual disturbances, delirium, oculogyric episodes and hallucinations.1 Amantadine causes CNS side effects in about 15–30% of people, as well as dose-related abnormalities in psychomotor testing.
    Go to context

  • Emergence of resistant virus does not appear to cause a rebound in illness in immunocompetent adults, but may be associated with protracted illness and shedding in immunocompromised hosts.22 Importantly, resistant virus can be spread to others and has caused failures of antiviral prophylaxis under close contact conditions, as in nursing homes23 and households.1 The resistant viruses appear to retain wild-type pathogenicity and cause an influenza illness indistinguishable from that caused by susceptible strains.
    Go to context

FG Hayden, FY Aoki. Amantadine, rimantadine, and related agents. SL Barriere (Ed.) Antimicrobial Therapy and Vaccines (Williams & Wilkins, Baltimore, 1999) (1344 - 1365) 1999
2

References in context

  • The neuraminidase inhibitors are novel drugs, designed on the basis of the three-dimensional structure of the influenza A and B neuraminidase2 (see Chapter 2).
    Go to context

  • Zanamivir and oseltamivir are analogues of sialic acid, as shown in Figure 23.2 These compounds specifically inhibit all nine NA subtypes in nature, including the subtypes contained in the avian strains of influenza A H5N1, H7N7 and H9N2 that have infected humans (see also Chapter 3).
    Go to context

  • Zanamivir and oseltamivir are analogues of sialic acid, as shown in Figure 23.2 These compounds specifically inhibit all nine NA subtypes in nature, including the subtypes contained in the avian strains of influenza A H5N1, H7N7 and H9N2 that have infected humans (see also Chapter 3).
    Go to context

  • The inhibition of neuraminidase on both influenza A and B viruses has three important consequences.2 First, it hinders the passage of the virus through the mucus of the respiratory tract and thus retards initial infection of epithelial cells.
    Go to context

PM Colman. Influenza virus neuraminidase: structure, antibodies, and inhibitors. Crossref. Protein Sci 3 (1994) (1687 - 1696) 1994
3

References in context

  • At low, pharmacologically relevant concentrations (<0.75 µg/ml), amantadine and rimantadine specifically inhibit the ion channel activity of the M2 protein, probably through direct binding to the pore region of the protein.3 In doing so, the drugs inhibit acidification of the interior of susceptible viruses and dissociation of the M1 protein from the viral nucleocapsid (Figure 22), which is a necessary step in the uncoating of the viral genome during infection (see Chapter 2).
    Go to context

C Wang, K Takeuchi, LH Pinto, RA Lamb. Ion channel activity of influenza A virus M2 protein: characterization of the amantadine block. J Virol 67 (1993) (5585 - 5594) 1993
4

References in context

  • In addition, within the infected cell, M2 protects newly synthesized HA against premature exposure to low pH by transiently neutralizing the pH of the trans-Golgi network, while HA is in transit to the cell surface.4 Amantadine and rimantadine counteract this protection and thus indirectly induce a premature conformational change in HA, inactivating the protein (Figure 22).
    Go to context

RW Ruigrok, EM Hirst, AJ Hay. The specific inhibition of influenza A virus maturation by amantadine: an electron microscopic examination. Crossref. J Gen Virol 72 (1991) (191 - 194) 1991
5

References in context

  • The UK National Institute for Clinical Excellence (NICE) no longer approves the use of amantadine for treatment of influenza,5 while the USA and Canada have also recently changed the recommendations for prophylaxis and treatment with amantidine and rimantidine, the reasons for which will be discussed below.
    Go to context

National Institute for Clinical Excellence. Guidance on the use of zanamivir, oseltamivir and amantadine for the treatment of influenza. In. Flu – zanamivir (review), amantadine and oseltamivir 58 (2003) (www.nice.org.uk) 2003
6

References in context

  • Evidence for the effectiveness of these four antiviral agents is based primarily on studies of uncomplicated influenza in adults.6 None of the drugs has been shown to prevent serious complications, such as pneumonia or the exacerbation of underlying disease.
    Go to context

Food and Drug Administration. Subject: safe and appropriate use of influenza drugs [Public Health Advisory] (US Department of Health and Human Services, Food and Drug Administration, Rockville, MD, 2000) 2000
7

References in context

  • Current guidelines advise against the use of zanamivir in patients with hyperreactive airways, unless the patient is closely monitored and has a fast-acting inhaled broncho-dilator available when inhaling zanamivir.7 Other less frequent side effects include diarrhoea, nausea, headache and dizziness.
    Go to context

Prevention and control of influenza: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 51 (2002) (1) 2002
8

References in context

  • Both of the M2 blockers are 70–90% effective in preventing illness from influenza A infection in healthy adults.8 When used as prophylaxis, they permit subclinical infection (whilst preventing illness) and allow development of protective antibodies.
    Go to context

V Demicheli, T Jefferson, D Rivetti, J Deeks. Prevention and early treatment of influenza in healthy adults. Vaccine 18 (2000) (957 - 1003) 2000
9

References in context

  • As indicated above, under specific conditions, influenza antivirals may be used for prevention of influenza infection.
    Go to context

KG Nicholson. Use of antivirals in influenza in the elderly: prophylaxis and therapy. Crossref. Gerontology 42 (1996) (280 - 289) 1996
10

References in context

AS Monto, ME Pichichero, SJ Blanckenberg, et al.. Zanamivir prophylaxis: an effective strategy for the prevention of influenza types A and B within households. Crossref. J Infect Dis 186 (2002) (1582 - 1588) 2002
11

References in context

FG Hayden, RL Atmar, M Schilling, et al.. Use of the selective oral neuraminidase inhibitor oseltamivir to prevent influenza. Crossref. New Engl J Med 341 (1999) (1336 - 1343) 1999
12

References in context

PH Peters Jr, S Gravenstein, P Norwood, et al.. Long-term use of oseltamivir for the prophylaxis of influenza in a vaccinated frail older population. Crossref. J Am Geriatr Soc 49 (2001) (1025 - 1031) 2001
13

References in context

  • For the purposes of prevention, after an outbreak has been reported, vulnerable adults can be vaccinated and simultaneously receive prophylactic treatment for 2–3 weeks until sufficient antibodies have been generated by vaccination.13,14 In individuals who remain unvaccinated, the drug must be taken each day for the duration of influenza activity in the community to be maximally effective as prophylaxis.
    Go to context

PA Gross, C Russo, S Dran, P Cataruozolo, G Munk, SC Lancey. Time to earliest peak serum antibody response to influenza vaccine in the elderly. Clin Diagn Lab Immunol 4 (1997) (491 - 492) 1997
14

References in context

  • For the purposes of prevention, after an outbreak has been reported, vulnerable adults can be vaccinated and simultaneously receive prophylactic treatment for 2–3 weeks until sufficient antibodies have been generated by vaccination.13,14 In individuals who remain unvaccinated, the drug must be taken each day for the duration of influenza activity in the community to be maximally effective as prophylaxis.
    Go to context

KA Brokstad, RJ Cox, J Olofsson, R Jonsson, LR Haaheim. Parenteral influenza vaccination induces a rapid systemic and local immune response. Crossref. J Infect Dis 171 (1995) (198 - 203) 1995
15

References in context

  • When an outbreak occurs in a nursing home, all residents should receive prophylaxis, whether or not they have been vaccinated, as vaccination is only ∼60% effective in preventing laboratory-confirmed influenza illness among elderly people in this setting.15 This should continue for a minimum of 2 weeks and until approximately 1 week after the last case has been identified.
    Go to context

R Guy, S Lambert, H Kelly. Estimating influenza vaccine effectiveness in an outbreak when anti-viral medications were used as a control measure. Crossref. Aust NZ J Public Health 29 (2005) (540 - 543) 2005
16

References in context

  • The dose of drug should be determined on an individual basis.16 Prevention can also be considered for controlling outbreaks in, for example, dormitories, schools, cruise ships.
    Go to context

  • In addition, the efficacy of these drugs in the absence of vaccination in the very young16 and the very old31 also remain in question in both pandemic and interpandemic influenza seasons.
    Go to context

R Dolin. Influenza – interpandemic as well as pandemic disease. Crossref. New Engl J Med 353 (2005) (2535 - 2537) 2005
17

References in context

  • A recent review article addressed the cost-effectiveness of treatment of ILI with antiviral agents.17 Treatment with amantadine, zanamivir or oseltamivir was examined in eight studies.
    Go to context

LD Lynd, R Goeree, BJ O'Brien. Antiviral agents for influenza; a comparison of cost-effectiveness data. Crossref. Pharmacoeconomics 23 (2005) (1083 - 1106) 2005
18

References in context

  • One study included an economic analysis of prophylactic use of antivirals instead of, or on top of, vaccination.18 Analyses were mostly directed at net costs per symptom-day averted or quality-adjusted life-year (QALY) gained.
    Go to context

  • One study included an economic analysis of prophylactic use of antivirals instead of, or on top of, vaccination.18 Analyses were mostly directed at net costs per symptom-day averted or quality-adjusted life-year (QALY) gained.
    Go to context

D Turner, A Wailoo, A Nicholson, et al.. Systematic review and economic decision modelling for the prevention and treatment of influenza A and B (National Institute of Clinical Excellence (NICE), Leicester (UK), 2002) 2002
19

References in context

  • A recent review article addressed the cost-effectiveness of treatment of ILI with antiviral agents.17 Treatment with amantadine, zanamivir or oseltamivir was examined in eight studies.
    Go to context

NA Risebrough, SK Bowles, AE Simor, et al.. Economic evaluation of oseltamivir phosphate for postexposure prophylaxis of influenza in long-term care facilities. Crossref. J Am Geriatr Soc 53 (2005) (444 - 451) 2005
20

References in context

  • Resistant viruses may emerge in patients within 2–4 days after the start of therapy.20 Although resistant virus was previously uncommon (<1%),21 recent reports from the CDC in the USA and the Public Health Agency of Canada confirm a rise in the last 2 years from 1.9% to 91% of isolates of influenza A (H3N2) strains that are now resistant to amantidine and rimantidine.**www.cdc.gov/flu/professionals/treatment/0506antiviralguide.htm For the 2005–06 influenza season, there is an interim recommendation against the use of amantidine and rimantidine in both countries.
    Go to context

FG Hayden. Amantadine and rimantadine: clinical aspects. DD Richman (Ed.) Antiviral Drug Resistance (Wiley, New York, 1996) 1996
21

References in context

  • Resistant viruses may emerge in patients within 2–4 days after the start of therapy.20 Although resistant virus was previously uncommon (<1%),21 recent reports from the CDC in the USA and the Public Health Agency of Canada confirm a rise in the last 2 years from 1.9% to 91% of isolates of influenza A (H3N2) strains that are now resistant to amantidine and rimantidine.**www.cdc.gov/flu/professionals/treatment/0506antiviralguide.htm For the 2005–06 influenza season, there is an interim recommendation against the use of amantidine and rimantidine in both countries.
    Go to context

T Ziegler, ML Hemphill, ML Ziegler, et al.. Low incidence of rimantadine resistance in field isolates of influenza A viruses. Crossref. J Infect Dis 180 (1999) (935 - 939) 1999
22

References in context

  • Emergence of resistant virus does not appear to cause a rebound in illness in immunocompetent adults, but may be associated with protracted illness and shedding in immunocompromised hosts.22 Importantly, resistant virus can be spread to others and has caused failures of antiviral prophylaxis under close contact conditions, as in nursing homes23 and households.1 The resistant viruses appear to retain wild-type pathogenicity and cause an influenza illness indistinguishable from that caused by susceptible strains.
    Go to context

JA Englund, RE Champlin, PR Wyde, et al.. Common emergence of amantadine- and rimantadine-resistant influenza A viruses in symptomatic immunocompromised adults. Clin Infect Dis 26 (1998) (1418 - 1424) 1998
23

References in context

  • Emergence of resistant virus does not appear to cause a rebound in illness in immunocompetent adults, but may be associated with protracted illness and shedding in immunocompromised hosts.22 Importantly, resistant virus can be spread to others and has caused failures of antiviral prophylaxis under close contact conditions, as in nursing homes23 and households.1 The resistant viruses appear to retain wild-type pathogenicity and cause an influenza illness indistinguishable from that caused by susceptible strains.
    Go to context

S Gravenstein, P Drinka, D Osterweil, et al.. Inhaled zanamivir versus rimantadine for the control of influenza in a highly vaccinated long-term care population. Crossref. J Am Med Dir Assoc 6 (2005) (359 - 366) 2005
24

References in context

  • To date, the use of NAIs for both prophylaxis and treatment has not been associated with clinically relevant development of antiviral resistance during interpandemic use – although, as discussed below, the avian H5N1 virus does appear to develop resistance to oseltamivir in the treatment of H5N1 disease.24,25 The lack of resistance development of the NAIs often makes them, despite the fact that they are expensive, the preferred drugs relative to the low-cost amantadine and rimantadine, but ultimately cost considerations may also influence the choice of the drug that is used.
    Go to context

  • Recent reports of the development of resistance to oseltamivir during the treatment of H5N1 disease24,25 raise concerns about the potential for induction and spread of antiviral-resistant H5N1 strains.
    Go to context

MD De Jong, TT Tran, HK Truong, et al.. Oseltamivir resistance during treatment of influenza A (H5N1) infection. Crossref. New Engl J Med 353 (2005) (2667 - 2672) 2005
25

References in context

  • To date, the use of NAIs for both prophylaxis and treatment has not been associated with clinically relevant development of antiviral resistance during interpandemic use – although, as discussed below, the avian H5N1 virus does appear to develop resistance to oseltamivir in the treatment of H5N1 disease.24,25 The lack of resistance development of the NAIs often makes them, despite the fact that they are expensive, the preferred drugs relative to the low-cost amantadine and rimantadine, but ultimately cost considerations may also influence the choice of the drug that is used.
    Go to context

  • Recent reports of the development of resistance to oseltamivir during the treatment of H5N1 disease24,25 raise concerns about the potential for induction and spread of antiviral-resistant H5N1 strains.
    Go to context

QM Le, M Kiso, K Someya, et al.. Avian flu: isolation of drug-resistant H5N1 virus. Nature 437 (2005) (754) 2005
26

References in context

  • An essential component of pandemic planning is the use of antiviral drugs early in the pandemic to treat illness and reduce transmission of the virus.26–28 This would buy time until a vaccine against the pandemic strain can be produced and available in sufficient quantities for mass vaccination.
    Go to context

  • The need for large stockpiles of lower cost, more efficacious and easily administered medications has been identified.27 Plans could include the use of antivirals to treat severe illness during a pandemic and prophylax all health-care and related support workers, but this plan may have limited feasibility from a governmental perspective.32 Governments are attempting to stockpile oseltamivir to be used in an influenza pandemic, but who would receive the drug when supplies are limited?
    Go to context

AS Monto. The role of antivirals in the control of influenza. Crossref. Vaccine 21 (2003) (1796 - 1800) 2003
27

References in context

  • An essential component of pandemic planning is the use of antiviral drugs early in the pandemic to treat illness and reduce transmission of the virus.26–28 This would buy time until a vaccine against the pandemic strain can be produced and available in sufficient quantities for mass vaccination.
    Go to context

  • The need for large stockpiles of lower cost, more efficacious and easily administered medications has been identified.27 Plans could include the use of antivirals to treat severe illness during a pandemic and prophylax all health-care and related support workers, but this plan may have limited feasibility from a governmental perspective.32 Governments are attempting to stockpile oseltamivir to be used in an influenza pandemic, but who would receive the drug when supplies are limited?
    Go to context

  • The need for large stockpiles of lower cost, more efficacious and easily administered medications has been identified.27 Plans could include the use of antivirals to treat severe illness during a pandemic and prophylax all health-care and related support workers, but this plan may have limited feasibility from a governmental perspective.32 Governments are attempting to stockpile oseltamivir to be used in an influenza pandemic, but who would receive the drug when supplies are limited?
    Go to context

K Stohr. Preventing and treating influenza. Crossref. Br Med J 326 (2003) (1223 - 1224) 2003
28

References in context

  • An essential component of pandemic planning is the use of antiviral drugs early in the pandemic to treat illness and reduce transmission of the virus.26–28 This would buy time until a vaccine against the pandemic strain can be produced and available in sufficient quantities for mass vaccination.
    Go to context

  • The need for large stockpiles of lower cost, more efficacious and easily administered medications has been identified.27 Plans could include the use of antivirals to treat severe illness during a pandemic and prophylax all health-care and related support workers, but this plan may have limited feasibility from a governmental perspective.32 Governments are attempting to stockpile oseltamivir to be used in an influenza pandemic, but who would receive the drug when supplies are limited?
    Go to context

AS Monto. Vaccines and antiviral drugs in pandemic preparedness. Crossref. Emerg Inf Dis 12 (2006) (55 - 60) 2006
29

References in context

  • An essential component of pandemic planning is the use of antiviral drugs early in the pandemic to treat illness and reduce transmission of the virus.26–28 This would buy time until a vaccine against the pandemic strain can be produced and available in sufficient quantities for mass vaccination.
    Go to context

NM Ferguson, DA Cummings, S Cauchemez, et al.. Strategies for containing an emerging influenza pandemic in Southeast Asia. Crossref. Nature 437 (2005) (209 - 214) 2005
30

References in context

  • An essential component of pandemic planning is the use of antiviral drugs early in the pandemic to treat illness and reduce transmission of the virus.26–28 This would buy time until a vaccine against the pandemic strain can be produced and available in sufficient quantities for mass vaccination.
    Go to context

IM Longini, ME Halloran, A Nizam, Y Yang. Containing pandemic influenza with antiviral agents. Crossref. Am J Epidemiol 159 (2004) (623 - 633) 2004
31

References in context

  • In addition, the efficacy of these drugs in the absence of vaccination in the very young16 and the very old31 also remain in question in both pandemic and interpandemic influenza seasons.
    Go to context

A Ambrozaitis, S Gravenstein, GA van Essen, et al.. Inhaled zanamivir versus placebo for the prevention of influenza outbreaks in an unvaccinated long-term care population. Crossref. J Am Med Dir Assoc 6 (2005) (367 - 374) 2005
32

References in context

  • The need for large stockpiles of lower cost, more efficacious and easily administered medications has been identified.27 Plans could include the use of antivirals to treat severe illness during a pandemic and prophylax all health-care and related support workers, but this plan may have limited feasibility from a governmental perspective.32 Governments are attempting to stockpile oseltamivir to be used in an influenza pandemic, but who would receive the drug when supplies are limited?
    Go to context

S Cinti, C Chenoweth, AS Monto. Preparing for pandemic influenza: should hospitals stockpile oseltamivir?. Crossref. Infect Control Hosp Epidemiol 26 (2005) (852 - 854) 2005

« Back to Resource Center