Elsevier Health Sciences

Topics

« Back to Resource Center

Antivirals: Treatment, Prophylaxis and Pandemic Control

Development of drug resistance

Resistance to amantadine and rimantadine occurs as a result of amino acid substitutions in the transmembrane portion of the M2 protein. Resistant viruses may emerge in patients within 2–4 days after the start of therapy. 20 x FG Hayden. Amantadine and rimantadine: clinical aspects. DD Richman (Ed.) Antiviral Drug Resistance (Wiley, New York, 1996) Although resistant virus was previously uncommon (<1%), 21 x T Ziegler, ML Hemphill, ML Ziegler, et al.. Low incidence of rimantadine resistance in field isolates of influenza A viruses. J Infect Dis 180 (1999) (935 - 939) Crossref. 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. As there has been no documented resistance to the NAIs, the interim recommendation advises that oseltamivir (prophylaxis and treatment) and zanamivir (treatment) be selected if an antiviral medication is to be used for the treatment and prophylaxis of influenza. Further, high-risk groups should be given priority for use of these antiviral medications.

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 x 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) Importantly, resistant virus can be spread to others and has caused failures of antiviral prophylaxis under close contact conditions, as in nursing homes 23 x 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. J Am Med Dir Assoc 6 (2005) (359 - 366) Crossref. and households. 1 x FG Hayden, FY Aoki. Amantadine, rimantadine, and related agents. SL Barriere (Ed.) Antimicrobial Therapy and Vaccines (Williams & Wilkins, Baltimore, 1999) (1344 - 1365) The resistant viruses appear to retain wild-type pathogenicity and cause an influenza illness indistinguishable from that caused by susceptible strains.

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, x MD De Jong, TT Tran, HK Truong, et al.. Oseltamivir resistance during treatment of influenza A (H5N1) infection. New Engl J Med 353 (2005) (2667 - 2672) Crossref. 25 x QM Le, M Kiso, K Someya, et al.. Avian flu: isolation of drug-resistant H5N1 virus. Nature 437 (2005) (754) 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.

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
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

« Back to Resource Center