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Rimantadine scientific update

 

Cochrane Database Syst Rev. 2006 Apr 19;(2):CD001169.
Jefferson T, Demicheli V, Di Pietrantonj C, Rivetti D.
Health Reviews Ltd, Via Adige 28a, Anguillara Sabazia, Roma, Italy, 00061.

Amantadine and rimantadine for influenza A in adults.

BACKGROUND: Amantadine hydrochloride and rimantadine hydrochloride have antiviral properties, but they are not widely used due to a lack of knowledge of their potential value and concerns about possible adverse effects. OBJECTIVES: The objective of this review was to assess the efficacy, effectiveness and safety ("effects") of amantadine and rimantadine in healthy adults. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 3, 2005), MEDLINE (2003 to August Week 4, 2005), EMBASE (October 2003 to July 2005) and reference lists of articles. SELECTION CRITERIA: Randomised and quasi-randomised studies comparing amantadine and/or rimantadine with placebo, control medication or no intervention, or comparing doses or schedules of amantadine and/or rimantadine in healthy adults. DATA COLLECTION AND ANALYSIS: For prophylaxis (prevention) trials the numbers of participants with clinical influenza (influenza-like-illness or ILI) or with confirmed influenza A and adverse effects were analysed. Analysis for treatment trials was of the mean duration of fever, length of hospital stay and adverse effects. MAIN RESULTS: Amantadine prevented 25% of ILI cases (95% confidence interval (CI) 13% to 36%), and 61% of influenza A cases (95% CI 35% to 76%). Amantadine reduced duration of fever by one day (95% CI 0.7 to 1.2). Rimantadine demonstrated comparable effectiveness, but there were fewer trials and the results for prophylaxis were not statistically significant. Both amantadine and rimantadine induced significant gastrointestinal adverse effects. Adverse effects of the central nervous system and study withdrawals were significantly more common with amantadine than rimantadine. Neither drug affected the rate of viral shedding from the nose and the course of asymptomatic influenza. AUTHORS' CONCLUSIONS: Amantadine and rimantadine have comparable efficacy and effectiveness in relieving or treating symptoms of influenza A in healthy adults, although rimantadine induces fewer adverse effects than amantadine. The effectiveness of both drugs in interrupting transmission is probably low. Routine use of both drugs should be discouraged and both drugs should only be used when all other measures fail.


J Am Geriatr Soc. 2007 Jun;55(6):923-6.
Drinka PJ, Haupt T.
Wisconsin Veterans Home, King, WI 54946, USA.

Emergence of rimantadine-resistant virus within 6 days of starting rimantadine prophylaxis with oseltamivir treatment of symptomatic cases.

OBJECTIVES: To report on the detection of rimantadine resistance within 6 days of starting rimantadine prophylaxis. DESIGN: Observational prospective study. SETTING: Fifty-bed nursing unit during the 2004/05 influenza season. PARTICIPANTS: All residents. INTERVENTION: Clinical monitoring for new onset of respiratory illness followed by collection of nasopharyngeal swabs for Directigen AB testing and influenza culture. After outbreak identification, rimantadine was administered as prophylaxis, whereas oseltamivir was used to treat symptomatic cases. Laboratory monitoring for the emergence of rimantadine resistance was reinitiated on the fifth day of rimantadine prophylaxis. MEASUREMENTS: Tabulation of respiratory illnesses, rapid tests and cultures yielding influenza A, and rimantadine sensitivity determination in five index isolates. RESULTS: A total of 15 symptomatic cases were identified over 8 days. Amantadine sensitivity was determined in five cases. Three initial cases were sensitive to rimantadine, whereas two cases identified after 6 days of rimantadine prophylaxis were resistant to rimantadine. CONCLUSION: The Centers for Disease Control and Prevention reported that 91% of isolates collected early the following season (2005/06) were resistant to rimantadine. Rimantadine treatment is no longer recommended. This experience anticipated the new recommendations. If reemergence of sensitivity follows discontinuation of rimantadine use, using rimantadine as prophylaxis and oseltamivir for treatment of symptomatic cases might be efficacious and economical on a national scale.


Cochrane Database Syst Rev. 2008 Jan 23;(1):CD002745.
Alves Galvão MG, Rocha Crispino Santos MA, Alves da Cunha AJ.

Amantadine and rimantadine for influenza A in children and the elderly.

BACKGROUND: Although amantadine (AMT) and rimantadine (RMT) are used to relieve or treat influenza A symptoms in healthy adults, little is known about the effectiveness and safety of these antivirals in preventing and treating influenza A in children and the elderly. OBJECTIVES: The aim of this review was to systematically consider evidence on the effectiveness and safety of AMT and RMT in preventing and treating influenza A in children and the elderly. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, 2007, issue 3); MEDLINE (1966 to July 2007) and EMBASE (1980 to July 2007). SELECTION CRITERIA: Randomised or quasi-randomised trials comparing AMT and/or RMT in children and the elderly with placebo, control, other antivirals or comparing different doses or schedules of AMT and/or RMT or no intervention. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion and assessed methodological quality. Disagreements were resolved by consensus. In all comparisons except for one, the trials in children and in the elderly were analysed separately. Data were analysed and reported using Cochrane Review Manager 4.2. software. MAIN RESULTS: In children, RMT was effective in the abatement of fever on day three of treatment. AMT showed a prophylactic effect against influenza A infection. AMT and RMT were not related to an increase in the occurrence of adverse effects. RMT also was considered to be well tolerated by the elderly, but showed no prophylactic effect. Different doses were comparable in the prophylaxis of influenza in the elderly, as well as in reporting adverse effects. Zanamivir prevented influenza A more effectively than RMT in the elderly. AUTHORS' CONCLUSIONS: AMT was effective in the prophylaxis of influenza A in children. As confounding matters might have affected our findings, caution should be taken when considering which patients should to be given this prophylactic. Our conclusions about effectiveness of both antivirals for the treatment of influenza A in children were limited to a proven benefit of RMT in the abatement of fever on day three of treatment. Due to the small number of available studies we could not reach a definitive conclusion on the safety of AMT or the effectiveness of RMT in preventing influenza in children and the elderly.


Pediatrics. 2008 Apr;121(4):e1016-31.
Bocchini JA Jr, Bernstein HH, Bradley JS, Brady MT, Byington CL, Dennehy PH, Frenck RW Jr, Glode MP, Keyserling HL, Kimberlin DW, Long SS, Rubin LG, Bortolussi R, Clover RD, Fischer MA, Gorman RL, Pratt RD, Schuchat A, Schwartz B, Starke JR, Baker CJ
American Academy of Pediatrics Committee on Infectious Diseases.

Prevention of influenza: recommendations for influenza immunization of children, 2007-2008.

The American Academy of Pediatrics recommends annual influenza immunization for all children with high-risk conditions who are 6 months of age and older, for all healthy children ages 6 through 59 months, for all household contacts and out-of-home caregivers of children with high-risk conditions and of healthy children younger than 5 years, and for all health care professionals. To more fully protect against the morbidity and mortality of influenza, increased efforts are needed to identify and immunize all children at high risk and all healthy children ages 6 through 59 months and to inform their parents when annual immunizations are due. Previously unimmunized children who are at least 6 months of age but younger than 9 years should receive 2 doses of influenza vaccine, given 1 month apart, beginning as soon as possible on the basis of local availability during the influenza season. If children in this cohort received only 1 dose for the first time in the previous season, it is recommended that 2 doses be administered in the current season. This recommendation applies only to the influenza season that follows the first year that a child younger than 9 years receives influenza vaccine. A child who then also fails to receive 2 doses the next year should be given only 1 dose per year from that point on. Influenza vaccine should also continue to be offered throughout the influenza season, even after influenza activity has been documented in a community. On the basis of global surveillance of circulating virus strains, the influenza vaccine may change from year to year; indeed, 1 of the 3 strains in the 2007-2008 vaccine is different from the previous year's vaccine. All health care professionals, influenza campaign organizers, and public health agencies should develop plans for expanding outreach and infrastructure to immunize all children for whom influenza vaccine is recommended. Appropriate prioritization of administering influenza vaccine will also be necessary when vaccine supplies are delayed or limited. Because the influenza season often extends into March, immunization against influenza is recommended to continue through late winter and early spring. Lastly, it is recommended that for the 2007-2008 season, and likely beyond, health care professionals do not prescribe amantadine or rimantadine for influenza treatment or chemoprophylaxis, because widespread resistance to these antiviral medications now exists among influenza A viral strains. However, oseltamivir and zanamivir can be prescribed for treatment or chemoprophylaxis, because influenza A and B strains remain susceptible.


S Afr Med J. 2008 Mar;98(3 Pt 2):224-30.
Green RJ, Feldman C, Schoub B, Richards GA, Madhi SA, Zar HJ, Lalloo U; Guideline Committee of 1999, Klugman K, Phillips D, Cameron NA, Eggers RR.
Department of Paediatrics and Child Health, University of Pretoria, Pretoria.

Influenza guideline for South Africa--update 2008.

OBJECTIVE: The South African Thoracic Society, in conjunction with interested stakeholders, published a Guideline for Influenza Management in Adults in 1999. This year the South African Thoracic Society (SATS) identified the need to revise that guideline for the following reasons: * To indicate the viral strains that are to be incorporated into the vaccine for the 2008 season * To add important new data regarding treatment of influenza * To add a section on influenza in children * To clarify issues in managing and preventing influenza in HIV-infected individuals. INFLUENZA VIRUS: The influenza virus genus belongs to the family orthomyxoviridae. The haemagglutinin (HA) protein is the outermost protein, responsible for attachment to the host receptor, and is critical in determining the host's immune response to the virus. Changes in the antigenic epitopes of HA therefore allow the virus to escape the host's specific immune response. The genus is classified into three types, A, B and C, on the basis of the antigenic epitopes of the nucleoprotein (NP). Type A, which is widespread in nature in birds and mammals, is the most important type clinically and epidemiologically. It is further divided into subtypes on the basis of the antigenic epitopes of the HA and neuraminidase (NA) proteins. Each of the human subtypes H1N1, H2N2 and H3N2 are further subdivided into strains on the basis of more subtle antigenic properties of the HA protein. INFLUENZA VACCINATION: Influenza vaccine is the mainstay of influenza prevention strategies. All persons who are at high risk of influenza and its complications because of underlying medical conditions or who are receiving regular medical care for conditions such as chronic pulmonary and cardiac disease, chronic renal diseases, neuromuscular diseases, diabetes mellitus and similar metabolic disorders, and individuals who are immunosuppressed (including HIV-infected persons with CD4 counts above 100 cells/microl and HIV-infected children with CD4 counts >15%), should be vaccinated. Vaccines should be given from at least 2 months prior to the onset of autumn (March in South Africa). The recommended vaccine formulation for 2008 is: * A/Solomon Islands/3/2006 (H1N1) (IVR-145) * A/Brisbane/10/2007 (H3N2) (IVR-147) * B/Florida/4/2006 or B/Brisbane/3/2007. TREATMENT OF INFLUENZA: Influenza illness is characterised by the acute onset of systemic and respiratory signs occurring in autumn or winter. Recommendations for the Prevention and Control of Influenza have indicated that neither amantadine nor rimantadine should be used for the treatment or chemoprophylaxis of influenza A. NA inhibitors are an important adjunct to influenza vaccination, in both the prevention and treatment of influenza. Because of concerns about the possibility of the development of viral resistance with overuse of these agents, it is recommended that NA inhibitors in the treatment of influenza should be reserved for high-risk or sicker influenza patients.


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