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      Zanamivir for the prevention of influenza in adults and children age 5 years and older

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          Abstract

          On a yearly basis there are 3–5 million severe cases and 250,000–500,000 deaths worldwide attributed to influenza. Four antiviral medications are currently available on the market; however, resistance has resulted in the armamentarium being shrunk to two remaining active treatment options for influenza. These two neuraminidase inhibitors, oseltamivir and zanamivir, are recommended for the treatment and prophylaxis of influenza A and B in children and adults. Zanamivir, which is the focus of this review, is an inhaled antiviral that has shown benefit in the community, household, and nursing home population for post-exposure prophylaxis. Zanamivir protection rates range from 67%–84% in clinical trials of adults and children. Although the influenza vaccine remains the best modality to combat the disease, zanamivir may also assist in decreasing morbidity associated with influenza A and B.

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          Inhaled zanamivir for the prevention of influenza in families. Zanamivir Family Study Group.

          F Hayden, Larisa Gubareva, Christopher J. Hammond … (2000)
          As prophylaxis against influenza in families, amantadine and rimantadine have had inconsistent effectiveness, partly because of the transmission of drug-resistant variants from treated index patients. We performed a double-blind, placebo-controlled study of inhaled zanamivir for the treatment and prevention of influenza in families. We enrolled families (with two to five members and at least one child who was five years of age or older) before the 1998-1999 influenza season. If an influenza-like illness developed in one member, the family was randomly assigned to receive either inhaled zanamivir or placebo. The family member with the index illness was treated with either 10 mg of inhaled zanamivir (163 subjects) or placebo (158) twice a day for 5 days, and the other family members received either 10 mg of zanamivir (414 subjects) or placebo (423) once a day as prophylaxis for 10 days. The primary end point was the proportion of families in which at least one household contact had symptomatic, laboratory-confirmed influenza. The proportion of families with at least one initially healthy household contact in whom influenza developed was smaller in the zanamivir group than in the placebo group (4 percent vs. 19 percent, P<0.001); the difference represented a 79 percent reduction in the proportion of families with at least one affected contact. Zanamivir provided protection against both influenza A and influenza B. A neuraminidase-inhibition assay and sequencing of the neuraminidase and hemagglutinin genes revealed no zanamivir-resistant variants. Among the subjects with index cases of laboratory-confirmed influenza, the median duration of symptoms was 2.5 days shorter in the zanamivir group than in the placebo group (5.0 vs. 7.5 days, P=0.01). Zanamivir was well tolerated. When combined with the treatment of index cases, prophylactic treatment of family members with once-daily inhaled zanamivir is well tolerated and prevents the development of influenza. In this study there was no evidence of the emergence of resistant influenza variants.
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            Zanamivir in the prevention of influenza among healthy adults: a randomized controlled trial.

            Dimity Crisp, D. Robinson, A. Hinson … (1999)
            The neuraminidase inhibitor zanamivir, a sialic acid analog administered directly to the respiratory tract, has been demonstrated in clinical studies to be effective in treatment of type A and B influenza. It has also been shown to prevent influenza infection and disease in an experimental model. To examine the efficacy of zanamivir, administered once daily, in the prevention of influenza infection and disease. Double-blind, randomized, placebo-controlled trial. Two midwestern university communities. A total of 1107 healthy adults (mean age [range], 29 [18-69] years) were recruited in November 1997, before the influenza season. At the start of the influenza outbreak, 554 subjects were randomized to receive placebo and 553 to receive zanamivir. The drug, 10 mg once per day, or identical placebo was administered by oral inhalation for a 4-week period. Illness occurrence was recorded by participants daily and records were evaluated weekly. Specimens were collected for viral isolation when symptoms were reported within 3 days of illness onset. Infection was also identified by testing paired serum samples for rise in antibody titer against the circulating influenza viruses. Zanamivir was 67% efficacious (95% confidence interval [CI], 39%-83%; P<.001) in preventing laboratory-confirmed clinical influenza meeting the case definition and 84% efficacious (95% CI, 55%-94%; P=.001) in preventing laboratory-confirmed illnesses with fever. All influenza infections occurring during the season, with or without symptoms, were prevented with an efficacy of 31% (95% CI, 4%-50%; P=.03). The nature and incidence of adverse events in the zanamivir group did not differ from placebo. Compliance with the once-daily dosage was high. Zanamivir administered once daily is efficacious and well tolerated in the prevention of influenza for a 4-week period in healthy adults.
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              Zanamivir prophylaxis: an effective strategy for the prevention of influenza types A and B within households.

              Shauna C. Kerr, Steve J Blanckenberg, Michael Pichichero … (2002)
              A double-blind, randomized study of inhaled zanamivir for the prevention of influenza in families was conducted. Once a person with a suspected case of influenza was identified (index patient), treatment of all other household members (contacts) > or =5 years old was initiated. Contacts received either 10 mg zanamivir or placebo inhaled once daily for 10 days. Index patients received relief medication only. In total, 487 households (242 placebo and 245 zanamivir) were enrolled, with 1291 contacts randomly assigned to receive prophylaxis. Four percent of zanamivir versus 19% of placebo households (P<.001) had at least 1 contact who developed symptomatic, laboratory-confirmed influenza, representing 81% protective efficacy (95% confidence interval, 64%-90%). Protective efficacy was similarly high for individuals (82%) and against both influenza types A and B (78% and 85%, respectively, for households). Zanamivir was well tolerated and was effective in preventing influenza types A and B within households where the index patient was not treated.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Ther Clin Risk Manag
                Journal ID (publisher-id): Therapeutics and Clinical Risk Management
                Title: Therapeutics and Clinical Risk Management
                Publisher: Dove Medical Press
                ISSN (Print): 1176-6336
                ISSN (Electronic): 1178-203X
                Publication date (Print): June 2007
                Publication date (Electronic): June 2007
                Volume: 3
                Issue: 3
                Pages: 461-465
                Affiliations
                [1 ]Auburn University Harrison School of Pharmacy Huntsville, AL, USA
                [2 ]Huntsville Hospital Huntsville, AL, USA
                Author notes
                Correspondence: Lea S Eiland UAB/Division of Pediatrics, 301 Governors Drive, Huntsville, AL, 35801, USA Tel +1 256 551 4445 Fax +1 256 551 4453 Email eilanls@ 123456auburn.edu
                Article
                PMC ID: 2386359
                PubMed ID: 18488077
                SO-VID: e0aa75db-7cdd-4c02-b7fb-f2eae67c77b5
                Copyright © © 2007 Dove Medical Press Limited. All rights reserved
                History
                Categories
                Subject: Review

                ScienceOpen disciplines: Medicine
                Keywords: nursing home,relenza,flu,prophylaxis,community,neuraminidase inhibitors,household
                Data availability:
                ScienceOpen disciplines: Medicine
                Keywords: nursing home, relenza, flu, prophylaxis, community, neuraminidase inhibitors, household

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