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Antivirals for the treatment and prevention of epidemic and pandemic influenza.

ABSTRACT: Influenza is a highly contagious and debilitating disease that imposes an excess burden of complications and mortality. Antiviral therapy is the primary intervention for treatment and post-exposure prophylaxis (PEP) of influenza. Amantadine and rimantadine are members of the M2 class of antiviral agents and are moderately effective in influenza management. However, their utility is compromised by high levels of resistance, tolerability concerns and a lack of efficacy against influenza B. An alternative class of agents, the neuraminidase inhibitors (NIs), represent the most advanced form of antiviral therapy available, and act by specifically inhibiting the neuraminidase enzymes that are present on all influenza subtypes. Two NIs, oseltamivir and zanamivir, are currently available for clinical use. Oseltamivir, the most widely used NI, is administered orally as a prodrug (oseltamivir carboxylate) and systemically distributed to all potential infection sites. Zanamivir, a second NI, is administered by inhalation via a disk inhaler and deposited primarily in the respiratory tract. When administered within 48 hours of symptom onset, both agents significantly reduce illness duration and symptom severity, and decrease the rate of influenza-associated complications. With oseltamivir, greater benefits are detected with earlier treatment initiation (<12 hours). In PEP, both NIs effectively protect the close contacts of index cases from symptomatic influenza. Oseltamivir and zanamivir are generally well tolerated and associated with a low level of resistance. Emerging evidence supports the activity of both NIs against the H5N1avian influenza infection, which is a pandemic candidate. However, the WHO currently recommends the use of oseltamivir for the management of suspected cases, given the systemic nature of the H5N1 challenge. Ongoing studies are exploring the effectiveness of oseltamivir, zanamivir and other NIs for pandemic management.

SUBMITTER: Oxford JS

PROVIDER: S-EPMC4634659 | biostudies-other | 2007 Jan

REPOSITORIES: biostudies-other

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Project description:BACKGROUND:Systematic reviews of randomized, controlled trials in patients with influenza suggest a lack of evidence about the effects of antiviral therapy on several patient-important outcomes of influenza. PURPOSE:To systematically review observational studies for benefits and harms of oseltamivir, zanamivir, amantadine, or rimantadine in the treatment of influenza. DATA SOURCES:MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, CINAHL, SIGLE, the Chinese Biomedical Literature Database, Panteleimon, and LILACS up to November 2010; contact with pharmaceutical companies; and reference lists. STUDY SELECTION:Observational studies in any language that compared single antiviral therapy with no therapy or other antiviral therapy, or that had no comparator, for influenza or influenza-like illness. DATA EXTRACTION:Two independent investigators extracted data. Confidence in the estimates of the obtained effects (quality of evidence) was assessed by using the Grading of Recommendations Assessment, Development, and Evaluation approach. DATA SYNTHESIS:74 studies fulfilled the inclusion criteria. Meta-analyses of the few studies providing effects with adjustment for confounders suggest that, in high-risk populations, oral oseltamivir may reduce mortality (odds ratio, 0.23 [95% CI, 0.13 to 0.43]; low-quality evidence), hospitalization (odds ratio, 0.75 [CI, 0.66 to 0.89]; low-quality evidence), and duration of symptoms (33 hours [CI, 21 to 45 hours]; very low-quality evidence) compared with no treatment. Earlier treatment with oseltamivir was generally associated with better outcomes. Inhaled zanamivir may lead to shorter symptom duration (23 hours [CI, 17 to 28 hours]; moderate-quality evidence) and fewer hospitalizations (odds ratio, 0.66 [CI, 0.37 to 1.18]) but more complications than no treatment. Direct comparison of oral oseltamivir and inhaled zanamivir suggests no important differences in key outcomes. Data from 1 study suggest that oral amantadine may reduce mortality and pneumonia associated with influenza A. No included study evaluated rimantadine. LIMITATIONS:Mortality was assessed in high-risk patients, and generalizability is limited. The overall body of evidence is limited by risk for confounding and selection, reporting, and publication bias. CONCLUSION:Therapy with oral oseltamivir and inhaled zanamivir may provide a net benefit over no treatment of influenza. However, as with the randomized trials, the confidence in the estimates of the effects for decision making is low to very low. PRIMARY FUNDING SOURCES: World Health Organization and McMaster University.

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Antivirals for the treatment and prevention of epidemic and pandemic influenza.

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