Effect of Oseltamivir (Tamiflur) for the Prevention and Treatment of Influenza During an Influenza Pandemic

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Effect of Oseltamivir (Tamiflur) for the Prevention and Treatment of Influenza During an Influenza Pandemic Effect of oseltamivir (TamifluR) for the prevention and treatment of influenza during an influenza pandemic This is an excerpt from the full technical report, which is written in Norwegian. The excerpt provides the report’s main messages in English. N0. 01–2005 Systematic reviews Title Effect of oseltamivir (TamifluR) for the prevention and treatment of influenza during an influenza pandemic Norwegian title Effekt av oseltamivir (Tamiflu®) ved profylakse og behandling av influensa – implikasjoner for nasjonal beredskap mot pandemisk influensa Institution Norwegian Knowledge Centre for the Health Services (Nasjonalt kunnskapssenter for helsetjenesten) John-Arne Røttingen, Director Authors Berit Mørland, department Director Arne Broch Brantsæter, Jan Eilert Fuglesang, Lars R. Haaheim, Øistein Løvoll, Ragnar Salmén, Haakon Sjursen, Ivar S. Kristiansen, Torbjørn Wisløff, Ida-Kristin Ørjasæter Elvsaas, Ellen Nilsen ISBN 82-8121-017-6 ISSN 1503-9544 Report No. 1 – 2005 Project number – Type of report Systematic reviews No. of pages 86 Client The Norwegian Directorate of Health Subject heading Oseltamivir; Influenza, Human; Pandemics; Primary Prevention (MeSH) Keywords TamifluR Citation Brantsæter A B, Fuglesang JE, Haaheim L R., Løvoll Ø, Salmén R, Sjursen H, Kristiansen I S., Wisløff T, Ørjasæter Elvsaas IK, Nilsen E. Effect of oseltamivir (TamifluR) for the prevention and treatment of influenza during an influenza pandemic. Report from Kunnskapssenteret no. 1−2005. Oslo: Norwegian Knowledge Centre for the Health Services, 2005. Norwegian Knowledge Centre for the Health Services summarizes and disseminates evidence concerning the effect of treatments, methods, and interventions in health services, in addition to monitoring health service quality. Our goal is to support good decision making in order to provide patients in Norway with the best possible care. The Centre is organized under The Norwegian Directorate for Health, but is scientifically and professionally independent. The Centre has no authority to develop health policy or responsibility to implement policies. We would like to thank all contributers for their expertise in this project. Norwegian Knowledge Centre for the Health Services assumes final responsibility for the content of this report. Norwegian Knowledge Centre for the Health Services Oslo, 2005 8. English summary The Norwegian Health Services Research Centre was during the spring 2004 asked by the Directorate for Health and Social Affairs to make an evaluation of the effect of oseltamivir (Tamiflu®) for the prevention and treatment of influenza during an influenza pandemic. A group of experts with experience in the field was constituted in May 2004 to assist the Norwegian Health Services Research Centre with this report. 8.1 Background Influenza pandemics are sudden and unpredictable, yet inevitable, events. They have caused several global health emergencies during the last century. A pandemic breaks out when a new suBtype of influenza virus A arises to which there is little or no immunity in the population. A pandemic most proBaBly will cause greater morBidity and mortality than annual winter outBreaks. Vaccination is the principal means to comBat the impact of influenza. An emerging pandemic virus will create a surge in worldwide vaccine demand, and new approaches to immunisation strategies may be needed to ensure optimum protection of unprimed individuals when vaccine supply is limited. A new class of antiviral agents has been developed that specifically inhiBits influenza virus neuraminidase, an enzyme essential for viral replication. Oseltamivir is a potent and specific inhiBitor of the neuraminidase enzyme of influenza virus types A and B. Oseltamivir is licensed in Norway for the treatment of influenza in adults and children aged one year or older. The drug is also licensed for prophylaxis of influenza in adults and adolescents 13 years or older. 8.2 Objectives The objective of this study was to assess the effects of oseltamivir (Tamiflu®) in the prevention and treatment of influenza and to evaluate the cost-effectiveness of oseltamivir, with special reference to an influenza pandemic. 8.3 Literature Search Relevant databases that were searched were The Cochrane Library, DataBase of ABstracts of Reviews of Effectiveness (DARE), International Network of Agencies of Health Technology Assessment (INAHTA) database, National Guidelines Clearinghouse, Medline and Embase. The literature search includes studies from 1980 to October 2004. 133 abstracts were reviewed. 66 possibly relevant studies were assessed, and 15 studies included in the report. In addition, two sets of guidelines were included. 8.4 Main results / Conclusions Oseltamivir reduces the duration of illness with 1-2 days in previously healthy adults and children with clinical influenza. 49 Severity of illness was significantly reduced by oseltamivir in previously healthy adults, and the frequency and duration of fever was significantly reduced in previously healthy adults and children. Oseltamivir treatment reduces lower respiratory tract complications, antibiotic use, and hospitalization in both healthy and “at risk” adults (age ≥ 65 years, individuals with underlying chronic respiratory or cardiovascular problems). Oseltamivir reduces the duration of cough, fever, time to resolution of illness and frequency of hospitalization in both previously healthy adults, children and “at risk” adults. The frequencies of secondary complications like bronchitis, sinusitis, otitis media, pneumonia, in addition to antibiotic use, were also reduced in most patients. Use of oseltamivir for prophylaxis for periods of five days to six weeks provides a protective effect of 58-89 % against clinical influenza in healthy adults. Prophylaxis for six weeks in a vaccinated frail, elderly population gave a protective effect of 92 %. Children given postexposure prophylaxis for 10 days achieved a protective effect of 55-80 %. Nausea was reported more often in previously healthy adults given oseltamivir than placebo (4.5- 18.0 % versus 2.6-7.4 %), as was also the case for vomiting (3.3-14.1 % versus 3.0-3.4 %). Emesis was reported by 14.3 % and 8,5 % of the children given oseltamivir and placebo respectively. The adverse events were transient and of mild to moderate character. Headache was reported with a higher frequency in the oseltamivir group than in the placebo group in adults “at risk” (8.3 % versus 5.5 %). Oseltamivir-resistant mutants occurred in 5.5-18.0 % of children with clinical influenza and in ≤ 4 % of adults. Use of oseltamivir for prophylaxis for six weeks including the whole Norwegian population will imply a cost of NOK 1 900 million. Treatment with oseltamivir for five days (with a pandemic virus given an attack rate of 40 %) will imply a cost of NOK 180 million. 50.
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