A noninferiority randomized open-label pilot study of 3- versus 7-day influenza postexposure prophylaxis with oseltamivir in hospitalized children.

Short influenza postexposure prophylaxis (PEP) showed high efficacy in adults, but studies in children are lacking. This randomized open-label pilot trial aimed to verify noninferiority of a 3- versus 7-day prophylaxis with oral oseltamivir in hospitalized children. Influenza contacts were randomized to the 3- or 7-day group and efficacy, relative risk of adverse events (AEs), and the cumulative costs of drugs and AEs management were compared. The intention-to-treat (ITT) analysis included 59 children (n = 28 and n = 31 in the 3- and 7-day group, respectively). The efficacy was 100% (95% CI 87.7-100%) versus 93.6% (95% CI 78.6-99.2%) in the 3- and 7-day group; the differences were statistically insignificant. A per-protocol (PP) analysis including 56 patients (n = 27 and n = 29, respectively) showed 100% (95% CI 87.2-100%) and 93.1% (95% CI 77.2-99.2%) efficacy, respectively, without statistical significance. Differences were within the predefined noninferiority margin with an efficacy difference Δ = 6.45 percentage points (p.p.) with 1-sided 95% CI (- 2.8, - 1.31, p = 0.86; ITT) and Δ = 6.9 p.p. (1-sided 95% CI - 2.83, - 1.27, p = 0.85; PP). Adverse events did not differ significantly, while the cumulative costs of the prophylaxis and AEs management were higher in the 7-day group (median 10.5 euro vs. 4.5 euro, p < 0.01). This pilot study showed the noninferiority of the 3-day versus 7-day PEP, which was associated with lower costs.Trial registration number: NCT04297462, 5th March 2020, restrospectively registered.

A cost-effectiveness analysis of reduced viral transmission with baloxavir marboxil versus oseltamivir or no treatment for seasonal and pandemic influenza management in the United Kingdom.

BACKGROUND: Baloxavir marboxil is an oral, single-dose, cap-dependent endonuclease inhibitor that reduces the duration of influenza symptoms and rapidly stops viral shedding. We developed a susceptible, exposed, infected, recovered (SEIR) model to inform a cost-effectiveness model (CEM) of baloxavir versus oseltamivir or no antiviral treatment in the UK. RESEARCH DESIGN AND METHODS: The SEIR model estimated the attack rates among otherwise healthy and high-risk individuals in seasonal and pandemic settings. The CEM assumed that a proportion of infected patients would receive antiviral treatment. Results were reported at the population level (per 10,000 at risk of infection). RESULTS: The SEIR model estimated greater reductions in infections with baloxavir. In a seasonal setting, baloxavir provided incremental cost-effectiveness ratios (ICERs) of £1884 per quality-adjusted life-year (QALY) gained versus oseltamivir and a dominant cost-effectiveness position versus no antiviral treatment in the total population; ICERs of £2574/QALY versus oseltamivir and £128/QALY versus no antiviral treatment were seen in the high-risk population. Baloxavir was also cost-effective versus oseltamivir or no antiviral treatment and reduced population-level health system occupancy concerns during a pandemic. CONCLUSION: Baloxavir treatment resulted in the fewest influenza cases and was cost-effective versus oseltamivir or no antiviral treatment from a UK National Health Service perspective.

Baloxavir marboxil ('baloxavir') is a prescription medicine for people who become ill with influenza (or 'the flu') that can reduce how long flu symptoms last and the likelihood of complications from the flu that may require going to the hospital. Baloxavir can also reduce the amount and duration of virus shed by infected individuals thus potentially slow or stop the flu from spreading to healthy people. We studied differences in reducing predicted flu infections between baloxavir and another flu treatment, known as oseltamivir, or no flu treatment at all. Treatment with baloxavir resulted in fewer flu infections in the UK population than oseltamivir or no treatment. We then studied how these differences might affect costs between baloxavir and oseltamivir or no treatment at a population level in the UK. Overall, in the majority of scenarios explored in the model, baloxavir was cost-effective as an antiviral treatment for people with the flu in the UK.

Comparative efficacy assessment of antiviral alone and antiviral-antibiotic combination in prevention of influenza-B infection associated complications.

OBJECTIVE: The study aimed to compare the efficacy of antiviral drug alone and antiviral-antibiotic combination therapy in prevention of complications associated with influenza B hospitalized patients. METHOD: Laboratory confirmed influenza B hospitalized patients presented in emergency room after 48 hours of symptoms onset were identified and divided into two groups; Group-1 patients were initiated on Antiviral drug (oseltamivir) alone while Group-2 patients were initiated on Antiviral drug (oseltamivir) in combination with Antibiotic for at least 3 days. Patients were evaluated for different clinical outcomes among both treatment group. RESULTS: A total of 153 and 131 patients were identified for Group-1 and Group-2, respectively. Clinical outcomes such as secondary bacterial infections (20.9%-vs-9.1%; P = 0.031), need of respiratory support (28.7%-vs-12.9%; P = 0.002), length of hospitalization stay (6.57-vs-4.95 days; P = <0.001), incidences of ICU admission (15.7%-vs-7.6%; P = 0.036), early clinical failure (32.6%-vs-16.1%; P = 0.01), and time to clinical stability (4.83-vs-4.1 days; P = 0.001) were found to be statistically less significant (P-value <0.05) for Group-2 patients. CONCLUSION: Early initiation of antibiotic therapy in combination with oseltamivir was found to be more efficacious than oseltamivir alone in prevention of influenza B-associated complications especially in high-risk influenza patients.

Influenza in solid organ transplant recipients: epidemiology, management, and outcomes.

Introduction: In solid organ transplant (SOT) recipients, influenza is associated with significant morbidity, including high hospital admission and mortality rates. Influenza may also impair allograft outcomes, in particular in lung transplant recipients. Early treatment with antivirals and seasonal vaccination contribute to reduce influenza-associated morbidity in this population.Areas covered: We selected a number of publications by searching into Pubmed to review the epidemiology, clinical presentation, outcomes, and management of influenza in SOT recipients. We discuss current treatment options and recent advances in the development of new vaccination strategies.Expert opinion: Our review showed that despite recent studies addressing the current epidemiology of influenza in SOT recipients, data in this population remain sparse. Large international multi-season cohort studies should better describe the actual burden of influenza. Although oseltamivir is an effective drug and should be given to all SOT recipients, the use of novel antivirals and combination therapies need to be tested prospectively in this population. Finally, recent studies aiming to improve the immunogenicity of influenza vaccine in SOT recipients showed promising results, in particular with the use of high-dose vaccines and booster-dose. Clinical trials using clinical endpoints would be important to foster the introduction of these vaccines in the routine clinical practice.

Evaluación de uso en EsSalud de oseltamiri 75mg cápsula / Evaluation of use in EsSalud of oseltamiri 75mg capsule

Se procedió a evaluar la autorización de uso de oseltamivir en el marco de la Directiva Número 003-IETSI-ESSALUD-2016, "Normativa para la Autorización y Uso de Productos Farmacéuticos No Incluidos en el Petitorio Farmacológico de ESSALUD", cuyo numeral 8.15 establece "En el caso de las solicitudes de uso de productos farmacéuticos no incluidos en el Petitorio Farmacológico de ESSALUD para Prioridades o Intervenciones Sanitaras de caráter nacional propuestas por las Gerencias o unidades orgánicas a cargo de las mismas, éstas deben ser presentadas ante el IETSI para su evaluación". La Guía Técnica de "Atención de la Insuficiencia Respiratoria Aguda en pacientes con Influenza" del MINSA, aprobada mediante Resolución Ministerial Número 503-2010/MINSA, del 22 de junio del 2010 y en cuyo ámbito de aplicación se incluye a ESSALUD, estandariza los procedimientos de manejo de los pacientes con Influenza, teniendo a Oseltamivir como una terapia antiviral reservada sólo para las formas graves de la enfermedad. Oseltamivir se encuentra considerado dentro de la Lista Modelo de Medicamentos Esenciales de la OMS. SIn embargo, no se encuentra incluido dentro del Petitorio Nacional Único de Medicamentos Esenciales ni dentro del Petitorio Farmacológico de ESSALUD. Se considera procedente la aprobación del uso de Oseltamivir como producto farmacéutico no incluido en el Petitorio Farmacológico de ESSALUD, considerando lo normado por la Autoridad Nacional en Salud y de acuerdo al numeral 8.15 de la Directiva Número 003-IETSI-ESSALUD-2016.

Neuraminidase inhibitors for influenza: a systematic review and meta-analysis of regulatory and mortality data.

BACKGROUND: Neuraminidase inhibitors (NIs) are stockpiled and recommended by public health agencies for treating and preventing seasonal and pandemic influenza. They are used clinically worldwide. OBJECTIVES: To (1) describe the potential benefits and harms of NIs for influenza in all age groups by reviewing all clinical study reports (CSRs) of published and unpublished randomised, placebo-controlled trials and regulatory comments; and (2) determine the effect of oseltamivir (Tamiflu(®), Roche) treatment on mortality in patients with 2009A/H1N1 influenza. METHODS: We searched trial registries, electronic databases and corresponded with regulators and sponsors to identify randomised trials of NIs. We requested full CSRs and accessed regulators' comments. We included only those trials for which we had CSRs. To examine the effects of oseltamivir on 2009A/H1N1 influenza mortality, we requested individual patient data (IPD) from corresponding authors of all included observational studies. RESULTS: Effect of oseltamivir and zanamivir (Relenza®, GlaxoSmithKline) in the prevention and treatment of influenza: Oseltamivir reduced the time to first alleviation of symptoms in adults by 16.8 hours [95% confidence interval (CI) 8.4 to 25.1 hours]. Zanamivir reduced the time to first alleviation of symptoms in adults by 0.60 days (95% CI 0.39 to 0.81 days). Oseltamivir reduced unverified pneumonia in adult treatment [risk difference (RD) 1.00%, 95% CI 0.22% to 1.49%]; similar findings were observed with zanamivir prophylaxis in adults (RD 0.32%, 95% CI 0.09% to 0.41%). Oseltamivir treatment of adults increased the risk of nausea (RD 3.66%, 95% CI 0.90% to 7.39%) and vomiting (RD 4.56%, 95% CI 2.39% to 7.58%). In the treatment of children, oseltamivir induced vomiting (RD 5.34%, 95% CI 1.75% to 10.29%). Both oseltamivir and zanamivir prophylaxis reduced the risk of symptomatic influenza in individuals (oseltamivir RD 3.05%, 95% CI 1.83% to 3.88%; zanamivir RD 1.98%, 95% CI 0.98% to 2.54%) and in households (oseltamivir RD 13.6%, 95% CI 9.52% to 15.47%; zanamivir RD 14.84%, 95% CI 12.18% to 16.55%). Oseltamivir increased psychiatric adverse events in the combined on- and off-treatment periods (RD 1.06%, 95% CI 0.07% to 2.76%) and the risk of headaches while on treatment (RD 3.15%, 95% CI 0.88% to 5.78%). Effect of oseltamivir on mortality in patients with 2009A/H1N1 influenza: Analysis of summary data of 30 studies as well as IPD of four studies showed evidence of time-dependent bias. After adjusting for time-dependent bias and potential confounding variables, competing risks analysis of the IPD showed insufficient evidence that oseltamivir reduced the risk of mortality (hazard ratio 1.03, 95% CI 0.64 to 1.65). CONCLUSIONS: Oseltamivir and zanamivir cause small reductions in the time to first alleviation of influenza symptoms in adults. The use of oseltamivir increases the risk of nausea, vomiting, psychiatric events in adults and vomiting in children. Oseltamivir has no protective effect on mortality among patients with 2009A/H1N1 influenza. Prophylaxis with either NI may reduce symptomatic influenza in individuals and in households. The balance between benefits and harms should be considered when making decisions about use of NIs for either prophylaxis or treatment of influenza. STUDY REGISTRATION: This study is registered as PROSPERO CRD42012002245. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Barriers to positive policy change that aims to increase access to medicines through reclassification: the case of oseltamivir in New Zealand.

OBJECTIVES: This study aims to identify and explore emergent barriers to consumers accessing oseltamivir without prescription following policy change introduced in New Zealand to increase access via community pharmacies. METHODS: Semi-structured interviews were conducted with 26 community pharmacists immediately following the first season of oseltamivir availability without prescription in October 2007. Interviews were transcribed verbatim and coded using a framework approach to identify themes. KEY FINDINGS: Non-prescription sales of oseltamivir were slow during this period. Participants acknowledged that they may have missed opportunities to recommend oseltamivir and attributed this to a range of reasons. Pharmacy-related barriers identified included limited pharmacist confidence, concerns about efficacy and safety of the product, location of the product in the pharmacy, affordability and the role of support staff. Many pharmacists adopted a 'risk-benefit analysis' that balanced symptom severity with perceived value for money. Consumer barriers included cost, limited awareness of availability and limited ability to correctly self-diagnose and manage influenza. CONCLUSIONS: Complexity in the factors that influenced pharmacist motivation to supply oseltamivir without prescription highlighted the potential for positive policy change to be hindered by multiple barriers. Greater understanding of such barriers is important for effective transition of medicines from prescription to non-prescription availability to achieve increased consumer access through reclassification. Concerns that pharmacists are influenced by commercial priorities when medicines are newly reclassified were not substantiated in this study.

Oseltamivir Population Pharmacokinetics in the Ferret: Model Application for Pharmacokinetic/Pharmacodynamic Study Design.

The ferret is a suitable small animal model for preclinical evaluation of efficacy of antiviral drugs against various influenza strains, including highly pathogenic H5N1 viruses. Rigorous pharmacokinetics/pharmacodynamics (PK/PD) assessment of ferret data has not been conducted, perhaps due to insufficient information on oseltamivir PK. Here, based on PK data from several studies on both uninfected and influenza-infected groups (i.e., with influenza A viruses of H5N1 and H3N2 subtypes and an influenza B virus) and several types of anesthesia we developed a population PK model for the active compound oseltamivir carboxylate (OC) in the ferret. The ferret OC population PK model incorporated delayed first-order input, two-compartment distribution, and first-order elimination to successfully describe OC PK. Influenza infection did not affect model parameters, but anesthesia did. The conclusion that OC PK was not influenced by influenza infection must be viewed with caution because the influenza infections in the studies included here resulted in mild clinical symptoms in terms of temperature, body weight, and activity scores. Monte Carlo simulations were used to determine that administration of a 5.08 mg/kg dose of oseltamivir phosphate to ferret every 12 h for 5 days results in the same median OC area under the plasma concentration-time curve 0-12 h (i.e., 3220 mg h/mL) as that observed in humans during steady state at the approved dose of 75 mg twice daily for 5 days. Modeling indicated that PK variability for OC in the ferret model is high, and can be affected by anesthesia. Therefore, for proper interpretation of PK/PD data, sparse PK sampling to allow the OC PK determination in individual animals is important. Another consideration in appropriate design of PK/PD studies is achieving an influenza infection with pronounced clinical symptoms and efficient virus replication, which will allow adequate evaluation of drug effects.

Prompt Oseltamivir Therapy Reduces Medical Care and Mortality for Patients With Influenza Infection: An Asian Population Cohort Study.

There are limited population-based studies on the progress of oseltamivir therapy for influenza infection.Using insurance claims data of 2005, 2009, and 2010, the authors established an "in-time" cohort and a "lag-time" cohort representing influenza patients taking the medicine within and not within 1 week to examine the treatment progress. Incident outpatient visit, emergency care and hospitalization, and fatality were compared between the 2 cohorts in the first week and the second week of follow-up periods, after the oseltamivir therapy.A total of 112,492 subjects diagnosed with influenza on oseltamivir therapy in 2005, 2009, and 2010 were identified. The multivariate logistic regression analysis showed that the in-time treatment was superior to the lag-time treatment with less repeat outpatient visits, hospitalizations, and fatality. The overall corresponding in-time treatment to lag-time treatment odds ratios (OR) were 0.50, 0.54, and 0.71 (all P value < 0.05), respectively. The in-time to lag-time ORs of all events were 0.50 in 2009 and 0.54 in 2010.Our study demonstrates that the in-time oseltamivir therapy leads to significantly better treatment outcomes. Oseltamivir should be administered as early as the onset of influenza symptoms appears.

Pharmacokinetics and safety of oseltamivir in patients with end-stage renal disease treated with automated peritoneal dialysis.

AIMS: Patients with end-stage renal disease (ESRD) are at increased risk of developing complications associated with influenza infection. Oseltamivir is indicated for influenza treatment in ESRD patients, but the disposition is poorly understood in this patient population. This study aimed to characterize the pharmacokinetics and tolerability of oseltamivir in automated peritoneal dialysis (APD) and construct a pharmacokinetic model to assist with optimized dosing. METHODS: Ten adults with ESRD were prescribed an aggressive APD regimen consisting of three continuous cycler-assisted peritoneal dialysis (CCPD) sessions during the day and two continuous ambulatory (CAPD) sessions overnight. Oseltamivir was administered as a single 75 mg dose, immediately before APD treatment. RESULTS: Oseltamivir was rapidly eliminated via first-pass metabolism, with most of the dose (Fraction metabolized = 0.964) reaching the circulation as the active metabolite, oseltamivir carboxylate. This metabolite was cleared slowly and was quantifiable throughout the sampling interval. The disposition of oseltamivir and oseltamivir carboxylate was described by a two- and a one-compartment model, respectively. Metabolite clearance by CCPD [0.32 l h(-1) (70 kg)(-1) ] was 1.9-fold faster than via CAPD [0.17 l h(-1) (70 kg)(-1) ], with renal elimination being dominant in patients with residual urine production. Model simulations showed that a single 75 mg dose attained target exposures in patients with negligible or low urine clearance. However, higher doses are recommended for further investigation in patients with high residual renal function. In all patients, oseltamivir was well tolerated. CONCLUSIONS: In APD patients with anuria or low residual renal elimination, a single 75 mg dose of oseltamivir produced exposures at the upper end of the safety margin.

Bleeding events following concurrent use of warfarin and oseltamivir by Medicare beneficiaries.

BACKGROUND: During the 2009 H1N1 influenza pandemic, the UK Medicines and Healthcare Products Regulatory Agency received case reports suggesting a potentiation of warfarin anticoagulation by the antiviral drug oseltamivir. We evaluated this putative interaction using Medicare data. OBJECTIVE: To determine the frequency of bleeding following addition of oseltamivir or comparator drugs among Medicare beneficiaries taking warfarin. METHODS: This was a retrospective cohort evaluation using Medicare nationwide data. Cohort members were Medicare Parts A, B, and D beneficiaries from June 30, 2006 to October 31, 2010 receiving warfarin for at least 1 month prior to a concomitant drug of interest (oseltamivir, ampicillin, trimethoprim-sulfamethoxazole (TMP-SMX), and angiotensin-converting enzyme (ACE) inhibitors). Bleeding within 14 days of new prescriptions for oseltamivir or comparators was identified using inpatient or emergency department ICD-9 (International Classification of Diseases, ninth revision) discharge diagnosis codes for gastrointestinal hemorrhage, epistaxis, hematuria, and intracranial bleeding. Patients with bleeding within 30 days preceding the prescription concomitant to warfarin were excluded. RESULTS: With concomitant ACE inhibitors as reference, adjusted odds ratios (ORs) for any bleeding events within 14 days were 1.47 (95% confidence interval [CI] = 1.08-1.88), 1.24 (95% CI = 0.97-1.57), and 2.74 (95% CI = 2.53-3.03), for warfarin plus ampicillin, oseltamivir, and TMP-SMX, respectively. In a sensitivity analysis, adjusted ORs over a 7-day period were 1.89 (95% CI = 1.29-2.59), 1.47 (95% CI = 1.06-2.02), and 3.07 (95% CI = 2.76-3.49) for warfarin plus ampicillin, oseltamivir, and TMP-SMX, respectively. CONCLUSIONS: Bleeding with oseltamivir plus warfarin was not significantly increased over a 14-day observation period; a sensitivity analysis showed a statistically significant increase over a 7-day period; in contrast, the data consistently showed the known tendency of TMP-SMX to potentiate the effects of warfarin. The results should be interpreted with the limitations of this approach in mind, including the inability to control for unmeasured confounders.

U.S. utilization patterns of influenza antiviral medications during the 2009 H1N1 influenza pandemic.

BACKGROUND: The 2009 H1N1 influenza pandemic in the United States occurred from April 2009 to April 2010. The 2009 H1N1 influenza virus was susceptible to neuraminidase inhibitors (oseltamivir and zanamivir). OBJECTIVES: To characterize the 2009 H1N1 influenza pandemic in the United States from April 2009 to April 2010 using weekly influenza antiviral prescription utilization data and the CDC's weekly reports of the number of visits for influenza-like-illnesses by the Influenza Sentinel Provider Surveillance Network. METHODS: A proprietary outpatient data source used by the FDA, which captures adjudicated U.S. prescription claims for select influenza antiviral drugs, was used to conduct this analysis. Data were extracted weekly and analyzed for surveillance during the pandemic. Results were compiled at the end of the pandemic. RESULTS: Oseltamivir has dominated the U.S. influenza antiviral market share of dispensed prescriptions since approval in October 1999 and was the primary influenza antiviral drug used during the 2009 H1N1 influenza pandemic. However, commercial availability of the suspension formulation of oseltamivir was reduced by high demand during the pandemic. Dispensed prescription trends of other influenza antiviral medications studied followed that those of oseltamivir, even antivirals for which the 2009 H1N1 strains showed resistance. CONCLUSION: Weekly prescription utilization of all influenza antivirals used to treat influenza during the seasonal influenza outbreak followed the same trend of weekly reports of the number of visits for influenza-like-illnesses (ILI) by the Influenza Sentinel Provider Surveillance Network. The ILI epidemic curve resembled dispensed antiviral prescription trends (both overall and stratified by age), providing some corroboration for the surveillance data.

Oseltamivir in seasonal, pandemic, and avian influenza: a comprehensive review of 10-years clinical experience.

Oseltamivir (Tamiflu®; F. Hoffmann-La Roche Ltd, Basel, Switzerland) is an orally administered antiviral for the treatment and prevention of influenza A and B infections that is registered in more than 100 countries worldwide. More than 83 million patients have been exposed to the product since its introduction. Oseltamivir is recommended by the World Health Organization (WHO) for use in the clinical management of pandemic and seasonal influenza of varying severity, and as the primary antiviral agent for treatment of avian H5N1 influenza infection in humans. This article is a nonsystematic review of the experience gained from the first 10 years of using oseltamivir for influenza infections since its launch in early 2000, emphasizing recent advances in our understanding of the product and its clinical utility in five main areas. The article reviews the pharmacokinetics of oseltamivir and its active metabolite, oseltamivir carboxylate, including information on special populations such as children and elderly adults, and the co-administration of oseltamivir with other agents. This is followed by a summary of data on the effectiveness of oseltamivir treatment and prophylaxis in patients with all types of influenza, including pandemic (H1N1) 2009 and avian H5N1 influenza. The implications of changes in susceptibility of circulating influenza viruses to oseltamivir and other antiviral agents are also described, as is the emergence of antiviral resistance during and after the 2009 pandemic. The fourth main section deals with the safety profile of oseltamivir in standard and special patient populations, and reviews spontaneously reported adverse event data from the pandemic and pre-pandemic periods and the topical issue of neuropsychiatric adverse events. Finally, the article considers the pharmacoeconomics of oseltamivir in comparison with vaccination and usual care regimens, and as a component of pandemic influenza mitigation strategies.

Assessment of the efficacy of the neuraminidase inhibitor oseltamivir against 2009 pandemic H1N1 influenza virus in ferrets.

Pandemic 2009 influenza A (H1N1) virus (H1N1pdm) is different from contemporary seasonal human viruses in that it can cause infection deep in the lungs of critical care patients. Here we establish a mammalian animal model and assessed the efficacy of the neuraminidase (NA) inhibitor oseltamivir treatment against H1N1pdm virus infection. Oseltamivir (25 mg/kg/day twice daily for 5 days) was orally administered to groups of ferrets, starting either 2 or 24 h after inoculation with 10(6)PFU of A/California/04/2009 (H1N1) influenza virus. We determined that virus replication was restricted to 1 or 2 of 4 lung lobes in oseltamivir-treated animals, while virus was consistently isolated from 4 of 4 lung lobes in control animals (1.5-3.8log(10)PFU/g). Analysis of arterial blood oxygenation revealed less pronounced changes in partial oxygen and carbon dioxide pressure in oseltamivir-treated ferrets, and histologic examination confirmed reduced pneumonia. Treated animals had significantly decreased inflammatory responses in the upper respiratory tract (P < 0.05), less fever and weight loss, and less reduction of activity. Virus titers in the nasal washes of treated and control ferrets did not differ significantly. NA sequencing and fluorescence-based phenotypic assays identified no oseltamivir-resistant variants. Overall, oseltamivir treatment decreases the signs of infection and reduced the spread of H1N1pdm influenza virus in the lungs of ferrets and therefore impeded the development of viral pneumonia.

Mixed treatment comparison with multiple outcomes reported inconsistently across trials: evaluation of antivirals for treatment of influenza A and B.

We present a mixed treatment meta-analysis of antivirals for treatment of influenza, where some trials report summary measures on at least one of the two outcomes: time to alleviation of fever and time to alleviation of symptoms. The synthesis is further complicated by the variety of summary measures reported: mean time, median time and proportion symptom free at the end of follow-up. We compare several models using the deviance information criteria and the contribution of different evidence sources to the residual deviance to aid model selection. A Weibull model with exchangeable treatment effects that are independent for each outcome but have a common random effect mean for the two outcomes gives the best fit according to these criteria. This model allows us to summarize treatment effect on two outcomes in a single summary measure and draw conclusions as to the most effective treatment. Amantadine and Oseltamivir were the most effective treatments, with the probability of being most effective of 0.56 and 0.37, respectively. Amantadine reduces the duration of symptoms by an estimated 2.8 days, and Oseltamivir 2.6 days, compared with placebo. The models provide flexible methods for synthesis of evidence on multiple treatments in the absence of head-to-head trial data, when different summary measures are used and either different clinical outcomes are reported or where the same outcomes are reported at different or multiple time points.

Oseltamivir and the risk of influenza-related complications and hospitalizations in patients with diabetes.

OBJECTIVE: This subgroup analysis of a retrospective cohort study examined, from a managed care perspective, the risk of influenza-related complications and hospitalizations in patients with diabetes who were prescribed oseltamivir for the treatment of influenza and those who were not prescribed antiviral treatment. METHODS: Health insurance claims data from the Thomson Healthcare MarketScan Research Database for 6 influenza seasons (October 1-March 31) between 2000 and 2006 were used to identify patients aged >/=18 years with influenza and diabetes. Patients who received a prescription for oseltamivir within 1 day of a diagnosis of influenza were compared with those who received no antiviral treatment. Outcomes included the frequency of pneumonia, respiratory diagnoses, and otitis media and its complications, and rates of hospitalization within 14 days of the diagnosis of influenza. Cox proportional hazards regression was used to determine the relative risk (RR) of influenza-related complications and hospitalizations. RESULTS: A total of 9090 patients with diabetes and a diagnosis of influenza were identified who met all study criteria. Of these, 2919 (32%) received a prescription for oseltamivir and 6171 (68%) received no antiviral treatment. Patients receiving oseltamivir had a significant 17% reduction in the risk of respiratory illnesses (RR = 0.83; 95% CI, 0.73-0.93) and a 30% reduction in the risk of hospitalization for any reason (RR = 0.70; 95% CI, 0.52-0.94). There were no significant differences between the oseltamivir and control groups in terms of the risks for pneumonia (RR = 0.87; 95% CI, 0.64-1.18), otitis media and its complications (RR = 0.96; 95% CI, 0.48-1.91), or hospitalization for pneumonia (RR = 0.81; 95% CI, 0.41-1.58). CONCLUSION: In this retrospective study, the risk of influenza-associated respiratory illnesses and the number of hospitalizations for any reason were reduced in patients with diabetes who were prescribed oseltamivir compared with an unmatched group that was not prescribed antiviral therapy.

The safety of oseltamivir in patients with influenza: analysis of healthcare claims data from six influenza seasons.

CONTEXT: Recently, neuropsychiatric events associated with oseltamivir treatment have been reported, mainly in pediatric patients in Japan. OBJECTIVE: To explore the influence of oseltamivir treatment on central nervous system (CNS)-related and neuropsychiatric events in adults, children, and adolescents with influenza. DESIGN: A retrospective cohort study using propensity-matched data for 6 influenza seasons (2000-2006). SETTING: Claims data were obtained from the Thomson Healthcare MarketScan Research Database. PATIENTS: Patients of all ages and in subgroups aged 12 years or younger, 13-17 years, and 18-49 years diagnosed with influenza. MAIN OUTCOME MEASURES: Claims for CNS and neuropsychiatric events within 14 and 30 days following influenza diagnosis were compared between patients prescribed oseltamivir and those not prescribed antiviral treatment. RESULTS: Data for 40,704 patients prescribed oseltamivir (9599 aged 12 years or younger; 4615, 13-17 years; and 16,910, 18-49 years) and 40,704 matched controls (9599 aged 12 years or younger; 4621, 13-17 years; and 16,898, 18-49 years) were analyzed. None of the CNS-related and neuropsychiatric events was more likely to occur in patients prescribed oseltamivir. Overall, CNS-related or neuropsychiatric events (odds ratio [OR] 0.76; 95% confidence intervals [CI]: 0.68, 0.84), psychiatric events (OR 0.82; 95% CI: 0.70, 0.96), and disturbances of consciousness (OR 0.61; 95% CI: 0.48, 0.76) within 14 days after influenza diagnosis were all less likely in patients given oseltamivir. Findings were similar within the 30-day post-index time window and across all age groups. CONCLUSIONS: No increase in CNS-related and neuropsychiatric events was observed in adults, children, or adolescents with influenza who were prescribed oseltamivir in this study.