A Randomized Study of Standard versus Double dose Oseltamivir for Treating Influenza in the Community

Dixit, Rashmi; Khandaker, Gulam; Hay, Peter; McPhie, Kenneth; Taylor, Janette; Rashid, Harunor; Heron, Leon; Dwyer, Dominic E.; Booy, Robert

doi:10.3851/imp2807

Cited by 11 publications

(13 citation statements)

References 41 publications

(47 reference statements)

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“…Similarly, several observational studies indicate that enteric oseltamivir reaches comparable plasma concentrations to non-critically ill patients in those receiving extracorporeal membrane oxygenation (ECMO) and renal replacement therapy [80][81][82][83][84][85][86][87], although dosing should be reduced in patients with significant renal impairment. There is scant evidence that increased NAI dosing (e.g., twice daily dosing) in critically ill patients provides additional clinical benefit than standard dosing [80,[88][89][90][91][92]. Of note, studies also suggest that increased oseltamivir dosing does not provide additional clinical benefit in obese adults, including extreme obesity (BMI > 40) [93,94].…”

Section: Treatment Of Influenzamentioning

confidence: 99%

Influenza virus-related critical illness: prevention, diagnosis, treatment

2019

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Annual seasonal influenza epidemics of variable severity result in significant morbidity and mortality in the United States (U.S.) and worldwide. In temperate climate countries, including the U.S., influenza activity peaks during the winter months. Annual influenza vaccination is recommended for all persons in the U.S. aged 6 months and older, and among those at increased risk for influenza-related complications in other parts of the world (e.g. young children, elderly). Observational studies have reported effectiveness of influenza vaccination to reduce the risks of severe disease requiring hospitalization, intensive care unit admission, and death. A diagnosis of influenza should be considered in critically ill patients admitted with complications such as exacerbation of underlying chronic comorbidities, community-acquired pneumonia, and respiratory failure during influenza season. Molecular tests are recommended for influenza testing of respiratory specimens in hospitalized patients. Antigen detection assays are not recommended in critically ill patients because of lower sensitivity; negative results of these tests should not be used to make clinical decisions, and respiratory specimens should be tested for influenza by molecular assays. Because critically ill patients with lower respiratory tract disease may have cleared influenza virus in the upper respiratory tract, but have prolonged influenza viral replication in the lower respiratory tract, an endotracheal aspirate (preferentially) or bronchoalveolar lavage fluid specimen (if collected for other diagnostic purposes) should be tested by molecular assay for detection of influenza viruses. Observational studies have reported that antiviral treatment of critically ill adult influenza patients with a neuraminidase inhibitor is associated with survival benefit. Since earlier initiation of antiviral treatment is associated with the greatest clinical benefit, standard-dose oseltamivir (75 mg twice daily in adults) for enteric administration is recommended as soon as possible as it is well absorbed in critically ill patients. Based upon observational data that suggest harms, adjunctive corticosteroid treatment is currently not recommended for children or adults hospitalized with influenza, including critically ill patients, unless clinically indicated for another reason, such as treatment of asthma or COPD exacerbation, or septic shock. A number of pharmaceutical agents are in development for treatment of severe influenza.

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Section: Treatment Of Influenzamentioning

confidence: 99%

Influenza virus-related critical illness: prevention, diagnosis, treatment

2019

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“…The sample size ranged from 36 to 19 893 (a total of 20 947). Among the included studies, four were RCTs 6‐9 and the other six were cohort studies (four retrospective studies 10‐13 and two prospective studies 14,15 ). Among the ten studies, five were conducted in North America 7,10‐13 and two in Asia 8,15 .…”

Section: Resultsmentioning

confidence: 99%

Comparison of double‐dose vs standard‐dose oseltamivir in the treatment of influenza: A systematic review and meta‐analysis

Liu

Qin

2020

J Clin Pharm Ther

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What is known and objective The effect of double‐dose oseltamivir on mortality in patients with influenza remains controversial. We systematically reviewed the literature to investigate whether double‐dose oseltamivir influences mortality in patients with influenza. Methods PubMed, Excerpta Medica Database (Embase) and Cochrane Central Register of Controlled Trials (CENTRAL) were searched for randomized controlled trials (RCTs) and observational studies regarding the effect of double‐dose oseltamivir on mortality in patients with influenza. The primary outcome was all‐cause mortality. The Mantel‐Haenszel method with random effects model was used to calculate pooled odds ratios (ORs) and 95% confidence intervals (CIs). Results and discussion Ten studies (four RCTs and six observational studies), involving 20 947 patients, were included. Pooled analysis suggested that double‐dose oseltamivir was not associated with decreased mortality in patients with influenza, both in RCTs (OR, 1.29; 95% CI, 0.52‐3.15; P = .58) and observational studies (OR, 1.59; 95% CI, 0.79‐3.19; P = .20; I2 = 51%). Double‐dose oseltamivir did not show statistical benefit on the virologic clearance rate (OR, 1.26; 95% CI, 0.85‐1.88; P = .25; I2 = 0%) or the incidence of adverse events (AEs) (OR, 1.52; 95% CI, 0.85‐2.72; P = .15; I2 = 59%). What is new and conclusion Current evidence indicates that double‐dose oseltamivir does not decrease mortality or have advantages on the outcome of virologic clearance rate and incidence of AEs. However, the finding largely relied on the data from observational studies, which may potentially have led to selection bias. Therefore, high‐quality and adequately powered RCTs are warranted.

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“…The standard dosage of oseltamivir in adults is 75 mg twice daily and requires dose adjustment for diminished renal function as well as in pediatric populations. Double-dose oseltamivir has been used in critically ill transplant recipients, although recent evidence in the immune competent population indicates that higher doses have no additional benefit [49,50]. The typical duration of treatment is 5 days; however, longer durations have been suggested by some experts if symptoms are ongoing.…”

Section: Influenzamentioning

confidence: 99%

Post-transplant Viral Respiratory Infections in the Older Patient: Epidemiology, Diagnosis, and Management

Law

Kumar

2017

Drugs Aging

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Organ and stem cell transplantation has been one of the greatest advances in modern medicine, and is the primary treatment modality for many end-stage diseases. As our population ages, so do the transplant recipients, and with that comes many new challenges. Respiratory viruses have been a large contributor to the mortality and morbidity of solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) recipients. Respiratory viruses are generally a long-term complication of transplantation and primarily acquired in the community. With the emergence of molecular methods, newer respiratory viruses are being detected. Respiratory viruses appear to cause severe disease in the older transplant population. Influenza vaccine remains the mainstay of prevention in transplant recipients, although immunogenicity of current vaccines is suboptimal. Limited therapies are available for other respiratory viruses. The next decade will likely bring newer antivirals and vaccines to the forefront. Our goal is to provide the most up to date knowledge of respiratory viral infections in our aging transplant population.

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A Randomized Study of Standard versus Double dose Oseltamivir for Treating Influenza in the Community

Abstract: DD oseltamivir did not appear to provide a clinical or virological advantage, nor reduce the emergence of oseltamivir resistance, but our study was underpowered. Adverse events occurred more frequently on DD compared to SD oseltamivir.

Cited by 11 publications

References 41 publications

Influenza virus-related critical illness: prevention, diagnosis, treatment

Influenza virus-related critical illness: prevention, diagnosis, treatment

Comparison of double‐dose vs standard‐dose oseltamivir in the treatment of influenza: A systematic review and meta‐analysis

Post-transplant Viral Respiratory Infections in the Older Patient: Epidemiology, Diagnosis, and Management

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