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Anales de Pediatria May 2019Influenza is a generally a benign disease, but occasionally it can cause serious complications. There is controversy about the benefits of antiviral treatment. (Review)
Review
INTRODUCTION
Influenza is a generally a benign disease, but occasionally it can cause serious complications. There is controversy about the benefits of antiviral treatment.
OBJECTIVES
To provide some recommendations on the treatment with oseltamivir in paediatric patients with influenza, based on the best data available and valid in our environment.
METHODS
The Respiratory Infections Group of the Spanish Society of Paediatric Infectious Diseases carried out a review of the literature. The findings were analysed using the GRADE methodology, and recommendations were made.
RESULTS
The systematic use of diagnostic tests for influenza in the outpatient setting, or in the emergency room, in immunocompetent patients with a compatible clinical picture is not recommended. If the aim is to prevent serious events, the use of antivirals is not recommended for the vast majority of healthy and asthmatic patients with influenza or suspected seasonal flu. The systematic use of oseltamivir in patients admitted to hospital with influenza is not recommended. Oseltamivir treatment is recommended in any patients with influenza and pneumonia or severe illness, and critically ill patients, especially during the first 48hours of illness. The treatment of patients with risk factors is recommended, considering their underlying disease. Influenza vaccination, together with basic isolation measures, continue to be the main tool in the prevention of influenza.
CONCLUSION
In some situations, there are sufficient data to issue clear recommendations. In other situations, the data are incomplete, and only allows weak recommendations.
Topics: Adolescent; Age Factors; Antiviral Agents; Child; Critical Illness; Humans; Influenza, Human; Oseltamivir; Risk Factors; Time Factors
PubMed: 30797703
DOI: 10.1016/j.anpedi.2019.01.009 -
Drug Discovery Today Aug 2020Influenza A and B viruses cause seasonal worldwide influenza epidemics each winter, and are a major public health concern and cause of morbidity and mortality. A... (Review)
Review
Influenza A and B viruses cause seasonal worldwide influenza epidemics each winter, and are a major public health concern and cause of morbidity and mortality. A substantial reduction in influenza-related deaths can be attributed to both vaccination and administration of oseltamivir (OS), which is approved for oral administration and inhibits viral neuraminidase (NA), a transmembrane protein. OS carboxylate (OSC), the active form of OS, is formed by the action of endogenous esterase, which targets NA and is shown to significantly reduce influenza-related deaths. However, the development of resistance in various viral variants, including H3N2 and H5N1, has raised concern about the effectiveness of OS. This comprehensive review covers a range of OS analogs shown to be effective against influenza virus, comparing different types of substituent group that contribute to the activity and bioavailability of these compounds.
Topics: Animals; Antiviral Agents; Humans; Life Cycle Stages; Neuraminidase; Orthomyxoviridae; Orthomyxoviridae Infections; Oseltamivir
PubMed: 32554062
DOI: 10.1016/j.drudis.2020.06.004 -
Lancet (London, England) Jan 2020Antivirals are infrequently prescribed in European primary care for influenza-like illness, mostly because of perceived ineffectiveness in real world primary care and... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
Antivirals are infrequently prescribed in European primary care for influenza-like illness, mostly because of perceived ineffectiveness in real world primary care and because individuals who will especially benefit have not been identified in independent trials. We aimed to determine whether adding antiviral treatment to usual primary care for patients with influenza-like illness reduces time to recovery overall and in key subgroups.
METHODS
We did an open-label, pragmatic, adaptive, randomised controlled trial of adding oseltamivir to usual care in patients aged 1 year and older presenting with influenza-like illness in primary care. The primary endpoint was time to recovery, defined as return to usual activities, with fever, headache, and muscle ache minor or absent. The trial was designed and powered to assess oseltamivir benefit overall and in 36 prespecified subgroups defined by age, comorbidity, previous symptom duration, and symptom severity, using a Bayesian piece-wise exponential primary analysis model. The trial is registered with the ISRCTN Registry, number ISRCTN 27908921.
FINDINGS
Between Jan 15, 2016, and April 12, 2018, we recruited 3266 participants in 15 European countries during three seasonal influenza seasons, allocated 1629 to usual care plus oseltamivir and 1637 to usual care, and ascertained the primary outcome in 1533 (94%) and 1526 (93%). 1590 (52%) of 3059 participants had PCR-confirmed influenza infection. Time to recovery was shorter in participants randomly assigned to oseltamivir (hazard ratio 1·29, 95% Bayesian credible interval [BCrI] 1·20-1·39) overall and in 30 of the 36 prespecified subgroups, with estimated hazard ratios ranging from 1·13 to 1·72. The estimated absolute mean benefit from oseltamivir was 1·02 days (95% [BCrI] 0·74-1·31) overall, and in the prespecified subgroups, ranged from 0·70 (95% BCrI 0·30-1·20) in patients younger than 12 years, with less severe symptoms, no comorbidities, and shorter previous illness duration to 3·20 (95% BCrI 1·00-5·50) in patients aged 65 years or older who had more severe illness, comorbidities, and longer previous illness duration. Regarding harms, an increased burden of vomiting or nausea was observed in the oseltamivir group.
INTERPRETATION
Primary care patients with influenza-like illness treated with oseltamivir recovered one day sooner on average than those managed by usual care alone. Older, sicker patients with comorbidities and longer previous symptom duration recovered 2-3 days sooner.
FUNDING
European Commission's Seventh Framework Programme.
Topics: Adolescent; Adult; Aged; Antiviral Agents; Child; Child, Preschool; Combined Modality Therapy; Europe; Female; Humans; Infant; Influenza, Human; Male; Middle Aged; Oseltamivir; Primary Health Care; Severity of Illness Index; Time Factors; Treatment Outcome; Young Adult
PubMed: 31839279
DOI: 10.1016/S0140-6736(19)32982-4 -
Seminars in Perinatology Dec 2014Pregnancy predisposes women to disproportionate morbidity and mortality from influenza infections. This is true for both seasonal epidemics as well as occasional... (Review)
Review
Pregnancy predisposes women to disproportionate morbidity and mortality from influenza infections. This is true for both seasonal epidemics as well as occasional pandemics. Inactivated yearly influenza vaccines are the best available method of disease prevention and are recommended for all pregnant women in any trimester of pregnancy and postpartum. Oseltamivir (Tamiflu(®)) is currently the first-line recommended and most commonly used pharmaceutical agent for influenza prophylaxis and treatment. Oseltamivir has been demonstrated to prevent disease among exposed individuals, as well as to shorten the duration of illness and lessen the likelihood of complications among those infected. The physiologic adaptations of pregnancy may alter the pharmacokinetics and pharmacodynamics of this important drug. Updated evidence regarding these potential alterations, current knowledge gaps, and future investigative directions is discussed.
Topics: Antiviral Agents; Female; Humans; Influenza, Human; Oseltamivir; Pregnancy; Pregnancy Complications, Infectious
PubMed: 25281358
DOI: 10.1053/j.semperi.2014.08.015 -
Expert Review of Respiratory Medicine 2016Influenza is a common disease affecting many children each year. In a number of cases, particularly in children <2 years old and in those with severe chronic underlying... (Review)
Review
Influenza is a common disease affecting many children each year. In a number of cases, particularly in children <2 years old and in those with severe chronic underlying disease, influenza can be complicated by lower respiratory tract infections, acute otitis media, rhinosinusitis, febrile seizures, dehydration or encephalopathy. Oseltamivir is the influenza virus drug that is most commonly studied in children for both the treatment and prevention of influenza. To avoid the risk that children with mild influenza or patients suffering from different viral infections receive oseltamivir, oseltamivir treatment should be recommended only in severe influenza cases, especially if confirmed by reliable laboratory tests. However, therapy must be initiated considering the risk of complications and the presence of severe clinical manifestations at age- and weight-appropriate doses. Because the vaccine remains the best option for preventing influenza and its complications, prophylaxis using oseltamivir should only be considered in select patients.
Topics: Antiviral Agents; Child; Dose-Response Relationship, Drug; Drug Resistance, Viral; Humans; Influenza, Human; Oseltamivir; Treatment Outcome
PubMed: 26616633
DOI: 10.1586/17476348.2016.1126182 -
Therapeutic Drug Monitoring Feb 2021Oseltamivir is indicated for the treatment and prophylaxis of influenza infections. Achieving therapeutic concentrations EARLY in the course of the infection impacts... (Review)
Review
Oseltamivir-Current Dosing Recommendations Reduce the Therapeutic Benefit in Patients With Mild to Moderate Renal Function and/or Large Body Mass: A Review of the Literature With Recommendations to Optimize Dosing, Including the Use of Therapeutic Drug Monitoring.
PURPOSE
Oseltamivir is indicated for the treatment and prophylaxis of influenza infections. Achieving therapeutic concentrations EARLY in the course of the infection impacts greatly on the magnitude of benefit. Oseltamivir is renally cleared and dose reductions are advised for patients with renal impairment. The purpose of this review was to determine whether these dose reductions facilitate the early attainment of therapeutic concentrations. The review also examined the effect of body mass on the same outcome.
METHOD
Oseltamivir is administered as a prodrug and converted to the active carboxylate moiety in the liver. Published articles that included oseltamivir carboxylate (OC) pharmacokinetics in patients with renal impairment and those with large body mass were reviewed. Concentrations of OC achieved in the first 24 hours were compared with those from patients with normal renal function and body mass.
RESULTS
Studies that informed dosage regimens for patients with mild to moderately impaired renal function focused on attaining steady-state concentrations similar to those observed in patients with normal renal function. They overlooked the importance of achieving therapeutic concentrations EARLY in the course of the infection. As a result, many patients will not attain therapeutic concentrations until too late in the infection. This is also true for patients with a large body mass.
CONCLUSIONS
Current dosing advice for oseltamivir in patients with mild to moderate renal impairment and those with a larger body mass are likely to reduce (or even negate) its efficacy. The first dose should be 75 mg for patients with normal body mass and proportionately larger when body mass is larger. Subsequent doses should be reduced in proportion to the degree of renal impairment. Timely therapeutic drug monitoring can provide invaluable dosing (and other) information to the clinician treating patients with influenza and could improve patient outcomes.
Topics: Antiviral Agents; Body Mass Index; Drug Monitoring; Humans; Influenza, Human; Kidney; Oseltamivir
PubMed: 32947554
DOI: 10.1097/FTD.0000000000000797 -
Pharmacotherapy Mar 2020
Topics: Antiviral Agents; Drug Approval; Humans; Influenza, Human; Nonprescription Drugs; Oseltamivir; United States; United States Food and Drug Administration
PubMed: 32048321
DOI: 10.1002/phar.2370 -
Yakugaku Zasshi : Journal of the... 2019Although the anti-influenza virus drug oseltamivir ameliorates the fever of influenza, adverse events related to its hypothermic effect have been reported. We found that... (Review)
Review
Although the anti-influenza virus drug oseltamivir ameliorates the fever of influenza, adverse events related to its hypothermic effect have been reported. We found that oseltamivir causes dose-dependent hypothermia in normal mice, and have been studying the pharmacological mechanisms responsible for 12 years. Oseltamivir blocks nicotinic cholinergic transmission at sympathetic ganglia and reduces sympathetic modulation of brown adipose tissue (BAT), a heat generator. Oseltamivir was found to target the ion channels of nicotinic acetylcholine receptors, as demonstrated by patch clamp experiments with cells expressing the human α3β4 nicotinic receptor. Metabolized oseltamivir carboxylate, which inhibits the influenza virus neuraminidase, did not elicit hypothermia and ion channel suppression. Body temperature was decreased by intracerebroventricular administration of oseltamivir. Because this hypothermic effect was inhibited by dopamine D receptor blockade, it was suggested that oseltamivir centrally stimulates the D receptor. In Japan, the package inserts for oseltamivir and amantadine indicate very similar adverse neuropsychiatric reactions for the two drugs (abnormal behavior, consciousness disturbance, convulsion, delirium, delusion, hallucination). A literature search revealed that in some previous studies, oseltamivir and amantadine were shown to block the ion channel systems and activate the dopaminergic nervous system via several mechanisms. Therefore the similarity of the adverse reactions elicited by oseltamivir and amantadine was considered attributable to their similar pharmacological effects.
Topics: Adipose Tissue, Brown; Amantadine; Animals; Antipyretics; Antiviral Agents; Body Temperature; Dose-Response Relationship, Drug; Humans; Hypothermia; Mice; Oseltamivir; Rats; Receptors, Dopamine D2; Receptors, Nicotinic
PubMed: 31061347
DOI: 10.1248/yakushi.18-00191 -
The Journal of Antimicrobial... Apr 2010Seasonal influenza viruses cause annual disease epidemics that affect individuals at low and high risk for secondary illnesses. Influenza vaccines are widely used in... (Review)
Review
Seasonal influenza viruses cause annual disease epidemics that affect individuals at low and high risk for secondary illnesses. Influenza vaccines are widely used in high-risk patients to prevent infection, but the protection afforded varies by population; uptake is also limited in some groups. Antiviral drugs for influenza are now readily available. Oseltamivir is the most widely used antiviral for the treatment and prophylaxis of seasonal influenza, and its efficacy and safety are now well established in a variety of populations. In addition to decreasing the severity and duration of the symptoms of influenza, clinical and epidemiological studies demonstrate that oseltamivir significantly reduces the frequency of secondary illnesses and exacerbation of underlying conditions; survival is also significantly improved in seriously ill patients who are hospitalized with severe influenza. Resistant viruses are isolated with a low frequency during oseltamivir treatment (0.33% in adults and 4.0% in children among almost 2000 oseltamivir-treated patients enrolled onto Roche-sponsored clinical trials of oseltamivir treatment during the oseltamivir development programme). However, an oseltamivir-resistant influenza A (H1N1) virus emerged in Europe during the 2007-08 season and circulated in the southern and northern hemispheres in 2008-09. No link with oseltamivir usage could be detected, and the clinical impact of these viruses was limited. Oseltamivir-susceptible pandemic (H1N1) 2009 viruses now predominate in many countries. Oseltamivir is generally well tolerated, with a similar adverse event profile to placebo.
Topics: Amino Acid Substitution; Antiviral Agents; Chemoprevention; Clinical Trials as Topic; Drug Resistance, Viral; Humans; Influenza A Virus, H1N1 Subtype; Influenza A Virus, H3N2 Subtype; Influenza B virus; Influenza, Human; Mutation, Missense; Oseltamivir; Seasons; Treatment Outcome
PubMed: 20215131
DOI: 10.1093/jac/dkq012 -
Advances in Therapy Nov 2011Oseltamivir (Tamiflu®; F. Hoffmann-La Roche Ltd, Basel, Switzerland) is an orally administered antiviral for the treatment and prevention of influenza A and B... (Review)
Review
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.
Topics: Adult; Aged; Antiviral Agents; Child; Drug Monitoring; Drug Resistance, Viral; Humans; Influenza A Virus, H1N1 Subtype; Influenza A Virus, H5N1 Subtype; Influenza B virus; Influenza, Human; Oseltamivir; Pandemics; Pharmacovigilance; Practice Guidelines as Topic; Product Surveillance, Postmarketing; Vaccination; World Health Organization
PubMed: 22057727
DOI: 10.1007/s12325-011-0072-7